ORCID Profile
0000-0002-1182-9792
Current Organisations
Perth Childrens Hospital
,
Royal Australasian College of Physicians
,
Menzies Centre for Population
,
Australian Academy of Health & Medical Sciences
,
Australian Faculty of Public Health Medicine
,
University of Sydney
,
University of Melbourne
,
University of Western Australia
,
Charles Darwin University
,
Telethon Kids Institute
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Publications
A national prospective surveillance study of acute rheumatic fever in Australian children.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2013
Improvement in rheumatic fever and rheumatic heart disease management and prevention using a health centre-based continuous quality improvement approach
Publisher: Springer Science and Business Media LLC
Date: 12-2013
Comparison of group A streptococcal titres in healthy children and those with pharyngitis and skin infections
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.JINF.2021.10.014
Abstract: Rates of acute rheumatic fever, a sequelae of group A Streptococcal (GAS) infection, remain unacceptably high in Indigenous Māori and Pacific children in New Zealand. This prospective study aimed to describe GAS antibody titres in healthy children (5-14 years) by ethnicity, and to determine how paired titres vary with GAS culture positive and negative pharyngitis, and GAS skin infections. Analysis included 887 children (32% Māori, 36% Pacific, 33% European/Other) from Auckland, New Zealand. Cases comprise 772 children who had a sore throat or skin infection, which resulted in a swab taken for culture. Healthy controls were asymptomatic (N = 154) and matched by age, ethnicity and region. All participants had a serum s le, with a second s le collected from cases only. Sera were analysed for anti-streptolysin O (ASO) and anti-DNase-B (ADB) antibodies. Healthy Māori and Pacific children had higher GAS antibody titres than healthy European/Other children. Children with GAS-positive sore throat had the highest mean ASO titres and children with GAS-positive skin infection had the highest mean ADB titres. When a two-fold increase or an upper limit of normal cut-off (ASO 450 IU/ml, ADB 400 U/ml) was applied to titres from children with GAS-positive sore throat, 62.1% were classified as having serologically confirmed GAS pharyngitis and 37.9% had GAS detected without serological response. Elevated ASO titres were associated with GAS pharyngitis and elevated ADB titres were associated with GAS skin infections in New Zealand children. Higher ASO/ADB titres in healthy Māori and Pacific children could indicate a greater prior exposure to GAS infections.
Group A streptococcus, pyoderma, and rheumatic fever
Publisher: Elsevier BV
Date: 05-1996
DOI: 10.1016/S0140-6736(96)90797-7
Abstract: Background Austrian pharmacists are not authorised to administer immunisations, and evidence about their willingness to immunise is lacking. Aim The aim of this study is to investigate Austrian community pharmacists' willingness to administer immunisations in the future. Method This study is designed as a cross-sectional online survey based on the theoretical domains framework (TDF). The validated and piloted questionnaire obtained ethical approval by Robert Gordon University. Outcome measures included pharmacists' willingness to immunise, service requirements, barriers and education needs. Results The questionnaire was sent out to 3086 community pharmacists of which 380 responses were included in the final analysis (12.3%). Willingness to administer immunisations after appropriate training and legislative regulation was stated by 82.6% (n = 314) of participants. It was demonstrated that pharmacists willing to immunise were significantly younger than their counterpart (38 [IQR 31-49] years vs. 45 [IQR 37.5-54] years OR 1.06 1.03-1.09, 95% CI p < 0.001). 'Legal liability' was considered the most critical barrier to service implementation, 'seeing blood' and 'close patient contact' as least critical. Pharmacists not willing to immunise showed a higher probability to evaluate personnel resources (OR 2.98 1.35-6.58, 95% CI p = 0.007), close patient contact (OR 2.79 1.46-5.34, 95% CI p = 0.002) and management of side effects (OR 2.62 1.21-5.67, 95% CI p = 0.015) as (highly) critical. The majority assessed the 'right timing for training' to be after the foundation training with a 2-yearly renewal. Conclusion Austrian community pharmacists show a strong willingness to administer immunisations while highlighting important requirements and barriers towards service implementation.
Strongyloides seroprevalence before and after an ivermectin mass drug administration in a remote Australian Aboriginal community
Publisher: Public Library of Science (PLoS)
Date: 15-05-2017
School-based intervention to address self-regulation and executive functioning in children attending primary schools in remote Australian Aboriginal communities
Publisher: Public Library of Science (PLoS)
Date: 24-06-2020
Acute Rheumatic Fever and Chronic Rheumatic Disease
Publisher: Springer London
Date: 18-09-2013
The burden and cost of hospitalised varicella and zoster in Australian children
Publisher: Elsevier BV
Date: 12-2004
DOI: 10.1016/J.VACCINE.2004.07.025
Abstract: Economic analyses of varicella-zoster virus (VZV) immunisation are sensitive to the costs of hospitalised cases, so there is a need to validate VZV hospitalisation data. To assess the accuracy of hospital VZV coding data and to apply these parameters to a population-based s le to estimate incidence and costs. A 3-year retrospective chart review from one hospital to document clinical features and validate coding data. A separate 9-year analysis of discharge data from two hospitals draining a defined region of suburban Melbourne, with adjustment for miscoding and estimates of direct hospital costs. After correction for miscoding, 224 patients were admitted to one hospital over 3 years, 79% with varicella and 21% with zoster. Miscoding resulted in a 15% underestimate of zoster cases and a 4% overestimate of varicella cases. Thirty-six percent of varicella admissions compared to 80% of zoster admissions were immunocompromised and/or had chronic disease. Compared to otherwise-healthy patients, immunocompromised patients were admitted earlier in their illness and had lower complication rates. Forty-two percent of immunocompromised/chronic disease patients with varicella had a known exposure, usually from a family member. The incidence of hospitalised varicella and zoster in under 15-year olds was 15.7 and 1.8 per 100,000 per year, respectively. This suggests that there are 615 varicella hospitalisations and 72 zoster hospitalisations in this age group each year in Australia, at a total direct cost of over 2.2 million AU dollars. These results highlight the considerable burden of hospitalised zoster and the importance of immunising non-immune contacts of immunocompromised in iduals. They also support previous estimates of the incidence of hospitalised varicella in Australian children and adolescents, although direct medical costs may be higher than those previously estimated.
Acute rheumatic fever (ARF) in non-Aboriginal patients in the Northern Territory
Publisher: Wiley
Date: 02-1998
Preventing urinary tract infections in early childhood.
Publisher: Springer New York
Date: 11-12-2013
DOI: 10.1007/978-1-4614-4726-9_18
Abstract: Urinary tract infection (UTI) is common in children, causes them considerable discomfort, as well as distress to parents and has a tendency to recur. Approximately 20% of those children who experience one infection will have a repeat episode. Since 1975, 11 trials of long-term antibiotics compared with placebo or no treatment in 1,550 children have been published. Results have been heterogeneous, but the largest trial demonstrated a small reduction (6% absolute risk reduction, risk ratio 0.65) in the risk of repeat symptomatic UTI over 12 months of treatment. This effect was consistent across sub groups of children based upon age, gender, vesicoureteric reflux status and number of prior infections. Trials involving re-implantation surgery (and antibiotics compared with antibiotics alone) for the sub-group of children with vesicoureteric reflux have not shown a reduction in repeat UTI, with the possible exception of a very small benefit for febrile UTI. Systematic reviews have shown that circumcision reduces the risk of repeat infection but 111 circumcisions would need to be performed to prevent one UTI in unpredisposed boys. Given the need for anaesthesia and the risk of surgical complication, net clinical benefit is probably restricted to those who are predisposed (such as those with recurrent infection). Many small trials in complementary therapies have been published and many suggest some benefit, however inclusion of children is limited. Only three trials involving 394 children for cranberry products, two trials with a total of 252 children for probiotics and one trial with 24 children for vitamin A are published. Estimates of efficacy vary widely and imprecision is evident. Multiple interventions to prevent UTI in children exist. Of those, long-term low dose antibiotics has the strongest evidence base, but the benefit is small. Circumcision in boys reduces the risk substantially, but should be restricted to those at risk. There is little evidence of benefit of re-implantation alone, and the benefit of this procedure over antibiotics alone is very small. Cranberry concentrate is probably effective.
Reply to Letter Regarding Article, “Acute Rheumatic Fever and Rheumatic Heart Disease: Incidence and Progression in the Northern Territory of Australia, 1997 to 2010”
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-03-2014
Working towards a Group A Streptococcal vaccine: Report of a collaborative Trans-Tasman workshop
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1016/J.VACCINE.2014.05.017
Abstract: Group A Streptococcus (GAS) infections represent a major public health burden in both developing and developed countries. In Australia and New Zealand GAS associated diseases are serious problems in Indigenous populations and a major cause of health inequality. Political recognition of these inequalities is providing impetus for strategies that reduce GAS disease and the development of a GAS vaccine now has governmental support in both Australia and New Zealand. Accordingly, an expert workshop was convened in March 2013 to consider available data on GAS vaccines. M-protein based vaccines constructed from the hyper-variable N-terminal region (30-valent vaccine) or the conserved C-repeat domain (J8 vaccine) were reviewed together with vaccine candidates identified using multi high-throughput approaches. Performing a comprehensive assessment of regional GAS strain epidemiology, defining the immune correlates of protection, and the establishment of clinical trial sites were identified as critical activities for a Trans-Tasman vaccine development programme.
Sore throat: Is it such a big deal anymore?
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.JINF.2015.04.010
Abstract: Sore throat remains a common disease of childhood, and a major cost and cause for antibiotic prescriptions. The management of sore throat remains controversial in affluent countries with various guidelines available and overall poor adherence to those guidelines. Group A streptococcus is the commonest bacterial cause with important sequelae including acute rheumatic fever (ARF). The driver for diagnosis and treatment is still questionable. In most affluent populations it is difficult to justify antibiotic treatment on the basis of preventing ARF, whereas this remains the major driver for sore throat management in populations at higher risk of ARF. Reduction in severity and duration of symptoms may be a reasonable basis to consider antibiotic treatment, and thus accurate diagnosis of GAS pharyngitis, particularly in those with more severe symptoms. The potential role of rapid tests in diagnosis appears to be increasing.
Going with the flow: Pre-service teacher learning in, about and with community
Publisher: Springer Singapore
Date: 2017
Group A streptococcal vaccines: facts versus fantasy
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2009
Leuconostoc sepsis in association with continous enteral feeding
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-1994
Utility of auscultatory screening for detecting rheumatic heart disease in high-risk children in Australia's Northern Territory
Publisher: AMPCo
Date: 08-2013
DOI: 10.5694/MJA13.10520
Abstract: To evaluate the utility of auscultatory screening for detecting echocardiographically confirmed rheumatic heart disease (RHD) in high-risk children in the Northern Territory, Australia. Cross-sectional screening survey. Twelve rural and remote communities in the NT between September 2008 and June 2010. 1015 predominantly Indigenous schoolchildren aged 5-15 2013s. All children underwent transthoracic echocardiography, using a portable cardiovascular ultrasound machine, and cardiac auscultation by a doctor and a nurse. Sonographers and auscultators were blinded to each others' findings and the clinical history of the children. Echocardiograms were reported offsite, using a standardised protocol, by cardiologists who were also blinded to the clinical findings. Presence of a cardiac murmur as identified by nurses (any murmur) and doctors (any murmur, and "suspicious" or "pathological" murmurs), compared with echocardiogram findings. RHD was defined according to the 2012 World Heart Federation criteria for echocardiographic diagnosis of RHD. Of the 1015 children screened, 34 (3.3%) had abnormalities identified on their echocardiogram 24 met echocardiographic criteria for definite or borderline RHD, and 10 had isolated congenital anomalies. Detection of any murmur by a nurse had a sensitivity of 47.1%, specificity of 74.8% and positive predictive value (PPV) of 6.1%. Doctor identification of any murmur had 38.2% sensitivity, 75.1% specificity and 5.1% PPV, and the corresponding values for doctor detection of suspicious or pathological murmurs were 20.6%, 92.2% and 8.3%. For all auscultation approaches, negative predictive value was more than 97%, but the majority of participants with cardiac abnormalities were not identified. The results were no different when only definite RHD and congenital abnormalities were considered as true cases. Sensitivity and positive predictive value of cardiac auscultation compared with echocardiography is poor, regardless of the expertise of the auscultator. Although negative predictive value is high, most cases of heart disease were missed by auscultation, suggesting that cardiac auscultation should no longer be used to screen for RHD in high-risk schoolchildren in Australia.
Standardizing clinical care measures of rheumatic heart disease in pregnancy: A qualitative synthesis
Publisher: Wiley
Date: 31-05-2019
DOI: 10.1111/BIRT.12435
Abstract: Rheumatic heart disease (RHD) is a preventable cardiac condition that escalates risk in pregnancy. Models of care informed by evidence-based clinical guidelines are essential to optimal health outcomes. There are no published reviews that systematically explore approaches to care provision for pregnant women with RHD and examine reported measures. The review objective was to improve understanding of how attributes of care for these women are reported and how they align with guidelines. A search of 13 databases was supported by hand-searching. Papers that met inclusion criteria were appraised using CASP/JBI checklists. A content analysis of extracted data from the findings sections of included papers was undertaken, informed by attributes of quality care identified previously from existing guidelines. The 43 included studies were predominantly conducted in tertiary care centers of low-income and middle-income countries. Cardiac guidelines were referred to in 25 of 43 studies. Poorer outcomes were associated with higher risk scores (detailed in 36 of 41 quantitative studies). Indicators associated with increased risk include anticoagulation during pregnancy (28 of 41 reported) and late booking (gestation documented in 15 of 41 studies). Limited access to cardiac interventions was discussed (19 of 43) in the context of poorer outcomes. Conversely, early assessment and access to regular multidisciplinary care were emphasized in promoting optimal outcomes for women and their babies. Despite often complex care requirements in challenging environments, pregnancy provides an opportunity to strengthen health system responses and address whole-of-life health for women with RHD. A standard set of core indicators is proposed to more accurately benchmark care pathways, outcomes, and burden.
Streptococcus pyogenes recruits collagen via surface-bound fibronectin: a novel colonization and immune evasion mechanism
Publisher: Wiley
Date: 15-01-2003
DOI: 10.1046/J.1365-2958.2003.03352.X
Abstract: This study aimed to characterize matrix assembly mechanisms on the surface of the human pathogen Streptococcus pyogenes. Among 125 S. pyogenes isolates, 61% were able to recruit collagen type IV via surface-bound fibronectin. Streptococcus gordonii expressing the fibronectin-binding repeat domain of S. pyogenes SfbI protein was equally potent in recruiting collagen, indicating that this domain was sufficient to promote fibronectin-mediated collagen recruitment. Electron microscopic analysis of streptococci revealed that fibronectin-mediated collagen recruitment led to matrix deposition on and between streptococcal cells, which induced the formation of large bacterial aggregates. Furthermore, collagen-recruiting streptococci were able to colonize collagen fibres and were protected from adhering to human polymorphonuclear cells in the presence of opsonizing antibodies. Fibronectin-mediated collagen recruitment thus represents a novel aggregation, colonization and immune evasion mechanism of S. pyogenes.
Acute rheumatic fever and rheumatic heart disease in Fiji: prospective surveillance, 2005–2007
Publisher: Wiley
Date: 02-2009
DOI: 10.5694/J.1326-5377.2009.TB02312.X
Abstract: To determine the incidence and clinical features of acute rheumatic fever (ARF) in Fiji, and the clinical features of patients presenting to hospital in Fiji with rheumatic heart disease (RHD). A prospective surveillance study at the Colonial War Memorial Hospital in Suva over a 23-month period from December 2005 to November 2007. Incidence of ARF clinical features of ARF and RHD. The average annualised incidence of definite cases of ARF in children aged 5-15 years was 15.2 per 100,000 (95% CI, 9.0-22.6). The clinical features of ARF were similar to those in classic descriptions. Carditis was very common, occurring in 79% of cases. There were 103 admissions for RHD in which detailed information was collected, with the most common reason for admission being cardiac failure (51%). The median age at admission with RHD was 26.8 years, and there were 10 deaths of patients with RHD (case fatality rate, 9.7%). Although apparently declining in incidence since the middle of the 20th century, ARF remains a significant health problem in Fiji. RHD affects young people, leading to premature morbidity and mortality. There is an urgent need for effective control of ARF and RHD in Fiji.
Preliminary consultation on preferred product characteristics of benzathine penicillin G for secondary prophylaxis of rheumatic fever
Publisher: Springer Science and Business Media LLC
Date: 27-07-2016
DOI: 10.1007/S13346-016-0313-Z
Abstract: Rheumatic fever is caused by an abnormal immune reaction to group A streptococcal infection. Secondary prophylaxis with antibiotics is recommended for people after their initial episode of rheumatic fever to prevent recurrent group A streptococcal infections, recurrences of rheumatic fever and progression to rheumatic heart disease. This secondary prophylaxis must be maintained for at least a decade after the last episode of rheumatic fever. Benzathine penicillin G is the first line antibiotic for secondary prophylaxis, delivered intramuscularly every 2 to 4 weeks. However, adherence to recommended secondary prophylaxis regimens is a global challenge. This paper outlines a consultation with global experts in rheumatic heart disease on the characteristics of benzathine penicillin G formulations which could be changed to improve adherence with secondary prophylaxis. Characteristics included dose interval, pain, administration mechanism, cold chain independence and cost. A s le target product profile for reformulated benzathine penicillin G is presented.
Group A streptococcal vaccines: Paving a path for accelerated development
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.VACCINE.2012.09.045
Abstract: Group A streptococci (GAS) are important causes of morbidity and mortality worldwide. These organisms cause a wide spectrum of disease, ranging from uncomplicated sore throat to invasive, life-threatening infections, as well as immune complications such as acute rheumatic fever (ARF), rheumatic heart disease (RHD) and acute post-streptococcal glomerulonephritis (APSGN). Vaccine prevention of GAS infections and their immunological complications has been a goal of researchers for decades. Several vaccine candidates against GAS infection are in various stages of pre-clinical and clinical development, including M protein-based vaccines (N-terminal vaccine candidates and M protein conserved region vaccines), and non-M protein vaccine candidates representing conserved GAS antigens. Some of the obstacles to GAS vaccine development are related to the complexity of the global epidemiology of GAS infections, the limitation in the criteria for selection of antigens to include in combination vaccines as well as the issues around autoimmunity and vaccine safety, among others. Overcoming these obstacles will require collaborative efforts to develop innovative strategies that address key steps in the pre-clinical and clinical development process, as well as clearly defining the global burden of GAS diseases and the molecular epidemiology of infections. Specific recommendations are presented for an accelerated plan leading to the introduction of a broadly protective vaccine designed for deployment in low-, middle-, and high-income countries.
Environmental and social determinants of acute rheumatic fever
Publisher: Cambridge University Press (CUP)
Date: 2019
DOI: 10.1017/S0950268818003527
Abstract: Acute rheumatic fever (ARF), an auto-immune response to a group A Streptococcus infection and precursor to rheumatic heart disease (RHD), remains endemic in many socio-economically disadvantaged settings. A Global Resolution on ARF and RHD was recently adopted at the 71st World Health Assembly where governments committed to improving efforts to prevent and control ARF and RHD. To inform these efforts, the objectives of this study were to examine associations between childhood ARF in the UK between 1958 and 1969 and a range of environmental and social factors. Of 17 416 children from the nationally representative birth cohort of the National Child Development Study, ARF was reported in 23 children during early childhood (between birth and the 7-year follow-up) and in 29 additional children during middle childhood (between the 7- and 11-year follow-ups). Risk factors associated with ARF in both early and middle childhood were: a large family size attendance at a private nursery or class a history of nephritis, kidney or urinary tract infections and a history of throat or ear infections. Risk factors for ARF in early childhood alone were families with fathers in a professional or semi-professional occupation and families who moved out of their local neighbourhood. Risk factors in late childhood alone included overcrowding and free school meals. These data suggest that prevention strategies in ARF endemic settings may be enhanced by targeting, for ex le, new members entering a community and children in environments of close contact, such as a nursery or shared bedrooms.
Diversity of emm sequence types in group A beta-haemolytic streptococci in two remote Northern Territory Indigenous communities: implications for vaccine development.
Publisher: Elsevier BV
Date: 07-2010
DOI: 10.1016/J.VACCINE.2010.05.046
Abstract: There is a high burden of disease due to group A streptococcus (GAS) in remote Northern Territory (NT) Indigenous communities. A proposed 26-valent GAS M-type vaccine covers 80-90% of pharyngeal and invasive isolates in the US. We examined the ersity and distribution of emm types in two remote Indigenous communities in the NT Top End over a 17-year period and compared them to the proposed vaccine types. Eighty emm types were identified between 1991 and 2007. Diversity in both communities was high (overall Simpson's index 0.976), but varied between communities. Prior to 2004, 71 emm types were identified and an additional 9 emm types were identified during a period of active surveillance in 2004-2005. The proposed 26-valent vaccine would be expected to cover only 20% of emm types recovered in this study. Of the 80 emm types, 16 (20%) were new sequence types identified since the last assignment of M types in 2002. The ersity of streptococcal isolates was higher than that reported from most industrialized countries, and similar to that described in several developing countries. A vaccine based on such a variable antigen is unlikely to provide effective protection in the highest risk populations.
The Diagnosis and Management of Chronic Rheumatic Heart Disease—An Australian Guideline
Publisher: Elsevier BV
Date: 08-2008
Prevention and treatment of rheumatic heart disease in the developing world
Publisher: Springer Science and Business Media LLC
Date: 15-09-2009
DOI: 10.1038/NRCARDIO.2009.162
Abstract: The prevalence of rheumatic heart disease (RHD) in industrialized countries has declined dramatically over the last century, but the disease remains an important global health problem with the burden of disease shouldered by developing countries. Indeed, data from epidemiologic surveys, which used echocardiography as the primary screening tool, indicate that the prevalence of RHD in developing nations might have been substantially underestimated. Despite the high burden of disease globally, there has never been a sustained and comprehensive international strategy to control RHD. The current focus of global efforts to combat the disease is on strengthening secondary prophylaxis strategies, although very few active national programs have been implemented. RHD will continue to cause high morbidity and mortality among the world's poorest populations unless current prevention initiatives expand and new programs are established.
The epidemiology of invasive group A streptococcal disease in Victoria, Australia
Publisher: AMPCo
Date: 06-2007
DOI: 10.5694/J.1326-5377.2007.TB01054.X
Abstract: To estimate the incidence and severity of invasive group A streptococcal infection in Victoria, Australia. Prospective active surveillance study. Public and private laboratories, hospitals and general practitioners throughout Victoria. People in Victoria diagnosed with group A streptococcal disease notified to the surveillance system between 1 March 2002 and 31 August 2004. Confirmed invasive group A streptococcal disease. We identified 333 confirmed cases: an average annual incidence rate of 2.7 (95% CI, 2.3-3.2) per 100,000 population per year. Rates were highest in people aged 65 years and older and those younger than 5 years. The case-fatality rate was 7.8%. Streptococcal toxic shock syndrome occurred in 48 patients (14.4%), with a case-fatality rate of 23%. Thirty cases of necrotising fasciitis were reported five (17%) of these patients died. Type 1 (23%) was the most frequently identified emm sequence type in all age groups. All tested isolates were susceptible to penicillin and clindamycin. Two isolates (4%) were resistant to erythromycin. The incidence of invasive group A streptococcal disease in temperate Australia is greater than previously appreciated and warrants greater public health attention, including its designation as a notifiable disease.
Evaluating the use of penicillin to control outbreaks of acute poststreptococcal glomerulonephritis
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-1999
DOI: 10.1097/00006454-199904000-00003
Abstract: Outbreaks of acute poststreptococcal glomerulonephritis (APSGN), occur every few years in remote Australian Aboriginal communities. Intervention with benzathine penicillin G (BPG) to all children is effective in reducing streptococcal carriage in a community, but its effectiveness in arresting outbreaks of APSGN has not been established. To study nine recent community outbreaks of APSGN in Australia's Northern Territory and compare them with outbreaks reported in the literature to assess the impact of intervention with BPG. Because randomized controlled trials have not been conducted for this purpose, we assessed data from published observational studies and relevant experiences in the Northern Territory (NT). Eight of the nine outbreaks in the NT were studied prospectively. An outbreak was defined as two or more clinical cases of APSGN occurring within 1 week in a single community. Three intervention methods were used: intramuscular BPG to all children ages 3 to 15 years BPG only to children with skin lesions and BPG only to child contacts of clinical cases. The attack rates, number of clinical cases before and after the interventions were documented and the coverage of children with penicillin were estimated. A review of the literature found very little evidence either for or against the effectiveness of intervention with BPG. In our study four communities used the first method of intervention. The community with the lowest uptake of penicillin continued to have cases in untreated children for 9 further weeks, two communities had no new cases from 3 weeks after the intervention and the fourth had a single further case after 4 weeks. The one community that used the second method had a high initial attack rate but no further cases from 1 week after the intervention. Three communities used the third method and in one community no intervention was attempted. Our observational study supports the use of BPG in the community to prevent new cases of APSGN. It suggests that targeted treatment of children with skin sores and household contacts of cases, rather than attempted treatment of all children in the community, could be an effective method of intervention.
Skin Disorders, Including Pyoderma, Scabies, and Tinea Infections
Publisher: Elsevier BV
Date: 12-2009
DOI: 10.1016/J.PCL.2009.09.002
Abstract: Pyoderma, scabies, and tinea are common childhood skin disorders too often considered to be merely of nuisance value. More than 111 million children are believed to have pyoderma, with many also co-infected with scabies, tinea, or both. These skin disorders cannot be differentiated by ethnicity or socioeconomic status but, in high-prevalence areas, poverty and overcrowded living conditions are important underlying social determinants. Each is transmitted primarily through direct skin-to-skin contact. For many Indigenous children, these skin conditions are part of everyday life. Although rarely directly resulting in hospitalization or death, there is a high and largely unmet demand for effective management at the primary health-care level, particularly for pyoderma and scabies. Despite particularly high prevalence in some settings, treatment is not sought for many children, and when sought, the clinical benefit from such consultations is variable. The lack of standard, evidence-based recommendations is of much concern. The current evidence base for clinical diagnosis and treatment of these common childhood skin disorders is highlighted.
Superantigen genes in group A streptococcal isolates and their relationship with emm types
Publisher: Microbiology Society
Date: 10-2008
DOI: 10.1099/JMM.0.2008/001156-0
Abstract: Superantigens are important virulence factors in the pathogenesis of invasive disease caused by group A streptococcus (GAS). There has been a recent re-emergence of this disease worldwide. A number of novel superantigens have been described recently. This study investigated 107 isolates of GAS for possession of each of the 11 currently known superantigen genes to determine the prevalence, co-occurrence and genetic restriction amongst different emm types of GAS. The results were compared with those in previously published studies. Superantigen genes were not randomly distributed amongst GAS isolates. Certain combinations of superantigen genes were more common and the majority of emm types showed restricted superantigen profiles. This is the first prevalence study of GAS isolates to include the complete range of known superantigen genes and their restriction amongst emm types. This study contributes to the understanding of the relationship between superantigen genes and emm types, and highlights the importance of comprehensive studies in different populations.
Development of an opsonophagocytic killing assay for group a streptococcus
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1016/J.VACCINE.2018.05.056
Abstract: Group A Streptococcus (GAS) or Streptococcus pyogenes is responsible for an estimated 500,000 deaths worldwide each year. Protection against GAS infection is thought to be mediated by phagocytosis, enhanced by bacteria-specific antibody. There are no licenced GAS vaccines, despite many promising candidates in preclinical and early stage clinical development, the most advanced of which are based on the GAS M-protein. Vaccine progress has been hindered, in part, by the lack of a standardised functional assay suitable for vaccine evaluation. Current assays, developed over 50 years ago, rely on non-immune human whole blood as a source of neutrophils and complement. Variations in complement and neutrophil activity between donors result in variable data that is difficult to interpret. We have developed an opsonophagocytic killing assay (OPKA) for GAS that utilises dimethylformamide (DMF)-differentiated human promyelocytic leukemia cells (HL-60) as a source of neutrophils and baby rabbit complement, thus removing the major sources of variation in current assays. We have standardised the OPKA for several clinically relevant GAS strain types (emm1, emm6 and emm12) and have shown antibody-specific killing for each emm-type using M-protein specific rabbit antisera. Specificity was demonstrated by pre-incubation of the antisera with homologous M-protein antigens that blocked antibody-specific killing. Additional qualifications of the GAS OPKA, including the assessment of the accuracy, precision, linearity and the lower limit of quantification, were also performed. This GAS OPKA assay has the potential to provide a robust and reproducible platform to accelerate GAS vaccine development.
Host-dependent resistance of Group A Streptococcus to sulfamethoxazole mediated by a horizontally-acquired reduced folate transporter.
Publisher: Springer Science and Business Media LLC
Date: 30-11-2022
DOI: 10.1038/S41467-022-34243-3
Abstract: Described antimicrobial resistance mechanisms enable bacteria to avoid the direct effects of antibiotics and can be monitored by in vitro susceptibility testing and genetic methods. Here we describe a mechanism of sulfamethoxazole resistance that requires a host metabolite for activity. Using a combination of in vitro evolution and metabolic rescue experiments, we identify an energy-coupling factor (ECF) transporter S component gene ( thfT ) that enables Group A Streptococcus to acquire extracellular reduced folate compounds. ThfT likely expands the substrate specificity of an endogenous ECF transporter to acquire reduced folate compounds directly from the host, thereby bypassing the inhibition of folate biosynthesis by sulfamethoxazole. As such, ThfT is a functional equivalent of eukaryotic folate uptake pathways that confers very high levels of resistance to sulfamethoxazole, yet remains undetectable when Group A Streptococcus is grown in the absence of reduced folates. Our study highlights the need to understand how antibiotic susceptibility of pathogens might function during infections to identify additional mechanisms of resistance and reduce ineffective antibiotic use and treatment failures, which in turn further contribute to the spread of antimicrobial resistance genes amongst bacterial pathogens.
Australian researchers oppose funding from the Foundation for a Smoke-Free World
Publisher: Elsevier BV
Date: 12-2018
Missing Piece Study protocol
Publisher: BMJ
Date: 04-2022
DOI: 10.1136/BMJOPEN-2021-057296
Abstract: Group A β-haemolytic Streptococcus (GAS), a Gram-positive bacterium, causes skin, mucosal and systemic infections. Repeated GAS infections can lead to autoimmune diseases acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Aboriginal and Torres Strait Islander peoples in Australia have the highest rates of ARF and RHD in the world. Despite this, the contemporaneous prevalence and incidence of GAS pharyngitis and impetigo in remote Australia remains unknown. To address this, we have designed a prospective surveillance study of GAS pharyngitis and impetigo to collect coincident contemporary evidence to inform and enhance primary prevention strategies for ARF. The Missing Piece Study aims to document the epidemiology of GAS pharyngitis and impetigo through collection of clinical, serological, microbiological and bacterial genomic data among remote-living Australian children. The study comprises two components: (1) screening of all children at school for GAS pharyngitis and impetigo up to three times a year and (2) weekly active surveillance visits to detect new cases of pharyngitis and impetigo. Environmental swabbing in remote schools will be included, to inform environmental health interventions. In addition, the application of new diagnostic technologies, microbiome analysis and bacterial genomic evaluations will enhance primary prevention strategies, having direct bearing on clinical care, vaccine development and surveillance for vaccine clinical trials. Ethical approval has been obtained from the Western Australian Aboriginal Health Ethics Committee (Ref: 892) and Human Research Ethics Committee of the University of Western Australia (Ref: RA/4/20/5101). Study findings will be shared with community members, teachers and children at participating schools, together with academic and medical services. Sharing findings in an appropriate manner is important and will be done in a suitable way which includes plain language summaries and presentations. Finally, findings and updates will also be disseminated to collaborators, researchers and health planners through peer-reviewed journal publications.
Sulfamethoxazole-Trimethoprim (Cotrimoxazole) for Skin and Soft Tissue Infections Including Impetigo, Cellulitis, and Abscess
Publisher: Oxford University Press (OUP)
Date: 2017
DOI: 10.1093/OFID/OFX232
Abstract: Skin and soft tissue infections (SSTI) affect millions of people globally, which represents a significant burden on ambulatory care and hospital settings. The role of sulfamethoxazole-trimethoprim (SXT) in SSTI treatment, particularly when group A Streptococcus (GAS) is involved, is controversial. We conducted a systematic review of clinical trials and observational studies that address the utility of SXT for SSTI treatment, caused by either GAS or Staphylococcus aureus, including methicillin-resistant (MRSA). We identified 196 studies, and 15 underwent full text review by 2 reviewers. Observational studies, which mainly focused on SSTI due to S aureus, supported the use of SXT when compared with clindamycin or β-lactams. Of 10 randomized controlled trials, 8 demonstrated the efficacy of SXT for SSTI treatment including conditions involving GAS. These findings support SXT use for treatment of impetigo and purulent cellulitis (without an additional β-lactam agent) and abscess and wound infection. For nonpurulent cellulitis, β-lactams remain the treatment of choice.
Diagnosis and treatment of invasive group A streptococcal infections
Publisher: Informa UK Limited
Date: 03-2008
Abstract: Invasive group A streptococcal infections are serious infections that carry a high mortality. The aim was to review current methods of diagnosis and treatment of invasive group A streptococcal infections as well as to provide background on the pathogenesis and epidemiology of these infections. The most recent literature regarding pathogenesis, epidemiology, diagnosis and treatment of invasive group A streptococcal infections is reviewed. The incidence of invasive group A streptococcal infections in industrialised countries is in the order of 3 per 100,000, whereas in developing countries available evidence suggests that the incidence is several-fold higher. Management of invasive group A streptococcal infections includes supportive care, surgical debridement of necrotic tissue, correct use of antibiotics, intravenous immunoglobulin and contact prophylaxis. Recent studies suggest that the early use of intravenous immunoglobulin may reduce the need for radical debridement of tissue in cases of necrotising fasciitis.
New normal ranges of antistreptolysin O and antideoxyribonuclease B titres for Australian children
Publisher: Wiley
Date: 11-2005
DOI: 10.1111/J.1440-1754.2005.00726.X
Abstract: To determine age-specific upper limit of normal (ULN) values of the ASO and ADB titres in children aged 4-14 years in urban Melbourne. Serology is often used to diagnose a preceding Streptococcus pyogenes infection, particularly in potential cases of rheumatic fever and post-streptococcal glomerulonephritis. The most commonly used antigens are antistreptolysin O (ASO) and antideoxyribonuclease B (ADB). Reference ranges used in Australia for these serological markers are usually based on data in adults from other countries. There are no age-specific reference values for Australian children. Sixty-six sera from children with no history of recent streptococcal infection were obtained in May-June 2002. The children were ided into three age groups for analysis: 4-5 (n = 20), 6-9 (n = 19) and 10-14 (n = 25) years. The geometric mean titre and ULN (defined as the 80th percentile) for the ASO and ADB titres for each age group were determined in both international and log units. The ULN for ASO titres in each age group was 120 (2.08 log units), 480 (2.68) and 320 (2.51). The ULN for ADB titres in each age group was 100 (2.00 log units), 400 (2.60) and 380 (2.58). The ASO and ADB ULN values in school-aged children are higher than the current reference ranges suggest.
The burden of bacterial skin infection, scabies and atopic dermatitis among urban-living Indigenous children in high-income countries: a protocol for a systematic review
Publisher: Springer Science and Business Media LLC
Date: 09-08-2022
DOI: 10.1186/S13643-022-02038-8
Abstract: Bacterial skin infections and scabies disproportionately affect children in resource-poor countries as well as underprivileged children in high-income countries. Atopic dermatitis is a common childhood dermatosis that predisposes to bacterial skin infection. In Australia, at any one time, almost half of all Aboriginal and Torres Strait Islander children living remotely will have impetigo, and up to one-third will also have scabies. Yet, there is a gap in knowledge of the skin infection burden for urban-living Australian Aboriginal and Torres Strait Islander children, as well as atopic dermatitis which may be a contributing factor. The objective of this study is to provide a global background on the burden of these disorders in Indigenous urban-living children in high-income countries. These countries share a similar history of colonisation, dispossession and subsequent ongoing negative impacts on Indigenous people. This protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols statement. Observational studies reporting incidence and/or prevalence data on bacterial skin infection, scabies and/or atopic dermatitis in urban-living Indigenous children in high-income countries will be included. Literature searches will be conducted in several international electronic databases (from 1990 onwards), including MEDLINE, Embase, EmCare, Web of Science and PubMed. Reference lists and citation records of all included articles will be scanned for additional relevant manuscripts. Two investigators will independently perform eligibility assessment of titles, abstract and full-text manuscripts, following which both investigators will independently extract data. Where there is disagreement, the senior author will determine eligibility. The methodological quality of selected studies will be appraised using an appropriate tool. Data will be tabulated and narratively synthesised. We expect there will be insufficient data to perform meta-analysis. This study will identify and evaluate epidemiological data on bacterial skin infection, scabies and atopic dermatitis in urban-living Indigenous children in high-income countries. Where available, the clinical features, risk factors, comorbidities and complications of these common childhood skin disorders will be described. The evidence will highlight the burden of disease in this population, to contribute to global burden of disease estimates and identify gaps in the current literature to provide direction for future research. PROSPERO CRD42021277288
Incidence of acute rheumatic fever in northern and western Uganda: a prospective, population-based study
Publisher: Elsevier BV
Date: 10-2021
Acute rheumatic fever and rheumatic heart disease in indigenous populations.
Publisher: Elsevier BV
Date: 12-2009
DOI: 10.1016/J.PCL.2009.09.011
Abstract: Acute rheumatic fever and rheumatic heart disease are diseases of socioeconomic disadvantage. These diseases are common in developing countries and in Indigenous populations in industrialized countries. Clinicians who work with Indigenous populations need to maintain a high index of suspicion for the potential diagnosis of acute rheumatic fever, particularly in patients presenting with joint pain. Inexpensive medicines, such as aspirin, are the mainstay of symptomatic treatment of rheumatic fever however, antiinflammatory treatment has no effect on the long-term rate of progression or severity of chronic valvular disease. The current focus of global efforts at prevention of rheumatic heart disease is on secondary prevention (regular administration of penicillin to prevent recurrent rheumatic fever), although primary prevention (timely treatment of streptococcal pharyngitis to prevent rheumatic fever) is also important in populations in which it is feasible.
Acute Rheumatic Fever and Rheumatic Heart Disease
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 30-07-2013
DOI: 10.1161/CIRCULATIONAHA.113.001477
Abstract: Although acute rheumatic fever (ARF) and its sequel, rheumatic heart disease (RHD), continue to cause a large burden of morbidity and mortality in disadvantaged populations, most studies investigating the effectiveness of control programs date from the 1950s. A control program, including a disease register, in the Northern Territory of Australia where the Indigenous population has high rates of ARF and RHD allowed us to examine current disease incidence and progression. ARF and RHD incidence rates, ARF recurrence rates, progression rates from ARF to RHD to heart failure, and RHD survival and mortality rates were calculated for Northern Territory residents from 1997 to 2010. For Indigenous people, ARF incidence was highest in the 5- to 14-year age group (males, 162 per 100 000 females, 228 per 100 000). There was little evidence that the incidence of ARF or RHD had declined. The ARF recurrence rate declined by 9% per year after diagnosis. After a first ARF diagnosis, 61% developed RHD within 10 years. After RHD diagnosis, 27% developed heart failure within 5 years. For Indigenous RHD patients, the relative survival rate was 88.4% at 10 years after diagnosis and the standardized mortality ratio was 1.56 (95% confidence interval, 1.23–1.96). For Indigenous Australians in the Northern Territory, ARF and RHD incidence and associated mortality remain very high. The reduction in ARF recurrence indicates that the RHD control program has improved secondary prophylaxis a decline in RHD incidence is expected to follow.
Reference exome data for Australian Aboriginal populations to support health-based research
Publisher: Springer Science and Business Media LLC
Date: 29-04-2020
DOI: 10.1038/S41597-020-0463-1
Abstract: Whole exome sequencing (WES) is a popular and successful technology which is widely used in both research and clinical settings. However, there is a paucity of reference data for Aboriginal Australians to underpin the translation of health-based genomic research. Here we provide a catalogue of variants called after sequencing the exomes of 50 Aboriginal in iduals from the Northern Territory (NT) of Australia and compare these to 72 previously published exomes from a Western Australian (WA) population of Martu origin. Sequence data for both NT and WA s les were processed using an ‘intersect-then-combine’ (ITC) approach, using GATK and SAMtools to call variants. A total of 289,829 variants were identified in at least one in idual in the NT cohort and 248,374 variants in at least one in idual in the WA cohort. Of these, 166,719 variants were present in both cohorts, whilst 123,110 variants were private to the NT cohort and 81,655 were private to the WA cohort. Our data set provides a useful reference point for genomic studies on Aboriginal Australians.
SKIN SORES IN ABORIGINAL CHILDREN
Publisher: Wiley
Date: 12-1995
Community Epidemiology of Human Metapneumovirus, Human Coronavirus NL63, and Other Respiratory Viruses in Healthy Preschool-Aged Children Using Parent-Collected Specimens
Publisher: American Academy of Pediatrics (AAP)
Date: 10-2007
Abstract: OBJECTIVES. The purpose of this work was to assess the impact of recently described human metapneumovirus and human coronavirus NL63 compared with other respiratory viruses by using sensitive molecular techniques in a cohort of healthy preschool-aged children. We also aimed to assess the use of parent collection to obtain an adequate respiratory specimen from acutely unwell children in the community. PATIENTS AND METHODS. The community epidemiology and burden of human metapneumovirus and other respiratory viruses (influenza A, influenza B, respiratory syncytial virus, parainfluenza viruses, adenoviruses, and picornaviruses) were examined in a cohort of 234 preschool-aged children from Melbourne, Australia, over a 12-month period by using polymerase chain reaction testing. Parents collected a daily symptom diary for the duration of the study and were taught to collect a combined nose-throat swab and complete an impact diary when the study child had an acute respiratory illness. RESULTS. The average incidence of acute respiratory illness was 0.48 per child-month for the duration of the study, with a winter peak. Of 543 illnesses with ≥1 specimen returned, 33 were positive for human metapneumovirus (6.1%) and 18 for human coronavirus NL63 (3.3%). Of all of the viruses for which we tested, human metapneumovirus and human coronavirus NL63 were most strongly linked to child care attendance, occurring in 82% and 78% of infected children, respectively. Picornaviruses were the most commonly identified virus group (269 [49.5%]). Influenza virus and adenovirus illnesses had the greatest impact, with fever in more than three quarters and requiring, on average, & local doctor visit per illness. CONCLUSIONS. Recently identified human metapneumovirus and human coronavirus NL63 are important pathogens in community-based illness in children, particularly in those who attend child care. Picornaviruses were detected in half of the nose-throat swabs collected during acute respiratory illness in children but resulted in milder illnesses influenza and adenovirus caused the highest-impact illnesses. The use of parent-collected specimens should be considered for additional community-based epidemiologic studies and vaccine trials.
Cumulative incidence of rheumatic fever in an endemic region: a guide to the susceptibility of the population?
Publisher: Cambridge University Press (CUP)
Date: 04-2000
DOI: 10.1017/S0950268800003514
Abstract: Aboriginal Australians in northern Australia are subject to endemic infection with group A streptococci, with correspondingly high rates of acute rheumatic fever and rheumatic heart disease. For 12 communities with good ascertainment, the estimated lifetime cumulative incidence of acute rheumatic fever was approximately 5·7%, whereas over the whole population, with less adequate ascertainment, the cumulative incidence was only 2·7%. The corresponding prevalences of established rheumatic heart disease were substantially less than the cumulative incidences of acute rheumatic fever, at least in part because of poor ascertainment. The cumulative incidence of acute rheumatic fever estimates the proportion of susceptible in iduals in endemically exposed populations. Our figures of 2·7–5·7% susceptible are consistent with others in the literature. Such comparisons suggest that the major part of the variation in rheumatic fever incidence between populations is due to differences in streptococcal exposure and treatment, rather than to any difference in (genetic) susceptibility.
Impact of the 23-valent pneumococcal polysaccharide vaccination in pregnancy against infant acute lower respiratory infections in the Northern Territory of Australia
Publisher: Springer Science and Business Media LLC
Date: 12-2018
Evaluation of a screening protocol using auscultation and portable echocardiography to detect asymptomatic rheumatic heart disease in Tongan schoolchildren
Publisher: Springer Science and Business Media LLC
Date: 08-04-2008
Abstract: Rheumatic heart disease (RHD) is an important problem in developing countries however, many cases are detected only when the disease has progressed to cardiac failure. Screening can detect cases earlier, but there are no screening guidelines. We performed a cross-sectional screening study in Tonga among 5,053 primary school children, in whom auscultation followed by echocardiography of those with heart murmurs were used to identify RHD. We also analyzed whether a three-stage screening protocol of auscultation performed by a medical student to detect any heart murmur, second-stage auscultation performed by a local pediatrician to differentiate pathological from innocent murmurs and echocardiography of those with pathological murmurs altered outcomes. The prevalence of definite RHD was 33.2 per 1,000. The prevalence of RHD increased significantly with age, peaking at 42.6 per 1,000 in children aged 10-12 years. Most valve lesions (91 [54%] of 169) were mild. Auscultation to detect pathological murmurs was poorly sensitive (46.4%), and the finding of any murmur on auscultation did not affect the likelihood of detecting pathology on echocardiography. The finding of a pathological murmur did significantly increase the likelihood of detecting pathology on echocardiography, but still missed 54% of those with pathology (mainly RHD) detected on echocardiography. Screening is a useful method for detecting asymptomatic RHD in regions of high prevalence and we report a high echocardiographically confirmed prevalence. The most appropriate screening strategy remains to be confirmed, however, and implementation will depend on the availability of echocardiography and trained staff.
High burden of infectious disease and antibiotic use in early life in Australian Aboriginal communities.
Publisher: Elsevier BV
Date: 04-2019
Abstract: To quantify the childhood infectious disease burden and antibiotic use in the Northern Territory's East Arnhem region through synthesis and analysis of historical data resources. We combined primary health clinic data originally reported in three separate publications stemming from the East Arnhem Healthy Skin Project (Jan-01 to Sep-07). Common statistical techniques were used to explore the prevalence of infectious conditions and the seasonality of infections, and to measure rates of antibiotic use. There was a high monthly prevalence of respiratory (mean: 32% [95% confidence interval (CI): 20%, 34%]) and skin (mean: 20% [95%CI: 19%, 22%]) infectious syndromes, with upper respiratory tract infections (mean: 29% [95%CI: 27%, 31%]) and skin sores (mean: 15% [95%CI: 14%, 17%]) the most common conditions. Antibiotics were frequently prescribed with 95% (95%CI: 91%, 97%) of children having received at least one antibiotic prescription by their first birthday, and 47% having received six antibiotic prescriptions skin sores being a key driver. Early life infections drive high antibiotic prescribing rates in remote Aboriginal communities. Implications for public health: Eliminating skin disease could reduce antibiotic use by almost 20% in children under five years of age in this population.
Rheumatic fever in Indigenous Australian children
Publisher: Wiley
Date: 20-09-2010
DOI: 10.1111/J.1440-1754.2010.01841.X
Abstract: Rheumatic heart disease (RHD) caused by acute rheumatic fever (ARF) is a disease of poverty, poor hygiene and poor living standards. RHD remains one of the major causes of childhood cardiac disease in developing nations. Within developed nations, there has been a dramatic drop in the prevalence of RHD because of the improvement of living standards, access to health care and the widespread availability of penicillin-based drugs. Despite a dramatic reduction of RHD in Australia overall, it continues to be a major contributor to childhood and adult cardiac disease in Indigenous communities throughout northern and central Australia. Currently, Australia has among the highest recorded rates of ARF and RHD in the world. The most accurate epidemiological data in Australia come from the Northern Territory's RHD control programme. In the Northern Territory, 92% of people with RHD are Indigenous, of whom 85% live in remote communities and towns. The incidence of ARF is highest in 5-14-year-olds, ranging from 150 to 380 per 100,000. Prevalence rates of RHD since 2000 have steadily increased to almost 2% of the Indigenous population in the Northern Territory, 3.2% in those aged 35-44 years. Living in remote communities is a contributing factor to ARF/RHD as well as a major barrier for adequate follow-up and care. Impediments to ARF/RHD control include the paucity of specialist services, rapid turnover of health staff, lack of knowledge of ARF/RHD by health staff, patients and communities, and the high mobility of the Indigenous population. Fortunately, the recently announced National Rheumatic Fever Strategy, comprising recurrent funding to the Northern Territory, Queensland and Western Australia for control programmes, as well as the creation of a National Coordination Unit suggest that RHD control in Australia is now a tangible prospect. For the disease to be eradicated, Australia will have to address the underpinning determinants of poverty, social and living conditions.
Pediatric rheumatic heart disease in the developing world: echocardiographic versus clinical screening
Publisher: Springer Science and Business Media LLC
Date: 27-11-2007
Professionalism and everyday practices in early childhood education and care: Singaporean pre-service teachers’ perspectives
Publisher: Informa UK Limited
Date: 16-02-2023
Caring for Pregnant Women with Rheumatic Heart Disease: A Qualitative Study of Health Service Provider Perspectives
Publisher: Ubiquity Press, Ltd.
Date: 22-12-2021
DOI: 10.5334/GH.1086
Global epidemiology of valvular heart disease
Publisher: Springer Science and Business Media LLC
Date: 25-06-2021
DOI: 10.1038/S41569-021-00570-Z
Abstract: Valvular heart disease (VHD) is a major contributor to loss of physical function, quality of life and longevity. The epidemiology of VHD varies substantially around the world, with a predominance of functional and degenerative disease in high-income countries, and a predominance of rheumatic heart disease in low-income and middle-income countries. Reflecting this distribution, rheumatic heart disease remains by far the most common manifestation of VHD worldwide and affects approximately 41 million people. By contrast, the prevalence of calcific aortic stenosis and degenerative mitral valve disease is 9 and 24 million people, respectively. Despite a reduction in global mortality related to rheumatic heart disease since 1900, the death rate has remained fairly static since 2000. Meanwhile, deaths from calcific aortic stenosis have continued to rise in the past 20 years. Epidemiological data on other important acquired and congenital forms of VHD are limited. An ageing population and advances in therapies make an examination of the changing global epidemiology of VHD crucial for advances in clinical practice and formulation of health policy. In this Review, we discuss the global burden of VHD, geographical variation in the presentation and clinical management, and temporal trends in disease burden.
Rheumatic heart disease across the Western Pacific
Publisher: BMJ
Date: 10-2017
Lessons learned in the development of sustained release penicillin drug delivery systems for the prophylactic treatment of rheumatic heart disease (RHD)
Publisher: Springer Science and Business Media LLC
Date: 05-02-2018
DOI: 10.1007/S13346-018-0482-Z
Abstract: The current prophylactic treatment to prevent rheumatic heart disease requires four-weekly intramuscular injection of a suspension of the poorly soluble benzathine salt form of penicillin G (BPG) often for more than 10 years. In seeking to reduce the frequency of administration to improve adherence, biodegradable polymer matrices have been investigated. Poly(lactide-co-glycolide) (PLGA)-based in situ forming precursor systems containing N-methyl-2-pyrrolidone as solvent and PLGA-based monolithic implants for surgical implantation containing BPG were developed. Long-term release studies indicated low and plateaued release of penicillin G, but continual favourable release profiles for the benzathine counterion, indicating degradation of the polymer and generation of acidic microenvironment being detrimental to penicillin stability. In order to avoid the issue of the acidic product, poly(caprolactone)(PCL) implants were also investigated, with favourable penicillin G release behaviour being achieved, and slow release over 180 days. However, when taking into account the mass of polymer, and the total dose of drug calculated from literature pharmacokinetic parameters for penicillin G, we concluded that an implant size of over 7 g would still be required. This may preclude clinical deployment of a polymer matrix type delivery system for this indication in children and adolescents. Therefore, we have learned that biodegradable PLGA-type systems are not suitable for development of sustained release BPG treatments and that although the PCL system provides favourable release behaviour, the total size of the implant may still present a hurdle for future development.
Severe adverse events following benzathine penicillin G injection for rheumatic heart disease prophylaxis: cardiac compromise more likely than anaphylaxis
Publisher: BMJ
Date: 06-2019
DOI: 10.1136/HEARTASIA-2019-011191
Abstract: Secondary prophylaxis through long-term antibiotic administration is essential to prevent the progression of acute rheumatic fever to rheumatic heart disease (RHD). Benzathine penicillin G (BPG) has been shown to be the most efficacious antibiotic for this purpose however, adverse events associated with BPG administration have been anecdotally reported. This study therefore aimed to collate case reports of adverse events associated with BPG administration for RHD prophylaxis. A literature review was used to explore reported adverse reactions to BPG and inform development of a case report questionnaire. This questionnaire was circulated through professional networks to solicit retrospective reports of adverse events from treating physicians. Returned surveys were tabulated and thematically analysed. Reactions were assessed using the Brighton Collaboration case definition to identity potential anaphylaxis. We obtained 10 case reports from various locations, with patients ranging in age from early-teens to adults. All patients had clinical or echocardiogram-obtained evidence of valvular disease. The majority of patients (80%) had received BPG prior to the event with no previous adverse reaction. In eight cases, the reaction was fatal in one case resuscitation was successful and in one case treatment was not required. Only three cases met Level 1 Brighton criteria consistent with anaphylaxis. These results indicate that anaphylaxis is not a major cause of adverse reactions to BPG. An alternative mechanism for sudden death following BPG administration in people with severe RHD is proposed.
Efficacy of a trivalent influenza vaccine against seasonal strains and against 2009 pandemic H1N1: A randomized, placebo-controlled trial.
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.VACCINE.2016.08.038
Abstract: Before pandemic H1N1 vaccines were available, the potential benefit of existing seasonal trivalent inactivated influenza vaccines (IIV3s) against influenza due to the 2009 pandemic H1N1 influenza strain was investigated, with conflicting results. This study assessed the efficacy of seasonal IIV3s against influenza due to 2008 and 2009 seasonal influenza strains and against the 2009 pandemic H1N1 strain. This observer-blind, randomized, placebo-controlled study enrolled adults aged 18-64years during 2008 and 2009 in Australia and New Zealand. Participants were randomized 2:1 to receive IIV3 or placebo. The primary objective was to demonstrate the efficacy of IIV3 against laboratory-confirmed influenza. Participants reporting an influenza-like illness during the period from 14days after vaccination until 30 November of each study year were tested for influenza by real-time reverse transcription polymerase chain reaction. Over a study period of 2years, 15,044 participants were enrolled (mean age±standard deviation: 35.5±14.7years 54.4% female). Vaccine efficacy of the 2008 and 2009 IIV3s against influenza due to any strain was 42% (95% confidence interval [CI]: 30%, 52%), whereas vaccine efficacy against influenza due to the vaccine-matched strains was 60% (95% CI: 44%, 72%). Vaccine efficacy of the 2009 IIV3 against influenza due to the 2009 pandemic H1N1 strain was 38% (95% CI: 19%, 53%). No vaccine-related deaths or serious adverse events were reported. Solicited local and systemic adverse events were more frequent in IIV3 recipients than placebo recipients (local: IIV3 74.6% vs placebo 20.4%, p<0.001 systemic: IIV3 46.6% vs placebo 39.1%, p<0.001). The 2008 and 2009 IIV3s were efficacious against influenza due to seasonal influenza strains and the 2009 IIV3 demonstrated moderate efficacy against influenza due to the 2009 pandemic H1N1 strain. Funded by CSL Limited, ClinicalTrials.gov identifier NCT00562484.
The inequitable burden of group A streptococcal diseases in Indigenous Australians
Publisher: AMPCo
Date: 09-2016
DOI: 10.5694/MJA16.00400
Echocardiographic Screening for Rheumatic Heart Disease in Indigenous Australian Children: A Cost–Utility Analysis
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2017
Abstract: Rheumatic heart disease ( RHD ) remains a leading cause of cardiovascular morbidity and mortality in children and young adults in disadvantaged populations. The emergence of echocardiographic screening provides the opportunity for early disease detection and intervention. Using our own multistate model of RHD progression derived from Australian RHD register data, we performed a cost–utility analysis of echocardiographic screening in indigenous Australian children, with the dual aims of informing policy decisions in Australia and providing a model that could be adapted in other countries. We simulated the outcomes of 2 screening strategies, assuming that RHD could be detected 1, 2, or 3 years earlier by screening. Outcomes included reductions in heart failure, surgery, mortality, disability‐adjusted life‐years, and corresponding costs. Only a strategy of screening all indigenous 5‐ to 12‐year‐olds in half of their communities in alternate years was found to be cost‐effective (incremental cost‐effectiveness ratio less than AU$50 000 per disability‐adjusted life‐year averted), assuming that RHD can be detected at least 2 years earlier by screening however, this result was sensitive to a number of assumptions. Additional modeling of improved adherence to secondary prophylaxis alone resulted in dramatic reductions in heart failure, surgery, and death these outcomes improved even further when combined with screening. Echocardiographic screening for RHD is cost‐effective in our context, assuming that RHD can be detected ≥2 years earlier by screening. Our model can be adapted to any other setting but will require local data or acceptable assumptions for model parameters.
Rheumatic Heart Disease in Pregnancy: New Strategies for an Old Disease?
Publisher: Ubiquity Press, Ltd.
Date: 2021
DOI: 10.5334/GH.1079
High risk of early sub-therapeutic penicillin concentrations after intramuscular benzathine penicillin G injections in Ethiopian children and adults with rheumatic heart disease
Publisher: Public Library of Science (PLoS)
Date: 11-06-2021
DOI: 10.1371/JOURNAL.PNTD.0009399
Abstract: Intramuscular benzathine penicillin G (BPG) injections are a cornerstone of secondary prophylaxis to prevent acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Uncertainties regarding inter-ethnic and preparation variability, and target exposure profiles of BPG injection are key knowledge gaps for RHD control. To evaluate BPG pharmacokinetics (PK) in patients receiving 4-weekly doses in Ethiopia, we conducted a prospective cohort study of ARF/RHD patients attending cardiology outpatient clinics. Serum s les were collected weekly for one month after injection and assayed with a liquid chromatography-mass spectroscopy assay. Concentration-time datasets for BPG were analyzed by nonlinear mixed effects modelling using NONMEM. A total of 190 penicillin concentration s les from 74 patients were included in the final PK model. The median age, weight, BMI was 21 years, 47 kg and 18 kg/m 2 , respectively. When compared with estimates derived from Indigenous Australian patients, the estimate for median (95% confidence interval) volume of distribution (V/F) was lower (54.8 [43.9–66.3] l.70kg -1 ) whilst the absorption half-life (t 1/2-abs2 ) was longer (12.0 [8.75–17.7] days). The median (IQR) percentage of time where the concentrations remained above 20 ng/mL and 10 ng/mL within the 28-day treatment cycle was 42.5% (27.5–60) and 73% (58.5–99), respectively. The majority of Ethiopian patients receiving BPG as secondary prophylaxis to prevent RHD do not attain target concentrations for more than two weeks during each 4-weekly injection cycle, highlighting the limitations of current BPG strategies. Between-population variation, together with PK differences between different preparations may be important considerations for ARF/RHD control programs.
Mortality due to acute rheumatic fever and rheumatic heart disease in the Northern Territory: a preventable cause of death in Aboriginal people
Publisher: Elsevier BV
Date: 04-1999
DOI: 10.1111/J.1467-842X.1999.TB01227.X
Abstract: To determine the death rates and effect on premature mortality in the Northern Territory of acute rheumatic fever and rheumatic heart disease. We ascertained deaths due to acute rheumatic fever and rheumatic heart disease for the period 1979-96 from death certificates, a database of all patients with these diseases and mortuary records. Crude and age-standardised death rates were calculated, as were years of potential life lost before age 65, between 15 and 65, and before age 70. Of 182 deaths, 171 (94%) were in Aboriginal people. The mean age at death of Aboriginal people was 35.7 years, compared to 67.3 years in non-Aboriginal people. The age-standardised death rate in Aboriginal people was 30.2 per 100,000 person-years, compared to 1.1 in non-Aboriginal people. Acute carditis caused 13 deaths at a mean age of 14.2 years. Mortality in Aboriginal people was highest in the > 30 age groups and in females. Premature mortality for Aboriginal people was more than four times that from developing countries. Acute rheumatic fever and rheumatic heart disease are not only common in Aboriginal people, they affect and often kill people in their most productive years. A co-ordinated control program should help in the short term, but will not address underlying causes of these and other preventable diseases.
Rotavirus and the Indigenous Children of the Australian Outback: Monovalent Vaccine Effective in a High‐Burden Setting
Publisher: Oxford University Press (OUP)
Date: 08-2009
DOI: 10.1086/600395
Abstract: Indigenous children living in arid Central Australia experience frequent outbreaks of rotavirus gastroenteritis. A widespread outbreak of G9 rotavirus infection occurred several months after introduction of the RIX4414 rotavirus vaccine. We performed a retrospective case-control study to determine vaccine efficacy during the outbreak. Two doses provided an estimated vaccine efficacy of 77.7% (95% confidence interval, 40.2%-91.7%) against hospitalization for gastroenteritis. Vaccine efficacy was 84.5% (95% confidence interval, 23.4%-96.9%) against confirmed cases of rotavirus infection. Vaccination was effective in this high-burden setting.
Searching for a technology-driven acute rheumatic fever test: the START study protocol
Publisher: BMJ
Date: 09-2021
DOI: 10.1136/BMJOPEN-2021-053720
Abstract: The absence of a diagnostic test for acute rheumatic fever (ARF) is a major impediment in managing this serious childhood condition. ARF is an autoimmune condition triggered by infection with group A Streptococcus . It is the precursor to rheumatic heart disease (RHD), a leading cause of health inequity and premature mortality for Indigenous peoples of Australia, New Zealand and internationally. ‘Searching for a Technology-Driven Acute Rheumatic Fever Test’ (START) is a biomarker discovery study that aims to detect and test a biomarker signature that distinguishes ARF cases from non-ARF, and use systems biology and serology to better understand ARF pathogenesis. Eligible participants with ARF diagnosed by an expert clinical panel according to the 2015 Revised Jones Criteria, aged 5–30 years, will be recruited from three hospitals in Australia and New Zealand. Age, sex and ethnicity-matched in iduals who are healthy or have non-ARF acute diagnoses or RHD, will be recruited as controls. In the discovery cohort, blood s les collected at baseline, and during convalescence in a subset, will be interrogated by comprehensive profiling to generate possible diagnostic biomarker signatures. A biomarker validation cohort will subsequently be used to test promising combinations of biomarkers. By defining the first biomarker signatures able to discriminate between ARF and other clinical conditions, the START study has the potential to transform the approach to ARF diagnosis and RHD prevention. The study has approval from the Northern Territory Department of Health and Menzies School of Health Research ethics committee and the New Zealand Health and Disability Ethics Committee. It will be conducted according to ethical standards for research involving Indigenous Australians and New Zealand Māori and Pacific Peoples. Indigenous investigators and governance groups will provide oversight of study processes and advise on cultural matters.
Missed opportunities for a diagnosis of acute otitis media in Aboriginal children
Publisher: Wiley
Date: 09-2003
DOI: 10.1046/J.1440-1754.2003.00210.X
Abstract: Severe otitis media and its sequelae are common in rural and remote Aboriginal children. Identification of acute otitis media (AOM) is likely to reduce the number of children who go on to develop chronic suppurative otitis media and associated complications. The aim of this study was to compare the diagnoses made by researchers with that documented in the medical records of children admitted to the paediatric isolation ward of the Royal Darwin Hospital, Darwin, Northern Territory. Children aged <8 years admitted to Royal Darwin Hospital were eligible for assessment by pneumatic otoscopy, video-otoscopy and tympanometry. A diagnosis was made for each child according to the state of their worst ear. Comparisons were made between the researcher diagnoses of ear disease and those documented in the hospital notes by medical staff. Thirty-one children were enrolled during 32 admissions. Most were aged <2 years, Aboriginal, and resided in remote communities. Sixty-one video-otoscopic assessments were attempted and sufficiently good images to allow diagnosis were obtained in 105 of 122 ears. Acute otitis media was diagnosed by the research team in 20 of 32 child admissions. Of 29 children who had ear examinations documented by hospital staff, only seven had a diagnosis of AOM recorded. Overall, the research team were almost three times more likely to make this diagnosis (relative risk 2.9, 95% confidence interval 1.6, 5.2). This difference was unlikely to have occurred by chance (P = 0.0002, McNemar's Chi-squared test). In this small study, young Aboriginal children with clear bulging of their tympanic membrane were not diagnosed with AOM by medical staff. Further training in diagnosis, including cleaning of the ear canal, may lead to more accurate assessment and appropriate recommendations for ongoing management.
The ORVAC trial protocol: a phase IV, double-blind, randomised, placebo-controlled clinical trial of a third scheduled dose of Rotarix rotavirus vaccine in Australian Indigenous infants to improve pro
Publisher: BMJ
Date: 11-2019
DOI: 10.1136/BMJOPEN-2019-032549
Abstract: Rotavirus vaccines were introduced into the Australian National Immunisation Program in 2007. Despite this, Northern Territory Indigenous children continue to be hospitalised with rotavirus at a rate more than 20 times higher than non-Indigenous children in other Australian jurisdictions, with evidence of waning protection in the second year of life. We hypothesised that scheduling an additional (third) dose of oral human rotavirus vaccine (Rotarix, GlaxoSmithKline) for children aged 6 to months would improve protection against clinically significant all-cause gastroenteritis. This Bayesian adaptive clinical trial will investigate whether routinely scheduling an additional dose of Rotarix for Australian Indigenous children aged 6 to months old confers significantly better protection against clinically important all-cause gastroenteritis than the current two-dose schedule at 2 and 4 months old. There are two coprimary endpoints: (1) seroconversion from baseline serum anti-rotavirus immunoglobulin A (IgA) titre U/mL prior to an additional dose of Rotarix lacebo to serum anti-rotavirus IgA titre U/mL following the administration of the additional dose of Rotarix lacebo and (2) time from randomisation to medical attendance (up to age 36 months old) for which the primary reason is acute gastroenteritis/diarrhoea. Secondary endpoints include the change in anti-rotavirus IgA log titre, time to hospitalisation for all-cause diarrhoea and for rotavirus-confirmed gastroenteritis/diarrhoea, and rotavirus notification. Analysis will be based on Bayesian inference with adaptive s le size. Ethics approval has been granted by Central Australian Human Research Ethics Committee (HREC-16-426) and Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research (HREC-2016-2658). Study investigators will ensure the trial is conducted in accordance with the principles of the Declaration of Helsinki and with the ICH Guidelines for Good Clinical Practice. In idual participant consent will be obtained. Results will be disseminated via peer-reviewed publication. The trial is registered with Clinicaltrials.gov ( NCT02941107 ) and important modifications to this protocol will be updated. NCT02941107 Pre-results.
High burden of invasive β-haemolytic streptococcal infections in Fiji
Publisher: Cambridge University Press (CUP)
Date: 16-07-2007
DOI: 10.1017/S095026880700917X
Abstract: We undertook a 5-year retrospective study of group A streptococcal (GAS) bacteraemia in Fiji, supplemented by a 9-month detailed retrospective study of β-haemolytic streptococcal (BHS) infections. The all-age incidence of GAS bacteraemia over 5 years was 11·6/100 000. Indigenous Fijians were 4·7 times more likely to present with invasive BHS disease than people of other ethnicities, and 6·4 times more likely than Indo-Fijians. The case-fatality rate for invasive BHS infections was 28%. emm -typing was performed on 23 isolates: 17 different emm -types were found, and the emm -type profile was different from that found in industrialized nations. These data support the contentions that elevated rates of invasive BHS and GAS infections are widespread in developing countries, and that the profile of invasive organisms in these settings reflects a wide ersity of emm -types and a paucity of types typically found in industrialized countries.
10-Valent pneumococcal non-typeable H. influenzae protein D conjugate vaccine (PHiD-CV10) versus 13-valent pneumococcal conjugate vaccine (PCV13) as a booster dose to broaden and strengthen protection from otitis media (PREVIX_BOOST) in Australian Aboriginal children: Study protocol for a randomised controlled trial
Publisher: BMJ
Date: 05-2020
DOI: 10.1136/BMJOPEN-2019-033511
Abstract: Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) are major otitis media pathogens that densely co-colonise the nasopharynx and infect the middle ear of Australian Aboriginal infants from very early in life. Our co-primary hypotheses are that at 18 months of age infants receiving 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) compared with those receiving 13-valent pneumococcal conjugate vaccine (PCV13) as a booster at 12 months of age will have higher antibody levels to Haemophilus influenzae protein D and that infants receiving PCV13 will have higher antibody levels to PCV13-only serotypes 3, 6A and 19A. Our randomised controlled trial will enrol 270 Aboriginal children at 12 months of age to a booster dose of either PHiD-CV10 or PCV13. Children who completed the three-dose primary course schedules of PHiD-CV10 at 2, 4, 6 months of age PCV13 at 2, 4, 6 months of age or a combination schedule of PHiD-CV10 at 1, 2, 4 months of age plus PCV13 at 6 months of age are eligible. The co-primary assessor-blinded outcomes when the infants are 18 months of age are as follows: (a) IgG geometric mean concentration (GMC) and proportion with IgG ≥100 EU/mL for protein D, and (b) IgG GMC and the proportion with IgG ≥0.35 µg/mL for pneumococcal serotypes 3, 6A and 19A. Secondary immunogenicity comparisons of six primary and booster dose schedules of 10 shared serotypes at 18 months of age, nasopharyngeal carriage, all forms of otitis media, hearing loss and developmental milestones at 18, 24, 30 and 36 months of age will be reported. Ethics committees of NT Department of Health, Menzies, WA Department of Health and WA Aboriginal Health approved the study. Results will be presented to communities, at conferences and published in peer-reviewed journals. NCT01735084 .
Acute rheumatic fever
Publisher: Elsevier BV
Date: 07-2005
High burden of impetigo and scabies in a tropical country
Publisher: Public Library of Science (PLoS)
Date: 23-06-2009
The Spectrum, Severity and Outcomes of Rheumatic Mitral Valve Disease in Pregnant Women in Australia and New Zealand
Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.HLC.2021.10.017
Abstract: Rheumatic heart disease (RHD) poses significant perinatal risks. We aimed to describe the spectrum, severity and outcomes of rheumatic mitral valve disease in pregnancy in Australia and New Zealand. A prospective, population-based cohort study of pregnant women with RHD recruited 2013-14 through the hospital-based Australasian Maternity Outcomes Surveillance System. Outcome measures included maternal and perinatal morbidity and mortality. Univariable and multivariable logistic regression analyses were undertaken to test for predictors of adverse maternal and perinatal outcomes. Of 274 pregnant women identified with RHD, 124 (45.3%) had mitral stenosis (MS) and 150 (54.7%) had isolated mitral regurgitation (MR). One woman with mild MS/moderate MR died. There were six (2.2%) stillbirths and two (0.7%) neonatal deaths. Babies born to women with MS were twice as likely to be small-for-gestational-age (22.7% vs 11.4%, p=0.013). In women with MS, use of cardiac medication (AOR 7.42) and having severe stenosis (AOR 16.35) were independently associated with adverse cardiac outcomes, while New York Heart Association (NYHA) class >1 (AOR 3.94) was an independent predictor of adverse perinatal events. In women with isolated MR, use of cardiac medications (AOR 7.03) and use of anticoagulants (AOR 6.05) were independently associated with adverse cardiac outcomes. Careful monitoring and specialist care for women with RHD in pregnancy is required, particularly for women with severe MS, those on cardiac medication, and those on anticoagulation, as these are associated with increased risk of adverse maternal cardiac outcomes. In the context of pregnancy, contraception and preconception planning are important for young women diagnosed with RHD.
Position statement of the World Heart Federation on the prevention and control of rheumatic heart disease
Publisher: Springer Science and Business Media LLC
Date: 02-04-2013
Abstract: In the 21(st) century, rheumatic fever (RF) and rheumatic heart disease (RHD) are neglected diseases of marginalized communities. Globally, RHD remains the most-common cardiovascular disease in young people aged <25 years. Although RF and RHD have been almost eradicated in areas with established economies, migration from low-income to high-income settings might be responsible for a new burden of RHD in high-income countries. The World Heart Federation (WHF) and its Working Group on RF and RHD unites global experts, combines their experience and enthusiasm, and provides a platform for RHD control. This paper is a declaration of the WHF institutional strategic goal--a 25% reduction in premature deaths from RF and RHD among in iduals aged <25 years by the year 2025. The position statement affirms WHF commitments to five key strategic targets: comprehensive register-based control programmes, global access to benzathine penicillin G, identification and development of public figures as 'RHD ch ions', expansion of RHD training hubs, and support for vaccine development. In this paper, we also review existing barriers to RF and RHD control and identify the actions required to change the trajectory of control for these diseases. This approach provides the foundation for governments, civil society, patient advocates, clinicians, researchers, and funding agencies to develop partnerships and unify global efforts to control RF and RHD. The WHF plans to expand this position statement to an operational plan that will be founded on science, research, and quantifiable progress indicators to impact positively on the millions of people who are affected by RHD and its long-term sequelae.
Status of research and development of vaccines for Streptococcus pyogenes
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.VACCINE.2016.03.073
Abstract: Streptococcus pyogenes is an important global pathogen, causing considerable morbidity and mortality, especially in low and middle income countries where rheumatic heart disease and invasive infections are common. There is a number of promising vaccine candidates, most notably those based on the M protein, the key virulence factor for the bacterium. Vaccines against Streptococcus pyogenes are considered as impeded vaccines because of a number of crucial barriers to development. Considerable effort is needed by key players to bring current vaccine candidates through phase III clinical trials and there is a clear need to develop a roadmap for future development of current and new candidates.
Echocardiographic screening in a resource poor setting: Borderline rheumatic heart disease could be a normal variant
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.IJCARD.2014.03.004
Abstract: To estimate the echocardiography confirmed prevalence of rheumatic heart disease (RHD) in school children in Fiji. Cross-sectional observational study. Ten primary schools in Fiji. School children aged 5-14 years. Each child had an echocardiogram performed by an echocardiographic technician subsequently read by a paediatric cardiologist not involved with field screening, and auscultation performed by a paediatrician. Echocardiographic criteria for RHD diagnosis were based on those previously published by the National Institutes of Health (NIH) and World Health Organization (WHO), and data were also analyzed using the new World Heart Federation (WHF) criteria. Prevalence figures were calculated with binomial 95% confidence intervals. Using the modified NIH/WHO criteria the prevalence of definite RHD prevalence was 7.2 cases per 1000 (95% CI 3.7-12.5), and the prevalence of probable RHD 28.2 cases per 1000 (95% CI 20.8-37.3). By applying the WHF criteria the prevalence of definite and borderline RHD was 8.4 cases per 1000 (95% CI 4.6-14.1) and 10.8 cases per 1000 (95% CI 6.4-17.0) respectively. Definite RHD was more common in females (OR 5.1, 95% CI 1.1-48.3) and in children who attended school in a rural location (OR 2.3, 95% CI 0.6-13.50). Auscultation was poorly sensitive compared to echocardiography (30%). There is a high burden of undiagnosed RHD in Fiji. Auscultation is poorly sensitive when compared to echocardiography in the detection of asymptomatic RHD. The results of this study highlight the importance of the use of highly sensitive and specific diagnostic criteria for echocardiography diagnosis of RHD.
Invasive Staphylococcus aureus Infections in Children in Tropical Northern Australia
Publisher: Oxford University Press (OUP)
Date: 26-03-2014
DOI: 10.1093/JPIDS/PIU013
Abstract: Despite a high burden of staphylococcal skin disease in children and high incidence of Staphylococcus aureus bacteremia in adult Indigenous populations in northern Australia, there are few studies describing incidence or clinical information of invasive S aureus (ISA) infections in children. We conducted a retrospective review for all cases of S aureus bacteremia and sterile site infections, for children under 15 years, in northern Australia over a 4-year period (2007-2010). Cases were categorized as neonatal (<28 days) and pediatric (≥28 days). Forty-four cases (9 neonatal, 35 pediatric) were identified. The annual incidence of ISA was 27.9 cases per 100 000 population. Among pediatric cases, the annual incidence was significantly higher in the Indigenous (46.6) compared with the non-Indigenous (4.4) population (IRR: 10.6 [95% confidence interval, 3.8-41.4]). Pediatric infections were predominantly community-associated (86%). Clinical infection sites included osteoarticular (66%), pleuropulmonary (29%), and endocarditis (9%), and multifocal disease was common (20%). Eighty-three percent of pediatric cases presented with sepsis 34% resulted in intensive care admission. Neonatal cases were all born prematurely 89% were late-onset infections. Overall, 27% of infections were due to methicillin-resistant S aureus (MRSA). Compared with methicillin-sensitive S aureus (MSSA), there was no difference in severity or presentation in pediatric MRSA cases, but a higher proportion of MRSA cases were readmitted. The annual incidence of ISA infection in this study is among the highest described, largely due to a disproportionate burden in Indigenous children. Infections are frequently severe and infection with MRSA is common. Children presenting with suspected ISA in this region should be treated empirically for MRSA.
Failure to vaccinate or failure of vaccine? Effectiveness of the 23-valent pneumococcal polysaccharide vaccine program in Indigenous adults in the Northern Territory of Australia
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.VACCINE.2009.12.066
Abstract: Over the last decade, there has been no discernible reduction in Invasive Pneumococcal Disease (IPD) amongst Indigenous adults in the Northern Territory (NT) of Australia, despite increasing vaccination coverage. We examined the utility of two common methods, the screening method and the indirect method, to determine the 23-valent pneumococcal polysaccharide vaccine effectiveness (VE) in prevention of IPD amongst Indigenous adults in this setting. VE was calculated for the period 2001-2005 across two distinct geographical areas where the disease burden was known to differ. VE against vaccine-type IPD was 3.4% (95% CI -43, 35) for the NT. However, population vaccination coverage varied widely according to geographical region and where this was within the range appropriate for the use of the screening method, VE was within the expected range (67.2%, 95% CI 47, 80). VE according to the indirect cohort appeared unreliable in this setting due to the analysis being based on a very limited number of non-vaccine-type IPD cases. Surveillance based estimates of VE such as these need to be considered with caution, but the results suggest failure to vaccinate is the most likely reason vaccine-type IPD has not reduced in this setting.
A population pharmacokinetic study of benzathine benzylpenicillin G administration in children and adolescents with rheumatic heart disease: new insights for improved secondary prophylaxis strategies
Publisher: Oxford University Press (OUP)
Date: 15-04-2019
DOI: 10.1093/JAC/DKZ076
Invasive Infections Caused by Lancefield Groups C/G and A Streptococcus, Western Australia, Australia, 2000–2018
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 11-2022
Repeat pneumococcal polysaccharide vaccine in Indigenous Australian adults is associated with decreased immune responsiveness
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.VACCINE.2017.04.040
Abstract: Indigenous adults residing in the Northern Territory of Australia experience elevated rates of invasive pneumococcal disease despite the routine use of 23-valent pneumococcal polysaccharide vaccine (23vPPV). We hypothesised that the limited protection from 23vPPV may be due to hyporesponsiveness as a result of vaccine failure from repeated vaccination. To explore this possibility, we evaluated the immune response to a first and second dose of 23vPPV in Indigenous adults and a first dose of 23vPPV in non-Indigenous adults. Serotype-specific IgG was measured by ELISA for all 23 vaccine serotypes at baseline and at one month post-vaccination. In iduals were considered to have an adequate immune response if paired sera demonstrated either: a four-fold rise in antibody concentration a two-fold rise if the post vaccination antibody was >1.3μg/ml but 4.0μg/ml for at least half of the serotypes tested (12/23). Our per-protocol analysis included the comparison of outcomes for three groups: Indigenous adults receiving a second 23vPPV dose (N=20) and Indigenous (N=60) and non-Indigenous adults (N=25) receiving their first 23vPPV dose. All non-Indigenous adults receiving a first dose of 23vPPV mounted an adequate immune response (25/25). There was no significant difference in the proportion of in iduals with an adequate response using our definition (primary endpoint), with 88% of Indigenous adults mounted an adequate response following first dose 23vPPV (53/60) compared to 70% having an adequate response following a second dose of 23vPPV (14/20 p=0.05). The risk difference between Indigenous participants receiving first dose compared to non-Indigenous participants receiving first dose was significant when comparing a response threshold of at least 70% (-27%, 95% CI: -43% to -11% p=0.01) and 90% (-38%, 95% CI: -60% to -16% p=0.006) of serotypes with a positive response. Indigenous participants demonstrated a poorer response to a first dose 23vPPV compared to their non-Indigenous counterparts, with lower IgG following a second 23vPPV dose. These findings highlight the critical need to evaluate the efficacy of future pneumococcal vaccine programs in the Australian Indigenous populations that recommend repeated doses of 23vPPV.
Pediatric sepsis in the developing world
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.JINF.2015.04.016
Abstract: Sepsis is the leading killer of children worldwide, but this is not reflected in estimates of global mortality. While it is important to classify deaths according to specific causes such as pneumonia, malaria and diarrheal diseases, we contend that it is a mistake to ignore the unifying feature of all of these deaths--they are due to sepsis. The issue of highlighting sepsis as the end result of severe infections is not merely cosmetic but is important for a provision of care especially in resource limited environments where skilled healthcare workers are in short supply and care is being delivered by teams with limited training and clinical skills. Highlighting sepsis and the few simple emergency therapeutic interventions needed will focus on the actual problems that confront clinicians in regions with limited resources.
Evolution, evidence and effect of secondary prophylaxis against rheumatic fever
Publisher: Medknow
Date: 2015
Targeting a Novel Plasmodium falciparum Purine Recycling Pathway with Specific Immucillins
Publisher: Elsevier BV
Date: 03-2005
Disease burden and health-care climic attendances for young children in remote Aboriginal communities of northern Australia
Publisher: WHO Press
Date: 04-2008
Refining Risk Stratification Among Children With Latent Rheumatic Heart Disease
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-06-2023
Invasive Group A Streptococcal Disease
Publisher: Springer Science and Business Media LLC
Date: 06-2012
The prevention, diagnosis and management of central venous line infections in children
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.JINF.2015.04.029
Abstract: With advancing paediatric healthcare, the use of central venous lines has become a fundamental part of management of neonates and children. Uses include haemodynamic monitoring and the delivery of lifesaving treatments such as intravenous fluids, blood products, antibiotics, chemotherapy, haemodialysis and total parenteral nutrition (TPN). Despite preventative measures, central venous catheter-related infections are common, with rates of 0.5-2.8/1000 catheter days in children and 0.6-2.5/1000 catheter days in neonates. Central line infections in children are associated with increased mortality, increased length of hospital and intensive care unit stay, treatment interruptions, and increased complications. Prevention is paramount, using a variety of measures including tunnelling of long-term devices, chlorhexidine antisepsis, maximum sterile barriers, aseptic non-touch technique, minimal line accessing, and evidence-based care bundles. Diagnosis of central line infections in children is challenging. Available s les are often limited to a single central line blood culture, as clinicians are reluctant to perform painful venepuncture on children with a central, pain-free, access device. With the advancing evidence basis for antibiotic lock therapy for treatment, paediatricians are pushing the boundaries of line retention if safe to do so, due to among other reasons, often limited venous access sites. This review evaluates the available paediatric studies on management of central venous line infections and refers to consensus guidelines such as those of the Infectious Diseases Society of America (IDSA).
Talking skin: attitudes and practices around skin infections, treatment options, and their clinical management in a remote region in Western Australia
Publisher: Rural and Remote Health
Date: 21-09-2019
DOI: 10.22605/RRH5227
Pain in the Backside: Exploring Subcutaneous Benzathine Penicillin G Acceptability
Publisher: Elsevier BV
Date: 2019
Modelling study of the ability to diagnose acute rheumatic fever at different levels of the Ugandan healthcare system
Publisher: BMJ
Date: 03-2022
DOI: 10.1136/BMJOPEN-2021-050478
Abstract: To determine the ability to accurately diagnose acute rheumatic fever (ARF) given the resources available at three levels of the Ugandan healthcare system. Using data obtained from a large epidemiological database on ARF conducted in three districts of Uganda, we selected variables that might positively or negatively predict rheumatic fever based on diagnostic capacity at three levels/tiers of the Ugandan healthcare system. Variables were put into three statistical models that were built sequentially. Multiple logistic regression was used to estimate ORs and 95% CI of predictors of ARF. Performance of the models was determined using Akaike information criterion, adjusted R2, concordance C statistic, Brier score and adequacy index. A model with clinical predictor variables available at a lower-level health centre (tier 1) predicted ARF with an optimism corrected area under the curve (AUC) (c-statistic) of 0.69. Adding tests available at the district level (tier 2, ECG, complete blood count and malaria testing) increased the AUC to 0.76. A model that additionally included diagnostic tests available at the national referral hospital (tier 3, echocardiography, anti-streptolysin O titres, erythrocyte sedimentation rate/C-reactive protein) had the best performance with an AUC of 0.91. Reducing the burden of rheumatic heart disease in low and middle-income countries requires overcoming challenges of ARF diagnosis. Ensuring that possible cases can be evaluated using electrocardiography and relatively simple blood tests will improve diagnostic accuracy somewhat, but access to echocardiography and tests to confirm recent streptococcal infection will have the greatest impact.
Harmonizing Surveillance Methodologies for Group A Streptococcal Diseases( )
Publisher: Oxford University Press (OUP)
Date: 15-09-2022
DOI: 10.1093/OFID/OFAC210
Abstract: Group A Streptococcus (Strep A) is responsible for a significant global health and economic burden. The recent prioritization of Strep A vaccine development by the World Health Organization has prompted global research activities and collaborations. To progress this prioritization, establishment of robust surveillance for Strep A to generate updated regional disease burden estimates and to establish platforms for future impact evaluation is essential. Through the activities of the Strep A Vaccine Global Consortium (SAVAC), we have refined and harmonized surveillance protocols for 7 Strep A disease endpoints with a view that these will form part of surveillance standards for ongoing research and public health activities.
Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species
Publisher: Proceedings of the National Academy of Sciences
Date: 16-05-2019
Abstract: Ultra-high dose-rate (≥100 Gy⋅s −1 ) irradiation, termed FLASH radiotherapy, affords some remarkable (if not unexpected) normal tissue sparing in the irradiated brain when compared with conventional dose rates (0.07–0.1 Gy⋅s −1 ) used in clinical practice. Radiation-induced neurocognitive deficits, persistent neuroinflammation, and the structural degradation of mature neurons, typical of conventional dose-rate exposures, were resolved significantly in a preclinical mouse model exposed to FLASH radiotherapy. These benefits persisted over a 6-mon postirradiation interval and were caused, in part, by a mechanism involving reduced reactive oxygen species. Since normal tissue injury during and following radiotherapy dictates the maximum tolerated dose, the capability to ameliorate these adverse side effects holds significant promise for improving therapeutic outcome for cancer survivors worldwide.
Rheumatic fever in a high incidence population: the importance of monoarthritis and low grade fever
Publisher: BMJ
Date: 09-2001
DOI: 10.1136/ADC.85.3.223
Abstract: To describe the clinical features of rheumatic fever and to assess the Jones criteria in a population and setting similar to that in many developing countries. The charts of 555 cases of confirmed acute rheumatic fever in 367 patients (97% Aboriginal) and more than 200 possible rheumatic fever cases from the tropical "Top End" of Australia's Northern Territory were reviewed retrospectively. Most clinical features were similar to classic descriptions. However, monoarthritis occurred in 17% of confirmed non-chorea cases and 35% of unconfirmed cases, including up to 27 in whom the diagnosis was missed because monoarthritis is not a major manifestation. Only 71% and 25% of confirmed non-chorea cases would have had fever using cut off values of 38 degrees C and 39 degrees C, respectively. In 17% of confirmed non-chorea cases, anti-DNase B titres were raised but antistreptolysin O titres were normal. Although features of recurrences tended to correlate with initial episodes, there were numerous exceptions. Monoarthritis and low grade fever are important manifestations of rheumatic fever in this population. Streptococcal serology results may support a possible role for pyoderma in rheumatic fever pathogenesis. When recurrences of rheumatic fever are common, the absence of carditis at the first episode does not reliably predict the absence of carditis with recurrences.
Short-course oral co-trimoxazole versus intramuscular benzathine benzylpenicillin for impetigo in a highly endemic region: An open-label, randomised, controlled, non-inferiority trial
Publisher: Elsevier BV
Date: 12-2014
Acute Hematogenous Osteomyelitis in Children
Publisher: Springer Science and Business Media LLC
Date: 2004
DOI: 10.2165/00148581-200406060-00002
Abstract: Acute hematogenous osteomyelitis is most common in children and has the potential to cause life-long musculoskeletal deformities. Most cases are caused by Staphylococcus aureus. Haemophilus influenzae type b (Hib) is now rare in countries that routinely use the Hib vaccine. Although magnetic resonance imaging is the preferred modality in localized disease, scintigraphy is often preferred as the first line of investigation because it helps to clarify the location of infection and exclude the presence of multifocal disease. Where the presentation is typical, there is no underlying disease, there is a low prevalence of community-acquired methicillin-resistant S. aureus (CA-MRSA), and there is a good response to antibacterial therapy, a diagnostic bone aspirate or biopsy is not necessary. The first-line antibacterial choice in most circumstances is a beta-lactamase-resistant penicillin. If CA-MRSA is suspected, the first-line options include clindamycin, the addition of an aminoglycoside or, rarely, vancomycin. In most patients, the total duration of therapy can be substantially shorter than the traditional 6 weeks, and oral therapy can be commenced after a brief course of intravenous antibacterials. We recommend 3 days of intravenous therapy followed by 3 weeks of high-dose oral antibacterials, provided there is no underlying illness, the presentation is typical and acute, and there has been a good response to treatment initially. Any deviation from this requires more intensive confirmation of the diagnosis (with imaging and/or biopsy or aspiration), and prolongation of intravenous therapy and total duration of treatment. Close monitoring and follow-up for at least 2 years are advised to detect complications.
Successful treatment of foscarnet-resistant herpes simplex stomatitis with intravenous cidofovir in a child
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2001
DOI: 10.1097/00006454-200111000-00016
Abstract: A leukemic child developed recurrent herpes simplex virus lesions shortly after receiving a bone marrow transplant and while taking acyclovir. The isolate was resistant to acyclovir and foscarnet in vitro. The lesions responded to a course of cidofovir.
The global burden of sore throat and group A Streptococcus pharyngitis: A systematic review and meta-analysis
Publisher: Elsevier BV
Date: 08-2017
A regional initiative to reduce skin infections amongst aboriginal children living in remote communities of the Northern Territory, Australia.
Publisher: Public Library of Science (PLoS)
Date: 24-11-2009
Clinical Epidemiology of Rheumatic Fever and Rheumatic Heart Disease in Tropical Australia
Publisher: Springer US
Date: 1997
Time to tackle rheumatic heart disease: Data needed to drive global policy dialogues
Publisher: Informa UK Limited
Date: 07-09-2018
DOI: 10.1080/17441692.2018.1515970
Abstract: Rheumatic heart disease (RHD) is an avoidable disease of poverty that persists predominantly in low resource settings and among Indigenous and other high-risk populations in some high-income nations. Following a period of relative global policy inertia on RHD, recent years have seen a resurgence of research, policy and civil society activity to tackle RHD this has culminated in growing momentum at the highest levels of global health diplomacy to definitively address this disease of disadvantage. RHD is inextricably entangled with the global development agenda, and effective RHD action requires concerted efforts both within and beyond the health policy sphere. This report provides an update on the contemporary global and regional policy landscapes relevant to RHD, and highlights the fundamental importance of good data to inform these policy dialogues, monitor systems responses and ensure that no one is left behind.
Case-control evaluation of the effectiveness of the G1P[8] human rotavirus vaccine during an outbreak of rotavirus G2P[4] infection in central Australia.
Publisher: Oxford University Press (OUP)
Date: 17-12-2011
DOI: 10.1093/CID/CIQ101
Abstract: The human rotavirus vaccine was evaluated during an outbreak of rotavirus G2P[4] infection in central Australia. No overall protective effect against hospitalization was demonstrated, raising concerns over the durability of vaccine protection against heterotypic strains. Two and a half years after commencing routine vaccination with human rotavirus vaccine, an outbreak of rotavirus G2P[4] infection occurred in central Australia. Vaccine effectiveness against a P[8]-containing strain (G9P[8]) had been demonstrated previously in this setting. This subsequent outbreak provided the opportunity to evaluate vaccine effectiveness against hospitalizations for a non-vaccine-related genotype in the same population. A case-control study was nested within a cohort of vaccine-eligible children listed on a population-based immunization register. Children with rotavirus-confirmed gastroenteritis were in idually matched by date of birth and Indigenous status with 4 control subjects. Forty-one cases met the inclusion criteria, and 21 were severe cases among infants aged <12 months. Nineteen (46%) of 41 case patients had received 2 doses of human rotavirus vaccine, compared with 87 (53%) of 164 control subjects. Vaccine effectiveness against rotavirus-related hospitalization was 19% (odds ratio, .81 95% confidence interval, .32-2.05) for 2 doses compared with none. On secondary analysis, there was evidence of a protective effect against disease complicated by acidosis in the subset of infants aged <12 months (odds ratio, .15 95% confidence interval, .03-.84). Evidence was not found for an overall protective effect of human rotavirus vaccine against hospitalization for rotavirus disease in this setting. Post hoc analyses suggested a protective effect against severe disease in young infants.
Treatment of Group A streptococcal infections
Publisher: Elsevier BV
Date: 11-2010
Epidemiology and risk factors for recurrent severe lower limb cellulitis: a longitudinal cohort study
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.CMI.2018.01.023
Abstract: To describe the epidemiology and risk factors for recurrence of severe lower leg cellulitis (LLC). A longitudinal cohort study using state-wide data of adults presenting with recurrent LLC following a primary episode occurring between January 2002 and December 2013. The incidence of recurrent LLC was estimated using the cumulative incidence function, accounting for mortality. Independent risk factors for recurrence were identified using Fine-Gray sub-distribution and Cox proportional hazards models. Of 36 276 patients presenting with their first episode of LLC, 4598 had at least one recurrence during the follow-up period. The cumulative incidence of first, second, and third recurrences at 12 months since previous infection was 6.3% (95% CI 6.0-6.5), 17.2% (95% CI 16.1-18.4), and 29.4% (95% CI 26.8-31.9), respectively, and at 5 years was 13.9% (95% CI 13.5-14.3), 35.9% (95% CI 34.2-37.5), and 52.9% (95% CI 49.5-56.2), respectively. The length of hospitalization increased from 3 days for the primary episode to 4 and 5 days for first and all subsequent recurrences, respectively. Independent risk factors for recurrent LLC included age, ethnicity (Indigenous Australian), local factors relating to lower leg pathology, conditions that commonly result in peripheral oedema, and systemic conditions that may be associated with increased leg size. LLC recurrences are frequent, and each episode increases the likelihood of subsequent recurrence and length of hospitalization. These data provide context and scope to develop workable and effective strategies to prevent secondary episodes for all cases of primary LLC.
Severe lower limb cellulitis: defining the epidemiology and risk factors for primary episodes in a population-based case-control study
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.CMI.2018.01.024
Abstract: To describe the epidemiology and risk factors for primary episodes of severe lower leg cellulitis (LLC). This was a longitudinal cohort study using state-wide data linkage of adults presenting to Western Australian (WA) hospitals with a first ever LLC from January 2002 to December 2013. The study aimed at determining risk factors, medical records from the index patient, together with comparable data from controls matched by age, sex, postcode, and month of admission. During the period, 36 276 patients presented with their first episode of LLC. The incidence increased by 4.7% per annum, reaching 204.8 (95% CI 198.6-211.1) per 100 000 population by December 2013. Analysis of 29 062 case-control pairs showed several conditions with lower limb pathology were independently associated with LLC, including varicose veins (AOR 2.95, 95% CI 2.50-3.48, p < 0.001), lymphoedema (AOR 2.65, 95% CI 1.71-4.10, p < 0.001), tinea pedis (AOR 3.05, 95% CI 1.45-6.42, p 0.003), and saphenous vein harvest during coronary artery bypass grafting (AOR 1.74, 95% CI 1.32-2.30, p < 0.001). Also associated with LLC was obesity (AOR 2.05, 95% CI 1.82-2.31, p < 0.001), renal disease (AOR 1.28, 95% CI 1.14-1.44, p < 0.001), rheumatologic conditions (AOR 2.12, 95% CI 1.72-2.60, p < 0.001), hemiplegia araplegia (AOR 1.31, 95% CI 1.13-1.52, p < 0.001), and liver disease (AOR 1.77, 95% CI 1.51-2.06, p < 0.001). LLC presents a major burden to the health sector and is increasing with an ageing population. Given the high rates of recurrence, long-term morbidity, and economic impact, efforts to reduce primary episodes should be incorporated into the infectious diseases and healthy ageing research agenda.
Improving primary prevention of acute rheumatic fever in Australia: consensus primary care priorities identified through an eDelphi process
Publisher: BMJ
Date: 03-2022
DOI: 10.1136/BMJOPEN-2021-056239
Abstract: To establish the priorities of primary care providers to improve assessment and treatment of skin sores and sore throats among Aboriginal and Torres Strait Islander people at risk of acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Modified eDelphi survey, informed by an expert focus group and literature review. Primary care services in any one of the five Australian states or territories with a high burden of ARF. People working in any primary care role within the last 5 years in jurisdiction with a high burden of ARF. Nine people participated in the scoping expert focus group which informed identification of an access framework for subsequent literature review. Fifteen broad concepts, comprising 29 strategies and 63 different actions, were identified on this review. These concepts were presented to participants in a two-round eDelphi survey. Twenty-six participants from five jurisdictions participated, 16/26 (62%) completed both survey rounds. Seven strategies were endorsed as high priorities. Most were demand-side strategies with a focus on engaging communities and in iduals in accessible, comprehensive, culturally appropriate primary healthcare. Eight strategies were not endorsed as high priority, all of which were supply-side approaches. Qualitative responses highlighted the importance of a comprehensive primary healthcare approach as standard of care rather than disease-specific strategies related to management of skin sores and sore throat. Primary care staff priorities should inform Australia’s commitments to reduce the burden of RHD. In particular, strategies to support comprehensive Aboriginal and Torres Strait Islander primary care services rather than an exclusive focus on discrete, disease-specific initiatives are needed.
The American Heart Association’s Call to Action for Reducing the Global Burden of Rheumatic Heart Disease: A Policy Statement From the American Heart Association
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-11-2020
DOI: 10.1161/CIR.0000000000000922
Abstract: Rheumatic heart disease (RHD) affects ≈40 million people and claims nearly 300 000 lives each year. The historic passing of a World Health Assembly resolution on RHD in 2018 now mandates a coordinated global response. The American Heart Association is committed to serving as a global ch ion and leader in RHD care and prevention. Here, we pledge support in 5 key areas: (1) professional healthcare worker education and training, (2) technical support for the implementation of evidence-based strategies for rheumatic fever/RHD prevention, (3) access to essential medications and technologies, (4) research, and (5) advocacy to increase global awareness, resources, and capacity for RHD control. In bolstering the efforts of the American Heart Association to combat RHD, we hope to inspire others to collaborate, communicate, and contribute.
Barriers and Enablers of Health Service Utilisation for Childhood Skin Infections in Remote Aboriginal Communities of Western Australia
Publisher: MDPI AG
Date: 28-01-2020
Abstract: In Australia, children living in remote Aboriginal communities experience high rates of skin infections and associated complications. Prompt presentation to primary care health services is crucial for early diagnosis and treatment. We performed a qualitative study in four remote Aboriginal communities in the Pilbara region of Western Australia to explore factors that affected health service utilisation for childhood skin infections in this setting. The study consisted of semistructured interviews and focus group discussions with parents and carers (n = 16), healthcare practitioners (n = 15) and other community service providers (n = 25). We used Andersen’s health service utilisation model as an analytical framework. Our analysis captured a wide range of barriers that may undermine timely use of health services for childhood skin infections. These included general factors that illustrate the importance of cultural competency amongst healthcare providers, patient-centred care and community engagement. Relating specifically to health service utilisation for childhood skin infections, we identified their apparent normalisation and the common use of painful benzathine penicillin G injections for their treatment as important barriers. Health service utilisation in this setting may be enhanced by improving general awareness of the significance of childhood skin infections, actively engaging parents and carers in consultation and treatment processes and strengthening community involvement in health service activities.
The high burden of rheumatic heart disease found on autopsy in Fiji
Publisher: Cambridge University Press (CUP)
Date: 20-12-2007
Study protocol for controlled human infection for penicillin G againstStreptococcus pyogenes: a double-blinded, placebo-controlled, randomised trial to determine the minimum concentration requi
Publisher: BMJ
Date: 12-2022
DOI: 10.1136/BMJOPEN-2022-064022
Abstract: Regular intramuscular benzathine penicillin G injections have been the cornerstone of rheumatic heart disease (RHD) secondary prophylaxis since the 1950s. As the pharmacological correlate of protection remains unknown, it is difficult to recommend changes to this established regimen. Determining the minimum effective penicillin exposure required to prevent Streptococcus pyogenes infection will accelerate development of new long-acting penicillins for RHD prevention as well as inform opportunities to improve existing regimens. The CHIPS trial will address this knowledge gap by directly testing protection afforded by different steady state plasma concentrations of penicillin in an established model of experimental human S. pyogenes pharyngitis. This is a double-blinded, placebo-controlled, randomised experimental human infection study. Sixty healthy adult volunteers aged 18–40 years will be recruited and randomised 1:1:1:1:1 to continuous intravenous penicillin infusions targeting five different steady state plasma concentrations of 0 (placebo), 3, 6, 12 and 20 ng/mL via a midline catheter. Each participant’s penicillin pharmacokinetic parameters will be established prior to the challenge, to ensure accurate dosing for the continuous infusion. Following the challenge with a well-characterised strain of S. pyogenes , participants will be observed for up to 6 days for the development of pharyngitis and treated with antibiotics prior to discharge. The primary objective is to determine the minimum effective steady-state plasma penicillin concentration required to prevent experimental pharyngitis. Secondary objectives will explore systemic and mucosal immunoinflammatory responses during pharyngitis, bacterial colonisation dynamics, environmental contamination and qualitative evaluation of the participant experience. Ethical approval has been obtained (Bellberry Human Research Ethics Committee). Findings will be reported in peer-reviewed publications and presented at national/international stakeholder forums. ACTRN12621000751875.
Prospective Surveillance of Invasive Group A Streptococcal Disease, Fiji, 2005–2007
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 02-2009
Practical challenges of conducting research into rheumatic fever in remote Aboriginal communities
Publisher: AMPCo
Date: 05-2006
DOI: 10.5694/J.1326-5377.2006.TB00346.X
Abstract: Before embarking on an epidemiological study of acute rheumatic fever in remote Aboriginal communities, researchers engaged in the processes of community consultation, consent and household enrollment. Community expectations and time constraints are not necessarily those of the funding bodies, and a considerable investment of time and local engagement was required before the project proceeded with local support. The remoteness of the communities, harsh climate and limited infrastructure made working conditions difficult. Nevertheless, the study was completed and the results are being returned to the local councils and households. The research team continues to maintain its relationship with each study community.
Cardiac remodelling as a result of pre-term birth: implications for future cardiovascular disease
Publisher: Oxford University Press (OUP)
Date: 07-05-2010
Abstract: Pre-term birth affects 10-12% of live births and occurs when the myocardium is still developing therefore, the final structure of the myocardium could be altered. We hypothesized that, in response to pre-term birth, structural remodelling occurs within the myocardium which enables the immature heart muscle to adapt to the haemodynamic transition at birth but results in persistent alterations in its structure. Our objective was to determine how pre-term birth alters the final structure of the myocardium. Using sheep, pre-term birth was induced at 0.9 of term hearts were examined at 9 weeks after term-equivalent age, when cardiomyocyte proliferation and maturation have ceased. In pre-term lambs, we found that cardiomyocytes of both ventricles and the interventricular septum were hypertrophied. Cardiomyocyte maturation in pre-term lambs was altered in that there was a greater proportion of mononucleated, polyploid (4n) cardiomyocytes in both ventricles compared with controls importantly, induction of polyploidy is associated with irreversible stress-related changes in DNA. We also found a six- to seven-fold increase in collagen deposition, usually accompanied by lymphocytic infiltration. We conclude that pre-term birth leads to remodelling of the myocardium that alters its final structure. This may programme for long-term cardiac vulnerability.
Rheumatic heart disease in Indigenous young peoples
Publisher: Elsevier BV
Date: 06-2021
Underdiagnosis of acute rheumatic fever in primary care settings in a developing country
Publisher: Wiley
Date: 04-09-2009
DOI: 10.1111/J.1365-3156.2009.02385.X
Abstract: To determine the incidence rate, characterize the clinical features and assess the diagnostic evaluation of children presenting with features of acute rheumatic fever (ARF) at two clinics in a region of Fiji where rheumatic heart disease is known to be endemic. We reviewed 5 years (2003-2008) of primary care records from 15 841 patients aged 4-20 years using a pre-determined case definition for ARF and we reviewed detailed clinical data from 944 cases with features of possible ARF. The crude incidence of first episodes of definite ARF in this setting among patients aged 4-20 years was 24.9 per 100 000 person-years. Joint involvement suggestive of a potential first presentation of ARF but not sufficient for a definite retrospective diagnosis was documented in a further 94 records. There were another 514 cases of joint involvement less suggestive of ARF and 316 cases of unexplained fever with no evidence of localized infection. Patients presenting with potential features of ARF seldom had a diagnostic evaluation sufficient to exclude its diagnosis. The incidence of ARF at these clinics is nearly twice that reported in a local hospital-based study, but it is likely to under-represent the actual number of cases presenting to primary care. There is a need for better surveillance for ARF and to develop simple and practical approaches to diagnosing ARF in primary care in low-resource settings.
A subtle presentation of acute rheumatic fever in remote northern Australia
Publisher: Wiley
Date: 04-1996
DOI: 10.1111/J.1445-5994.1996.TB00898.X
Abstract: Concern for public health has been growing with the increasing volume of cases of COVID-19 in India. To combat this pandemic, India has implemented nationwide lockdowns, and unlocking phases continue with certain restrictions in different parts of the country. The lockdown has required people to adopt social-distance measures to minimize contacts in order to reduce the risks of additional infection. Nevertheless, the lockdown has already impacted economic activities and other dimensions of the health of in iduals and society. Although many countries have helped their people through advanced welfare protection networks and numerous support aids, several emerging economies face specific difficulties to adapt to the pandemic due to vulnerable communities and scarce resources. However, certain lower-income countries need more rigorous analysis to implement more effective strategies to combat COVID-19. Accordingly, the current systematic review addresses the impacts of the COVID-19 pandemic and lockdowns in India in relation to health and the economy. This work also provides further information on health inequalities, eco-nomic and social disparities in the country due to the COVID-19 pandemic and lockdowns and also contributes pragmatic suggestions for overcoming these challenges. These observations will be useful to the relevant local and national officials for improving and adopting novel strategies to face lockdown challenges.
Community-associated methicillin-resistant Staphylococcus aureus skin infections in the tropics.
Publisher: Elsevier BV
Date: 2011
DOI: 10.1016/J.DET.2010.09.005
Abstract: Skin and soft tissue infections (SSTI) caused by Staphylococcus aureus are very common, particularly in children, in tropical regions. The proportion of S aureus SSTI caused by community-associated methicillin-resistant S aureus (CA-MRSA) varies according to region, but is up to 25% in some areas. There are erse CA-MRSA clones, including several that harbor Panton-Valentine leukocidin. Key predisposing factors for staphylococcal infections are scabies infestation, overcrowding, poor hygiene, and inadequate water supplies. In the setting of a community outbreak of staphylococcal SSTI, interventions intended to improve personal and community hygiene are likely to be the most practical, effective, and achievable. Options for oral treatment of clinical infections caused by CA-MRSA include clindamycin and trimethoprim-sulfamethoxazole. Although rapid diagnostics are now available, and 2 vaccines have reached clinical trials, neither of these is likely to be of use in tropical, developing regions in the near future.
Sedimented professional identities: early childhood education pre-service teachers
Publisher: Informa UK Limited
Date: 18-05-2020
Ten-year follow-up of a cohort with rheumatic heart disease (RHD)
Publisher: Wiley
Date: 12-1997
DOI: 10.1111/J.1445-5994.1997.TB01000.X
Abstract: Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) occur at among the highest rates in the world in Aboriginal Australians of the Northern Territory. To follow-up a previously-described cohort of Aboriginal children with RHD, in order to understand better the outcome of ARF and RHD in this population, and to identify areas where the impact of these diseases might be lessened Of a cohort of 33 children seen between 1980 and 1984, 27 survived until July, 1984. Twenty-five of the survivors were followed up for a mean of 10.6 years to a mean age of 24.1 years. The two deaths during follow-up were both due to RHD. Six people underwent valve replacement surgery all were clinically healthy when last seen. Complications included two thromboembolic events and two episodes of endocarditis. Deterioration of RHD severity was associated with ARF recurrences (relative risk 3.6 95% CI 1.7-7.6), and resolution of RHD was associated with having only mild valve lesions initially (risk difference 0.58 95% CI 0.30 to 0.86). During follow-up, valve lesions tended either to resolve or to become more complex and severe, with a higher proportion of aortic valve lesions and multiple valve lesions. Of seven children with suspected past ARF, excluded from the original cohort because of normal cardiac findings at the time, three developed RHD, including one who died due to RHD and two with moderate or severe valve lesions. In Aboriginal Australians, poor outcomes of RHD are common, and are associated with ARF recurrences and early onset of more severe valve lesions. A coordinated ARF and RHD control programme is needed in this region, using a centralised register of patients, and concentrating on strategies to improve adherence to secondary prophylaxis regimens, better clinical care (including newer surgical techniques) and education of patients, families, and health staff.
Active Case Finding for Rheumatic Fever in an Endemic Country
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-08-2020
Abstract: Despite the high burden of rheumatic heart disease in sub‐Saharan Africa, diagnosis with acute rheumatic fever (ARF) is exceedingly rare. Here, we report the results of the first prospective epidemiologic survey to diagnose and characterize ARF at the community level in Africa. A cross‐sectional study was conducted in Lira, Uganda, to inform the design of a broader epidemiologic survey. Key messages were distributed in the community, and children aged 3 to 17 years were included if they had either (1) fever and joint pain, (2) suspicion of carditis, or (3) suspicion of chorea, with ARF diagnoses made by the 2015 Jones Criteria. Over 6 months, 201 children met criteria for participation, with a median age of 11 years (interquartile range, 6.5) and 103 (51%) female. At final diagnosis, 51 children (25%) had definite ARF, 11 (6%) had possible ARF, 2 (1%) had rheumatic heart disease without evidence of ARF, 78 (39%) had a known alternative diagnosis (10 influenza, 62 malaria, 2 sickle cell crises, 2 typhoid fever, 2 congenital heart disease), and 59 (30%) had an unknown alternative diagnosis. ARF persists within rheumatic heart disease–endemic communities in Africa, despite the low rates reported in the literature. Early data collection has enabled refinement of our study design to best capture the incidence of ARF and to answer important questions on community sensitization, healthcare worker and teacher education, and simplified diagnostics for low‐resource areas. This study also generated data to support further exploration of the relationship between malaria and ARF diagnosis in rheumatic heart disease/malaria‐endemic countries.
Immunogenicity of a third scheduled dose of rotavirus vaccine in Australian Indigenous infants to improve protection against gastroenteritis: a phase IV, double-blind, randomised, placebo-controlled clinical trial
Publisher: Cold Spring Harbor Laboratory
Date: 27-09-2021
DOI: 10.1101/2021.09.26.21264122
Abstract: The oral rotavirus vaccine, Rotarix (GlaxoSmithKline), is licensed for use in infants as two doses in the first six months of life. For infants living in settings with high child-mortality, and also for rural and remote Australian Aboriginal infants, clinical protection conferred by two doses of Rotarix appears to be reduced. We assessed the effect of an additional dose of Rotarix on vaccine immune responses among Aboriginal children who are 6 to 12 months old. ORVAC is a two-stage, double-blind, randomised, placebo-controlled trial conducted across regional urban and remote locations of Australia’s Northern Territory. Aboriginal children 6 to 12 months old who had received one or two prior doses of Rotarix were randomised 1:1 to receive an additional dose of Rotarix or matched placebo. The primary immunological endpoint was seroresponse defined as an anti-rotavirus IgA level ≥ 20 AU/mL, approximately one month following Rotarix or placebo. ClinicalTrials.gov ( NCT02941107 ). Between March 2018 and August 2020, 253 infants were enrolled. Of these, 178 infants (70%) had analysable serological results after follow-up 89 randomised to Rotarix and 89 to placebo. The proportion with a seroresponse was 85% after Rotarix compared to 71% after placebo the probability of a higher rate of seroresponse in the Rotarix than the placebo arm was 99%. There were no occurrences of intussusception or any serious adverse events attributed to Rotarix or placebo in the 28 days following the additional dose of Rotarix or placebo. An additional dose of Rotarix among Australian Aboriginal infants 6 to 12 months old increased the proportion with a vaccine seroresponse. If it can be proven that this translates into better protection against disease, scheduling an additional dose may be a viable strategy for further reducing the global burden of rotavirus disease. NHMRC (GNT1086952). Rotavirus vaccine programs have reduced the global burden of gastroenteritis disease among young children, but rotavirus still causes ,000 child deaths each year. A recent systematic review in the Lancet Global Healt h found that the effectiveness of oral rotavirus vaccines is variable, from 45 – 58% in settings with high child mortality to 83%-85% in settings with low child mortality. In high child mortality settings there is also evidence of waning effectiveness after 12 months old. Reduced vaccine effectiveness has also been reported among Australian Aboriginal children. Previous trials have failed to demonstrate improved rotavirus vaccine effectiveness with strategies such as withholding breastfeeding, or co-administering vaccines with probiotics or zinc. Pre-licensure studies of Rotarix in Africa did not clearly indicate whether a three-dose Rotarix schedule had benefit over a two-dose schedule, although all vaccine doses were given before infants were six months old when maternal antibodies may impede vaccine responses. Trials in Bangladesh and Mali found that a third Rotarix dose given after 6 months old improved the immune response to vaccine. In the first stage of our novel two-stage randomised clinical trial, we showed that scheduling an additional Rotarix dose for remote Australian Aboriginal infants after 6 months old increased the proportion with evidence of vaccine seroresponse. Scheduling an additional dose of Rotarix after 6 months old is feasible, and trials in three settings have now demonstrated that it improves immune responses. Trials should now be conducted in a number of high burden settings to determine whether this strategy results in improved clinical protection against severe gastroenteritis.
Is caseload midwifery a healthy work-form? – A survey of burnout among midwives in Denmark
Publisher: Elsevier BV
Date: 03-2017
Invasive pneumococcal disease in Fiji: clinical syndromes, epidemiology, and the potential impact of pneumococcal conjugate vaccine.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2010
Pneumococcal nasopharyngeal carriage and patterns of penicillin resistance in young children in Fiji
Publisher: Informa UK Limited
Date: 09-2006
Increasing Severity of Invasive Group A Streptococcal Disease in Australia: Clinical and Molecular Epidemiological Features and Identification of a New Virulent M-Nontypeable Clone
Publisher: Oxford University Press (OUP)
Date: 11-1995
DOI: 10.1093/CLINIDS/21.5.1220
Abstract: We conducted a 12-year review of all cases of group A streptococcal (GAS) bacteremia that were seen at Royal Children's Hospital in Melbourne, Australia, from 1982 through 1993. Forty-two cases were identified. There was a trend towards increased incidence of infections, as well as a clear increase in their severity, during the study period more previously healthy children were affected during the last 6 years of the study (80% of cases) than during the first 6 years (47% of cases), and more complications occurred during the latter period than during the former (40% vs. 20%, respectively, with an 88% complication rate over the last 12 months). Seventy-four GAS isolates (41 invasive, 23 noninvasive, and 10 indeterminate) were analyzed. An M type 1 clone that was positive for the pyrogenic exotoxin A gene (speA) and that has been found to cause invasive disease in the Northern Hemisphere was most frequent among invasive isolates. Molecular typing also identified a genetically distinct strain that was virulent, mucoid, and M nontypable. Invasive GAS disease in Melbourne has become increasingly aggressive. Newer typing methods should be used in conjunction with traditional serotyping in order to maintain epidemiological surveillance of virulent strains.
Comparison of Citrated Human Blood, Citrated Sheep Blood, and Defibrinated Sheep Blood Mueller-Hinton Agar Preparations for Antimicrobial Susceptibility Testing of Streptococcus pneumon
Publisher: American Society for Microbiology
Date: 10-2010
DOI: 10.1128/JCM.02357-09
Abstract: The use of Mueller-Hinton agar supplemented with citrated human or citrated sheep blood was compared with the use of routinely used Mueller-Hinton agar supplemented with defibrinated sheep blood for antimicrobial susceptibility testing of Streptococcus pneumoniae . The alternate supplements were found to be unsatisfactory, particularly for testing resistant isolates, and therefore are not recommended.
Echocardiographic screening for rheumatic heart disease in high and low risk Australian children
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-05-2014
DOI: 10.1161/CIRCULATIONAHA.113.003495
Abstract: Echocardiographic screening for rheumatic heart disease (RHD) is becoming more widespread, but screening studies to date have used different echocardiographic definitions. The World Heart Federation has recently published new criteria for the echocardiographic diagnosis of RHD. We aimed to establish the prevalence of RHD in high-risk Indigenous Australian children using these criteria and to compare the findings with a group of Australian children at low risk for RHD. Portable echocardiography was performed on high-risk Indigenous children aged 5 to15 years living in remote communities of northern Australia. A comparison group of low-risk, non-Indigenous children living in urban centers was also screened. Echocardiograms were reported in a standardized, blinded fashion. Of 3946 high-risk children, 34 met World Heart Federation criteria for definite RHD (prevalence, 8.6 per 1000 [95% confidence interval, 6.0–12.0]) and 66 for borderline RHD (prevalence, 16.7 per 1000 [95% confidence interval, 13.0–21.2]). Of 1053 low-risk children, none met the criteria for definite RHD, and 5 met the criteria for borderline RHD. High-risk children were more likely to have definite or borderline RHD than low-risk children (adjusted odds ratio, 5.7 [95% confidence interval, 2.3–14.1] P .001). The prevalence of definite RHD in high-risk Indigenous Australian children approximates what we expected in our population, and no definite RHD was identified in the low-risk group. This study suggests that definite RHD, as defined by the World Heart Federation criteria, is likely to represent true disease. Borderline RHD was identified in children at both low and high risk, highlighting the need for longitudinal studies to evaluate the clinical significance of this finding.
Community management of endemic scabies in remote aboriginal communities of northern Australia
Publisher: Public Library of Science (PLoS)
Date: 26-05-2009
Low positive predictive value of International Classification of Diseases, 10th Revision codes in relation to rheumatic heart disease: a challenge for global surveillance
Publisher: Wiley
Date: 03-2019
DOI: 10.1111/IMJ.14221
Abstract: International Classification of Diseases, 10th Revision codes for rheumatic heart disease (RHD) include valvular heart disease of unspecified origin, limiting their usefulness for estimating RHD burden. A cross-disciplinary national consultation developed an algorithm to improve RHD identification in hospital data. The algorithm has been operationalised and piloted. The algorithm developed categorised 32% of RHD-coded patients as probable ossible RHD. We outline a series of research initiatives to improve identification of RHD in administrative data thereby contributing to monitoring the RHD burden globally.
Global emm type distribution of group A streptococci: systematic review and implications for vaccine development
Publisher: Elsevier BV
Date: 10-2009
Body distribution of impetigo and association with host and pathogen factors
Publisher: PeerJ
Date: 12-10-2022
DOI: 10.7717/PEERJ.14154
Abstract: Impetigo or skin sores are estimated to affect million people worldwide. Detailed descriptions of the anatomical location of skin sores are lacking. We used prospectively collected data from a randomised control trial of treatments for impetigo in Aboriginal children in Australia. We generated heat-map distributions of skin sores on the human body from 56 predefined anatomical locations and stratified skin sore distribution by sex, age, causative pathogen and co-infection with scabies, tinea and head lice. We compared the distribution of sores between males and females, between sores with only Streptococcus pyogenes and sores with only Staphylococcus aureus and across age groups with a Fisher’s exact test. There were 663 episodes of impetigo infections among 508 children enrolled in the trial. For all 663 episodes, the lower limbs were the most affected body sites followed by the distal upper limbs, face and scalp. On the anterior surface of the body, the pre-tibial region was the most affected while on the posterior surface, the dorsum of the hands and calves predominated. There was no observable difference between males and females in distribution of sores. Children up to 3 years of age were more likely to have sores on the upper posterior lower limbs and scalp than older age groups, with the distribution of sores differing across age groups ( p = 3 × 10 −5 ). Sores from which only Staphylococcus aureus was cultured differed in distribution to those with only Streptococcus pyogenes cultured ( p = 3 × 10 −4 ) and were more commonly found on the upper posterior lower limbs. Skin sores were predominantly found on exposed regions of the lower leg and distal upper limbs. The distribution of sores varied by age group and pathogen. These results highlight key areas of the body for clinicians to pay attention to when examining children for skin sores.
Au Promotional Effects on the Synthesis of H2O2 Directly from H2 and O2 on Supported Pd−Au Alloy Catalysts
Publisher: American Chemical Society (ACS)
Date: 26-05-2007
DOI: 10.1021/JP072934G
B‐cell antigen D8/17 is a marker of rheumatic fever susceptibility in Aboriginal Australians and can be tested in remote settings
Publisher: AMPCo
Date: 05-2006
DOI: 10.5694/J.1326-5377.2006.TB00345.X
Abstract: To test the B-cell antigen D8/17 as a marker of past rheumatic fever (RF) in a predominantly Aboriginal Australian population, and to evaluate technical modifications to allow its use in remote settings. Cross-sectional survey in a remote Aboriginal community, a regional tertiary referral hospital and a tertiary paediatric centre in Melbourne. 106 people, including three with acute RF, 38 with a history of past RF, 20 relatives of these people, and 45 healthy controls. D8/17 expression in B cells. Blood was collected from each participant and the expression of D8/17 and CD19 in each s le was analysed by flow cytometry. The mean proportion of D8/17-positive B cells was 39.3% (SD, 11.8) in patients with previous RF, 22.5% (SD, 5.2) in first-degree relatives, 11.6% (SD, 7.2) in controls, and 83.7% (SD, 10.1) in patients with acute RF (analysis of variance test between means, P = 0.001). A cut-off of 22.1% of D8/17-positive B cells to indicate past RF yielded the highest percentage of correct results (95.4%). Delayed staining of whole blood (mean, 0.55 days SD, 0.2) gave equivalent results to immediate staining, but the D8/17 assay on peripheral blood mononuclear cells was unreliable. The B-cell antigen D8/17 accurately identifies Australians with a past history of RF, and the assay is feasible in remote settings with access to facilities capable of performing D8/17 staining within half a day of s le collection.
Systematic review of rheumatic heart disease prevalencein children in developing countries: The role of environmental factors
Publisher: Wiley
Date: 06-2002
DOI: 10.1046/J.1440-1754.2002.00772.X
Abstract: To consider the worldwide prevalence of rheumatic heart disease in children in developing countries using surveys with uniform methodologies, and to consider the effect of environmental factors including socio-economic status, overcrowding, urbanization, nutrition and access to medical services on the distribution of rheumatic heart disease in developing countries. Sixty-one surveys of the prevalence of rheumatic heart disease in developing countries were found using a systematic review of MEDLINE from January 1976 to July 1999. Twenty-four studies were selected for comparison based on their uniform methodological and diagnostic techniques. There is a high prevalence of rheumatic heart disease in the Pacific region with a lower prevalence in the Indian subcontinent, Asian, sub-Saharan African, Mediterranean, Latin American and Caribbean regions. However, aside from the Indian subcontinent, these regions have not been well studied, and it may be that the true prevalence is actually higher. There is a lack of good quality prevalence surveys of rheumatic heart disease in developing countries. It appears that a threshold level where higher socio-economic status is associated with reduced prevalence of rheumatic heart disease is not reached in developing countries. Therefore, differences in prevalence between socio-economic groups in the one area cannot be detected. A similar case can be made for overcrowding. Many regions need well-designed studies of rheumatic heart disease that incorporate assessment of environmental factors as well as the study of the microbiological epidemiology of rheumatic heart disease and group A streptococci.
Childhood invasive pneumococcal disease in Tasmania, 1994-2000
Publisher: Wiley
Date: 10-2002
DOI: 10.1046/J.1440-1754.2002.00035.X
Abstract: To describe the burden of invasive pneumococcal disease in Tasmanian children, including age-specific incidence and antibiotic-resistance pattern. A population-based retrospective study was carried out, examining cases of childhood disease associated with isolates of Streptococcus pneumoniae from normally sterile sites, identified via scrutiny of laboratory records at all major Tasmanian laboratories during a 7-year period between January 1994 and December 2000. Medical records were sub-sequently examined for information describing the clinical syndrome and course of disease. Invasive pneumococcal disease was identified in 76 children during the 7-year period. The incidence per 100 000 children was 28.5 (95% CI 22.0-36.3) in children under 5 years and 54.3 (95% CI 40.2-71.8) in children under 2 years. The incidence of meningitis in children younger than 2 years was 12.2 (95% CI 6.1-21.8). Penicillin resistance was observed in 2.6% of cases, with no high level resistance. Predisposing conditions were identified in 34% of children with invasive disease. The incidence of invasive pneumococcal disease was comparable to many urban populations in Australia. The high rate of predisposing conditions supports the recommendations of the Australian Technical Advisory Group on Immunisation for targeted immunization in this group. The paucity of data describing Indigenous status is an argument for improved data collection in this area. The low level of penicillin resistance necessitates ongoing surveillance, and the lack of serotype information requires prospective data collection.
Molecular typing ofStreptococcus pyogenesfrom remote Aboriginal communities where rheumatic fever is common and pyoderma is the predominant streptococcal infection
Publisher: Cambridge University Press (CUP)
Date: 19-02-2007
DOI: 10.1017/S0950268807008023
Abstract: Aboriginal Australians in remote communities have high rates of rheumatic heart disease (RHD) yet pharyngitis is reportedly rare whilst pyoderma is common. Some strains of group A streptococci (GAS) have preference for the throat and others for the skin depending on M protein type. A study in three remote communities provided 350 GAS isolates for emm sequence typing, 244 were also emm pattern typed. There was 100% correlation between emm sequence and pattern type. Patterns D and E (non-throat tropic) made up 71% of throat and 87% of skin isolates although patterns A–C (throat tropic) were more common in the throat than the skin (RR 2·3, 95% CI 1·4–3·8) whilst the opposite was found for pattern D (RR 2·2, 95% CI 1·7–3·0). Pattern E favoured the throat (RR 1·4, 95% CI 1·1–1·8). Where environmental factors predispose to skin infection, emm pattern types D and E prevail, whatever the recovery site.
Ending rheumatic heart disease in Australia
Publisher: AMPCo
Date: 11-2020
DOI: 10.5694/MJA2.50853
Rheumatic Heart Disease in Developing Countries
Publisher: Massachusetts Medical Society
Date: 15-11-2007
DOI: 10.1056/NEJMC072541
Left ventricular remodelling in rheumatic heart disease – trends over time and implications for follow-up in childhood
Publisher: Springer Science and Business Media LLC
Date: 15-09-2023
Modeling the potential health impact of prospective Strep A vaccines
Publisher: Springer Science and Business Media LLC
Date: 10-06-2023
DOI: 10.1038/S41541-023-00668-0
Abstract: The World Health Organization published the preferred product characteristics for a Group A Streptococcus (Strep A) vaccine in 2018. Based on these parameters for the age of vaccination, vaccine efficacy, duration of protection from vaccine-derived immunity, and vaccination coverage, we developed a static cohort model to estimate the projected health impact of Strep A vaccination at the global, regional, and national levels and by country-income category. We used the model to analyse six strategic scenarios. Based on Strep A vaccine introduction between 2022 and 2034 for the primary scenario, we estimated vaccination at birth for 30 vaccinated cohorts could avert 2.5 billion episodes of pharyngitis, 354 million episodes of impetigo, 1.4 million episodes of invasive disease, 24 million episodes of cellulitis, and 6 million cases of rheumatic heart disease globally. Vaccination impact in terms of burden averted per fully vaccinated in idual is highest in North America for cellulitis and in Sub-Saharan Africa for rheumatic heart disease.
Proteins Encoded in Genomic Regions Associated with Immune-Mediated Disease Physically Interact and Suggest Underlying Biology
Publisher: Public Library of Science (PLoS)
Date: 13-01-2011
What Drives Industry 4.0 Technologies Adoption? Evidence from a SEM-Neural Network Approach in the Context of Vietnamese Firms
Publisher: MDPI AG
Date: 30-03-2023
DOI: 10.3390/SU15075969
Abstract: The development of the Industrial Revolution 4.0 has far-reaching effects on all aspects of life, the economy, and society, bringing various growth opportunities for businesses. However, businesses are still hesitant to apply these new technologies. On a research s le from a survey of 396 Vietnamese enterprises, the study uses the SEM-neural network method to determine the relationship and importance of five groups of factors affecting the firms’ Industry 4.0 technologies adoption. The results suggest that five groups of factors, including Perceived characteristics, Technological competencies, CEO characteristics, Environmental characteristics, and Subjective Norms, all positively and significantly impact the Industry 4.0 technologies adoption in Vietnam. In particular, Technological competencies are the most influential factors according to the SEM method, while Subjective norms factors have the most decisive impact according to the neural-network method. Moreover, the research also found that adopting Industry 4.0 technologies depends on different company characteristics, such as age, size, status, and industry.
The high prevalence and impact of rheumatic heart disease in pregnancy in First Nations populations in a high-income setting: a prospective cohort study
Publisher: Wiley
Date: 09-10-2020
Abstract: To describe the epidemiology of rheumatic heart disease (RHD) in pregnancy in Australia and New Zealand (A&NZ). Prospective population-based study. Hospital-based maternity units throughout A&NZ. Pregnant women with RHD with a birth outcome of ≥20 weeks of gestation between January 2013 and December 2014. We identified eligible women using the Australasian Maternity Outcomes Surveillance System (AMOSS). De-identified antenatal, perinatal and postnatal data were collected and analysed. Prevalence of RHD in pregnancy. Perinatal morbidity and mortality. There were 311 pregnancies associated with women with RHD (4.3/10 000 women giving birth, 95% CI 3.9-4.8). In Australia, 78% were Aboriginal or Torres Strait Islander (60.4/10 000, 95% CI 50.7-70.0), while in New Zealand 90% were Māori or Pasifika (27.2/10 000, 95% CI 22.0-32.3). One woman (0.3%) died and one in ten was admitted to coronary or intensive care units postpartum. There were 314 births with seven stillbirths (22.3/1000 births) and two neonatal deaths (6.5/1000 births). Sixty-six (21%) live-born babies were preterm and one in three was admitted to neonatal intensive care or special care units. Rheumatic heart disease in pregnancy persists in disadvantaged First Nations populations in A&NZ. It is associated with significant cardiac and perinatal morbidity. Preconception planning and counselling and RHD screening in at-risk pregnant women are essential for good maternal and baby outcomes. Rheumatic heart disease in pregnancy persists in First Nations people in Australia and New Zealand and is associated with major cardiac and perinatal morbidity.
Myositis complicating benzathine penicillin-G injection in a case of rheumatic heart disease
Publisher: Elsevier BV
Date: 2016
Progress Toward a Global Group A Streptococcal Vaccine
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2013
Burden of cardiovascular diseases in the Eastern Mediterranean Region, 1990–2015: findings from the Global Burden of Disease 2015 study
Publisher: Springer Science and Business Media LLC
Date: 03-08-2017
Recovering Streptococci from the Throat, a Practical Alternative to Direct Plating in Remote Tropical Communities
Publisher: American Society for Microbiology
Date: 02-2006
DOI: 10.1128/JCM.44.2.547-552.2006
Abstract: Throat swabs are regarded as the “gold standard” for diagnosing streptococcal pharyngitis and for surveillance research. Culturing throats in remote tropical settings is logistically difficult, and these settings are commonly burdened by high rates of streptococcal disease. The survival of streptococci on swabs may depend on whether they are of “throat” or “skin” type, as determined by emm pattern typing. The aims of this study were to compare the recovery rates of beta-hemolytic streptococci (BHS) using three different transport methods and to determine whether the recovery rates correlated with the emm pattern type. Monthly duplicate throat swabs were taken from occupants of selected households in three remote Aboriginal communities. Paired swabs were separated and handled in one of three ways: (i) direct inoculation onto culture media with cold-box transport (plated), (ii) sealed in a bag with a silica gel desiccant and cold-box transport (desiccant), and (iii) transport at ambient temperature and humidity (ambient). emm pattern typing was done by standard methods. Over 23 months, 4,842 throat swabs were taken, and 4,122 were paired. BHS were recovered on 11.5% of the 4,842 occasions (group A, 4.5% group C, 1.7% group G, 5.4%). Results from paired swabs showed the plated method was superior to desiccant and desiccant was better than ambient. Pooled data indicated that plated and desiccant were equivalent, and both were significantly better than ambient. There was no correlation between the emm pattern type and recovery of group A streptococci by different methods. In tropical and remote settings, cold-box transport with desiccant and subsequent inoculation of culture plates in the laboratory is a practical alternative to direct plating.
Inter-rater and intra-rater reliability and agreement of echocardiographic diagnosis of rheumatic heart disease using the World Heart Federation evidence-based criteria
Publisher: BMJ
Date: 06-2019
DOI: 10.1136/HEARTASIA-2019-011233
Abstract: Different definitions have been used for screening for rheumatic heart disease (RHD). This led to the development of the 2012 evidence-based World Heart Federation (WHF) echocardiographic criteria. The objective of this study is to determine the intra-rater and inter-rater reliability and agreement in differentiating no RHD from mild RHD using the WHF echocardiographic criteria. A standard set of 200 echocardiograms was collated from prior population-based surveys and uploaded for blinded web-based reporting. Fifteen international cardiologists reported on and categorised each echocardiogram as no RHD, borderline or definite RHD. Intra-rater and inter-rater reliability was calculated using Cohen’s and Fleiss’ free-marginal multirater kappa (κ) statistics, respectively. Agreement assessment was expressed as percentages. Subanalyses assessed reproducibility and agreement parameters in detecting in idual components of WHF criteria. S le size from a statistical standpoint was 3000, based on repeated reporting of the 200 studies. The inter-rater and intra-rater reliability of diagnosing definite RHD was substantial with a kappa of 0.65 and 0.69, respectively. The diagnosis of pathological mitral and aortic regurgitation was reliable and almost perfect, kappa of 0.79 and 0.86, respectively. Agreement for morphological changes of RHD was variable ranging from 0.54 to 0.93 κ. The WHF echocardiographic criteria enable reproducible categorisation of echocardiograms as definite RHD versus no or borderline RHD and hence it would be a suitable tool for screening and monitoring disease progression. The study highlights the strengths and limitations of the WHF echo criteria and provides a platform for future revisions.
Use of a Single-Nucleotide Polymorphism Genotyping System To Demonstrate the Unique Epidemiology of Methicillin-Resistant Staphylococcus aureus in Remote Aboriginal Comm
Publisher: American Society for Microbiology
Date: 10-2006
DOI: 10.1128/JCM.00836-06
Abstract: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a major public health problem in Australia, as in many other parts of the world. High rates of CA-MRSA skin and soft tissue infection have been reported from Aboriginal communities. We used a single-nucleotide polymorphism (SNP) genotyping typing system based on the multilocus sequence type (MLST) database to investigate the epidemiology of CA-MRSA and methicillin-sensitive S. aureus (MSSA) over a 12-month period in three remote Aboriginal communities of Northern Australia. This was supplemented by real-time PCR for Panton-Valentine leukocidin (PVL) genes, staphylococcal cassette chromosome mec (SCC mec ) typing, and antimicrobial susceptibility testing. S. aureus was recovered from pyoderma lesions on 221 occasions and throat swabs on 44 occasions. The median monthly recovery rate of S. aureus from skin sores was 58% (interquartile range, 62 to 78%), and there was no seasonal variation. Twenty-three percent of isolates were CA-MRSA the proportion was similar across the communities and did not vary over the study period. Erythromycin resistance was found in 47% of CA-MRSA and 21% of MSSA. SNP-based typing identified 14 different clonal complexes (cc) however, cc75 was predominant, accounting for 71% of CA-MRSA isolates. These were confirmed as ST75-like by using an additional SNP and MLST of selected isolates. All but one of the cc75 isolates had SSC mec type IV (one had type V), and all were PVL negative. Monthly tracking of SNP-based cc types showed a highly dynamic process. ST75-MRSA-IV appears to be unique to the region and probably evolved de novo in remote Aboriginal communities.
emm and C-Repeat Region Molecular Typing of Beta-Hemolytic Streptococci in a Tropical Country: Implications for Vaccine Development
Publisher: American Society for Microbiology
Date: 08-2009
DOI: 10.1128/JCM.00312-09
Abstract: We designed a study to investigate the molecular epidemiology of group A streptococcal (GAS) and group C and G streptococcal (GCS and GGS) disease in Fiji, a country which is known to have a high burden of streptococcal disease. Molecular typing of the N-terminal portion ( emm typing) of the M protein was performed with 817 isolates (535 GAS and 282 GCS/GGS). We also performed genotyping of the C-repeat region in 769 of these isolates to identify J14 sequence types. The profile of emm types for Fiji was very different from that found for the United States and Europe. There were no dominant emm types and a large number of overlapping types among clinical disease states. Commonly found GAS emm types in industrialized countries, including emm1 , emm12 , and emm28 , were not found among GAS isolates from Fiji. Over 93% of GAS isolates and over 99% of GCS/GGS isolates that underwent J14 sequence typing contained either J14.0 or J14.1. Our data have implications for GAS vaccine development in developing countries and suggest that a vaccine based upon the conserved region of the M protein may be a feasible option for Fiji and potentially for other tropical developing countries.
The case for global investment in rheumatic heart-disease control
Publisher: WHO Press
Date: 08-09-2014
Genome-wide analysis of genetic risk factors for rheumatic heart disease in aboriginal australians provides support for pathogenic molecular mimicry
Publisher: Oxford University Press (OUP)
Date: 26-09-2017
Abstract: Rheumatic heart disease (RHD) after group A streptococcus (GAS) infections is heritable and prevalent in Indigenous populations. Molecular mimicry between human and GAS proteins triggers proinflammatory cardiac valve-reactive T cells. Genome-wide genetic analysis was undertaken in 1263 Aboriginal Australians (398 RHD cases 865 controls). Single-nucleotide polymorphisms were genotyped using Illumina HumanCoreExome BeadChips. Direct typing and imputation was used to fine-map the human leukocyte antigen (HLA) region. Epitope binding affinities were mapped for human cross-reactive GAS proteins, including M5 and M6. The strongest genetic association was intronic to HLA-DQA1 (rs9272622 P = 1.86 × 10-7). Conditional analyses showed rs9272622 and/or DQA1*AA16 account for the HLA signal. HLA-DQA1*0101_DQB1*0503 (odds ratio [OR], 1.44 95% confidence interval [CI], 1.09-1.90 P = 9.56 × 10-3) and HLA-DQA1*0103_DQB1*0601 (OR, 1.27 95% CI, 1.07-1.52 P = 7.15 × 10-3) were risk haplotypes HLA_DQA1*0301-DQB1*0402 (OR 0.30, 95%CI 0.14-0.65, P = 2.36 × 10-3) was protective. Human myosin cross-reactive N-terminal and B repeat epitopes of GAS M5/M6 bind with higher affinity to DQA1/DQB1 alpha/beta dimers for the 2-risk haplotypes than the protective haplotype. Variation at HLA_DQA1-DQB1 is the major genetic risk factor for RHD in Aboriginal Australians studied here. Cross-reactive epitopes bind with higher affinity to alpha/beta dimers formed by risk haplotypes, supporting molecular mimicry as the key mechanism of RHD pathogenesis.
Ability of clinical isolates of group A streptococci to adhere to and invade HEp-2 epithelial cells
Publisher: Microbiology Society
Date: 10-1998
DOI: 10.1099/00222615-47-10-899
Abstract: In idual strains of group A streptococci (GAS) differ in virulence, but the reasons for these differences are incompletely understood. To determine if the ability of GAS to cause invasive disease corresponded with their capacity to adhere to or invade epithelial cells, 63 clinical isolates of GAS (40 from patients with systemic infection and 23 from superficial disease) were examined in quantitative assays of bacterial adhesion to and invasion of HEp-2 cells, a continuous line of human pharyngeal epithelial cells. The results showed that in idual isolates of GAS varied considerably in their ability to adhere to and penetrate HEp-2 cells. However, on the whole, strains from patients with invasive disease adhered to cells in numbers c.1.5 greater than those from superficial infection. Paradoxically, strains from patients with invasive disease invaded HEp-2 cells to a significantly lesser extent than those from superficial sites, with a two-fold difference in invasion index (defined as the percentage of cell-associated bacteria located intracellularly). To determine if these differences were caused by differences in the production of hyaluronic acid capsule or M protein by the two groups of bacteria, the adherence and invasive capacities of bacteria carrying defined mutations in the genes for these factors were examined. Although M6-protein-deficient [corrected] bacteria were less adherent to HEp-2 cells than the wild-type, neither the hyaluronic acid capsule nor the M protein had a significant influence on the ability of GAS to adhere to or invade HEp-2 cells. The results of this study demonstrate that there are biological differences between GAS isolates associated with invasive and superficial diseases and that these differences can be demonstrated by an assay of bacterial adherence to and invasion of HEp-2 epithelial cells.
High Incidence of Haemophilus influenzae Type b Infection in Children in Pacific Island Countries
Publisher: Oxford University Press (OUP)
Date: 15-12-2003
DOI: 10.1086/379717
Advances in the diagnosis and management of central venous access device infections in children
Publisher: Springer New York
Date: 03-09-2011
DOI: 10.1007/978-1-4419-7185-2_8
Abstract: Infection is a well-known complication of central venous access device (CVAD) use, with an incidence of 3-6 bloodstream infections per 1,000 catheter days in children. Prevention of CVAD infections has improved with new strategies including the use of chlorhexidine antisepsis, bundles, maximal sterile barriers for insertion, prophylactic locks, antibiotic impregnated catheters and tunnelling of long-term devices. Despite these strategies, catheter-related bloodstream infections (CRBSIs) continue to be an important health problem. New approaches to diagnosis include differential time to positivity and quantification of blood cultures and molecular diagnostics. The management of CRBSIs includes techniques for line salvage including ethanol, antibiotic, hydrochloric acid, taurolidine and urokinase locks. When these fail, line removal and antimicrobial therapy are recommended.
Interchangeability, immunogenicity and safety of a combined 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (Synflorix) and 13-valent-PCV (Prevenar13) schedule at 1-2-4-6 months
Publisher: Elsevier BV
Date: 04-2021
The burden of atopic dermatitis and bacterial skin infections among urban‐living Indigenous children and young people in high‐income countries: A systematic review
Publisher: Wiley
Date: 09-11-2022
DOI: 10.1111/PDE.15153
Abstract: A high burden of bacterial skin infections (BSI) is well documented in remote‐living Indigenous children and young people (CYP) in high‐income countries (HIC). Atopic dermatitis (AD) is the most common chronic inflammatory skin condition seen in CYP and predisposes to BSI. Despite the rate of urbanization for Indigenous people increasing globally, research is lacking on the burden of AD and BSI for urban‐living Indigenous CYP in HIC. Indigenous people in HIC share a history of colonization, displacement and subsequent ongoing negative impacts on health. To provide a global background on the burden of AD and BSI in urban‐living Indigenous CYP in HIC. A systematic review of primary observational studies on AD and BSI in English containing epidemiologic data was performed. MEDLINE, EMBASE, EMCARE, Web of Science, and PubMed databases were searched for articles between January 1990 and December 2021. From 2278 original manuscripts, 16 were included: seven manuscripts documenting eight studies on AD and nine manuscripts documenting nine studies on BSI. Current and severe symptoms of AD were more common in urban‐living Indigenous CYP in HIC compared with their non‐Indigenous peers, with children having a higher prevalence than adolescents. Urban‐living Indigenous CYP in HIC had a higher incidence of all measures of BSI compared with their non‐Indigenous peers, and were over‐represented for all measures of BSI compared with their proportion of the background population. Limitations include incomplete representation of all Indigenous populations in HIC. A significant burden of AD and BSI exists in urban‐living Indigenous CYP in HIC.
Host-dependent resistance of Group A Streptococcus to sulfamethoxazole mediated by a horizontally-acquired ECF transporter S component
Publisher: Research Square Platform LLC
Date: 24-03-2022
DOI: 10.21203/RS.3.RS-1390946/V1
Abstract: Described antimicrobial resistance mechanisms enable bacteria to avoid the direct effects of antibiotics and can be monitored by in vitro susceptibility testing and genetic methods. We have identified a new mechanism of sulfamethoxazole resistance that requires a host metabolite for activity. Using a combination of in vitro evolution and metabolic rescue experiments, we identified an energy-coupling factor (ECF) transporter S component gene ( thfT ) that enables Group A Streptococcus to acquire extracellular tetrahydrofolate and related compounds. ThfT likely modifies the substrate specificity of an ECF transporter to acquire the end products of folate biosynthesis. As ThfT-mediated resistance is undetectable by routine surveillance methods, our study highlights the need to understand antibiotic susceptibility during infection to reduce inappropriate antibiotic use and treatment failures.
Rheumatic Heart Disease Severity, Progression and Outcomes: A Multi‐State Model
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2017
Abstract: Rheumatic heart disease ( RHD ) remains a disease of international importance, yet little has been published about disease progression in a contemporary patient cohort. Multi‐state models provide a well‐established method of estimating rates of transition between disease states, and can be used to evaluate the cost‐effectiveness of potential interventions. We aimed to create a multi‐state model for RHD progression using serial clinical data from a cohort of Australian patients. The Northern Territory RHD register was used to identify all Indigenous residents diagnosed with RHD between the ages of 5 and 24 years in the time period 1999–2012. Disease severity over time, surgeries, and deaths were evaluated for 591 patients. Of 96 (16.2%) patients with severe RHD at diagnosis, 50% had proceeded to valve surgery by 2 years, and 10% were dead within 6 years. Of those diagnosed with moderate RHD , there was a similar chance of disease regression or progression over time. Patients with mild RHD at diagnosis were the most stable, with 64% remaining mild after 10 years however, 11.4% progressed to severe RHD and half of these required surgery. The prognosis of young Indigenous Australians diagnosed with severe RHD is bleak interventions must focus on earlier detection and treatment if the observed natural history is to be improved. This multi‐state model can be used to predict the effect of different interventions on disease progression and the associated costs.
Controlling acute rheumatic fever and rheumatic heart disease in developing countries
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2015
Improving delivery of secondary prophylaxis for rheumatic heart disease in remote Indigenous communities: study protocol for a stepped-wedge randomised trial
Publisher: Springer Science and Business Media LLC
Date: 27-01-2016
Quality of benzathine penicillin G: A multinational cross‐sectional study
Publisher: Wiley
Date: 22-10-2020
DOI: 10.1002/PRP2.668
Rheumatic heart disease among adults in a mining community of Papua, Indonesia: findings from an occupational cohort
Publisher: BMJ
Date: 07-2015
Subclinical carditis in rheumatic fever: A systematic review
Publisher: Elsevier BV
Date: 06-2007
DOI: 10.1016/J.IJCARD.2006.07.046
Abstract: Subclinical carditis (SCC)--pathological valvular regurgitation detected on echocardiography that is not evident clinically--has been reported in acute rheumatic fever (ARF), but its significance is unknown. We aimed to review the existing literature on the prevalence and outcome of SCC in ARF. We conducted a systematic literature review using MEDLINE. Prevalences of SCC in ARF ranged from 0% (in one study only) to 53% in 23 articles. The weighted pooled prevalence of SCC in ARF was 16.8% (95%CI 11.9 to 21.6). This increased slightly to 18.1% (95%CI 11.1 to 25.2) by analysing only the 10 studies that applied full World Health Organization criteria for SCC diagnosis. The weighted pooled prevalence of persistence or deterioration of SCC 3 to 23 months after ARF diagnosis was 44.7% (95%CI 19.3 to 70.2) from 11 articles. SCC is relatively common in ARF. Although some studies suggest that SCC lesions may persist or deteriorate, the available data are insufficient and of poor quality, so no confident conclusions can be drawn about the prognosis of SCC. Until better studies are conducted, clinicians will have to make management decisions that are not evidence-based. These decisions will have important practical implications for the use of echocardiography acutely and during follow-up, diagnosis of ARF, and duration of secondary prophylaxis in patients with SCC.
Susceptibility to Acute Rheumatic Fever Based on Differential Expression of Genes Involved in Cytotoxicity, Chemotaxis, and Apoptosis
Publisher: American Society for Microbiology
Date: 02-2014
DOI: 10.1128/IAI.01152-13
Abstract: It is unknown why only some in iduals are susceptible to acute rheumatic fever (ARF). We investigated whether there are differences in the immune response, detectable by gene expression, between in iduals who are susceptible to ARF and those who are not. Peripheral blood mononuclear cells (PBMCs) from 15 ARF-susceptible and 10 nonsusceptible (control) adults were stimulated with rheumatogenic (Rh+) group A streptococci (GAS) or nonrheumatogenic (Rh−) GAS. RNA from stimulated PBMCs from each subject was cohybridized with RNA from unstimulated PBMCs on oligonucleotide arrays to compare gene expression. Thirty-four genes were significantly differentially expressed between ARF-susceptible and control groups after stimulation with Rh+ GAS. A total of 982 genes were differentially expressed between Rh+ GAS- and Rh− GAS-stimulated s les from ARF-susceptible in iduals. Thirteen genes were differentially expressed in the same direction (predominantly decreased) between the two study groups and between the two stimulation conditions, giving a strong indication of their involvement. Seven of these were immune response genes involved in cytotoxicity, chemotaxis, and apoptosis. There was variability in the degree of expression change between in iduals. The high proportion of differentially expressed apoptotic and immune response genes supports the current model of autoimmune and cytokine dysregulation in ARF. This study also raises the possibility that a “failed” immune response, involving decreased expression of cytotoxic and apoptotic genes, contributes to the immunopathogenesis of ARF.
The 2015 revision of the Jones criteria for the diagnosis of acute rheumatic fever: implications for practice in low-income and middle-income countries
Publisher: BMJ
Date: 08-2015
Seasonal and regional patterns of lower leg cellulitis in Western Australia
Publisher: Wiley
Date: 02-2019
DOI: 10.1111/IMJ.14034
Abstract: Lower leg cellulitis (LLC) is a common infection that is usually caused by Streptococcus pyogenes or other beta-haemolytic streptococci. We hypothesised that in Western Australia (WA), LLC is a summer disease and would be more common in the northern, tropical regions. We conducted a statewide data linkage of adult patients presenting to WA hospitals with a first ever diagnosis of LLC, from January 2002 through December 2013 according to the region and season. A total of 36 276 cases presented with a primary episode of LLC. The northern regions of the Kimberley (2.26 (2.13-2.39), P < 0.001) and midwest (1.13 (1.06-1.20), P < 0.001) had higher incidence rates than the Perth metropolitan region, while the southern regions of Southwest, Great Southern and Goldfields had lower incidence rates (0.89 (0.85-0.93), P < 0.001 0.81 (0.75-0.88), P < 0.001 and 0.77 (0.71-0.83), P < 0.001, respectively). The total number of primary cases was higher in summer (10 570 (29.1%, 95% confidence interval 28.7-29.6), P < 0.0001) and autumn (9306 (25.7%, 95% confidence interval 25.2-26.1), P = 0.004). Seasonality of LLC was observed in all WA regions except those in the Kimberley, Pilbara and Great Southern regions. In most non-tropical regions of WA, LLC is a summer disease, while in the warmer tropical regions of WA where year-round temperatures are higher, no seasonality was observed, but overall incidence of LLC presentations were higher. These findings may have important implications for public health messaging and research around prevention of LLC.
Rheumatic chorea in northern Australia: a clinical and epidemiological study
Publisher: BMJ
Date: 04-1999
DOI: 10.1136/ADC.80.4.353
Abstract: To describe the epidemiology and clinical features of Sydenham's chorea in the Aboriginal population of northern Australia a review was conducted of 158 episodes in 108 people: 106 were Aborigines, 79 were female, and the mean age was 10.9 years at first episode. Chorea occurred in 28% of cases of acute rheumatic fever, carditis occurred in 25% of episodes of chorea, and arthritis in 8%. Patients with carditis or arthritis tended to have raised acute phase reactants and streptococcal serology. Two episodes lasted at least 30 months. Mean time to first recurrence of chorea was 2.1 years compared with 1.2 years to second recurrence. Established rheumatic heart disease developed in 58% of cases and was more likely in those presenting with acute carditis, although most people who developed rheumatic heart disease did not have evidence of acute carditis with chorea. Differences in the patterns of chorea and other manifestations of acute rheumatic fever in different populations may hold clues to its pathogenesis. Long term adherence to secondary prophylaxis is crucial following all episodes of acute rheumatic fever, including chorea, to prevent recurrence.
Evaluation of safety and immunogenicity of a group A streptococcus vaccine candidate (MJ8VAX) in a randomized clinical trial
Publisher: Public Library of Science (PLoS)
Date: 02-07-2018
A systematic framework for prioritising burden of disease data required for vaccine development and implementation
Publisher: Oxford University Press (OUP)
Date: 19-04-2022
DOI: 10.1093/CID/CIAC291
Abstract: Vaccine development and implementation decisions need to be guided by accurate and robust burden of disease data. We developed an innovative systematic framework outlining the properties of such data that are needed to advance vaccine development and evaluation, and prioritize research and surveillance activities. We focus on 4 objectives—advocacy, regulatory oversight and licensure, policy and post-licensure evaluation, and post-licensure financing—and identify key stakeholders and specific requirements for burden of disease data aligned with each objective. We apply this framework to group A Streptococcus, a pathogen with an underrecognized global burden, and give specific ex les pertinent to 8 clinical endpoints. This dynamic framework can be adapted for any disease with a vaccine in development and can be updated as vaccine candidates progress through clinical trials. This framework will also help with research and innovation priority setting of the Immunization Agenda 2030 (IA2030) and accelerate development of future vaccines.
Pneumococcal vaccination and otitis media in Australian Aboriginal infants: comparison of two birth cohorts before and after introduction of vaccination
Publisher: Springer Science and Business Media LLC
Date: 19-02-2009
Rheumatic heart disease in Indigenous children in northern Australia: Differences in prevalence and the challenges of screening
Publisher: AMPCo
Date: 09-2015
DOI: 10.5694/MJA15.00139
Abstract: To compare regional differences in the prevalence of rheumatic heart disease (RHD) detected by echocardiographic screening in high-risk Indigenous Australian children, and to describe the logistical and other practical challenges of RHD screening. Cross-sectional screening survey performed between September 2008 and November 2010. Thirty-two remote communities in four regions of northern and central Australia. 3946 Aboriginal or Torres Strait Islander children aged 5-15 years. Portable echocardiography was performed by cardiac sonographers. Echocardiograms were recorded and reported offsite by a pool of cardiologists. RHD was diagnosed according to 2012 World Heart Federation criteria. The prevalence of definite RHD differed between regions, from 4.7/1000 in Far North Queensland to 15.0/1000 in the Top End of the Northern Territory. The prevalence of definite RHD was greater in the Top End than in other regions (odds ratio, 2.3 95% CI, 1.2-4.6, P = 0.01). Fifty-three per cent of detected cases of definite RHD were new cases the prevalence of new cases of definite RHD was 4.6/1000 for the entire s le and 7.0/1000 in the Top End. Evaluation of socioeconomic data suggests that the Top End group was the most disadvantaged in our study population. The prevalence of definite RHD in remote Indigenous Australian children is significant, with a substantial level of undetected disease. Important differences were noted between regions, with the Top End having the highest prevalence of definite RHD, perhaps explained by socioeconomic factors. Regional differences must be considered when evaluating the potential benefit of widespread echocardiographic screening in Australia.
Group A Streptococcus.
Publisher: Elsevier
Date: 2012
Extensive Diversity of Streptococcus pyogenes in a Remote Human Population Reflects Global-Scale Transmission Rather than Localised Diversification
Publisher: Public Library of Science (PLoS)
Date: 16-09-2013
Treatment, prevention and public health management of impetigo, scabies, crusted scabies and fungal skin infections in endemic populations: a systematic review
Publisher: Wiley
Date: 28-01-2019
DOI: 10.1111/TMI.13198
Opsonophagocytic activity following a reduced dose 7-valent pneumococcal conjugate vaccine infant primary series and 23-valent pneumococcal polysaccharide vaccine at 12 months of age.
Publisher: Elsevier BV
Date: 2010
Clinic Attendances during the First 12 Months of Life for Aboriginal Children in Five Remote Communities of Northern Australia
Publisher: Public Library of Science (PLoS)
Date: 03-2013
Evaluating the role of asymptomatic throat carriage of Streptococcus pyogenes in impetigo transmission in remote Aboriginal communities in Northern Territory, Australia: a retrospective genomic analys
Publisher: Elsevier BV
Date: 07-2023
RE-AIM evaluation of a teacher-delivered programme to improve the self-regulation of children attending Australian Aboriginal community primary schools
Publisher: Informa UK Limited
Date: 07-10-2020
Rheumatic heart disease in The Gambia: clinical and valvular aspects at presentation and evolution under penicillin prophylaxis
Publisher: Springer Science and Business Media LLC
Date: 18-10-2021
DOI: 10.1186/S12872-021-02308-8
Abstract: Rheumatic heart disease (RHD) remains the leading cause of cardiac-related deaths and disability in children and young adults worldwide. In The Gambia, the RHD burden is thought to be high although no data are available and no control programme is yet implemented. We conducted a pilot study to generate baseline data on the clinical and valvular characteristics of RHD patients at first presentation, adherence to penicillin prophylaxis and the evolution of lesions over time. All patients registered with acute rheumatic fever (ARF) or RHD at two Gambian referral hospitals were invited for a clinical review that included echocardiography. In addition, patients were interviewed about potential risk factors, disease history, and treatment adherence. All clinical and echocardiography information at first presentation and during follow-up was retrieved from medical records. Among 255 registered RHD patients, 35 had died, 127 were examined, and 111 confirmed RHD patients were enrolled, 64% of them females. The case fatality rate in 2017 was estimated at 19.6%. At first presentation, median age was 13 years (IQR [9 18]), 57% patients had late stage heart failure, and 84.1% a pathological heart murmur. Although 53.2% of them reported history of recurrent sore throat, only 32.2% of them had sought medical treatment. A history suggestive of ARF was reported by 48.7% patients out of whom only 15.8% were adequately treated. Two third of the patients (65.5%) to whom it was prescribed were fully adherent to penicillin prophylaxis. Progressive worsening and repeated hospitalisation was experienced by 46.8% of the patients. 17 patients had cardiac surgery, but they represented only 18.1% of the 94 patients estimated eligible for cardiac surgery. This study highlights for the first time in The Gambia the devastating consequences of RHD on the health of adolescents and young adults. Our findings suggest a high burden of disease that remains largely undetected and without appropriate secondary prophylaxis. There is a need for the urgent implementation of an effective national RHD control programto decrease the unacceptably high mortality rate, improve case detection and management, and increase community awareness of this disease.
World Heart Federation criteria for echocardiographic diagnosis of rheumatic heart disease--an evidence-based guideline.
Publisher: Springer Science and Business Media LLC
Date: 28-02-2012
Acute rheumatic fever and rheumatic heart disease
Publisher: Springer Science and Business Media LLC
Date: 14-01-2016
DOI: 10.1038/NRDP.2015.84
Transiently increased IgE responses in infants and pre-schoolers receiving only acellular Diphtheria–Pertussis–Tetanus (DTaP) vaccines compared to those initially receiving at least one dose of cellul
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.VACCINE.2016.05.048
Abstract: Several previous studies have highlighted the strong Th2-polarising and IgE-promoting activity of the DTaP vaccine, but there is no evidence that this has pathological consequences and accordingly there is no current interest amongst vaccine developers in reformulating DTaP to attenuate these properties. In light of an apparent resurgence in pertussis in many countries, and emerging evidence from other areas of paediatric immunology of IgE-mediated interference with host defence mechanisms, this issue requires more detailed clarification. We have re-evaluated the impact of DTaP-only versus mixed DTwP/DTaP vaccination on Th2-dependent "bystander" IgE responses in three cohorts of children under different priming conditions, encompassing both vaccine-targeted and unrelated antigens including food allergens. We confirm the generalised IgE-trophic activity of the DTaP vaccine in pre-schoolers and demonstrate similar (albeit transient) effects in infants. We additionally demonstrate that use of an alternative mixed infant priming schedule encompassing an initial dose of DTwP significantly attenuates this property. Central to our interpretation of these findings are studies demonstrating: (i) mixed DTwP/DTaP priming improves resistance to pertussis disease and attenuates the IgE-stimulatory component of long term vaccine-specific memory (ii) IgE-mediated mechanisms can interfere with innate antiviral immunity and accordingly exacerbate airway symptoms in infected children. These observations, taken together with the data presented here, suggest a plausible mechanistic link between baseline pertussis-specific IgE titres in DTaP vaccinees and susceptibility to pertussis disease, which merits testing. Retrospective IgE analyses on sera collected from children at the time of presentation with pertussis could resolve this issue.
Comparison of three methods for the recovery of skin pathogens from impetigo swabs collected in a remote community of Northern Territory, Australia
Publisher: Oxford University Press (OUP)
Date: 23-04-2013
Abstract: Impetigo is a common infection in children living in remote areas. Immediate plating of impetigo swabs is the gold standard for bacterial recovery but is rarely feasible in remote regions. Bacterial culture increases our understanding of antibiotic resistance and strain ersity, which guides treatment protocols and epidemiological monitoring. We investigated three practical alternatives for recovering Streptococcus pyogenes and Staphylococcus aureus from transported swabs: dry swabs transported at 4°C with desiccant and plated within 48 h swabs inoculated into skim milk tryptone glucose glycerol broth (STGGB), transported at 4°C, stored at -70°C and plated within 61 days and ESwabs inoculated into Amies broth, transported at 4°C and plated within 48 h. Detection of Strep. pyogenes and Staph. aureus from simultaneously collected swabs was compared for the dry vs STGGB (36 sores) and the STGGB vs Amies (39 sores) methods. Swabs were collected from 43 children (75 sores s led) in a remote community of Northern Territory, Australia in November 2011. The children had impetigo and were participating in the Skin Sore Trial [Australian Clinical Trials Registry ACTRN12609000858291]. Recovery of Strep. pyogenes for dry vs STGGB was 72% (26/36) and 92% (33/36) and for STGGB vs Amies was 92% (36/39) for both methods. Staphylococcus aureus recovery for dry vs STGGB was 69% (25/36) and 72% 26/36) and for STGGB vs Amies was 74% (29/39) and 85% (33/39). STGGB and Amies media provided higher recovery of Strep. pyogenes than dry swabs. These results and the opportunity to batch and store specimens for molecular studies support the use of STGGB transport media for future impetigo research.
Reply to Banderet-Uglioni et al
Publisher: Oxford University Press (OUP)
Date: 23-10-2014
DOI: 10.1093/CID/CIU829
The Global Epidemiology of Impetigo: A Systematic Review of the Population Prevalence of Impetigo and Pyoderma
Publisher: Public Library of Science (PLoS)
Date: 28-08-2015
Standardising and Assessing Digital Images for Use in Clinical Trials: A Practical, Reproducible Method That Blinds the Assessor to Treatment Allocation
Publisher: Public Library of Science (PLoS)
Date: 06-11-2014
The “surreptitious staphylococcus”staphylococcus lugdunensis endocarditis in a child
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2002
DOI: 10.1097/00006454-200210000-00023
Abstract: A child with congenital heart disease developed infective endocarditis caused by Staphylococcus lugdunensis. Despite an apparent excellent response to initial antibiotic treatment in clinical, inflammatory and echocardiographic indices, the patient's valve damage progressed silently and surgical intervention was required. This case highlights the potential for misidentification of S. lugdunensis, its usual susceptibility to penicillin and in particular the aggressive nature of endocarditis caused by this coagulase-negative staphylococcus. The epidemiology and treatment of endocarditis caused by this organism are reviewed.
Epidemiology ofStreptococcus dysgalactiaesubsp.equisimilisin Tropical Communities, Northern Australia
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 11-2007
Burden of Acute Sore Throat and Group A Streptococcal Pharyngitis in School-aged Children and Their Families in Australia
Publisher: American Academy of Pediatrics (AAP)
Date: 11-2007
Abstract: OBJECTIVE. The objective of this study was to determine the incidence, transmission, carriage, and risk factors for group A streptococcal pharyngitis in school-aged children and their families. METHODS. A 16-month, prospective, family-based cohort study was undertaken from August 2001 through December 2002 in Melbourne, Australia. A total of 202 families (853 people) with at least 1 child aged 3 to 12 years were randomly selected from 3 primary care practices across suburban Melbourne to collect surveillance data for acute group A streptococcal pharyngitis, including serology for index and secondary cases and intermittent carriage data. Cohort retention was 97% for 16 months. RESULTS. The incidence of acute sore throat, group A streptococcal swab–positive pharyngitis, and serologically confirmed group A streptococcal pharyngitis was 33, 13, and 8 per 100 child-years, respectively, for school-aged children (5–12 years) and 60, 20, and 15 per 100 family-years, respectively. Sore throat was less common in adults than children, but adults with sore throat were as likely as children to have group A streptococcal culture–positive or serologically proven pharyngitis. In families who had a primary case, 43% had at least 1 secondary case, and in family members who were at risk, 13% contracted a secondary case. The spring, summer, and winter carriage rates for children were 13%, 8%, and 16%, respectively, and for adults the rate was 2% across all seasons. CONCLUSIONS. Group A streptococcal pharyngitis is still common, and the peak incidence occurs in school-aged children. However, the incidence in adults is higher than expected, and the number of secondary cases in families may be an important factor when considering the potential benefits of treatment.
Global Burden of Cardiovascular Diseases and Risk Factors, 1990–2019
Publisher: Elsevier BV
Date: 12-2020
Rheumatic heart disease in Timor‐Leste school students: an echocardiography‐based prevalence study
Publisher: AMPCo
Date: 04-2018
DOI: 10.5694/MJA17.00666
Abstract: To determine the prevalence of rheumatic heart disease (RHD) in school-aged children and young people in Timor-Leste. Prospective cross-sectional survey. Echocardiography was performed by Australian cardiologists to determine the presence of RHD. Demographic data were also collected. Patients in whom RHD was detected were entered into a register to allow monitoring of adherence to secondary prophylaxis the first dose of benzathine penicillin G (BPG) was administered on the day of screening. Schools in urban (Dili) and rural (Ermera) Timor-Leste. School students aged 5-20 years. Definite and borderline RHD, as defined by World Heart Federation echocardiographic criteria. 1365 participants were screened their median age was 11 years (IQR, 9-14 years), and 53% were girls. The estimated prevalence of definite RHD was 18.3 cases per 1000 population (95% CI, 12.3-27.0 per 1000), and of definite or borderline RHD 35.2 per 1000 (95% CI, 26.5-46.4 per 1000). Definite (adjusted odds ratio [aOR], 3.5 95% CI, 1.3-9.4) and definite or borderline RHD (aOR, 2.7 95% CI, 1.4-5.2) were more prevalent among girls than boys. Eleven children (0.8%) had congenital heart disease. Of the 25 children in whom definite RHD was identified, 21 (84%) received education and a first dose of BPG on the day of screening all 25 have since received education about primary care for RHD and have commenced penicillin prophylaxis. The rates of RHD in Timor-Leste are among the highest in the world, and prevalence is higher among girls than boys. Community engagement is essential for ensuring follow-up and the effective delivery of secondary prophylaxis.
Lessons learned in genetic research with Indigenous Australian participants
Publisher: AMPCo
Date: 04-02-2020
DOI: 10.5694/MJA2.50499
Secondary prophylaxis is important for the prevention of recurrent rheumatic fever in the Pacific.
Publisher: Springer Science and Business Media LLC
Date: 11-04-2011
Demographics and utilisation of health services by paediatric refugees from East Africa
Publisher: CSIRO Publishing
Date: 2004
DOI: 10.1071/AH042720040
Abstract: Regina Cooke is a Clinical Fellow at the Royal Children's Hospital, Melbourne. Sally Murray is an Honorary Fellow of the University of Melbourne and former Program Coordinator of the Victorian Immigrant Health Program, Department of Paediatrics, University of Melbourne. Jonathan Carapetis is an Infectious Diseases Physician, Royal Children's Hospital, Senior Lecturer, Department of Paediatrics,University of Melbourne and Research Fellow, Murdoch Children's Research Institute. James Rice is a Clinical Fellow at University of British Columbia, Canada and formerly of Royal Children's Hospital, Melbourne. Nigisti Mulholland is a Social Scientist, formerly of Royal Children's Hospital, Melbourne.Susan Skull is Deputy Director of the Clinical Epidemiology and Biostatistics Unit, Royal Children's Hospital, and Senior Lecturer, Department of Paediatrics, University of Melbourne.Little is known of difficulties in accessing health care for recently arrived paediatric refugees in Australia. We reviewedroutinely collected data for all 199 East African children attending a hospital Immigrant Health Clinic for the first time over a 16 month period. Although 63% of parents reported medical consultations since arrival, 77% of this group reported outstanding, unaddressed health problems. Availability of interpreters and information on health services were the main factors hindering access to care. These data have informed future service planning at the Clinic.Ongoing data collection is key to maintaining a responsive, targeted service for a continually changing population.
The overuse of intrapartum cardiotocography (CTG) for low-risk women: An actor-network theory analysis of data from focus groups
Publisher: Elsevier BV
Date: 11-2022
DOI: 10.1016/J.WOMBI.2022.01.003
Abstract: There is an overuse of cardiotocography for intrapartum fetal monitoring for low-risk women in high-income countries, despite recommendations from evidence-based guidelines. To understand why midwives use cardiotocography for low-risk women despite evidence-based recommendations and to understand the roles of the cardiotocograph machine. This qualitative study used focus groups for data collection. Thirty-one midwives and three student midwives participated from four different countries: New Zealand, Australia, Denmark, and Norway. Constant comparative analysis, informed by an actor-network theory framework, was the method of data analysis. Cardiotocography was multifaceted and influenced all attendants in the birth environment. The cardiotocograph itself is assigned different roles within the complex networks surrounding childbirth. The cardiotocograph's roles were as a babysitter, the midwives' partner, an agent of shared responsibility, a protector that 'covers your back', a disturber of normal birth, and a requested guest. The application of the actor-network theory enabled us to understand how midwives perceive cardiotocography. The assigned roles of the cardiotocograph shape its everyday use more than evidence-based guidelines. Discussion of these inconsistencies must inform the use of cardiotocography in the care of women with low-risk pregnancies. We found that the cardiotocograph is a multifaceted actant that influences practice by performing different roles. Drawing on this study, we suggest that actor-network theory could be a helpful theoretical perspective to critically reflect upon the increasing use of technologies within maternity care.
Immunogenicity of a Third Scheduled Dose of Rotarix in Australian Indigenous Infants: A Phase IV, Double-blind, Randomized, Placebo-Controlled Clinical Trial
Publisher: Oxford University Press (OUP)
Date: 04-02-2022
Abstract: Rotarix (GlaxoSmithKline) oral rotavirus vaccine is licensed as 2 doses in the first 6 months of life. In settings with high child mortality rates, clinical protection conferred by 2 doses of Rotarix is reduced. We assessed vaccine immune response when an additional dose of Rotarix was given to Australian Aboriginal children 6 to & months old. ORVAC is a 2-stage, double-blind, randomized, placebo-controlled trial. Australian Aboriginal children 6 to & months old who had received 1 or 2 prior doses of Rotarix rotavirus vaccine were randomized 1:1 to receive an additional dose of Rotarix or matched placebo. The primary immunological end point was seroresponse defined as an anti-rotavirus immunoglobulin A level ≥20 AU/mL, 28–56 days after the additional dose of Rotarix or placebo. Between March 2018 and August 2020, a total of 253 infants were enrolled. Of these, 178 infants (70%) had analyzable serological results after follow-up 89 were randomized to receive Rotarix, and 89 to receive placebo. The proportion with seroresponse was 85% after Rotarix compared with 72% after placebo. There were no occurrences of intussusception or any serious adverse events. An additional dose of Rotarix administered to Australian Aboriginal infants 6 to & months old increased the proportion with a vaccine seroresponse. NCT02941107.
Roadmap to incorporating group A Streptococcus molecular point‐of‐care testing for remote Australia: a key activity to eliminate rheumatic heart disease
Publisher: Wiley
Date: 28-08-2022
DOI: 10.5694/MJA2.51692
Formal Infectious Diseases Consultations at a Tertiary Pediatric Hospital
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2014
Group A Streptococcus, Acute Rheumatic Fever and Rheumatic Heart Disease
Publisher: Springer Science and Business Media LLC
Date: 02-2017
Clinical implications of inducible beta-lactamase activity in Gram-negative bacteremia in children
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2002
DOI: 10.1097/00006454-200210000-00010
Abstract: Organisms of the spp., indole-positive spp., spp. and (ESCaPPM) group are a common cause of hospital-acquired bacteremia and share the potential to develop beta-lactam resistance during therapy. The emergence of such resistance may have adverse consequences, but the frequency with which this occurs has not been studied in children. It has been suggested that such organisms should be treated with combination antimicrobials or carbapenems, but the optimal regimen is uncertain. AIM To determine the frequency with which beta-lactam resistance develops during ESCaPPM sepsis in children and the optimal treatment of such sepsis. A review of the case notes and microbiologic records of all cases of ESCaPPM bacteremia and meningitis managed at a tertiary children's hospital during a 6-year period. Fifty-eight cases were identified, and in three (5%) cases beta-lactam resistance emerged during treatment, with adverse clinical consequences in two cases. Clinical and microbiologic outcome was similar in those treated with carbapenems and in those treated with a beta-lactam and aminoglycoside combination. Cefotaxime resistance was found in 57, 30, 24 and 7% of children who had received carbapenems, cephalosporins, penicillins or no/other antimicrobials in the month before ESCaPPM sepsis, respectively. The emergence of beta-lactam resistance during treatment of ESCaPPM sepsis is uncommon in our hospital but can have adverse consequences. Where isolates are reported as susceptible to both classes of drugs, an extended spectrum penicillin in combination with an aminoglycoside may be preferable first line treatment of ESCaPPM sepsis to a carbapenem or quinolone.
Rheumatic Fever Follow-Up Study (RhFFUS) protocol: A cohort study investigating the significance of minor echocardiographic abnormalities in Aboriginal Australian and Torres Strait Islander children
Publisher: Springer Science and Business Media LLC
Date: 27-11-2012
PO648 Benzathine Penicillin G Pharmacokinetics In a Predominately Australian Aboriginal Adolescent Population, a Prospective Observational Study
Publisher: Ubiquity Press, Ltd.
Date: 12-2018
Opsonic human antibodies from an endemic population specific for a conserved epitope on the M protein of group A streptococci
Publisher: Wiley
Date: 11-1996
DOI: 10.1046/J.1365-2567.1996.D01-754.X
Abstract: This study demonstrates the presence of epitope-specific opsonic human antibodies in a population living in an area endemic for group A streptococci (GAS) infection. Antibodies recognizing a conserved C-terminal region epitope (p145, sequence in single letter amino acids: LRRDLDASREAKKQVEKALE) of the M protein of GAS were isolated from human patients by affinity chromatography and were shown to be of the immunoglobulin G1 (IgG1) and IgG3 subclasses. These antibodies could reduce the number of colonies of serotype 5 GAS in an in vitro opsonization assay by 71-92%, compared with an equal amount of IgG from control adult donors living in non-endemic areas and without antibodies to p145. Addition of the peptide, p145, completely inhibited this opsonization. Indirect immunofluorescence showed that p145-specific antibodies were capable of binding to the surface of M5 GAS whereas control IgG did not. Using chimeric peptides, which contain overlapping segments of p145, each 12 amino acids in length, inserted into a known helical peptide derived from the DNA binding protein of yeast, GCN4, we have been able to further define two minimal regions within p145, referred to as pJ2 and pJ7. These peptides, pJ2 and pJ7, were able to inhibit opsonization by p145 specific antibodies. Finally, we have observed an association between the age-related development of immunity to GAS and the acquisition of antibodies to the conserved epitope, p145, raising the possibility of using this epitope as a target in a prophylactic vaccine administered during early childhood.
Global research priorities in rheumatic fever and rheumatic heart disease
Publisher: Medknow
Date: 2011
Success of a scabies control program in an Australian Aboriginal community
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-1997
DOI: 10.1097/00006454-199705000-00008
Abstract: To adapt, implement and evaluate a model of scabies control in an Australian Aboriginal community. After initially examining the population, we offered all residents treatment with 5% permethrin cream. Visits were made during the ensuing 25 months to rescreen and to treat new-cases of scabies and contacts. The prevalence of scabies was reduced from 28.8% before the program to < 10% during the entire period (from 32.3% to < 10% in children) (P < 0.01 for each visit). The initial prevalence of pyoderma in children was 69.4%, which was reduced and maintained at approximately one-half that rate during the last 16 months (P 2 years. It could prove useful for other communities with high rates of scabies and pyoderma.
Low Rates of Streptococcal Pharyngitis and High Rates of Pyoderma in Australian Aboriginal Communities Where Acute Rheumatic Fever Is Hyperendemic
Publisher: Oxford University Press (OUP)
Date: 15-09-2006
DOI: 10.1086/506938
Abstract: Acute rheumatic fever is a major cause of heart disease in Aboriginal Australians. The epidemiology differs from that observed in regions with temperate climates streptococcal pharyngitis is reportedly rare, and pyoderma is highly prevalent. A link between pyoderma and acute rheumatic fever has been proposed but is yet to be proven. Group C beta-hemolytic streptococci and group G beta-hemolytic streptococci have also been also implicated in the pathogenesis. Monthly, prospective surveillance of selected households was conducted in 3 remote Aboriginal communities. People were questioned about sore throat and pyoderma swab specimens were obtained from all throats and any pyoderma lesions. Household population density was determined. From data collected during 531 household visits, the childhood incidence of sore throat was calculated to be 8 cases per 100 person-years, with no cases of symptomatic group A beta-hemolytic streptococci pharyngitis. The median point prevalence for throat carriage was 3.7% for group A beta-hemolytic streptococci, 0.7% for group C beta-hemolytic streptococci, and 5.1% for group G beta-hemolytic streptococci. Group A beta-hemolytic streptococci were recovered from the throats of 19.5% of children at some time during the study. There was no seasonal trend or correlation with overcrowding. Almost 40% of children had pyoderma at least once, and the prevalence was greatest during the dry season. In community 1, the prevalence of pyoderma correlated with household crowding. Group C and G beta-hemolytic streptococci were rarely recovered from pyoderma lesions. These data are consistent with the hypothesis that recurrent skin infections immunize against throat colonization and infection. High rates of acute rheumatic fever were not driven by symptomatic group A beta-hemolytic streptococci throat infection. Group G and C beta-hemolytic streptococci were found in the throat but rarely in pyoderma lesions.
Establishing Cutoffs for Streptococcal Antibody Titers in Uganda: Implications for Rheumatic Fever Diagnosis
Publisher: Cold Spring Harbor Laboratory
Date: 29-10-2019
DOI: 10.1101/19010447
Abstract: Central to rheumatic fever (RF) diagnosis is evidence of streptococcal exposure, specifically antistreptolysin O (ASO) and antideoxyribonuclease B (ADB) antibodies. It is unknown if these antibody titers should be adjusted to the background exposure rates of GAS or if published standards should be used. Here, we establish the normal values of ASO and ADB in Uganda and examine RF case detection using published vs. population-specific thresholds. Participants (age 0-50 years) were recruited. ASO was measured in-country by nephelometric technique. ADB s les were sent to Australia (PathWest) for ADB determination by enzyme inhibition assay, andthe 80% upper limit values by age were established. The published standard values for ASO (200IU/ml) and ADB (375IU/ml) were compared to the Ugandan 80% upper limit of normal values (ULN) for RF case detection in children 5-15 years. Of the 428 participants, 16 were excluded from analysis (9 sore throat, 1 skin sores, 5 fever, 4 echocardiograms showing occult RHD), and 183 of the remaining were children 5-15 years. The median ASO titer in this age group was 220 IU/ml, with the 80th percentile value of 389 IU/ml. The median ADB titer in this age group was 375 IU/ml, with the 80th percentile value of 568 IU/ml. Application of new Ugandan cutoffs to 528 children enrolled in our prospective RF study, reduced the number of definite RF cases to 120/528 (22·7%), as compared to 173/528 (32·8%) using published normal values. The 80th percentile ULN for ASO and ADB are higher in Uganda than in other countries. Applying these higher values to RF diagnosis in Uganda results in higher diagnostic specificity, but some unknown loss in sensitivity. Implications of over-diagnosis and missed cases will be explored through a longitudinal follow-up study of children in the RF research program. This work was supported by American Heart Association Grant #17SFRN33670607 / Andrea Beaton / 2017 and DELTAS Africa Initiative. We searched PubMed for data on normal values of streptococcal antibody titers within erse populations between database inception and January 1, 2019, using the search terms (rheumatic fever) OR (streptococcal antibodies). Nine studies were identified, but only one was from sub-Saharan Africa (2018, Ethiopia) and it was limited by vague exclusion criteria and lack of data on anti-DNase B. Given the high burden of rheumatic heart disease in sub-Saharan Africa, further data is needed to determine normal streptococcal antibody titers in this population and to assess the clinical impact of different cutoffs for RF diagnosis. Our study utilized a rigorous approach to exclude patients with history of recent possible streptococcal exposure including skin and throat infection and employed echocardiography to exclude patients with pre-existing rheumatic heart disease. Additionally, this study was conducted in parallel to a larger epidemiological cohort study of rheumatic fever in Uganda, allowing us, for the first time, to prospectively determine how utilization of different streptococcal antibody titer cutoffs affect diagnosis of rheumatic fever. Rheumatic fever remains a challenging diagnosis based on a clinical decision rule with imperfect sensitivity and specificity. Improved understanding of streptococcal antibody titers in rheumatic heart disease endemic populations may improve diagnostic performance. Our study also points to the need for development of a rheumatic fever diagnostic test, in order to provide a more definitive assessment of risk.
SToP (See, Treat, Prevent) skin sores and scabies trial: study protocol for a cluster randomised, stepped-wedge trial for skin disease control in remote Western Australia
Publisher: BMJ
Date: 09-2019
DOI: 10.1136/BMJOPEN-2019-030635
Abstract: Skin is important in Australian Aboriginal culture informing kinship and identity. In many remote Aboriginal communities, scabies and impetigo are very common. Untreated skin infections are painful, itchy and frequently go untreated due to under-recognition and lack of awareness of their potential serious complications. We hypothesise that the skin infection burden in remote Aboriginal communities can be reduced by implementing streamlined training and treatment pathways integrated with environmental health and health promotion activities, tested in the See, Treat, Prevent (SToP skin sores and scabies) trial. SToP will evaluate a skin control programme using a stepped-wedge, cluster randomised trial design with three intervention components (the ‘SToP activities’): (1) seeing skin infections (development of training resources implemented within a community dermatology model) (2) treating skin infections (employing the latest evidence for impetigo, and scabies treatment) and (3) preventing skin infections (embedded, culturally informed health promotion and environmental health activities). Four community clusters in the remote Kimberley region of Western Australia will participate. Following baseline data collection, two clusters will be randomly allocated to the SToP activities. At 12 months, the remaining two clusters will transition to the SToP activities. The primary outcome is the diagnosis of impetigo in children (5–9 years) at school-based surveillance. Secondary outcome measures include scabies diagnosis, other child health indicators, resistance to cotrimoxazole in circulating pathogenic bacteria, determining the economic burden of skin disease and evaluating the cost effectiveness of SToP activities. This study protocol was approved by the health ethics review committees at the Child and Adolescent Health Service (Approval number RGS0000000584), the Western Australian Aboriginal Health Ethics Committee (Reference number: 819) and the University of Western Australia (Reference RA/4/20/4123). Study findings will be shared with community members, academic and medical communities via publications and presentations, and in reports to funders. Authorship for all publications based on this study will be determined in line with the Uniform Requirements for Manuscripts Submitted to Biomedical Journals published by the International Committee of Medical Journal Editors. Sharing results with organisations and communities who contributed to the study is paramount. The results of the SToP trial will be shared with participants in a suitable format, such as a single summary page provided to participants or presentations to communities, the Kimberly Aboriginal Health Planning Forum Research Subcommittee and other stakeholders as appropriate and as requested. Communication and dissemination will require ongoing consultation with Aboriginal communities to determine appropriate formats. ACTRN12618000520235.
Universities and tobacco money
Publisher: BMJ
Date: 13-10-2001
Preliminary validation of a novel high-resolution melt-based typing method based on the multilocus sequence typing scheme of Streptococcus pyogenes
Publisher: Elsevier BV
Date: 09-2011
Screening for intestinal parasites in recently arrived children from East Africa
Publisher: Wiley
Date: 08-2003
DOI: 10.1046/J.1440-1754.2003.00188.X
Abstract: Intestinal parasitic carriage is common in East African populations with a wide spectrum of clinical severity. There are scant data on the rates of carriage in East African immigrants to Australia. This study describes the prevalence of and risk factors for intestinal parasite carriage among children recently arrived from East African countries. Children aged 0-17 years, who attended an outpatient clinic, were born in East Africa and had immigrated since 1998 were eligible to participate. A single preserved stool specimen was collected for faecal microscopy, and blood tests were conducted for Strongyloides and Schistosoma serology, full blood examination and serum ferritin. One hundred and thirty-five children (median age 8.1 years, range 1.0-17.5) participated, of whom 133 (99%) provided a stool specimen. Parasites were detected in 50% of s les, and 18% of children carried a possibly pathogenic species. No child was symptomatic at diagnosis. Positive or equivocal serology occurred in 11% of children for Strongyloides and 2% for Schistosoma. Anaemia and iron deficiency were detected in 16% of all children. Those carrying an intestinal parasite were older (mean age 9.8 vs 7.4 years, P= 0.002) and less likely to be anaemic (odds ratio 0.37, 95% confidence interval 0.14-0.96) than those who were not carriers. Carriage of intestinal parasites is common among children from East Africa. Those carrying pathogenic organisms require treatment and follow up to ensure eradication. The results of this survey support the need for routine assessment of newly arrived immigrants from East Africa for intestinal parasites, anaemia and iron deficiency.
Acute rheumatic fever: an important differential diagnosis of septic arthritis
Publisher: Oxford University Press (OUP)
Date: 15-10-2007
Abstract: We present three cases of suspected septic arthritis in which the joint fluid was sterile. Subsequently all three patients were diagnosed with established moderate-severe rheumatic heart disease. In retrospect it is likely that the earlier presentations were in fact episodes of acute rheumatic fever but were not recognized as such. These cases underline the importance of acute rheumatic fever as a differential diagnosis of septic arthritis when the joint fluid is sterile, particularly in regions where there are high rates of acute rheumatic fever and rheumatic heart disease.
Persistence of acute rheumatic fever in a tertiary children's hospital
Publisher: Wiley
Date: 29-12-2011
DOI: 10.1111/J.1440-1754.2010.01935.X
Abstract: To identify and describe all children admitted with acute rheumatic fever (ARF) to a tertiary paediatric hospital in Sydney over a 9-year period and to describe their demographic and clinical characteristics, management and short-term outcomes. Delays in diagnosis, recurrence of ARF and use of secondary prophylaxis were also documented. Retrospective review of medical records for children aged < 15 years admitted to the Children's Hospital at Westmead, Sydney, with ARF (International Classification of Diseases (ICD)-10 classification I0.0-109.9) during 2000-2008. Only cases meeting the National Heart Foundation of Australia diagnostic criteria for ARF were included. Twenty-six children met the National Heart Foundation of Australia criteria for ARF. The median age was 11.5 years (range 5.8-14.6) and 15 (58%) were male. Ten (38%) identified as Pacific Islander, and 5 (19%) as Aboriginal and Torres Strait Islander (ATSI). Most (n= 20, 77%) lived in suburban Sydney, and 69% were classified in the two most disadvantaged quintiles on the Index of Relative Socioeconomic Disadvantage and Advantage. Four (15%) had Sydenham's chorea, and 81% had carditis (mitral and/or aortic regurgitation). Six (23%) children had previous ARF. Antibiotic prophylaxis to prevent recurrent ARF was prescribed in all cases, but 50% received oral penicillin, rather than by intramuscular injection. Barriers to timely diagnosis were identified in 81%, including delayed presentation and delayed referral. Most children presenting to the hospital with ARF lived in disadvantaged areas of Sydney. Pacific Islander and Aboriginal and Torres Strait Islander children were over-represented. Mitigation of RHD requires early identification of ARF and appropriate delivery of secondary prophylaxis.
Ascertaining infectious disease burden through primary care clinic attendance among young Aboriginal children living in four remote communities in Western Australia
Publisher: Public Library of Science (PLoS)
Date: 17-09-2018
Epidemiology of nasopharyngeal carriage of respiratory bacterial pathogens in children and adults: cross-sectional surveys in a population with high rates of pneumococcal disease
Publisher: Springer Science and Business Media LLC
Date: 23-10-2010
The clinical course of acute otitis media in high-risk Australian Aboriginal children: a longitudinal study
Publisher: Springer Science and Business Media LLC
Date: 14-06-2005
An infant with fever and convulsions
Publisher: Springer Science and Business Media LLC
Date: 06-1996
DOI: 10.1007/BF01955194
Abstract: Wind turbines have been recognised as an alternative and clean-energy source with a low environmental impact. The selection of sites for wind-farm often creates serious conservation concerns on bio ersity. Wind turbines have become a serious threat to migratory birds as they collide with the turbine blades in some regions across the globe, while the impact on terrestrial mammals is relatively less explored. In this context, we assessed the responses of birds and mammals to the wind turbines in central Karnataka, India from January 2016 to May 2018 using carcass searches to quantify animal collisions (i.e., birds and bats), fixed radius point count for bird population parameters, and an occupancy framework for assessing the factor that determines the spatial occurrence of terrestrial mammals. The mean annual animal fatality rate per wind turbine was 0.26/year. Species richness, abundance, and unique species of birds were relatively higher in control sites over wind turbine sites. Species and functional compositions of birds in control sites were different from wind turbine sites, explaining the varied patterns of bird assemblages of different feeding guilds. Blackbuck, Chinkara, Golden Jackal, and Jungle Cat were less likely to occupy sites with a high number of wind turbines. The study indicates that certain bird and mammal species avoided wind turbine-dominated sites, affecting their distribution pattern. This is of concern to the management of the forested areas with wind turbines. We raised conservation issues and mitigating measures to overcome the negative effects of wind turbines on animals.
Serotype-specific avidity is achieved following a single dose of the 7-valent pneumococcal conjugate vaccine, and is enhanced by 23-valent pneumococcal polysaccharide booster at 12 months.
Publisher: Elsevier BV
Date: 06-2011
Apparent Contrasting Rates of Pharyngitis and Pyoderma in Regions where Rheumatic Heart Disease is Highly Prevalent
Publisher: Elsevier BV
Date: 08-2007
DOI: 10.1016/J.HLC.2007.02.087
Abstract: The aim of the study was to describe the epidemiology of pharyngitis and pyoderma in a Central Australian Aboriginal community with a high prevalence of rheumatic heart disease (RHD) and compare it to communities in the Top End of the Northern Territory. Following ethics approval and community consultation, selected households were enrolled and visited over a 13-month period. People were asked if they had a sore throat and/or skin sores and asked about current or recent use of antibiotics all throats and any pyoderma lesions were swabbed for bacterial culture. Beta-haemolytic streptococci (BHS), including group A streptococcus (GAS), were identified in the central laboratory using standard methods. Household crowding was also assessed. Results were then compared to those from the Top End study. Sore throat was relatively common (480 episodes per 100 person years), although there was only one case of GAS pharyngitis in 326 consultations. Only 5.5% of children <15 years had pyoderma during the course of the study. This is the opposite picture to that reported in the Top End where symptomatic pharyngitis is rare and pyoderma is common. Although the data are limited, the epidemiology of pharyngitis and pyoderma in this Central Australian Aboriginal community appears to be more akin to that seen in temperate climates rather than tropical Top End communities. In this community, RHD preventative measure should continue to include aggressive treatment of pharyngitis according to recommendations.
Serotypes of respiratory tract isolates of Streptococcus pneumoniae from Jamaican children
Publisher: Elsevier BV
Date: 03-2003
DOI: 10.1016/S1201-9712(03)90039-7
Abstract: Data are lacking on the pneumococcal serotypes present in many developing regions, including the Caribbean. We examined the serotypes of nasopharyngeal (NP) isolates of pneumococci obtained from Jamaican children. We obtained NP s les from children seen in the Emergency Department at the Bustamante Children's Hospital. The s les were transported to Canada for isolation and serotyping of pneumococci. We obtained 94 isolates from 276 children median age 3.4 years. The majority (57%) had symptoms of acute respiratory infection at the time of s ling. The main serotypes carried were 6B (20.5%), 19F (14.5%), and 14 (8.4%). Non-typable isolates accounted for 10.8% of the isolates. Fifty-nine per cent of the serotypes were present among the 11 being considered for candidate pneumococcal conjugate vaccines (95% CI 48-70%) the corresponding proportion present in the recently licensed 7-valent vaccine was 57% (95% CI 45-67%). A significant proportion of the serotypes found is absent from those to be included in future conjugate vaccines (P<0.0001 reference=85% expected serotype representation). Less than 5% of isolates were non-susceptible to penicillin (3.2%), cefotaxime-ceftriaxone (3.2%) and cefuroxime (3.2%), while 8.4% and 1.l% of isolates were resistant to trimethoprim-sulfamethoxazole and erythromycin respectively. There were three isolates with resistance to two or more classes of drug. These isolates were all resistant to penicillin (MIC 2 micro g/mL) the serotypes were 14, 23F, and 19F. A significant proportion of the serotypes found is absent from those to be included in future conjugate vaccines.
Development of a sustained release implant of benzathine penicillin G for secondary prophylaxis of rheumatic heart disease
Publisher: Elsevier BV
Date: 08-2023
Qualitative Evaluation of a Complex Intervention to Improve Rheumatic Heart Disease Secondary Prophylaxis
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-07-2018
Abstract: Rheumatic heart disease is a high‐burden condition in Australian Aboriginal communities. We evaluated a stepped‐wedge, community, randomized trial at 10 Aboriginal communities from 2013 to 2015. A multifaceted intervention was implemented using quality improvement and chronic care model approaches to improve delivery of penicillin prophylaxis for rheumatic heart disease. The trial did not improve penicillin adherence. This mixed‐methods evaluation, designed a priori , aimed to determine the association between methodological approaches and outcomes. An evaluation framework was developed to measure the success of project implementation and of the underlying program theory. The program theory posited that penicillin delivery would be improved through activities implemented at clinics that addressed elements of the chronic care model. Qualitative data were derived from interviews with health‐center staff, informants, and clients participant observation and project officer reports. Quantitative data comprised numbers and types of “action items,” which were developed by participating clinic staff with project officers to improve delivery of penicillin injections. Interview data from 121 health‐center staff, 22 informants, and 72 clients revealed barriers to achieving the trial's aims, including project‐level factors (short trial duration), implementation factors (types of activities implemented), and contextual factors (high staff turnover and the complex sociocultural environment). Insufficient actions were implemented addressing “self‐management support” and “community linkage” streams of the chronic care model. Increased momentum was evident in later stages of the study. The program theory underpinning the study was sound. The limited impact made by the study on adherence was attributable to complex implementation challenges.
Genome-wide analysis of genetic risk factors for rheumatic heart disease in Aboriginal Australians provides support for pathogenic molecular mimicry
Publisher: Cold Spring Harbor Laboratory
Date: 13-09-2017
DOI: 10.1101/188334
Abstract: Rheumatic heart disease (RHD) following Group A Streptococcus (GAS) infections is heritable and prevalent in Indigenous populations. Molecular mimicry between human and GAS proteins triggers pro-inflammatory cardiac valve-reactive T-cells. Genome-wide genetic analysis was undertaken in 1263 Aboriginal Australians (398 RHD cases 865 controls). Single nucleotide polymorphisms (SNPs) were genotyped using Illumina HumanCoreExome BeadChips. Direct typing and imputation was used to fine-map the human leukocyte antigen (HLA) region. Epitope binding affinities were mapped for human cross-reactive GAS proteins, including M5 and M6. The strongest genetic association was intronic to HLA-DQA1 (rs9272622 P=1.86x10 −7 ). Conditional analyses showed rs9272622 and/or DQA1*AA16 account for the HLA signal. HLA-DQA1*0101_DQB1*0503 (OR 1.44, 95%CI 1.09-1.90, P=9.56x10 −3 ) and HLA-DQA1*0103_DQB1*0601 (OR 1.27, 95%CI 1.07-1.52, P=7.15x10 −3 ) were risk haplotypes HLA_DQA1*0301-DQB1*0402 (OR 0.30, 95%CI 0.14-0.65, P=2.36x10 −3 ) was protective. Human myosin cross-reactive N-terminal and B repeat epitopes of GAS M5/M6 bind with higher affinity to DQA1/DQB1 alpha/beta dimers for the two risk haplotypes than the protective haplotype. Variation at HLA_DQA1-DQB1 is the major genetic risk factor for RHD in Aboriginal Australians studied here. Cross-reactive epitopes bind with higher affinity to alpha/beta dimers formed by risk haplotypes, supporting molecular mimicry as the key mechanism of RHD pathogenesis.
Risk factors for group A streptococcal pharyngitis and skin infections: A case control study
Publisher: Elsevier BV
Date: 09-2022
Rheumatic Heart Disease Worldwide
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.JACC.2018.06.063
Abstract: Rheumatic heart disease (RHD) is a preventable heart condition that remains endemic among vulnerable groups in many countries. After a period of relative neglect, there has been a resurging interest in RHD worldwide over the past decade. In this Scientific Expert Panel, the authors summarize recent advances in the science of RHD and sketch out priorities for current action and future research. Key questions for laboratory research into disease pathogenesis and epidemiological research on the burden of disease are identified. The authors present a variety of pressing clinical research questions on optimal RHD prevention and advanced care. In addition, they propose a policy and implementation research agenda that can help translate current evidence into tangible action. The authors maintain that, despite knowledge gaps, there is sufficient evidence for national and global action on RHD, and they argue that RHD is a model for strengthening health systems to address other cardiovascular diseases in limited-resource countries.
Is Streptococcus pyogenes Resistant or Susceptible to Trimethoprim-Sulfamethoxazole?
Publisher: American Society for Microbiology
Date: 12-2012
DOI: 10.1128/JCM.02195-12
Abstract: Streptococcus pyogenes is commonly believed to be resistant to trimethoprim-sulfamethoxazole (SXT), resulting in reservations about using SXT for skin and soft tissue infections (SSTI) where S. pyogenes is involved. S. pyogenes ' in vitro susceptibility to SXT depends on the medium's thymidine content. Thymidine allows S. pyogenes to bypass the sulfur-mediated inhibition of folate metabolism and, historically, has resulted in apparently reduced susceptibility of S. pyogenes to sulfur antibacterials. The low thymidine concentration in Mueller-Hinton agar (MHA) is now regulated. We explored S. pyogenes susceptibility to SXT on various media. Using two sets of 100 clinical S. pyogenes isolates, we tested for susceptibility using SXT Etests on MHA containing defibrinated horse blood and 20 mg/liter β-NAD (MHF), MHA with sheep blood (MHS), MHA alone, MHA with horse blood (MHBA), and MHA with lysed horse blood (MHLHBA). European Committee on Antibacterial Susceptibility Testing (EUCAST) breakpoints defined susceptibility (MIC, ≤1 mg/liter) and resistance (MIC, mg/liter). In study 1, 99% of S. pyogenes isolates were susceptible to SXT on MHA, MHBA, and MHLHBA, with geometric mean MICs of 0.04, 0.04, and 0.05 mg/liter, respectively. In study 2, all 100 S. pyogenes isolates were susceptible to SXT on MHF, MHS, MHA, and MHLHBA with geometric mean MICs of 0.07, 0.16, 0.07, and 0.09 mg/liter, respectively. This study confirms the in vitro susceptibility of S. pyogenes to SXT, providing support for the use of SXT for SSTIs. A clinical trial using SXT for impetigo is ongoing.
Whole genome sequencing reveals extensive community-level transmission of group AStreptococcusin remote communities
Publisher: Cambridge University Press (CUP)
Date: 02-2016
DOI: 10.1017/S095026881500326X
Abstract: Impetigo is common in remote Indigenous children of northern Australia, with the primary driver in this context being Streptococcus pyogenes [or group A Streptococcus (GAS)]. To reduce the high burden of impetigo, the transmission dynamics of GAS must be more clearly elucidated. We performed whole genome sequencing on 31 GAS isolates collected in a single community from children in 11 households with ⩾2 GAS-infected children. We aimed to determine whether transmission was occurring principally within households or across the community. The 31 isolates were represented by nine multilocus sequence types and isolates within each sequence type differed from one another by only 0–3 single nucleotide polymorphisms. There was evidence of extensive transmission both within households and across the community. Our findings suggest that strategies to reduce the burden of impetigo in this setting will need to extend beyond in idual households, and incorporate multi-faceted, community-wide approaches.
East African immigrant children in Australia have poor immunisation coverage
Publisher: Wiley
Date: 12-2011
DOI: 10.1111/J.1440-1754.2011.02099.X
Abstract: To provide data on the immunisation status of recently arrived East African children and adolescents in Australia. A prospective audit was conducted at a hospital-based paediatric immigrant health clinic, in Melbourne, Australia, over the time period November 2000-January 2002. Study subjects were consecutive children and adolescents born in East Africa, arriving in Australia after January 1998. Vaccination status was ascertained by parent report and review of patient-held records where available, and by serological testing for immunity to hepatitis B, tetanus, diphtheria, rubella and measles. Among 136 participants, 132 (97%) had incomplete or unknown immunisation status based on parent report and vaccination records written records were available for 5/136 (4%) of participants. Only 21/136 (15%) had serological immunity to all five of measles, rubella, tetanus, diphtheria and hepatitis B, despite a total of 395 visits to vaccine providers by participants since migration. A higher proportion of children had serological immunity to measles (90%) compared to the proportion with serological immunity to rubella (77%), tetanus (61%), diphtheria (45%) and hepatitis B (33%). The predictive value of parent-reported vaccination status for serological immunity was poor. Paediatric East African immigrants in Victoria are very likely to be inadequately immunised and parent-reported vaccination status does not predict serological immunity. Full catch-up immunisation is recommended where immunisation status is unknown and written records are unavailable. Consideration should be given to policy and program development to provide timely and complete immunisation coverage in this group after arrival in Australia.
Joining the dots: The links between education and health and implications for Indigenous children
Publisher: Wiley
Date: 12-2009
DOI: 10.1111/J.1440-1754.2009.01596.X
Abstract: This paper provides a general overview of the literature investigating the nexus between education and health discussing the relationship between these domains at in idual, family and community levels. We then briefly examine the programme and research implications of such a framework for interventions aimed at improving education and health, with specific reference to young Indigenous Australians. We find that while education and health are inextricably linked, throughout the life course and at different levels of influence, there is less empirical work exploring this relationship in an Indigenous context. Given the gravity of literacy and numeracy failure rates in school-based education and its potential impact on Indigenous health, we assert an urgent case for rigorous research into interventions that address the barriers to effectiveness in implementing quality educational experiences and opportunities for Indigenous children.
Proneural gene-linked neurogenesis in zebrafish cerebellum
Publisher: Elsevier BV
Date: 07-2010
DOI: 10.1016/J.YDBIO.2010.03.024
Abstract: In mammals, cerebellar neurons are categorized as glutamatergic or GABAergic, and are derived from progenitors that express the proneural genes atoh1 or ptf1a, respectively. In zebrafish, three atoh1 genes, atoh1a, atoh1b, and atoh1c, are expressed in overlapping but distinct expression domains in the upper rhombic lip (URL): ptf1a is expressed exclusively in the ventricular zone (VZ). Using transgenic lines expressing fluorescent proteins under the control of the regulatory elements of atoh1a and ptf1a, we traced the lineages of the cerebellar neurons. The atoh1(+) progenitors gave rise not only to granule cells but also to neurons of the anteroventral rhombencephalon. The ptf1a(+) progenitors generated Purkinje cells. The olig2(+) eurydendroid cells, which are glutamatergic, were derived mostly from ptf1a(+) progenitors in the VZ but some originated from the atoh1(+) progenitors in the URL. In the adult cerebellum, atoh1a, atoh1b, and atoh1c are expressed in the molecular layer of the valvula cerebelli and of the medial corpus cerebelli, and ptf1a was detected in the VZ. The proneural gene expression patterns coincided with the sites of proliferating neuronal progenitors in the adult cerebellum. Our data indicate that proneural gene-linked neurogenesis is evolutionarily conserved in the cerebellum among vertebrates, and that the continuously generated neurons help remodel neural circuits in the adult zebrafish cerebellum.
Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015
Publisher: Elsevier BV
Date: 07-2017
Impact of an Ivermectin Mass Drug Administration on Scabies Prevalence in a Remote Australian Aboriginal Community
Publisher: Public Library of Science (PLoS)
Date: 30-10-2015
Community leadership and empowerment are essential for eliminating rheumatic heart disease
Publisher: AMPCo
Date: 11-07-2020
DOI: 10.5694/MJA2.50695
Epidemiology and Prevention of Group A Streptococcal Infections: Acute Respiratory Tract Infections, Skin Infections, and their Sequelae at the Close of the Twentieth Century
Publisher: Oxford University Press (OUP)
Date: 02-1999
DOI: 10.1086/515114
Abstract: Infections of the upper respiratory tract and skin due to group A Streptococcus are common, and the organism is highly transmissible. In industrialized countries and to some extent in developing countries, control efforts continue to emphasize that group A streptococcal pharyngitis should be properly diagnosed and appropriately treated. In developing countries and in indigenous populations where the burden of group A streptococcal diseases appears greatest, the epidemiology is less completely defined and may differ from that in industrialized countries. There is a need for accurately collected epidemiological data from developing countries, which may also further clarify the pathogenesis of group A streptococcal infections and their sequelae. While proper treatment of group A streptococcal pharyngitis continues to be essential in all populations, it may be appropriate in developing countries to consider additional strategies to reduce rates of pyoderma.
Trough Concentrations of Vancomycin
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2012
Immunogenicity following one, two, or three doses of the 7-valent pneumococcal conjugate vaccine
Publisher: Elsevier BV
Date: 09-2009
Functional analysis of IgA antibodies specific for a conserved epitope within the M protein of group A streptococci from Australian Aboriginal endemic communities.
Publisher: Oxford University Press (OUP)
Date: 04-1999
Abstract: The mucosa is one of the initial sites of group A streptococcal (GAS) infection and salivary IgA (sIgA) is thought to be critical to immunity. However, the target epitopes of sIgA and the function of sIgA in GAS immunity, in particular the role of accessory cells and complement, is largely unknown. We studied the aquisition and the function of sIgA specific for a conserved region epitope, p145 (sequence: LRRDLDASREAKKQVEKALE) of the M protein. Peptide 145-specific sIgA is highly prevalent within an Aboriginal population living in an area endemic for GAS and acquisition of p145-specific sIgA increases with age, consistent with a role for such antibodies in immunity to GAS. Human sIgA and IgG specific for p145 were affinity purified and shown to opsonize M5 GAS in vitro. Opsonization could be specifically inhibited by the addition of free p145 to the antibodies during assay. Opsonization of GAS was totally dependent on the presence of both complement and polymorphonuclear leukocytes, and, moreover, affinity-purified p145-specific sIgA was shown to fix complement in the presence of M5 GAS. These data show that mucosal IgA to this conserved region peptide within the M protein has an important role in human immunity against GAS and may be useful in a broad-based cross-protective anti-streptococcal vaccine.
Acute rheumatic fever
Publisher: Elsevier BV
Date: 10-2005
Some of the People, Some of the Time
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-02-2009
DOI: 10.1161/CIRCULATIONAHA.108.792135
Abstract: Acute rheumatic fever is a major cause of heart disease in large parts of the world, but it remains unknown why only a small fraction of those who are infected with rheumatogenic group A streptococci develop an abnormal immune response that leads to acute rheumatic fever. An understanding of the mechanisms underlying host susceptibility can provide important insights into pathogenesis that in turn can inform new treatments. Extensive searches for susceptibility factors have been undertaken, including human leukocyte antigens, B-cell alloantigens, and cytokine genes. Although significant associations have been found between genetic factors and acute rheumatic fever, study results often conflict with each other. This review explores current understanding about host susceptibility to acute rheumatic fever and provides an overall perspective to the number of studies that have recently addressed this subject.
Penicillin G concentrations required for prophylaxis against Group A Streptococcus infection evaluated using a hollow fibre model and mathematical modelling
Publisher: Oxford University Press (OUP)
Date: 26-04-2022
DOI: 10.1093/JAC/DKAC124
Abstract: Acute rheumatic fever (ARF), an autoimmune reaction to Group A Streptococcus (Streptococcus pyogenes Strep A) infection, can cause rheumatic heart disease (RHD). New formulations of long-acting penicillins are being developed for secondary prophylaxis of ARF and RHD. To evaluate the penicillin G concentrations required to suppress growth of Strep A. Broth microdilution MIC and MBC for Strep A strains M75611024, M1T15448 and M18MGAS8232 were determined. All strains were studied in a hollow fibre model (initial inoculum 4 log10 cfu/mL). Constant penicillin G concentrations of 0.008, 0.016 and 0.05 mg/L were examined against all strains, plus 0.012 mg/L against M18MGAS8232. Viable counts were determined over 144 h. Subsequently, all penicillin G-treated cartridges were emptied, reinoculated with 5 log10 cfu/mL and counts determined over a further 144 h. Mathematical modelling was performed. MIC and MBC were 0.008 mg/L for all strains small subpopulations of M75611024 and M1T15448, but not M18MGAS8232, grew at 1× MIC. Following the first inoculation, 0.008 mg/L achieved limited killing and/or stasis against M75611024 and M1T15448, with subsequent growth to ∼6 log10 cfu/mL. Following both inocula, concentrations ≥0.016 mg/L suppressed M75611024 and M1T15448 to & log10 cfu/mL from 6 h onwards with eradication. Concentrations ≥0.008 mg/L suppressed M18MGAS8232 to & log10 cfu/mL from 24 h onwards with eradication after both inoculations. Mathematical modelling well described all strains using a single set of parameter estimates, except for different maximum bacterial concentrations and proportions of bacteria growing at 1× MIC. In the absence of validated animal and human challenge models, the study provides guidance on penicillin G target concentrations for development of new penicillin formulations.
Immunogenicity, otitis media, hearing impairment, and nasopharyngeal carriage 6-months after 13-valent or ten-valent booster pneumococcal conjugate vaccines, stratified by mixed priming schedules: PREVIX_COMBO and PREVIX_BOOST randomised controlled trials
Publisher: Elsevier BV
Date: 09-2022
Hyporesponsiveness to re-challenge dose following pneumococcal polysaccharide vaccine at 12 months of age, a randomized controlled trial.
Publisher: Elsevier BV
Date: 04-2010
Progress towards a coordinated, national paediatric antimicrobial resistance surveillance programme: Staphylococcus aureus, enterococcal and Gram-negative bacteraemia in Australia
Publisher: Oxford University Press (OUP)
Date: 10-03-2020
DOI: 10.1093/JAC/DKAA065
Abstract: There is increasing knowledge of antimicrobial usage in children yet limited availability of nationally representative paediatric-specific data on antimicrobial resistance. Paediatric data from this national surveillance programme are presented to explore differences between childhood and adult bloodstream infections and antimicrobial resistance surveillance. Using information collected from a prospective coordinated antimicrobial resistance surveillance programme, children ≤18 years and adults & years with a positive blood culture for Staphylococcus aureus, Enterococcus spp. or Gram-negative spp. presenting to one of 34 Australian hospitals during 2013–16 were evaluated. Consistent methodologies for key sepsis pathogens were employed and a comparative analysis between children and adults was conducted. There are stark contrasts between children and adults in this national antimicrobial resistance (AMR) data set. Notable differences include lower rates of AMR, different clinical and molecular phenotypes and lower mortality amongst children. The burden of Gram-negative resistance is disproportionately experienced in children, with higher odds of death with an ESBL versus non-ESBL bacteraemia in comparison with adults. These data support that children are not just ‘little adults’ in the AMR era, and analyses by age group are important to detect differences in antibiotic susceptibility, clinical phenotype and genetic virulence factors. Antimicrobial surveillance incorporated into routine laboratory practice is vital to inform an array of wider applications including antimicrobial guidelines, stewardship and direction for prioritization of novel antimicrobial development.
Post-infectious group A streptococcal autoimmune syndromes and the heart
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.AUTREV.2015.04.005
Abstract: There is a pressing need to reduce the high global disease burden of rheumatic heart disease (RHD) and its harbinger, acute rheumatic fever (ARF). ARF is a classical ex le of an autoimmune syndrome and is of particular immunological interest because it follows a known antecedent infection with group A streptococcus (GAS). However, the poorly understood immunopathology of these post-infectious diseases means that, compared to much progress in other immune-mediated diseases, we still lack useful biomarkers, new therapies or an effective vaccine in ARF and RHD. Here, we summarise recent literature on the complex interaction between GAS and the human host that culminates in ARF and the subsequent development of RHD. We contrast ARF with other post-infectious streptococcal immune syndromes - post-streptococcal glomerulonephritis (PSGN) and the still controversial paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), in order to highlight the potential significance of variations in the host immune response to GAS. We discuss a model for the pathogenesis of ARF and RHD in terms of current immunological concepts and the potential for application of in depth "omics" technologies to these ancient scourges.
Continued Challenge of Rheumatic Heart Disease: The Gap of Understanding or the Gap of Implementation?
Publisher: Ubiquity Press, Ltd.
Date: 09-2013
The second rheumatic heart disease forum report
Publisher: Ubiquity Press, Ltd.
Date: 09-2013
DOI: 10.1016/J.GHEART.2013.08.006
Abstract: The second rheumatic heart disease (RHD) forum was held on February 18, 2013, at the Sixth World Congress of Pediatric Cardiology and Cardiac Surgery in Cape Town, South Africa, to focus attention on key areas in global RHD control, management, and prevention. Building on the foundation of the first RHD forum, over 150 interested participants met to discuss critical issues on the RHD landscape. Unique to this meeting was a mixture of erse backgrounds and disciplines, all crucially important to the conversation around RHD control and prevention. Some clear priorities have emerged for RHD activities in the next era: the necessity for political intervention and policy change increasing the health workforce by incorporating teaching, training, and task-shifting revitalizing the research agenda by merging basic, clinical, and translational research and obtaining universal access to high-quality penicillin. There was also an urgent request for new resources for existing resources to be further developed, improved, and shared across platforms and for resources to be supported in the nonmedical arena. Finally, the necessity of involving the patient community in the ongoing discussion was highlighted. The participants of both the first and second RHD forum represent a new, thriving, and growing community of RHD activists who should usher in a new era of significant improvements in RHD control and prevention.
How many doses make a difference? An analysis of secondary prevention of rheumatic fever and rheumatic heart disease
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-12-2018
Abstract: Acute rheumatic fever ( ARF ) and rheumatic heart disease cause substantial burdens worldwide. Long‐term antibiotic secondary prophylaxis is used to prevent disease progression, but evidence for benefits of different adherence levels is limited. Using data from northern Australia, we identified factors associated with adherence, and the association between adherence and ARF recurrence, progression to rheumatic heart disease, worsening or improvement of rheumatic heart disease, and mortality. Factors associated with adherence (percent of doses administered) were analyzed using logistic regression. Nested case–control and case–crossover designs were used to investigate associations with clinical outcomes conditional logistic regression was used to estimate odds ratios ( OR ) with 95% CIs Adherence estimates (7728) were analyzed. Being female, younger, having more‐severe disease, and living remotely were associated with higher adherence. Alcohol misuse was associated with lower adherence. The risk of ARF recurrence did not decrease until ≈40% of doses had been administered. Receiving % was associated with a 4‐fold increase in the odds of ARF recurrence (case–control OR : 4.00 [95% CI : 1.7–9.29], case–crossover OR : 3.31 [95% CI : 1.09–10.07]) and appeared to be associated with increased all‐cause mortality (case–control OR : 1.90 [95% CI : 0.89–4.06] case–crossover OR 1.91 [95% CI : 0.51–7.12]). We show for the first time that increased adherence to penicillin prophylaxis is associated with reduced ARF recurrence, and a likely reduction in mortality, in our setting. These findings can motivate patients to receive doses since even relatively low adherence can be beneficial, and additional doses further reduce adverse clinical outcomes.
Controlled human infection for vaccination against Streptococcus pyogenes (CHIVAS): Establishing a group A Streptococcus pharyngitis human infection study
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.VACCINE.2019.03.059
Abstract: Group A Streptococcus (GAS) is a highly-adapted and human-restricted pathogen responsible for a high global burden of disease across a erse clinical spectrum. Vaccine development has been impeded by scientific, regulatory, and commercial obstacles. Human infection studies (HIS) are increasingly contributing to drug, diagnostics, and vaccine development, reducing uncertainty at early stages, especially for pathogens with animal models that incompletely reproduce key elements of human disease. We review the small number of historical GAS HIS and present the study protocol for a dose-ranging inpatient study in healthy adults. The primary objective of the study is to establish a new GAS pharyngitis HIS with an attack rate of at least 60% as a safe and reliable platform for vaccine evaluation and pathogenesis research. According to an adaptive dose-ranging study design, emm75 GAS doses manufactured in keeping with principles of Good Manufacturing Practice will be directly applied by swab to the pharynx of carefully screened healthy adult volunteers at low risk of severe complicated GAS disease. Participants will remain as closely monitored inpatients for up to six days, observed for development of the primary outcome of acute symptomatic pharyngitis, as defined by clinical and microbiological criteria. All participants will be treated with antibiotics and followed as outpatients for six months. An intensive s ling schedule will facilitate extensive studies of host and organism dynamics during experimental pharyngitis. Ethics approval has been obtained and the study has been registered at ClinicalTrials.gov (NCT03361163).
Global, regional, and national levels of neonatal, infant, and under-5 mortality during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013
Publisher: Elsevier BV
Date: 09-2014
Preventing recurrent rheumatic fever: the role of register based programmes
Publisher: BMJ
Date: 09-2005
The dynamic nature of group A streptococcal epidemiology in tropical communities with high rates of rheumatic heart disease
Publisher: Cambridge University Press (CUP)
Date: 31-05-2007
DOI: 10.1017/S0950268807008655
Abstract: Prospective surveillance was conducted in three remote Aboriginal communities with high rates of rheumatic heart disease in order to investigate the epidemiology of group A β-haemolytic streptococci (GAS). At each household visit, participants were asked about sore throat. Swabs were taken from all throats and any skin sores. GAS isolates were emm sequence and pattern-typed using standard laboratory methods. There were 531 household visits 43 different emm types and subtypes ( emm ST) were recovered. Four epidemiological patterns were observed. Multiple emm ST were present in the population at any one time and household acquisition rates were high. Household acquisition was most commonly via 5- to 9-year-olds. Following acquisition, there was a 1 in 5 chance of secondary detection in the household. Throat detection of emm ST was brief, usually months. The epidemiology of GAS in these remote Aboriginal communities is a highly dynamic process characterized by emm ST ersity and turnover.
A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease
Publisher: Elsevier BV
Date: 12-2012
The synthesis and immune stimulating action of mannose-capped lysine-based dendrimers
Publisher: Elsevier BV
Date: 04-2019
Screening for rheumatic heart disease: current approaches and controversies.
Publisher: Springer Science and Business Media LLC
Date: 13-11-2012
DOI: 10.1038/NRCARDIO.2012.157
Abstract: Rheumatic heart disease (RHD) is a leading cause of cardiac disease among children in developing nations, and in indigenous populations of some industrialized countries. In endemic areas, RHD has long been a target of screening programmes that, historically, have relied on cardiac auscultation. The evolution of portable echocardiographic equipment has changed the face of screening for RHD over the past 5 years, with greatly improved sensitivity. However, concerns have been raised about the specificity of echocardiography, and the interpretation of minor abnormalities poses new challenges. The natural history of RHD in children with subclinical abnormalities detected by echocardiographic screening remains unknown, and long-term follow-up studies are needed to evaluate the significance of detecting these changes at an early stage. For a disease to be deemed suitable for screening from a public health perspective, it needs to fulfil a number of criteria. RHD meets some, but not all, of these criteria. If screening programmes are to identify additional cases of RHD, parallel improvements in the systems that deliver secondary prophylaxis are essential.
Acute rheumatic fever: a chink in the chain that links the heart to the throat?
Publisher: Elsevier BV
Date: 04-2004
Cross-sectional study of population-specific streptococcal antibody titres in Uganda
Publisher: BMJ
Date: 29-06-2020
DOI: 10.1136/ARCHDISCHILD-2020-318859
Abstract: Despite substantial variation of streptococcal antibody titres among global populations, there is no data on normal values in sub-Saharan Africa. The objective of this study was to establish normal values for antistreptolysin O (ASO) and antideoxyribonuclease B (ADB) antibodies in Uganda. This was an observational cross-sectional study. This study was conducted at Mulago National Referral Hospital, which is located in the capital city, K ala, and includes the Uganda Heart Institute. Participants (aged 0–50 years) were recruited. Of 428 participants, 22 were excluded from analysis, and 183 (44.4%) of the remaining were children aged 5–15 years. ASO was measured in-country by nephelometric technique. ADB s les were sent to Australia (PathWest) for analysis by enzyme inhibition assay: 80% upper limit values were established. The median ASO titre in this age group was 220 IU/mL, with the 80th percentile value of 389 IU/mL. The median ADB titre in this age group was 375 IU/mL, with the 80th percentile value of 568 IU/mL. The estimated Ugandan paediatric population standardised 80% upper-limit-of-normal ASO and ADB titres is higher than many global populations. Appropriateness of using population-specific antibody cutoffs is yet to be determined and has important implications for the sensitivity and specificity of rheumatic fever diagnosis.
Primary prevention of rheumatic fever in the 21st century: evaluation of a national programme
Publisher: Oxford University Press (OUP)
Date: 27-07-2018
DOI: 10.1093/IJE/DYY150
Abstract: Acute rheumatic fever (ARF) has largely disappeared from high-income countries. However, in New Zealand (NZ) rates remain high in indigenous (Māori) and Pacific populations. In 2011, NZ launched an intensive and unparalleled primary Rheumatic Fever Prevention Programme (RFPP). We evaluated the impact of the school-based sore throat service component of the RFPP. The evaluation used national trends of all-age first episode ARF hospitalisation rates before (2009-11) and after (2012-16) implementation of the RFPP. A retrospective cohort study compared first-episode ARF incidence during time-not-exposed (23 093 207 person-days) and time-exposed (68 465 350 person-days) with a school-based sore throat service among children aged 5-12 years from 2012 to 2016. Following implementation of the RFPP, the national ARF incidence rate declined by 28% from 4.0 per 100 000 [95% confidence interval (CI) 3.5-4.6] at baseline (2009-11) to 2.9 per 100 000 by 2016 (95% CI 2.4-3.4, P <0.01). The school-based sore throat service effectiveness overall was 23% [95% CI -6%-44% rate ratio (RR) 0.77, 95% CI 0.56-1.06]. Effectiveness was greater in one high-risk region with high coverage (46%, 95% CI 16%-66% RR 0.54, 95% CI 0.34-0.84). Population-based primary prevention of ARF through sore throat management may be effective in well-resourced settings like NZ where high-risk populations are geographically concentrated. Where high-risk populations are dispersed, a school-based primary prevention approach appears ineffective and is expensive.
ABRACADABRA aids Indigenous and non-Indigenous early literacy in Australia: Evidence from a multisite randomized controlled trial
Publisher: Elsevier BV
Date: 09-2013
The stark reality of rheumatic heart disease
Publisher: Oxford University Press (OUP)
Date: 12-01-2015
Azetidine Based Transition State Analogue Inhibitors of N-Ribosyl Hydrolases and Phosphorylases
Publisher: American Chemical Society (ACS)
Date: 02-2008
DOI: 10.1021/JM701265N
Abstract: N-ribosyl phosphorylases and hydrolases catalyze nucleophilic displacement reactions by migration of the cationic ribooxacarbenium carbon from the fixed purine to phosphate and water nucleophiles, respectively. As the lysis reaction progresses along the reaction coordinate, the distance between the purine and carbocation increases and the distance between carbocation and nucleophile decreases. Immucillin-H and DADMe-immucillin-H have been shown previously to be potent inhibitors of purine nucleoside phosphorylases and lie more toward the reactant and products side of this reaction coordinate, respectively. Both these enzyme inhibitors, which are currently in human clinical trials for different indications, are chiral and expensive to manufacture. We now report the synthesis of azetidine analogues of the DADMe-immucillins, which, despite their lack of stereochemical complexity, remain potent inhibitors (equilibrium dissociation constants as low as 229 pM) of purine nucleoside phosphorylase (PNP), methylthioadenosine phosphorylase (MTAP), and methylthioadenosine nucleosidase (MTAN), with potential utility as drug candidates.
Hospital admissions for skin infections among Western Australian children and adolescents from 1996 to 2012
Publisher: Public Library of Science (PLoS)
Date: 30-11-2017
Protocol for the systematic review of the prevention, treatment and public health management of impetigo, scabies and fungal skin infections in resource-limited settings
Publisher: Springer Science and Business Media LLC
Date: 23-09-2016
A controlled human infection model of Streptococcus pyogenes pharyngitis (CHIVAS-M75): an observational, dose-finding study
Publisher: Elsevier BV
Date: 07-2021
The Cutter Incident: How America's First Polio Vaccine Led to the Growing Vaccine Crisis
Publisher: BMJ
Date: 23-03-2006
Population pharmacokinetic study of benzathine penicillin G administration in Indigenous children and young adults with rheumatic heart disease in the Northern Territory, Australia
Publisher: Oxford University Press (OUP)
Date: 13-07-2022
DOI: 10.1093/JAC/DKAC231
Abstract: Benzathine penicillin G (BPG) is the cornerstone of secondary prophylaxis to prevent Streptococcus pyogenes infections, which precede acute rheumatic fever (ARF). The paucity of pharmacokinetic (PK) data from children and adolescents from populations at the highest risk of ARF and rheumatic heart disease (RHD) poses a challenge for determining the optimal dosing and frequency of injections and undermines efforts to develop improved regimens. We conducted a 6 month longitudinal PK study of young people receiving BPG for secondary prophylaxis. Throat and skin swabs were collected for microbiological culture along with dried blood spot (DBS) s les for penicillin concentrations. DBSs were assayed using LC-MS/MS. Penicillin concentration datasets were analysed using non-linear mixed-effects modelling and simulations performed using published BMI-for-age and weight-for-age data. Nineteen participants provided 75 throat swabs, 3 skin swabs and 216 penicillin s les. Throat cultures grew group C and G Streptococcus. Despite no participant maintaining penicillin concentration ng/mL between doses, there were no S. pyogenes throat infections and no ARF. The median (range) observed durations ng/mL for the low- and high-BMI groups were 14.5 (11.0-24.25) and 15.0 (7.5-18.25) days, respectively. Few patients at highest risk of ARF/RHD receiving BPG for secondary prophylaxis maintain penicillin concentrations above the target of 20 ng/mL beyond 2 weeks during each monthly dosing interval. These PK data suggest that some high-risk in iduals may get inadequate protection from every 4 week dosing. Future research should explore this gap in knowledge and PK differences between different populations to inform future dosing schedules.
Validation of an Integrated Management of Childhood Illness algorithm for managing common skin conditions in Fiji
Publisher: WHO Press
Date: 03-2009
Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global
Publisher: Elsevier BV
Date: 08-2015
Whole genome sequencing and molecular epidemiology of paediatric Staphylococcus aureus bacteraemia
Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.JGAR.2022.03.012
Abstract: The role Staphylococcus aureus antimicrobial resistance genes and toxins play in disease severity, management and outcome in childhood is an emerging field requiring further exploration. A prospective multisite study of Australian and New Zealand children hospitalised with S. aureus bacteraemia (SAB) occurred over 24 months (2017-2018). Whole genome sequencing (WGS) data were paired with clinical information from the ISAIAH cohort. 353 SAB isolates were sequenced 85% methicillin-susceptible S. aureus ([MSSA], 301/353) and 15% methicillin-resistant S. aureus ([MRSA], 52/353). There were 92 sequence types (STs), most commonly ST5 (18%) and ST30 (8%), grouped into 23 clonal complexes (CCs), most frequently CC5 (21%) and CC30 (12%). MSSA comprised the majority of healthcare-associated SAB (87%, 109/125), with principal clones CC15 (48%, 11/21) and CC8 (33%, 7/21). Panton-Valentine leukocidin (PVL)-positive SAB occurred in 22% (76/353) predominantly MSSA (59%, 45/76), community-onset (92%, 70/76) infections. For community-onset SAB, the only microbiological independent predictor of poor outcomes was PVL positivity (aOR 2.6 [CI 1.0-6.2]). From this WGS paediatric SAB data, we demonstrate the previously under-recognized role MSSA has in harbouring genetic virulence and causing healthcare-associated infections. PVL positivity was the only molecular independent predictor of poor outcomes in children. These findings underscore the need for further research to define the potential implications PVL-producing strains may have on approaches to S. aureus clinical management.
Skin infections and infestations in Aboriginal communities in northern Australia
Publisher: Wiley
Date: 08-2000
DOI: 10.1046/J.1440-0960.2000.00417.X
Abstract: The most important skin infections in Aboriginal communities in central and northern Australia are scabies and streptococcal pyoderma. Scabies is endemic in many remote Aboriginal communities, with prevalences in children up to 50%. The cycles of scabies transmission underlie much of the pyoderma. Up to 70% of children have skin sores, with group A streptococcus (GAS) the major pathogen. Group A streptococcus is responsible for the continuing outbreaks of post-streptococcal glomerulonephritis and acute rheumatic fever (ARF). The cycles of scabies transmission in dogs and humans do not appear to significantly overlap. Guidelines have been developed for community control of scabies and skin sores and successful community initiated coordinated programmes have occurred. The anthropophilic dermatophyte Trichophyton rubrum is ubiquitous in many communities, again reflecting living conditions. Other skin infections related to the tropical environment include melioidosis, nocardiosis, Chromobacterium violaceum and chromoblastomycosis. Sustainable and long-term improvements in scabies, skin sores and GAS-related disease and tinea require fundamental changes that address social and economic inequities and, in particular, living conditions and overcrowding.
Ivermectin worthy of further investigation
Publisher: WHO Press
Date: 10-2009
Defining and Assessing the School Readiness of Indigenous Australian Children
Publisher: SAGE Publications
Date: 03-2011
DOI: 10.1177/183693911103600112
Abstract: THE RESEARCH EVIDENCE THAT underpins the school readiness of Indigenous Australian children is reviewed in this article, followed by identification of issues requiring research attention. Two key questions are considered: 1. How is school readiness defined and how applicable are definitions to Indigenous contexts? 2. What methods of school readiness assessment are applied to Indigenous children and are the tools appropriate or effective? General definitions of school readiness are outlined. An ecological view defines school readiness as ready services, schools, communities and families. This view is scrutinised in detail to consider whether services, schools and communities are ready to promote Indigenous children's education. Extended families are pivotal social constructions in many Indigenous contexts. The extent to which this is recognised in the ecological view of school readiness is assessed. Thereafter, the methods of assessing children's school readiness are reviewed, highlighting the shortfall in techniques specifically designed and validated for Indigenous Australians and the variable applicability of the techniques currently in use.
Is it time for clinical trials of invasive group A and groups C and G Streptococcus infections?
Publisher: Elsevier BV
Date: 09-2023
Treatment of sore throat in light of the Cochrane verdict: is the jury still out?
Publisher: Wiley
Date: 11-2002
DOI: 10.5694/J.1326-5377.2002.TB04925.X
Abstract: There are few good-quality studies of the effectiveness of antibiotic treatment of proven group A streptococcal (GAS) pharyngitis in children available data suggest that antibiotics may reduce symptom duration. While there is limited justification for antibiotic treatment of GAS pharyngitis to prevent acute rheumatic fever in non-Indigenous Australians, there is no justification for routine antibiotic treatment of all patients with sore throat. Two strategies are open to clinicians: not to treat GAS pharyngitis with antibiotics, in which case no investigations should be done or to treat cases of sore throat with clinical features that suggest GAS, in which case diagnosis should be confirmed with a throat swab, and penicillin started while awaiting the result. Penicillin should be discontinued if the swab is negative, or continued for 10 days if it is positive for GAS. Surveillance of GAS infections and acute rheumatic fever is needed in Australia, as are further studies of effectiveness (including cost-effectiveness) of antibiotic treatment of proven GAS pharyngitis.
Antibiotic Prophylaxis for the Prevention of Recurrent Urinary Tract Infections in Children
Publisher: Springer US
Date: 2006
Antibiotic prophylaxis and recurrent urinary tract infection in children.
Publisher: Massachusetts Medical Society
Date: 29-10-2009
Towards Understanding the Pathogenesis of Rheumatic Fever
Publisher: Informa UK Limited
Date: 1996
DOI: 10.3109/03009749609080000
Abstract: Acute rheumatic fever results from an immunological response to group A streptococcal infection, but the exact nature of this response, and of the underlying host and organism characteristics, continues to evade researchers. Earlier models of rheumatic fever pathogenesis emphasised the importance of humoral immunity, but more recent work suggests that cellular immunity may play a primary role. Greater understanding of these disease mechanisms is allowing researchers to move towards the development of a vaccine for rheumatic fever.
The microbiology of impetigo in indigenous children: associations between Streptococcus pyogenes, Staphylococcus aureus, scabies, and nasal carriage
Publisher: Springer Science and Business Media LLC
Date: 12-2014
Safety and immunogenicity of the 23-valent pneumococcal polysaccharide vaccine at 12 months of age, following one, two, or three doses of the 7-valent pneumococcal conjugate vaccine in infancy.
Publisher: Elsevier BV
Date: 04-2010
Pneumococcal conjugate vaccines PREVenar13 and SynflorIX in sequence or alone in high-risk Indigenous infants (PREV-IX_COMBO): protocol of a randomised controlled trial
Publisher: BMJ
Date: 16-01-2015
Skin disease in the first two years of life in Aboriginal children in East Arnhem Land
Publisher: Wiley
Date: 02-09-2011
DOI: 10.1111/J.1440-0960.2011.00806.X
Abstract: The most common skin infections affecting children in remote Aboriginal communities are scabies and impetigo. Group A streptococcal skin infections are linked to the high rates of heart and renal disease occurring in Aboriginal Australians. A retrospective review of medical records was conducted in a primary health care centre in the East Arnhem region of the Northern Territory. Data was collected from all presentations to the clinic in the first 2 years of life for 99 children born between 2001 and 2005 as a component of the East Arnhem Regional Healthy Skin Project. The median number of presentations to the clinic in the first 2 years of life was 32. Skin disease was recorded in 22% of all presentations. By 1 year of age 82% of children had presented to the clinic with their first episode of impetigo and 68% with their first episode of scabies. Antibiotics were administered to 49% of children with impetigo. Skin infections are a major reason for presentation to primary health clinics and contribute to the high disease burden experienced by children in the first 2 years of life. This high frequency of presentation provides multiple opportunities for intervention and monitoring.
Subcutaneous administration of benzathine benzylpenicillin G has favourable pharmacokinetic characteristics for the prevention of rheumatic heart disease compared with intramuscular injection: a randomized, crossover, population pharmacokinetic study in healthy adult volunteers
Publisher: Oxford University Press (OUP)
Date: 22-07-2020
DOI: 10.1093/JAC/DKAA282
Abstract: Benzathine penicillin G has been used as monthly deep intramuscular (IM) injections since the 1950s for secondary prevention of acute rheumatic fever and rheumatic heart disease (RHD). Injection frequency and pain are major programmatic barriers for adherence, prompting calls for development of better long-acting penicillin preparations to prevent RHD. We hypothesized that subcutaneous (SC) administration of benzathine penicillin G could delay penicillin absorption when compared with IM injections. To compare the pharmacokinetic profile and tolerability of benzathine penicillin G according to different routes of administration, 15 healthy males participated in a randomized crossover study to receive benzathine penicillin G by either SC or IM routes, with a 10 week washout period before the second dose by the alternative route. Ultrasound guidance confirmed injection location. Penicillin concentrations and pain scores were measured for 6 weeks following injections. SC administration was well tolerated with no significant differences in pain scores. Following SC injection, the principal absorption half-life (95% CI) was 20.1 (16.3–29.5) days and 89.6% (87.1%–92.0%) of the drug was directed via this pathway compared with 10.2 (8.6–12.5) days and 71.3% (64.9%–77.4%) following IM administration. Lower peak and higher trough penicillin concentrations resulted following SC injection. Simulations demonstrated that SC infusion of higher doses of benzathine penicillin G could provide therapeutic penicillin concentrations for 3 months. SC administration of benzathine penicillin G is safe and significantly delays penicillin absorption. High-dose benzathine penicillin G via the SC route would fulfil many product characteristics required for the next generation of longer-acting penicillins for use in RHD.
Screening for rheumatic heart disease: quality and agreement of focused cardiac ultrasound by briefly trained health workers
Publisher: Springer Science and Business Media LLC
Date: 02-2016
Perinatal risk factors associated with skin infection hospitalisation in Western Australian Aboriginal and Non-Aboriginal children
Publisher: Wiley
Date: 09-2019
DOI: 10.1111/PPE.12573
Abstract: Hospitalisation with skin infection in Western Australian (WA) Aboriginal children is common, with the highest rates in infants and children from remote WA. We aimed to quantify infant, maternal, and sociodemographic risk factors for skin infection hospitalisation in WA children, focussing on Aboriginal children aged <17 years. We conducted a retrospective population-based cohort study with linked perinatal and hospitalisation data on WA-born children (1996-2012), of whom 31 348 (6.7%) were Aboriginal. We used Cox regression to calculate adjusted hazard ratios and associated population attributable fractions (PAFs) for perinatal factors attributed to first hospitalisation with skin infection. To identify specific risk factors for early-onset infection, we further restricted the cohort to infants aged <1 year. Overall, 5439 (17.4%) Aboriginal and 6750 (1.5%) non-Aboriginal children were hospitalised at least once with a skin infection. Aboriginal infants aged <1 year had the highest skin infection hospitalisation rate (63.2 per 1000 child-years). The strongest risk factors in Aboriginal children aged <17 years were socio-economic disadvantage, very remote location at birth, and multi-parity (≥3 previous pregnancies) accounting for 24%, 23%, and 15% of skin infection hospitalisations, respectively. Other risk factors included maternal age <20 years, maternal smoking during pregnancy, and low birthweight. We have quantified the relative influence of perinatal risk factors associated with skin infection hospitalisations in WA children, providing measures indicating which factors have the potential to reduce the most hospitalisations. Our evidence not only supports existing calls for substantial government investment in addressing underlying social and environmental barriers to healthy skin in WA Aboriginal children but also identifies potential areas to target health promotion messaging at in iduals/families on maternal smoking during pregnancy and skin hygiene for families.
PneuMum: Impact from a randomised controlled trial of maternal 23-valent pneumococcal polysaccharide vaccination on middle ear disease amongst Indigenous infants, Northern Territory, Australia
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.VACCINE.2015.10.101
Abstract: We assessed maternal 23-valent pneumococcal polysaccharide (23vPPV) vaccine efficacy (VE) against middle ear disease and pneumococcal carriage amongst Australian Indigenous infants. In an open label, allocation concealed, outcome-assessor blinded, community stratified, randomised controlled trial, healthy pregnant Indigenous women aged 17-39 years in the Northern Territory of Australia received the 23vPPV (1:1:1) at: 30-36 weeks gestation, birth, or were unvaccinated (ClinicalTrials.gov NCT00714064). Co-primary outcomes were the point prevalences of infant middle ear disease and 23vPPV-type carriage at age 7 months. The consent rate was 50% (313/632). Among 227 eligible participants randomised, retention rates were 86% (66/77) controls 89% (67/75) pregnancy vaccinees 88% (66/75) birth vaccinees. At infant age 7 months, ear disease prevalence was: 71% (47/66) controls, 63% (42/67) pregnancy vaccinees, 76% (50/66) birth vaccinees and 23vPPV-type carriage was: 26% (17/66) controls, 18% (12/67) pregnancy vaccinees, 18% (12/66) birth vaccinees. For pregnancy vaccinees, VE was 12% (95% CI -12% to 31%) against infant ear disease and 30% (95% CI -34% to 64%) against 23vPPV-type carriage. In a post-hoc analysis, VE against infant ear disease concurrent with carriage of 23vPPV or related types was 51% (95% CI -2% to 76%). There were no serious adverse effects following receipt of the 23vPPV in pregnancy or at birth. In a high risk population, our study was unable to demonstrate efficacy of 23vPPV in pregnancy against the co-primary outcomes of either all-cause infant ear disease or 23vPPV-type nasopharyngeal carriage at age 7 months. Efficacy against ear disease concurrent with carriage of vaccine-related serotypes (a more specific outcome) suggests 23vPPV in pregnancy may complement childhood pneumococcal vaccination programs.
Group a streptococcal diseases and their global burden.
Publisher: Springer Berlin Heidelberg
Date: 2013
DOI: 10.1007/82_2012_280
Abstract: Group A streptococcus (GAS) or Streptococcus pyogenes has been recognised as an important human pathogen since early days of modern microbiology, and it remains among the top ten causes of mortality from an infectious disease. Clinical manifestations attributable to this organism are perhaps the most erse of any single human pathogen. These encompass invasive GAS infections, with high mortality rates despite effective antimicrobials, toxin-mediated diseases including scarlet fever and streptococcal toxic shock syndrome, the autoimmune sequelae of rheumatic fever and glomerulonephritis with potential for long-term disability, and nuisance manifestations of superficial skin and pharyngeal infection, which continue to consume a sizable proportion of healthcare resources. Although an historical perspective indicates major overall reductions in GAS infection rates in the modern era, chiefly as a result of widespread improvements in socioeconomic circumstances, this pathogen remains as a leading infectious cause of global morbidity and mortality. More than 18 million people globally are estimated to suffer from serious GAS disease. This burden disproportionally affects least affluent populations, and is a major cause of illness and death among children and young adults, including pregnant women, in low-resource settings. We review GAS transmission characteristics and prevention strategies, historical and geographical trends and report on the estimated global burden disease attributable to GAS. The lack of systematic reporting makes accurate estimation of rates difficult. This highlights the need to support improved surveillance and epidemiological research in low-resource settings, in order to enable better assessment of national and global disease burdens, target control strategies appropriately and assess the success of control interventions.
Clinical outcomes for young people with screening-detected and clinically-diagnosed rheumatic heart disease in Fiji
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.IJCARD.2017.04.004
Abstract: Echocardiographic screening is under consideration as a disease control strategy for rheumatic heart disease (RHD). However, clinical outcomes of young people with screening-detected RHD are unknown. We aimed to describe the outcomes for a cohort with screening-detected RHD, in comparison to patients with clinically-diagnosed RHD. A retrospective cohort study included all young people with screening-detected RHD in the Central Division of Fiji in the primary cohort. Screen-negative and clinically-diagnosed comparison groups were matched 1:1 to the primary cohort. Data were collected on mortality, clinical complications and healthcare utilisation from the electronic and paper health records and existing databases. Seventy participants were included in each group. Demographic characteristics of the groups were similar (median age 11years, 69% female, median follow-up 7years). There were nine (12.9%) RHD-related deaths in the clinically-diagnosed group and one (1.4%) in the screening-detected group (Incident Rate Ratio: 9.6, 95% CI 1.3-420.6). Complications of RHD were observed in 39 (55.7%) clinically-diagnosed cases, four (20%) screening-detected cases and one (1.4%) screen-negative case. There were significant differences in the cumulative complication curves of the groups (p<0.001). Rates of admission and surgery were highest in the clinically-diagnosed group, and higher in the screening-detected than screen-negative group. Young people with screening-detected RHD have worse health outcomes than screen-negative cases in Fiji. The prognosis of clinically-diagnosed RHD remains poor, with very high mortality and complication rates. Further studies in other settings will inform RHD screening policy. Comprehensive control strategies are required for disease prevention.
Understanding group A streptococcal pharyngitis and skin infections as causes of rheumatic fever: protocol for a prospective disease incidence study
Publisher: Springer Science and Business Media LLC
Date: 17-07-2019
Single Parasternal-Long-Axis-View-Sweep Screening Echocardiographic Protocol to Detect Rheumatic Heart Disease: A Prospective Study of Diagnostic Accuracy
Publisher: Elsevier BV
Date: 06-2020
DOI: 10.1016/J.HLC.2019.02.196
Abstract: Echocardiographic screening in school-aged children can detect rheumatic heart disease (RHD) prior to the manifestation of symptoms of heart failure. The challenge is making this practical and affordable on a global scale. This study aims to evaluate the diagnostic utility of an ultra-abbreviated echocardiographic screening protocol involving a single parasternal-long-axis-view-sweep of the heart (SPLASH) in two dimensional (2D) and colour Doppler imaging (index test). This prospective study of diagnostic accuracy compared the diagnostic utility of the index screening test with a comprehensive reference test (standard echocardiographic screening protocols) as per World Heart Federation (WHF) echocardiographic criteria. School students in Timor-Leste aged 5-20 years were enrolled. Both index and reference test images were acquired by cardiologists on Vivid I or Q machines (GE Healthcare, Marlborough, MA, USA). A total of 1,365 participants were screened median age was 11 years. The estimated prevalence of definite and borderline RHD was 35.2 per 1,000. Congenital heart disease was identified in 11 children (0.8%) with two needing cardiac surgery. Abnormal SPLASH views were found in 109/1365 (7.99%). No cases of RHD or significant congenital heart disease were missed. Sensitivity and specificity of the abbreviated protocol for detecting RHD were 1.0 and 0.95 respectively. A simplified echocardiography screening protocol using SPLASH is highly sensitive and specific and could significantly improve the efficiency of RHD screening. It has the potential to expedite training of health workers whilst protecting the modesty of students.
Seven key actions to eradicate rheumatic heart disease in Africa: the Addis Ababa communiqué
Publisher: Clinics Cardive Publishing
Date: 06-07-2016
Starting the SToP trial
Publisher: Public Library of Science (PLoS)
Date: 11-10-2022
DOI: 10.1371/JOURNAL.PONE.0273631
Abstract: Recruitment in research can be challenging in Australian Aboriginal contexts. We aimed to evaluate the SToP (See, Treat, Prevent skin infections) trial recruitment approach for Aboriginal families to identify barriers and facilitators and understand the utility of the visual resource used. This qualitative participatory action research used purposive s ling to conduct six semi-structured interviews with staff and five yarning sessions with Aboriginal community members from the nine communities involved in the SToP trial that were audio recorded and transcribed verbatim before thematic analysis. Community members valued the employment of local Aboriginal facilitators who used the flipchart to clearly explain the importance of healthy skin and the rationale for the SToP trial while conducting recruitment. A prolonged process, under-developed administrative systems and stigma of the research topic emerged as barriers. Partnering with a local Aboriginal organisation, employing Aboriginal researchers, and utilising flip charts for recruitment was seen by some as successful. Strengthening governance with more planning and support for recordkeeping emerged as future success factors. Our findings validate the importance of partnership for this critical phase of a research project. Recruitment strategies should be co-designed with Aboriginal research partners. Further, recruitment rates for the SToP trial provide a firm foundation for building partnerships between organisations and ensuring Aboriginal perspectives determine recruitment methods.
Estimation of the force of infection and infectious period of skin sores in remote Australian communities using interval-censored data
Publisher: Public Library of Science (PLoS)
Date: 05-10-2020
Modes of transmission and attack rates of group A Streptococcal infection
Publisher: Springer Science and Business Media LLC
Date: 31-03-2021
DOI: 10.1186/S13643-021-01641-5
Abstract: Group A Streptococcus (Strep A) is an important cause of mortality and morbidity globally. This bacterium is responsible for a range of different infections and post-infectious sequelae. Summarising the current knowledge of Strep A transmission to humans will address gaps in the evidence and inform prevention and control strategies. The objective of this study is to evaluate the modes of transmission and attack rates of group A streptococcal infection in human populations. This systematic review protocol was prepared according to the Preferred Reporting Items for Systematic reviews and Meta-analysis Protocols (PRISMA-P) 2015 Statement. Using a comprehensive search strategy to identify any transmission studies that have been published in English since 1980, full-text articles will be identified and considered for inclusion against predefined criteria. We will include all studies reporting on Strep A transmission, who have identified a mode of transmission, and who reported attack rates. Risk of bias will be appraised using an appropriate tool. Our results will be described narratively and where feasible and appropriate, a meta-analysis utilizing the random-effects model will be used to aggregate the incidence proportions (attack rates) for each mode of transmission. In addition, we will also evaluate the emm genotype variants of the M protein causing Strep A infection and the association with transmission routes and attack rates, if any, by setting, socioeconomic background and geographical regions. We anticipate that this review will contribute to elucidating Strep A modes of transmission which in turn, will serve to inform evidence-based strategies including environmental health activities to reduce the transmission of Strep A in populations at risk of severe disease. Systematic review registration: PROSPERO ( CRD42019138472 ).
Disparity in Mortality From Rheumatic Heart Disease in Indigenous Australians
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-07-2015
Abstract: Recent estimates of the global burden of rheumatic heart disease (RHD) have highlighted the paucity of reliable RHD mortality data from populations most affected by RHD. We investigated RHD mortality rates and trends for Indigenous and non‐Indigenous Australians in the Northern Territory (NT) for the period 1977–2005 and seminationally (NT plus 4 other states, covering 89% of Indigenous Australians) from 1997 to 2005 using vital statistics data. All analysis was undertaken by Indigenous status, sex, and age at death. In the NT, 90% of all deaths from RHD were among Indigenous persons however, the Indigenous population makes up only 30.4% of the NT population. The death rate ratio (Indigenous compared with non‐Indigenous) was 54.80 in the NT and 12.74 in the other 4 states (estimated at the median age of 50 years). Non‐Indigenous death rates were low for all age groups except ≥65 years, indicating RHD deaths in the elderly non‐Indigenous population. Death rates decreased at a more rapid rate for non‐Indigenous than Indigenous persons in the NT between 1997 and 2005. Indigenous persons in other parts of Australia showed lower death rates than their NT counterparts, but the death rates for Indigenous persons in all states were still much higher than rates for non‐Indigenous Australians. Indigenous Australians are much more likely to die from RHD than other Australians. Among the Indigenous population, RHD mortality is much higher in the NT than elsewhere in Australia, exceeding levels reported in many industrialized countries more than a century ago. With the paucity of data from high‐prevalence areas, these data contribute substantially to understanding the global burden of RHD mortality.
Prevalence of rheumatic heart disease in young adults from New Caledonia
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.ACVD.2014.07.053
Abstract: Rheumatic heart disease (RHD) is an important public health issue, particularly in the Pacific region, but its true burden is unknown. To evaluate the prevalence of rheumatic heart disease (RHD) in young adults from New Caledonia, based on echocardiography, and to evaluate the accuracy of dynamic criteria, focusing on mitral valve (MV) leaflet motion. Blind analysis of echocardiography by three cardiologists diagnosis of RHD required at least one dynamic criterion (exaggerated or restricted MV leaflet motion) subjects with morphological criteria (MV leaflet thickening), but without dynamic criteria, were considered as borderline. There were 834 subjects from three socioeconomic groups, aged 18-22 years: 699 had normal echocardiography 93 (11.5%) had physiological regurgitation nine (0.9%) had borderline RHD and five (0.59%) had RHD. The prevalence of RHD in New Caledonia was thus estimated at 5.9 per 1000 (95% confidence interval 2.6-12.2). The RHD cases were of Pacific ethnicity. Physiological regurgitation was more frequent in Pacific subjects (13.7%) than in non-Pacific subjects (6.9% P<0.0001). RHD was more prevalent in the lowest socioeconomic group. No disagreement occurred between the three reviewers concerning analysis of dynamic criteria all disagreements were related to morphological criteria. The prevalence of echocardiographically diagnosed RHD in adults in New Caledonia is estimated at 5.9 per 1000 it occurs most frequently in Pacific subjects and those with low incomes. Dynamic criteria were more accurate and reproducible than standard morphological criteria.
An Australian guideline for rheumatic fever and rheumatic heart disease: an abridged outline
Publisher: AMPCo
Date: 06-2007
DOI: 10.5694/J.1326-5377.2007.TB01059.X
Abstract: Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are diseases of poverty. They occur at world-record rates in Indigenous Australians, yet in idual cases are often poorly managed, and most jurisdictions with high rates of these diseases do not have formal control strategies in place. New Australian guidelines formulated in 2005 by the National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand for diagnosis and management of ARF and RHD are a valuable resource for clinicians and policymakers. Key recommendations of the guidelines include: New diagnostic criteria for ARF in high-risk populations, including Indigenous Australians, which include echocardiographic evidence of subclinical valvular disease, and polyarthralgia or aseptic monoarthritis as major manifestations. Clear guidance about treatment of ARF. Non-steroidal anti-inflammatory drugs should be withheld until the diagnosis is confirmed, and corticosteroids may be an option in severe acute carditis. Most cases of chorea do not require medication, but use of carbamazepine or sodium valproate is recommended if medication is needed. Clear guidance about dose, dosing frequency and duration of secondary prophylaxis. Benzathine penicillin G is the preferred medication for this purpose. Establishment of a coordinated control program for all regions of Australia where there are populations with high prevalence of ARF and RHD. Key elements and indicators for evaluation are recommended. Active screening and legislated notification of ARF and RHD, where possible. Development of a structured care plan for all patients with a history of ARF or with established RHD, to be recorded in the patient's primary health care record.
Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: A systematic analysis for the Global Burden of Disease Study 2013
Publisher: Elsevier BV
Date: 2015
Invasive group A streptococcal infection in the Northern Territory, Australia: Case report and review of the literature
Publisher: Wiley
Date: 23-06-2014
DOI: 10.1111/JPC.12659
Abstract: The increasing incidence of invasive group A streptococcus has been well documented in the temperate climates of North America, Europe and the United Kingdom. Studies also suggest that there are high rates of invasive group A streptococcus infection within the indigenous population of Northern Australia. This review article presents the case of infant Aboriginal twins with invasive group A streptococcal infection complicated by streptococcal toxic shock syndrome, highlighting both the severity and high transmissibility of invasive group A streptococcal disease. We review the epidemiology of group A streptococcal infection and suggest a potential role for chemoprophylaxis of household contacts to reduce the burden of disease within the indigenous population of Northern Australia.
Clinical development strategy for a candidate group A streptococcal vaccine
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.VACCINE.2017.02.060
Abstract: GroupA streptococci (GAS) cause a wide spectrum of diseases ranging from benign pharyngitis and skin infections to severe invasive disease and the immune sequelae rheumatic fever and rheumatic heart disease. Pharyngitis, one of the most frequent diseases caused by GAS, is highly prevalent in school-age children in temperate climates and a major cause of antibiotic use. An efficacious vaccine would reduce disease burden associated with pharyngitis and the need of care for sick children. Importantly, GAS pharyngitis is recognised as the main precursor for acute rheumatic fever so a vaccine that is efficacious against GAS pharyngitis should also prevent acute rheumatic fever and rheumatic heart disease. It may also prevent post-streptococcal glomerulonephritis and invasive disease since GAS pharyngitis is one of the precursors for these clinical syndromes. There has been no clearly articulated pathway for clinical trial design leading to GAS vaccine registration. This review outlines a clinical development strategy detailing the phases of development required for registration of a candidate GAS vaccine for GAS pharyngitis initially, followed by impetigo and associated sequelae. The major advantages of a strategy first focused on GAS pharyngitis is an early proof of principle, that can be followed by studies for other clinical syndromes. The end goal being the availability of a preventive tool for the most prevalent GAS-associated diseases globally.
Labour outcomes in caseload midwifery and standard care: a register-based cohort study
Publisher: Springer Science and Business Media LLC
Date: 12-2018
Prospective Study of a Real-Time PCR That Is Highly Sensitive, Specific, and Clinically Useful for Diagnosis of Meningococcal Disease in Children
Publisher: American Society for Microbiology
Date: 07-2004
DOI: 10.1128/JCM.42.7.2919-2925.2004
Abstract: Due to the early administration of antibiotics, meningococcal disease is increasingly difficult to diagnose by culturing. Laboratory studies have shown PCR to be sensitive and specific, but there have been few clinical studies. The objectives of this study were to determine the diagnostic accuracy and clinical usefulness of meningococcal PCR through a prospective comparison of real-time PCR, nested PCR, and standard culturing of blood and cerebrospinal fluid (CSF). The setting was a tertiary-care pediatric hospital in Australia, and the participans were 118 children admitted with possible septicemia or meningitis. The main outcome measures—sensitivity, specificity, and positive and negative predictive values—were compared to a “gold standard ” fulfilling clinical and laboratory criteria. For 24 cases of meningococcal disease diagnosed by the gold standard, culturing of blood or CSF was positive for 15 (63%), nested PCR was positive for 21 (88%), and real-time PCR was positive for 23 (96%). The sensitivity, specificity, and positive and negative predictive values of real-time PCR (the most sensitive test) for all specimens were, respectively, 96% (95% confidence interval, 79 to 99%), 100% (95% confidence interval, 96 to100%), 100% (95% confidence interval, 85 to 100%), and 99% (95% confidence interval, 94 to 100%). Of 54 patients with suspected meningococcal disease at admission, 23 had positive PCR results. Only one PCR specimen was positive in a patient thought unlikely to have meningococcal disease at admission. Blood PCR remained positive for 33% of patients tested at up to 72 h. Real-time PCR has high positive and negative predictive values in this clinical setting, with better confirmation of cases than nested PCR. Targeting patients for PCR based on admission criteria appears to be practical, and the test may remain useful for several days after the start of antibiotic administration.
Prevalence of group A β-hemolytic streptococcal throat carriage and prospective pilot surveillance of streptococcal sore throat in Ugandan school children
Publisher: Elsevier BV
Date: 04-2020
DOI: 10.1016/J.IJID.2020.01.013
Abstract: Group A β-hemolytic Streptococcus (GAS), also known as Streptococcus pyogenes, is responsible for an annual 600 million cases of acute pharyngitis globally, with 92% of those infections occurring in low-resource settings. Further knowledge of the acute streptococcal pharyngitis burden in low-resource settings is essential if serious post-streptococcal complications - rheumatic fever (RF) and its long-term sequel rheumatic heart disease (RHD) - are to be prevented. Two studies were conducted in school-aged children (5-16 years): a cross-sectional study of streptococcal pharyngeal carriage followed by a prospective cohort study of streptococcal sore throat over 4 weeks from March to April 2017. The cross-sectional study revealed an overall prevalence of GAS carriage of 15.9% (79/496, 95% confidence interval 12.8-19.5%). Among 532 children enrolled in the prospective cohort study, 358 (67%) reported 528 sore throats, with 221 (41.1%) experiencing at least one GAS-positive sore throat. The overall GAS-positive rate for sore throat was 41.8% (221/528). The GAS pharyngeal carriage rates seen in Uganda (15.9%, 95% confidence interval 12.8-19.5%) are higher than the most recent pooled results globally, at 12% (range 6-28%). Additionally, pilot data suggest a substantially higher percentage of sore throat that was GAS-positive (41.8%) compared to pooled global rates when active recruitment is employed.
Rheumatic heart disease mortality in Indigenous and non-Indigenous Australians between 2010 and 2017
Publisher: BMJ
Date: 03-2023
DOI: 10.1136/HEARTJNL-2022-322146
Abstract: To generate contemporary age-specific mortality rates for Indigenous and non-Indigenous Australians aged years who died from rheumatic heart disease (RHD) between 2013 and 2017, and to ascertain the underlying causes of death (COD) of a prevalent RHD cohort aged years who died during the same period. For this retrospective, cross-sectional epidemiological study, Australian RHD deaths for 2013–2017 were investigated by first, mortality rates generated using Australian Bureau of Statistics death registrations where RHD was a coded COD, and second COD analyses of death records for a prevalent RHD cohort identified from RHD register and hospitalisations. All analyses were undertaken by Indigenous status and age group (0–24, 25–44, 45–64 years). Age-specific RHD mortality rates per 100 000 were 0.32, 2.63 and 7.41 among Indigenous 0–24, 25–44 and 45–64 year olds, respectively, and the age-standardised mortality ratio (Indigenous vs non-Indigenous 0–64 year olds) was 14.0. Within the prevalent cohort who died (n=726), RHD was the underlying COD in 15.0% of all deaths, increasing to 24.6% when RHD was included as associated COD. However, other cardiovascular and non-cardiovascular conditions were the underlying COD in 34% and 43% respectively. Premature mortality in people with RHD aged years has approximately halved in Australia since 1997–2005, most notably among younger Indigenous people. Mortality rates based solely on underlying COD potentially underestimates true RHD mortality burden. Further strategies are required to reduce the high Indigenous to non-Indigenous mortality rate disparity, in addition to optimising major comorbidities that contribute to non-RHD mortality.
Pneumococcal Nasopharyngeal Carriage following Reduced Doses of a 7-Valent Pneumococcal Conjugate Vaccine and a 23-Valent Pneumococcal Polysaccharide Vaccine Booster
Publisher: American Society for Microbiology
Date: 12-2010
DOI: 10.1128/CVI.00117-10
Abstract: This study was conducted to evaluate the effect of a reduced-dose 7-valent pneumococcal conjugate vaccine (PCV) primary series followed by a 23-valent pneumococcal polysaccharide vaccine (23vPPS) booster on nasopharyngeal (NP) pneumococcal carriage. For this purpose, Fijian infants aged 6 weeks were randomized to receive 0, 1, 2, or 3 PCV doses. Within each group, half received 23vPPS at 12 months. NP swabs were taken at 6, 9, 12, and 17 months and were cultured for Streptococcus pneumoniae. Isolates were serotyped by multiplex PCR and a reverse line blot assay. There were no significant differences in PCV vaccine type (VT) carriage between the 3- and 2-dose groups at 12 months. NP VT carriage was significantly higher ( P , .01) in the unvaccinated group than in the 3-dose group at the age of 9 months. There appeared to be a PCV dose effect in the cumulative proportion of infants carrying the VT, with less VT carriage occurring with more doses of PCV. Non-PCV serotype (NVT) carriage rates were similar for all PCV groups. When groups were pooled by receipt or nonreceipt of 23vPPS at 12 months, there were no differences in pneumococcal, VT, or NVT carriage rates between the 2 groups at the age of 17 months. In conclusion, there appeared to be a PCV dose effect on VT carriage, with less VT carriage occurring with more doses of PCV. By the age of 17 months, NVT carriage rates were similar for all groups. 23vPPS had no impact on carriage, despite the substantial boosts in antibody levels.
Disseminated, Multiclonal Epstein-Barr Virus-Associated Lymphoproliferative Disease in a Patient with Hematological and Immunological Anomalies Molecular Analysis Correlates with Morphological Appeara
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-1995
DOI: 10.1097/00019606-199503000-00008
Abstract: We report a case of a 21-year-old woman with hematopoietic, immunological, and congenital dysmorphic abnormalities, who died following rapidly progressive, disseminated Epstein-Barr virus (EBV)-associated lymphoproliferative disease (LPD). Polymerase chain reaction (PCR) lification of formalin-fixed paraffin-embedded tissue showed differences in the clonality of each separate lymphoproliferative lesion examined, as determined by immunoglobulin heavy chain (IgH) gene rearrangement. PCR analysis also demonstrated that all lesions contained EBV genome. Since DNA had been extracted from paraffin blocks, a direct comparison of morphology and clonality could be made in each in idual lesion. The evidence from this study indicates that the monoclonal tumors arose de novo in multiple sites and that the polyclonal background observed in some lesions reflected a substantial concomitant inflammatory response.
Standardization of Epidemiological Surveillance of Acute Poststreptococcal Glomerulonephritis
Publisher: Oxford University Press (OUP)
Date: 15-09-2022
DOI: 10.1093/OFID/OFAC346
Abstract: Acute poststreptococcal glomerulonephritis (APSGN) is an immune complex-induced glomerulonephritis that develops as a sequela of streptococcal infections. This article provides guidelines for the surveillance of APSGN due to group A Streptococcus (Strep A). The primary objectives of APSGN surveillance are to monitor trends in age- and sex-specific incidence, describe the demographic and clinical characteristics of patients with APSGN, document accompanying risk factors, then monitor trends in frequency of complications, illness duration, hospitalization rates, and mortality. This document provides surveillance case definitions for APSGN, including clinical and subclinical APSGN based on clinical and laboratory evidence. It also details case classifications that can be used to differentiate between confirmed and probable cases, and it discusses the current investigations used to provide evidence of antecedent Strep A infection. The type of surveillance recommended depends on the burden of APSGN in the community and the objectives of surveillance. Strategies for minimal surveillance and enhanced surveillance of APSGN are provided. Furthermore, a discussion covers the surveillance population and additional APSGN-specific surveillance considerations such as contact testing, active follow up of cases and contacts, frequency of reporting, surveillance visits, period of surveillance, and community engagement. Finally, the document presents core data elements to be collected on case report forms, along with guidance for documenting the course and severity of APSGN.
Fetal Alcohol Spectrum Disorder (FASD): Knowledge, attitudes, experiences and practices of the Western Australian youth custodial workforce
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.IJLP.2018.05.008
Abstract: Fetal Alcohol Spectrum Disorder (FASD) is a condition caused by prenatal alcohol exposure and characterised by lifelong physical, behavioural and cognitive abnormalities. Primary disabilities, such as impairment in memory, attention, cognition, language, executive function, and adaptive function, can lead to young people with FASD becoming engaged with the justice system. Little is known about the extent of FASD in youth detention in Australia, or of the capacity custodial staff have to manage and support young people with FASD. In tandem with a study assessing the prevalence of FASD among youth in detention in Western Australia (WA), this study aims to establish the current knowledge, attitudes, experiences and practices regarding FASD and other neurodevelopmental impairments among youth custodial officers in order to develop training resources for this workforce. We invited youth custodial officers in the only youth detention centre in WA to participate in an online or hardcopy survey. The survey was developed following extensive consultation with the workforce and investigated their knowledge, attitudes, experiences and practices relating to FASD and other neurodevelopmental impairments. This included experience working with young people with FASD and other impairments, and attitudes towards relevant training. 112 youth custodial officers (51% of the youth custodial workforce) completed the survey. While many respondents had heard of FASD (77%) and understood it is relevant to the justice system (74%), limited in-depth FASD knowledge existed. Many respondents were unsure or unaware that FASD is permanent brain damage (53%) and cannot be outgrown (57%). Respondents were infrequently informed if a young person in detention had a diagnosis of FASD. Almost all custodial officers indicated motivation to complete training to further understand FASD (92%) and other neurodevelopmental impairments (94%), with particular interest in the application of management strategies appropriate for affected young people. A lack of specific knowledge, inadequate training to recognise and manage young people with neurodevelopmental impairments, and inconsistent information-sharing processes reduce the ability of the custodial workforce to care for young people with FASD and other neurodevelopmental impairments. These findings have supported the development and evaluation of training resources targeting the specific needs and requests of the WA youth custodial workforce, and this is now underway.
Immunogenicity for 16 serotypes of a unique schedule of pneumococcal vaccines in a high-risk population
Publisher: Elsevier BV
Date: 07-2008
DOI: 10.1016/J.VACCINE.2008.05.012
Abstract: A unique schedule of 7-valent pneumococcal conjugate vaccine (7PCV) at 2, 4 and 6 months of age and 23-valent pneumococcal polysaccharide vaccine (23PPV) at 18 months commenced for Australian Aboriginal infants in 2001. Anti-capsular IgG concentrations in vaccinated and non-vaccinated (historic control) infants were determined (blinded) by (22F absorbed) ELISA. One month after dose 3 of 7PCV, geometric mean concentrations (GMCs) were >1.95 microg/ml and at least 89% of infants had IgG >0.35 microg/ml to all 7PCV serotypes. One month post-23PPV, IgG to 7PCV serotypes was >0.35 microg/ml for more than 96% infants (>1.3 microg/ml for at least 70%), and IgG to non-7PCV serotypes was >0.35 microg/ml for more than 50% infants (including serotype 6A, but not 12F (17%) or 19A (44%). 7PCV and 23PPV are immunogenic in this population.
Indirect effects of childhood pneumococcal vaccination on pneumococcal carriage among adults and older children in Australian Aboriginal communities
Publisher: Elsevier BV
Date: 03-2007
DOI: 10.1016/J.VACCINE.2006.09.015
Abstract: Nasopharyngeal carriage of Streptococcus pneumoniae in unimmunised adults and older children in three remote Australian Aboriginal communities was compared in 2002 and 2004. Universal childhood pneumococcal vaccination with a catch-up program was introduced in late 2001. Carriage prevalence across all age groups of pneumococcal serotypes included in the 7-valent vaccine was 10% in both 2002 and 2004 (12 and 30 months after introduction of vaccination). This carriage prevalence was lower than anticipated. It is likely that indirect effects of childhood vaccination occurred before the 2002 survey. To further assess indirect effects on carriage of childhood pneumococcal vaccination, data prior to 2002 are required. Between 12 and 30 months following introduction of conjugate pneumococcal vaccination, indirect effects on carriage were unchanged.
Prevention of rheumatic fever.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2010
Rheumatic heart disease and its control in the Pacific
Publisher: Informa UK Limited
Date: 12-2009
DOI: 10.1586/ERC.09.145
Abstract: Rheumatic fever and rheumatic heart disease continue to be a huge public-health burden on many Pacific Island countries. Prevalence reported in some nations are some of the highest seen globally, yet many countries in the region do not have national disease registers. Despite the will of many Pacific Island countries, there are a number of barriers to the implementation and sustainability of effective coordinated prevention programs, including limited funding and competing health priorities. In promising recent developments, a number of countries in the region have been able to develop or strengthen national rheumatic heart disease registers. These registers allow for more effective delivery of secondary prophylaxis, the mainstay of disease control in the Pacific. Primary prevention of rheumatic fever and screening for rheumatic heart disease are important adjunctive strategies. Recent advances in screening methods, focusing on portable echocardiography, may allow for the early detection of rheumatic heart disease in the community.
Qualitative assessment of healthy volunteer experience receiving subcutaneous infusions of high-dose benzathine penicillin G (SCIP) provides insights into design of late phase clinical studies
Publisher: Public Library of Science (PLoS)
Date: 27-04-2023
DOI: 10.1371/JOURNAL.PONE.0285037
Abstract: Secondary prophylaxis to prevent rheumatic heart disease (RHD) progression, in the form of four-weekly intramuscular benzathine benzylpenicillin G (BPG) injections, has remained unchanged since 1955. Qualitative investigations into patient preference have highlighted the need for long-acting penicillins to be delivered less frequently, ideally with reduced pain. We describe the experience of healthy volunteers participating in a phase-I safety, tolerability and pharmacokinetic trial of s ub c utaneous i nfusions of high-dose benzathine p enicillin G (BPG)–the SCIP study (Australian New Zealand Clinical Trials Registry ACTRN12622000916741). Participants (n = 24) received between 6.9 mL to 20.7 mL (3–9 times the standard dose) of BPG as a single infusion into the abdominal subcutaneous tissues via a spring-driven syringe pump over approximately 20 minutes. Semi-structured interviews at four time points were recorded, transcribed verbatim and thematically analysed. Tolerability and specific descriptors of the experience were explored, alongside thoughts on how the intervention could be improved for future trials in children and young adults receiving monthly BPG intramuscular injections for RHD. Participants tolerated the infusion well and were able describe their experiences throughout. Most reported minimal pain, substantiated via quantitative pain scores. Abdominal bruising at the infusion site did not concern participants nor impair normal activities. Insight into how SCIP could be improved for children included the use of topical analgesia, distractions via television or personal devices, a drawn-out infusion time with reduced delivery speed, and alternative infusion sites. Trust in the trial team was high. Qualitative research is an important adjunct for early-phase clinical trials, particularly when adherence to the planned intervention is a key driver of success. These results will inform later-phase SCIP trials in people living with RHD and other indications.
The fall and rise of Group A Streptococcus diseases
Publisher: Cambridge University Press (CUP)
Date: 15-08-2019
DOI: 10.1017/S0950268818002285
Abstract: Streptococcus pyogenes (or Group A Streptococcus , GAS) is a Gram-positive human pathogen responsible for a erse array of superficial, invasive and immune-related diseases. GAS infections have historically been diseases of poverty and overcrowding, and remain a significant problem in the developing world and in disadvantaged populations within developed countries. With improved living conditions and access to antibiotics, the rates of GAS diseases in developed societies have gradually declined during the 20th century. However, genetic changes in circulating GAS strains and/or changes in host susceptibility to infection can lead to dramatic increases in the rates of specific diseases. No situations exemplify this more than the global upsurge of invasive GAS disease that originated in the 1980s and the regional increases in scarlet fever in north-east Asia and the UK. In each case, increased disease rates have been associated with the emergence of new GAS strains with increased disease-causing capability. Global surveillance for new GAS strains with increased virulence is important and determining why certain populations suddenly become susceptible to circulating strains remains a research priority. Here, we overview the changing epidemiology of GAS infections and the genetic alterations that accompany the emergence of GAS strains with increased capacity to cause disease.
Toward the Global Control of Human Scabies: Introducing the International Alliance for the Control of Scabies
Publisher: Public Library of Science (PLoS)
Date: 08-08-2013
Management of invasive group A streptococcal infections
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.JINF.2014.08.005
Abstract: Invasive group A streptococcal (GAS) disease in children includes deep soft tissue infection, bacteraemia, bacteraemic pneumonia, meningitis and osteomyelitis. The expression of toxins and super antigens by GAS can complicate infection by triggering an overwhelming systemic inflammatory response, referred to as streptococcal toxic shock syndrome (STSS). The onset and progression of GAS disease can be rapid, and the associated mortality high. Prompt antibiotics therapy and early surgical debridement of infected tissue are essential. Adjunctive therapy with intravenous immunoglobulin and hyperbaric therapy may improve outcomes in severe disease. Nosocomial outbreaks and secondary cases in close personal contacts are not uncommon infection control measures and consideration of prophylactic antibiotics to those at high risk are important aspects of disease control. To reduce a substantial part of the global burden of GAS disease, an affordable GAS vaccine with efficacy against a broad number of strains is needed.
Strain Prevalence, Rather than Innate Virulence Potential, Is the Major Factor Responsible for an Increase in Serious Group A Streptococcus Infections
Publisher: Oxford University Press (OUP)
Date: 06-2007
DOI: 10.1086/513875
Abstract: It is postulated that the surge in incidence and severity of group A streptococcus (GAS) infections since the 1980s is due to the emergence of strains of GAS with increased virulence. We used active, population-based surveillance of invasive GAS disease, serologically confirmed pharyngitis, and carriage to determine whether particular strains were associated with invasive disease. Two hundred twenty GAS isolates were collected--78 invasive, 34 pharyngitis, and 108 carriage. Isolates were characterized using emm typing, random lification of polymorphic DNA (RAPD) profiling, and superantigen genotyping. emm1, emm12, and emm28 predominated in invasive disease and accounted for 30.8%, 12.8%, and 12.8% of all isolates, respectively. emm1, emm75, emm28, and emm4 were the most frequently isolated emm types in pharyngitis, and emm12 and emm1 predominated in carriage. emm12 was significantly associated with carriage rather than disease. There were no other significant associations between emm type and disease or carriage. There were no associations between any RAPD profile or superantigen genotype and invasive disease, pharyngitis, or carriage. One RAPD profile accounted for most cases of necrotizing fasciitis, which suggests that this strain might have particular features promoting connective-tissue infection. These data suggest that the emergence of GAS strains with increased virulence is not the main factor responsible for the surge in GAS-related infections. The prevalence of particular emm types, RAPD profiles, or superantigen genes in invasive disease may simply indicate widespread transmission of these strains in the population, rather than a particular ability to cause disease.
Current issues regarding the use of pneumococcal conjugate and polysaccharide vaccines in Australian children
Publisher: Wiley
Date: 04-2005
DOI: 10.1111/J.1440-1754.2005.00588.X
Abstract: To present the results of child pneumococcal vaccination studies in the setting of current Australian disease epidemiology and immunization policy, and issues that clinicians should consider in discussions with families. This paper includes a narrative review of randomized, controlled, double blind studies and systematic reviews which evaluated the efficacy of child pneumococcal vaccination. 7PCV is expected to prevent > 80% of childhood invasive pneumococcal disease (IPD, includes meningitis, septicaemia/bacteraemia) and the associated mortality. 7PCV may prevent 6% of all pneumonia, 18% of radiographically-defined pneumonia, 6% of all otitis media (OM) and 20%-40% of tympanostomy tube procedures. It may also reduce IPD due to antibiotic-resistant pneumococci, and prevent IPD in unvaccinated in iduals. The impact of replacement disease caused by non-vaccine serotypes is not yet known. Pneumococcal polysaccharide vaccines given to 2-year-old children may prevent approximately 19% of all and 26% of recurrent OM. The Australian Standard Vaccination Schedule recommends universal infant immunization with seven-valent pneumococcal conjugate vaccine (7PCV). Universal infant 7PCV will prevent pneumococcal diseases and deaths. The potential for its impact to be reduced in the long-term by serotype replacement must be closely monitored. Information concerning disease epidemiology, vaccine efficacy and safety, disease risk perception and national costs may prove useful in discussions with families.
Impact of heart disease on maternal, fetal and neonatal outcomes in a low-resource setting
Publisher: BMJ
Date: 10-11-2018
DOI: 10.1136/HEARTJNL-2018-313810
Abstract: The burden of pre-existing cardiovascular disease and the contribution to adverse pregnancy outcomes are not robustly quantified, particularly in low-income countries. We aimed to determine both the prevalence of maternal heart disease through active case finding and its attributable risk to adverse pregnancy outcomes. We conducted a 24-month prospective longitudinal investigation in three Ugandan health centres, using echocardiography for active case finding during antenatal care. Women with and without heart disease were followed to 6 weeks post partum to determine pregnancy outcomes. Prevalence of heart disease was calculated. Per cent attributable risk estimates were generated for maternal, fetal and neonatal mortality. Screening echocardiography was performed in 3506 women. The prevalence of heart disease was 17 per 1000 women (95% CI 13 to 21) 15 per 1000 was rheumatic heart disease. Only 3.4% of women (2/58) had prior diagnosis. Cardiovascular complications occurred in 51% of women with heart disease, most commonly heart failure. Per cent attributable risk of heart disease on maternal mortality was 88.6% in the exposed population and 10.8% in the overall population. Population attributable risk of heart disease on fetal death was 1.1% and 6.0% for neonatal mortality Occult maternal heart disease may be responsible for a substantial proportion of adverse pregnancy outcomes in low-resource settings. Rheumatic heart disease is, by far, the most common condition, urging global prioritisation of this neglected cardiovascular disease.
Development of Group A streptococcal vaccines: an unmet global health need
Publisher: Informa UK Limited
Date: 03-12-2015
DOI: 10.1586/14760584.2016.1116946
Abstract: Group A Streptococcus (GAS) infections are a significant global cause of morbidity and mortality. GAS diseases disproportionally affect those living in conditions characterized by poverty and social injustice, in both developing countries and in marginalized populations of industrialized nations. In Australia and New Zealand, GAS-associated Acute Rheumatic Fever (ARF) is a major cause of health inequality disproportionally affecting indigenous children. Recognition of these inequalities by the governments of Australia and New Zealand has resulted in the formation of a Trans-Tasman Coalition to Advance New Vaccines for group A Streptococcus (CANVAS). This review provides an update on the current status of GAS vaccine development, and describes global efforts by CANVAS and others to accelerate the development of GAS vaccines.
Duration of antibiotics in children with osteomyelitis and septic arthritis
Publisher: Wiley
Date: 08-2002
DOI: 10.1046/J.1440-1754.2002.00007.X
Abstract: To evaluate the outcomes of children with acute osteomyelitis and septic arthritis at a hospital where short-duration antibiotic treatment (< or = 3.5 weeks) was considered routine. We carried out a retrospective chart review, with telephone interviews to follow up and determine long-term outcomes. Patients were selected to be at low risk for complications (illness < or = 14 days, no underlying disease, uncomplicated presentation). Thirty-two children with osteomyelitis (OM), 34 with septic arthritis (SA) and five with OM and SA (OMSA) were included. Blood cultures were positive (mainly Staphylococcus aureus) in 15% of patients who had not had prior antibiotic treatment, and microbiological confirmation (positive blood culture, Gram stain or culture of surgical specimen) was obtained in 36%. The median duration of antibiotic treatment was 5.4, 4.4 and 5.0 weeks for OM, SA and OMSA, respectively. Only 22% of patients received antibiotics for 3.5 weeks or less. Overall, the recurrence rate was 1.4%. At follow-up, only two patients had mild occasional pain at the site of the original infection all patients had normal function. Contrary to expectations and local protocols, most patients were treated with conventional long-duration therapy. Patients treated for short courses had good outcomes. The low rate of complications may make randomized controlled equivalence trials unfeasible. Increasing evidence of the efficacy and safety of short-duration treatment (3-3.5 weeks) for acute, uncomplicated OM or SA in children suggests that this could be accepted as the standard treatment. However, this should be evaluated prospectively using a register, with at least 12 months' of follow-up.
Trimethoprim-sulfamethoxazole compared with benzathine penicillin for treatment of impetigo in Aboriginal children: A pilot randomised controlled trial
Publisher: Wiley
Date: 17-03-2010
DOI: 10.1111/J.1440-1754.2010.01697.X
Abstract: We conducted a pilot randomized controlled trial comparing trimethoprim-sulfamethoxazole to benzathine penicillin for treatment of impetigo in Aboriginal children. Treatment was successful in 7 of 7 children treated with trimethoprim-sulfamethoxazole and 5 of 6 treated with benzathine penicillin. Trimethoprim-sulfamethoxazole achieved microbiological clearance and healing of sores from which beta-hemolytic streptococci and community-associated methicillin-resistant Staphylococcus aureus were initially cultured.
The clinical and molecular epidemiology of Staphylococcus aureus infections in Fiji
Publisher: Springer Science and Business Media LLC
Date: 24-03-2014
Contemporary Incidence and Prevalence of Rheumatic Fever and Rheumatic Heart Disease in Australia Using Linked Data: The Case for Policy Change
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-10-2020
Abstract: In 2018, the World Health Organization prioritized control of acute rheumatic fever (ARF) and rheumatic heart disease (RHD), including disease surveillance. We developed strategies for estimating contemporary ARF/RHD incidence and prevalence in Australia (2015–2017) by age group, sex, and region for Indigenous and non‐Indigenous Australians based on innovative, direct methods. This population‐based study used linked administrative data from 5 Australian jurisdictions. A cohort of ARF (age years) and RHD cases ( years) were sourced from jurisdictional ARF/RHD registers, surgical registries, and inpatient data. We developed robust methods for epidemiologic case ascertainment for ARF/RHD. We calculated age‐specific and age‐standardized incidence and prevalence. Age‐standardized rate and prevalence ratios compared disease burden between demographic subgroups. Of 1425 ARF episodes, 72.1% were first‐ever, 88.8% in Indigenous people and 78.6% were aged years. The age‐standardized ARF first‐ever rates were 71.9 and 0.60/100 000 for Indigenous and non‐Indigenous populations, respectively (age‐standardized rate ratio=124.1 95% CI, 105.2–146.3). The 2017 Global Burden of Disease RHD prevalent counts for Australia ( years) underestimate the burden (1518 versus 6156 Australia‐wide extrapolated from our study). The Indigenous age‐standardized RHD prevalence (666.3/100 000) was 61.4 times higher (95% CI, 59.3–63.5) than non‐Indigenous (10.9/100 000). Female RHD prevalence was double that in males. Regions in northern Australia had the highest rates. This study provides the most accurate estimates to date of Australian ARF and RHD rates. The high Indigenous burden necessitates urgent government action. Findings suggest RHD may be underestimated in many high‐resource settings. The linked data methods outlined here have potential for global applicability.
Reply to “Susceptibility of Streptococcus pyogenes to Trimethoprim-Sulfamethoxazole”
Publisher: American Society for Microbiology
Date: 04-2013
DOI: 10.1128/JCM.03373-12
Standardization of Epidemiological Surveillance of Group A Streptococcal Pharyngitis
Publisher: Oxford University Press (OUP)
Date: 15-09-2022
DOI: 10.1093/OFID/OFAC251
Abstract: Pharyngitis, more commonly known as sore throat, is caused by viral and/or bacterial infections. Group A Streptococcus (Strep A) is the most common bacterial cause of pharyngitis. Strep A pharyngitis is an acute, self-limiting disease but if undertreated can lead to suppurative complications, nonsuppurative poststreptococcal immune-mediated diseases, and toxigenic presentations. We present a standardized surveillance protocol, including case definitions for pharyngitis and Strep A pharyngitis, as well as case classifications that can be used to differentiate between suspected, probable, and confirmed cases. We discuss the current tests used to detect Strep A among persons with pharyngitis, including throat culture and point-of-care tests. The type of surveillance methodology depends on the resources available and the objectives of surveillance. Active surveillance and laboratory confirmation is the preferred method for case detection. Participant eligibility, the surveillance population and additional considerations for surveillance of pharyngitis are addressed, including baseline s ling, community engagement, frequency of screening and season. Finally, we discuss the core elements of case report forms for pharyngitis and provide guidance for the recording of severity and pain associated with the course of an episode.
Penicillin Reactions in Patients With Severe Rheumatic Heart Disease: A Presidential Advisory From the American Heart Association
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2022
Abstract: Secondary antibiotic prophylaxis with regular intramuscular benzathine penicillin G (BPG) is the cornerstone of rheumatic heart disease management. However, there is a growing body of evidence that patients with rheumatic heart disease who have severe valvular heart disease with or without reduced ventricular function may be dying from cardiovascular compromise following BPG injections. This advisory responds to these concerns and is intended to: (1) raise awareness, (2) provide risk stratification, and (3) provide strategies for risk reduction. Based on available evidence and expert opinion, we have ided patients into low‐ and elevated‐risk groups, based on symptoms and the severity of underlying heart disease. Patients with elevated risk include those with severe mitral stenosis, aortic stenosis, and aortic insuffiency those with decreased left ventricular systolic dysfunction and those with New York Heart Association class III and IV symptoms. For these patients, we believe the risk of adverse reaction to BPG, specifically cardiovascular compromise, may outweigh its theoretical benefit. For patients with elevated risk, we newly advise that oral prophylaxis should be strongly considered. In addition, we advocate for a multifaceted strategy for vasovagal risk reduction in all patients with rheumatic heart disease receiving BPG. As current guidelines recommend, all low‐risk patients without a history of penicillin allergy or anaphylaxis should continue to be prescribed BPG for secondary antibiotic prophylaxis. We publish this advisory in the hopes of saving lives and avoiding events that can have devastating effects on patient and clinician confidence in BPG.
Standardization of Epidemiological Surveillance of Rheumatic Heart Disease
Publisher: Oxford University Press (OUP)
Date: 15-09-2022
DOI: 10.1093/OFID/OFAC250
Abstract: Rheumatic heart disease (RHD) is a long-term sequela of acute rheumatic fever (ARF), which classically begins after an untreated or undertreated infection caused by Streptococcus pyogenes (Strep A). RHD develops after the heart valves are permanently damaged due to ARF. RHD remains a leading cause of morbidity and mortality in young adults in resource-limited and low- and middle-income countries. This article presents case definitions for latent, suspected, and clinical RHD for persons with and without a history of ARF, and details case classifications, including differentiating between definite or borderline according to the 2012 World Heart Federation echocardiographic diagnostic criteria. This article also covers considerations specific to RHD surveillance methodology, including discussions on echocardiographic screening, where and how to conduct active or passive surveillance (eg, early childhood centers/schools, households, primary healthcare), participant eligibility, and the surveillance population. Additional considerations for RHD surveillance, including implications for secondary prophylaxis and follow-up, RHD registers, community engagement, and the negative impact of surveillance, are addressed. Finally, the core elements of case report forms for RHD, monitoring and audit requirements, quality control and assurance, and the ethics of conducting surveillance are discussed.
Global, Regional, and National Burden of Rheumatic Heart Disease, 1990–2015
Publisher: Massachusetts Medical Society
Date: 24-08-2017
Impetigo and scabies - Disease burden and modern treatment strategies.
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.JINF.2016.04.024
Abstract: Impetigo and scabies both present different challenges in resource-limited compared with industrialised settings. Severe complications of these skin infections are common in resource-limited settings, where the burden of disease is highest. The microbiology, risk factors for disease, diagnostic approaches and availability and suitability of therapies also vary according to setting. Taking this into account we aim to summarise recent data on the epidemiology of impetigo and scabies and describe the current evidence around approaches to in idual and community based treatment.
Culturally supported health promotion to See, Treat, Prevent (SToP) skin infections in Aboriginal children living in the Kimberley region of Western Australia
Publisher: Elsevier BV
Date: 06-2023
A pilot study to develop assessment tools for Group A Streptococcus surveillance studies
Publisher: PeerJ
Date: 14-03-2023
DOI: 10.7717/PEERJ.14945
Abstract: Group A Streptococcus (GAS) causes pharyngitis (sore throat) and impetigo (skin sores) GAS pharyngitis triggers rheumatic fever (RF) with epidemiological evidence supporting that GAS impetigo may also trigger RF in Australian Aboriginal children. Understanding the concurrent burden of these superficial GAS infections is critical to RF prevention. This pilot study aimed to trial tools for concurrent surveillance of sore throats and skins sore for contemporary studies of RF pathogenesis including development of a sore throat checklist for Aboriginal families and pharynx photography. Yarning circle conversations and semi-structured interviews were performed with Aboriginal caregivers and used to develop the language and composition of a sore throat checklist. The sore throat story checklist was combined with established methods of GAS pharyngitis and impetigo surveillance (examination, bacteriological culture, rapid antigen detection and serological tests) and new technologies (photography) and used for a pilot cross-sectional surveillance study of Aboriginal children attending their health clinic for a routine appointment. Feasibility, acceptability, and study costs were compiled. Ten Aboriginal caregivers participated in the sore-throat yarning circles a checklist was derived from predominant symptoms and their common descriptors. Over two days, 21 Aboriginal children were approached for the pilot surveillance study, of whom 17 were recruited median age was 9 years [IQR 5.5–13.5], 65% were female. One child declined throat swabbing and three declined finger pricks all other surveillance elements were completed by each child indicating high acceptability of surveillance assessments. Mean time for screening assessment was 19 minutes per child. Transport of clinical specimens enabled gold standard microbiological and serological testing for GAS. Retrospective examination of sore throat photography concorded with assessments performed on the day. Yarning circle conversations were effective in deriving culturally appropriate sore throat questionnaires for GAS pharyngitis surveillance. New and established tools were feasible, practical and acceptable to participants and enable surveillance to determine the burden of superficial GAS infections in communities at high risk of RF. Surveillance of GAS pharyngitis and impetgio in remote Australia informs primary RF prevention with potential global translation.
454. Perinatal Risk Factors Associated with Skin Infection Hospitalisation in Western Australian Aboriginal and Non-Aboriginal Children
Publisher: Oxford University Press (OUP)
Date: 10-2019
Abstract: Hospitalisation with skin infection in Western Australian (WA) Aboriginal children is common, with the highest rates in infants and children from remote WA. We aimed to quantify infant, maternal, and sociodemographic risk factors for skin infection hospitalization in WA children, focusing on Aboriginal children aged years. We conducted a retrospective population-based cohort study with linked perinatal and hospitalization data on WA-born children (1996–2012), of whom 31,348 (6.7%) were Aboriginal. We used Cox regression to calculate adjusted hazard ratios and associated population attributable fractions (PAFs) for perinatal factors attributed to the first hospitalization with skin infection. To identify specific risk factors for early-onset infection, we further restricted the cohort to infants aged year. Overall, 5,439 (17.4%) Aboriginal and 6,750 (1.5%) non-Aboriginal children were hospitalized at least once with a skin infection. Aboriginal infants aged year had the highest skin infection hospitalization rate (63.2/1,000 child-years). The strongest risk factors in Aboriginal children aged years were socio-economic disadvantage, very remote location at birth and multi-parity (≥3 previous pregnancies) accounting for 24%, 23% and 15% of skin infection hospitalizations, respectively. Other risk factors included maternal age years, maternal smoking during pregnancy and low birthweight. We have quantified the relative influence of perinatal risk factors associated with skin infection hospitalizations in WA children, providing measures indicating which factors have the potential to reduce the most hospitalizations. Our evidence supports existing calls for substantial government investment in addressing underlying social and environmental barriers to healthy skin in WA Aboriginal children but also identifies potential areas to target health promotion messaging at in iduals/families on maternal smoking during pregnancy and skin hygiene for families. All authors: No reported disclosures.
Calculation of the age of the first infection for skin sores and scabies in five remote communities in northern Australia
Publisher: Cambridge University Press (CUP)
Date: 08-05-2018
DOI: 10.1017/S0950268818001061
Abstract: Prevalence of skin sores and scabies in remote Australian Aboriginal communities remains unacceptably high, with Group A Streptococcus (GAS) the dominant pathogen. We aim to better understand the drivers of GAS transmission using mathematical models. To estimate the force of infection, we quantified the age of first skin sores and scabies infection by pooling historical data from three studies conducted across five remote Aboriginal communities for children born between 2001 and 2005. We estimated the age of the first infection using the Kaplan–Meier estimator parametric exponential mixture model and Cox proportional hazards. For skin sores, the mean age of the first infection was approximately 10 months and the median was 7 months, with some heterogeneity in median observed by the community. For scabies, the mean age of the first infection was approximately 9 months and the median was 8 months, with significant heterogeneity by the community and an enhanced risk for children born between October and December. The young age of the first infection with skin sores and scabies reflects the high disease burden in these communities.
Standardization of Epidemiological Surveillance of Group A Streptococcal Impetigo
Publisher: Oxford University Press (OUP)
Date: 15-09-2022
DOI: 10.1093/OFID/OFAC249
Abstract: Impetigo is a highly contagious bacterial infection of the superficial layer of skin. Impetigo is caused by group A Streptococcus (Strep A) and Staphylococcus aureus, alone or in combination, with the former predominating in many tropical climates. Strep A impetigo occurs mainly in early childhood, and the burden varies worldwide. It is an acute, self-limited disease, but many children experience frequent recurrences that make it a chronic illness in some endemic settings. We present a standardized surveillance protocol including case definitions for impetigo including both active (purulent, crusted) and resolving (flat, dry) phases and discuss the current tests used to detect Strep A among persons with impetigo. Case classifications that can be applied are detailed, including differentiating between incident (new) and prevalent (existing) cases of Strep A impetigo. The type of surveillance methodology depends on the burden of impetigo in the community. Active surveillance and laboratory confirmation is the preferred method for case detection, particularly in endemic settings. Participant eligibility, surveillance population and additional considerations for surveillance of impetigo, including examination of lesions, use of photographs to document lesions, and staff training requirements (including cultural awareness), are addressed. Finally, the core elements of case report forms for impetigo are presented and guidance for recording the course and severity of impetigo provided.
Letter by Carapetis Regarding Article, “Is Primary Prevention of Rheumatic Fever the Missing Link in the Control of Rheumatic Heart Disease in Africa?”
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 20-04-2010
A qualitative study of how caseload midwifery is constituted and experienced by Danish midwives
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.MIDW.2016.03.002
Abstract: the aim of this study is to advance knowledge about the working and living conditions of midwives in caseload midwifery and how this model of care is embedded in a standard maternity unit. This led to two research questions: 1) What constitutes caseload midwifery from the perspectives of the midwives? 2) How do midwives experience working in caseload midwifery? phenomenology of practice was the analytical approach to this qualitative study of caseload midwifery in Northern Denmark. The methodology was inspired by ethnography, and applied methods were field observations followed by interviews. thirteen midwives working in caseloads were observed during one or two days in the antenatal clinic and were interviewed at a later occasion. being recognised and the feeling of doing high quality care generate high job satisfaction. The obligation and pressure to perform well and the disadvantages to the midwives׳ personal lives are counterbalanced by the feeling of doing a meaningful and important job. Working in caseload midwifery creates a feeling of working in a self-governing model within the public hospital, without losing the technological benefits of a modern birth unit. Midwives in caseload midwifery worked on welcoming and including all pregnant women allocated to their care even women/families where relationships with the midwives were challenging were recognised and respected. caseload midwifery is a work-form with an embedded and inevitable commitment and obligation that brings forward the midwife׳s desire to do her utmost and in return receive appreciation, social recognition and a meaningful job with great job satisfaction. There is a balance between the advantages of a meaningful job and the disadvantages for the personal life of the midwife, but benefits were found to outweigh disadvantages. In expanding caseload midwifery, it is necessary to understand that the midwives׳ personal lives need to be prepared for this work-form. The number of women per full time midwife has to be surveilled as job-satisfaction is dependent on the midwives׳ ability of fulfilling expectations of being present at women׳s births.
High prevalence of asymptomatic vitamin D and iron deficiency in East African immigrant children and adolescents living in a temperate climate
Publisher: BMJ
Date: 12-2007
A qualitative study of how caseload midwifery is experienced by couples in Denmark
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.WOMBI.2016.09.003
Abstract: Caseload midwifery is expanding in Denmark. There is a need for elaborating in-depth, how caseload midwifery influences the partner and the woman during childbirth and how this model of care influences the early phases of labour. To follow, explore and elaborate women's and their partner's experiences of caseload midwifery. Phenomenology of practice was the analytical approach. The methodology was inspired by ethnography, and applied methods were field observations followed by interviews. Ten couples participated in the study. Most of the couples were observed from the onset of labour until childbirth. Afterwards, the couples were interviewed. The transition from home to hospital in early labour was experienced as positive. During birth, the partner felt involved and included by the midwife. The midwives remembered and recognized the couple's stories and wishes for childbirth and therefore they felt regarded as "more than numbers". Irrespective of different kinds of vulnerability or challenges among the participants, the relationship was named a professional friendship, characterised by equality and inclusiveness. One drawback of caseload midwifery was that the woman was at risk of being disappointed if her expectations of having a known midwife at birth were not fulfilled. From the perspective of women and their partners, attending caseload midwifery meant being recognised and cared for as an in idual. The partner felt included and acknowledged and experienced working in a team with the midwife. Caseload midwifery was able to solve problems concerning labour onset or gaining access to the labour ward.
Prospective Surveillance of Streptococcal Sore Throat in a Tropical Country
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2009
A Review of Cardiac Surgical Procedures and Their Outcomes for Paediatric Rheumatic Heart Disease in Western Australia
Publisher: Elsevier BV
Date: 10-2023
The NICE-GUT trial protocol: a randomised, placebo controlled trial of oral nitazoxanide for the empiric treatment of acute gastroenteritis among Australian Aboriginal children
Publisher: BMJ
Date: 02-2018
DOI: 10.1136/BMJOPEN-2017-019632
Abstract: Diarrhoeal disease is the second leading cause of death in children under 5 years globally, killing 525 000 annually. Australian Aboriginal and Torres Strait Islander (hereafter Aboriginal) children suffer a high burden of disease. Randomised trials in other populations suggest nitazoxanide accelerates recovery for children with Giardia , amoebiasis, Cryptosporidium, Rotavirus and Norovirus gastroenteritis, as well as in cases where no enteropathogens are found. This double blind, 1:1 randomised, placebo controlled trial is investigating the impact of oral nitazoxanide on acute gastroenteritis in hospitalised Australian Aboriginal children aged 3 months to years. Dosing is based on age-based dosing. The primary endpoint is the time to resolution of ‘significant illness’ defined as the time from randomisation to the time of clinical assessment as medically ready for discharge, or to the time of actual discharge from hospital, whichever occurs first. Secondary endpoints include duration of hospitalisation, symptom severity during the period of significant illness and following treatment, duration of rehydration and drug safety. Patients will be followed for medically significant events for 60 days. Analysis is based on Bayesian inference. Subgroup analysis will occur by pathogen type (bacteria, virus or parasite), rotavirus vaccination status, age and illness severity. Ethics approval has been granted by the Central Australian Human Research Ethics Committee (HREC-14–221) and the Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research (HREC2014-2172). Study investigators will ensure that the trial is conducted in accordance with the principles of the Declaration of Helsinki. In idual participant consent will be obtained. Results will be disseminated via peer-reviewed publication. ACTRN12614000381684.
Long-Term Outcomes From Acute Rheumatic Fever and Rheumatic Heart Disease
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-07-2016
DOI: 10.1161/CIRCULATIONAHA.115.020966
Abstract: We investigated adverse outcomes for people with acute rheumatic fever (ARF) and rheumatic heart disease (RHD) and the effect of comorbidities and demographic factors on these outcomes. Using linked data (RHD register, hospital, and mortality data) for residents of the Northern Territory of Australia, we calculated ARF recurrence rates, rates of progression from ARF to RHD to severe RHD, RHD complication rates (heart failure, endocarditis, stroke, and atrial fibrillation), and mortality rates for 572 in iduals diagnosed with ARF and 1248 with RHD in 1997 to 2013 (94.9% Indigenous). ARF recurrence was highest (incidence, 3.7 per 100 person-years) in the first year after the initial ARF episode, but low-level risk persisted for years. Progression to RHD was also highest (incidence, 35.9) in the first year, almost 10 times higher than ARF recurrence. The median age at RHD diagnosis in Indigenous people was young, especially among males (17 years). The development of complications was highest in the first year after RHD diagnosis: heart failure incidence rate per 100 person-years, 9.09 atrial fibrillation, 4.70 endocarditis, 1.00 and stroke, 0.58. Mortality was higher among Indigenous than non-Indigenous RHD patients (hazard ratio, 6.55 95% confidence interval, 2.45–17.51), of which 28% was explained by comorbid renal failure and hazardous alcohol use. RHD complications and mortality rates were higher for urban than for remote residents. This study provides important new prognostic information for ARF/RHD. The residual Indigenous survival disparity in RHD patients, which persisted after accounting for comorbidities, suggests that other factors contribute to mortality, warranting further research.
Improving Delivery of Secondary Prophylaxis for Rheumatic Heart Disease in a High‐Burden Setting: Outcome of a Stepped‐Wedge, Community, Randomized Trial
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-07-2018
Abstract: Health system strengthening is needed to improve delivery of secondary prophylaxis against rheumatic heart disease. We undertook a stepped‐wedge, randomized trial in northern Australia. Five pairs of Indigenous community clinics entered the study at 3‐month steps. Study phases comprised a 12 month baseline phase, 3 month transition phase, 12 month intensive phase and a 3‐ to 12‐month maintenance phase. Clinics received a multicomponent intervention supporting activities to improve penicillin delivery, aligned with the chronic care model, with continuous quality‐improvement feedback on adherence. The primary outcome was the proportion receiving ≥80% of scheduled penicillin injections. Secondary outcomes included “days at risk” of acute rheumatic fever recurrence related to late penicillin and acute rheumatic fever recurrence rates. Overall, 304 patients requiring prophylaxis were eligible. The proportion receiving ≥80% of scheduled injections during baseline was 141 of 304 (46%)—higher than anticipated. No effect attributable to the study was evident: in the intensive phase, 126 of 304 (41%) received ≥80% of scheduled injections (odds ratio compared with baseline: 0.78 95% confidence interval , 0.54–1.11). There was modest improvement in the maintenance phase among high‐adhering patients (43% received ≥90% of injections versus 30% [baseline] and 28% [intensive], P .001). Also, the proportion of days at risk in the whole cohort decreased in the maintenance phase (0.28 versus 0.32 [baseline] and 0.34 [intensive], P =0.001). A cute rheumatic fever recurrence rates did not differ between study sites during the intensive phase and the whole jurisdiction (3.0 versus 3.5 recurrences per 100 patient‐years, P =0.65). This strategy did not improve adherence to rheumatic heart disease secondary prophylaxis within the study time frame. Longer term primary care strengthening strategies are needed. URL : www.anzctr.org.au . Unique identifier: ACTRN 12613000223730.
The multiscale hierarchical structure of Heloderma suspectum osteoderms and their mechanical properties
Publisher: Elsevier BV
Date: 04-2020
Estimation of the force of infection and infectious period of skin sores in remote Australian communities using interval-censored data
Publisher: Cold Spring Harbor Laboratory
Date: 21-06-2019
DOI: 10.1101/674663
Abstract: Prevalence of impetigo (skin sores) remains high in remote Australian Aboriginal communities, Fiji, and other areas of socio-economic disadvantage. Skin sore infections, driven primarily in these settings by Group A Streptococcus (GAS) contribute substantially to the disease burden in these areas. Despite this, estimates for the force of infection, infectious period and basic reproductive ratio — all necessary for the construction of dynamic transmission models — have not been obtained. By utilising three datasets each containing longitudinal infection information on in iduals, we estimate each of these epidemiologically important parameters. With an eye to future study design, we also quantify the optimal s ling intervals for obtaining information about these parameters. We verify the estimation method through a simulation estimation study, and test each dataset to ensure suitability to the estimation method. We find that the force of infection differs by population prevalence, and the infectious period is estimated to be between 12 and 20 days. We also find that optimal s ling interval depends on setting, with an optimal s ling interval between 9 and 11 days in a high prevalence setting, and 21 and 27 days for a lower prevalence setting. These estimates unlock future model-based investigations on the transmission dynamics of GAS and skin sores.
Parasitic diseases of remote Indigenous communities in Australia
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1016/J.IJPARA.2010.04.002
Abstract: Indigenous Australians suffer significant disadvantage in health outcomes and have a life expectancy well below that of non-Indigenous Australians. Mortality rates of Indigenous Australians are higher than that of Indigenous populations in developed countries elsewhere in the world. A number of parasitic diseases which are uncommon in the rest of the Australian population contribute to the high burden of disease in many remote Indigenous communities. High rates of infection with enteric parasites such as Strongyloides stercoralis, hookworm and Trichuris have been recorded and infection of the skin with the ecto-parasitic mite Sarcoptes scabiei is also a substantial problem. Secondary infection of scabies lesions, including with Staphylococcus aureus and group A Streptococcus, can produce serious sequelae such as rheumatic fever and post-streptococcal glomerulonephritis. Transmission of many parasites in many remote communities is facilitated by overcrowded living conditions and infrastructure problems which result in poor sanitation and hygiene. Improvements in environmental health conditions must accompany medical initiatives to achieve sustainable improvement in the health of Indigenous Australians.
Towards Improving Point-of-Care Diagnosis of Non-malaria Febrile Illness: A Metabolomics Approach
Publisher: Public Library of Science (PLoS)
Date: 04-03-2016
Pilot study of nurse-led rheumatic heart disease echocardiography screening in Fiji – a novel approach in a resource-poor setting
Publisher: Cambridge University Press (CUP)
Date: 08-10-2012
DOI: 10.1017/S1047951112001321
Abstract: We designed a pilot study of a training module for nurses to perform rheumatic heart disease echocardiography screening in a resource-poor setting. The aim was to determine whether nurses given brief, focused, basic training in echocardiography could follow an algorithm to potentially identify cases of rheumatic heart disease requiring clinical referral, by undertaking basic two-dimensional and colour Doppler scans. Training consisted of a week-long workshop, followed by 2 weeks of supervised field experience. The nurses’ skills were tested on a blinded cohort of 50 children, and the results were compared for sensitivity and specificity against echocardiography undertaken by an expert, using standardised echocardiography definitions for definite and probable rheumatic heart disease. Analysis of the two nurses’ results revealed that when a mitral regurgitant jet length of 1.5 cm was used as the trigger for rheumatic heart disease identification, they had a sensitivity of 100% and 83%, respectively, and a specificity of 67.4% and 79%, respectively. This pilot supports the principle that nurses, given brief focused training and supervised field experience, can follow an algorithm to undertake rheumatic heart disease echocardiography in a developing country setting to facilitate clinical referral with reasonable accuracy. These results warrant further research, with a view to developing a module to guide rheumatic heart disease echocardiographic screening by nurses within the existing public health infrastructure in high-prevalence, resource-poor regions.
Contrasting molecular epidemiology of group A streptococci causing tropical and nontropical infections of the skin and throat
Publisher: Oxford University Press (OUP)
Date: 10-2000
DOI: 10.1086/315842
Abstract: Disease caused by group A streptococci (GAS) in tropical regions often takes the form of impetigo, whereas pharyngitis tends to predominate in temperate zones. GAS derived from asymptomatic throat infections and pyoderma lesions of rural Aboriginal Australians were evaluated for phylogenetic distant emm genes, which represent ecological markers for tissue site preference. On the basis of the percentage of total isolates from a given tissue, emm pattern A-C organisms exhibited a stronger predilection for the throat, whereas pattern D organisms preferred the skin. Only 16% of isolates collected by active surveillance displayed pattern A-C, which reflects the low incidence of oropharyngeal infection. Importantly, most (70%) pattern A-C organisms were isolated from skin sores, despite their innate tendency to infect the throat. Combined with findings from nontropical populations, analysis of the data supports the hypothesis that GAS tissue preferences are genetically predetermined and that host risk factors for infection strongly influence the differential reproduction of in idual clones.
An economic case for a vaccine to prevent group A streptococcus skin infections
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.VACCINE.2018.10.001
Abstract: Group A streptococcus (GAS) causes an exceptionally erse range of diseases, raising questions about the optimal product characteristics of a commercially viable vaccine. The objectives of this study were to (1) estimate the current health and economic burdens caused by 24 diseases attributable to GAS each year in Australia and (2) use these estimates to explore the value of a GAS vaccine for different clinical indications, age schedules, and population groups. For objective 1, we estimated the population heath and economic burdens by synthesising data from administrative databases, nationally representative surveys, literature reviews, public reimbursement schedules, and expert opinion. For objective 2, we modelled the prospective lifetime burden of GAS for all infants from birth, for children from 5 years of age, and for adults from 65 years of age. A vaccine was assumed to reduce each GAS disease by 70% for a period of 10 years, and the difference in outcomes between vaccinated and non-vaccinated cohorts were used to calculate the cost-effective value of vaccination. The annual health and economic burdens of GAS diseases totalled 23,528 disability-adjusted life years and AU$185.1 million in healthcare costs respectively approximately half of each measure was due to cellulitis, followed by other skin infections and throat infections. Reducing the incidence of throat infections, skin infections, and cellulitis in non-Indigenous cohorts resulted in 30%, 33%, and 28% of the total vaccine value for an infant schedule (cost-effective vaccine price AU$260 per course) 47%, 26%, and 22% of the value for a child schedule (AU$289) and 2%, 15% and 74% for an adult schedule (AU$489). A vaccine that prevents GAS cellulitis and other skin infections, in addition to throat infections, would maximise its value and commercial viability, with a cost-effective price in line with other recently-licensed and funded vaccines in Australia.
Scabies and risk of skin sores in remote Australian Aboriginal communities: A self-controlled case series study
Publisher: Public Library of Science (PLoS)
Date: 25-07-2018
Trial of a developmental screening tool in remote Australian Aboriginal communities: A cautionary tale
Publisher: Wiley
Date: 26-10-2011
DOI: 10.1111/J.1440-1754.2010.01883.X
Abstract: Aim: To trial the Brigance developmental screening tool as an instrument for identifying Australian Aboriginal children at risk of developmental disability and requiring diagnostic developmental assessment. Methods: We conducted a cross‐sectional study of Australian Aboriginal children, aged 3–7 years, resident in three remote communities in the Northern Territory. Following informed consent, children were screened by a paediatrician using the Brigance screen. Results: There were 195 children identified as eligible, and 124 (64%) participated. All children screened, scored below the cut‐off for detecting children likely to have developmental disabilities or academic delays. Furthermore, all children scored below the at‐risk cut‐offs that indicate high probability of disabilities in at‐risk children. Conclusions: The Brigance screen identified all children in these high‐risk Aboriginal communities as well behind their age peers. Language and cultural relevance, and the method of administration limit the use of this screening tool. However, we cannot ignore the uniformly poor performance on a mainstream tool used with children expected to succeed in a mainstream educational setting. Recommendations include adapting an appropriate instrument to guide developmental surveillance and monitoring in remote Australian Aboriginal communities. This study further supports the pressing need for quality early childhood services that address the significant risk confronting Aboriginal children and prepare them in a way that ensures school and future success.
Standardization of Epidemiological Surveillance of Acute Rheumatic Fever
Publisher: Oxford University Press (OUP)
Date: 15-09-2022
DOI: 10.1093/OFID/OFAC252
Abstract: Acute rheumatic fever (ARF) is a multiorgan inflammatory disorder that results from the body’s autoimmune response to pharyngitis or a skin infection caused by Streptococcus pyogenes (Strep A). Acute rheumatic fever mainly affects those in low- and middle-income nations, as well as in indigenous populations in wealthy nations, where initial Strep A infections may go undetected. A single episode of ARF puts a person at increased risk of developing long-term cardiac damage known as rheumatic heart disease. We present case definitions for both definite and possible ARF, including initial and recurrent episodes, according to the 2015 Jones Criteria, and we discuss current tests available to aid in the diagnosis. We outline the considerations specific to ARF surveillance methodology, including discussion on where and how to conduct active or passive surveillance (eg, early childhood centers/schools, households, primary healthcare, administrative database review), participant eligibility, and the surveillance population. Additional considerations for ARF surveillance, including implications for secondary prophylaxis and follow-up, ARF registers, community engagement, and the impact of surveillance, are addressed. Finally, the core elements of case report forms for ARF, monitoring and audit requirements, quality control and assurance, and the ethics of conducting surveillance are discussed.
The Path to Group A Streptococcus Vaccines: World Health Organization Research and Development Technology Roadmap and Preferred Product Characteristics
Publisher: Oxford University Press (OUP)
Date: 08-01-2019
DOI: 10.1093/CID/CIY1143
Abstract: Group A Streptococcus (GAS) infections result in a considerable underappreciated burden of acute and chronic disease globally. A 2018 World Health Assembly resolution calls for better control and prevention. Providing guidance on global health research needs is an important World Health Organization (WHO) activity, influencing prioritization of investments. Here, the role, status, and directions in GAS vaccines research are discussed. WHO preferred product characteristics and a research and development technology roadmap, briefly presented, offer an actionable framework for vaccine development to regulatory and policy decision making, availability, and use. GAS vaccines should be considered for global prevention of the range of clinical manifestations and associated antibiotic use. Impediments related to antigen ersity, safety concerns, and the difficulty to establish vaccine efficacy against rheumatic heart disease are discussed. Demonstration of vaccine efficacy against pharyngitis and skin infections constitutes a key near-term strategic goal. Investments and collaborative partnerships to ersify and advance vaccine candidates are needed.
As a Bacterial Culture Medium, Citrated Sheep Blood Agar Is a Practical Alternative to Citrated Human Blood Agar in Laboratories of Developing Countries
Publisher: American Society for Microbiology
Date: 09-2006
DOI: 10.1128/JCM.02631-05
Abstract: Human blood agar (HuBA) is widely used in developing countries for the isolation of bacteria from clinical specimens. This study compared citrated sheep blood agar (CSBA) and HuBA with defibrinated horse blood agar and defibrinated sheep blood agar (DSBA) for the isolation and antibiotic susceptibility testing of reference and clinical strains of Streptococcus pneumoniae , Streptococcus pyogenes , and Staphylococcus aureus . Reference and clinical strains of all organisms were diluted in brain heart infusion and a clinical specimen of cerebrospinal fluid and cultured on all agars. Viable counts, colony morphology, and colony size were recorded. Susceptibility testing for S. pneumoniae and S. pyogenes was performed on defibrinated sheep blood Mueller-Hinton agar, citrated sheep blood Mueller-Hinton agar (CSB MHA), and human blood Mueller-Hinton agar plates. For all organisms, the colony numbers were similar on all agars. Substantially smaller colony sizes and absent or minimal hemolysis were noted on HuBA for all organisms. Antibiotic susceptibility results for S. pneumoniae were similar for the two sheep blood agars however, larger zone sizes were displayed on HuBA, and quality control for the reference strain failed on HuBA. For S. pyogenes , larger zone sizes were demonstrated on HuBA and CSBA than on DSBA. Poor hemolysis made interpretation of the zone sizes difficult on HuBA. CSBA is an acceptable alternative for the isolation of these organisms. The characteristic morphology is not evident, and hemolysis is poor on HuBA and so HuBA is not recommended for use for the isolation or the susceptibility testing of any of these organisms. CSB MHA may be suitable for use for the susceptibility testing of S. pneumoniae .
Time to address the neglected burden of group A Streptococcus
Publisher: AMPCo
Date: 24-06-2021
DOI: 10.5694/MJA2.51149
Rheumatic Heart Disease in Asia
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 16-12-2008
A pilot study of the quality of informed consent materials for Aboriginal participants in clinical trials
Publisher: BMJ
Date: 08-2005
Reframe the Behaviour: Evaluation of a training intervention to increase capacity in managing detained youth with fetal alcohol spectrum disorder and neurodevelopmental impairments
Publisher: Informa UK Limited
Date: 04-08-2020
The economic and health burdens of diseases caused by group A Streptococcus in New Zealand
Publisher: Elsevier BV
Date: 02-2021
Dysregulated IL-1β-GM-CSF Axis in Acute Rheumatic Fever That Is Limited by Hydroxychloroquine
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-12-2018
DOI: 10.1161/CIRCULATIONAHA.118.033891
Abstract: Acute rheumatic fever (ARF) and rheumatic heart disease are autoimmune consequences of group A streptococcus infection and remain major causes of cardiovascular morbidity and mortality around the world. Improved treatment has been stymied by gaps in understanding key steps in the immunopathogenesis of ARF and rheumatic heart disease. This study aimed to identify (1) effector T cell cytokine(s) that might be dysregulated in the autoimmune response of patients with ARF by group A streptococcus, and (2) an immunomodulatory agent that suppresses this response and could be clinically translatable to high-risk patients with ARF. The immune response to group A streptococcus was analyzed in peripheral blood mononuclear cells from an Australian Aboriginal ARF cohort by a combination of multiplex cytokine array, flow cytometric analysis, and global gene expression analysis by RNA sequencing. The immunomodulatory drug hydroxychloroquine was tested for effects on this response. We found a dysregulated interleukin-1β-granulocyte-macrophage colony-stimulating factor (GM-CSF) cytokine axis in ARF peripheral blood mononuclear cells exposed to group A streptococcus in vitro, whereby persistent interleukin-1β production is coupled to overproduction of GM-CSF and selective expansion of CXCR3 + CCR4 − CCR6 − CD4 T cells. CXCR3 + CCR4 − CCR6 − CD4 T cells are the major source of GM-CSF in human CD4 T cells and CXCL10, a CXCR3 ligand and potent T helper 1 chemoattractant, was elevated in sera from patients with ARF. GM-CSF has recently emerged as a key T cell-derived effector cytokine in numerous autoimmune diseases, including myocarditis, and the production of CXCL10 may explain selective trafficking of these cells to the heart. We provide evidence that interleukin-1β lifies the expansion of GM-CSF-expressing CD4 T cells, which is effectively suppressed by hydroxychloroquine. RNA sequencing showed shifts in gene expression profiles and differentially expressed genes in peripheral blood mononuclear cells derived from patients at different clinical stages of ARF. Given the safety profile of hydroxychloroquine and its clinical pedigree in treating autoimmune diseases such as rheumatoid arthritis, where GM-CSF plays a pivotal role, we propose that hydroxychloroquine could be repurposed to reduce the risk of rheumatic heart disease after ARF.
Correction to: Lessons learned in the development of sustained release penicillin drug delivery systems for the prophylactic treatment of rheumatic heart disease (RHD)
Publisher: Springer Science and Business Media LLC
Date: 15-03-2018
DOI: 10.1007/S13346-018-0511-Y
Abstract: Jürgen B. Bulitta's name was misspelled in the original version of the article. It is correct as reflected here. The original article has been revised.
Adherence to secondary prophylaxis for rheumatic heart disease is underestimated by register data
Publisher: Public Library of Science (PLoS)
Date: 31-05-2017
Standardization of Epidemiological Surveillance of Group A Streptococcal Cellulitis
Publisher: Oxford University Press (OUP)
Date: 15-09-2022
DOI: 10.1093/OFID/OFAC267
Abstract: Cellulitis is an acute bacterial infection of the dermis and subcutaneous tissue usually found complicating a wound, ulcer, or dermatosis. This article provides guidelines for the surveillance of cellulitis. The primary objectives of cellulitis surveillance are to (1) monitor trends in rates of infection, (2) describe the demographic and clinical characteristics of patients with cellulitis, (3) estimate the frequency of complications, and (4) describe the risk factors associated with primary and recurrent cellulitis. This article includes case definitions for clinical cellulitis and group A streptococcal cellulitis, based on clinical and laboratory evidence, and case classifications for an initial and recurrent case. It is expected that surveillance for cellulitis will be for all-cause cellulitis, rather than specifically for Strep A cellulitis. Considerations of the type of surveillance are also presented, including identification of data sources and surveillance type. Minimal surveillance necessary for cellulitis is facility-based, passive surveillance. Prospective, active, facility-based surveillance is recommended for estimates of pathogen-specific cellulitis burden. Participant eligibility, surveillance population, and additional surveillance considerations such as active follow-up of cases, the use of International Classification of Disease diagnosis codes, and microbiological s ling of cases are discussed. Finally, the core data elements to be collected on case report forms are presented.
Frequently asked questions about varicella vaccine
Publisher: Therapeutic Guidelines Limited
Date: 02-2005
Current Issues in Managing Group A Streptococcal Infections
Publisher: Springer US
Date: 2004
Recurrent crepitant cellulitis caused by Clostridium perfringens
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2002
DOI: 10.1097/00006454-200212000-00021
Abstract: A previously healthy 13-year-old boy developed extensive subcutaneous emphysema of the lower limb after a penetrating injury to the knee. Clostridium perfringens was isolated from the wound. Despite surgical debridement and appropriate antibiotics, the emphysema recurred, and prolonged antibiotic treatment was required. This case highlights the distinction between gas gangrene and the lesser known entity of clostridial crepitant cellulitis.
The potential health impact of prospective Strep A vaccines: a modeling study
Publisher: Cold Spring Harbor Laboratory
Date: 03-08-2022
DOI: 10.1101/2022.08.01.22278298
Abstract: The World Health Organization published the preferred product characteristics for a Group A Streptococcus (Strep A) vaccine in 2018. Based on these parameters for the age of vaccination, vaccine efficacy, duration of protection from vaccine-derived immunity, and vaccination coverage, we developed a static cohort model to estimate the projected health impact of Strep A vaccination at the global, regional, and national levels and by country-income category. We used the model to analyse six strategic scenarios. Based on Strep A vaccine introduction between 2022 and 2034 for the primary scenario, we estimated vaccination at birth for 30 vaccinated cohorts could avert 2.5 billion episodes of pharyngitis, 345 million episodes of impetigo, 1.3 million episodes of invasive disease, 24 million episodes of cellulitis, and 6 million cases of rheumatic heart disease globally. Vaccination impact in terms of burden averted per fully vaccinated in idual is highest in North America for cellulitis and in Sub-Saharan Africa for rheumatic heart disease.
Standardization of Epidemiological Surveillance of Invasive Group A Streptococcal Infections
Publisher: Oxford University Press (OUP)
Date: 15-09-2022
DOI: 10.1093/OFID/OFAC281
Abstract: Invasive group A streptococcal (Strep A) infections occur when Streptococcus pyogenes, also known as beta-hemolytic group A Streptococcus, invades a normally sterile site in the body. This article provides guidelines for establishing surveillance for invasive Strep A infections. The primary objective of invasive Strep A surveillance is to monitor trends in rates of infection and determine the demographic and clinical characteristics of patients with laboratory-confirmed invasive Strep A infection, the age- and sex-specific incidence in the population of a defined geographic area, trends in risk factors, and the mortality rates and rates of nonfatal sequelae caused by invasive Strep A infections. This article includes clinical descriptions followed by case definitions, based on clinical and laboratory evidence, and case classifications (confirmed or probable, if applicable) for invasive Strep A infections and for 3 Strep A syndromes: streptococcal toxic shock syndrome, necrotizing fasciitis, and pregnancy-associated Strep A infection. Considerations of the type of surveillance are also presented, noting that most people who have invasive Strep A infections will present to hospital and that invasive Strep A is a notifiable disease in some countries. Minimal surveillance necessary for invasive Strep A infection is facility-based, passive surveillance. A resource-intensive but more informative approach is active case finding of laboratory-confirmed Strep A invasive infections among a large (eg, state-wide) and well defined population. Participant eligibility, surveillance population, and additional surveillance components such as the use of International Classification of Disease diagnosis codes, follow-up, period of surveillance, seasonality, and s le size are discussed. Finally, the core data elements to be collected on case report forms are presented.
Rheumatic heart disease: infectious disease origin, chronic care approach
Publisher: Springer Science and Business Media LLC
Date: 29-11-2017
Changes in the clinical and epidemiological features of group A streptococcal bacteraemia in Australia's Northern Territory
Publisher: Wiley
Date: 29-10-2014
DOI: 10.1111/TMI.12405
Abstract: Invasive group A streptococcus (iGAS) disease is an important cause of mortality globally. The incidence of iGAS in Australia's tropical Northern Territory (NT) has been previously reported as 32.2/100 000 in Indigenous people for the period 1991-1996. We aimed to measure the incidence and severity of iGAS disease in the NT since this time. We collected demographic data for all GAS blood culture isolates over a 12-year period (1998-2009) from the three hospital laboratories serving the tropical NT. We then collected detailed clinical information from hospital records and databases for the subset of these patients who were admitted to Royal Darwin Hospital during 2005-2009. There were 295 confirmed cases of GAS bacteraemia over the study period, with a mean (SD) age of 42.1 (22.0) years, and 163 (55.0%) were male. The annual age-adjusted incidence was 15.2 (95% CI 13.4-16.9)/100 000 overall and 59.4 (95% CI 51.2-67.6) in Indigenous Australians. For 2005-2009, there were 123 cases with the most common focus of infection being skin/soft tissue [44 (35.6%)] 29 patients (23.6%) required intensive care unit admission and 20 (16.3%) had streptococcal toxic shock syndrome. Antecedent sore throat or use of non-steroidal anti-inflammatory drugs was rare, but current or recent scabies, pyoderma and trauma were common. The incidence and severity of iGAS are high and increasing in tropical northern Australia, and urgent attention is needed to improve surveillance and the social determinants of health in this population. This study adds to emerging data suggesting increasing importance of iGAS in low- and middle-income settings globally.
Rheumatic Heart Disease in Developing Countries
Publisher: Massachusetts Medical Society
Date: 02-08-2007
DOI: 10.1056/NEJMP078039
Investigation of trimethoprim/sulfamethoxazole resistance in an emerging sequence type 5 methicillin-resistant Staphylococcus aureus clone reveals discrepant resistance reporting
Publisher: Elsevier BV
Date: 09-2018
Clinical and epidemiological features of group A streptococcal bacteraemia in a region with hyperendemic superficial streptococcal infection
Publisher: Cambridge University Press (CUP)
Date: 02-1999
DOI: 10.1017/S0950268898001952
Abstract: Reports of increasing incidence and severity of invasive group A streptococcal (GAS) infections come mainly from affluent populations where exposure to GAS is relatively infrequent. We conducted a 6-year retrospective review of GAS bacteraemia in the Northern Territory of Australia, comparing the Aboriginal population (24% of the study population), who have high rates of other streptococcal infections and sequelae, to the non-Aboriginal population. Of 72 episodes, 44 (61%) were in Aboriginal patients. All 12 cases in children were Aboriginal. Risk factors were implicated in 82% of episodes (91% in adults) and there was no significant difference in the proportion of Aboriginal compared to non-Aboriginal patients with at least one risk factor. Genetic typing of isolates revealed no dominant strains and no evidence of a clone which has been a common cause of these infections elsewhere.
Revision of the Jones Criteria for the Diagnosis of Acute Rheumatic Fever in the Era of Doppler Echocardiography
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-05-2015
DOI: 10.1161/CIR.0000000000000205
Abstract: Acute rheumatic fever remains a serious healthcare concern for the majority of the world’s population despite its decline in incidence in Europe and North America. The goal of this statement was to review the historic Jones criteria used to diagnose acute rheumatic fever in the context of the current epidemiology of the disease and to update those criteria to also take into account recent evidence supporting the use of Doppler echocardiography in the diagnosis of carditis as a major manifestation of acute rheumatic fever. To achieve this goal, the American Heart Association’s Council on Cardiovascular Disease in the Young and its Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee organized a writing group to comprehensively review and evaluate the impact of population-specific differences in acute rheumatic fever presentation and changes in presentation that can result from the now worldwide availability of nonsteroidal anti-inflammatory drugs. In addition, a methodological assessment of the numerous published studies that support the use of Doppler echocardiography as a means to diagnose cardiac involvement in acute rheumatic fever, even when overt clinical findings are not apparent, was undertaken to determine the evidence basis for defining subclinical carditis and including it as a major criterion of the Jones criteria. This effort has resulted in the first substantial revision to the Jones criteria by the American Heart Association since 1992 and the first application of the Classification of Recommendations and Levels of Evidence categories developed by the American College of Cardiology/American Heart Association to the Jones criteria. This revision of the Jones criteria now brings them into closer alignment with other international guidelines for the diagnosis of acute rheumatic fever by defining high-risk populations, recognizing variability in clinical presentation in these high-risk populations, and including Doppler echocardiography as a tool to diagnose cardiac involvement.
Focused cardiac ultrasound screening for rheumatic heart disease by briefly trained health workers: a study of diagnostic accuracy
Publisher: Elsevier BV
Date: 06-2016
Are minor echocardiographic changes associated with an increased risk of acute rheumatic fever or progression to rheumatic heart disease?
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.IJCARD.2015.07.005
Abstract: The World Heart Federation criteria for the echocardiographic diagnosis of rheumatic heart disease (RHD) include a category "Borderline" RHD which may represent the earliest evidence of RHD. We aimed to determine the significance of minor heart valve abnormalities, including Borderline RHD, in predicting the future risk of acute rheumatic fever (ARF) or RHD. A prospective cohort study of Aboriginal and Torres Strait Islander children aged 8 to 18 years was conducted. Cases comprised children with Borderline RHD or other minor non-specific valvular abnormalities (NSVAs) detected on prior echocardiography. Controls were children with a prior normal echocardiogram. Participants underwent a follow-up echocardiogram 2.5 to 5 years later to assess for progression of valvular changes and development of Definite RHD. Interval diagnoses of ARF were ascertained. There were 442 participants. Cases with Borderline RHD were at significantly greater risk of ARF (incidence rate ratio 8.8, 95% CI 1.4-53.8) and any echocardiographic progression of valve lesions (relative risk 8.19, 95% CI 2.43-27.53) than their Matched Controls. Cases with Borderline RHD were at increased risk of progression to Definite RHD (1 in 6 progressed) as were Cases with NSVAs (1 in 10 progressed). Children with Borderline RHD had an increased risk of ARF, progression of valvular lesions, and development of Definite RHD. These findings provide support for considering secondary antibiotic prophylaxis or ongoing surveillance echocardiography in high-risk children with Borderline RHD.
Initiating an undiagnosed diseases program in the Western Australian public health system
Publisher: Springer Science and Business Media LLC
Date: 03-05-2017
Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics
Publisher: Springer Science and Business Media LLC
Date: 27-05-2019
The Importance of Scabies Coinfection in the Treatment Considerations for Impetigo
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2016
Rheumatic heart disease in pregnancy: How can health services adapt to the needs of Indigenous women? A qualitative study.
Publisher: Wiley
Date: 06-11-2017
DOI: 10.1111/AJO.12744
Abstract: To study rheumatic heart disease health literacy and its impact on pregnancy, and to identify how health services could more effectively meet the needs of pregnant women with rheumatic heart disease. Researchers observed and interviewed a small number of Aboriginal women and their families during pregnancy, childbirth and postpartum as they interacted with the health system. An Aboriginal Yarning method of relationship building over time, participant observations and interviews with Aboriginal women were used in the study. The settings were urban, island and remote communities across the Northern Territory. Women were followed interstate if they were transferred during pregnancy. The participants were pregnant women and their families. We relied on participants' abilities to tell their own experiences so that researchers could interpret their understanding and perspective of rheumatic heart disease. Aboriginal women and their families rarely had rheumatic heart disease explained appropriately by health staff and therefore lacked understanding of the severity of their illness and its implications for childbearing. Health directives in written and spoken English with assumed biomedical knowledge were confusing and of limited use when delivered without interpreters or culturally appropriate health supports. Despite previous studies documenting poor communication and culturally inadequate care, health systems did not meet the needs of pregnant Aboriginal women with rheumatic heart disease. Language-appropriate health education that promotes a shared understanding should be relevant to the gender, life-stage and social context of women with rheumatic heart disease.
The future of acute rheumatic fever and rheumatic heart disease in Australia
Publisher: Wiley
Date: 08-2012
DOI: 10.5694/MJA12.10980
Author Correction: Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics
Publisher: Springer Science and Business Media LLC
Date: 19-07-2019
DOI: 10.1038/S41588-019-0482-Z
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Randomized, controlled trial comparing once daily and three times daily gentamicin in children with urinary tract infections
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2001
DOI: 10.1097/00006454-200103000-00004
Abstract: To undertake population pharmacokinetic modeling and to determine the safety and efficacy of once daily (OD) gentamicin dosing in children with severe urinary tract infections (UTI). An open, randomized, controlled trial comparing OD with three times daily (TD) gentamicin dosing in hospitalized children ages 1 month to 12 years with UTI. Daily doses (milligrams per kg per day) of gentamicin in both groups were 7.5 ( 10 years old). There were 179 children enrolled (90 OD, 89 TD). Baseline clinical characteristics and pathogens were similar, except that circulatory compromise and renal cortical scintigraphic defects were more common in the OD group. Median gentamicin treatment durations were 3.0 (OD) and 2.7 (TD) days. Mean peak gentamicin concentrations were 17.3 (OD) vs. 6.4 (TD) mg/l 99% of peak concentrations were >7 mg/l in the OD group whereas 16% of peak concentrations were or = 2 mg/l, whereas in the TD group only 0.7% were > or = 2 mg/l. Age or prior elevated peak concentrations did not predict high trough concentrations. Population pharmacokinetic modeling of the data fitted a one-compartment model with first order elimination. There were no clinical or bacteriologic failures. The two disease-related complications were confined to the OD group. No nephro- or ototoxicity was identified. With age-appropriate dosing and measurement of serum trough concentrations before the second dose, OD gentamicin is safe and effective for the treatment of UTI requiring parenteral treatment in children aged 1 month to 12 years.
Group A streptococcal infections in children
Publisher: Wiley
Date: 04-2007
DOI: 10.1111/J.1440-1754.2007.01051.X
Abstract: The group A streptococcus causes the widest range of disease in humans of all bacterial pathogens. Group A streptococcal diseases are more common in children than adults with diseases ranging from pharyngitis and impetigo to invasive infections and the post-streptococcal sequelae--acute rheumatic fever and acute post-streptococcal glomerulonephritis. The global burden of severe group A streptococcal disease is concentrated largely in developing countries and Indigenous populations such as Aboriginal Australians. Control of group A streptococcal disease is poor in these settings and the need for a vaccine has been argued. With an ever-increasing understanding of the group A streptococcus at a molecular level, new and sophisticated vaccines are currently in human trials and the next decade holds exciting prospects for curbing group A streptococcal diseases.
Normal Ranges of Streptococcal Antibody Titers Are Similar Whether Streptococci Are Endemic to the Setting or Not
Publisher: American Society for Microbiology
Date: 02-2009
DOI: 10.1128/CVI.00291-08
Abstract: Group A streptococcal (GAS) serology is used for the diagnosis of post-streptococcal diseases, such as acute rheumatic fever, and occasionally for the diagnosis of streptococcal pharyngitis. Experts recommend that the upper limits of normal for streptococcal serology be determined for in idual populations because of differences in the epidemiology of GAS between populations. Therefore, we performed a study to determine the values of the upper limit of normal for anti-streptolysin O (ASO) and anti-DNase B (ADB) titers in Fiji. Participants with a history of GAS disease, including pharyngitis or impetigo, were excluded. A total of 424 serum s les from people of all ages (with a s le enriched for school-aged children) were tested for their ASO and ADB titers. Reference values, including titers that were 80% of the upper limit of normal, were obtained by regression analysis by use of a curve-fitting method instead of the traditional nonparametric approach. Normal values for both the ASO titer and the ADB titer rose sharply during early childhood and then declined gradually with age. The estimated titers that were 80% of the upper limit or normal at age 10 years were 276 IU/ml for ASO and 499 IU/ml for ADB. Data from our study are similar to those found in countries with temperate climates, suggesting that a uniform upper limit of normal for streptococcal serology may be able to be applied globally.
Group A Streptococci from a Remote Community Have Novel Multilocus Genotypes but ShareemmTypes and Housekeeping Alleles with Isolates from Worldwide Sources
Publisher: Oxford University Press (OUP)
Date: 15-02-2004
DOI: 10.1086/381452
Preventing heart failure: a position paper of the Heart Failure Association in collaboration with the European Association of Preventive Cardiology.
Publisher: Wiley
Date: 2022
DOI: 10.1002/EJHF.2351
Abstract: The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present position paper aims to provide practical evidence-based information to support the implementation of effective preventive measures. After reviewing the most common risk factors, an overview of the population attributable risks in different continents is presented, to identify potentially effective opportunities for prevention and to inform preventive strategies. Finally, potential interventions that have been proposed and have been shown to be effective in preventing heart failure are listed.
Pediatric Staphylococcus aureus Bacteremia: Clinical Spectrum and Predictors of Poor Outcome
Publisher: Oxford University Press (OUP)
Date: 05-06-2022
DOI: 10.1093/CID/CIAB510
Abstract: Staphylococcus aureus is a common cause of bacteremia, yet the epidemiology and predictors of poor outcome remain inadequately defined in childhood. ISAIAH (Invasive Staphylococcus aureus Infections and Hospitalizations in children) is a prospective, cross-sectional study of S. aureus bacteremia (SAB) in children hospitalized in Australia and New Zealand over 24 months (2017–2018). Overall, 552 SABs were identified (incidence 4.4/100 000/year). Indigenous children, those from lower socioeconomic areas and neonates were overrepresented. Although 90-day mortality was infrequent, one-third experienced the composite of: length of stay & days (26%), intensive care unit admission (20%), relapse (4%), or death (3%). Predictors of mortality included prematurity (adjusted odds ratio [aOR],16.8 95% confidence interval [CI], 1.6–296.9), multifocal infection (aOR, 22.6 CI, 1.4–498.5), necrotizing pneumonia (aOR, 38.9 CI, 1.7–1754.6), multiorgan dysfunction (aOR, 26.5 CI, 4.1–268.8), and empiric vancomycin (aOR, 15.7 CI, 1.6–434.4) while infectious diseases (ID) consultation (aOR, 0.07 CI .004–.9) was protective. Neither MRSA nor vancomycin trough targets impacted survival however, empiric vancomycin was associated with nephrotoxicity (OR, 3.1 95% CI 1.3–8.1). High SAB incidence was demonstrated and for the first time in a pediatric setting, necrotizing pneumonia and multifocal infection were predictors of mortality, while ID consultation was protective. The need to reevaluate pediatric vancomycin trough targets and limit unnecessary empiric vancomycin exposure to reduce poor outcomes and nephrotoxicity is highlighted. One in 3 children experienced considerable SAB morbidity therefore, pediatric inclusion in future SAB comparator trials is paramount to improve outcomes.
Increasing incidence of invasive group A streptococcal disease in Western Australia, particularly among Indigenous people
Publisher: Wiley
Date: 05-06-2021
DOI: 10.5694/MJA2.51117
Comparison of approaches to rheumatic fever surveillance across Organisation for Economic Co-operation and Development countries
Publisher: Wiley
Date: 14-07-2015
DOI: 10.1111/JPC.12969
Abstract: Rheumatic fever (RF) prevention, control and surveillance are increasingly important priorities in New Zealand (NZ) and Australia. We compared RF surveillance across Organisation for Economic Co-operation and Development (OECD) member countries to assist in benchmarking and identifying useful approaches. A structured literature review was completed using Medline and PubMed databases, investigating RF incidence rates. Surveillance methods were noted. Health department websites were searched to assess whether addressing RF was a Government priority. Of 32 OECD member countries, nine reported RF incidence rates after 1999. Highest rates were seen in indigenous Australians, and NZ Māori and Pacific peoples. NZ and Australian surveillance systems are highly developed, with notification and register data compiled regularly. Only these two Governments appeared to prioritise RF surveillance and control. Other countries relied mainly on hospitalisation data. There is a lack of standardisation across incidence rate calculations. Israel and Italy may have relatively high RF rates among developed countries. RF lingers in specific populations in OECD member countries. At a minimum, RF registers are needed in higher incidence countries. Countries with low RF incidences should periodically review surveillance information to ensure rates are not increasing.
The global burden of group A streptococcal diseases
Publisher: Elsevier BV
Date: 11-2005
A systematic review of the evidence that swimming pools improve health and wellbeing in remote Aboriginal communities in Australia
Publisher: Elsevier BV
Date: 02-2016
Abstract: To provide an overview of the evidence for health and wellbeing benefits associated with swimming pools in remote Aboriginal* communities in Australia. Peer-reviewed and grey literature from 1990 to 2014 was searched to identify studies set in remote Australia that evaluated health and wellbeing benefits that have been associated with swimming pools. Studies were categorised using an evidence classification scale. Twelve studies met our search criteria. All prospective studies that collected data on skin infections found access to swimming pools to be associated with a drop of skin sore prevalence and -where measured- severity. Studies documenting ear and eye infections showed mixed outcomes. Many wider community and wellbeing benefits were documented in various studies, although many of these were primarily anecdotal in nature. Although a case can be made regarding skin infections and the broader wellbeing benefits that swimming pools may bring to remote Aboriginal communities, the benefit to ear and eye health remains unresolved. The decision to provide swimming pools to remote Aboriginal communities should not hinge on the demonstration of direct health benefits alone. Equity considerations and the potential broader benefits such amenities may entail are equally important.
Impact of single dose azithromycin on group A streptococci in the upper respiratory tract and skin of Aboriginal children
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2002
DOI: 10.1097/00006454-200205000-00005
Abstract: Aboriginal children living in remote Australia experience high rates of bacterial infection such as trachoma, otitis media and streptococcal skin infection, which often progress to associated chronic diseases in later life. In February, 1995, single dose azithromycin was given to 130 Aboriginal children with trachoma and their contacts. The impact of this program on respiratory and skin group A Streptococcus pyogenes carriage and infection was also monitored. Immediately before treatment 90% of children had skin sores, 38% of sores had pus and 74% of sores with pus had group A Streptococcus (GAS). Overall 57% of children had GAS skin infections. At 2 to 3 weeks and 2 and 6 months after treatment, this proportion was 10, 32 and 51%, respectively. For the upper respiratory tract GAS recovery rates were 8% before treatment and 0, 11 and 15% at the 2- to 3-week, 2-month and 6-month posttreatment visits, respectively. Multiple types occurred concurrently in in iduals, particularly after treatment. Identical types were sometimes recovered simultaneously from the upper respiratory tract and skin, suggesting that the high rates of acute rheumatic fever in this population in the absence of high rates of detectable throat GAS carriage could be related to high rates of skin GAS infection. There is an urgent need for education, adequate housing, scabies eradication and improved hygiene to reduce skin trauma and subsequent GAS infection in this population. Clinical trials are needed to determine how these measures can best be integrated with the trachoma eradication program to maximize health outcomes.
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