ORCID Profile
0000-0002-4638-8392
Current Organisations
Charles Darwin University
,
University of Sydney
,
Menzies School of Health Research
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Publisher: Elsevier BV
Date: 02-2017
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.IJPORL.2015.07.013
Abstract: Indigenous Australian children have a high prevalence of otitis media with effusion (OME) and associated conductive hearing loss. Only three microbiological studies of middle ear fluid (MEF) from Indigenous Australian children with OME have been reported. All of these were reliant on culture or species-specific PCR assays. The aim of this study was to characterise the middle ear fluid (MEF), adenoid and nasopharyngeal (NP) microbiomes of Indigenous Australian children, using culture-independent 16S rRNA gene sequencing. MEF, NP swabs and adenoid specimens were collected from 11 children in the Alice Springs region of Central Australia. Bacterial communities in these specimens were characterised using 16S rRNA gene sequencing. The microbiota in MEF s les were dominated (>50% relative abundance) by operational taxonomic units (OTUs) consistent with Alloiococcus otitidis (6/11), Haemophilus influenzae (3/11) or Streptococcus sp. (specifically, Mitis group streptococci which includes Streptococcus pneumoniae) (1/11). Anatomical site selectivity was indicated by the presence of a single conserved Haemophilus OTU in 7/11 MEF s les. In comparison, there were ten distinct Haemophilus OTUs observed across the NP and adenoid s les. Despite significant differences between the MEF and NP/adenoid microbiomes, Streptococcus sp., H. influenzae and Moraxella catarrhalis OTUs were common to all s le types. Co-occurrence of classical otopathogens in paired MEF and NP/Adenoid s les is consistent with earlier culture-based studies. These data highlight the need to further assess H. influenzae traits important in otitis media and to understand the role of canal flora, especially A. otitidis, in populations with a high prevalence of tympanic membrane perforation.
Publisher: Cambridge University Press (CUP)
Date: 16-01-2017
DOI: 10.1017/S0022215116009294
Abstract: To review research addressing the polymicrobial aetiology of otitis media in Indigenous Australian children in order to identify research gaps and inform best practice in effective prevention strategies and therapeutic interventions. Literature review. Studies of aspirated middle-ear fluid represented a minor component of the literature reviewed. Most studies relied upon specimens from middle-ear discharge or the nasopharynx. Culture-based middle-ear discharge studies have found that non-typeable Haemophilus influenzae and Streptococcus pneumoniae predominate, with Moraxella catarrhalis, Staphylococcus aureus and Streptococcus pyogenes isolated in a lower proportion of s les. Alloiococcus otitidis was detected in a number of studies however, its role in otitis media pathogenesis remains controversial. Nasopharyngeal colonisation is a risk factor for otitis media in Indigenous infants, and bacterial load of otopathogens in the nasopharynx can predict the ear state of Indigenous children. Most studies have used culture-based methods and specimens from middle-ear discharge or the nasopharynx. Findings from these studies are consistent with international literature, but reliance on culture may incorrectly characterise the microbiology of this condition. Advances in genomic technologies are now providing microbiologists with the ability to analyse the entire mixed bacterial communities (‘microbiomes’) of s les obtained from Indigenous children with otitis media.
Publisher: Elsevier BV
Date: 05-2011
Publisher: AMPCo
Date: 2010
DOI: 10.5694/J.1326-5377.2010.TB03396.X
Abstract: To compare the clinical effectiveness of single-dose azithromycin treatment with 7 days of amoxycillin treatment among Aboriginal children with acute otitis media (AOM) in rural and remote communities in the Northern Territory. Aboriginal children aged 6 months to 6 years living in 16 rural and remote communities were screened for AOM. Those diagnosed with AOM were randomly allocated to receive either azithromycin (30 mg/kg as a single dose) or amoxycillin (50mg/kg/day in two ided doses for a minimum of 7 days). We used a double-dummy method to ensure blinding. Our study was conducted from 24 March 2003 to 20 July 2005. Failure to cure AOM by the end of therapy nasal carriage of Streptococcus pneumoniae and non-capsular Haemophilus influenzae (NCHi). We followed 306 of 320 children (96%) allocated to the treatment groups. Single-dose azithromycin did not reduce (or increase) the risk of clinical failure (50% failure rate [82/165]) compared with amoxycillin (54% failure rate [83/155]) (risk difference [RD], - 4% [95% CI, - 15% to 7%] P = 0.504). Compared with amoxycillin, azithromycin significantly reduced the proportion of children with nasal carriage of S. pneumoniae (27% v 63% RD, - 36% [95% CI, - 47% to - 26%] P < 0.001) and NCHi (55% v 85% RD, - 30% [95% CI, - 40% to - 21%] P < 0.001). Nasal carriage of S. pneumoniae with intermediate or full resistance to penicillin was lower (but not significantly so) in the azithromycin group (10% v 16%), but this group had significantly increased carriage of azithromycin-resistant S. pneumoniae (10% v 3% RD, 7% [95% CI, 0.1% to 12%] P = 0.001). Carriage of beta-lactamase-producing NCHi was about 5% in both groups. Although azithromycin reduced nasal carriage of S. pneumoniae and NCHi, clinical failure was high in both treatment groups. The possibility of weekly azithromycin treatment in children with persistent AOM should be evaluated. Australian Clinical Trials Registry ACTRN 12609000691246.
Publisher: Elsevier BV
Date: 06-2010
DOI: 10.1016/J.MIMET.2010.03.006
Abstract: Nasopharyngeal carriage studies are needed to monitor changes in important bacterial pathogens in response to vaccination and antibiotics. Commercial swab transport followed by transfer to skim milk tryptone glucose glycerol broth for frozen storage is an option for studies of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis.
Publisher: Public Library of Science (PLoS)
Date: 28-03-2012
Publisher: American Society for Microbiology
Date: 15-06-2010
DOI: 10.1128/JVI.02658-09
Abstract: Exploration of the genetic ersity of WU polyomavirus (WUV) has been limited in terms of the specimen numbers and particularly the sizes of the genomic fragments analyzed. Using whole-genome sequencing of 48 WUV strains collected in four continents over a 5-year period and 16 publicly available whole-genome sequences, we identified three main WUV clades and five subtypes, provisionally termed Ia, Ib, Ic, II, IIIa, and IIIb. Overall nucleotide variation was low (0 to 1.2%). The discriminatory power of the previous VP2 fragment typing method was found to be limited, and a new, larger genotyping region within the VP2/1 interface was proposed.
Publisher: Wiley
Date: 08-1994
Publisher: AMPCo
Date: 07-2013
DOI: 10.5694/MJA13.10533
Abstract: To measure the impact of 4 weeks of daily swimming on rates of ear discharge among Aboriginal children with a tympanic membrane perforation (TMP) and on the microbiology of the nasopharynx and middle ear. A randomised controlled trial involving 89 Aboriginal children (aged 5-12 2013s) with a TMP, conducted in two remote Northern Territory Aboriginal communities from August to December 2009. 4 school weeks of daily swimming lessons (45 minutes) in a chlorinated pool. Proportions of children with ear discharge and respiratory and opportunistic bacteria in the nasopharynx and middle ear. Of 89 children randomly assigned to the swimming or non-swimming groups, 58 (26/41 swimmers and 32/48 non-swimmers) had ear discharge at baseline. After 4 weeks, 24 of 41 swimmers had ear discharge compared with 32 of 48 non-swimmers (risk difference, - 8% (95% CI, - 28% to 12%). There were no statistically significant changes in the microbiology of the nasopharynx or middle ear in swimmers or non-swimmers. Streptococcus pneumoniae and non-typeable Haemophilus influenzae were the dominant organisms cultured from the nasopharynx, and H. influenzae, Staphylococcus aureus and Pseudomonas aeruginosa were the dominant organisms in the middle ear. Swimming lessons for Aboriginal children in remote communities should be supported, but it is unlikely that they will substantially reduce rates of chronic suppurative otitis media and associated bacteria in the nasopharynx and middle ear. However, swimming was not associated with increased risk of ear discharge and we found no reason to discourage it. Australian New Zealand Clinical Trials Registry ACTRN12613000634774.
Publisher: Cambridge University Press (CUP)
Date: 08-1999
DOI: 10.1017/S0950268899002708
Abstract: There have been no previous longitudinal studies of otitis media conducted in non-Aboriginal Australian children. This paper describes the rate and risk factors for middle ear effusion (MEE) in children attending day care in Darwin, Australia. A prospective cohort study of 252 children under 4 years was conducted in 9 day care centres over 12 fortnights between 24 March and 15 September 1997. Tympanometry was conducted fortnightly and multivariate analysis used to determine risk factors predicting MEE. The outcome of interest was the rate of type B tympanograms per child detected in either ear at fortnightly examinations. After adjusting for clustering by child, MEE was detected on average 4·4 times in 12 fortnights (37% of all examinations conducted). Risk factors associated with presence of effusion were younger age, a family history of ear infection, previous grommets (tympanostomy tubes), ethnicity and the day care centre attended. A history of wheeze appeared protective. These effects were modest (RR 0·57–1·70). Middle ear effusion is very common in children attending day care in Darwin. This has clinical importance, since MEE during early childhood may affect optimal hearing, learning and speech development. There is little scope for modification for many of the risk factors for MEE predicted by this model. Further study of the day care environment is warranted.
Publisher: Wiley
Date: 07-02-2023
DOI: 10.1002/PED4.12364
Abstract: In remote communities of the Northern Territory, Australia, children experience high rates of otitis media (OM), commonly caused by non‐typeable Haemophilus influenzae (NTHi). Few data exist on antibiotic susceptibility of NTHi from OM. To determine whether population‐level nasopharyngeal NTHi antibiotic susceptibility data could inform antibiotic treatment for OM. NTHi isolates ( n = 92) collected from ear discharge between 2003 and 2013 were selected to time‐ and age‐match NTHi isolates from the nasopharyngeal carriage ( n = 95). Antimicrobial susceptibility were tested. Phylogenomic trees and a genome‐wide association study (GWAS) were performed to determine the similarity of nasopharyngeal and ear isolates at a population level. Among 174 NTHi isolates available for antimicrobial susceptibility testing, 10.3% (18/174) were resistant to icillin and 9.2% (16/174) were resistant to trimethoprim‐sulfamethoxazole. Small numbers of isolates (≤3) were resistant to tetracycline, chlor henicol, or amoxicillin‐clavulanic acid. There was no statistical difference in the proportion of icillin‐resistant ( P = 0.11) or trimethoprim‐sulfamethoxazole‐resistant isolates ( P = 0.70) between ear discharge and nasopharynx‐derived NTHi isolates. Three multi‐drug resistant NTHi isolates were identified. Phylogenomic trees showed no clustering of 187 Haemophilus influenzae isolates based on anatomical niche (nasopharynx or ear discharge), and no genetic variations that distinguished NTHi derived from ear discharge and nasopharyngeal carriage were evident in the GWAS. In this population‐level study, nasopharyngeal and ear discharge isolates did not represent distinct microbial populations. These results support tracking of population‐level nasopharyngeal NTHi antibiotic resistance patterns to inform clinical management of OM in this population.
Publisher: Public Library of Science (PLoS)
Date: 03-12-2013
Publisher: Springer Science and Business Media LLC
Date: 29-06-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2011
Publisher: Oxford University Press (OUP)
Date: 30-08-2019
Abstract: We analyse the optical morphologies of galaxies in the IllustrisTNG simulation at z ∼ 0 with a convolutional neural network trained on visual morphologies in the Sloan Digital Sky Survey. We generate mock SDSS images of a mass complete s le of $\\sim 12\\, 000$ galaxies in the simulation using the radiative transfer code SKIRT and include PSF and noise to match the SDSS r-band properties. The images are then processed through the exact same neural network used to estimate SDSS morphologies to classify simulated galaxies in four morphological classes (E, S0/a, Sab, Scd). The CNN model classifies simulated galaxies in one of the four main classes with the same uncertainty as for observed galaxies. The mass–size relations of the simulated galaxies ided by morphological type also reproduce well the slope and the normalization of observed relations which confirms a reasonable ersity of optical morphologies in the TNG suite. However we find a weak correlation between optical morphology and Sersic index in the TNG suite as opposed to SDSS which might require further investigation. The stellar mass functions (SMFs) decomposed into different morphologies still show some discrepancies with observations especially at the high-mass end. We find an overabundance of late-type galaxies ($\\sim 50{{\\ \\rm per\\ cent}}$ versus $\\sim 20{{\\ \\rm per\\ cent}}$) at the high-mass end [log(M*/M⊙) 11] of the SMF as compared to observations according to the CNN classifications and a lack of S0 galaxies ($\\sim 20{{\\ \\rm per\\ cent}}$ versus $\\sim 40{{\\ \\rm per\\ cent}}$) at intermediate masses. This work highlights the importance of detailed comparisons between observations and simulations in comparable conditions.
Publisher: American Society for Microbiology
Date: 12-2011
DOI: 10.1128/IAI.05663-11
Abstract: The capsular serotype has long been associated with the virulence of Streptococcus pneumoniae . Here we present an in-depth study of phenotypic and genetic differences between serotype 3 and serogroup 11 S. pneumoniae clinical isolates from both the general and indigenous populations of Australia. Both serotypes/groups included clonally unrelated strains with differences in well-known polymorphic virulence genes, such as nanA and pspA , as demonstrated by multilocus sequence typing and Western blot analysis. Nonetheless, the serotype 3 strains were consistently and significantly more virulent in mice than the serogroup 11 strains. Despite extensive genomic analysis, noncapsular genes common to one serotype/group but not the other were not identified. Nevertheless, following the conversion of a serotype 11A isolate to serotype 3 and subsequent analysis in an intranasal infection model, it was evident that both capsular and noncapsular factors determine the virulence phenotype in mice. However, it appears that these noncapsular factors vary from strain to strain.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2007
Publisher: American Society for Microbiology
Date: 1992
DOI: 10.1128/JCM.30.1.207-210.1992
Abstract: C ylobacter jejuni and/or C ylobacter coli was cultured from 218 of 1,078 patients of all age groups admitted to Alice Springs Hospital, Alice Springs, central Australia, between July 1988 and June 1989 for treatment of diarrhea. One hundred sixty-six C ylobacter colonies from 127 patients were subjected to O serotyping by using the Penner typing scheme. All except 29 colonies could be serotyped. A total of 46 serotypes were identified, and the predominant serotypes were O:8, 17, O:22, O:1,44, and O:19. A large proportion of colonies reacted with more than one antiserum, and nine serotypes had antigenic compositions not observed previously. Several patients had multiple infections with more than one serotype, and some patients were shown for the first time to be infected with up to three different serotypes. Repeated reinfections with different serotypes were seen in some patients. In some patients, provided it was not due to reinfection with the same serotype, long-term excretion of the same serotype was seen, and for the first time, one patient showed evidence of excretion of the same serotype for up to 73 days.
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.IJPORL.2016.05.011
Abstract: This study aims to monitor the prevalence of suppurative otitis media in remote Indigenous communities after introduction of 13-valent pneumococcal conjugate vaccine (PCV13) in October 2011. We previously reported a decline in suppurative OM following replacement of PCV7 by 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) in October 2009. We continued regular surveillance in remote Indigenous communities between February 2010 and August 2013. This analysis reports the general health, otitis media (OM), nasopharyngeal (NP) carriage and middle ear microbiology in children less than 36 months of age who received a primary course of at least two doses of PHiD-CV10 or PCV13, and not more than one dose of another pneumococcal vaccine. Mean ages of 511 PHiD-CV10- and 140 PCV13-vaccinated children were 19 and 13 months, respectively. Most children received 3-dose non-mixed PCV schedules. At the time of assessment, general health was poor and prevalence of risk factors was high in both groups: overall, around 14% of children had scabies, 20% had impetigo, 59% had runny nose and 39% had cough. Average household size was 8 persons, and 60% of the mothers smoked. Bilaterally normal middle ears were detected in 10% and 7%, respectively. OM with effusion (OME), almost all bilateral, was diagnosed in 52% and 50%, any suppurative OM (acute OM or any tympanic membrane perforation [TMP]) in 37% and 41%, and TMP in 14% and 12%, respectively. Children in the PCV13 group had significantly less NP carriage of combined Streptococcus pneumoniae (Spn) and non-typeable Haemophilus influenzae (NTHi) (62% versus 51%) but significantly more polymicrobial (Spn and NTHi) middle ear cultures (12% versus 43%), and significantly less Staphylococcus aureus-positive middle ears (40% versus 7%). Although NP carriage of pneumococcal serotype 19A was low in the PCV13 group, serotypes 19F and 23F persist. The general health, particularly ear health, of little children in remote Australian Indigenous communities remains in crisis. In particular, transition to PCV13 did not show substantial further improvement in ear health. Possible vaccine-related differences in microbiology, including potential beneficial effects of PHiD-CV10 on NTHi infection, need to be further evaluated in randomised trials.
Publisher: Springer Science and Business Media LLC
Date: 25-09-2017
Publisher: UNSW Canberra and USC
Date: 2021
DOI: 10.25907/00046
Publisher: Wiley
Date: 31-01-2023
DOI: 10.1002/HRDQ.21472
Abstract: Those who serve in military organizations typically develop a strong sense of identification with the defense force and those with whom they serve. However, when these in iduals leave military service, they can experience a sense of displacement or culture shock, making transition into a civilian career a difficult prospect. This paper sought to explore veterans' experiences during the transition into civilian work and, in particular, the impact of this transition on their identity as they are socialized in a civilian organization. The stories of 31 Australian Defence Force veterans were gathered via semi‐structured interviews to provide insight into the experiences during transition and the changing nature of their identity as they began working outside a military environment. The findings identify three stages of identity adjustment through which veterans pass during their transition: realizing, relinquishing, and reconceptualizing. While some encountered more struggles than others depending on their in idual circumstances, the findings provide unique insights for HRD theory and practice to enhance the transition of serving military to a civilian workforce.
Publisher: Elsevier BV
Date: 04-2011
DOI: 10.1016/J.VACCINE.2010.09.030
Abstract: This paper investigates Haemophilus influenzae type b (Hib) carriage in Indigenous children and children attending childcare centres in the Northern Territory of Australia, 1992-2005. More than 10 years after the introduction of the Hib conjugate vaccine, Hib carriage persists in Indigenous children (3.4%, 2003-2005) and children attending childcare centres (0.2%, 2004). This is the first Australian study to examine Hib carriage spanning the pre- and post-vaccination eras. Increasing carriage rates contribute to Hib disease resurgence especially in those with higher disease burdens, such as remote Indigenous Australians, ongoing carriage surveillance provides a sentinel warning system for invasive disease. Following the introduction of H. influenzae type b (Hib) conjugate vaccine to Australia in 1993 as a three dose (2, 4, 12 month) schedule, the incidence of Hib disease decreased dramatically in children, especially in those aged under 5 years. We investigate Hib carriage in Indigenous children and children attending childcare centres from the Northern Territory (NT) of Australia between 1992 and 2005. We report Hib carriage rates in this well vaccinated population, with previously documented high rates of invasive disease. Hib carriage was reviewed in nasopharyngeal or nasal swabs collected between 1992 and 2005 from over 2000 children (61% Indigenous) aged 0-6 years enrolled in 7 otitis media or carriage surveillance studies in the NT. More than 10 years after the introduction of the Hib conjugate vaccine, Hib carriage persists at low levels, but at a higher rate in Indigenous children (3.4%, 2003-2005) than children attending childcare centres (0.2%, 2004), in the NT of Australia. This is the first Australian study to examine Hib carriage spanning the pre- and post-vaccination eras. Ongoing carriage surveillance provides a sentinel warning system for invasive disease. This notifies public health professionals of potential invasive disease, creating early warning systems for intervention if Australian Indigenous children or children attending childcare centres are to follow current international trends associated with high rates of carriage preceding invasive disease-despite high vaccination rates. Internationally there is growing concern that increasing carriage rates are the driving force behind Hib disease resurgence especially in those with higher disease burdens, such as remote Indigenous Australians. Changes to the vaccination schedule from PRP-OMPC (PedvaxHIB(®)), to PRP-T (2, 4, 6, 12 months) from January 2010-may affect carriage and in time, invasive disease rates. This work is important for national and International comparisons as well as feeding back information to vaccine policy makers of the Hib carriage environment throughout this period.
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.
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.
Publisher: Elsevier BV
Date: 03-2007
DOI: 10.1016/J.VACCINE.2006.09.016
Abstract: Young Australian Aboriginal children in remote communities experience very high rates of pneumococcal carriage and otitis media. Prior to introduction of the 7-valent pneumococcal conjugate vaccine (7vPCV, Prevenar), serotype 16F was an important type found in nasal and ear discharge swabs. Since commencement of pneumococcal immunisation for Aboriginal infants in 2001, 16F has become the predominant established serotype in carriage and otitis media in young Aboriginal children. BOX typing and multi-locus sequence typing revealed a erse population of serotype 16F strains, and evidence of potential capsule switching from a vaccine serotype 4 to a serotype 16F.
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.
Publisher: Springer Science and Business Media LLC
Date: 12-2012
Abstract: Streptococcus pneumoniae (Pnc), nontypeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) are the most important bacterial pathogens associated with otitis media (OM). Previous studies have suggested that early upper respiratory tract (URT) bacterial carriage may increase risk of subsequent OM. We investigated associations between early onset of URT bacterial carriage and subsequent diagnosis of OM in Aboriginal and non-Aboriginal children living in the Kalgoorlie-Boulder region located in a semi-arid zone of Western Australia. Aboriginal and non-Aboriginal children who had nasopharyngeal aspirates collected at age 1- 3 months and at least one clinical examination for OM by an ear, nose and throat specialist before age 2 years were included in this analysis. Tympanometry to detect middle ear effusion was also performed at 2- to 6-monthly scheduled field visits from age 3 months. Multivariate regression models were used to investigate the relationship between early carriage and subsequent diagnosis of OM controlling for environmental factors. Carriage rates of Pnc, NTHi and Mcat at age 1- 3 months were 45%, 29% and 48%, respectively, in 66 Aboriginal children and 14%, 5% and 18% in 146 non-Aboriginal children. OM was diagnosed at least once in 71% of Aboriginal children and 43% of non-Aboriginal children. After controlling for age, sex, presence of other bacteria and environmental factors, early nasopharyngeal carriage of NTHi increased the risk of subsequent OM (odds ratio = 3.70, 95% CI 1.22-11.23) in Aboriginal children, while Mcat increased the risk of OM in non-Aboriginal children (odds ratio = 2.63, 95% CI 1.32-5.23). Early carriage of Pnc was not associated with increased risk of OM. Early NTHi carriage in Aboriginal children and Mcat in non-Aboriginal children is associated with increased risk of OM independent of environmental factors. In addition to addressing environmental risk factors for carriage such as overcrowding and exposure to environmental tobacco smoke, early administration of pneumococcal- Haemophilus influenzae D protein conjugate vaccine to reduce bacterial carriage in infants, may be beneficial for Aboriginal children such an approach is currently being evaluated in Australia.
Publisher: Wiley
Date: 11-2017
DOI: 10.1111/JPC.13757
Abstract: Otitis media (OM) is a common condition in Australia. It represents a spectrum of diseases from otitis media with effusion (OME) to chronic suppurative otitis media. For all the OM diagnoses, Australian Indigenous children have higher rates of early onset, severe and persistent disease. OME is the most common form of OM and often occurs after an upper respiratory tract infection. It can be difficult to diagnose (and often goes unrecognised). Hearing loss is the most important complication. The middle-ear effusion impedes the movement of the tympanic membrane and causes a conductive hearing loss of around 25 dB. Around 20% will have a hearing loss exceeding 35 dB. Children with early onset, persistent, bilateral OME and hearing loss (or speech delay) are most likely to benefit from interventions. However, the impact of all the effective treatment options is modest. Giving advice about effective communication strategies for young children is always appropriate. The best evidence from randomised trials supports not using antihistamines and/or decongestants, considering a trial of antibiotics and referral for tympanostomy tubes. Despite the availability of evidence-based guidelines, giving advice about treatment is a challenge because recommendations vary according to condition, age, risk of complications and parental preference. While most children with OME can be effectively managed in primary care, we need to get children who meet the criteria for simple ear, nose and throat procedures that improve hearing on to ear, nose and throat surgery waiting lists. Long delays in hearing support may contribute to life-long social and economic disadvantage.
Publisher: Public Library of Science (PLoS)
Date: 02-10-2009
Publisher: Springer Science and Business Media LLC
Date: 19-10-2015
Publisher: Springer Science and Business Media LLC
Date: 16-06-2021
DOI: 10.1186/S13063-021-05215-7
Abstract: Almost all Aboriginal children in remote communities have persistent bilateral otitis media affecting hearing and learning throughout early childhood and school years, with consequences for social and educational outcomes, and later employment opportunities. Current primary health care and specialist services do not have the resources to meet the complex needs of these children. This stepped-wedge cluster randomised trial will allocate 18 communities to one of five 6-monthly intervention start dates. Stratification will be by region and population size. The intervention (Hearing for Learning Initiative, HfLI) consists of six 20-h weeks of training (delivered over 3 months) that includes Certificate II in Aboriginal Primary Health Care (3 modules) and competencies in ear and hearing data collection (otoscopy, tympanometry and hearScreen), plus 3 weeks of assisted integration into the health service, then part-time employment as Ear Health Facilitators to the end of the trial. Unblinding will occur 6 months prior to each allocated start date, to allow Community Reference Groups to be involved in co-design of the HfLI implementation in their community. Relevant health service data will be extracted 6-monthly from all 18 communities. The primary outcome is the difference in proportion of children (0 to 16 years of age) who have at least one ear assessment (diagnosis) documented in their medical record within each 6-month period, compared to control periods (no HfLI). Secondary outcomes include data on sustainability, adherence to evidence-based clinical guidelines for otitis media, including follow-up and specialist referrals, and school attendance. Structured interviews with staff working in health and education services, Ear Health Trainees, Ear Health Facilitators and families will assess process outcomes and the HfLI broader impact. The impact of training and employment of Ear Health Facilitators on service enhancement will inform the health, education and employment sectors about effectiveness of skills and job creation that empowers community members to contribute to addressing issues of local importance, in this instance ear and hearing health of children. ClinicalTrials.gov NCT03916029 . Registered on 16 April 2019.
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.MIMET.2017.03.012
Abstract: The efficacy of chocolate agar, versus bacitracin, vancomycin, clindamycin, chocolate agar (BVCCA) for the isolation of non-typeable Haemophilus influenzae (NTHi) from nasopharyngeal swabs was determined. BVCCA cultured NTHi from 97.3% of NTHi-positive swabs, compared to 87.1% for chocolate agar. To maximise culture sensitivity, the use of both media is recommended.
Publisher: Springer Science and Business Media LLC
Date: 12-09-2015
DOI: 10.1007/S10096-015-2480-0
Abstract: Although long-term azithromycin decreases exacerbation frequency in bronchiectasis, increased macrolide resistance is concerning. We investigated macrolide resistance determinants in a secondary analysis of a multicenter randomized controlled trial. Indigenous Australian children living in remote regions and urban New Zealand Māori and Pacific Islander children with bronchiectasis were randomized to weekly azithromycin (30 mg/kg) or placebo for up to 24 months and followed post-intervention for up to 12 months. Nurses administered and recorded medications given and collected nasopharyngeal swabs 3-6 monthly for culture and antimicrobial susceptibility testing. Nasopharyngeal carriage of Haemophilus influenzae and Moraxella catarrhalis was significantly lower in azithromycin compared to placebo groups, while macrolide-resistant Streptococcus pneumoniae and Staphylococcus aureus carriage was significantly higher. Australian children, compared to New Zealand children, had higher carriage overall, significantly higher carriage of macrolide-resistant bacteria at baseline (16/38 versus 2/40 children) and during the intervention (69/152 versus 22/239 swabs), and lower mean adherence to study medication (63 % versus 92 %). Adherence ≥70 % (versus <70 %) in the Australian azithromycin group was associated with lower carriage of any pathogen [odds ratio (OR) 0.19, 95 % confidence interval (CI) 0.07-0.53] and fewer macrolide-resistant pathogens (OR 0.34, 95 % CI 0.14-0.81). Post-intervention (median 6 months), macrolide resistance in S. pneumoniae declined significantly in the azithromycin group, from 79 % (11/14) to 7 % (1/14) of positive swabs, but S. aureus strains remained 100 % macrolide resistant. Azithromycin treatment, the Australian remote setting, and adherence <70 % were significant independent determinants of macrolide resistance in children with bronchiectasis. Adherence to treatment may limit macrolide resistance by suppressing carriage.
Publisher: Springer Science and Business Media LLC
Date: 08-01-2013
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.VACCINE.2016.12.059
Abstract: Chronic endobronchial infections in children are responsible for a high disease burden. Streptococcus pneumoniae is frequently isolated however, few publications have described serotypes associated with non-invasive lower airway infection. Paired nasopharyngeal (NP) swabs and bronchoalveolar lavage (BAL) fluids were collected from children undergoing bronchoscopy for chronic cough. NP swabs were also collected from asymptomatic children in otitis media surveillance studies (controls). Specimens were processed and lower airway infection defined (⩾10 From 2007-2015, paired specimens were processed from 435 children with protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) or bronchiectasis. S. pneumoniae lower airway infection was detected in 95 children: 27% with PBB and 20% with CSLD/bronchiectasis. Most (91%) children were vaccinated with ⩾2 doses of 7-valent, 10-valent or 13-valent pneumococcal conjugate vaccine. Paired NP and BAL serotype distributions were very similar prevalent serotypes (>10 isolates) were 19A (9%), 19F, 6C, 35B, 15B, 16F, 15A, 15C, 23A, 23F and 11A. For 21 serotypes found in both NP and BAL specimens, ORs for infection were low range 0.46 (serotype 23B) to 2.15 (serotype 6A). In the 2008-2013 surveillance studies, NP swabs were collected from 1565 asymptomatic children 74% were pneumococcal carriers. For 21 of 22 serotypes found in both control NP swabs and BAL specimens, ORs for infection were similarly low range 0.33 (serotype 23B) to 3.29 (serotype 22F) none was significantly different from 1. The exception was serotype 7B with OR 8.84 (95% CI 1.46, 38.1). Most NP carriage serotypes have a similar propensity to cause lower airway infection in children with suppurative lung diseases. Further development of pneumococcal vaccines is needed to prevent non-invasive disease caused by commonly carried serotypes.
Publisher: Cambridge University Press (CUP)
Date: 04-1996
DOI: 10.1017/S0950268800052419
Abstract: Ribotyping with the restriction enzyme Xba I was used to study the dynamics of carriage of non-encapsulated Haemophilus influenzae (NCHi) in Aboriginal infants at risk of otitis media. Carriage rates of NCHi in the infants in the community were very high the median age for detection was 50 days and colonization was virtually 100% by 120 days of age and persisted at a high level throughout the first year of life [1]. Eighteen different ribotypes of NCHi were identified from 34 positive swabs taken from 3 infants over a period of 9 months. The same ribotypes were recovered for up to 3 months from consecutive swabs of in idual infants, and 12 of 27 swabs (44·4%) yielded two ribotypes from four colonies typed. Statistical analysis suggested that most swabs would have been positive for two ribotypes if enough colonies had been typed although the second most frequent ribotype was detected on average in only 13% of strains. Early colonization and carriage of multiple ribotypes of NCHi may help to explain the chronicity of carriage and thus the persistence of otitis media in Aboriginal infants.
Publisher: Oxford University Press (OUP)
Date: 1998
DOI: 10.1086/517046
Publisher: Elsevier BV
Date: 04-2021
Publisher: AIP Publishing
Date: 03-2016
DOI: 10.1063/1.4943860
Abstract: A flow model is formulated to investigate the hydrodynamic structure of the boundary layers of incompressible fluid in a rotating cylindrical cavity with steady radial inflow. The model considers mass and momentum transfer coupled between boundary layers and an inviscid core region. Dimensionless equations of motion are solved using integral methods and a space-marching technique. As the fluid moves radially inward, entraining boundary layers develop which can either meet or become non-entraining. Pressure and wall shear stress distributions, as well as velocity profiles predicted by the model, are compared to numerical simulations using the software OpenFOAM. Hydrodynamic structure of the boundary layers is governed by a Reynolds number, Re, a Rossby number, Ro, and the dimensionless radial velocity component at the periphery of the cavity, Uo. Results show that boundary layers merge for Re & & 10 and Ro & & 0.1, and boundary layers become predominantly non-entraining for low Ro, low Re, and high Uo. Results may contribute to improve the design of technology, such as heat exchange devices, and turbomachinery.
Publisher: Springer Science and Business Media LLC
Date: 04-08-2011
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.
Publisher: AMPCo
Date: 08-2002
Publisher: Springer Science and Business Media LLC
Date: 04-08-2011
Publisher: Springer Science and Business Media LLC
Date: 04-08-2011
Publisher: AMPCo
Date: 11-2009
DOI: 10.5694/J.1326-5377.2009.TB02927.X
Abstract: Otitis media is a common childhood illness associated with hearing loss, social disadvantage and medical costs. Prevalence and severity are high among Indigenous children. Respiratory bacterial and viral pathogens ascend the eustachian tube from the nasopharynx to the middle ear, causing inflammation, fluid accumulation, and bulging of the tympanic membrane, with or without pain. Among Australian Indigenous children, ear disease commences earlier in life, and involves multiple strains of bacterial pathogens at high density that persist longer. Persistent nasal discharge, overcrowded living conditions (particularly exposure to many children) and poor facilities for washing children perpetuate a vicious cycle of transmission and infection. Risk factors include environmental tobacco smoke, season, lack of breastfeeding, younger age and immature immune system, and possibly genetic factors. The innate immune system is a critical first response to infection, particularly as passive maternal antibodies decline and during the maturation of the infant adaptive immune response. The relative contributions of innate factors to protection from otitis media are currently not well understood. A ersity of antibodies that target strain-specific and conserved antigens are generated in response to natural exposure to otitis media pathogens (or to vaccines). Deficiencies in these antibodies may explain susceptibility to recurrent infections. Incremental contributions from all these elements are likely to be important in otitis media susceptibility versus protection. Effective medical and social strategies to prevent early age of onset are urgently needed.
Publisher: Elsevier BV
Date: 02-2010
DOI: 10.1016/J.VACCINE.2009.11.011
Abstract: Quantitation of specific IgG to polysaccharides (serotypes) of Streptococcus pneumoniae provides the basis for evaluating vaccine efficacy. Different enzyme-linked immunosorbent assay (ELISA) methods are used internationally, making comparisons between laboratories difficult. We undertook an inter-laboratory comparison between two international laboratories performing serotype-specific IgG ELISAs using a panel of well-characterized serum s les: the Murdoch Childrens Research Institute Pneumococcal Laboratory (Melbourne, Australia) and the Vaccine Immunology Laboratory, National Public Health Institute (Helsinki, Finland). While good agreement was found for the inter-laboratory comparison for most serotypes, differences in ELISA methodology influenced specific IgG measurement. Therefore, use of the World Health Organization (WHO)-based ELISA methods for measurement of serotype-specific IgG is reliable, accurate and provides consistent results between international laboratories.
Publisher: Springer Science and Business Media LLC
Date: 08-03-2021
DOI: 10.1186/S12887-021-02552-Z
Abstract: Aboriginal children living in Australian remote communities are at high risk of early and persistent otitis media, hearing loss, and social disadvantage. Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) are the primary pathogens. We compared otitis media outcomes in infants randomised to either a combination of Synflorix™ (PHiD-CV10, with protein D of NTHi) and Prevenar13™ (PCV13, with 3, 6A, and 19A), with recommended schedules for each vaccine alone. We previously reported superior broader overall immunogenicity of the combination schedule at 7 months, and early superiority of PHiD-CV10 compared to PCV13 at 4 months. In an open-label superiority trial, we randomised (1:1:1) Aboriginal infants at 28 to 38 days of age, to either Prevenar13™ (P) at 2–4-6 months (_PPP), Synflorix™ (S) at 2–4-6 months (_SSS), or Synflorix™ at 1–2-4 months plus Prevenar13™ at 6 months ( S SSP). Ears were assessed using tympanometry at 1 and 2 months, combined with otoscopy at 4, 6, and 7 months. A worst ear diagnosis was made for each child visit according to a severity hierarchy of normal, otitis media with effusion (OME), acute otitis media without perforation (AOMwoP), AOM with perforation (AOMwiP), and chronic suppurative otitis media (CSOM). Between September 2011 and September 2017, 425 infants were allocated to _PPP(143), _SSS(141) or S SSP(141). Ear assessments were successful in 96% scheduled visits. At 7 months prevalence of any OM was 91, 86, and 90% in the _PPP, _SSS, and S SSP groups, respectively. There were no significant differences in prevalence of any form of otitis media between vaccine groups at any age. Combined group prevalence of any OM was 43, 57, 82, 87, and 89% at 1, 2, 4, 6, and 7 months of age, respectively. Of 388 infants with ear assessments at 4, 6 and 7 months, 277 (71.4%) had OM that met criteria for specialist referral rAOM, pOME, or CSOM. Despite superior broader overall immunogenicity of the combination schedule at 7 months, and early superiority of PHiD-CV10 compared to PCV13 at 4 months, there were no significant differences in prevalence of otitis media nor healthy ears throughout the first months of life. ACTRN12610000544077 registered 06/07/2010 and ClinicalTrials.gov NCT01174849 registered 04/08/2010.
Publisher: Oxford University Press (OUP)
Date: 11-1999
DOI: 10.1086/313494
Publisher: Springer Science and Business Media LLC
Date: 24-07-2012
Publisher: Elsevier BV
Date: 12-2016
Publisher: Elsevier BV
Date: 08-2006
Publisher: Springer Science and Business Media LLC
Date: 21-05-2018
Publisher: Springer Science and Business Media LLC
Date: 03-03-2016
Publisher: Public Library of Science (PLoS)
Date: 04-02-2010
Publisher: Cambridge University Press (CUP)
Date: 02-2001
DOI: 10.1017/S0950268801005106
Abstract: The emergence of type 6B Streptococcus pneumoniae resistant to five antibiotics (penicillin, chlor henicol, trimethoprim–sulphamethoxazole, erythromycin and tetracycline) in both the Northern Territory and Queensland prompted an investigation of the genetic relatedness and patterns of migration of the isolates. Pulsed field gel electrophoresis of genomic DNA of 74 multiple drug-resistant (MDR) isolates cultured in both regions between August 1988 and June 1997 showed that 100% of MDR isolates from the Northern Territory and 96% of MDR strains from Queensland were genetically indistinguishable or closely related to the index strain. None of a further 65 type 6B isolates that were resistant to one or two, or susceptible to all of the above antibiotics, were clonally related to the MDR pneumococci. The geographical distribution of the MDR type 6B clone increased over time. The index strain, first isolated in Darwin in August 1988, was identified in Brisbane, 2900km distant, less than 4 years later and subsequently in other Queensland centres. Surveillance programmes are important to monitor the emergence and spread of potentially invasive MDR pneumococcal clones in countries that are well serviced by air and road transport.
Publisher: Elsevier BV
Date: 03-2007
Publisher: Elsevier BV
Date: 06-2020
Publisher: American Society for Microbiology
Date: 03-2010
DOI: 10.1128/JCM.01701-09
Abstract: Nonserotypeable pneumococci (NSP) are commonly carried by Australian Indigenous children in remote communities. The purpose of this study was to characterize carriage isolates of NSP from Indigenous children vaccinated with the seven-valent pneumococcal conjugate vaccine (PCV7) and to use these data to guide decisions on reporting of NSP. A total of 182 NSP were characterized by BOX typing, antibiogram analysis, and multilocus sequence typing (MLST) of common BOX types. NSP positive for the wzg capsule gene were analyzed by a multiplex PCR-based reverse line blot hybridization assay (mPCR/RLB-H) targeting capsule genes to determine the serotype. Among 182 NSP, 49 BOX types were identified. MLST of 10 representative isolates found 7 STs, including ST448 (which accounted for 11% of NSP). Non-penicillin susceptibility was evident in 51% of the isolates. Pneumococcal wzg sequences were detected in only 23 (13%) NSP, including 10 that contained an ∼1.2-kb insert in the region. mPCR/RLB-H identified serotype 14 wzy sequences in all 10 NSP, and 1 also contained a serotype 3-specific wze sequence. Among the remaining 13 wzg- positive NSP, few belonged to the serotypes represented in PCV7. It appears that most NSP identified in Australian Indigenous children are from a true nonencapsulated lineage. Few NSP represented serotypes in PCV7 that suppress capsular expression. High rates of carriage and penicillin resistance and the occasional presence of capsule genes suggest a role for NSP in the maintenance and survival of capsulated pneumococci. To avoid the inflation of pneumococcal carriage and antibiotic resistance rates, in clinical trials, we recommend separate reporting of rates of capsular strains and NSP and the exclusion of data for NSP from primary analyses.
Publisher: Public Library of Science (PLoS)
Date: 06-10-2011
Publisher: Public Library of Science (PLoS)
Date: 23-02-2023
DOI: 10.1371/JOURNAL.PONE.0280926
Abstract: Aboriginal and Torres Strait Islander children experience a high burden of otitis media. We collected data on symptoms associated with acute otitis media (AOM) in a clinical trial involving children receiving primary care at urban Aboriginal Medical Services. Two scales were employed to monitor symptoms over time: the AOM-Severity of Symptoms scale (AOM-SOS) and the AOM-Faces Scale (AOM-FS). This study took place at a mid-point of the un-blinded trial. We examined symptoms at enrolment and day 7, and compared the scales for trends, and bivariate correlation (Spearman’s rho) over 14 days. Responsiveness of the scales to clinical change was determined by Friedman’s test of trend in two subgroups stratified by day 7 AOM status. We interviewed parents/carers and research officers regarding their experience of the scales and analysed data thematically. Data derived from 224 children (18 months to 16 years median 3.6 years). Common symptoms associated with AOM at baseline were runny nose (40%), cough (38%) and irritability (36%). More than one third had no or minimal symptoms at baseline according to AOM-SOS (1-2/10) and AOM-FS scores (1-2/7). The scales performed similarly, and were moderately correlated, at all study points. Although scores decreased from day 0 to 14, trends and mean scores were the same whether AOM was persistent or resolved at day 7. Users preferred the simplicity of the AOM-FS but encountered challenges when interpreting it. We found minimally symptomatic AOM was common among Aboriginal and Torres Strait Islander children in urban settings. The AOM-SOS and AOM-FS functioned similarly. However, it is likely the scales measured concurrent symptoms related to upper respiratory tract infections, given they did not differentiate children with persistent or resolved AOM based on stringent diagnostic criteria. This appears to limit the research and clinical value of the scales in monitoring AOM treatment among Aboriginal and Torres Strait Islander children.
Publisher: Cambridge University Press (CUP)
Date: 2019
DOI: 10.1017/S0022215119000057
Abstract: Important ear problems can affect the outer ear, the middle ear and the inner ear. Globally, the greatest burden of disease is due to ear conditions that are associated with otorrhoea and hearing loss. This study reviewed the literature on the prevention and treatment of common ear conditions that are most relevant to settings with high rates of ear disease and limited resources. The grading of recommendations assessment, development and evaluation (‘GRADE’) approach was utilised to assess interventions. Accurate diagnosis of ear disease is challenging. Much of the preventable burden of ear disease is associated with otitis media. Nine otitis media interventions for which there is moderate to high certainty of effect were identified. While most interventions only provide modest benefit, the impact of treatment is more substantial in children with acute otitis media with perforation and chronic suppurative otitis media. Disease prevention through good hygiene practices, breastfeeding, reducing smoke exposure, immunisation and limiting noise exposure is recommended. Children with acute otitis media with perforation, chronic suppurative otitis media, complications of otitis media, and significant hearing loss should be prioritised for medical treatment.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-1994
DOI: 10.1097/00006454-199411000-00009
Abstract: Otitis media (OM) develops in the first months of life and persists throughout childhood in many rural Aboriginal children. We have followed Aboriginal and non-Aboriginal infants from birth to determine the relationship of the early onset of OM to nasopharyngeal colonization with respiratory pathogens. Aboriginal infants were colonized with multiple species of respiratory bacteria (Moraxella catarrhalis, Haemophilus influenzae, Streptococcus pneumoniae) at a rate of 5% per day and the timing of colonization predicted the onset of persistent OM in in idual Aboriginal infants. Non-Aboriginal infants became colonized by M. catarrhalis alone at the slower rate of 1% per day and experienced transient episodes of OM in the absence of colonization. We attribute early bacterial colonization in most Aboriginal infants to high rates of cross-infection due to overcrowding, poor hygiene and high rates of bacterial carriage. Early age of infection and the multiplicity of bacterial types may contribute to prolonged carriage and to eustachian tube damage leading to persistent OM. Thus Aboriginal infants are "otitis-prone" and might qualify for prophylactic antibiotics.
Publisher: Elsevier BV
Date: 12-2013
DOI: 10.1016/J.VACCINE.2013.08.062
Abstract: In 2003 the World Health Organization (WHO) convened a working group and published a set of standard methods for studies measuring nasopharyngeal carriage of Streptococcus pneumoniae (the pneumococcus). The working group recently reconvened under the auspices of the WHO and updated the consensus standard methods. These methods describe the collection, transport and storage of nasopharyngeal s les, as well as provide recommendations for the identification and serotyping of pneumococci using culture and non-culture based approaches. We outline the consensus position of the working group, the evidence supporting this position, areas worthy of future research, and the epidemiological role of carriage studies. Adherence to these methods will reduce variability in the conduct of pneumococcal carriage studies undertaken in the context of pneumococcal vaccine trials, implementation studies, and epidemiology studies more generally so variability in methodology does not confound the interpretation of study findings.
Publisher: AMPCo
Date: 11-2010
Publisher: Springer Science and Business Media LLC
Date: 23-10-2010
Publisher: Wiley
Date: 06-2021
DOI: 10.1002/PED4.12262
Abstract: Maternal urogenital human papillomavirus (HPV) infection may place neonates at risk of HPV acquisition and subsequently lower respiratory infections as HPV can influence development of immunity. The respiratory HPV prevalence is not known in remote‐dwelling Aboriginal infants, who are at high risk of respiratory infection and where the population prevalence of urogenital HPV in women is high. These data are necessary to inform HPV vaccination regimens. A retrospective analysis using PCR specific for HPV was performed on 64 stored nasopharyngeal swabs from remote‐dwelling Aboriginal infants 6 months of age, with and without hospitalised pneumonia. HPV DNA was not detected in any specimen. Despite the negative result, we cannot exclude a role for HPV in respiratory infections affecting infants in this population however, our data do not support HPV as an important contributor to acute respiratory infection in remote‐dwelling Aboriginal children.
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.
Publisher: Springer Science and Business Media LLC
Date: 14-06-2005
Publisher: Springer Science and Business Media LLC
Date: 04-08-2009
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.MIMET.2015.10.013
Abstract: Haemophilus influenzae remains a major cause of disease worldwide requiring continued study. Recently, isolates of Streptococcus pneumoniae and Moraxella catarrhalis, but not H. influenzae, were reported to survive long-term ultra-freeze storage in STGGB. We show that nontypeable H. influenzae isolates survive for up to 20 years when thawing is avoided.
Publisher: Elsevier BV
Date: 11-2020
Publisher: Informa UK Limited
Date: 19-05-2022
Publisher: Therapeutic Guidelines Limited
Date: 12-2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2005
DOI: 10.1097/01.INF.0000160945.87356.CA
Abstract: Australian Indigenous children living in remote areas have rates of tympanic membrane perforation as high as 60%, almost 100 times the prevalence in urban child care settings (<1%). Relative rates of pneumococcal nasal carriage do not reflect this difference in disease risk. Cross-sectional comparison of nasal carriage and hand contamination in children younger than 4 years of age from urban child-care centers and Indigenous children 3-7 years of age from a remote community. Almost identical methods of nasal swab collection, transport and culture were used. Data on pneumococcal antimicrobial susceptibility patterns and serotypes are also reported. For Indigenous children compared with children in child care, the relative risk of nasal carriage of either pneumococcus or noncapsular Haemophilus influenzae was <2-fold [relative risk, 1.7 95% confidence interval (CI), 1.5, 1.9], the risk of simultaneous nasal carriage was almost 3-fold (78% versus 28% relative risk, 2.9 95% CI 2.3, 3.5), and the risk of pneumococcal hand contamination was 8-fold higher (37% versus 4% relative risk, 8.4 95% CI 4.6, 15.2). For simultaneous hand contamination, the risk was 23-fold (8% versus 0.3% relative risk, 23.1 95% CI 2.9, 185.4). Remote Indigenous children also had a more erse serotype distribution (25 versus 14 serotypes identified). Simultaneous nasal carriage of Streptococcus pneumoniae and H. influenzae and hand contamination are simple indicators of risk for use in studies of otitis media in populations at risk for tympanic membrane perforation.
Publisher: American Society for Microbiology
Date: 07-1998
DOI: 10.1128/IAI.66.7.3403-3409.1998
Abstract: Immunization with Haemophilus influenzae type b (Hib) conjugate polysaccharide vaccines has dramatically reduced Hib disease worldwide. As in other populations, nasopharyngeal carriage of Hib declined markedly in Aboriginal infants following vaccination, although carriage has not been entirely eliminated. In this study, we describe the genetic characteristics and the carriage dynamics of longitudinal isolates of Hib, characterized by using several typing methods. In addition, carriage rates of nonencapsulated H. influenzae (NCHi) are high, and concurrent colonization with Hib and NCHi is common we also observed NCHi isolates which were genetically similar to Hib. There is a continuing need to promote Hib immunization and monitor H. influenzae carriage in populations in which the organism is highly endemic, not least because of the possibility of genetic exchange between Hib and NCHi strains in such populations.
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 06-2001
Publisher: American Astronomical Society
Date: 02-02-2021
Publisher: Wiley
Date: 23-04-2008
Publisher: John Wiley & Sons, Ltd
Date: 18-07-2002
Publisher: Wiley
Date: 10-2017
DOI: 10.1038/CTI.2017.46
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2006
Publisher: Public Library of Science (PLoS)
Date: 05-05-2011
Publisher: The American Association of Immunologists
Date: 15-05-2012
Abstract: RTS,S/AS01, a vaccine targeting pre-erythrocytic stages of Plasmodium falciparum, is undergoing clinical trials. We report an analysis of cellular immune response to component Ags of RTS,S—hepatitis B surface Ag (HBs) and P. falciparum circumsporozoite (CS) protein—among Tanzanian children in a phase IIb RTS,S/AS01E trial. RTS,S/AS01 E vaccinees make stronger T cell IFN-γ, CD69, and CD25 responses to HBs peptides than do controls, indicating that RTS,S boosts pre-existing HBs responses. T cell CD69 and CD25 responses to CS and CS-specific secreted IL-2 were augmented by RTS,S vaccination. Importantly, more than 50% of peptide-induced IFN-γ+ lymphocytes were NK cells, and the magnitude of the NK cell CD69 response to HBs peptides correlated with secreted IL-2 concentration. CD69 and CD25 expression and IL-2 secretion may represent sensitive markers of RTS,S-induced, CS-specific T cells. The potential for T cell-derived IL-2 to augment NK cell activation in RTS,S-vaccinated in iduals, and the relevance of this for protection, needs to be explored further.
Publisher: Springer Science and Business Media LLC
Date: 12-08-2013
Publisher: Elsevier BV
Date: 04-2006
Publisher: American Society for Microbiology
Date: 27-11-2014
DOI: 10.1128/CVI.00632-13
Abstract: Nontypeable Haemophilus influenzae (NTHi)-associated disease is a major health problem globally. Whole-genome sequence analysis identified the absence of hpd genes encoding Haemophilus protein D in 3 of 16 phylogenetically distinct NTHi isolates. This novel finding is of potential clinical significance, as protein D and hpd represent important NTHi vaccine antigen and diagnostic targets, respectively.
Publisher: Wiley
Date: 06-1996
DOI: 10.1111/J.1445-5994.1996.TB01928.X
Abstract: The prevalence of resistant Streptococcus pneumoniae (SP) is increasing world-wide. Pneumococcal prevalence and susceptibility patterns are not known for children in the Top End of the Northern Territory. To determine the prevalence of nasopharyngeal carriage of pneumococci in children hospitalised in Darwin, and the extent of penicillin and ceftriaxone resistance in these isolates. Nasopharyngeal swabs were collected on admission from 85 children who had not received antimicrobials for their admission illness. Antimicrobial resistance was determined following selective culture for SP isolates. Minimal inhibitory concentrations (MICs) for penicillin and ceftriaxone were determined using the E-test method. The overall prevalence of nasopharyngeal SP carriage was 44%. Carriage occurred more often in Aboriginal children from rural areas (56%) than in urban children (24%) (OR 3.94, 95% CI 1.35-11.78, p < 0.01). Thirty per cent of isolates were penicillin resistant, 35% were ceftriaxone resistant, and 49% were resistant to at least one of these. One isolate showed high-level resistance to both antimicrobials all other resistant isolates were of intermediate-level resistance. For the same isolate, MICs for ceftriaxone were more often higher than those for penicillin. Five isolates had intermediate resistance to ceftriaxone whilst remaining sensitive to penicillin. The prevalence of pneumococcal resistance to penicillin and ceftriaxone in hospitalised children in Darwin is much higher than previously reported in Australia. This has implications for future antimicrobial management and highlights the need for regular regional surveillance of SP resistance. The development of conjugate pneumococcal vaccines for children under two years is a priority.
Publisher: Rural and Remote Health
Date: 24-11-2019
DOI: 10.22605/RRH5267
Publisher: Elsevier BV
Date: 12-2009
Publisher: Springer Science and Business Media LLC
Date: 16-10-2018
Publisher: Wiley
Date: 25-02-2014
DOI: 10.1111/JPC.12496
Abstract: Does phone multimedia messages (MMS) to families of Indigenous children with tympanic membrane perforation (TMP): (i) increase clinic attendance (ii) improve ear health and (iii) provide a culturally appropriate method of health promotion? Fifty-three Australian Aboriginal children with a TMP living in remote community households with a mobile phone were randomised into intervention (n = 30) and control (n = 23) groups. MMS health messages in local languages were sent to the intervention group over 6 weeks. there was no significant difference in clinic attendance, with 1.3 clinic visits per child in both groups (mean difference -0.1 95% confidence interval (CI) -1.1, 0.9 P = 0.9). (i) there was no significant change in healed perforation (risk difference 6% 95% CI -10, 20 P = 0.6), middle ear discharge (risk difference -1% 95% CI -30, 30 P = 1.0) or perforation size (mean difference 3% 95% CI -11, 17 P = 0.7) between the groups (ii) 84% (95% CI 60, 90) in the control and 70% (95% CI 50, 80) in the intervention group were happy to receive MMS health messages in the future. The difference was not significant (risk difference -14% 95% CI -37, 8 P = 0.3). Although there was no improvement in clinic attendance or ear health, this randomised controlled trial of MMS in Indigenous languages demonstrated that MMS is a culturally appropriate form of health promotion. Mobile phones may enhance management of chronic disease in remote and disadvantaged populations.
Publisher: Springer Science and Business Media LLC
Date: 12-2018
Publisher: Wiley
Date: 12-01-2011
Publisher: Elsevier BV
Date: 03-2006
DOI: 10.1016/J.VACCINE.2006.09.006
Abstract: Australian Aboriginal children experience early, persistent and severe middle ear infections. We conducted a review of the medical literature that addressed acute otitis media (AOM) in Australian Aboriginal children. Comparisons were made with the recent guidelines on the diagnosis and management of AOM prepared by the American Academies of Pediatrics and Family Physicians (AAP & AAFP 2004). Otitis media in Aboriginal children living in remote communities begins in the first 3 months of life following early bacterial colonisation. Young children with persistent signs of suppurative disease (bulging of the tympanic membrane or middle ear discharge) are probably most at risk of developing chronic suppurative otitis media.
Publisher: Elsevier BV
Date: 03-2007
DOI: 10.1016/J.VACCINE.2006.09.005
Abstract: PneuMum is a randomised controlled maternal vaccination trial, using 23-valent Pneumococcal Polysaccharide Vaccine (23vPPV) during the third trimester or at delivery compared to vaccination at 7 months post delivery. The primary outcomes are infant middle ear disease and nasopharyngeal pneumococcal carriage at 7 months of age. PneuMum is the first vaccine trial to be conducted among Indigenous people in the Northern Territory. We describe the study design and the approach taken to develop the PneuMum message in collaboration with key Indigenous stakeholders and then to communicate the PneuMum message with Indigenous communities and potential participants. We hope that these methods will provide a model for future research involving Indigenous communities to ensure Indigenous involvement in research and ultimate improvements in Indigenous health.
Publisher: Elsevier BV
Date: 09-2011
DOI: 10.1016/J.MIMET.2011.06.016
Abstract: Nasopharyngeal carriage studies are needed to monitor changes in important bacterial pathogens in response to vaccination and antibiotics. The ability to store original specimens frozen in skim milk tryptone glucose glycerol broth (STGGB) allows additional studies to be conducted without the need for further expensive field collection. Although sub-cultured isolates remain viable in this medium for many years, limited data are available to indicate viability of relatively low numbers of organisms present in nasopharyngeal specimens stored frozen over long periods of time. We conducted several studies whereby swabs stored in STGGB at -70°C for up to 12 years were thawed and aliquots cultured. Recovery of Streptococcus pneumoniae (72% positive from 269 swabs), Haemophilus influenzae (62% from 214) and Moraxella catarrhalis (81% from 162) was not significantly different from the original cultures: 69% (Risk Difference [RD] 3.0, 95% Confidence Interval [CI] -4.7, 10.7), 66% (RD -4.7, 95% CI -13.8, 4.4) and 78% (RD 3.1, 95% CI -5.7, 11.9) positive respectively. There was no trend in recovery from swabs stored for increasing lengths of time. We conclude that studies which rely on the viability of these respiratory pathogens can be conducted using original swabs stored at -70°C for at least 12 years.
Publisher: Springer Science and Business Media LLC
Date: 03-10-2012
Publisher: Informa UK Limited
Date: 04-2009
DOI: 10.4161/HV.5.4.7050
Publisher: BMJ
Date: 12-2021
DOI: 10.1136/BMJOPEN-2021-050839
Abstract: To better understand how to undertake valuable, ethical and sustainable randomised controlled clinical trial (RCT) research within Aboriginal and Torres Strait Islander primary health services. In a qualitative approach, we utilised data collected between 2013 and 2020 during the planning and implementation of two RCTs. The data comprised agreed records of research meetings, and semistructured interviews with clinical trial stakeholders. The stakeholders were parents/carers of child participants, and site-based research officers, healthcare providers and community advisory groups. Our thematic analysis was informed by constructivist grounded theory. The RCTs investigated the management of otitis media in Aboriginal and Torres Strait Islander children, with the first RCT commencing recruitment in 2014 and the second in 2017. They took place in Aboriginal Medical Services (AMSs), large primary health services for Aboriginal and Torres Strait Islander people, based in urban and regional communities across two Australian states and one territory. We analysed data from 56 meetings and 67 interviews, generating themes on making research valuable and undertaking ethical and sustainable RCTs. Aboriginal and Torres Strait Islander leadership, and support of AMSs in their service delivery function were critical. The broad benefits of the trials were considered important to sustainability, including workforce development, enhanced ear healthcare and multidirectional research capacity building. Participants emphasised the long-term responsibility of research teams to deliver benefits to AMSs and communities regardless of RCT outcomes, and to focus on relationships, reciprocity and creating positive experiences of research. We identify principles and strategies to assist in undertaking ethical and sustainable RCTs within Aboriginal and Torres Strait Islander primary health services. Maintaining relationships with AMSs and focusing on mutual workforce development and capacity building creates opportunities for long-term benefits so that health research and RCTs work for Aboriginal and Torres Strait Islander peoples, services, communities and researchers. ACTRN12613001068752 (Pre-results) ACTRN12617001652369 (Pre-results).
Publisher: Oxford University Press (OUP)
Date: 03-1997
Abstract: In February 1995, single-dose azithromycin was given to children with trachoma and their household contacts who were children. For children with trachoma, rates of carriage of pneumococci immediately before treatment with azithromycin and 2-3 weeks, 2 months, and 6 months after treatment were 68% (54 of 79), 29% (11 of 38), 78% (29 of 37), and 87% (34 of 39), respectively. The proportion of carriage-positive children with azithromycin-resistant Streptococcus pneumoniae strains was 1 of 54 (1.9%) before treatment and then 6 of 11 (54.5%), 10 of 29 (34.5%), and 2 of 34 (5.9%) at follow-up visits. The profile of pneumococcal serotypes changed after azithromycin treatment. Azithromycin-resistant strains (serotypes 10F, 23A, and 45) were isolated from 1 (1.3%) of 79 pretreatment swab specimens, from 16 (21.3%) of 75 swab specimens collected up to 2 months after treatment, and from 2 (6%) of 32 obtained 6 months after treatment. Mathematical modeling showed a more rapid appearance of azithromycin-resistant pneumococcal strains in previously colonized children than in previously noncolonized children. Thus, it appears that the selective effect of azithromycin allowed the growth and transmission of preexisting azithromycin-resistant strains. More research is needed to clarify the clinical relevance and implications of azithromycin use.
Publisher: Springer Science and Business Media LLC
Date: 07-10-2020
DOI: 10.1186/S12889-020-09620-6
Abstract: The prevalence of otitis media (OM) and related hearing loss has remained persistently high among some groups of Australian Aboriginal children who are also reported to have poor academic outcomes. The general literature remains inconclusive about the association between OM-related hearing loss and academic performance in primary school. This study aimed to investigate this association in Aboriginal children living in the Northern Territory (NT) of Australia. A retrospective, observational cohort study was conducted for 2208 NT Aboriginal children, aged about 8 years, living in remote and very remote communities. The explanatory variable was audiometrically determined hearing level as recorded in the Remote Hearing Assessment dataset. The outcome variable consisted of scale scores in the five domains of the National Assessment Program – Literacy and Numeracy (NAPLAN) for Year 3. Other linked datasets used in the study included school attendance records, perinatal records and community level information on relative remoteness, socioeconomic disadvantage and housing crowdedness. Fixed effects linear regression models were used for statistical analyses. Compared with children with normal hearing and after controlling for a range of covariates, children with mild hearing impairment (HI) scored lower in Writing and Spelling by 15.0 points (95% CI: − 22.4 to − 7.6, p 0.0005) and 5.0 points (95% CI: − 9.6 to − 0.3, p = 0.037), equivalent to 7.3 and 2.1% of the mean score, respectively. Children with moderate or worse HI scored lower in Writing and Numeracy by 13.4 points (95% CI, − 24.8 to − 1.9, p = 0.022) and 15.2 points (95% CI, − 27.6 to − 2.7, p = 0.017), both equivalent to 6.3% of the mean score the respective domain. Other factors associated with poorer NAPLAN results included being male, lower Year 2 school attendance, low birthweight, average household size 5 persons, living in a very remote community and speaking English as a second language. OM-related HI was independently associated with poorer early year academic achievement in Aboriginal children living in remote NT communities. Interventions to improve academic outcomes for Aboriginal children must incorporate actions to address the negative impact associated with HI through early detection, effective treatment and ongoing support for affected children.
Publisher: Springer Science and Business Media LLC
Date: 31-10-2023
Publisher: Oxford University Press (OUP)
Date: 25-08-2018
Publisher: Oxford University Press (OUP)
Date: 07-1989
Abstract: Enteropathogenic Escherichia coli (EPEC) expresses a type III secretion system (T3SS) required for pathogenesis. Regulation of the genes encoding the T3SS is complex two major regulators control transcription, the silencer H-NS, and the related H-NS-like protein Ler. Our laboratory is interested in understanding the molecular differences that distinguish the anti-silencer Ler from H-NS, and how Ler differentially regulates EPEC virulence genes. Here, we demonstrate that mutated Ler proteins either containing H-NS alpha-helices 1 and 2, missing from Ler, or truncated for the 11 aa C-terminal extension compared with the related H-NS protein, did not appreciably alter Ler function. In contrast, mutating the proline at position 92 of Ler, in the conserved C-terminal DNA binding motif, eliminated Ler activity. Inserting 11 H-NS-specific amino acids, 11 alanines or 6 alanines into the Ler linker severely impaired the ability of Ler to increase LEE5 transcription. To extend our analysis, we constructed six chimeric proteins containing the N terminus, linker region or C terminus of Ler in different combinations with the complementary domains of H-NS, and monitored their in vivo activities. Replacing the Ler linker domain with that of H-NS, or replacing the Ler C-terminal, DNA binding domain with that of H-NS eliminated the ability of Ler to increase transcription at the LEE5 promoter. Thus, the linker and C-terminal domains of Ler and H-NS are not functionally equivalent. Conversely, replacing the H-NS linker region with that of Ler caused increased transcription at LEE5 in a strain deleted for hns. In summary, the interdomain linker specific to Ler is necessary for anti-silencing activity in EPEC.
Publisher: International Global Health Society
Date: 30-05-2022
Publisher: Elsevier BV
Date: 12-2010
DOI: 10.1016/J.JPEDS.2010.06.002
Abstract: To test the hypothesis that bacterial density, strain ersity, and concordance of pathogens between upper and lower airways are higher in children with bronchiectasis than in those with non-bronchiectatic conditions. Nasopharyngeal (NP) swabs and bronchoalveolar lavage (BAL) fluid were cultured from 45 Indigenous children with bronchiectasis and 30 non-Indigenous children with non-bronchiectatic respiratory symptoms. Lower airway infection was defined as >10(4) colony-forming units of respiratory bacteria/mL of BAL fluid. Concordance was determined by phenotype or genotype. NP carriage of Streptococcus pneumoniae, nontypable Haemophilus influenzae (NTHi), and Moraxella catarrhalis, and lower airway infection by NTHi (47% vs 3%), were detected significantly more often in the children with bronchiectasis than in those without this condition. BAL specimens from the infected Indigenous children also showed greater strain ersity (71% vs 0%). Strain concordance in NP and BAL cultures was high in both infected subgroups. The high density and ersity of respiratory bacteria, along with strain concordance between upper and lower airways, found in Indigenous children with bronchiectasis suggest a possible pathogenic role of recurrent aspiration of NP secretions.
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.VACCINE.2019.05.079
Abstract: Nontypeable Haemophilus influenzae (NTHi) is one of the main respiratory pathogens associated with otitis media and lung infections in Australian Indigenous children. PHiD-CV10, the 10-valent pneumococcal conjugate vaccine containing H. influenzae protein D was used in the Northern Territory infant vaccination schedule for two years from October 2009. NTHi isolates from nasopharyngeal and ear discharge s les collected before, during and after the PHiD-CV10 era were screened for the hpd gene by PCR. Target licon sequence, extracted from available genomic sequence data, was analysed to identify variability in this region. There was no statistically significant difference in the proportion of hpd#3-PCR negative isolates from each era overall 7% and 6% of nasopharyngeal and ear discharge isolates were negative, respectively. The nucleotide sequence data supported the hpd-PCR findings truncations of the hpd gene precluding lification and presumably expression of protein D were observed in approximately 7% of available genomes. In the Northern Territory of Australia, a population at high risk of NTHi-associated infection, PHiD-CV10 use did not select for hpd-PCR negative isolates.
Publisher: Oxford University Press (OUP)
Date: 10-2010
DOI: 10.1086/656190
Abstract: The RTS,S/AS01(E) malaria candidate vaccine is being developed for immunization of African infants through the Expanded Program of Immunization (EPI). This phase 2, randomized, open, controlled trial conducted in Ghana, Tanzania, and Gabon evaluated the safety and immunogenicity of RTS,S/AS01(E) when coadministered with EPI vaccines. Five hundred eleven infants were randomized to receive RTS,S/AS01(E) at 0, 1, and 2 months (in 3 doses with diphtheria, tetanus, and whole-cell pertussis conjugate [DTPw] hepatitis B [HepB] Haemophilus influenzae type b [Hib] and oral polio vaccine [OPV]), RTS,S/AS01(E) at 0, 1, and 7 months (2 doses with DTPwHepB/Hib+OPV and 1 dose with measles and yellow fever), or EPI vaccines only. The occurrences of serious adverse events were balanced across groups none were vaccine-related. One child from the control group died. Mild to moderate fever and diaper dermatitis occurred more frequently in the RTS,S/AS01(E) coadministration groups. RTS,S/AS01(E) generated high anti-circumsporozoite protein and anti-hepatitis B surface antigen antibody levels. Regarding EPI vaccine responses upon coadministration when considering both immunization schedules, despite a tendency toward lower geometric mean titers to some EPI antigens, predefined noninferiority criteria were met for all EPI antigens except for polio 3 when EPI vaccines were given with RTS,S/AS01(E) at 0, 1, and 2 months. However, when antibody levels at screening were taken into account, the rates of response to polio 3 antigens were comparable between groups. RTS,S/AS01(E) integrated in the EPI showed a favorable safety and immunogenicity evaluation. Trial registration. ClinicalTrials.gov identifier: NCT00436007 . GlaxoSmithKline study ID number: 106369 (Malaria-050).
Publisher: Springer Science and Business Media LLC
Date: 02-06-2008
Publisher: AMPCo
Date: 10-2003
Publisher: Elsevier BV
Date: 09-2022
Publisher: Springer Science and Business Media LLC
Date: 06-04-2020
DOI: 10.1186/S12889-020-8456-8
Abstract: International studies provide evidence of an association between child disabilities, including hearing impairment (HI), and child maltreatment. There are high prevalences of ear disease with associated HI, and child maltreatment among Australian Aboriginal children, but the link between HI and child maltreatment is unknown. This study investigates the association between HI and child maltreatment for Aboriginal children living in the Northern Territory (NT) of Australia. This was a retrospective cohort study of 3895 Aboriginal school-aged children (born between 1999 and 2008) living in remote NT communities. The study used linked in idual-level information from health, education and child protection services. The outcome variables were child maltreatment notifications and substantiations. The key explanatory variable, HI, was based on audiometric assessment. The Kaplan–Meier estimator method was used in univariate analysis Cox proportional hazards regression was used in multivariable analysis. A majority of the study cohort lived in very remote (94.5%) and most disadvantaged (93.1%) regions. Among all children in the study cohort, 56.1% had a record of either HI or unilateral hearing loss (UHL), and for those with a history of contact with child protection services ( n = 2757), 56.7% had a record of HI/UHL ( n = 1564). In the 1999–2003 birth cohort, by age 12 years, 53.5% of children with a record of moderate or worse HI had at least one maltreatment notification, compared to 47.3% of children with normal hearing. In the 2004–2008 cohort, the corresponding results were 83.4 and 71.7% respectively. In multivariable analysis, using the full cohort, children with moderate or worse HI had higher risk of any child maltreatment notification (adjusted Hazard Ratios (adjHR): 1.16, 95% CI:1.04–1.30), notification for neglect (adjHR:1.17, 95% CI:1.04–1.31) and substantiation (adjHR:1.20, 95% CI:1.04–1.40), than children with normal hearing. In the 2004–2008 birth cohort, children with moderate or worse HI had higher risk of a substantiated episode of physical abuse (adjHR:1.47, 95% CI:1.07–2.03) than children with normal hearing. Our findings demonstrate the urgent need for HI and child maltreatment prevention strategies through raised community awareness and inter-agency collaboration. Effective information-sharing between service providers is a critical first step to a public health approach in child protection.
Publisher: Springer Science and Business Media LLC
Date: 18-08-2016
Publisher: Wiley
Date: 12-2001
DOI: 10.1046/J.1440-1754.2001.00729.X
Abstract: Australian Aboriginal children experience the highest rates of bacterial respiratory diseases reported in the literature. Neonatal acquisition of multiple bacterial pathogenic species and strains predicts persistent and severe disease throughout childhood, particularly infective ear disease. The dynamics of bacterial nasopharyngeal colonization and transmission are poorly understood. The importance of host factors, bacterial competition and co-operation in the transition from asymptomatic carriage to disease are also uncertain. Treatment outcomes are poor, possibly due to the high density of bacterial infection following early age exposure, poor compliance and increasing levels of antibiotic resistance. The relationship between antibiotic use, clinical outcomes and bacterial resistance needs to be better understood in high-risk populations if the benefits associated with treatment are to be maximized. While there is an urgent need for vaccines, the early age of infection and the high rates of transmission and bacterial antigenic ersity mean these may also be less effective than predicted from studies in low-risk populations.
Publisher: American Society for Microbiology
Date: 06-2009
DOI: 10.1128/JCM.00046-09
Publisher: Springer Science and Business Media LLC
Date: 10-05-2006
Abstract: Nasal colonisation with otitis media (OM) pathogens, particularly Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis , is a precursor to the onset of OM. Many children experience asymptomatic nasal carriage of these pathogens whereas others will progress to otitis media with effusion (OME) or suppurative OM. We observed a disparity in the prevalence of suppurative OM between Aboriginal children living in remote communities and non-Aboriginal children attending child-care centres up to 60% and %, respectively. This could not be explained by the less dramatic difference in rates of carriage of respiratory bacterial pathogens (80% vs 50%, respectively). In this study, we measured nasal bacterial load to help explain the different propensity for suppurative OM in these two populations. Quantitative measures (colony counts and real-time quantitative PCR) of the respiratory pathogens S. pneumoniae, H. influenzae and M. catarrhalis , and total bacterial load were analysed in nasal swabs from Aboriginal children from remote communities, and non-Aboriginal children attending urban child-care centres. In both populations nearly all swabs were positive for at least one of these respiratory pathogens. Using either quantification method, positive correlations between bacterial load and ear state (no OM, OME, or suppurative OM) were observed. This relationship held for single and combined bacterial respiratory pathogens, total bacterial load, and the proportion of respiratory pathogens to total bacterial load. Comparison of Aboriginal and non-Aboriginal children, all with a diagnosis of OME, demonstrated significantly higher loads of S. pneumoniae and M. catarrhalis in the Aboriginal group. The increased bacterial load despite similar clinical condition may predict persistence of middle ear effusions and progression to suppurative OM in the Aboriginal population. Our data also demonstrated the presence of PCR-detectable non-cultivable respiratory pathogens in 36% of nasal swabs. This may have implications for the pathogenesis of OM including persistence of infection despite aggressive therapies. Nasal bacterial load was significantly higher among Aboriginal children and may explain their increased risk of suppurative OM. It was also positively correlated with ear state. We believe that a reduction in bacterial load in high-risk populations may be required before dramatic reductions in OM can be achieved.
Publisher: BMJ
Date: 07-2003
DOI: 10.1136/EBM.8.4.111
Publisher: Wiley
Date: 11-2009
DOI: 10.5694/J.1326-5377.2009.TB02932.X
Abstract: Otitis media affects nearly all children worldwide. Despite an enormous amount of research, our understanding of this common condition continues to be challenged. New pathogens involved in otitis media are still being identified. The importance of interactions between viral and bacterial infection and the role of new vaccines need to be clarified. The proposal that bacteria can become more resistant to therapy through biofilm formation and intracellular infection could have important implications for treatment. The most important clinical research findings have been summarised in systematic reviews. In developed countries, research supporting "watchful waiting" of otitis media with effusion and acute otitis media have had most impact on evidence-based clinical practice guidelines. Indigenous Australian children remain at risk of more severe otitis media. Research programs targeting this population have been well supported. Unfortunately, interventions that can dramatically improve outcomes have remained elusive. For children at high risk of otitis media, health care services should concentrate on accurate diagnosis, antibiotic treatment of suppurative infections, and scheduled follow-up of affected children. Despite the lack of recent studies, strategies to minimise the impact the hearing loss associated with otitis media are important. Improvements in education, hygiene practices, and living conditions are likely to reduce the incidence and severity of otitis media. Studies of these types of interventions are needed.
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.
Publisher: Springer Science and Business Media LLC
Date: 30-10-2019
DOI: 10.1186/S40352-019-0097-6
Abstract: High prevalence of chronic middle ear disease has persisted in Australian Aboriginal children, and the related hearing impairment (HI) has been implicated in a range of social outcomes. This study investigated the association between HI in early childhood and youth offending. This was a retrospective cohort study of 1533 Aboriginal children (born between 1996 and 2001) living in remote Northern Territory communities. The study used linked in idual-level information from health, education, child protection and youth justice services. The outcome variable was a youth being “found guilty of an offence”. The key explanatory variable, hearing impairment, was based on audiometric assessment. Other variables were: child maltreatment notifications, Year 7 school enrolment by mother, Year 7 school attendance and community ‘fixed- effects’. The Cox proportional hazards model was used to estimate the association between HI and youth offending and the Royston R 2 measure to estimate the separate contributions of risk factors to youth offending. The proportion of hearing loss was high in children with records of offence (boys: 55.6%, girls: 36.7%) and those without (boys: 46.1% girls: 49.0%). In univariate analysis, a higher risk of offending was found among boys with moderate or worse HI (HR: 1.77 [95% CI: 1.05–2.98]) and mild HI (HR: 1.54 [95% CI:1.06–2.23]). This association was attenuated in multivariable analysis (moderate HI, HR: 1.43 [95% CI:0.78–2.62] mild HI, HR: 1.37 [95% CI: 0.83–2.26]). No evidence for an association was found in girls. HI contributed 3.2% and 6.5% of variation in offending among boys and girls respectively. Factors contributing greater variance included: community ‘fixed-effects’ (boys: 14.6%, girls: 36.5%), child maltreatment notification (boys: 14.2%, girls: 23.9%) and year 7 school attendance (boys: 7.9% girls 12.1%). Enrolment by mother explained substantial variation for girls (25.4%) but not boys (0.2%). There was evidence, in univariate analysis, for an association between HI and youth offending for boys however this association was not evident after controlling for other factors. Our findings highlight a range of risk factors that underpin the pathway to youth-offending, demonstrating the urgent need for interagency collaboration to meet the complex needs of vulnerable children in the Northern Territory.
Publisher: Elsevier BV
Date: 03-2020
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.
Publisher: American Society for Microbiology
Date: 12-2007
DOI: 10.1128/JCM.01213-07
Publisher: American Society for Microbiology
Date: 02-2009
DOI: 10.1128/CVI.00283-08
Abstract: Seven-valent pneumococcal conjugate vaccination commenced in 2001 for Australian indigenous infants. Pneumococcal carriage surveillance detected substantial replacement with nonvaccine serotypes and a cluster of serotype 1 carriage. Our aim was to review Streptococcus pneumoniae serotype 1 carriage and invasive pneumococcal disease (IPD) data for this population and to analyze serotype 1 isolates. Carriage data were collected between 1992 and 2004 in the Darwin region, one of the five regions in the Northern Territory. Carriage data were also collected in 2003 and 2005 from four regions in the Northern Territory. Twenty-six cases of serotype 1 IPD were reported from 1994 to 2007 in the Northern Territory. Forty-four isolates were analyzed by BOX typing and 11 by multilocus sequence typing. In the Darwin region, 26 children were reported carrying serotype 1 (ST227) in 2002 but not during later surveillance. Scattered cases of serotype 1 carriage were noted in two other regions. Cocolonization of serotype 1 with other pneumococcal serotypes was common (34% serotype 1-positive swabs). In conclusion, pneumococcal carriage studies detected intermittent serotype 1 carriage and an ST227 cluster in children in indigenous communities in the Northern Territory of Australia. There was no apparent increase in serotype 1 IPD during this time. The rate of serotype 1 cocolonization with other pneumococcal serotypes suggests that carriage of this serotype may be underestimated.
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.MIMET.2012.12.013
Abstract: Correlation was observed between quantitative PCR and semi-quantitative culture for definition of Haemophilus influenzae infection in bronchoalveolar lavage specimens from 81 children with bronchiectasis. However, qPCR data correlated less well with airway neutrophilia, and supports continued use of culture as the gold standard for defining H. influenzae lower airway infection.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2008
Publisher: Elsevier BV
Date: 04-2021
Publisher: Springer Science and Business Media LLC
Date: 2008
Publisher: Springer Science and Business Media LLC
Date: 20-07-2005
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.MIMET.2018.12.013
Abstract: This study compared flocked (nylon) swabs and (non-flocked) rayon swabs for the detection of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in nasopharyngeal s les from 20 enrolled Indigenous children under the age of 6 years living in remote Australian Aboriginal communities, and determined which swab the child or parent perceived to be more comfortable. There was no evidence of a significant difference between flocked and rayon swabs in the recovery of common respiratory bacteria. Rayon swabs detected presence of S. pneumoniae (90% cf. 74%, p = 0.375), H. influenzae (79% cf. 74%, p = 1.00) and M. catarrhalis (79% cf. 74%, p = 1.00) at higher rates than the flocked swabs. Analysis of semi-quantitative growth scores also showed no significant differences in either the ranked distributions or medians. Rayon swabs median semi-quantitative growth scores were higher for S. pneumoniae (4 [IQR 1-5] cf. 3 [IQR 0-6], p = 0.699), and H. influenzae (2 [IQR1-5] cf. 1 [IQR0-5], p = 0.946). Sixty percent of participants preferred s les to be taken with flocked swabs. This study demonstrates that microbiological outcomes are not compromised when using flocked or rayon swabs in respiratory bacterial carriage studies in this population. Therefore, cost, methodological consistency across studies, and participant preference can be considered when choosing swab type.
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 .
Publisher: Elsevier BV
Date: 10-2007
Publisher: AMPCo
Date: 28-02-2021
DOI: 10.5694/MJA2.50953
Publisher: Wiley
Date: 18-09-2017
DOI: 10.1002/PPUL.23828
Abstract: Streptococcus pneumoniae (pneumococcus) is the main cause of bacterial pneumonia worldwide and has been studied extensively in this context. However, its role in chronic endobronchial infections and accompanying lower airway neutrophilic infiltration has received little attention. Severe and recurrent pneumonia are risk factors for chronic suppurative lung disease (CSLD) and bronchiectasis the latter causes considerable morbidity and, in some populations, premature death in children and adults. Protracted bacterial bronchitis (PBB) is another chronic endobronchial infection associated with substantial morbidity. In some children, PBB may progress to bronchiectasis. Although nontypeable Haemophilus influenzae is the main pathogen in PBB, CSLD and bronchiectasis, pneumococci are isolated commonly from the lower airways of children with these diagnoses. Here we review what is known currently about pneumococci in PBB, CSLD and bronchiectasis, including the importance of pneumococcal nasopharyngeal colonization and how persistence in the lower airways may contribute to the pathogenesis of these chronic pulmonary disorders. Antibiotic treatments, particularly long-term azithromycin therapy, are discussed together with antibiotic resistance and the impact of pneumococcal conjugate vaccines. Important areas requiring further investigation are identified, including immune responses associated with pneumococcal lower airway infection, alone and in combination with other respiratory pathogens, and microarray serotyping to improve detection of carriage and infection by multiple serotypes. Genome wide association studies of pneumococci from the upper and lower airways will help identify virulence and resistance determinants, including potential therapeutic targets and vaccine antigens to treat and prevent endobronchial infections. Much work is needed, but the benefits will be substantial.
Publisher: Springer Science and Business Media LLC
Date: 03-09-2013
Publisher: BMJ
Date: 08-2023
DOI: 10.1136/BMJRESP-2023-001646
Abstract: Globally, acute respiratory infections (ARIs) are a leading cause of childhood morbidity and mortality. While ARI-related mortality is low in Australia, First Nations infants are hospitalised with ARIs up to nine times more often than their non-First Nations counterparts. The gap is widest in the Northern Territory (NT) where rates of both acute and chronic respiratory infection are among the highest reported in the world. Vitamin D deficiency is common among NT First Nations neonates and associated with an increased risk of ARI hospitalisation. We hypothesise that perinatal vitamin D supplementation will reduce the risk of ARI in the first year of life. ‘D-Kids’ is a parallel (1:1), double-blind (allocation concealed), randomised placebo-controlled trial conducted among NT First Nations mother–infant pairs. Pregnant women and their babies (n=314) receive either vitamin D or placebo. Women receive 14 000 IU/week or placebo from 28 to 34 weeks gestation until birth and babies receive 4200 IU/week or placebo from birth until age 4 months. The primary outcome is the incidence of ARI episodes receiving medical attention in the first year of life. Secondary outcomes include circulating vitamin D level and nasal pathogen prevalence. Tertiary outcomes include infant immune cell phenotypes and challenge responses. Blood, nasal swabs, breast milk and saliva are collected longitudinally across four study visits: enrolment, birth, infant age 4 and 12 months. The s le size provides 90% power to detect a 27.5% relative reduction in new ARI episodes between groups. This trial is approved by the NT Human Research Ethics Committee (2018-3160). Study outcomes will be disseminated to participant families, communities, local policy-makers, the broader research and clinical community via written and oral reports, education workshops, peer-reviewed journals, national and international conferences. ACTRN12618001174279.
Publisher: Informa UK Limited
Date: 12-2011
Abstract: Prior to progression to Clinical Development Phase III, GlaxoSmithKline Biologicals performed a pooled analysis of phase two safety data following administration of 8860 doses of RTS,S/AS to 2981 children under 5 years old. RTS,S/AS was associated with increased rates of non-serious URTI, rash and diaper dermatitis graded mild or moderate. There was no significant increased rate of overall or single SAEs. Two episodes of simple febrile seizure were estimated to be related to vaccination. Significant decreased relative risks of death, any SAE, any SAE excluding malaria and pneumonia were observed. The results suggest a favourable risk-benefit balance which is to be confirmed in the ongoing Phase III trials.
Publisher: Wiley
Date: 27-03-2013
Abstract: To update progress on the effectiveness of vaccine for prevention of acute otitis media (AOM) and identification of promising candidate antigens against Streptococcus pneumoniae , nontypeable Haemophilus influenzae , and Moraxella catarrhalis . Literature searches were performed in OvidSP and PubMed restricted to articles published between June 2007 and September 2011. Search terms included otitis media, vaccines, vaccine antigens , and each of the otitis pathogens and candidate antigens identified in the ninth conference report. The current report provides further evidence for the effectiveness of pneumococcal conjugate vaccines (PCVs) in the prevention of otitis media. Observational studies demonstrate a greater decline in AOM episodes than reported in clinical efficacy trials. Unmet challenges include extending protection to additional serotypes and additional pathogens, the need to prevent early episodes, the development of correlates of protection for protein antigens, and the need to define where an otitis media vaccine strategy fits with priorities for child health. Acute otitis media continues to be a burden on children and families, especially those who suffer from frequent recurrences. The 7‐valent PCV (PCV7) has reduced the burden of disease as well as shifted the pneumococcal serotypes and the distribution of otopathogens currently reported in children with AOM. Antibiotic resistance remains an ongoing challenge. Multiple candidate antigens have demonstrated the necessary requirements of conservation, surface exposure, immunogenicity, and protection in animal models. Further research on the role of each antigen in pathogenesis, in the development of correlates of protection in animal models, and in new adjuvants to elicit responses in the youngest infants is likely to be productive and permit more antigens to move into human clinical trials.
Publisher: Frontiers Media SA
Date: 13-02-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2014
Publisher: Public Library of Science (PLoS)
Date: 05-08-2013
Publisher: Springer Science and Business Media LLC
Date: 14-04-2022
DOI: 10.1186/S13063-022-06145-8
Abstract: Otitis media with effusion (OME) is common and occurs at disproportionately higher rates among Indigenous children. Left untreated, OME can negatively affect language, development, learning, and health and wellbeing throughout the life-course. Currently, OME care includes observation for 3 months followed by consideration of surgical ventilation tube insertion. The use of a non-invasive, low-cost nasal balloon autoinflation device has been found beneficial in other populations but has not been investigated among Aboriginal and Torres Strait Islander children. This multi-centre, open-label, randomised controlled trial will determine the effectiveness of nasal balloon autoinflation compared to no nasal balloon autoinflation, for the treatment of OME among Aboriginal and Torres Strait Islander children in Australia. Children aged 3–16 years with unilateral or bilateral OME are being recruited from Aboriginal Health Services and the community. The primary outcome is the proportion of children showing tympanometric improvement of OME at 1 month. Improvement is defined as a change from bilateral type B tympanograms to at least one type A or C1 tympanogram, or from unilateral type B tympanogram to type A or C1 tympanogram in the index ear, without deterioration (type A or C1 to type C2, C3, or B tympanogram) in the contralateral ear. A s le size of 340 children (170 in each group) at 1 month will detect an absolute difference of 15% between groups with 80% power at 5% significance. Anticipating a 15% loss to follow-up, 400 children will be randomised. The primary analysis will be by intention to treat. Secondary outcomes include tympanometric changes at 3 and 6 months, hearing at 3 months, ear health-related quality of life (OMQ-14), and cost-effectiveness. A process evaluation including perspectives of parents or carers, health care providers, and researchers on trial implementation will also be undertaken. INFLATE will answer the important clinical question of whether nasal balloon autoinflation is an effective and acceptable treatment for Aboriginal and Torres Strait Islander children with OME. INFLATE will help fill the evidence gap for safe, low-cost, accessible OME therapies. Australia New Zealand Clinical Trials Registry ACTRN12617001652369 . Registered on 22 December 2017. The Australia New Zealand Clinical Trials Registry is a primary registry of the WHO ICTRP network and includes all items from the WHO Trial Registration data set. Retrospective registration.
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.
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.VACCINE.2015.12.048
Abstract: Early onset of persistent otitis media is a priority issue for Australian Indigenous populations. The objective is to determine the direct and short-term impact of one, two and three doses of any pneumococcal conjugate vaccine (PCV) formulation on nasopharyngeal (NP) carriage of Streptococcus pneumoniae (Spn) and non-typeable Haemophilus influenzae (NTHi), the otopathogens targeted by current PCVs. We searched MEDLINE (PubMed) and CENTRAL (Cochrane Library) to 29 September 2015. We also scanned reference lists of recent reviews and contacted authors. We included randomised controlled trials (RCTs) with a PCV schedule commencing ≤3 months of age that reported controlled non-cumulative group-specific prevalence data for carriage of Spn or NTHi at age<12 months. We performed a standard risk of bias assessment. We estimated the pooled relative risk (RR) and 95% confidence interval (95%CI) for each vaccine dose on NP carriage by meta-analysis. We included 16 RCTs involving 14,776 participants. The PCVs were conjugated to diphtheria toxin CRM197, diphtheria toxoid, tetanus toxoid or NTHi protein D and varied in valency (4-13). Controls were non-PCVs, placebo or no vaccine. The earliest carriage outcome was from 2 to 9 months of age. Compared to controls, there were no significant differences between one or two doses of PCV on vaccine-type (VT) pneumococcal carriage at ∼4 and ∼6 months respectively. However, VT carriage was significantly lower at ∼7 months RR 0.67 95%CI 0.56-0.81 from 9 studies and 7613 infants and non-vaccine type (NVT) carriage was higher RR 1.23 95%CI 1.09-1.40 from 8 studies and 5861 infants. No impact on overall pneumococcal or NTHi carriage was found. The primary PCV schedule had no significant short-term impact on overall pneumococcal or NTHi NP carriage and a limited impact on VT pneumococcal carriage before the third dose.
Publisher: American Society for Microbiology
Date: 07-2012
DOI: 10.1128/JCM.00566-12
Abstract: A PCR for protein D (hpd#3) was used to differentiate nontypeable Haemophilus influenzae (NTHI) from Haemophilus haemolyticus . While 90% of nasopharyngeal specimens and 100% of lower-airway specimens from 84 Indigenous Australian children with bronchiectasis had phenotypic NTHI isolates confirmed as H. influenzae , only 39% of oropharyngeal specimens with phenotypic NTHI had H. influenzae . The nasopharynx is therefore the preferred site for NTHI colonization studies, and NTHI is confirmed as an important lower-airway pathogen.
Publisher: American Society for Microbiology
Date: 05-2014
DOI: 10.1128/JCM.03448-13
Abstract: Nontypeable Haemophilus influenzae (NTHI) strains are responsible for respiratory-related infections which cause a significant burden of disease in Australian children. We previously identified a disparity in NTHI culture-defined carriage rates between Aboriginal and non-Aboriginal children (42% versus 11%). The aim of this study was to use molecular techniques to accurately determine the true NTHI carriage rates (excluding other culture-identical Haemophilus spp.) and assess whether the NTHI strain ersity correlates with the disparity in NTHI carriage rates. NTHI isolates were cultured from 595 nasopharyngeal aspirates collected longitudinally from asymptomatic Aboriginal ( n = 81) and non-Aboriginal ( n = 76) children aged 0 to 2 years living in the Kalgoorlie-Boulder region, Western Australia. NTHI-specific 16S rRNA gene PCR and PCR ribotyping were conducted on these isolates. Confirmation of NTHI by 16S rRNA gene PCR corrected the NTHI carriage rates from 42% to 36% in Aboriginal children and from 11% to 9% in non-Aboriginal children. A total of 75 different NTHI ribotypes were identified, with 51% unique to Aboriginal children and 13% unique to non-Aboriginal children ( P 0.0001). The strain richness (proportion of different NTHI ribotypes) was similar for Aboriginal (19%, 65/346) and non-Aboriginal children (19%, 37/192) ( P = 0.909). Persistent carriage of the same ribotype was rare in the two groups, but colonization with multiple NTHI strains was more common in Aboriginal children than in non-Aboriginal children. True NTHI carriage was less than that estimated by culture. The Aboriginal children were more likely to carry unique and multiple NTHI strains, which may contribute to the chronicity of NTHI colonization and subsequent disease.
Publisher: Elsevier BV
Date: 12-2019
Abstract: To investigate the association between hearing impairment (HI) and Year 1 school attendance in Aboriginal children in the Northern Territory (NT) of Australia. Observational cohort study (n=3,744) by analysing linked in idual-level information for Aboriginal children from the NT Government school attendance records, NT Perinatal Register and Remote Hearing Assessment dataset, and community level data for relative remoteness, socioeconomic disadvantage and housing crowdedness. Children with unilateral hearing loss, mild HI and moderate or worse HI had significantly lower Year 1 attendance than those with normal hearing, attending 5.6 (95%CI, -9.10 ∼-2.10), 4.0 (95%CI, -7.17 ∼-0.90) and 6.1 (95%CI, -10.71 ∼-1.49) days fewer, respectively. Other variables that yielded significant association were: male gender, having attended preschool less than 20% of available days, speaking English as second language, twin birth and average household size >5. Aboriginal children with any level of HI are likely to have lower school attendance rates in Year 1 than their peers with normal hearing. Implications for public health: In this population, where the prevalence of otitis media and accompanying HI remains extremely high, the early detection and management of hearing loss on entry into primary school should be included in the measures to improve school attendance.
Publisher: Oxford University Press (OUP)
Date: 07-2011
Publisher: American Society for Microbiology
Date: 11-2002
DOI: 10.1128/AAC.46.11.3648-3649.2002
Abstract: This is the first report of in vivo pneumococcal penicillin MIC drift from 4.0 to 16.0 mg/liter, possibly associated with alterations in the pbp1a gene. The case presented here is of an infant with early onset recurrent pneumonia and chronic bronchitis requiring repeated antibiotics.
Publisher: Springer Science and Business Media LLC
Date: 19-02-2009
Publisher: Elsevier BV
Date: 2008
DOI: 10.1016/J.IJPORL.2007.09.012
Abstract: For Indigenous Australian children living in remote communities, onset of otitis media commences within weeks of birth and is associated with early nasopharyngeal colonisation with multiple respiratory bacterial pathogens: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The high prevalence of eardrum perforation and the failure of standard therapies to cure or prevent OM in this population require urgent attention. The objective of this study was to measure the changes in nasopharyngeal bacterial flora between birth and first episode of otitis media. For 10 randomly selected Indigenous children with early onset otitis media, S. pneumoniae, H. influenzae, M. catarrhalis, S. aureus, and total bacterial load were enumerated in serial nasopharyngeal swabs using real-time quantitative PCR. Between 0 and 3 weeks of age, all 10 infants had bilaterally normal ears. At 3-6 weeks of age, seven of eight infants examined had otitis media. By 6-13 weeks of age, all 10 infants had otitis media. The relative density of respiratory pathogens among total nasopharyngeal flora increased significantly with onset of otitis media, and the majority of children became colonised with the three respiratory pathogens. There was no association between OM onset and S. aureus load. Onset of otitis media between 3 and 6 weeks of life was associated with a significant increase in all major bacterial OM pathogens (S. pneumoniae, H. influenzae, M. catarrhalis), as well as total bacterial load in the nasopharynx. Interventions to prevent acquisition of multiple OM pathogens in the first weeks of life are needed.
Publisher: Microbiology Society
Date: 09-1992
DOI: 10.1099/00222615-37-3-176
Abstract: Single specimens of diarrhoeal stool from 676 patients, mostly aboriginals aged less than 5 years, admitted to Alice Springs Hospital, central Australia, for diarrhoea between Sept. 1988 and Feb. 1989, were examined for C ylobacter spp. by culture on a blood-free medium with selective supplement (BFM Oxoid) and blood agar overlaid with a membrane filter (FM). C ylobacter spp. were isolated on either BFM or FM or both from 225 patients. C ylobacter spp. were isolated on BFM alone from 75 patients and on FM alone from 213 patients (p less than 0.001 chi 2 test). Most c ylobacters isolated on BFM were C. jejuni. All C. jejuni subsp. doylei, all "C. upsaliensis" except one, all C. laridis, C. fetus subsp. fetus and several uncharacterised C ylobacter isolates were isolated on FM only. C. jejuni was isolated on BFM but not FM from several patients, and vice versa. Serotyping of C. jejuni and C. coli isolated from both media showed the serotypes recovered from the two media to be different in some patients. In some patients concurrent infection with several species or serotypes (up to five) of C ylobacter, or both, was shown for the first time by the use of FM. We conclude that the use in combination of a selective medium and a non-selective medium with a filtration technique are better than either medium alone for the isolation of C ylobacter spp.
Publisher: Wiley
Date: 18-10-2006
Publisher: Wiley
Date: 05-10-1999
DOI: 10.1046/J.1440-1754.1999.355400.X
Abstract: There is evidence that the rapid rise in Streptococcus pneumoniae (SP) antimicrobial resistance seen in other countries may have commenced in Australia. Streptococcus pneumoniae carriage and resistance levels are described for urban Northern Territory children in day care. A prospective cohort study was conducted of 250 children in nine Darwin day care centres between 24 March and 15 September 1997. Each fortnight nasopharyngeal swabs were collected from children, and parents were interviewed about medications administered. Streptococcus pneumoniae was detected in 52% (1028/1974) of all nasopharyngeal swabs. Streptococcus pneumoniae was isolated from 92% (231/250) of children at some time. Penicillin resistance was found in 30% (312/1028) of isolates using a screening test. Of these, 256 (82%) had resistance confirmed by E-test. Two hundred and one (20% of all isolates) had intermediate penicillin resistance and 55 (5% of all isolates) had high level resistance. Ceftriaxone resistance was found in 19% of children's first isolates. Resistance to other antibiotics was also common: co-trimoxazole 45%, erythromycin 17%, tetracycline 17% and chlor henicol 13%. A total of 17% (172/1028) of the isolates were multiresistant. The average fortnightly proportion of children given antibiotics was 16% (405/2476). Levels of intermediate and high level penicillin resistance in this day care population are consistent with previous data from the Northern Territory, and considerably higher than the rest of Australia. The national trend of increasing pencillin resistance is likely to continue.
Publisher: Springer Science and Business Media LLC
Date: 11-08-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2008
Publisher: BMJ
Date: 16-01-2015
Publisher: Springer Science and Business Media LLC
Date: 08-10-2013
Publisher: Elsevier BV
Date: 10-1999
DOI: 10.1016/S0165-5876(99)00156-1
Abstract: Remote and rural Australian Aboriginal children achieve lower standards of numeracy and literacy than their non-Aboriginal peers. The reasons are complex, but extraordinarily high rates of conductive hearing loss (> 50%) are, in part, responsible for poor classroom success. In addition to the burden of acute bacterial respiratory illness (highest rates of invasive pneumococcal disease in the literature), chronic disease affects virtually every young child. In the Aboriginal community studied, otitis media commenced within 3 months of birth for all infants, progressed to chronic suppurative otitis media in 60% and did not resolve throughout early childhood. Our findings, supported by mathematical modelling, show that the vicious cycle of endemic chronic otitis media is perpetuated by high carriage rates of multiple species and multiple types of respiratory bacterial pathogens, by high cross-infection rates and thus, by early age of pathogen acquisition and prolonged carriage. Long-term damage to respiratory mucosa, possibly linked to later chronic bronchitis and bronchiectasis, follows a constant series of infections by each of the concurrently held pathogens, without periods of recovery. Overcrowding and poor hygiene promote this vicious cycle. Medical and social options for intervention are limited by poor resources, low expectations for health and a complex biology that includes antibiotic resistant pneumococci.
Publisher: CSIRO Publishing
Date: 03-10-2022
DOI: 10.1071/MA22035
Abstract: Where would we be without microbiology in tackling the high prevalence of otitis media (OM middle ear infection) and disabling hearing loss that disadvantage Australian First Nations children living in remote communities? Understanding the microbiology of OM in this population has been critical in directing innovative clinical trials research and developing appropriate evidence-based practice guidelines. While these processes are critical to reducing disadvantage associated with OM and disabling hearing loss, a remaining seemingly insurmountable gap has remained, threatening progress in improving the lives of children with ear and hearing problems. That gap is created by the crisis in primary health care workforce in remote communities. Short stay health professionals and fly-in fly-out specialist services are under-resourced to manage the complex needs of the community, including prevention and treatment of otitis media and hearing loss rehabilitation. Hence the rationale for the Hearing for Learning Initiative – a workforce enhancement model to improve sustainability, cultural appropriateness, and effectiveness of evidence-based ear and hearing health care for young children in remote settings. This paper summarises the role of microbiology in the pathway to the Hearing for Learning Initiative.
Publisher: Springer Science and Business Media LLC
Date: 07-06-2011
Publisher: Wiley
Date: 16-03-2022
DOI: 10.1111/HEX.13476
Abstract: Living with ear disease can have extensive impacts on physical, emotional and social well‐being. This study explored otitis media (OM) and its management from the perspective of caregivers of Aboriginal and Torres Strait Islander children. Semi‐structured interviews were conducted from 2015 to 2020 with caregivers of Aboriginal and Torres Strait Islander children with OM. Thematic analysis of transcripts was undertaken using a constructivist grounded theory approach through the leadership and the cultural lens of an Aboriginal community‐based researcher. Caregivers described OM as having profound impacts on their child's physical, developmental, and emotional well‐being, with long waits for specialist treatment contributing to extra strain on families. Children's well‐being suffered when OM was mistaken for poor behaviour and children were punished, with caregivers subsequently experiencing strong feelings of guilt. Concerns were conveyed about the social implications of having a sick child. The variable nature of OM symptoms meant that caregivers had to monitor closely for sequelae and advocate for appropriate treatment. Success in navigating the diagnosis and treatment of OM can be strongly impacted by the relationship between caregivers and health professionals and the perceived access to respectful, collaborative and informative healthcare. OM may have substantial social and emotional consequences for children and their caregivers. A holistic understanding of the way in which OM impacts multiple facets of health and well‐being, as well as recognition of challenges in accessing proper care and treatment, will aid families managing OM and its sequelae. Governing boards, managers, staff and community members from five Australian Aboriginal Medical Services were involved in the approval, management and conduct of this study and the wider clinical trials. The caregivers of Aboriginal and Torres Strait Islander patients at these services informed the interview study and guided its purpose.
Publisher: American Society for Microbiology
Date: 06-2008
DOI: 10.1128/JCM.00048-08
Abstract: The nasopharynx (NP) is the preferred site for detection of Streptococcus pneumoniae in young children, but NP s ling is not well tolerated. We compared nose blowing with paired nasal swabs. The sensitivity of nose blowing was 46% (95% confidence interval [CI] 38 to 56%), which increased to 94% (95% CI, 85 to 98%) for children with visible secretions.
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.
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.VACCINE.2018.02.054
Abstract: Nontypeable Haemophilus influenzae (NTHi), the most common bacterial lower airway infection in children with protracted bacterial bronchitis, is associated with progression to bronchiectasis. We determined whether vaccination with 10-valent pneumococcal NTHi protein-D conjugate vaccine (PHiD-CV) reduced NTHi lower airway infection compared to children not PHiD-CV-vaccinated. Our unique childhood vaccination schedule and prospective 9-year bronchoalveolar lavage (BAL) collection provided an exclusive opportunity to examine this hypothesis. Paired BAL fluids and nasopharyngeal (NP) swabs were collected from 543 children (2007-2016) undergoing bronchoscopy for chronic cough. Children who received a primary course of ≥2 doses of one pneumococcal conjugate vaccine (PCV) and <2 doses of another PCV were included in each vaccine group. Logistic regression determined associations between NTHi lower airway infection (≥10 Of 262 PCV7-vaccinated, 53 PHiD-CV-vaccinated and 166 PCV13-vaccinated children (62 had mixed schedules, <2 PCV doses or missing vaccination data), NTHi lower airway infection was detected in 89 (34%), 9 (17%) and 47 (28%), respectively. On multivariate regression, significant independent factors associated with reduced NTHi lower airway infection were PHiD-CV vaccination (OR PHiD-CV-vaccinated children were significantly less likely to have NTHi lower airway infection than children not PHiD-CV-vaccinated. PHiD-CV is likely an effective intervention for reducing NTHi endobronchial infection in children at risk of chronic suppurative lung diseases.
Publisher: Frontiers Media SA
Date: 14-04-2022
Abstract: Otitis media (OM) is a common childhood illness, often resolving without intervention and acute and long-term complications are rare. However, Australian Aboriginal and Torres Strait Islander infants and children experience a high burden of OM and are at high risk of complications (tympanic membrane perforation and chronic infections). Bacterial OM is commonly associated with Streptococcus pneumoniae , non-typeable Haemophilus influenzae , and Moraxella catarrhalis . BIGDATA is a data asset combining over 25 years of microbiology and OM surveillance research from the Ear Health Research Program at Menzies School of Health Research (Northern Territory, Australia), including 11 randomized controlled trials, four cohort studies, eight surveys in over 30 remote communities (including data from Western Australia), and five surveys of urban childcare centers including Aboriginal and Torres Strait Islander and non-Indigenous children. Outcome measures include clinical examinations (focusing on OM), antibiotic prescriptions, pneumococcal vaccination, modifiable risk factors such as smoking and household crowding, and nasopharyngeal and ear discharge microbiology including antimicrobial resistance testing. The initial series of projects are planned to address the following key knowledge gaps: (i) otitis media prevalence and severity over pre pneumococcal conjugate vaccines (PCVs) and three eras of increasing PCV valency (ii) impact of increasing valency PCVs on nasopharyngeal carriage dynamics of pneumococcal serotypes, and antimicrobial resistance (iii) impact of increasing valency PCVs on nasopharyngeal carriage dynamics and antimicrobial resistance of other otopathogens and (iv) serotype specific differences between children with acute OM and OM with effusion or without OM. These data will be utilized to identify research gaps, providing evidence-based prioritization for ongoing research. Data asset creation and priority analyses were approved by the Human Research Ethics Committee of Northern Territory Department of Health and Menzies School of Health Research (EC00153, 18-3281), the Child and Adolescent Health Service Human Research Ethics Committee and Western Australian Aboriginal Health Ethics Committee. Dissemination will be through peer review publication and conference presentations.
Publisher: Springer Science and Business Media LLC
Date: 27-07-2019
Publisher: Springer Science and Business Media LLC
Date: 05-09-2016
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.IJANTIMICAG.2012.05.018
Abstract: Indigenous Australian children have increased rates of bronchiectasis. Despite a lack of high-level evidence on effectiveness and antibiotic resistance, these children often receive long-term antibiotics. In this study, we determined the impact of recent macrolide (primarily azithromycin) and β-lactam antibiotic use on nasopharyngeal colonisation, lower airway infection (>10(4) CFU/mL of bronchoalveolar lavage fluid culture) and antibiotic resistance in non-typeable Haemophilus influenzae (NTHi), Streptococcus pneumoniae and Moraxella catarrhalis isolates from 104 Indigenous children with radiographically confirmed bronchiectasis. Recent antibiotic use was associated with significantly reduced nasopharyngeal carriage, especially of S. pneumoniae in 39 children who received macrolides [odds ratio (OR)=0.22, 95% confidence interval (CI) 0.08-0.63] and 26 children who received β-lactams (OR=0.07, 95% CI 0.01-0.32), but had no significant effect on lower airway infection involving any of the three pathogens. Children given macrolides were significantly more likely to carry (OR=4.58, 95% CI 1.14-21.7) and be infected by (OR=8.13, 95% CI 1.47-81.3) azithromycin-resistant S. pneumoniae. Children who received β-lactam antibiotics may be more likely to have lower airway infection with β-lactamase-positive icillin-resistant NTHi (OR=4.40, 95% CI 0.85-23.9). The risk of lower airway infection by antibiotic-resistant pathogens in children receiving antibiotics is of concern. Clinical trials to determine the overall benefit of long-term antibiotic therapy are underway.
Publisher: Springer Science and Business Media LLC
Date: 28-08-2008
Publisher: Wiley
Date: 29-07-2020
DOI: 10.1111/JPC.15044
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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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2014
End Date: 2019
Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
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Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2013
End Date: 2018
Funder: National Health and Medical Research Council
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