ORCID Profile
0000-0003-3690-5023
Current Organisations
University of the Sunshine Coast
,
University of Wollongong
,
Federal Institute of Education, Science and Technology of Ceará
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Publications
Fibronectin-binding protein gene recombination and horizontal transfer between group A and G streptococci
Publisher: American Society for Microbiology
Date: 11-2004
DOI: 10.1128/JCM.42.11.5357-5361.2004
Abstract: We report evidence of interspecies gene transfer between the important virulence factor genes sfbI and gfbA . Because the identified group G streptococcus gfbA types possess DNA cassettes that can be identified in a number of group A streptococcus strains, it appears that homologous recombination is occurring between these species.
M protein conserved region antibodies opsonise multiple strains of Streptococcus pyogenes with sequence variations in C-repeats
Publisher: Elsevier BV
Date: 05-2005
DOI: 10.1016/J.RESMIC.2004.12.009
Abstract: The development of a group A streptococcal (GAS) vaccine has focused on the M protein, a major virulence factor. Antibodies against the amino terminal domain of the M protein are generally protective but only provide type-specific immunity. J14, a 29-mer peptide sequence which contains a conserved epitope from the C-repeat region of the M protein, offers the possibility of a vaccine which will elicit protective opsonic antibodies against multiple GAS strains. In this study we have shown that antibodies raised against J14 are capable of opsonising 37 GAS isolates representing different emm types derived from a region in which GAS infection is endemic. We also demonstrate that J14 antisera is capable of opsonising GAS isolates containing J14 homologues but not J14-specific sequences, further increasing the strain coverage of this vaccine candidate. Isolates with three C-repeats were opsonised more efficiently than isolates with two repeats. Opsonisation of a strain with only a single C-repeat was dramatically lower than other strains tested. The number of C-repeats present in the M protein of in idual isolates therefore appears to be the critical factor in determining bactericidal capacity of J14 antisera. The reduced opsonic capacity of sera against this strain was shown to correlate with a reduced capacity to bind J14 antisera, as demonstrated by immunofluorescence microscopy and FACS analysis. In vivo challenge experiments also confirmed the protective efficacy of immunisation with J14 peptide.
Department of Error
Publisher: Elsevier BV
Date: 09-2017
Securing All intraVenous devices Effectively in hospitalised patients—the SAVE trial: study protocol for a multicentre randomised controlled trial
Publisher: BMJ
Date: 09-2015
Draft Genome Sequence of Roseomonas mucosa Strain AU37, Isolated from a Peripheral Intravenous Catheter
Publisher: American Society for Microbiology
Date: 13-04-2017
Abstract: Roseomonas mucosa is an opportunistic pathogen that causes infections in humans and is often associated with vascular catheter-related bacteremia. Here, we report the draft genome sequence of Roseomonas mucosa strain AU37, isolated from a peripheral intravenous catheter tip.
Molecular markers for discriminating Streptococcus pyogenes and S. dysgalactiae subspecies equisimilis
Publisher: Springer Science and Business Media LLC
Date: 12-03-2010
DOI: 10.1007/S10096-010-0899-X
Abstract: Given the increasing aetiological importance of Streptococcus dysgalactiae subspecies equisimilis in diseases which are primarily attributed to S. pyogenes, molecular markers are essential to distinguish these species and delineate their epidemiology more precisely. Many clinical microbiology laboratories rely on agglutination reactivity and biochemical tests to distinguish them. These methods have limitations which are particularly exacerbated when isolates with mixed properties are encountered. In order to provide additional distinguishing parameters that could be used to unequivocally discriminate these two common pathogens, we assess here three molecular targets: the speB gene, intergenic region upstream of the scpG gene (IRSG) and virPCR. Of these, the former two respectively gave positive and negative results for S. pyogenes, and negative and positive results for S. dysgalactiae subsp. equisimilis. Thus, a concerted use of these nucleic acid-based methods is particularly helpful in epidemiological surveillance to accurately assess the relative contribution of these species to streptococcal infections and diseases.
Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global B
Publisher: Elsevier BV
Date: 11-2018
Erratum: Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016 (The Lancet (2017) 390(10100) (1423–1459) (S014067361732336X) (10.1016/S0140-6736(17)32336-X))
Publisher: Elsevier BV
Date: 10-2017
Complement inhibitors from scabies mites promote streptococcal growth - A novel mechanism in infected epidermis?
Publisher: Public Library of Science (PLoS)
Date: 17-07-2012
Conjugative transfer of ICESde 3396 between three β-hemolytic streptococcal species
Publisher: Springer Science and Business Media LLC
Date: 12-08-2014
Differences among group A streptococcus epidemiological landscapes: Consequences for M protein-based vaccines?
Publisher: Informa UK Limited
Date: 12-2009
DOI: 10.1586/ERV.09.133
Abstract: Group A streptococcus (GAS) is a bacterial pathogen responsible for a wide array of disease pathologies in humans. GAS surface M protein plays multiple key roles in pathogenesis, and serves as a target for typing and vaccine development. In this review, we have compiled GAS epidemiological studies from several countries around the world to highlight the consequences on the theoretical efficacy of two different M protein-based vaccine strategies.
High diversity of group A streptococcal emm types in an Indian community: The need to tailor multivalent vaccines
Publisher: Oxford University Press (OUP)
Date: 2005
DOI: 10.1086/426443
Abstract: Concern about the emergence of antibiotic-resistant strains and about morbidity and/or mortality related to rheumatic fever and rheumatic heart disease has been a continuous impetus for the development of a safe, effective vaccine against group A Streptococcus (GAS). To date, >120 GAS M types are known, as identified by serological typing. In general, serum immunoglobulin G directed to the hypervariable NH2 terminal portion of M protein leads to complement fixation and opsonophagocytosis of the homologous streptococcal serotype by polymorphonuclear leukocytes, and the protection is type specific. The sequence variation at the N terminus ultimately affects the binding of opsonic antibodies. Because of hypervariability in these opsonic sequences from different M types, it was relevant to use epitopes derived from these multiple sequences in a "multivalent vaccine" design for evaluation of protection against these M types of GAS. Thus, any attempts to design vaccines for a given community will require information on N terminal-sequence typing and variation. In the present study, we performed molecular characterization of isolates recovered from patients in northern India--to our knowledge, for the first time--in an attempt to study the circulating M types and their N terminal sequence variability. We report tremendous ersity in GAS strains recovered from symptomatic patients, with implications on the design of appropriate vaccines. Fifty-nine isolates represented 33 different sequence types. Very few novel types and no predominant clones were found. The high ersity of emm types encountered in a single year suggests that any M protein-based multivalent vaccine would have to be specifically tailored for this region.
Dressings and securements for the prevention of peripheral intravenous catheter failure in adults (SAVE): a pragmatic, randomised controlled, superiority trial
Publisher: Elsevier BV
Date: 08-2018
Differences in virulence repertoire and cell invasive potential of Group A Streptococcus emm1-2 in comparison to emm1 genotype
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.IJMM.2014.04.011
Abstract: Group A streptococcus (GAS, Streptococcus pyogenes) type emm1 is widely associated with streptococcal invasive disease. This type is prevalent worldwide but is rare in India. Instead, emm1-2 type which is closely related to emm1 but is a distinct type is more prevalent. Although emm1 has been well characterized, information available on emm1-2 is rare. In this study we present a comparative study of both types. DNA microarray analysis showed segregation of emm1 and emm1-2 isolates into two distinct clusters. Out of 229 arrayed genes, 83-87% were present, 6-9% absent and 4-8% genes were ambiguous in emm1 isolates. emm1-2 strains harboured only 68-77%, 11-13% were absent and 10-20% ambiguous genes. Fourteen genes, present in all emm1, were completely absent in the emm1-2 isolates. sfb1 is a gene which encodes for Streptococcal fibronectin binding adhesin and invasin which has restricted distribution among different emm types of GAS. A variant of sfb1 (sfb1-2) was the only gene which was present in all emm1-2 isolates, but absent from all emm1 strains. Sfb1 and Sfb1-2 differ in sequences in the aromatic domain and the proline rich repeat region, whereas the fibronectin binding region was conserved and exhibited similar fibronectin binding activity. The presence of Sfb1-2 in emm1-2 strains was concomitant with significantly higher fibronectin-binding and invasion efficiency of HEp-2 cells when compared to emm1 isolates. The role of Sfb1-2 in invasion was confirmed by latex bead assay. emm1-2 isolates follow membrane ruffling mechanism during invasion and intracellularly follow classical endocytic pathway. Further studies are required to understand the correlation between the presence of emm1-2 isolates and the disease pattern in North India.
Molecular comparison of bacterial communities on peripheral intravenous catheters and matched skin swabs
Publisher: Public Library of Science (PLoS)
Date: 05-01-2016
Disease burden due to Streptococcus dysgalactiae subsp. equisimilis (group G and C streptococcus) is higher than that due to Streptococcus pyogenes among Mumbai school children
Publisher: Microbiology Society
Date: 02-2010
Abstract: Streptococcus pyogenes [group A streptococcus (GAS)], a human pathogen, and Streptococcus dysgalactiae subsp. equisimilis [human group G and C streptococcus (GGS/GCS)] are evolutionarily related, share the same tissue niche in humans, exchange genetic material, share up to half of their virulence-associated genes and cause a similar spectrum of diseases. Yet, GGS/GCS is often considered as a commensal bacterium and its role in streptococcal disease burden is under-recognized. While reports of the recovery of GGS/GCS from normally sterile sites are increasing, studies describing GGS/GCS throat colonization rates relative to GAS in the same population are very few. This study was carried out in India where the burden of streptococcal diseases, including rheumatic fever and rheumatic heart disease, is high. As part of a surveillance study, throat swabs were taken from 1504 children attending 7 municipal schools in Mumbai, India, during 2006–2008. GAS and GGS/GCS were identified on the basis of β -haemolytic activity, carbohydrate group and PYR test, and were subsequently typed. The GGS/GCS carriage rate (166/1504, 11 %) was eightfold higher than the GAS carriage (22/1504, 1.5 %) rate in this population. The 166 GGS/GCS isolates collected represented 21 different emm types (molecular types), and the 22 GAS isolates represented 15 different emm types. Although the rate of pharyngitis associated with GGS/GCS is marginally lower than with GAS, high rates of throat colonization by GGS/GCS underscore its importance in the pathogenesis of pharyngitis.
Moving forward: A mucosal vaccine against group A streptococcus
Publisher: Informa UK Limited
Date: 06-2009
DOI: 10.1586/ERV.09.33
Abstract: Streptococcus pyogenes, commonly referred to as group A streptococcus (GAS), colonizes the epithelial surfaces of the upper respiratory tract and the skin, where it causes a myriad of diseases that vary in clinical presentation and severity. Several candidate GAS vaccines are now approaching or have entered human clinical trials. However, the preclinical evaluation for the leading vaccine candidates has been premised on their ability to induce systemic protection through parenteral immunization. While systemic immunity has proven effective in preventing GAS dissemination and associated disease, it may not prove to be the optimal approach for inducing mucosal immunity against GAS. With this in mind, many researchers are moving toward testing the efficacy of their GAS vaccine candidate when delivered to the mucosal surface. This review discusses the interaction of GAS with the mucosal immune system and the approaches taken thus far in developing a mucosal GAS vaccine.
Does a Dedicated Lumen for Parenteral Nutrition Administration Reduce the Risk of Catheter-Related Bloodstream Infections? A Systematic Literature Review
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2018
DOI: 10.1097/NAN.0000000000000270
Abstract: Guidelines recommend using single-lumen central vascular access devices (CVADs) for the administration of parenteral nutrition (PN) or lipid-based solutions, or a dedicated lumen on a multilumen CVAD. Publications reviewed by the authors reported comparative rates of catheter-related bloodstream infection (CR-BSI) in patients with CVADs who received PN through a dedicated lumen compared with those who had PN administered through multilumen CVADs. Two studies included 650 patients with 1349 CVADs. CR-BSIs were equally distributed between the 2 groups. Both studies were poorly reported and had significant risk of bias. These results should be interpreted with caution.
Comparative in silico analysis of two vaccine candidates for group A streptococcus predicts that they both may have similar safety profiles
Publisher: Elsevier BV
Date: 05-2007
DOI: 10.1016/J.VACCINE.2007.01.079
Abstract: Concerns of immune cross-reactivity, between epitopes of the group A streptococcal (GAS) M-proteins and host proteins have hindered the progress of an effective GAS vaccine. An ideal M-protein based subunit vaccine should not elicit heart tissue cross-reactive antibody responses and should not activate M-protein specific CD4+ T-cells. In the current study we used a bioinformatic and immunoinformatic approach to assess the safety of J8 and J14, chimeric vaccine constructs containing a GAS derived M-protein epitope embedded in flanking GCN4 region. We demonstrate that at the primary amino acid level J8 and J14 show very little homology to human proteins. ProPred, RANKPEP and HLABIND algorithms failed to predict significant binding between the M-protein specific regions of J8 and J14 and class II binding alleles. A single peptide was predicted to bind to HLA class I allele B_2705. This data was supported by cellular proliferation assays demonstrating few peripheral blood mononuclear cells (PBMCs) from donors respond to J8 and J14. Reassuringly, there was no correlation between proliferation to these peptides, and proliferation to host proteins. This data suggests that J8 and J14 are unlikely to induce cross-reactive immune responses, and will be safe for use in humans.
In silico characterisation of the two-component system regulators of Streptococcus pyogenes
Publisher: Public Library of Science (PLoS)
Date: 21-06-2018
Does parenteral nutrition increase the risk of catheter-related bloodstream infection? A systematic literature review
Publisher: Wiley
Date: 27-06-2017
Abstract: Central venous access devices (CVADs) are used for parenteral nutrition (PN) delivery. We systematically reviewed research-based publications that reported comparative rates of catheter-related bloodstream infection (CRBSI) in patients with CVADs who received PN vs those who did not receive PN therapy. The literature search included the Cochrane Library, MEDLINE, CINAHL, and PubMed up to July 14, 2015, to identity studies that compared patients with a CVAD who did and did not have PN therapy. Eleven observational studies were identified, comprising 2854 participants with 6287 CVADs. Six studies produced significant results in favor of non-PN, 4 studies showed no evidence of a difference between PN and non-PN, and 1 study produced significant results in favor of PN when analyzed per patient with multiple CVADs. Incidence ranged from 0 to 6.6 CRBSIs per 1000 CVAD days in the PN patients and 0.39 to 3.6 CRBSIs per 1000 CVAD days in the non-PN patients. The Cochrane risk of bias assessment tool for nonrandomized studies of interventions was used. Eight studies were rated as moderate risk of bias, 2 as serious, and 1 as critical. The data presented in this systematic review are not sufficient to establish whether patients receiving PN are more at risk of developing CRBSI than those who do not. Future PN studies needs to adjust for baseline imbalances and improve quality and reporting.
emm and C-Repeat Region Molecular Typing of Beta-Hemolytic Streptococci in a Tropical Country: Implications for Vaccine Development
Publisher: American Society for Microbiology
Date: 08-2009
DOI: 10.1128/JCM.00312-09
Abstract: We designed a study to investigate the molecular epidemiology of group A streptococcal (GAS) and group C and G streptococcal (GCS and GGS) disease in Fiji, a country which is known to have a high burden of streptococcal disease. Molecular typing of the N-terminal portion ( emm typing) of the M protein was performed with 817 isolates (535 GAS and 282 GCS/GGS). We also performed genotyping of the C-repeat region in 769 of these isolates to identify J14 sequence types. The profile of emm types for Fiji was very different from that found for the United States and Europe. There were no dominant emm types and a large number of overlapping types among clinical disease states. Commonly found GAS emm types in industrialized countries, including emm1 , emm12 , and emm28 , were not found among GAS isolates from Fiji. Over 93% of GAS isolates and over 99% of GCS/GGS isolates that underwent J14 sequence typing contained either J14.0 or J14.1. Our data have implications for GAS vaccine development in developing countries and suggest that a vaccine based upon the conserved region of the M protein may be a feasible option for Fiji and potentially for other tropical developing countries.
Variations in the distribution of genes encoding virulence and extracellular proteins in group A streptococcus are largely restricted to 11 genomic loci
Publisher: Elsevier BV
Date: 03-2007
DOI: 10.1016/J.MICINF.2006.11.014
Abstract: Group A streptococcus (GAS) is a human pathogen associated with a wide range of human diseases that vary in symptoms and clinical severity. In this report we describe the use of a targeted low density array representing genes encoding classical virulence factors, purported virulence factors and other extracellular proteins to examine differences in the genetic profiles of 68 clinical GAS isolates. Of the 226 genes on the array (encoding 217 virulence factors or putative extracellular proteins and nine positive control house-keeping proteins) 62 had distributions that were statistically associated with specific GAS M-types. While 32 of these genes were bacteriophage related, the remaining 30 have not previously been described as bacteriophage associated. We show that these 'non-bacteriophage related' genes are found in 11 loci located in five greater chromosomal regions, often near classical GAS virulence factors, and often accompanied by genes associated with mobile genetic elements (MGEs). Many of these loci also demonstrated genetic variation within strains of the same M-type, suggesting these regions to be recombinatorial and mutational hotspots. Evidence for acquisition of genes from other species is also apparent in these loci. Our data suggests that imprecise recombination events involving MGEs not only result in acquisition of new genes, but can also result in deletion of flanking chromosomal genes. Thus MGE related events would appear to be the major contributor to variation of discrete virulence loci, which could account for the disease causing propensity of in idual strains. We believe that profiling of the 11 loci could be a meaningful tool in epidemiological GAS typing studies.
Characterisation of the urease gene cluster in Bordetella bronchiseptica
Publisher: Elsevier BV
Date: 02-1998
DOI: 10.1016/S0378-1119(97)00651-3
Abstract: Bordetella bronchiseptica is a common ureolytic mammalian respiratory pathogen. The urease operon of this organism is encoded within an 8.9 kb DNA fragment which contains the structural genes (ureA, ureB and ureC) and accessory genes (ureD and ureG) homologous to other urease genes. Uniquely, the ureE and ureF genes are fused to form a hybrid protein, UreEF, which may result in tighter coordination of the putative functions of the in idual accessory genes, nickel donation to the urease active site, and prevention of nickel incorporation until correct formation of the active site, respectively. The operon contains an additional open reading frame, UreJ, found only also in the Alcaligenes eutrophus urease operon. UreJ is also 37% homologous with HupE from Rhizobium leguminosarum bv. viciae, and may potentially be involved in nickel transport. A transcriptional activator, designated Bordetella bronchiseptica urease regulator (BbuR), is located directly upstream and in the opposite orientation to the urease operon. BbuR shares homology with members of the LysR regulatory protein family. LysR proteins have been shown to regulate urease in Klebsiella aerogenes (NAC), and catalase in Escherichia coli (OxyR), which offers the intracellular bacterium protection from phagolysosome damage. A putative BbuR binding site (5'-ATA-N9-TAT-3'), identical to the NAC-binding consensus sequence, was found 27 bp upstream of the urease promoter in B. bronchiseptica. We hypothesise that BbuR controls urease expression which is involved in protection of intracellular B. bronchiseptica from phagolysosomal damage. Comparison of the urease promoter regions of B. bronchiseptica, Bordetella parapertussis ATCC15311 and the urease-negative strain B. pertussis Tohama I revealed no differences in the ureD open reading frame between each species. A cluster of mutations in both B. pertussis and B. parapertussis was found upstream of the urease promoter, in a region proximal to the putative bbuR promoter. The inability of B. pertussis to produce urease may therefore reflect mutations in regulatory elements, and not mutations in the urease locus itself.
Peripherally InSerted CEntral catheter dressing and securement in patients with cancer: the PISCES trial. Protocol for a 2x2 factorial, superiority randomised controlled trial
Publisher: BMJ
Date: 06-2017
Anemia prevalence in women of reproductive age in low- and middle-income countries between 2000 and 2018
Publisher: Springer Science and Business Media LLC
Date: 10-2021
DOI: 10.1038/S41591-021-01498-0
Abstract: Anemia is a globally widespread condition in women and is associated with reduced economic productivity and increased mortality worldwide. Here we map annual 2000–2018 geospatial estimates of anemia prevalence in women of reproductive age (15–49 years) across 82 low- and middle-income countries (LMICs), stratify anemia by severity and aggregate results to policy-relevant administrative and national levels. Additionally, we provide subnational disparity analyses to provide a comprehensive overview of anemia prevalence inequalities within these countries and predict progress toward the World Health Organization’s Global Nutrition Target (WHO GNT) to reduce anemia by half by 2030. Our results demonstrate widespread moderate improvements in overall anemia prevalence but identify only three LMICs with a high probability of achieving the WHO GNT by 2030 at a national scale, and no LMIC is expected to achieve the target in all their subnational administrative units. Our maps show where large within-country disparities occur, as well as areas likely to fall short of the WHO GNT, offering precision public health tools so that adequate resource allocation and subsequent interventions can be targeted to the most vulnerable populations.
Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019
Publisher: Elsevier BV
Date: 10-2020
The nutritional requirements for biofilm formation by Group A streptococcus
Publisher: Elsevier BV
Date: 04-2006
Predicting the environmental suitability for onchocerciasis in Africa as an aid to elimination planning
Publisher: Public Library of Science (PLoS)
Date: 28-07-2021
DOI: 10.1371/JOURNAL.PNTD.0008824
Abstract: Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where onchocerciasis has been previously detected. This threshold value was then used to classify IUs (more suitable or less suitable) based on the location within the IU with the largest mean prediction. Mean estimates of environmental suitability suggest large areas across West and Central Africa, as well as focal areas of East Africa, are suitable for onchocerciasis transmission, consistent with the presence of current control and elimination of transmission efforts. The ROC analysis identified a mean environmental suitability index of 0·71 as a threshold to classify based on the location with the largest mean prediction within the IU. Of the IUs considered for mapping surveys, 50·2% exceed this threshold for suitability in at least one 5 × 5-km location. The formidable scale of data collection required to map onchocerciasis endemicity across the African continent presents an opportunity to use spatial data to identify areas likely to be suitable for onchocerciasis transmission. National onchocerciasis elimination programmes may wish to consider prioritising these IUs for mapping surveys as human resources, laboratory capacity, and programmatic schedules may constrain survey implementation, and possibly delaying MDA initiation in areas that would ultimately qualify.
Skin infections among Indigenous Australians in an urban setting in Far North Queensland
Publisher: Cambridge University Press (CUP)
Date: 24-10-2008
DOI: 10.1017/S0950268807009740
Abstract: Skin infections are highly prevalent in many Australian Aboriginal communities. This study aimed to determine the prevalence of group A streptococcus (GAS) and Staphylococcus aureus in skin sores of Indigenous people living in an urban setting. We undertook a cross-sectional study of 173 children and youths attending the Wuchopperen Clinic (Cairns) for treatment of skin infections. Participants were interviewed using a structured questionnaire, and a skin lesion swab obtained. The median age was 5·3 years, with 42% identifying themselves as Torres Strait Islanders and 34% as Aboriginal. Impetigo (65%) was the most frequent diagnosis reported followed by scabies (19%) 79% of the lesions had erythema and 70% had exudate. Of 118 lesions, 114 were positive for pathogenic bacteria, with GAS isolated in 84 cases and S. aureus in 92 both these species were recovered from 63 lesions. Significant ersity of emm -types of GAS was associated with skin lesions in Indigenous patients (22 emm -types identified). Fifteen of the 92 S. aureus isolates were suggestive of being community-acquired on the basis of antimicrobial susceptibility profile and nine of these strains were co-cultured from nine lesions. These results have implications for future changes of antibiotic policies for the treatment of skin infections in this population.
Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline
Publisher: Springer Science and Business Media LLC
Date: 04-08-2014
DOI: 10.1038/NCOMMS5544
Abstract: Streptococcus agalactiae (Group B Streptococcus , GBS) is a commensal of the digestive and genitourinary tracts of humans that emerged as the leading cause of bacterial neonatal infections in Europe and North America during the 1960s. Due to the lack of epidemiological and genomic data, the reasons for this emergence are unknown. Here we show by comparative genome analysis and phylogenetic reconstruction of 229 isolates that the rise of human GBS infections corresponds to the selection and worldwide dissemination of only a few clones. The parallel expansion of the clones is preceded by the insertion of integrative and conjugative elements conferring tetracycline resistance (TcR). Thus, we propose that the use of tetracycline from 1948 onwards led in humans to the complete replacement of a erse GBS population by only few TcR clones particularly well adapted to their host, causing the observed emergence of GBS diseases in neonates.
Horizontal gene transfer and recombination in Streptococcus dysgalactiae subsp. equisimilis
Publisher: Frontiers Media SA
Date: 15-12-2014
Phage 3396 from a Streptococcus dysgalactiae subsp. equisimilis Pathovar May Have Its Origins in Streptococcus pyogenes
Publisher: American Society for Microbiology
Date: 04-2007
DOI: 10.1128/JB.01590-06
Abstract: Streptococcus dysgalactiae subsp. equisimilis strains (group G streptococcus [GGS]) are largely defined as commensal organisms, which are closely related to the well-defined human pathogen, the group A streptococcus (GAS). While lateral gene transfers are emerging as a common theme in these species, little is known about the mechanisms and role of these transfers and their effect on the population structure of streptococci in nature. It is now becoming evident that bacteriophages are major contributors to the genotypic ersity of GAS and, consequently, are pivotal to the GAS strain structure. Furthermore, bacteriophages are strongly associated with altering the pathogenic potential of GAS. In contrast, little is know about phages from GGS and their role in the population dynamics of GGS. In this study we report the first complete genome sequence of a GGS phage, Φ3396. Exhibiting high homology to the GAS phage Φ315.1, the chimeric nature of Φ3396 is unraveled to reveal evidence of extensive ongoing genetic ersity and dissemination of streptococcal phages in nature. Furthermore, we expand on our recent findings to identify inducible Φ3396 homologues in GAS from a region of endemicity for GAS and GGS infection. Together, these findings provide new insights into not only the population structure of GGS but also the overall population structure of the streptococcal genus and the emergence of pathogenic variants.
Subnational mapping of HIV incidence and mortality among individuals aged 15–49 years in sub-Saharan Africa, 2000–18: a modelling study
Publisher: Elsevier BV
Date: 06-2021
Uncovering the mysteries of invasive streptococcal diseases
Publisher: Elsevier BV
Date: 04-2005
DOI: 10.1016/J.MOLMED.2005.02.001
Abstract: Group A streptococci, although considered extracellular pathogens, are capable of causing severe life-threatening invasive infections, such as necrotising fasciitis, bacteraemia and toxic-shock-like syndrome. A complete understanding of the mechanism by which these organisms cause invasive disease has been h ered by the extreme human specificity and high genetic ersity among group A streptococci. Three recent papers have uncovered some of the mysteries of streptococcal invasive diseases. Using two different technologies, these papers have contributed enormously towards our understanding of the molecular events underlying streptococcal invasive diseases.
Mapping inequalities in exclusive breastfeeding in low- and middle-income countries, 2000–2018
Publisher: Springer Science and Business Media LLC
Date: 03-06-2021
DOI: 10.1038/S41562-021-01108-6
Abstract: Exclusive breastfeeding (EBF)—giving infants only breast-milk for the first 6 months of life—is a component of optimal breastfeeding practices effective in preventing child morbidity and mortality. EBF practices are known to vary by population and comparable subnational estimates of prevalence and progress across low- and middle-income countries (LMICs) are required for planning policy and interventions. Here we present a geospatial analysis of EBF prevalence estimates from 2000 to 2018 across 94 LMICs mapped to policy-relevant administrative units (for ex le, districts), quantify subnational inequalities and their changes over time, and estimate probabilities of meeting the World Health Organization’s Global Nutrition Target (WHO GNT) of ≥70% EBF prevalence by 2030. While six LMICs are projected to meet the WHO GNT of ≥70% EBF prevalence at a national scale, only three are predicted to meet the target in all their district-level units by 2030.
Department of Error
Publisher: Elsevier BV
Date: 06-2019
Virulence gene profiling of GAS isolates from the Netherlands
Publisher: Elsevier BV
Date: 04-2006
Mapping geographical inequalities in oral rehydration therapy coverage in low-income and middle-income countries, 2000–17
Publisher: Elsevier BV
Date: 08-2020
Mapping geographical inequalities in access to drinking water and sanitation facilities in low-income and middle-income countries, 2000–17
Publisher: Elsevier BV
Date: 09-2020
Cardiac remodelling as a result of pre-term birth: implications for future cardiovascular disease
Publisher: Oxford University Press (OUP)
Date: 07-05-2010
Abstract: Pre-term birth affects 10-12% of live births and occurs when the myocardium is still developing therefore, the final structure of the myocardium could be altered. We hypothesized that, in response to pre-term birth, structural remodelling occurs within the myocardium which enables the immature heart muscle to adapt to the haemodynamic transition at birth but results in persistent alterations in its structure. Our objective was to determine how pre-term birth alters the final structure of the myocardium. Using sheep, pre-term birth was induced at 0.9 of term hearts were examined at 9 weeks after term-equivalent age, when cardiomyocyte proliferation and maturation have ceased. In pre-term lambs, we found that cardiomyocytes of both ventricles and the interventricular septum were hypertrophied. Cardiomyocyte maturation in pre-term lambs was altered in that there was a greater proportion of mononucleated, polyploid (4n) cardiomyocytes in both ventricles compared with controls importantly, induction of polyploidy is associated with irreversible stress-related changes in DNA. We also found a six- to seven-fold increase in collagen deposition, usually accompanied by lymphocytic infiltration. We conclude that pre-term birth leads to remodelling of the myocardium that alters its final structure. This may programme for long-term cardiac vulnerability.
Immunological response mounted by Aboriginal Australians living in the Northern Territory of Australia against Streptococcus pyogenes serum opacity factor
Publisher: Microbiology Society
Date: 2002
DOI: 10.1099/00221287-148-1-169
Abstract: Streptococcus pyogenes (Group A streptococcus) interacts with host fibronectin via a number of distinct surface components. The streptococcal serum opacity factor (SOF) is a cell-surface protein of S. pyogenes which causes opalescence of human serum and mediates bacterial binding to fibronectin. In this study, hexahistidyl-tagged fusion proteins encompassing full-length SOF, and domains of SOF encompassing opacity factor activity and fibronectin-binding regions, were used in the characterization of the Aboriginal immune response to SOF. Anti-SOF serum IgG responses were found to be significantly higher (P<0.0001) in Aboriginal adults and children when compared to a non-Aboriginal adult group. The Aboriginal immune response against the fibronectin-binding region of SOF was significantly reduced when compared to the response against the whole SOF protein and N-terminal domains examined in this study (P<0.001). This pattern of immune response was also observed in rabbits immunized with recombinant SOF. Comparison of the deduced amino acid sequence of SOF from a number of common Australian isolates with other SOF sequences revealed that the N-terminus of SOF exhibits sequence similarity values ranging from 42.9% to 96.5%. The C-terminus containing the fibronectin-binding domain and membrane-spanning regions was more highly conserved, exhibiting sequence similarity values ranging from 84.6% to 100% within the fibronectin-binding repeats. These data suggest that the immune response against SOF is directed toward the variable N-terminus of the SOF protein. Phylogenetic analysis indicated that the sof genes of S. pyogenes do not exhibit geographical variation.
Variability in the Distribution of Genes Encoding Virulence Factors and Putative Extracellular Proteins of Streptococcus pyogenes in India, a Region with High Streptococcal Disease Burden, and Implica
Publisher: American Society for Microbiology
Date: 12-09-2012
DOI: 10.1128/CVI.00112-12
Abstract: Streptococcus pyogenes causes a wide variety of human diseases and is a significant cause of morbidity and mortality. Attempts to develop a vaccine were h ered by the genetic ersity of S. pyogenes across different regions of the world. This study sought to identify streptococcal antigens suitable for a region-specific vaccine in India. We used a two-step approach, first performing epidemiological analysis to identify the conserved antigens among Indian isolates. The second step consisted of validating the identified antigens by serological analysis. The 201 streptococcal clinical isolates from India used in this study represented 69 different emm types, with emm 12 being the most prevalent. Virulence profiling of the North and South Indian S. pyogenes isolates with a custom-designed streptococcal virulence microarray identified seven conserved putative vaccine candidates. Collagen-like surface protein (SCI), putative secreted 5′-nucleotidase (PSNT), and C5a peptidase were found in 100% of the isolates, while R28, a putative surface antigen (PSA), and a hypothetical protein (HYP) were found in 90% of the isolates. A fibronectin binding protein, SfbI, was present in only 78% of the isolates. In order to validate the identified potential vaccine candidates, 185 serum s les obtained from patients with different clinical manifestations were tested for antibodies. Irrespective of clinical manifestations, serum s les showed high antibody titers to all proteins except for SCI and R28. Thus, the data indicate that PSNT, C5a peptidase, PSA, HYP, and SfbI are promising candidates for a region-specific streptococcal vaccine for the different parts of India.
Five insights from the Global Burden of Disease Study 2019
Publisher: Elsevier BV
Date: 10-2020
Intravascular device administration sets: replacement after standard versus prolonged use in hospitalised patients--a study protocol for a randomised controlled trial (The RSVP Trial)
Publisher: BMJ
Date: 03-02-2015
Immune response to superoxide dismutase in group A streptococcal infection
Publisher: Oxford University Press (OUP)
Date: 04-2004
Parenteral and mucosal delivery of a novel multi-epitope M protein-based group A streptococcal vaccine construct: Investigation of immunogenicity in mice
Publisher: Elsevier BV
Date: 06-2002
DOI: 10.1016/S0264-410X(02)00206-2
Abstract: Primary vaccine strategies against group A streptococci (GAS) have focused on the M protein--the target of opsonic antibodies important for protective immunity. We have previously reported protection of mice against GAS infection following parenteral delivery of a multi-epitope vaccine construct, referred to as a heteropolymer. This current report has assessed mucosal (intranasal (i.n.) and oral) delivery of the heteropolymer in mice with regard to the induction and specificity of mucosal and systemic antibody responses, and compared this to parenteral delivery. GAS-specific IgA responses were detected in saliva and gut upon i.n. and oral delivery of the heteropolymer co-administered with cholera toxin B subunit, respectively. High titre serum IgG responses were elicited to the heteropolymer following all routes of delivery when administered with adjuvant. Moreover, as with parenteral delivery, serum IgG antibodies were detected to the in idual heteropolymer peptides following i.n. but not oral delivery. These data support the potential of the i.n. route in the mucosal delivery of a GAS vaccine.
Antibody levels to the class I and II epitopes of the M protein and myosin are related to group A streptococcal exposure in endemic populations
Publisher: Oxford University Press (OUP)
Date: 10-2001
DOI: 10.1093/INTIMM/13.10.1335
Abstract: Rheumatic fever (RF)/rheumatic heart disease (RHD) and post-streptococcal glomerulonephritis are thought to be autoimmune diseases, and follow group A streptococcal (GAS) infection. Different GAS M types have been associated with rheumatogenicity or nephritogenicity and categorized into either of two distinct classes (I or II) based on amino acid sequences present within the repeat region ('C' repeats) of the M protein. Sera from ARF patients have previously been shown to contain elevated levels of antibodies to the class I-specific epitope and myosin with the class I-specific antibodies also being cross-reactive to myosin, suggesting a disease association. This study shows that immunoreactivity of the class I-specific peptide and myosin does not differ between controls and acute RF (ARF)/RHD in populations that are highly endemic for GAS, raising the possibility that the association is related to GAS exposure, not the presence of ARF/RHD. Peptide inhibition studies suggest that the class I epitope may be conformational and residue 10 of the peptide is critical for antibody binding. We demonstrate that correlation of antibody levels between the class I and II epitope is due to class II-specific antibodies recognizing a common epitope with class I which is contained within the sequence RDL-ASRE. Our results suggest that antibody prevalence to class I and II epitopes and myosin is associated with GAS exposure, and that antibodies to these epitopes are not an indicator of disease nor a pathogenic factor in endemic populations.
Mapping routine measles vaccination in low- and middle-income countries
Publisher: Springer Science and Business Media LLC
Date: 16-12-2020
DOI: 10.1038/S41586-020-03043-4
Abstract: The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs) 1–4 . Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19) 5–8 . Here we generated annual estimates of routine childhood MCV1 coverage at 5 × 5-km 2 pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children.
Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017
Publisher: Springer Science and Business Media LLC
Date: 20-04-2020
DOI: 10.1038/S41591-020-0807-6
Abstract: A double burden of malnutrition occurs when in iduals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of % in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic.
Culture-independent detection of chlorhexidine resistance genes qacA/B and smr in bacterial DNA recovered from body sites treated with chlorhexidine-containing dressings
Publisher: Microbiology Society
Date: 04-2017
DOI: 10.1099/JMM.0.000463
Abstract: Dressings containing chlorhexidine gluconate (CHG) are increasingly used in clinical environments for prevention of infection at central venous catheter insertion sites. Increased tolerance to this biocide in staphylococci is primarily associated with the presence of qacA/B and smr genes. We used a culture-independent method to assess the prevalence of these genes in 78 DNA specimens recovered from the skin of 43 patients at catheter insertion sites in the arm that were covered with CHG dressings. Of the 78 DNA specimens analysed, 52 (67 %) possessed qacA/B and 14 (18 %) possessed smr all s les positive for smr were also positive for qacA/B. These prevalence rates were not statistically greater than those observed in a subs le of specimens taken from non-CHG treated contralateral arms and non-CHG-dressing exposed arms. A statistically greater proportion of specimens with greater than 72 h exposure to CHG dressings were qac-positive (P=0.04), suggesting that the patients were contaminated with bacteria or DNA containing qacA/B during their hospital stay. The presence of qac genes was not positively associated with the presence of DNA specific for Staphylococcusepidermidis and Staphylococcusaureus in these specimens. Our results show that CHG genes are highly prevalent on hospital patients' skin, even in the absence of viable bacteria.
Global, regional, and national burden of meningitis, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016
Publisher: Elsevier BV
Date: 12-2018
Recombination drives genetic diversification of streptococcus dysgalactiae subspecies equisimilis in a region of streptococcal endemicity
Publisher: Public Library of Science (PLoS)
Date: 03-08-2011
Structural optimisation of a conformational epitope improves antigenicity when expressed as a recombinant fusion protein
Publisher: Elsevier BV
Date: 11-2009
DOI: 10.1016/J.VACCINE.2009.08.049
Abstract: A conformationally restricted B cell epitope has been identified as a potential safe vaccine candidate from the major group A streptococcal virulence factor, the M protein. To maintain alpha-helical secondary structure, the minimal epitope is flanked with heterologous sequences to produce the chimeric vaccine candidate called J14. As a strategy toward developing an affordable multivalent GAS vaccine, we have expressed J14 recombinantly with a second GAS protective antigen H12 (rJ14H12). When administered to mice sub-cutaneously, the fusion protein stimulated a strong serum IgG response to the H12 component, but J14 was poorly immunogenic. To increase the immunogenicity of J14 when expressed with the model fusion partner, amino acid modifications were made to the initial recombinant J14 construct to produce rJJo. These changes stabilised the alpha-helical conformation of the recombinant antigen as assessed by circular dichroism. Mice immunised with rJJoH12, the fusion protein incorporating JJo, effectively stimulated a humoral response to both of the included antigens. These data support the feasibility of developing a multivalent vaccine incorporating the conformationally restricted protective antigen J14.
Microbiological pattern of arterial catheters in the intensive care unit
Publisher: Springer Science and Business Media LLC
Date: 2010
Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019: a comprehensive demographic analysis for the Global Burden of Disease Study 2019
Publisher: Elsevier BV
Date: 10-2020
Virulence Profiling of Streptococcus dysgalactiae Subspecies equisimilis Isolated from Infected Humans Reveals 2 Distinct Genetic Lineages That Do Not Segregate with Their Phenotypes or Propensity to
Publisher: Oxford University Press (OUP)
Date: 06-2007
DOI: 10.1086/516780
Abstract: In spite of the emerging importance of Streptococcus dysgalactiae subspecies equisimilis (human group C streptococci [GCS] and group G streptococci [GGS]) in human health, its molecular makeup remains largely undefined. Apart from sharing a phylogenetic relationship with the human pathogen group A streptococci (GAS), GCS/GGS and GAS colonize the same ecological niche and exhibit considerable overlap in their disease profiles. Such similarities imply that the virulence factors associated with diseases may also be similar. In this study, we used a targeted microarray containing 216 GAS virulence genes to profile the virulence gene repertoires of 58 S. dysgalactiae subspecies equisimilis isolates recovered during human infections. We performed comparative analyses to investigate the relationship between GAS virulence genes in and the invasive potential of GCS/GGS. Up to one-half of the GAS virulence genes represented in the microarray were identified in GCS/GGS. No statistical differences were observed between isolates harboring the group C versus group G carbohydrates however, clustering algorithms revealed 2 genetically distinct clusters of S. dysgalactiae subspecies equisimilis isolates. No relationship was observed between the virulence profile of GCS/GGS and the propensity for disease or the tissue site of isolation. This is, to our knowledge, the first comprehensive analysis of the virulence profile of S. dysgalactiae subspecies equisimilis, and it enables novel insights into the pathogen's genetic basis of disease propensity shared with GAS. Human group C and group G streptococci may not be considered to be separate species in fact, they may constitute 2 distinct lineages. Additional incongruent relationships were observed between virulence profiles and GCS/GGS disease propensity.
Global burden of 87 risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019
Publisher: Elsevier BV
Date: 10-2020
Distribution of group A streptococcal virulence genes in group C and G streptococci
Publisher: Elsevier BV
Date: 04-2006
Genetic variation in group A streptococci
Publisher: Elsevier BV
Date: 11-2007
DOI: 10.1016/J.IJMM.2007.02.007
Abstract: Group A streptococcus (GAS) is responsible for a range of human diseases that vary in their clinical manifestations and severity. While numerous virulence factors have been described, the way these factors interact to promote different streptococcal diseases is less clear. In order to identify multifactorial relationships between GAS and the human host, novel high-throughput techniques such as microarrays are necessary. We have performed comparative studies using custom-designed virulence arrays to enhance our understanding of the high degree of genotypic variation that occurs in streptococci. This study has pointed to mobile genetic elements as the major agents that promote variation. Our results show that multiple combinations of genes might bring about similar clinical pictures. This adds further complexity to the intricate relationship between pathogen and host.
Effect of Delaying Replacement of Parenteral Nutrition Intravenous Administration Sets: Preclinical Experiments and a Dynamic Laboratory Model of Microbial Colonization
Publisher: Wiley
Date: 08-01-2018
DOI: 10.1002/JPEN.1039
Abstract: Recommendations prescribe daily intravenous administration set (IVAS) replacement for parenteral nutrition (PN) comprising intravenous fat emulsions (IVFE) due to risk of micro-organism growth and resultant central-line associated bloodstream infections (CLABSIs), but system disconnection for this practice may allow contamination and CLABSIs. Laboratory experiments and model development were used to simulate PN administration after contamination from healthcare workers' hands. This study observed the growth of micro-organisms known to cause CLABSIs in a variety of PN and other IV fluids and developed a model to investigate the effect of delaying IVAS replacement on microbial growth for up to 7 days. Micro-organisms grew at different rates and were affected by solution type. In static experiments, growth was supported in IVFE and all-in-one PN, but suppressed in 50% glucose. Growth patterns were consistent over time for Staphylococcus epidermidis, Staphylococcus aureus, and Candida albicans in IVFE, all-in-one PN, and 0.9% sodium chloride in both static and dynamic experiments. C. albicans grew exponentially to clinically significant numbers in all-in-one PN and IVFE IVAS after 30 hours, but negligible growth of S. epidermidis or S. aureus occurred for 7 days. All-in-one PN and IVFE support the C. albicans growth after minimal initial contamination, with micro-organisms migrating from the fluid bag to the central venous access device. Improved aseptic nontouch technique during clinical practice is vital to prevent contamination. Daily IVAS replacement of for all-in-one PN and IVFE should continue until the safety of prolonging IVAS replacement is confirmed by randomized trials.
Population Genetics of Streptococcus dysgalactiae Subspecies equisimilis Reveals Widely Dispersed Clones and Extensive Recombination
Publisher: Public Library of Science (PLoS)
Date: 23-07-2010
Global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases
Publisher: Elsevier BV
Date: 12-2019
DrsG from Streptococcus dysgalactiae subsp. equisimilis Inhibits the Antimicrobial Peptide LL-37
Publisher: American Society for Microbiology
Date: 06-2014
DOI: 10.1128/IAI.01411-13
Abstract: SIC and DRS are related proteins present in only 4 of the Streptococcus pyogenes emm types. These proteins inhibit complement-mediated lysis and/or the activity of certain antimicrobial peptides (AMPs). A gene encoding a homologue of these proteins, herein called DrsG, has been identified in the related bacterium Streptococcus dysgalactiae subsp. equisimilis . Here we show that geographically dispersed isolates representing 14 of 50 emm types examined possess variants of drsG . However, not all isolates within the drsG -positive emm types possess the gene. Sequence comparisons also revealed a high degree of conservation in different S. dysgalactiae subsp. equisimilis emm types. To examine the biological activity of DrsG, recombinant versions of two major DrsG variants, DrsGS and DrsGL, were expressed and purified. Western blot analysis using antisera raised to these proteins demonstrated both variants to be expressed and secreted into culture supernatants. Unlike SIC, but similar to DRS, DrsG does not inhibit complement-mediated lysis. However, like both SIC and DRS, DrsG is a ligand of the cathelicidin LL-37 and is inhibitory to its bactericidal activity in in vitro assays. Conservation of prolines in the C-terminal region also suggests that these residues are important in the biology of this family of proteins. This is the first report demonstrating the activity of an AMP-inhibitory protein in S. dysgalactiae subsp. equisimilis and suggests that inhibition of AMP activity is the primary function of this family of proteins. The acquisition of the complement-inhibitory activity of SIC may reflect its continuing evolution.
Seropositivity for antibodies to DRS-G, a virulence factor from Streptococcus dysgalactiae subsp. equisimilis, is an independent risk factor for poststreptococcus glomerulonephritis and chronic kidney disease in Mumbai, India
Publisher: American Society for Microbiology
Date: 08-2015
DOI: 10.1128/CVI.00275-15
Abstract: The disease spectrum caused by Streptococcus dysgalactiae subsp. equisimilis resembles that of S. pyogenes (group A streptococcus [GAS]). These two bacterial species are closely related and possess many common virulence characteristics. While some GAS strains express virulence factors called streptococcal inhibitor of complement (SIC) and distantly related to SIC (DRS), some S. dysgalactiae subsp. equisimilis isolates express an orthologue of DRS, which is referred to as DRS-G. We reported previously that seropositivity for either anti-SIC or anti-DRS antibodies (Abs) is associated with poststreptococcal glomerulonephritis (PSGN). However, only seropositivity for anti-SIC Abs is associated with chronic kidney disease (CKD). We now extend the study to test whether seropositivity for anti-DRS-G Abs is also associated with these renal diseases. Stored serum s les collected for our previous study were tested by an enzyme-linked immunosorbent assay (ELISA) for Abs to DRS-G. The s les represented sera from 100 CKD adult patients, 70 adult end-stage renal disease (ESRD) patients, 25 PSGN pediatric patients, and corresponding age-matched control subjects. The proportion of PSGN, CKD, and ESRD patients who showed seroreaction to anti-DRS-G Abs was significantly higher than that of the corresponding age-matched controls, who in general exhibited seropositivity rates commensurate with the isolation rate of drsG -positive S. dysgalactiae subsp. equisimilis in the community during this study period. Since higher rates of seropositivity for anti-DRS-G Abs in the renal disease categories are resultant of previous infections with DRS-G-positive S. dysgalactiae subsp. equisimilis strains, we conclude the seropositivity is an additional risk factor for these renal diseases. In this regard, anti-DRS-G Abs have attributes similar to those of the anti-SIC Abs.
The global distribution of lymphatic filariasis, 2000–18: a geospatial analysis
Publisher: Elsevier BV
Date: 09-2020
Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000–17: analysis for the Global Burden of Disease Study 2017
Publisher: Elsevier BV
Date: 06-2020
Evidence for increased horizontal gene transfers among streptococci from group A streptococcal endemic regions
Publisher: Elsevier BV
Date: 04-2006
Department of Error
Publisher: Elsevier BV
Date: 06-2020
Genomic Location and Variation of the Gene for CRS, a Complement Binding Protein in the M57 Strains of Streptococcus pyogenes
Publisher: American Society for Microbiology
Date: 12-2003
DOI: 10.1128/IAI.71.12.6701-6706.2003
Abstract: All isolates of serotype M1 of group A streptococci possess a gene for streptococcal inhibitor of complement (SIC) in the mga regulon, which harbors genes for other virulence factors, such as M and M-like proteins, C5a peptidase, and a regulator. In serotype M57 the gene for a protein that is closely related to SIC ( crs57 ) is located outside the mga regulon. We mapped the location of the crs57 gene in six strains of emm57 (gene encoding the M57 protein) sequence types to an intergenic region between the ABC transporter gene (SPy0778) and the gene for a small ribosomal protein ( rpsU ). The noncoding sequences on both sides of crs57 exhibited high degrees of identity to the corresponding regions of sic from M1 strains. This included one of the inverted repeat sequences of IS 1562 but not the insertion element itself. These observations suggest that crs57 was recently acquired by serotype M57 or its progenitor via horizontal acquisition from serotype M1. The six emm57 sequence type isolates analyzed in this study belong to two distinct molecular types (vir types VT8 and VT101). Although the crs57 sequences from VT8 strains had very few substitution mutations, the VT101 crs57 sequence had a large number of such mutations. The CRS57 proteins from these strains are secretory products and have the ability to bind to complement proteins. All these proteins contain several tryptophan-rich repeats designated DWS motifs and internal repeat sequences. In all of these structural and biochemical characteristics CRS57 resembles SIC from M1 strains. Hence, CRS57 has a functional role similar to that of SIC in an M1 strain.
Reply to Dale and Shulman.
Publisher: Oxford University Press (OUP)
Date: 24-09-2019
A Novel Integrative Conjugative Element Mediates Genetic Transfer from Group G Streptococcus to Other ß-Hemolytic Streptococci
Publisher: American Society for Microbiology
Date: 04-2009
DOI: 10.1128/JB.01624-08
Abstract: Lateral gene transfer is a significant contributor to the ongoing evolution of many bacterial pathogens, including β-hemolytic streptococci. Here we provide the first characterization of a novel integrative conjugative element (ICE), ICE Sde 3396, from Streptococcus dysgalactiae subsp. equisimilis (group G streptococcus [GGS]), a bacterium commonly found in the throat and skin of humans. ICE Sde 3396 is 64 kb in size and encodes 66 putative open reading frames. ICE Sde 3396 shares 38 open reading frames with a putative ICE from Streptococcus agalactiae (group B streptococcus [GBS]), ICE Sa 2603. In addition to genes involves in conjugal processes, ICE Sde 3396 also carries genes predicted to be involved in virulence and resistance to various metals. A major feature of ICE Sde 3396 differentiating it from ICE Sa 2603 is the presence of an 18-kb internal recombinogenic region containing four unique gene clusters, which appear to have been acquired from streptococcal and nonstreptococcal bacterial species. The four clusters include two cadmium resistance operons, an arsenic resistance operon, and genes with orthologues in a group A streptococcus (GAS) prophage. Streptococci that naturally harbor ICE Sde 3396 have increased resistance to cadmium and arsenate, indicating the functionality of genes present in the 18-kb recombinogenic region. By marking ICE Sde 3396 with a kanamycin resistance gene, we demonstrate that the ICE is transferable to other GGS isolates as well as GBS and GAS. To investigate the presence of the ICE in clinical streptococcal isolates, we screened 69 isolates (30 GGS, 19 GBS, and 20 GAS isolates) for the presence of three separate regions of ICE Sde 3396. Eleven isolates possessed all three regions, suggesting they harbored ICE Sde 3396-like elements. Another four isolates possessed ICE Sa 2603-like elements. We propose that ICE Sde 3396 is a mobile genetic element that is capable of acquiring DNA from multiple bacterial sources and is a vehicle for dissemination of this DNA through the wider β-hemolytic streptococcal population.
Genes for the majority of group A streptococcal virulence factors and extracellular surface proteins do not confer an increased propensity to cause invasive disease
Publisher: Oxford University Press (OUP)
Date: 10-2006
DOI: 10.1086/507537
Abstract: The factors behind the reemergence of severe, invasive group A streptococcal (GAS) diseases are unclear, but it could be caused by altered genetic endowment in these organisms. However, data from previous studies assessing the association between single genetic factors and invasive disease are often conflicting, suggesting that other, as-yet unidentified factors are necessary for the development of this class of disease. In this study, we used a targeted GAS virulence microarray containing 226 GAS genes to determine the virulence gene repertoires of 68 GAS isolates (42 associated with invasive disease and 28 associated with noninvasive disease) collected in a defined geographic location during a contiguous time period. We then employed 3 advanced machine learning methods (genetic algorithm neural network, support vector machines, and classification trees) to identify genes with an increased association with invasive disease. Virulence gene profiles of in idual GAS isolates varied extensively among these geographically and temporally related strains. Using genetic algorithm neural network analysis, we identified 3 genes with a marginal overrepresentation in invasive disease isolates. Significantly, 2 of these genes, ssa and mf4, encoded superantigens but were only present in a restricted set of GAS M-types. The third gene, spa, was found in variable distributions in all M-types in the study. Our comprehensive analysis of GAS virulence profiles provides strong evidence for the incongruent relationships among any of the 226 genes represented on the array and the overall propensity of GAS to cause invasive disease, underscoring the pathogenic complexity of these diseases, as well as the importance of multiple bacteria and/or host factors.
Mapping subnational HIV mortality in six Latin American countries with incomplete vital registration systems
Publisher: Springer Science and Business Media LLC
Date: 08-01-2021
DOI: 10.1186/S12916-020-01876-4
Abstract: Human immunodeficiency virus (HIV) remains a public health priority in Latin America. While the burden of HIV is historically concentrated in urban areas and high-risk groups, subnational estimates that cover multiple countries and years are missing. This paucity is partially due to incomplete vital registration (VR) systems and statistical challenges related to estimating mortality rates in areas with low numbers of HIV deaths. In this analysis, we address this gap and provide novel estimates of the HIV mortality rate and the number of HIV deaths by age group, sex, and municipality in Brazil, Colombia, Costa Rica, Ecuador, Guatemala, and Mexico. We performed an ecological study using VR data ranging from 2000 to 2017, dependent on in idual country data availability. We modeled HIV mortality using a Bayesian spatially explicit mixed-effects regression model that incorporates prior information on VR completeness. We calibrated our results to the Global Burden of Disease Study 2017. All countries displayed over a 40-fold difference in HIV mortality between municipalities with the highest and lowest age-standardized HIV mortality rate in the last year of study for men, and over a 20-fold difference for women. Despite decreases in national HIV mortality in all countries—apart from Ecuador—across the period of study, we found broad variation in relative changes in HIV mortality at the municipality level and increasing relative inequality over time in all countries. In all six countries included in this analysis, 50% or more HIV deaths were concentrated in fewer than 10% of municipalities in the latest year of study. In addition, national age patterns reflected shifts in mortality to older age groups—the median age group among decedents ranged from 30 to 45 years of age at the municipality level in Brazil, Colombia, and Mexico in 2017. Our subnational estimates of HIV mortality revealed significant spatial variation and erging local trends in HIV mortality over time and by age. This analysis provides a framework for incorporating data and uncertainty from incomplete VR systems and can help guide more geographically precise public health intervention to support HIV-related care and reduce HIV-related deaths.
The streptococcal M protein: A highly versatile molecule
Publisher: Elsevier BV
Date: 06-2010
DOI: 10.1016/J.TIM.2010.02.007
Abstract: Interaction of the M-protein of group A Streptococcus (GAS) with its numerous host binding partners might assist the bacteria in evading host immune responses. Although the extensive ersity of this protein has been highlighted by different GAS typing schemes, most of the structural and functional information has been obtained from a limited number of types. Increasing numbers of epidemiological, clinical and biological reports suggest that the structure and function of the M protein is less conserved than previously thought. This review focuses on the known interactions between M proteins and host ligand proteins, emphasizing that our understanding of this well-studied molecule is fragmented.
Inter-species genetic movement may blur the epidemiology of streptococcal diseases in endemic regions
Publisher: Elsevier BV
Date: 07-2005
DOI: 10.1016/J.MICINF.2005.03.018
Abstract: Streptococcus dysgalactiae subsp. equisimilis (human group G streptococcus, GGS) is generally regarded as a commensal organism but can cause a spectrum of human diseases very similar to that caused by S. pyogenes (group A streptococcus, GAS). Lateral acquisition of genes between these two phylogenetically closely related species is well documented. However, the extent and mechanisms of lateral acquisitions is not known. We report here genomic subtraction between a pathogenic GGS isolate and a community GGS isolate and analyses of the gene sequences unique to the pathovar. Our results show that cross-species genetic transfers are common between GGS and two closely related human pathogens, GAS and the group B streptococcus. We also demonstrate that mobile genetic elements, such as phages and transposons, play an important role in the ongoing inter-species transfers of genetic traits between extant organisms in the community. Furthermore, lateral gene transfers between GAS and GGS may occur more frequently in geographical regions of high GAS endemicity. These observations may have important implications in understanding the epidemiology of streptococcal diseases in such regions.
Mapping child growth failure across low- and middle-income countries
Publisher: Springer Science and Business Media LLC
Date: 08-01-2020
DOI: 10.1038/S41586-019-1878-8
Abstract: Childhood malnutrition is associated with high morbidity and mortality globally 1 . Undernourished children are more likely to experience cognitive, physical, and metabolic developmental impairments that can lead to later cardiovascular disease, reduced intellectual ability and school attainment, and reduced economic productivity in adulthood 2 . Child growth failure (CGF), expressed as stunting, wasting, and underweight in children under five years of age (0–59 months), is a specific subset of undernutrition characterized by insufficient height or weight against age-specific growth reference standards 3–5 . The prevalence of stunting, wasting, or underweight in children under five is the proportion of children with a height-for-age, weight-for-height, or weight-for-age z -score, respectively, that is more than two standard deviations below the World Health Organization’s median growth reference standards for a healthy population 6 . Subnational estimates of CGF report substantial heterogeneity within countries, but are available primarily at the first administrative level (for ex le, states or provinces) 7 the uneven geographical distribution of CGF has motivated further calls for assessments that can match the local scale of many public health programmes 8 . Building from our previous work mapping CGF in Africa 9 , here we provide the first, to our knowledge, mapped high-spatial-resolution estimates of CGF indicators from 2000 to 2017 across 105 low- and middle-income countries (LMICs), where 99% of affected children live 1 , aggregated to policy-relevant first and second (for ex le, districts or counties) administrative-level units and national levels. Despite remarkable declines over the study period, many LMICs remain far from the ambitious World Health Organization Global Nutrition Targets to reduce stunting by 40% and wasting to less than 5% by 2025. Large disparities in prevalence and progress exist across and within countries our maps identify high-prevalence areas even within nations otherwise succeeding in reducing overall CGF prevalence. By highlighting where the highest-need populations reside, these geospatial estimates can support policy-makers in planning interventions that are adapted locally and in efficiently directing resources towards reducing CGF and its health implications.
Correction: Corrigendum: Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline
Publisher: Springer Science and Business Media LLC
Date: 28-01-2015
DOI: 10.1038/NCOMMS7108
Group G Streptococcus Induces an Autoimmune Carditis Mediated by Interleukin 17A and Interferon γ in the Lewis Rat Model of Rheumatic Heart Disease
Publisher: Oxford University Press (OUP)
Date: 09-12-2017
Abstract: Acute rheumatic fever and rheumatic heart disease (ARF/RHD) have long been described as autoimmune sequelae of Streptococcus pyogenes or group A streptococcal (GAS) infection. Both antibody and T-cell responses against immunodominant GAS virulence factors, including M protein, cross-react with host tissue proteins, triggering an inflammatory response leading to permanent heart damage. However, in some ARF/RHD-endemic regions, throat carriage of GAS is low. Because Streptococcus dysgalactiae subspecies equisimilis organisms, also known as β-hemolytic group C streptococci and group G streptococci (GGS), also express M protein, we postulated that streptococci other than GAS may have the potential to initiate or exacerbate ARF/RHD. Using a model initially developed to investigate the uniquely human disease of ARF/RHD, we have discovered that GGS causes interleukin 17A/interferon γ-induced myocarditis and valvulitis, hallmarks of ARF/RHD. Remarkably the histological, immunological, and functional changes in the hearts of rats exposed to GGS are identical to those exposed to GAS. Furthermore, antibody cross-reactivity to cardiac myosin was comparable in both GGS- and GAS-exposed animals, providing additional evidence that GGS can induce and/or exacerbate ARF/RHD.
Measuring universal health coverage based on an index of effective coverage of health services in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study
Publisher: Elsevier BV
Date: 10-2020
Molecular analysis of thebvg-repressed urease ofBordetella bronchiseptica
Publisher: Elsevier BV
Date: 11-1996
Abstract: Bordetella bronchiseptica is a ureolytic mammalian respiratory pathogen. We have investigated the regulation of urease in B. bronchiseptica and the potential role of this enzyme in eukaryotic invasion and intracellular survival. Our results indicate urease is a bordetella virulence repressed gene. Urease activity in virulent B. bronchiseptica BB7865 is up-regulated from basal levels by 5 gl1 magnesium sulphate at 37 degrees C. At 30 degrees C, urease activity remained at basal levels, even in the presence on magnesium sulphate, suggesting a second temperature dependent mechanism of urease regulation was also operating. Urease was not inducible by 10 mM urea nor up-regulated in nitrogen limiting conditions. To evaluate the role of urease in intracellular invasion and survival urease-negative mutants of B. bronchiseptica BB7865 and B. bronchiseptica BB7866 were created by transposon mutagenesis, and compared to the urease-positive parental strains in a HeLa cell invasion assay. We demonstrate that increasing the concentration of urea in the assay increased survival of the urease-positive but not urease-negative strains after 24 h, suggesting that urease does have a role in intracellular survival. Partial DNA sequence analysis of an 11.0 kb EcoRI DNA fragment encoding urease activity revealed an open reading frame containing 50%, 45%, 45%, and 41% homology to the UreA urease subunit protein of Klebsiella aerogenes, Proteus vulgaris, Helicobacter pylori and Proteus mirabilis respectively. We also show Bordetella pertussis to contain sequences homologous with a DNA probe containing the gene encoding UreA of B. bronchiseptica indicating the possible presence of cryptic urease genes in this species.
Mapping disparities in education across low- and middle-income countries
Publisher: Springer Science and Business Media LLC
Date: 25-12-2019
DOI: 10.1038/S41586-019-1872-1
Abstract: Educational attainment is an important social determinant of maternal, newborn, and child health 1–3 . As a tool for promoting gender equity, it has gained increasing traction in popular media, international aid strategies, and global agenda-setting 4–6 . The global health agenda is increasingly focused on evidence of precision public health, which illustrates the subnational distribution of disease and illness 7,8 however, an agenda focused on future equity must integrate comparable evidence on the distribution of social determinants of health 9–11 . Here we expand on the available precision SDG evidence by estimating the subnational distribution of educational attainment, including the proportions of in iduals who have completed key levels of schooling, across all low- and middle-income countries from 2000 to 2017. Previous analyses have focused on geographical disparities in average attainment across Africa or for specific countries, but—to our knowledge—no analysis has examined the subnational proportions of in iduals who completed specific levels of education across all low- and middle-income countries 12–14 . By geolocating subnational data for more than 184 million person-years across 528 data sources, we precisely identify inequalities across geography as well as within populations.
Mapping 123 million neonatal, infant and child deaths between 2000 and 2017
Publisher: Springer Science and Business Media LLC
Date: 16-10-2019
DOI: 10.1038/S41586-019-1545-0
Abstract: Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations.
Author Correction: Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017
Publisher: Springer Science and Business Media LLC
Date: 02-07-2020
DOI: 10.1038/S41591-020-0972-7
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Global and regional burden of chronic respiratory disease in 2016 arising from non-infectious airborne occupational exposures: a systematic analysis for the Global Burden of Disease Study 2016
Publisher: BMJ
Date: 13-02-2020
DOI: 10.1136/OEMED-2019-106013
Abstract: This paper presents detailed analysis of the global and regional burden of chronic respiratory disease arising from occupational airborne exposures, as estimated in the Global Burden of Disease 2016 study. The burden of chronic obstructive pulmonary disease (COPD) due to occupational exposure to particulate matter, gases and fumes, and secondhand smoke, and the burden of asthma resulting from occupational exposure to asthmagens, was estimated using the population attributable fraction (PAF), calculated using exposure prevalence and relative risks from the literature. PAFs were applied to the number of deaths and disability-adjusted life years (DALYs) for COPD and asthma. Pneumoconioses were estimated directly from cause of death data. Age-standardised rates were based only on persons aged 15 years and above. The estimated PAFs (based on DALYs) were 17% (95% uncertainty interval (UI) 14%–20%) for COPD and 10% (95% UI 9%–11%) for asthma. There were estimated to be 519 000 (95% UI 441,000–609,000) deaths from chronic respiratory disease in 2016 due to occupational airborne risk factors (COPD: 460,100 [95% UI 382,000–551,000] asthma: 37,600 [95% UI 28,400–47,900] pneumoconioses: 21,500 [95% UI 17,900–25,400]. The equivalent overall burden estimate was 13.6 million (95% UI 11.9–15.5 million) DALYs (COPD: 10.7 [95% UI 9.0–12.5] million asthma: 2.3 [95% UI 1.9–2.9] million pneumoconioses: 0.58 [95% UI 0.46–0.67] million). Rates were highest in males older persons and mainly in Oceania, Asia and sub-Saharan Africa and decreased from 1990 to 2016. Workplace exposures resulting in COPD, asthma and pneumoconiosis continue to be important contributors to the burden of disease in all regions of the world. This should be reducible through improved prevention and control of relevant exposures.
Measuring routine childhood vaccination coverage in 204 countries and territories, 1980–2019: a systematic analysis for the Global Burden of Disease Study 2020, Release 1
Publisher: Elsevier BV
Date: 08-2021
Identification and assessment of new vaccine candidates for group A streptococcal infections
Publisher: Elsevier BV
Date: 07-2004
Global and regional burden of cancer in 2016 arising from occupational exposure to selected carcinogens: a systematic analysis for the Global Burden of Disease Study 2016
Publisher: BMJ
Date: 13-02-2020
DOI: 10.1136/OEMED-2019-106012
Abstract: This study provides a detailed analysis of the global and regional burden of cancer due to occupational carcinogens from the Global Burden of Disease 2016 study. The burden of cancer due to 14 International Agency for Research on Cancer Group 1 occupational carcinogens was estimated using the population attributable fraction, based on past population exposure prevalence and relative risks from the literature. The results were used to calculate attributable deaths and disability-adjusted life years (DALYs). There were an estimated 349 000 (95% Uncertainty Interval 269 000 to 427 000) deaths and 7.2 (5.8 to 8.6) million DALYs in 2016 due to exposure to the included occupational carcinogens—3.9% (3.2% to 4.6%) of all cancer deaths and 3.4% (2.7% to 4.0%) of all cancer DALYs 79% of deaths were of males and 88% were of people aged 55 –79 years. Lung cancer accounted for 86% of the deaths, mesothelioma for 7.9% and laryngeal cancer for 2.1%. Asbestos was responsible for the largest number of deaths due to occupational carcinogens (63%) other important risk factors were secondhand smoke (14%), silica (14%) and diesel engine exhaust (5%). The highest mortality rates were in high-income regions, largely due to asbestos-related cancers, whereas in other regions cancer deaths from secondhand smoke, silica and diesel engine exhaust were more prominent. From 1990 to 2016, there was a decrease in the rate for deaths (−10%) and DALYs (−15%) due to exposure to occupational carcinogens. Work-related carcinogens are responsible for considerable disease burden worldwide. The results provide guidance for prevention and control initiatives.
Related Organisations
Federal Institute Of Education, Science And Technology Of Ceará
Location: Brazil
Related Funding Activities
No related grants have been discovered for Francisco Rogerlândio Martins-Melo.