Paediatrics (RCH) - Research Publications
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ItemThe clinical and molecular epidemiology of Staphylococcus aureus infections in Fiji(BMC, 2014-03-24)BACKGROUND: There are few data describing the microbiology and genetic typing of Staphylococcus aureus that cause infections in developing countries. METHODS: In this study we observed S. aureus infections in Pacific Island nation of Fiji in both the community and hospital setting with an emphasis on clonal complex (CC) genotyping and antimicrobial susceptibility. RESULTS: S. aureus was commonly found in impetigo lesions of school children and was recovered from 57% of impetigo lesions frequently in conjunction with group A streptococcal infection. Methicillin-resistant S. aureus (MRSA) comprised 7% (20/299) of isolates and were all non-multi-resistant and all genotyped as CC1. In contrast, there was a diverse selection of 17 CCs among the 105 genotyped methicillin-susceptible S.aureus (MSSA) strains. Isolates of the rare, phylogenetically divergent and non-pigmented CC75 lineage (also called S. argenteus) were found in Fiji.From hospitalized patients the available 36 MRSA isolates from a 9-month period were represented by five CCs. The most common CCs were CC1 and CC239. CC1 is likely to be a community-acquired strain, reflecting what was found in the school children, whereas the CC239 is the very successful multi-drug resistant MRSA nosocomial lineage. Of 17 MSSA isolates, 59% carried genes for Panton-Valentine leukocidin. The S. aureus bacteraemia incidence rate of 50 per 100,000 population is among the highest reported in the literature and likely reflects the high overall burden of staphylococcal infections in this population. CONCLUSIONS: S. aureus is an important cause of disease in Fiji and there is considerable genotypic diversity in community skin infections in Fijian schoolchildren. Community acquired- (CA)- MRSA is present at a relatively low prevalence (6.7%) and was solely to CC1 (CA-MRSA). The globally successful CC239 is also a significant pathogen in Fiji.
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ItemReal-time qPCR improves meningitis pathogen detection in invasive bacterial-vaccine preventable disease surveillance in Fiji(NATURE PORTFOLIO, 2016-12-23)As part of the World Health Organization Invasive Bacterial-Vaccine Preventable Diseases (IB-VPD) surveillance in Suva, Fiji, cerebrospinal fluid (CSF) samples from suspected meningitis patients of all ages were examined by traditional methods (culture, Gram stain, and latex agglutination for bacterial antigen) and qPCR for Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. Of 266 samples tested, pathogens were identified in 47 (17.7%). S. pneumoniae was the most common pathogen detected (n = 17) followed by N. meningitidis (n = 13). The use of qPCR significantly increased detection of IB-VPD pathogens (P = 0.0001): of 35 samples that were qPCR positive for S. pneumoniae, N. meningitidis, and H. influenzae, only 10 were culture positive. This was particularly relevant for N. meningitidis, as only 1/13 cases was culture positive. Molecular serotyping by microarray was used to determine pneumococcal serotypes from 9 of 16 (56%) of samples using DNA directly extracted from CSF specimens. Results indicate that qPCR significantly increases detection of S. pneumoniae, N. meningitidis, and H. influenzae in CSF, and that application of molecular diagnostics is a feasible way to enhance local and global surveillance for IB-VPD.
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ItemEpidemiology and risk factors for typhoid fever in Central Division, Fiji, 2014-2017: A case-control study(PUBLIC LIBRARY SCIENCE, 2018-06)BACKGROUND: Typhoid fever is endemic in Fiji, with high reported annual incidence. We sought to identify the sources and modes of transmission of typhoid fever in Fiji with the aim to inform disease control. METHODOLOGY/PRINCIPAL FINDINGS: We identified and surveyed patients with blood culture-confirmed typhoid fever from January 2014 through January 2017. For each typhoid fever case we matched two controls by age interval, gender, ethnicity, and residential area. Univariable and multivariable analysis were used to evaluate associations between exposures and risk for typhoid fever. We enrolled 175 patients with typhoid fever and 349 controls. Of the cases, the median (range) age was 29 (2-67) years, 86 (49%) were male, and 84 (48%) lived in a rural area. On multivariable analysis, interrupted water availability (odds ratio [OR] = 2.17; 95% confidence interval [CI] 1.18-4.00), drinking surface water in the last 2 weeks (OR = 3.61; 95% CI 1.44-9.06), eating unwashed produce (OR = 2.69; 95% CI 1.48-4.91), and having an unimproved or damaged sanitation facility (OR = 4.30; 95% CI 1.14-16.21) were significantly associated with typhoid fever. Frequent handwashing after defecating (OR = 0.57; 95% CI 0.35-0.93) and using soap for handwashing (OR = 0.61; 95% CI 0.37-0.95) were independently associated with a lower odds of typhoid fever. CONCLUSIONS: Poor sanitation facilities appear to be a major source of Salmonella Typhi in Fiji, with transmission by drinking contaminated surface water and consuming unwashed produce. Improved sanitation facilities and protection of surface water sources and produce from contamination by human feces are likely to contribute to typhoid control in Fiji.
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ItemEpidemiology of intussusception before and after rotavirus vaccine introduction in Fiji(NATURE PUBLISHING GROUP, 2018-07-25)In 2012, Fiji introduced rotavirus vaccine (Rotarix, GSK) into the national immunisation schedule. We describe the intussusception epidemiology prior to rotavirus vaccine, temporal association of intussusception cases to administration of rotavirus vaccine, and estimate the additional number of intussusception cases that may be associated with rotavirus vaccine. A retrospective review of intussusception cases for children aged <24 months old was undertaken between January 2007 and October 2012 pre-vaccine. All admissions and deaths with a discharge diagnosis of intussusception, bowel obstruction, paralytic ileus, or intussusception ICD10-AM codes were extracted from national databases and hospital records. Nationwide active intussusception surveillance was established for three years post-vaccine (2013-2015). There were 24 definite intussusception cases in the pre-rotavirus vaccine period, 96% were confirmed by surgery. The median age was 6.5 months. The incidence rate was 22.2 (95% CI: 13.9-33.7) per 100,000 infants. There were no deaths. Active surveillance identified 25 definite intussusception cases, 96% of which were among children who were age-eligible for rotavirus vaccine. None were potentially vaccine related. We estimated one to five additional cases of intussusception every five years. The incidence of intussusception pre-rotavirus vaccine in Fiji is low. Intussusception associated with rotavirus vaccine is likely a rare event in Fiji.
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ItemIdentification of Klebsiella capsule synthesis loci from whole genome data(MICROBIOLOGY SOC, 2016-12)Klebsiella pneumoniae is a growing cause of healthcare-associated infections for which multi-drug resistance is a concern. Its polysaccharide capsule is a major virulence determinant and epidemiological marker. However, little is known about capsule epidemiology since serological typing is not widely accessible and many isolates are serologically non-typeable. Molecular typing techniques provide useful insights, but existing methods fail to take full advantage of the information in whole genome sequences. We investigated the diversity of the capsule synthesis loci (K-loci) among 2503 K. pneumoniae genomes. We incorporated analyses of full-length K-locus nucleotide sequences and also clustered protein-encoding sequences to identify, annotate and compare K-locus structures. We propose a standardized nomenclature for K-loci and present a curated reference database. A total of 134 distinct K-loci were identified, including 31 novel types. Comparative analyses indicated 508 unique protein-encoding gene clusters that appear to reassort via homologous recombination. Extensive intra- and inter-locus nucleotide diversity was detected among the wzi and wzc genes, indicating that current molecular typing schemes based on these genes are inadequate. As a solution, we introduce Kaptive, a novel software tool that automates the process of identifying K-loci based on full locus information extracted from whole genome sequences (https://github.com/katholt/Kaptive). This work highlights the extensive diversity of Klebsiella K-loci and the proteins that they encode. The nomenclature, reference database and novel typing method presented here will become essential resources for genomic surveillance and epidemiological investigations of this pathogen.
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ItemGenetic diversity, mobilisation and spread of the yersiniabactin-encoding mobile element ICEKp in Klebsiella pneumoniae populations(MICROBIOLOGY SOC, 2018-09)Mobile genetic elements (MGEs) that frequently transfer within and between bacterial species play a critical role in bacterial evolution, and often carry key accessory genes that associate with a bacteria's ability to cause disease. MGEs carrying antimicrobial resistance (AMR) and/or virulence determinants are common in the opportunistic pathogen Klebsiella pneumoniae, which is a leading cause of highly drug-resistant infections in hospitals. Well-characterised virulence determinants in K. pneumoniae include the polyketide synthesis loci ybt and clb (also known as pks), encoding the iron-scavenging siderophore yersiniabactin and genotoxin colibactin, respectively. These loci are located within an MGE called ICEKp, which is the most common virulence-associated MGE of K. pneumoniae, providing a mechanism for these virulence factors to spread within the population. Here we apply population genomics to investigate the prevalence, evolution and mobility of ybt and clb in K. pneumoniae populations through comparative analysis of 2498 whole-genome sequences. The ybt locus was detected in 40 % of K. pneumoniae genomes, particularly amongst those associated with invasive infections. We identified 17 distinct ybt lineages and 3 clb lineages, each associated with one of 14 different structural variants of ICEKp. Comparison with the wider population of the family Enterobacteriaceae revealed occasional ICEKp acquisition by other members. The clb locus was present in 14 % of all K. pneumoniae and 38.4 % of ybt+ genomes. Hundreds of independent ICEKp integration events were detected affecting hundreds of phylogenetically distinct K. pneumoniae lineages, including at least 19 in the globally-disseminated carbapenem-resistant clone CG258. A novel plasmid-encoded form of ybt was also identified, representing a new mechanism for ybt dispersal in K. pneumoniae populations. These data indicate that MGEs carrying ybt and clb circulate freely in the K. pneumoniae population, including among multidrug-resistant strains, and should be considered a target for genomic surveillance along with AMR determinants.
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ItemSafety and immunogenicity of the 23-valent pneumococcal polysaccharide vaccine at 12 months of age, following one, two, or three doses of the 7-valent pneumococcal conjugate vaccine in infancy(ELSEVIER SCI LTD, 2010-04-19)Fijian infants aged 6 weeks were stratified by ethnicity and randomized to receive 0, 1, 2, or 3 PCV-7 doses with or without the 23-valent pneumococcal polysaccharide vaccine (PPV-23) at 12 months. Strong booster effects for all 7 PCV-7 serotypes were elicited, and for 4/7 serotypes these responses were highest in the single PCV-7 group. There were fourfold rises in GMC for all non-PCV-7 serotypes. By 17 months the PPV-23 group still had significantly higher GMC (each p<0.001) for all serotypes. The PPV-23 was well tolerated and induced excellent responses for all serotypes which were greatest in the single PCV-7 group.
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ItemHyporesponsiveness to re-challenge dose following pneumococcal polysaccharide vaccine at 12 months of age, a randomized controlled trial(ELSEVIER SCI LTD, 2010-04-26)BACKGROUND: To evaluate the immunological impact of the 23-valent pneumococcal polysaccharide vaccine (23vPPS) at 12 months, for children who have received zero to three infant doses of seven-valent pneumococcal conjugate vaccine (PCV), on responses to a subsequent exposure to a small dose of 23vPPS (mPPS). METHODS: Five hundred and fifty-two Fijian infants were stratified by ethnicity and randomized into eight groups to receive zero, one, two, or three PCV doses at 14 weeks, six and 14 weeks, or six, ten, and 14 weeks. Within each group, half received 23vPPS at 12 months and all received mPPS at 17 months. Sera were taken prior and one month post-mPPS. FINDINGS: By 17 months, geometric mean antibody concentrations (GMC) to all 23 serotypes in 23vPPS were significantly higher in children who had received 23vPPS at 12 months compared to those who had not. Post-mPPS, children who had not received the 12 month 23vPPS had a significantly higher GMC for all PCV serotypes compared with those who had (each p<0.02). For the non-PCV serotypes, children who had not received the 12 month 23vPPS had significantly higher GMC for six of 16 non-PCV serotypes (7F, 9N, 12F, 19A, 22F, 33F) than those who did (each p<0.02). After adjusting for the pre-mPPS level, exposure to 23vPPS was associated with a lower response to mPPS for all serotypes (each p<0.001). INTERPRETATION: Despite higher antibody concentrations at 17 months in children who had received 23vPPS at 12 months, the response to a re-challenge was poor for all 23 serotypes compared to children who had not received the 12 month 23vPPS.