Infectious Diseases - Research Publications

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    Streptococcus gallolyticus subsp pasteurianus meningitis complicated by venous sinus thrombosis: A case report
    Wardle, M ; Mu, A ; Tong, SYC (ELSEVIER SCI LTD, 2018-06)
    A case of Streptococcus gallolyticus subsp. pasteurianus meningitis, unusually occurring in a splenectomized patient and complicated by cerebral venous thrombosis, is described. Following presentation with meningism and diagnosis and management of S. gallolyticus meningitis, the patient presented again with a further 4days of fevers and subsequently developed left-sided paresthesias. Cerebral imaging revealed a venous thrombus in the right frontal cortical veins and left sigmoid sinus. The patient recovered following 4 weeks of intravenous ceftriaxone and anticoagulation with enoxaparin and then warfarin. Apart from the splenectomy, no underlying cause was found. The patient was commenced on life-long prophylactic amoxicillin, given appropriate vaccinations, and anticoagulated with warfarin. After initial difficulties, identification of the causative organism to the subspecies level was confirmed by analysis of short-read whole genome sequencing data. This case demonstrates two features that have not previously been reported for S. gallolyticus subsp. pasteurianus infections: splenectomy as a potential risk factor and that infection may be complicated by cerebral venous thrombosis. The resolution provided by whole genome sequencing was valuable in accurately identifying the bacterial subspecies.
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    Perinatal risk factors associated with skin infection hospitalisation in Western Australian Aboriginal and Non-Aboriginal children
    Barnes, R ; Bowen, AC ; Walker, R ; Tong, SYC ; McVernon, J ; Campbell, PT ; Fathima, P ; de Klerk, NH ; Wu, Y ; Blyth, CC ; Carapetis, JR ; Moore, HC (WILEY, 2019-09)
    BACKGROUND: Hospitalisation with skin infection in Western Australian (WA) Aboriginal children is common, with the highest rates in infants and children from remote WA. OBJECTIVE: We aimed to quantify infant, maternal, and sociodemographic risk factors for skin infection hospitalisation in WA children, focussing on Aboriginal children aged <17 years. METHODS: We conducted a retrospective population-based cohort study with linked perinatal and hospitalisation data on WA-born children (1996-2012), of whom 31 348 (6.7%) were Aboriginal. We used Cox regression to calculate adjusted hazard ratios and associated population attributable fractions (PAFs) for perinatal factors attributed to first hospitalisation with skin infection. To identify specific risk factors for early-onset infection, we further restricted the cohort to infants aged <1 year. RESULTS: Overall, 5439 (17.4%) Aboriginal and 6750 (1.5%) non-Aboriginal children were hospitalised at least once with a skin infection. Aboriginal infants aged <1 year had the highest skin infection hospitalisation rate (63.2 per 1000 child-years). The strongest risk factors in Aboriginal children aged <17 years were socio-economic disadvantage, very remote location at birth, and multi-parity (≥3 previous pregnancies) accounting for 24%, 23%, and 15% of skin infection hospitalisations, respectively. Other risk factors included maternal age <20 years, maternal smoking during pregnancy, and low birthweight. CONCLUSIONS: We have quantified the relative influence of perinatal risk factors associated with skin infection hospitalisations in WA children, providing measures indicating which factors have the potential to reduce the most hospitalisations. Our evidence not only supports existing calls for substantial government investment in addressing underlying social and environmental barriers to healthy skin in WA Aboriginal children but also identifies potential areas to target health promotion messaging at individuals/families on maternal smoking during pregnancy and skin hygiene for families.
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    An urgent need for antimicrobial stewardship in Indigenous rural and remote primary health care
    Bowen, AC ; Daveson, K ; Anderson, L ; Tong, SYC (WILEY, 2019-07)
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    Mycobacterial mimicry in a man from Myanmar
    Griffin, DWJ ; Huang, GKL ; Lachapelle, P ; Tong, SYC ; Mahanty, S (WILEY, 2019-05)
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    Burden of skin disease in two remote primary healthcare centres in northern and central Australia
    Thomas, L ; Bowen, AC ; Ly, M ; Connors, C ; Andrews, R ; Tong, SYC (WILEY, 2019-03)
    The burden of skin infections across all age groups in remote Australian Indigenous communities is currently unknown. In a retrospective audit of 439 residents from two remote communities presenting to health clinics, skin conditions were the most common reason for presentation (1603/7392, 22%) and 330/439 (75%) residents presented at least once with a skin infection. Skin infections are an under-appreciated and dominant reason for presentation to primary healthcare centres in these indigenous communities and public health campaigns to address this should incorporate all age groups.
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    Global Scale Dissemination of ST93: A Divergent Staphylococcus aureus Epidemic Lineage That Has Recently Emerged From Remote Northern Australia
    van Hal, SJ ; Steinig, EJ ; Andersson, P ; Holden, MTG ; Harris, SR ; Nimmo, GR ; Williamson, DA ; Heffernan, H ; Ritchie, SR ; Kearns, AM ; Ellington, MJ ; Dickson, E ; De Lencastre, H ; Coombs, GW ; Bentley, SD ; Parkhill, J ; Holt, DC ; Giffard, PM ; Tong, SYC (FRONTIERS MEDIA SA, 2018-07-09)
    Background: In Australia, community-associated methicillin-resistant Staphylococcus aureus (MRSA) lineage sequence type (ST) 93 has rapidly risen to dominance since being described in the early 1990s. We examined 459 ST93 genome sequences from Australia, New Zealand, Samoa, and Europe to investigate the evolutionary history of ST93, its emergence in Australia and subsequent spread overseas. Results: Comparisons with other S. aureus genomes indicate that ST93 is an early diverging and recombinant lineage, comprising of segments from the ST59/ST121 lineage and from a divergent but currently unsampled Staphylococcal population. However, within extant ST93 strains limited genetic diversity was apparent with the most recent common ancestor dated to 1977 (95% highest posterior density 1973-1981). An epidemic ST93 population arose from a methicillin-susceptible progenitor in remote Northern Australia, which has a proportionally large Indigenous population, with documented overcrowded housing and a high burden of skin infection. Methicillin-resistance was acquired three times in these regions, with a clade harboring a staphylococcal cassette chromosome mec (SCCmec) IVa expanding and spreading to Australia's east coast by 2000. We observed sporadic and non-sustained introductions of ST93-MRSA-IVa to the United Kingdom. In contrast, in New Zealand, ST93-MRSA-IVa was sustainably transmitted with clonal expansion within the Pacific Islander population, who experience similar disadvantages as Australian Indigenous populations. Conclusion: ST93 has a highly recombinant genome including portions derived from an early diverging S. aureus population. Our findings highlight the need to understand host population factors in the emergence and spread of antimicrobial resistant community pathogens.
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    High-Resolution Melting Genotyping of Enterococcus faecium Based on Multilocus Sequence Typing Derived Single Nucleotide Polymorphisms
    Tong, SYC ; Xie, S ; Richardson, LJ ; Ballard, SA ; Dakh, F ; Grabsch, EA ; Grayson, ML ; Howden, BP ; Johnson, PDR ; Giffard, PM ; Msadek, T (PUBLIC LIBRARY SCIENCE, 2011-12-16)
    We have developed a single nucleotide polymorphism (SNP) nucleated high-resolution melting (HRM) technique to genotype Enterococcus faecium. Eight SNPs were derived from the E. faecium multilocus sequence typing (MLST) database and amplified fragments containing these SNPs were interrogated by HRM. We tested the HRM genotyping scheme on 85 E. faecium bloodstream isolates and compared the results with MLST, pulsed-field gel electrophoresis (PFGE) and an allele specific real-time PCR (AS kinetic PCR) SNP typing method. In silico analysis based on predicted HRM curves according to the G+C content of each fragment for all 567 sequence types (STs) in the MLST database together with empiric data from the 85 isolates demonstrated that HRM analysis resolves E. faecium into 231 "melting types" (MelTs) and provides a Simpson's Index of Diversity (D) of 0.991 with respect to MLST. This is a significant improvement on the AS kinetic PCR SNP typing scheme that resolves 61 SNP types with D of 0.95. The MelTs were concordant with the known ST of the isolates. For the 85 isolates, there were 13 PFGE patterns, 17 STs, 14 MelTs and eight SNP types. There was excellent concordance between PFGE, MLST and MelTs with Adjusted Rand Indices of PFGE to MelT 0.936 and ST to MelT 0.973. In conclusion, this HRM based method appears rapid and reproducible. The results are concordant with MLST and the MLST based population structure.
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    The clinical and molecular epidemiology of Staphylococcus aureus infections in Fiji
    Jenney, A ; Holt, D ; Ritika, R ; Southwell, P ; Pravin, S ; Buadromo, E ; Carapetis, J ; Tong, S ; Steer, A (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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    Protocol for the systematic review of the prevention, treatment and public health management of impetigo, scabies and fungal skin infections in resource-limited settings
    May, P ; Bowen, A ; Tong, S ; Steer, A ; Prince, S ; Andrews, R ; Currie, B ; Carapetis, J (BMC, 2016)
    BACKGROUND: Impetigo, scabies, and fungal skin infections disproportionately affect populations in resource-limited settings. Evidence for standard treatment of skin infections predominantly stem from hospital-based studies in high-income countries. The evidence for treatment in resource-limited settings is less clear, as studies in these populations may lack randomisation and control groups for cultural, ethical or economic reasons. Likewise, a synthesis of the evidence for public health control within endemic populations is also lacking. We propose a systematic review of the evidence for the prevention, treatment and public health management of skin infections in resource-limited settings, to inform the development of guidelines for the standardised and streamlined clinical and public health management of skin infections in endemic populations. METHODS: The protocol has been designed in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols statement. All trial designs and analytical observational study designs will be eligible for inclusion. A systematic search of the peer-reviewed literature will include PubMed, Excertpa Medica and Global Health. Grey literature databases will also be systematically searched, and clinical trials registries scanned for future relevant studies. The primary outcome of interest will be the clinical cure or decrease in prevalence of impetigo, scabies, crusted scabies, tinea capitis, tinea corporis or tinea unguium. Two independent reviewers will perform eligibility assessment and data extraction using standardised electronic forms. Risk of bias assessment will be undertaken by two independent reviewers according to the Cochrane Risk of Bias tool. Data will be tabulated and narratively synthesised. We expect there will be insufficient data to conduct meta-analysis. The final body of evidence will be reported against the Grades of Recommendation, Assessment, Development and Evaluation grading system. DISCUSSION: The evidence derived from the systematic review will be used to inform the development of guidelines for the management of skin infections in resource-limited settings. The evidence derived will be intended for use by clinicians, public health practitioners and policy makers in the treatment of skin infections and the development of skin infection control programmes. The review will identify any gaps in the current evidence to provide direction for future research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015029453.
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    Contaminated fingers: a potential cause of Chlamydia trachomatis-positive urine specimens
    Giffard, PM ; Lilliebridge, RA ; Wilson, J ; Murray, G ; Phillips, S ; Tabrizi, SN ; Garland, SM ; Martin, L ; Singh, G ; Tong, SYC ; Holt, DC ; Andersson, P (BMJ PUBLISHING GROUP, 2018-02)
    OBJECTIVES: The detection of an STI agent in a urogenital tract (UGT) specimen from a young child is regarded as being indicative of sexual abuse. However, the probabilities of contamination events that could conceivably lead to STI positive specimens in the absence of sexual contact are unclear. The objective was to estimate the potential for fingers that have come in contact with Chlamydia trachomatis-positive urine to detectably contaminate C. trachomatis-negative urine. METHODS: The study design was based on self-experimentation. Dilutions of C. trachomatis elementary bodies (EBs) were prepared. A participant contacted an EB dilution then a urine surrogate specimen. The experiment was performed by three participants using three C. trachomatis isolates, of genotype E, F and B. Two surrogate urine contact methods were used to mimic contamination of a carer assisting with a child's urine collection. All EB dilutions and urine surrogate specimens were subjected to C. trachomatis assay and quantification in a real-time PCR-based diagnostic system. RESULTS: The amplimer crossing point (Cq) for EB dilutions was 10.0±1.6 less than for corresponding finger contacted urine specimens, which corresponds to ~10 µL of EB suspension transferred. This was largely independent of participant identity, C. trachomatis strain or EB dilution. Hand decontamination led to large reductions in EBs transferred, but transfer remained consistently detectable. Recent Cq data from C. trachomatis-positive clinical urine specimens were collated, and 20% clearly contained sufficient C. trachomatis to detectably contaminate another specimen by finger-mediated transfer, as in this experiment. CONCLUSIONS: This study directly demonstrated the potential for urine contaminated fingers to convert a C. trachomatis-negative urine specimen to C. trachomatis positive as a result of contact. Accordingly, procedures for urine specimen collection, particularly from children, need to be designed to prevent contamination.