Publications by authors named "Deborah A Williamson"

157 Publications

Evolutionary dynamics of multidrug resistant Salmonella enterica serovar 4,[5],12:i:- in Australia.

Nat Commun 2021 08 9;12(1):4786. Epub 2021 Aug 9.

Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.

Salmonella enterica serovar 4,[5],12:i:- (Salmonella 4,[5],12:i:-) is a monophasic variant of Salmonella Typhimurium that has emerged as a global cause of multidrug resistant salmonellosis. We used Bayesian phylodynamics, genomic epidemiology, and phenotypic characterization to describe the emergence and evolution of Salmonella 4,[5],12:i:- in Australia. We show that the interruption of the genetic region surrounding the phase II flagellin, FljB, causing a monophasic phenotype, represents a stepwise evolutionary event through the accumulation of mobile resistance elements with minimal impairment to bacterial fitness. We identify three lineages with different population dynamics and discrete antimicrobial resistance profiles emerged, likely reflecting differential antimicrobial selection pressures. Two lineages are associated with travel to South-East Asia and the third lineage is endemic to Australia. Moreover antimicrobial-resistant Salmonella 4,[5],12:i- lineages efficiently infected and survived in host phagocytes and epithelial cells without eliciting significant cellular cytotoxicity, suggesting a suppression of host immune response that may facilitate the persistence of Salmonella 4,[5],12:i:-.
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http://dx.doi.org/10.1038/s41467-021-25073-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8352879PMC
August 2021

Scabies and impetigo in Samoa: A school-based clinical and molecular epidemiological study.

Lancet Reg Health West Pac 2021 Jan 29;6:100081. Epub 2020 Dec 29.

Department of Preventive and Social Medicine, University of Otago, New Zealand.

Background: Common infections of the skin such as impetigo and scabies represent a large burden of disease globally, being particularly prevalent in tropical and resource-limited settings. Efforts to address these infections through mass drug administrations have recently been shown as efficacious and safe. In Samoa, a Pacific Island nation, there is a marked lack of epidemiological data for these neglected tropical diseases, or appreciation of their drivers in this setting.

Methods: An observational, cross-sectional survey of children aged between 4 and 15 years attending primary schools in rural areas of Upolu Island, Samoa was carried out to assess the prevalence of impetigo and scabies in schoolchildren residing in rural Samoa, integrated with descriptive epidemiological and microbial genomic data. A phylogenetic assessment of local isolated from Samoan schoolchildren was performed to estimate putative community transmission.

Findings: In this survey, the prevalence of impetigo observed in Samoan schoolchildren was one of the highest described globally (57•1%, 95% CI [53•8-60•5%], 476/833). Associations between active impetigo and age and gender were noted, with younger children and males more commonly affected (aOR2•8 [1•8-4•7]and aOR1•8 [1•3-2•5], respectively). The prevalence of scabies was similar to that seen in other South Pacific island countries (14•4%, 95% CI [12•2-17•0%], 120/833). Transmission of was predicted, primarily between those children attending the same school. Carriage of was notably low, with pharyngeal carriage observed in less than 2% of schoolchildren, consistent with earlier studies from Samoa.

Interpretation: This study describes a considerable burden of disease attributed to impetigo and scabies in Samoa. These findings will be valuable in addressing the public health challenge posed by these conditions, providing baseline prevalence data and highlighting practical strategies to reduce transmission of relevant microbes and parasites in this setting.

Tala Tomua: O a'afiaga o le pa'u i fa'ama'i o le po'u (impetigo) ma le utu o le pa'u (scabies), ua tele naua le fanau ua maua ai i le pasefika, ma le lalolagi atoa. O fuafuaga vaai mamao ma polokalame e fofoina ai nei faafitauli, e aofia ai le inumaga o fualaau e tapeina ai nei fa'ama'i, ua aliali mai ai e mafai ona faatamaia nei fa'ama'i. E le o tele ni tusitusiga ma faamaumauga i totonu o Samoa, pe ta'atele nei fa'amai o le pa'u pe leai. Ona o le le faatauaina o nei fa'ama'i, e le o iloa fo'i ni mafuaga ma nisi tulaga e faateleina ai nei fa'ama'i o le pa'u i Samoa.

Faatinoina O Le Suesuega: O le suesuega faasaenisi i le fanau aoga i le va o le 4 ma le 15 tausaga o loo ao'oga i le tulaga lua i nisi o nu'u i tua i Upolu, na faatinoina ai suesuega lea, ia suesueina ai le aotelega ma fainumera o le fanau ua maua i fa'ama'I o le po'u (impetigo) ma le utu o le pa'u (scabies). O lenei foi suesuega, na fia iloa ai fo'i po'o a ituaiga siama eseese o loo maua i luga o pa'u ma tino o le fanau aoga, ina ia iloa ai foi auala ua pipisi ai nei siama mai le isi tamaitiiti i le isi, ona mafua ai lea o nei fa'ama'i o le pa'u.

Tanuuga O Le Suesuega: Ua faailoa mai i le suesuega, le ta'atele o le fa'ama'i o le po'u (impetigo) ua maua ai le fanau aoga (57%), i aoga na faia ai le suesuega. O se fainumera ua maualuga tele i le lalolagi atoa. E toatele atu nisi o le fanau laiti (younger) ma tama (male) e maua i le po'u nai lo isi tamaiti. O le fainumera o le utu o le pa'u (scabies) (14·4%) e tai tutusa lava ma isi motu o le Pasefika. O le feaveaina o le siama faapitoa (staph aureus) ua tupu lea i le fanau ua ao'oga i le aoga e tasi. E le toatele foi nisi o le fanau (2%) na maua i le siama faapitoa o le fa'ai (strep pyogenes) e ona mafua ai le fiva rumatika. O lenei fainumera ua tai tutusa ma suesuega faasaenisi na fai muamua i Samoa.

Aotelega: O le aotelega la o lenei suesuega faasaenisi, ua faailoaina mai ai le tele naua o le fa'ama'i o le pa'u, o po'u (impetigo) ma le utu o le pa'u (scabies) i Samoa nei. O nei foi suesuega o le a aoga tele ini polokalame ma ni fuafuaga mamao e fa'afoisia ai nei faafitauli i le soifua maloloina o le fanau i Samoa. O le a avea foi nei fainumera e faamaumauina mo le silafia e le atunuu ma le soifua maloloina, le ta'atele o nei fa'amai o le pa'u, mo le tapenaina o ni fofo talafeagai ise taimi o i luma, ina ia faaitiitina ai le pipisi o nei siami i fanau ao'oga i Samoa.
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http://dx.doi.org/10.1016/j.lanwpc.2020.100081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315614PMC
January 2021

An implementation science approach to evaluating pathogen whole genome sequencing in public health.

Genome Med 2021 07 28;13(1):121. Epub 2021 Jul 28.

Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.

Background: Pathogen whole genome sequencing (WGS) is being incorporated into public health surveillance and disease control systems worldwide and has the potential to make significant contributions to infectious disease surveillance, outbreak investigation and infection prevention and control. However, to date, there are limited data regarding (i) the optimal models for integration of genomic data into epidemiological investigations and (ii) how to quantify and evaluate public health impacts resulting from genomic epidemiological investigations.

Methods: We developed the Pathogen Genomics in Public HeAlth Surveillance Evaluation (PG-PHASE) Framework to guide examination of the use of WGS in public health surveillance and disease control. We illustrate the use of this framework with three pathogens as case studies: Listeria monocytogenes, Mycobacterium tuberculosis and SARS-CoV-2.

Results: The framework utilises an adaptable whole-of-system approach towards understanding how interconnected elements in the public health application of pathogen genomics contribute to public health processes and outcomes. The three phases of the PG-PHASE Framework are designed to support understanding of WGS laboratory processes, analysis, reporting and data sharing, and how genomic data are utilised in public health practice across all stages, from the decision to send an isolate or sample for sequencing to the use of sequence data in public health surveillance, investigation and decision-making. Importantly, the phases can be used separately or in conjunction, depending on the need of the evaluator. Subsequent to conducting evaluation underpinned by the framework, avenues may be developed for strategic investment or interventions to improve utilisation of whole genome sequencing.

Conclusions: Comprehensive evaluation is critical to support health departments, public health laboratories and other stakeholders to successfully incorporate microbial genomics into public health practice. The PG-PHASE Framework aims to assist public health laboratories, health departments and authorities who are either considering transitioning to whole genome sequencing or intending to assess the integration of WGS in public health practice, including the capacity to detect and respond to outbreaks and associated costs, challenges and facilitators in the utilisation of microbial genomics and public health impacts.
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http://dx.doi.org/10.1186/s13073-021-00934-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317677PMC
July 2021

Adding saliva testing to oropharyngeal and deep nasal swab testing increases PCR detection of SARS-CoV-2 in primary care and children.

Med J Aust 2021 Jul 20. Epub 2021 Jul 20.

The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC.

Objective: To compare the concordance and acceptability of saliva testing with standard-of-care oropharyngeal and bilateral deep nasal swab testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in children and in general practice.

Design: Prospective multicentre diagnostic validation study.

Setting: Royal Children's Hospital, and two general practices (cohealth, West Melbourne; Cirqit Health, Altona North) in Melbourne, July-October 2020.

Participants: 1050 people who provided paired saliva and oropharyngeal-nasal swabs for SARS-CoV-2 testing.

Main Outcome Measures: Numbers of cases in which SARS-CoV-2 was detected in either specimen type by real-time polymerase chain reaction; concordance of results for paired specimens; positive percent agreement (PPA) for virus detection, by specimen type.

Results: SARS-CoV-2 was detected in 54 of 1050 people with assessable specimens (5%), including 19 cases (35%) in which both specimens were positive. The overall PPA was 72% (95% CI, 58-84%) for saliva and 63% (95% CI, 49-76%) for oropharyngeal-nasal swabs. For the 35 positive specimens from people aged 10 years or more, PPA was 86% (95% CI, 70-95%) for saliva and 63% (95% CI, 45-79%) for oropharyngeal-nasal swabs. Adding saliva testing to standard-of-care oropharyngeal-nasal swab testing increased overall case detection by 59% (95% CI, 29-95%). Providing saliva was preferred to an oropharyngeal-nasal swab by most participants (75%), including 141 of 153 children under 10 years of age (92%).

Conclusion: In children over 10 years of age and adults, saliva testing alone may be suitable for SARS-CoV-2 detection, while for children under 10, saliva testing may be suitable as an adjunct to oropharyngeal-nasal swab testing for increasing case detection.
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http://dx.doi.org/10.5694/mja2.51188DOI Listing
July 2021

Evaluation of 6 Commercial SARS-CoV-2 Serology Assays Detecting Different Antibodies for Clinical Testing and Serosurveillance.

Open Forum Infect Dis 2021 Jul 10;8(7):ofab239. Epub 2021 May 10.

Victorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital, The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.

Background: Serological testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complements nucleic acid tests for patient diagnosis and enables monitoring of population susceptibility to inform the coronavirus disease 2019 (COVID-19) pandemic response. It is important to understand the reliability of assays with different antigen or antibody targets to detect humoral immunity after SARS-CoV-2 infection and to understand how antibody (Ab) binding assays compare to those detecting neutralizing antibody (nAb), particularly as we move into the era of vaccines.

Methods: We evaluated the performance of 6 commercially available enzyme-linked immunosorbent assays (ELISAs), including a surrogate virus neutralization test (sVNT), for detection of SARS-CoV-2 immunoglobulins (IgA, IgM, IgG), total or nAb. A result subset was compared with a cell culture-based microneutralization (MN) assay. We tested sera from patients with prior reverse transcription polymerase chain reaction-confirmed SARS-CoV-2 infection, prepandemic sera, and potential cross-reactive sera from patients with other non-COVID-19 acute infections.

Results: For sera collected >14 days post-symptom onset, the assay achieving the highest sensitivity was the Wantai total Ab at 100% (95% CI, 94.6%-100%), followed by 93.1% for Euroimmun NCP-IgG, 93.1% for GenScript sVNT, 90.3% for Euroimmun S1-IgG, 88.9% for Euroimmun S1-IgA, and 83.3% for Wantai IgM. Specificity for the best-performing assay was 99.5% for the Wantai total Ab, and for the lowest-performing assay it was 97.1% for sVNT (as per the Instructions for Use [IFU]). The Wantai Total Ab had the best agreement with MN at 98% followed by Euroimmun S1-IgA, Euro NCP-IgG, and sVNT (as per IFU) with 97%, 97% and 95%, respectively; Wantai IgM had the poorest agreement at 93%.

Conclusions: Performance characteristics of the SARS-CoV-2 serology assays detecting different antibody types are consistent with those found in previously published reports. Evaluation of the surrogate virus neutralization test in comparison to the Ab binding assays and a cell culture-based neutralization assay showed good result correlation between all assays. However, correlation between the cell-based neutralization test and some assays detecting Ab's not specifically involved in neutralization was higher than with the sVNT. This study demonstrates the reliability of different assays to detect the humoral immune response following SARS-CoV-2 infection, which can be used to optimize serological test algorithms for assessing antibody responses post-SARS-CoV-2 infection or vaccination.
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http://dx.doi.org/10.1093/ofid/ofab239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136026PMC
July 2021

A comparison of cotton-tipped and nylon flocked swabs for culture of Neisseria gonorrhoeae from oropharyngeal samples.

Diagn Microbiol Infect Dis 2021 Jun 18;101(3):115455. Epub 2021 Jun 18.

Melbourne Sexual Health Centre, Alfred Health, Melbourne, Victoria, Australia; Central Clinical School, Monash University, Melbourne, Victoria, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia. Electronic address:

Our aim was to determine if there was a difference in culture positivity for oropharyngeal gonorrhoea when sampling using a nylon-flocked versus cotton-tipped swab. We collected FLOQSwabs and cotton-tipped swabs from individuals aged ≥ 18 years who had untreated oropharyngeal gonorrhoea detected by NAAT between November 2019-June 2020.Of 78 participants, 32 (41.0%) were culture-positive for N. gonorrhoeae from either swab. Of these 32, 29 (90.6%, 95%CI: 75.0%-98.0%) were positive on both swabs, one (3.1%, 95%CI: 0.0%-16.2%) tested positive on FLOQSwab only and two (6.2%, 95%CI: 0.1%-20.8%) tested positive on cotton-tipped swabs only. There was moderate agreement between the swabs in the amount of bacterial growth (Cohen's Kappa (k)=0.745; 95%CI: 0.622-0.868, p<0.001). Our results showed that the proportion of positive results was comparable using the FLOQSwabs versus the cotton-tipped swabs for oropharyngeal gonorrhoea culture.
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http://dx.doi.org/10.1016/j.diagmicrobio.2021.115455DOI Listing
June 2021

Genomics-informed responses in the elimination of COVID-19 in Victoria, Australia: an observational, genomic epidemiological study.

Lancet Public Health 2021 08 10;6(8):e547-e556. Epub 2021 Jul 10.

Victorian Department of Health, Melbourne, VIC, Australia.

Background: A cornerstone of Australia's ability to control COVID-19 has been effective border control with an extensive supervised quarantine programme. However, a rapid recrudescence of COVID-19 was observed in the state of Victoria in June, 2020. We aim to describe the genomic findings that located the source of this second wave and show the role of genomic epidemiology in the successful elimination of COVID-19 for a second time in Australia.

Methods: In this observational, genomic epidemiological study, we did genomic sequencing of all laboratory-confirmed cases of COVID-19 diagnosed in Victoria, Australia between Jan 25, 2020, and Jan 31, 2021. We did phylogenetic analyses, genomic cluster discovery, and integrated results with epidemiological data (detailed information on demographics, risk factors, and exposure) collected via interview by the Victorian Government Department of Health. Genomic transmission networks were used to group multiple genomic clusters when epidemiological and genomic data suggested they arose from a single importation event and diversified within Victoria. To identify transmission of emergent lineages between Victoria and other states or territories in Australia, all publicly available SARS-CoV-2 sequences uploaded before Feb 11, 2021, were obtained from the national sequence sharing programme AusTrakka, and epidemiological data were obtained from the submitting laboratories. We did phylodynamic analyses to estimate the growth rate, doubling time, and number of days from the first local infection to the collection of the first sequenced genome for the dominant local cluster, and compared our growth estimates to previously published estimates from a similar growth phase of lineage B.1.1.7 (also known as the Alpha variant) in the UK.

Findings: Between Jan 25, 2020, and Jan 31, 2021, there were 20 451 laboratory-confirmed cases of COVID-19 in Victoria, Australia, of which 15 431 were submitted for sequencing, and 11 711 met all quality control metrics and were included in our analysis. We identified 595 genomic clusters, with a median of five cases per cluster (IQR 2-11). Overall, samples from 11 503 (98·2%) of 11 711 cases clustered with another sample in Victoria, either within a genomic cluster or transmission network. Genomic analysis revealed that 10 426 cases, including 10 416 (98·4%) of 10 584 locally acquired cases, diagnosed during the second wave (between June and October, 2020) were derived from a single incursion from hotel quarantine, with the outbreak lineage (transmission network G, lineage D.2) rapidly detected in other Australian states and territories. Phylodynamic analyses indicated that the epidemic growth rate of the outbreak lineage in Victoria during the initial growth phase (samples collected between June 4 and July 9, 2020; 47·4 putative transmission events, per branch, per year [1/years; 95% credible interval 26·0-85·0]), was similar to that of other reported variants, such as B.1.1.7 in the UK (mean approximately 71·5 1/years). Strict interventions were implemented, and the outbreak lineage has not been detected in Australia since Oct 29, 2020. Subsequent cases represented independent international or interstate introductions, with limited local spread.

Interpretation: Our study highlights how rapid escalation of clonal outbreaks can occur from a single incursion. However, strict quarantine measures and decisive public health responses to emergent cases are effective, even with high epidemic growth rates. Real-time genomic surveillance can alter the way in which public health agencies view and respond to COVID-19 outbreaks.

Funding: The Victorian Government, the National Health and Medical Research Council Australia, and the Medical Research Future Fund.
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http://dx.doi.org/10.1016/S2468-2667(21)00133-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270762PMC
August 2021

The performance of the Xpert MTB/RIF Version G4 in a low tuberculosis incidence setting.

Pathology 2021 Jul 1. Epub 2021 Jul 1.

Mycobacterial Reference Laboratory, Victorian Infectious Diseases Reference Laboratory, Melbourne, Vic, Australia; Department of Microbiology, Royal Melbourne Hospital, Parkville, Vic, Australia; Microbiological Diagnostic Unit Public Health Laboratory, Peter Doherty Institute, Melbourne, Vic, Australia.

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http://dx.doi.org/10.1016/j.pathol.2021.03.007DOI Listing
July 2021

Threat of COVID-19 impacting on a quaternary healthcare service: a retrospective cohort study of administrative data.

BMJ Open 2021 06 24;11(6):e045975. Epub 2021 Jun 24.

Department of General Medicine, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.

Objectives: The threat of a pandemic, over and above the disease itself, may have significant and broad effects on a healthcare system. We aimed to describe the impact of the SARS-CoV-2 pandemic (during a relatively low transmission period) and associated societal restrictions on presentations, admissions and outpatient visits.

Design: We compared hospital activity in 2020 with the preceding 5 years, 2015-2019, using a retrospective cohort study design.

Setting: Quaternary hospital in Melbourne, Australia.

Participants: Emergency department presentations, hospital admissions and outpatient visits from 1 January 2015 to 30 June 2020, n=896 934 episodes of care.

Intervention: In Australia, the initial peak COVID-19 phase was March-April.

Primary And Secondary Outcome Measures: Separate linear regression models were fitted to estimate the impact of the pandemic on the number, type and severity of emergency presentations, hospital admissions and outpatient visits.

Results: During the peak COVID-19 phase (March and April 2020), there were marked reductions in emergency presentations (10 389 observed vs 14 678 expected; 29% reduction; p<0.05) and hospital admissions (5972 observed vs 8368 expected; 28% reduction; p<0.05). Stroke (114 observed vs 177 expected; 35% reduction; p<0.05) and trauma (1336 observed vs 1764 expected; 24% reduction; p<0.05) presentations decreased; acute myocardial infarctions were unchanged. There was an increase in the proportion of hospital admissions requiring intensive care (7.0% observed vs 6.0% expected; p<0.05) or resulting in death (2.2% observed vs 1.5% expected; p<0.05). Outpatient attendances remained similar (30 267 observed vs 31 980 expected; 5% reduction; not significant) but telephone/telehealth consultations increased from 2.5% to 45% (p<0.05) of total consultations.

Conclusions: Although case numbers of COVID-19 were relatively low in Australia during the first 6 months of 2020, the impact on hospital activity was profound.
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http://dx.doi.org/10.1136/bmjopen-2020-045975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228577PMC
June 2021

Ethnically Disparate Disease Progression and Outcomes among Acute Rheumatic Fever Patients in New Zealand, 1989-2015.

Emerg Infect Dis 2021 07;27(7)

We investigated outcomes for patients born after 1983 and hospitalized with initial acute rheumatic fever (ARF) in New Zealand during 1989-2012. We linked ARF progression outcome data (recurrent hospitalization for ARF, hospitalization for rheumatic heart disease [RHD], and death from circulatory causes) for 1989-2015. Retrospective analysis identified initial RHD patients <40 years of age who were hospitalized during 2010-2015 and previously hospitalized for ARF. Most (86.4%) of the 2,182 initial ARF patients did not experience disease progression by the end of 2015. Progression probability after 26.8 years of theoretical follow-up was 24.0%; probability of death, 1.0%. Progression was more rapid and ≈2 times more likely for indigenous Māori or Pacific Islander patients. Of 435 initial RHD patients, 82.2% had not been previously hospitalized for ARF. This young cohort demonstrated low mortality rates but considerable illness, especially among underserved populations. A national patient register could help monitor, prevent, and reduce ARF progression.
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http://dx.doi.org/10.3201/eid2707.203045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237904PMC
July 2021

Infrared Based Saliva Screening Test for COVID-19.

Angew Chem Int Ed Engl 2021 07 29;60(31):17102-17107. Epub 2021 Jun 29.

Centre for Biospectroscopy and School of Chemistry, Monash University, Clayton Campus, 3800, Victoria, Australia.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented need for diagnostic testing that is critical in controlling the spread of COVID-19. We propose a portable infrared spectrometer with purpose-built transflection accessory for rapid point-of-care detection of COVID-19 markers in saliva. Initially, purified virion particles were characterized with Raman spectroscopy, synchrotron infrared (IR) and AFM-IR. A data set comprising 171 transflection infrared spectra from 29 subjects testing positive for SARS-CoV-2 by RT-qPCR and 28 testing negative, was modeled using Monte Carlo Double Cross Validation with 50 randomized test and model sets. The testing sensitivity was 93 % (27/29) with a specificity of 82 % (23/28) that included positive samples on the limit of detection for RT-qPCR. Herein, we demonstrate a proof-of-concept high throughput infrared COVID-19 test that is rapid, inexpensive, portable and utilizes sample self-collection thus minimizing the risk to healthcare workers and ideally suited to mass screening.
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http://dx.doi.org/10.1002/anie.202104453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222893PMC
July 2021

Limited clinical value of early repeat RT-PCR testing for SARS-CoV-2.

Med J Aust 2021 07 25;215(1):42-43. Epub 2021 May 25.

Royal Melbourne Hospital, Melbourne, VIC.

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http://dx.doi.org/10.5694/mja2.51102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242732PMC
July 2021

Global population structure and genotyping framework for genomic surveillance of the major dysentery pathogen, Shigella sonnei.

Nat Commun 2021 05 11;12(1):2684. Epub 2021 May 11.

Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, VIC, Australia.

Shigella sonnei is the most common agent of shigellosis in high-income countries, and causes a significant disease burden in low- and middle-income countries. Antimicrobial resistance is increasingly common in all settings. Whole genome sequencing (WGS) is increasingly utilised for S. sonnei outbreak investigation and surveillance, but comparison of data between studies and labs is challenging. Here, we present a genomic framework and genotyping scheme for S. sonnei to efficiently identify genotype and resistance determinants from WGS data. The scheme is implemented in the software package Mykrobe and tested on thousands of genomes. Applying this approach to analyse >4,000 S. sonnei isolates sequenced in public health labs in three countries identified several common genotypes associated with increased rates of ciprofloxacin resistance and azithromycin resistance, confirming intercontinental spread of highly-resistant S. sonnei clones and demonstrating the genomic framework can facilitate monitoring the spread of resistant clones, including those that have recently emerged, at local and global scales.
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http://dx.doi.org/10.1038/s41467-021-22700-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113504PMC
May 2021

Transcriptional and epi-transcriptional dynamics of SARS-CoV-2 during cellular infection.

Cell Rep 2021 05 23;35(6):109108. Epub 2021 Apr 23.

Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; Department of Clinical Pathology, University of Melbourne, Melbourne, VIC 3000, Australia; Department of Infectious Disease, Imperial College London, London SW7 2AZ, UK; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia. Electronic address:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses subgenomic RNA (sgRNA) to produce viral proteins for replication and immune evasion. We apply long-read RNA and cDNA sequencing to in vitro human and primate infection models to study transcriptional dynamics. Transcription-regulating sequence (TRS)-dependent sgRNA upregulates earlier in infection than TRS-independent sgRNA. An abundant class of TRS-independent sgRNA consisting of a portion of open reading frame 1ab (ORF1ab) containing nsp1 joins to ORF10, and the 3' untranslated region (UTR) upregulates at 48 h post-infection in human cell lines. We identify double-junction sgRNA containing both TRS-dependent and -independent junctions. We find multiple sites at which the SARS-CoV-2 genome is consistently more modified than sgRNA and that sgRNA modifications are stable across transcript clusters, host cells, and time since infection. Our work highlights the dynamic nature of the SARS-CoV-2 transcriptome during its replication cycle.
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http://dx.doi.org/10.1016/j.celrep.2021.109108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062406PMC
May 2021

Multi-site assessment of rapid, point-of-care antigen testing for the diagnosis of SARS-CoV-2 infection in a low-prevalence setting: A validation and implementation study.

Lancet Reg Health West Pac 2021 Apr 2;9:100115. Epub 2021 Mar 2.

Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Australia.

Background: In Australia, COVID-19 diagnosis relies on RT-PCR testing which is relatively costly and time-consuming. To date, few studies have assessed the performance and implementation of rapid antigen-based SARS-CoV-2 testing in a setting with a low prevalence of COVID-19 infections, such as Australia.

Methods: This study recruited participants presenting for COVID-19 testing at three Melbourne metropolitan hospitals during a period of low COVID-19 prevalence. The Abbott PanBio COVID-19 Ag point-of-care test was performed alongside RT-PCR. In addition, participants with COVID-19 notified to the Victorian Government were invited to provide additional swabs to aid validation. Implementation challenges were also documented.

Findings: The specificity of the Abbott PanBio COVID-19 Ag test was 99.96% (95% CI 99.73 - 100%). Sensitivity amongst participants with RT-PCR-confirmed infection was dependent upon the duration of symptoms reported, ranging from 77.3% (duration 1 to 33 days) to 100% in those within seven days of symptom onset. A range of implementation challenges were identified which may inform future COVID-19 testing strategies in a low prevalence setting.

Interpretation: Given the high specificity, antigen-based tests may be most useful in rapidly triaging public health and hospital resources while expediting confirmatory RT-PCR testing. Considering the limitations in test sensitivity and the potential for rapid transmission in susceptible populations, particularly in hospital settings, careful consideration is required for implementation of antigen testing in a low prevalence setting.

Funding: This work was funded by the Victorian Department of Health and Human Services. The funder was not involved in data analysis or manuscript preparation.
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http://dx.doi.org/10.1016/j.lanwpc.2021.100115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076656PMC
April 2021

Treponema pallidum detection in lesion and non-lesion sites in men who have sex with men with early syphilis: a prospective, cross-sectional study.

Lancet Infect Dis 2021 09 22;21(9):1324-1331. Epub 2021 Apr 22.

Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC, Australia; Central Clinical School, Faculty of Nursing, Medicine and Health Sciences, Monash University, Melbourne, VIC, Australia.

Background: Syphilis transmission is increasing, and precisely how Treponema pallidum is transmitted sexually from person to person is unclear. We aimed to determine the frequency of T pallidum shedding from potentially asymptomatic sites and the stage of infection at which shedding is most frequent in men who have sex with men (MSM), who have been disproportionately affected by syphilis.

Methods: We did a prospective, cross-sectional study in MSM recruited from Melbourne Sexual Health Centre (Melbourne, VIC, Australia). Men were eligible if they were aged 18 years or older, reported sex with men during the past 12 months, and had laboratory confirmed primary, secondary, or early latent syphilis, consistent with Australian definitions. Primary and secondary syphilis lesions were swabbed and non-lesion samples were collected via oral rinse, oral cavity swab, anal canal swab, urine, and semen. Samples were tested for T pallidum using PCR assays targeting polA (lesion and non-lesion samples) and 47 kDa (non-lesion samples only) gene targets. The primary outcome was the proportion of men with T pallidum detected from potentially asymptomatic sites-namely, the mouth, anus, urethra, and semen.

Findings: Between Nov 30, 2015, and May 23, 2019, 246 MSM were screened for inclusion, of whom 200 had serologically confirmed early syphilis and were included in the study: 54 (27%) of 200 had primary syphilis, 93 (47%) had secondary syphilis, and 53 (27%) had early latent syphilis. T pallidum DNA was detected in 48 (24%; 95% CI 18·3-30·5) of 200 men by oral rinse or oral lesion swab, or both, of whom 24 had no oral lesions. Oral T pallidum detection was most frequent in those with secondary syphilis compared with those at other stages of disease (41 [44%] of 93 vs seven [7%] of 107; p<0·0001), and in men with rapid plasma reagin titres of 1/64 or higher compared with those with lower titres (37 [32%] of 117 vs 11 [13%] of 83; p=0·0026). T pallidum was detected by anal canal swab or anal lesion swab, or both, in 45 (23·0%; 95% CI 17·3-29·5) of 196 men with available samples, of whom ten had no anal lesion. Furthermore, T pallidum was detected in urine samples of 12 (6·1%, 3·2-10·3) of 198 men and in semen samples from six (12·0%, 4·5-24·3) of 50 men who provided samples. Among the 93 men with secondary syphilis, 69 (74%) had T pallidum detected at any site, and 24 (26%) had detection at two or more separate sites. Among the 54 men with primary syphilis, 49 (91%) had T pallidum detected at any site, and 11 (20%) had detection at two or more separate sites. Among the 53 men with early latent syphilis, four (8%) had T pallidum detected at any site and none had T pallidum detected at two or more separate sites.

Interpretation: Unrecognised oral and anal shedding of T pallidum occurs in MSM with early syphilis, most frequently in those with secondary syphilis, suggesting secondary syphilis is the most infectious stage and that earlier detection and treatment of syphilis to prevent progression to the secondary stage might improve syphilis control. Future research is needed to ascertain the contribution of shedding of T pallidum from non-lesion sites to transmission of syphilis.

Funding: Australian National Health and Medical Research Council.
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http://dx.doi.org/10.1016/S1473-3099(20)30838-0DOI Listing
September 2021

Spatial and temporal epidemiology of infectious syphilis in Victoria, Australia, 2015-2018.

Sex Transm Dis 2021 Apr 14. Epub 2021 Apr 14.

Melbourne Sexual Health Centre, Alfred Health, Melbourne, Victoria, Australia Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia Department of Health, Melbourne, Victoria, Australia Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, The University of Melbourne at The Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia Centre for Excellence in Rural Sexual Health, Melbourne Medical School, The University of Melbourne, Melbourne, Victoria, Australia Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.

Abstract: This analysis of notified syphilis cases in Victoria, Australia between 2015 and 2018 shows the syphilis epidemic in Victoria has become more generalised, with increases among heterosexual men and women residing in outer Melbourne suburbs - areas that differ from those of gay men.
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http://dx.doi.org/10.1097/OLQ.0000000000001438DOI Listing
April 2021

Oropharyngeal gonorrhoea infections among heterosexual women and heterosexual men with urogenital gonorrhoea attending a sexual health clinic in Melbourne, Australia.

Clin Microbiol Infect 2021 May 6. Epub 2021 May 6.

Central Clinical School, Monash University, Melbourne, Victoria, Australia; Melbourne Sexual Health Centre, Alfred Health, Melbourne, Victoria, Australia; Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia. Electronic address:

Objectives: There is limited evidence about the transmission and prevalence of oropharyngeal gonorrhoea in heterosexuals. From August 2017, Melbourne Sexual Health Centre (MSHC) began testing for oropharyngeal gonorrhoea among heterosexuals with untreated urogenital gonorrhoea. This study aims to determine the positivity of oropharyngeal gonorrhoea among heterosexuals diagnosed with urogenital gonorrhoea at MSHC between August 2017 and May 2020.

Methods: We included individuals who had oropharyngeal gonorrhoea testing within 30 days of initial testing. We reported the number and proportion of oropharyngeal gonorrhoea positivity, stratified by gender and contact of gonorrhoea. The χ test was performed to compare the oropharyngeal gonorrhoea positivity between groups.

Results: Of 617 individuals with untreated urogenital gonorrhoea, 424 (68.7%) were tested for oropharyngeal gonorrhoea. Oropharyngeal gonorrhoea positivity was 38.9% (95%CI 34.2-43.7%, 165/424), and was higher in women than in men (115/252, 45.6% versus 50/172, 29.1%, p = 0.001). Furthermore, oropharyngeal gonorrhoea positivity was higher among individuals who were contacts of gonorrhoea cases compared to those who were not (29/44, 65.9% versus 136/380, 35.8%, p < 0.001). There was also no significant difference between women who were sex workers and those who were not (30/78, 38.5% versus 85/174, 48.9%, p = 0.126).

Conclusions: Our data suggest that oropharyngeal gonorrhoea infection is common among heterosexual women and heterosexual men with untreated urogenital gonorrhoea. Testing heterosexual women and heterosexual men for oropharyngeal gonorrhoea will identify a significant proportion with unrecognized oropharyngeal infections whose recommended treatment is different in some countries.
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http://dx.doi.org/10.1016/j.cmi.2021.03.033DOI Listing
May 2021

Timing of primary syphilis treatment and impact on the development of treponemal antibodies: a cross-sectional clinic-based study.

Sex Transm Infect 2021 Mar 29. Epub 2021 Mar 29.

Melbourne Sexual Health Centre, Alfred Health, Carlton, Victoria, Australia.

Background: Serology is negative in a proportion of primary syphilis cases where PCR testing is positive. We aimed to identify discordant, PCR-positive, serology-negative primary syphilis cases and any clinical or laboratory factors associated with failure to subsequently seroconvert.

Methods: Serodiscordant primary syphilis cases that were PCR-positive and serology-negative (including rapid plasma reagin, particle agglutination, enzyme immunoassay or chemiluminescence assay) were identified from the Melbourne Sexual Health Centre electronic records between April 2011 and December 2019. Clinical and laboratory associations were examined.

Results: There were 814 primary syphilis cases in the study period and 38 (4.7%) were serodiscordant, 35 in men who have sex with men. Thirty-two had follow-up serology performed a median of 24 days later, of which 16 (50%) seroconverted, mostly (81%) within 6 weeks. Failure to seroconvert was significantly associated with treatment on day 1. Of the 12 cases treated on day 1, 10 (83%) failed to seroconvert compared with 6 of 20 (30%) among those who were treated after day 1.

Discussion: Earlier treatment of primary syphilis can prevent the development of serological markers. PCR can identify primary syphilis lesions before the development of serological markers and improve diagnosis of early primary syphilis lesions. Serology alone will miss a proportion of primary syphilis infections and should be repeated if a diagnosis of syphilis is being considered.
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http://dx.doi.org/10.1136/sextrans-2020-054739DOI Listing
March 2021

Cost of whole genome sequencing for non-typhoidal Salmonella enterica.

PLoS One 2021 19;16(3):e0248561. Epub 2021 Mar 19.

Research School of Population Health, The Australian National University, Canberra, Australian Capital Territory, Australia.

Background: While whole genome sequencing (WGS) may be more expensive than traditional testing and polymerase chain reaction (PCR), simple cost comparisons ignore the potential for WGS to reduce the societal costs of non-typhoidal Salmonella enterica through public health action to prevent illness.

Methods: We determined how many cases the use of WGS data would need to prevent to be cost-equal to serotyping and MLVA, or culture independent testing based on PCR in Australia. We then examined the costs and cost-savings of current typing methods compared with WGS in outbreak scenarios.

Results: A median of 275 (90% CrI -55-775) or 1.9% (90% CrI -0.4%-5.4%) of notified serotyped Salmonella cases would need to be prevented for WGS to be cost-equal to current typing methods and 1,550 (90% CrI 820-2,725) or 9.6% of all notified Salmonella cases would need to be prevented to be cost-equal to PCR. WGS is likely to result in cost savings in prolonged outbreaks, where data can support earlier public health action.

Conclusions: Despite currently having a higher cost per isolate, routine WGS of Salmonella was no more expensive than existing typing methods or PCR where >2% of illness was averted.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248561PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978342PMC
March 2021

Antiseptic mouthwash for gonorrhoea prevention (OMEGA): a randomised, double-blind, parallel-group, multicentre trial.

Lancet Infect Dis 2021 05 4;21(5):647-656. Epub 2021 Mar 4.

Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC, Australia; Central Clinical School, Monash University, Melbourne, VIC, Australia; China-Australia Joint Research Centre for Infectious Diseases, School of Public Health, Xi'an Jiaotong University, Xi'an, China.

Background: To address the increasing incidence of gonorrhoea and antimicrobial resistance, we compared the efficacy of Listerine and Biotène mouthwashes for preventing gonorrhoea among men who have sex with men (MSM).

Methods: The OMEGA trial was a multicentre, parallel-group, double-blind randomised controlled trial among MSM, done at three urban sexual health clinics and one general practice clinic in Australia. Men were eligible if they were diagnosed with oropharyngeal gonorrhoea by nucleic acid amplification test (NAAT) in the previous 30 days or were aged 16-24 years. They were randomly assigned to receive Listerine (intervention) or Biotène (control) via a computer-generated sequence (1:1 ratio, block size of four). Participants, clinicians, data collectors, data analysts, and outcome adjudicators were masked to the interventions after assignment. Participants were instructed to rinse and gargle with 20 mL of mouthwash for 60 s at least once daily for 12 weeks. Oropharyngeal swabs were collected by research nurses every 6 weeks, and participants provided saliva samples every 3 weeks, to be tested for Neisseria gonorrhoeae with NAAT and quantitative PCR. The primary outcome was proportion of MSM diagnosed with oropharyngeal N gonorrhoeae infection at any point over the 12-week period, defined as a positive result for either oropharyngeal swabs or saliva samples by NAAT, and the cumulative incidence of oropharyngeal gonorrhoea at the week 12 visit. A modified intention-to-treat analysis for the primary outcome was done that included men who provided at least one follow-up specimen over the 12-week study period. The trial was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12616000247471).

Findings: Between March 30, 2016, and Oct 26, 2018, 786 MSM were screened and 256 were excluded. 264 MSM were randomly assigned to the Biotène group and 266 to the Listerine group. The analysis population included 227 (86%) men in the Biotène group and 219 (82%) in the Listerine group. Oropharyngeal gonorrhoea was detected in ten (4%) of 227 of MSM in the Biotène group and in 15 (7%) of 219 in the Listerine group (adjusted risk difference 2·5%, 95% CI -1·8 to 6·8). The cumulative incidence of oropharyngeal gonorrhoea at the week 12 visit did not differ between the two mouthwash groups (adjusted risk difference 3·1%, 95% CI -1·4 to 7·7).

Interpretation: Listerine did not reduce the incidence of oropharyngeal gonorrhoea compared with Biotène. However, previous research suggests that mouthwash might reduce the infectivity of oropharyngeal gonorrhoea; therefore, further studies of mouthwash examining its inhibitory effect on N gonorrhoeae are warranted to determine if it has a potential role for the prevention of transmission.

Funding: Australian National Health and Medical Research Council.
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http://dx.doi.org/10.1016/S1473-3099(20)30704-0DOI Listing
May 2021

Reflex Detection of Ciprofloxacin Resistance in Neisseria gonorrhoeae by Use of the SpeeDx ResistancePlus GC Assay.

J Clin Microbiol 2021 04 20;59(5). Epub 2021 Apr 20.

Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia

Resistance-guided therapy (RGT) for gonorrhea may reduce unnecessary use of broad-spectrum antibiotics. When reflexed from the Aptima Combo 2 assay, the ResistancePlus GC assay demonstrated 94.8% sensitivity and 100.0% specificity for detection. Of the 379 concordant -positive samples, 86.8% were found to possess the S91F mutation, which was highly predictive for ciprofloxacin resistance and stable across 3,144 publicly available genomes. Our work supports the feasibility of implementing RGT for gonorrhea into routine molecular workflows.
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http://dx.doi.org/10.1128/JCM.00089-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091848PMC
April 2021

Serological Profiling of Group A Streptococcus Infections in Acute Rheumatic Fever.

Clin Infect Dis 2021 Feb 26. Epub 2021 Feb 26.

School of Medical Sciences, University of Auckland, Auckland, New Zealand.

Rheumatic fever is a serious post-infectious sequela of Group A Streptococcus (GAS). Prior GAS exposures were mapped in sera using a large panel of M-type specific peptides. Rheumatic fever patients had serological evidence of significantly more GAS exposures than matched controls suggesting immune priming by repeat infections contributes to pathogenesis.
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http://dx.doi.org/10.1093/cid/ciab180DOI Listing
February 2021

Clinical relevance of topical antibiotic use in co-selecting for multidrug-resistant : Insights from and models.

Antimicrob Agents Chemother 2021 Feb 16. Epub 2021 Feb 16.

Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia

Topical antibiotic preparations, such as fusidic acid (FA) or mupirocin, are used in the prevention and treatment of superficial skin infections caused by staphylococci. Previous genomic epidemiology work has suggested an association between the widespread use of topical antibiotics and the emergence of methicillin resistant in some settings. In this study, we provide experimental proof of co-selection for multidrug resistance in following exposure to FA or mupirocin. Through targeted mutagenesis and phenotypic analyses, we confirmed that carriage confers resistance to FA, and carriage confers high-level resistance to mupirocin in multiple genetic backgrounds. experiments demonstrated that carriage of and confer a competitive advantage in the presence of sub-inhibitory concentrations of FA and mupirocin, respectively. Further, we used a porcine skin colonisation model to show that clinically relevant concentrations of topical antibiotics can co-select for presence of unrelated antimicrobial resistance determinants, such as , , and , in or harbouring These findings provide valuable insights on the role of acquired FA or mupirocin resistance in co-selecting for broader antibiotic resistance in , prompting greater need for judicious use of topical antibiotics.
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http://dx.doi.org/10.1128/AAC.02048-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092865PMC
February 2021

Culture obtained from urethral swab of asymptomatic men who screen positive for by urine nucleic acid amplification testing.

Sex Transm Infect 2021 Feb 1. Epub 2021 Feb 1.

Sexual Health Unit, Melbourne Sexual Health Centre, Alfred Health, Carlton, Victoria, Australia.

Background: In a previous study of men attending Melbourne Sexual Health Centre who had detected by urine Aptima Combo 2 (AC2) testing, 11% were asymptomatic. This study aimed to determine whether can be cultured from asymptomatic men screening positive for by nucleic acid amplification testing (NAAT) of urine.

Methods: Between 1 July 2017 and 31 March 2019, all men attending Melbourne Sexual Health Centre were tested for by AC2 testing of urine whether urethral symptoms were reported or not. NAAT-positive men were recalled and a urethral swab performed for gonococcal culture using modified Thayer-Martin media with determination of minimum inhibitory concentrations (MICs) by agar dilution.

Results: There were 1001 cases (860 individuals) positive for by urine AC2: 892 (89%) reported urethral symptoms; 109 (11%) did not. Twenty-five asymptomatic cases were excluded because of antibiotic use at or following screening. Of the remaining 84 asymptomatic men, 41 (49%) had a urethral swab performed a median of 5 days after screening. Twenty-one men had urethral discharge at the return visit, 11 of whom reported the discharge at the return visit. Of the 41 men who were swabbed, 31 (76%; 95% CI 60% to 88%) were culture positive for . Among the 21 men who subsequently developed discharge, 19 (90%; 95% CI 70% to 99%) were culture positive. Among the 20 men who remained asymptomatic, 12 (60%; 95% CI 36% to 81%) were culture positive. MIC profiles were obtained from all isolates.

Conclusions: Gonorrhoea was isolated in most but not all asymptomatic men screening positive for by urine NAAT. Clinicians should consider performing urethral culture in such men to ensure optimal surveillance for antimicrobial resistance. Isolation of by culture in men without discharge indicates these are true infections with viable organisms.
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http://dx.doi.org/10.1136/sextrans-2020-054690DOI Listing
February 2021

Clinical Presentation of Incident Syphilis Among Men Who Have Sex with Men Taking HIV Pre-Exposure Prophylaxis in Melbourne, Australia.

Clin Infect Dis 2021 Aug;73(4):e934-e937

Melbourne Sexual Health Centre, Alfred Health, Melbourne, Victoria, Australia.

Background: Current international guidelines on human immunodeficieny virus (HIV) Pre-Exposure Prophylaxis (PrEP) recommend serological screening for syphilis at routine 3-monthly PrEP appointments. The aim of our study was to describe the pattern of clinical presentation of syphilis among men who have sex with men (MSM) taking PrEP. We were interested in whether syphilis is detected through screening at scheduled3-monthly PrEP clinic appointments or whether primary or secondary syphilis presented at unscheduled interval visits.

Methods: This was a retrospective study of MSM attending the PrEP clinic at the Melbourne Sexual Health Centre between February 2016 and March 2019. Serological screening for syphilis was routinely undertaken at 3-monthly PrEP clinic appointments. Diagnoses of early syphilis were identified from PrEP clinic visits and from interim walk-in STI clinic attendances.

Results: There were 69 cases of early syphilis among 61 MSM taking PrEP during the study period. There were 24 (35%) primary, 16 (23%) secondary, and 29 (42%) early latent infections. The incidence of early syphilis was 8.6 per 100 person-years. A substantial proportion of primary (58%) and secondary (44%) syphilis diagnoses were made at interim STI clinic attendances, between PrEP appointments.

Conclusions: Syphilis screening at routine 3-monthly PrEP visits alone fails to detect a proportion of primary and secondary syphilis infections and may be insufficient in preventing onward transmission. Education of MSM taking PrEP regarding the risk of syphilis and symptom recognition is necessary together with access to syphilis testing between PrEP visits.
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http://dx.doi.org/10.1093/cid/ciab052DOI Listing
August 2021

Comparison of the patterns of chlamydia and gonorrhoea at the oropharynx, anorectum and urethra among men who have sex with men.

Sex Transm Infect 2021 Jan 12. Epub 2021 Jan 12.

Melbourne Sexual Health Centre, Alfred Health, Melbourne, Victoria, Australia

Objective: Chlamydia and gonorrhoea are common sexually transmitted infections that infect the oropharynx, anorectum and urethra in men who have sex with men (MSM). This study aimed to examine the pattern of infection at more than one site (multisite) for chlamydia and gonorrhoea among MSM.

Methods: This was a retrospective study of MSM attending the Melbourne Sexual Health Centre for the first time between 2018 and 2019. We included MSM aged ≥16 years who had tested for and at all three sites (oropharynx, anorectum and urethra). We compared infections that occurred at a single site (termed single-site infection) and those that occurred at more than one site (termed multisite infections).

Results: Of the 3938 men who were tested for chlamydia and gonorrhoea, 498/3938 men (12.6%, 95% CI 11.5% to 13.6%) had chlamydia at any site, of whom 400/498 (80.3%, 95% CI 78.9% to 81.2%) had single-site chlamydia infection, and 98/498 (19.7%, 95% CI 16.2% to 23.1%) had multisite infections. A similar proportion of men had gonorrhoea at any site (447/3938, 11.4%, 95% CI 10.3% to 12.2%), but among these 447 men, single-site infection was less common (256/447, 57.3%, 95% CI 52.6% to 61.7%, p<0.001) and multisite infection (191/447, 42.7%, 95% CI 38.2% to 47.3%, p<0.001) was more common than chlamydia. There were also marked differences by anatomical site. Urethral infection commonly occurred as single sites (75/122, 61.5%, 95% CI 52.8% to 70.1%) for chlamydia but uncommonly occurred for gonorrhoea (12/100, 12.0%, 95% CI 5.6% to 18.3%, p<0.001). In contrast, anorectal infection uncommonly occurred as multisite infection for chlamydia (98/394, 24.9%, 95% CI 20.6% to 29.1%) but was common (184/309, 59.5%, 95% CI 54.0% to 64.9%, p<0.001) for gonorrhoea.

Conclusions: The markedly different pattern of site-specific infection for chlamydia and gonorrhoea infections among the same MSM suggests significant differences in the transmissibility between anatomical sites and the duration of each infection at each site.
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http://dx.doi.org/10.1136/sextrans-2020-054632DOI Listing
January 2021

Detection of SARS-CoV-2 in saliva: implications for specimen transport and storage.

J Med Microbiol 2021 Feb;70(2)

Microbiological Diagnostic Unit, Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.

Saliva has recently been proposed as a suitable specimen for the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Use of saliva as a diagnostic specimen may present opportunities for SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) testing in remote and low-resource settings. Determining the stability of SARS-CoV-2 RNA in saliva over time is an important step in determining optimal storage and transport times. We undertook an study to assess whether SARS-CoV-2 could be detected in contrived saliva samples. The contrived saliva samples comprised 10 ml pooled saliva spiked with gamma-irradiated SARS-CoV-2 to achieve a concentration of 2.58×10 copies ml SARS-CoV-2, which was subsequently divided into 2 ml aliquots comprising: (i) neat saliva; and a 1 : 1 dilution with (ii) normal saline; (iii) viral transport media, and (iv) liquid Amies medium. Contrived samples were made in quadruplicate, with two samples of each stored at either: (i) room temperature or (ii) 4 °C. SARS-CoV-2 was detected in all SARS-CoV-2 spiked samples at time point 0, day 1, 3 and 7 at both storage temperatures using the N gene RT-PCR assay and time point 0, day 1 and day 7 using the Xpert Xpress SARS-CoV-2 (Cepheid, Sunnyvale, USA) RT-PCR assay. The ability to detect SARS-CoV-2 in saliva over a 1 week period is an important finding that presents further opportunities for saliva testing as a diagnostic specimen for the diagnosis of SARS-CoV-2.
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http://dx.doi.org/10.1099/jmm.0.001285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131016PMC
February 2021

Evaluation of ResistancePlus MG FleXible, a 'near-patient' test for the detection of and macrolide resistance mutations, using freshly collected clinical samples.

J Med Microbiol 2021 Jan;70(1)

Central Clinical School, Monash University, Melbourne, VIC, Australia.

is a sexually transmitted pathogen with increasing resistance to first- and second-line antimicrobials. The 'near-patient test' ResistancePlus MG FleXible (SpeeDx) detects plus four macrolide resistance mutations (MRMs), facilitating same-day patient follow up. This assay has not been assessed on freshly collected samples. Our goal was to evaluate the performance of the ResistancePlus MG FleXible test against the standard of care open platform test. ResistancePlus MG FleXible (analysed on the Cepheid GeneXpert platform) was evaluated on freshly collected samples and compared to the standard of care open platform test ResistancePlus MG (SpeeDx) analysed on the LightCycler 480 II (Roche). For 270 valid tests, ResistancePlus MG FleXible yielded a high positive per cent agreement (PPA) of 94.1% [96/102; 95 % confidence interval (CI): 87.6-97.8 %] and negative per cent agreement (NPA) of 95.2% (160/168; 95 % CI: 90.8-97.9%) for detection compared to the reference assay (kappa for test concordance of 0.89; 95 % CI: 0.83-0.95). Performance was similar across different sample types. For the detection of MRMs, ResistancePlus MG FleXible had a PPA of 97.1% (66/68; 95% CI: 89.8-99.6) and NPA of 78.6% (22/28; 95 % CI: 59.0-91.7), with test comparison kappa of 0.79 (95 % CI: 0.65-0.93). Notably, of six discordant results (i.e. determined to be wild type by the reference assay), five were positive for MRMs by Sanger sequencing, indicating that the ResistancePlus MG FleXible assay has an improved performance for mutation detection. ResistancePlus MG FleXible had comparable test performance for detection as the open platform assay, with improved detection of MRMs. The ResistancePlus MG FleXible 'near-patient' assay can deliver a rapid result to expedite appropriate treatment.
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http://dx.doi.org/10.1099/jmm.0.001271DOI Listing
January 2021

Incidence and duration of incident oropharyngeal gonorrhoea and chlamydia infections among men who have sex with men: prospective cohort study.

Sex Transm Infect 2021 Sep 18;97(6):452-457. Epub 2020 Nov 18.

Melbourne Sexual Health Centre, Alfred Health, Melbourne, Victoria, Australia.

Objectives: This prospective cohort study aimed to determine the natural history and incidence of oropharyngeal gonorrhoea and chlamydia among a cohort of men who have sex with men (MSM) over a 12-week period, and to examine risk factors associated with incident oropharyngeal infections.

Methods: MSM either aged ≥18 years and had a diagnosis of oropharyngeal gonorrhoea by nucleic acid amplification test (NAAT) in the past 3 months or aged 18-35 years who were HIV-negative taking pre-exposure prophylaxis (PrEP) were eligible for this study. Enrolled men were followed up for 12 weeks. Oropharyngeal swabs were collected at week 0 (baseline) and week 12 (end of study). Between these time points, weekly saliva specimens and the number of tongue kissing, penile-oral and insertive rimming partners were collected by post. Oropharyngeal swabs and saliva specimens were tested by NAAT for and . Poisson regression was performed to examine the risk factors (weekly number of partners) associated with incident oropharyngeal gonorrhoea.

Results: A total of 100 MSM were recruited. The incidence of oropharyngeal gonorrhoea and chlamydia was 62 (95% CI 37 to 105) and 9 (95% CI 2 to 35)/100 person-years, respectively. The median duration of incident oropharyngeal infection with gonorrhoea was 28 days (IQR=21-36, n=7). The incidence rate ratio (IRR) for oropharyngeal gonorrhoea increased with an increased number of kissing partners (IRR=1.08; 95% CI 1.03 to 1.12) an increased number of penile-oral sex partners (IRR=1.07, 95% CI 1.01 to 1.14) but not with an increased number of insertive rimming partners (IRR=1.11, 95% CI 0.96 to 1.29) or other demographic factors. The IRR and duration of incident oropharyngeal chlamydia were not calculated due to the small number of cases (n=2).

Conclusions: MSM have a high incidence of oropharyngeal gonorrhoea and the median duration of infection was less than 3 months.
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http://dx.doi.org/10.1136/sextrans-2020-054764DOI Listing
September 2021
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