Melbourne School of Population and Global Health - Research Publications

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    Treponema pallidum PCR screening at mucosal sites of asymptomatic men who have sex with men taking HIV pre-exposure prophylaxis
    Aung, ET ; Fairley, CK ; Williamson, DA ; Azzato, F ; Wigan, R ; Tran, J ; Buchanan, A ; Schmidt, T ; Chow, EPF ; Chen, MY ; Realegeno, S (AMER SOC MICROBIOLOGY, 2023)
    Early detection and treatment of syphilis will reduce the infectious period and transmission. We aimed to determine whether screening men who have sex with men (MSM) taking HIV pre-exposure prophylaxis (PrEP) for syphilis using Treponema pallidum polymerase chain reaction (PCR) could detect syphilis before the appearance of syphilis antibodies in serology. MSM attending 3-monthly PrEP clinic visits in Melbourne, Australia, were screened with a PCR assay targeting the polA gene of T. pallidum from an anal swab and an oral rinse between November 2019 and March 2020. Participants were serologically screened for syphilis using chemiluminescence immunoassay. A total of 309 asymptomatic participants provided an anal swab and oral rinse sample for T. pallidum PCR screening. Two syphilis cases (0.6%) were detected: one man had a positive serology only; another man had T. pallidum detected by PCR from an anal swab and a positive serology. PCR positivity was 0.3% (n = 1) for anal swabs and 0% (n = 0) for oral rinse. In this study, T. pallidum PCR screening at routine PrEP clinic visits did not identify additional cases of early syphilis over serological screening performed at these visits. IMPORTANCE With the ongoing syphilis epidemic in men who have sex with men (MSM), we investigated the role of using Treponema pallidum polymerase chain reaction (PCR) testing at the oral cavity and anus in MSM taking pre-exposure prophylaxis for the early detection of syphilis. We evaluated whether the PCR tests from these mucosal sites can detect syphilis infection early, before the development of syphilis antibodies in serology. Our study found two syphilis cases among 309 MSM, and only one syphilis case had a positive anal PCR swab, although serology was positive. We conclude that additional PCR testing is likely to be expensive and would not be cost effective for individuals who regularly screen for syphilis. However, future studies with a larger sample size are required.
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    A Systematic Review of Kissing as a Risk Factor for Oropharyngeal Gonorrhea or Chlamydia
    Charleson, F ; Tran, J ; Kolobaric, A ; Case, R ; Fairley, CK ; Hocking, JS ; Chow, EPF (LIPPINCOTT WILLIAMS & WILKINS, 2023-07)
    BACKGROUND: Tongue kissing is a poorly studied risk factor for sexually transmitted infections (STIs). We undertook the first systematic review to assess whether kissing is a risk factor for gonorrhea or chlamydia of the oropharynx. METHODS: Online databases (MEDLINE, EMBASE, CINAHL, Web of Science, Cochrane) and reference lists were searched until September 30, 2022. The eligibility criteria for studies included: any peer-reviewed study design in the English language; gonorrhea or chlamydia diagnosed by nucleic acid amplification test, or an infection self-reported by a patient; tongue kissing or its equivalent measured as an exposure. Studies were appraised using a quality scoring tool and qualitatively synthesized. RESULTS: Of 8248 studies screened, 6 were eligible for review. All were conducted among men who have sex with men in Australia, including 3 prospective cohort studies, 2 cross-sectional studies, and 1 age-matched case-control study. In summary, all 5 studies examining gonorrhea found an unadjusted association between kissing and oropharyngeal gonorrhea. Two cross-sectional studies found that tongue kissing was an independent risk factor for oropharyngeal gonorrhea after adjusting for other confounders, such as participant demographic characteristics and other sexual practices. In contrast, a single eligible prospective cohort study found no association between kissing and oropharyngeal chlamydia. CONCLUSIONS: This systematic review summarized the existing evidence that suggests that tongue kissing may be a risk factor for oropharyngeal gonorrhea but not chlamydia. Reinforcing the message that oropharyngeal gonorrhea could be transmitted through kissing may inform the development of novel approaches to prevent and treat gonorrhea.
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    Mpox knowledge, vaccination and intention to reduce sexual risk practices among men who have sex with men and transgender people in response to the 2022 mpox outbreak: a cross-sectional study in Victoria, Australia
    Chow, EPF ; Samra, RS ; Bradshaw, CS ; Chen, MY ; Williamson, DA ; Towns, JM ; Maddaford, K ; Mercury, F ; Fairley, CK ; Ong, J (CSIRO PUBLISHING, 2023)
    BACKGROUND: The first mpox case was reported in May 2022 in Australia. Most cases have been diagnosed in men who have sex with men (MSM). This study aimed to examine community understanding of mpox, attitudes towards vaccination, and potential changes in sexual practices surrounding the mpox outbreak among MSM and transgender people in Victoria, Australia. METHODS: Participants were recruited from sexual health clinics and communities in Victoria, Australia, in August-October 2022. Participants were asked about their understanding and knowledge of mpox, vaccination uptake and intentions to change sexual practices. Univariable and multivariable logistic regression was performed to examine the factors associated with mpox vaccine uptake. RESULTS: Most participants (97.8%, 525/537) had heard about mpox and 10.5% (55/525) knew someone who had had mpox. Of the 12 mpox knowledge questions, the median score of correct answers was 10 (IQR=8-11) out of a maximum of 12. More than a third (36.6%, 191/522) had been vaccinated against mpox. MSM who had a good knowledge of mpox had the highest odds of receiving mpox vaccine compared with those who had poor knowledge (aOR=4.05; 95% CI: 1.54-10.61). To prevent mpox, half reported they would reduce having sex with casual partners, stop having chemsex (used drugs for the purpose of sex), stop attending sex-on-premises-venues, and stop having group sex. A quarter reported they would increase condom use for anal sex. CONCLUSIONS: One-third of high-risk participants and a substantial proportion of participants intended to reduce or stop certain practices, which may explain the large reduction in mpox cases.
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    The role of syphilis self-testing as an additional syphilis testing approach in key populations: a systematic review and meta-analysis
    Towns, JM ; Tieosapjaroen, W ; Mello, MB ; Baggaley, RC ; Johnson, CC ; Jamil, MS ; Rowley, J ; Barr-DiChiara, M ; Terris-Prestholt, F ; Chen, MY ; Chow, EPF ; Fairley, CK ; Zhang, L ; Ong, JJ (ELSEVIER SCI LTD, 2023-09)
    BACKGROUND: Syphilis is causing epidemics in many countries. Syphilis self-testing (SST) has potential to increase testing and treatment coverage in the same manner as documented for self-testing of, for example, HIV, hepatitis C virus, and COVID-19. We aimed to synthesise current evidence on the utility of SST. METHODS: We conducted a systematic review and, where possible, meta-analysis. We searched MEDLINE, Embase, CINAHL, Scopus, and Web of Science for publications published from Jan 1, 2000, to Oct 13, 2022. We included publications with original data on any syphilis rapid tests, including dual HIV-syphilis tests. Study populations were not restricted. We used random-effects meta-analysis to calculate the pooled proportion of people offered SST who undertook the test. The systematic review was registered in PROSPERO (CRD42022302129). FINDINGS: In total, 40 499 citations were identified. 11 publications from seven studies from the USA, Zimbabwe, and China met eligibility criteria. Of those, four studies reported data from men who have sex with men and five studies used dual HIV-SST. Using data from one randomised controlled trial and three observational studies, the pooled proportion of people who received SST kits who undertook the test was 88% (95% CI 85-91). No studies provided data on the sensitivity or specificity of SST. Overall, user and provider preference for SST was high, with participants reporting convenience, privacy, rapid results, autonomy, trust in blood-based tests, decreased facility contact, and time savings, with individuals being able to correctly self-test. Publications from China reported that SST had lower costs per person tested than existing facility-based testing options. INTERPRETATION: Our review builds on the literature for self-testing across different disease areas and demonstrates that SST has the potential to reach underserved populations. As this review found that SST use was acceptable and feasible to implement, SST can be used as an additional syphilis testing approach. Since no data on the sensitivity and specificity of SST were found, further implementation research will be required to guide the best strategies for SST service delivery and future scale-up. FUNDING: WHO, Australian National Health and Medical Research Council, and Unitaid.
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    Rapid detection of monkeypox virus using a CRISPR-Cas12a mediated assay: a laboratory validation and evaluation
    Low, SJ ; O'Neill, M ; Kerry, WJ ; Krysiak, M ; Papadakis, G ; Whitehead, LW ; Savic, I ; Prestedge, J ; Williams, L ; Cooney, JP ; Tran, T ; Lim, CK ; Caly, L ; Towns, JM ; Bradshaw, CS ; Fairley, C ; Chow, EPF ; Chen, MY ; Pellegrini, M ; Pasricha, S ; Williamson, DA (Elsevier, 2023-10)
    BACKGROUND: The 2022 outbreak of mpox (formerly known as monkeypox) led to the spread of monkeypox virus (MPXV) in over 110 countries, demanding effective disease management and surveillance. As current diagnostics rely largely on centralised laboratory testing, our objective was to develop a simple rapid point-of-care assay to detect MPXV in clinical samples using isothermal amplification coupled with CRISPR and CRISPR-associated protein (Cas) technology. METHODS: In this proof-of-concept study, we developed a portable isothermal amplification CRISPR-Cas12a-based assay for the detection of MPXV. We designed a panel of 22 primer-guide RNA sets using pangenome and gene-agnostic approaches, and subsequently shortlisted the three sets producing the strongest signals for evaluation of analytical sensitivity and specificity using a fluorescence-based readout. The set displaying 100% specificity and the lowest limit of detection (LOD) was selected for further assay validation using both a fluorescence-based and lateral-flow readout. Assay specificity was confirmed using a panel of viral and bacterial pathogens. Finally, we did a blind concordance study on genomic DNA extracted from 185 clinical samples, comparing assay results with a gold-standard quantitative PCR (qPCR) assay. We identified the optimal time to detection and analysed the performance of the assay relative to qPCR using receiver operating characteristic (ROC) curves. We also assessed the compatibility with lateral-flow strips, both visually and computationally, where strips were interpreted blinded to the fluorescence results on the basis of the presence or absence of test bands. FINDINGS: With an optimal run duration of approximately 45 min from isothermal amplification to CRISPR-assay readout, the MPXV recombinase polymerase amplification CRISPR-Cas12a-based assay with the selected primer-guide set had an LOD of 1 copy per μL and 100% specificity against tested viral pathogens. Blinded concordance testing of 185 clinical samples resulted in 100% sensitivity (95% CI 89·3-100) and 99·3% specificity (95% CI 95·7-100) using the fluorescence readout. For optimal time to detection by fluorescence readout, we estimated the areas under the ROC curve to be 0·98 at 2 min and 0·99 at 4 min. Lateral-flow strips had 100% sensitivity (89·3-100) and 98·6% specificity (94·7-100) with both visual and computational assessment. Overall, lateral-flow results were highly concordant with fluorescence-based readouts (179 of 185 tests, 96·8% concordant), with discrepancies associated with low viral load samples. INTERPRETATION: Our assay for the diagnosis of mpox displayed good performance characteristics compared with qPCR. Although optimisation of the assay will be required before deployment, its usability and versatility present a potential solution to MPXV detection in low-resource and remote settings, as well as a means of community-based, on-site testing. FUNDING: Victorian Medical Research Accelerator Fund and the Australian Government Department of Health.
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    Intra- and interhost genomic diversity of monkeypox virus
    Taouk, ML ; Steinig, E ; Taiaroa, G ; Savic, I ; Tran, T ; Higgins, N ; Tran, S ; Lee, A ; Braddick, M ; Moso, MA ; Chow, EPF ; Fairley, CK ; Towns, J ; Chen, MY ; Caly, L ; Lim, CK ; Williamson, DA (WILEY, 2023-08)
    The impact and frequency of infectious disease outbreaks demonstrate the need for timely genomic surveillance to inform public health responses. In the largest known outbreak of mpox, genomic surveillance efforts have primarily focused on high-incidence nations in Europe and the Americas, with a paucity of data from South-East Asia and the Western Pacific. Here we analyzed 102 monkeypox virus (MPXV) genomes sampled from 56 individuals in Melbourne, Australia. All genomes fell within the 2022 MPXV outbreak lineage (B.1), with likely onward local transmission detected. We observed within-host diversity and instances of co-infection, and highlight further examples of structural variation and apolipoprotein B editing complex-driven micro-evolution in the current MPXV outbreak. Updating our understanding of MPXV emergence and diversification will inform public health measures and enable monitoring of the virus' evolutionary trajectory throughout the mpox outbreak.
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    Positivity and Risk Factors for Trichomonas vaginalis Among Women Attending a Sexual Health Clinic in Melbourne, 2006 to 2019
    Abraham, E ; Fairley, CK ; Denham, I ; Bradshaw, CS ; Farquharson, RM ; Vodstrcil, LA ; Plummer, EL ; Ong, JJ ; Chen, MY ; Phillips, TR ; Chow, EPF (LIPPINCOTT WILLIAMS & WILKINS, 2022-11)
    BACKGROUND: Trichomonas vaginalis is not a notifiable disease in Australia in most states, resulting in limited Australian epidemiological studies. This study aimed to examine the positivity of T. vaginalis in women attending the Melbourne Sexual Health Centre (MSHC) and identify associated factors. METHODS: All women 16 years or older who were tested for T. vaginalis at MSHC from 2006 to 2019 were included. The diagnostic method changed from culture to nucleic acid amplification test in August 2018. The annual positivity of T. vaginalis was calculated. Because of the data completeness, we performed a generalized estimating equations multivariable logistic regression using data from 2011 to 2019 to examine factors associated with T. vaginalis positivity. RESULTS: From 2006 to 2019, 69,739 tests for T. vaginalis were conducted, and 294 tested positive (0.42%; 95% confidence interval [CI], 0.37%-0.47%). Approximately 60% of women tested reported symptoms. After adjusting for potential confounders including the change in diagnostic method, there was a 21% (95% CI, 12%-31%) annual increase in T. vaginalis positivity between 2011 and 2019. Women with concurrent syphilis had the highest odds of testing positive for T. vaginalis (adjusted odds ratio [aOR], 21.55; 95% CI, 6.96-66.78), followed by women who had injected drugs in the last 12 months (aOR, 6.99; 95% CI, 4.11-11.87), were 35 years or older (aOR, 3.47; 95% CI, 2.26-5.35), or had concurrent chlamydia (aOR, 1.77; 95% CI, 1.05-2.99). CONCLUSIONS: The rising positivity of T. vaginalis at MSHC irrespective of change in diagnostic method suggests a concurrent community-wide rise in Melbourne. Given the rising positivity, testing informed by risk factors should be considered.
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    The acceptability and usability of two HIV self-test kits among men who have sex with men: a randomised crossover trial
    Lee, DYL ; Ong, JJ ; Smith, K ; Jamil, MS ; McIver, R ; Wigan, R ; Maddaford, K ; McNulty, A ; Kaldor, JM ; Fairley, CK ; Bavinton, B ; Chen, M ; Chow, EP ; Grulich, AE ; Holt, M ; Conway, DP ; Stoove, M ; Wand, H ; Guy, RJ (WILEY, 2022-08-01)
    OBJECTIVES: To compare the usability and acceptability of oral fluid- and blood-based HIV self-test kits among men who have sex with men in Australia. DESIGN: Randomised crossover trial. SETTING, PARTICIPANTS: Gay, bisexual, and other men aged 18 years or older who have sex with men, who attended two metropolitan sexual health clinics in Sydney and Melbourne, 7 January - 10 December 2019. MAIN OUTCOME MEASURES: Ease of use of HIV self-test kits; preferred HIV self-test type; difficulties encountered during HIV self-testing. RESULTS: 170 men were recruited (median age, 34 years; interquartile range, 29-43 years); 144 identified as gay (85%), 96 were born outside Australia (57%). Participants were more likely to report the oral fluid HIV self-test was easy to use than the blood-based self-test (oral fluid, 99%; blood, 86%; odds ratio [OR], 3.0; 95% confidence interval [CI], 1.4-6.6). The oral fluid test was preferred by 98 participants (58%; 95% CI, 50-65%), the blood-based test by 69 (41%; 95% CI, 33-48%). Difficulties with the oral fluid test kit identified by observing nurses included problems placing the buffer solution into the stand (40 of 170 participants, 24%) and not swabbing both gums (23 of 169, 14%); difficulties with the blood-based test kit included problems filling the device test channel (69 of 170, 41%) and squeezing the finger firmly enough to generate a blood drop (42 of 170, 25%). No participant received an invalid result with the oral fluid self-test; two of 162 participants (1%) received invalid results with the blood self-test. After adjusting for age, education level, and ethnic background, characteristics associated with higher odds of using HIV self-testing in the future were overseas birth (adjusted OR, 3.07; 95% CI, 1.42-6.64), and self-evaluated ease of use and confidence in using the kits. CONCLUSION: It is important to provide options for obtaining both oral fluid- and blood-based HIV self-tests. The usability and acceptability of both kits were high, but the ease of use and perceived accuracy influenced test kit preference.
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    Salutogenic-based interventions among community-dwelling older adults: a systematic review and meta-analysis
    Chow, EKM ; Seah, B ; Chan, JJY ; Wang, W (OXFORD UNIV PRESS, 2023-06-01)
    Salutogenesis is a health-promoting orientation and sense of coherence (SOC) is a vital coping factor associated with quality of life (QOL) and self-efficacy. Although salutogenic-based interventions showed potential in improving health outcomes, the application of salutogenic concepts and effectiveness on SOC, QOL and self-efficacy among community-dwelling older adults remained unclear. This review aimed to consolidate evidence on salutogenic approaches and evaluate the effectiveness of salutogenic-based interventions on SOC, QOL and self-efficacy in community-dwelling older adults. Databases systematically searched include PubMed, CINAHL, Embase, Cochrane Central Register of Controlled Trials, Scopus, Medline, PsycINFO and ProQuest Dissertations & Theses Global electronic databases. Two reviewers screened study eligibility, assessed risk of bias and extracted data of included studies independently. Meta-analyses on SOC and QOL were performed using RevMan. Where meta-analysis was not possible, narrative synthesis was employed. Eight studies involving 1201 older adults were included in this review. Subgroup analysis on SOC showed significant effects favouring salutogenic-based interventions using the empowering self-management model or strengths/resource-based approaches. However, results were mixed for the reflection-based approach. No significant effect favouring salutogenic-based interventions on QOL outcomes were found. High heterogeneity was observed for the outcome on self-efficacy. Two SOC strengthening processes, empowerment and reflection, were found to potentially underlie salutogenic-based intervention mechanisms. Effectiveness of salutogenic-based interventions on SOC, QOL and self-efficacy among community-dwelling older adults remained inconclusive due to high heterogeneity. Future salutogenic-based interventions should employ longitudinal designs and standardization on intervention delivery, utilizing a dual pathway via empowerment and reflection.
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    Time to healthcare seeking following the onset of symptoms among men and women attending a sexual health clinic in Melbourne, Australia
    Farquharson, RM ; Fairley, CK ; Abraham, E ; Bradshaw, CS ; Plummer, EL ; Ong, JJ ; Vodstrcil, LA ; Chen, MY ; Phillips, TR ; Chow, EPF (FRONTIERS MEDIA SA, 2022-10-25)
    BACKGROUND: Timely diagnosis and treatment of sexually transmitted infections (STIs) underpin their control by reducing the duration of infectiousness. There are currently limited data exploring healthcare seeking among individuals with STI symptoms. METHODS: We analyzed data on individuals reporting STI symptoms at the Melbourne Sexual Health Centre (MSHC) between August 2017 and December 2020. We calculated the time between symptom onset and clinic attendance by risk group for 13 STI diagnoses. We performed univariable and multivariable logistic regression analyses to explore factors associated with delayed healthcare seeking (greater than 7 days). RESULTS: Among 7,032 symptomatic clinic attendances, the shortest time to healthcare seeking was among individuals diagnosed with gonococcal urethritis (median 3 days), and the longest was among individuals diagnosed with genital warts (median 60 days). Individuals diagnosed with gonococcal urethritis sought care earlier than individuals diagnosed with non-gonococcal urethritis (median 3 vs. 6 days, p < 0.001), and individuals diagnosed with genital herpes sought care earlier than individuals diagnosed with primary syphilis (median 4 vs. 14 days, p < 0.001). Men who have sex with men, and men taking human immunodeficiency virus pre-exposure prophylaxis (PrEP), were least likely to delay healthcare seeking. Both men and women who delayed healthcare seeking were more likely to live further from the clinic than those who did not delay their presentation [p trend < 0.001 (men) and p trend = 0.049 (women)]. CONCLUSION: Improved local access to healthcare alongside targeted strategies to encourage early healthcare seeking among groups at increased likelihood of delay may reduce STI-associated morbidity and transmission.