Janet M Towns1, David E Leslie2, Ian Denham3, Rebecca Wigan3, Francesca Azzato2, Deborah A Williamson4, Darren Lee5, Eric P F Chow6, Christopher K Fairley7, Stephen R Graves8, Lei Zhang9, Marcus Y Chen7. 1. Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC, Australia; Central Clinical School, Faculty of Nursing, Medicine and Health Sciences, Monash University, Melbourne, VIC, Australia. Electronic address: jtowns@mshc.org.au. 2. Victorian Infectious Diseases Reference Laboratory, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia. 3. Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC, Australia. 4. Microbiological Diagnostic Unit Public Health Laboratory, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; Department of Microbiology, Royal Melbourne Hospital, Melbourne, VIC, Australia. 5. Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia. 6. Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC, Australia; Central Clinical School, Faculty of Nursing, Medicine and Health Sciences, Monash University, Melbourne, VIC, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia. 7. Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC, Australia; Central Clinical School, Faculty of Nursing, Medicine and Health Sciences, Monash University, Melbourne, VIC, Australia. 8. Australian Rickettsial Reference Laboratory, Barwon Health, Geelong, VIC, Australia. 9. Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC, Australia; Central Clinical School, Faculty of Nursing, Medicine and Health Sciences, Monash University, Melbourne, VIC, Australia; China-Australia Joint Research Center for Infectious Diseases, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China; Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
Abstract
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.
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.
Authors: Ei T Aung; Christopher K Fairley; Jason J Ong; Tiffany R Phillips; Marcus Y Chen; Julien Tran; Kate Maddaford; Elena R Rodriguez; Eric P F Chow Journal: Sci Rep Date: 2022-05-27 Impact factor: 4.996
Authors: Eric P F Chow; Darren Lee; Stephanie Bond; Christopher K Fairley; Kate Maddaford; Rebecca Wigan; Glenda Fehler; Sigrid A Lange; Vesna De Petra; Melanie Bissessor; Catriona S Bradshaw; Benjamin P Howden; Jane S Hocking; Deborah A Williamson; Marcus Y Chen Journal: Open Forum Infect Dis Date: 2021-03-19 Impact factor: 3.835
Authors: Ei T Aung; Christopher K Fairley; Jason J Ong; Tiffany P Phillips; Julien Tran; Marcus Y Chen; Kate Maddaford; Eric P F Chow Journal: Front Med (Lausanne) Date: 2022-08-01
Authors: H C A Zondag; S A Nieuwenburg; M Himschoot; A P van Dam; M F Schim van der Loeff; H J C de Vries; S M Bruisten Journal: Microbiol Spectr Date: 2022-06-23
Authors: Nicolas Morando; Eliška Vrbová; Asunta Melgar; Roberto Daniel Rabinovich; David Šmajs; María A Pando Journal: Sci Rep Date: 2022-09-29 Impact factor: 4.996
Authors: S A Nieuwenburg; H C A Zondag; S M Bruisten; V W Jongen; M F Schim van der Loeff; A P van Dam; H J C de Vries Journal: Clin Infect Dis Date: 2022-09-29 Impact factor: 20.999