Globally, 94% of Treponema pallidum subsp. pallidum (TPA) clinical strains belong to the SS14-like group and 6% to the Nichols-like group, with a prevalence of macrolide resistance of 90%. Our goal was to determine whether local TPA strain distribution and macrolide resistance frequency have changed significantly since our last report, which revealed that Buenos Aires had a high frequency of Nichols-like strains (27%) and low levels of macrolide resistance (14%). Swab samples from patients with suspected syphilis were collected during 2015-2019 and loci TP0136, TP0548, TP0705 were sequenced in order to perform multilocus sequence typing. Strains were classified as Nichols-like or SS14-like. The presence of macrolide resistance-associated mutations was determined by examination of the 23S rDNA gene sequence. Of 46 typeable samples, 37% were classified as Nichols-like and 63% as SS14-like. Macrolide resistance prevalence was 45.7%. Seven allelic profiles were found, five were SS14-like and two were Nichols-like. The frequency of Nichols-like strains increased between studies (26.8% vs. 37%, p = 0.36). A dramatic increase was found in the frequency of macrolide resistant strains between studies (14.3% vs. 45.7%, p = 0.005). Our results are in agreement with international trends and underscore the need to pursue further TPA molecular typing studies in South America.

CONICET Universidad de Buenos Aires Instituto de Investigaciones Biomédicas en Retrovirus y Sida Buenos Aires Argentina

Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic

Programa de Enfermedades de Transmisión Sexual Hospital de Clínicas José de San Martín Universidad de Buenos Aires Buenos Aires Argentina

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Radolf JD, et al. Treponema pallidum, the syphilis spirochete: Making a living as a stealth pathogen. Nat. Rev. Microbiol. 2016;14:744–759. PubMed PMC

World Health Organization. Global progress report on HIV, viral hepatitis and sexually transmitted infections, 2021: Accountability for the global health sector strategies 2016–2021: Actions for impact: Web annex 2: Data methods. https://apps.who.int/iris/bitstream/handle/10665/342813/9789240030992-eng.pdf?sequence=1&isAllowed=y (2021).

Dirección de Sida y ETS & Ministerio de Salud de la Nación. Boletín N° 38: Respuesta al VIH y las ITS en la Argentina. https://bancos.salud.gob.ar/recurso/boletin-ndeg-38-respuesta-al-vih-y-las-its-en-la-argentina (2021).

Pando MA, et al. Prevalence of HIV and other sexually transmitted infections among female commercial sex workers in Argentina. Am. J. Trop. Med. Hyg. 2006;74:233–238. PubMed

Pando MA, et al. HIV and other sexually transmitted infections among men who have sex with men recruited by RDS in Buenos Aires, Argentina: High HIV and HPV infection. PLoS ONE. 2012;7:e39834. PubMed PMC

Pando MA, et al. Violence as a barrier for HIV prevention among female sex workers in Argentina. PLoS ONE. 2013;8:e54147. PubMed PMC

dos Ramos Farías MS, et al. First report on sexually transmitted infections among trans (male to female transvestites, transsexuals, or transgender) and male sex workers in Argentina: High HIV, HPV, HBV, and syphilis prevalence. Int. J. Infect. Dis. 2011;15:e635–e640. PubMed

Beale MA, et al. Global phylogeny of Treponema pallidum lineages reveals recent expansion and spread of contemporary syphilis. Nat. Microbiol. 2021;6:1549–1560. PubMed PMC

Pla-Díaz M, et al. Evolutionary processes in the emergence and recent spread of the syphilis agent, Treponema pallidum. Mol. Biol. Evol. 2022;39:318. PubMed PMC

Pillay A, et al. Molecular subtyping of Treponema pallidum subspecies pallidum. Sex. Transm. Dis. 1998;25:408–414. PubMed

Katz KA, et al. Molecular epidemiology of syphilis—San Francisco, 2004–2007. Sex. Transm. Dis. 2010;37:660–663. PubMed

Marra CM, et al. Enhanced molecular typing of Treponema pallidum: Geographical distribution of strain types and association with neurosyphilis. J. Infect. Dis. 2010;202:1380–1388. PubMed PMC

Flasarová M, et al. Molekulární detekce a typizace Treponema pallidum subsp. pallidum v klinickém materiálu. Epidemiol. Mikrobiol. Imunol. 2006;55:105–111. PubMed

Grillová L, et al. Molecular characterization of Treponema pallidum subsp. pallidum in Switzerland and France with a new multilocus sequence typing scheme. PLoS ONE. 2018;13:e0200773. PubMed PMC

Grillová L, Jolley K, Šmajs D, Picardeau M. A public database for the new MLST scheme for Treponema pallidum subsp. pallidum: Surveillance and epidemiology of the causative agent of syphilis. PeerJ. 2019;6:e6182. PubMed PMC

Gallo Vaulet L, et al. Molecular typing of Treponema pallidum isolates from Buenos Aires, Argentina: Frequent Nichols-like isolates and low levels of macrolide resistance. PLoS ONE. 2017;12:e0172905. PubMed PMC

Arora N, et al. Origin of modern syphilis and emergence of a pandemic Treponema pallidum cluster. Nat. Microbiol. 2017;2:16245. PubMed

Stamm LV. Syphilis: Antibiotic treatment and resistance. Epidemiol. Infect. 2015;143:1567–1574. PubMed PMC

Grillová L, et al. Molecular typing of Treponema pallidum in the Czech Republic during 2011 to 2013: Increased prevalence of identified genotypes and of isolates with macrolide resistance. J. Clin. Microbiol. 2014;52:3693–3700. PubMed PMC

Flasarová M, et al. Sequencing-based molecular typing of Treponema pallidum strains in the Czech Republic: All identified genotypes are related to the sequence of the SS14 strain. Acta Derm. Venerol. 2012;92:669–674. PubMed

Cruz AR, et al. Secondary syphilis in Cali, Colombia: New concepts in disease pathogenesis. PLoS Negl. Trop. Dis. 2010;4:e690. PubMed PMC

Flores JA, et al. Treponema pallidum pallidum genotypes and macrolide resistance status in syphilitic lesions among patients at 2 sexually transmitted infection clinics in Lima, Peru. Sex. Transm. Dis. 2016;43:465–466. PubMed

Lieberman NAP, et al. Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar. PLoS Negl. Trop. Dis. 2021;15:e0010063. PubMed PMC

Nishiki S, Lee K, Kanai M, Nakayama SI, Ohnishi M. Phylogenetic and genetic characterization of Treponema pallidum strains from syphilis patients in Japan by whole-genome sequence analysis from global perspectives. Sci. Rep. 2021;11:3154. PubMed PMC

Šmajs D, Strouhal M, Knauf S. Genetics of human and animal uncultivable treponemal pathogens. Infect. Genet. Evol. 2018;61:92–107. PubMed

Fernández-Naval C, et al. Multilocus sequence typing of Treponema pallidum subsp. pallidum in Barcelona. Future Microbiol. 2021;16:967–976. PubMed

Noda AA, Matos N, Blanco O, Rodríguez I, Stamm LV. First report of the 23S rRNA gene A2058G point mutation associated with macrolide resistance in Treponema pallidum from syphilis patients in Cuba. Sex. Transm. Dis. 2016;43:332–334. PubMed

Read P, et al. Treponema pallidum strain types and association with macrolide resistance in Sydney, Australia: New TP0548 gene types identified. J. Clin. Microbiol. 2016;54:2172–2174. PubMed PMC

Xiao Y, et al. Molecular subtyping and surveillance of resistance genes in Treponema pallidum DNA from patients with secondary and latent syphilis in Hunan, China. Sex. Transm. Dis. 2016;43:310–316. PubMed

Martin IE, Gu W, Yang Y, Tsang RSW. Macrolide resistance and molecular types of Treponema pallidum causing primary syphilis in Shanghai, China. Clin. Infect. Dis. 2009;49:515–521. PubMed

Li Z, et al. Two Mutations associated with macrolide resistance in Treponema pallidum in Shandong, China. J. Clin. Microbiol. 2013;51:4270–4271. PubMed PMC

Chen X-S, et al. High prevalence of azithromycin resistance to Treponema pallidum in geographically different areas in China. Clin. Microbiol. Infect. 2013;19:975–979. PubMed

Lukehart SA, et al. Macrolide resistance in Treponema pallidum in the United States and Ireland. N. Engl. J. Med. 2004;351:154–158. PubMed

Muldoon EG, Walsh A, Crowley B, Mulcahy F. Treponema pallidum azithromycin resistance in Dublin, Ireland. Sex. Transm. Dis. 2012;39:784–786. PubMed

Fernández-Naval C, et al. Enhanced molecular typing and macrolide and tetracycline-resistance mutations of Treponema pallidum in Barcelona. Future Microbiol. 2019;14:1099–1108. PubMed

Tipple C, McClure MO, Taylor GP. High prevalence of macrolide resistant Treponema pallidum strains in a London centre. Sex. Transm. Infect. 2011;87:486–488. PubMed

Grimes M, et al. Two mutations associated with macrolide resistance in Treponema pallidum: Increasing prevalence and correlation with molecular strain type in Seattle, Washington. Sex. Transm. Dis. 2012;39:954–958. PubMed PMC

Marra CM, et al. Antibiotic selection may contribute to increases in macrolide-resistant Treponema pallidum. J. Infect. Dis. 2006;194:1771–1773. PubMed

Su JR. Prevalence of the 23S rRNA A2058G point mutation and molecular subtypes in Treponema pallidum in the United States, 2007 to 2009. Sex. Transm. Dis. 2012;39:794–798. PubMed

Šmajs D, Grillová L, Paštěková L. Macrolide resistance in the syphilis spirochete, Treponema pallidum ssp. pallidum: Can we also expect macrolide-resistant yaws strains? Am. J. Trop. Med. Hyg. 2015;93:678–683. PubMed PMC

Maito MA. Use of commercialized antibiotics in Argentine Republic pharmacies (2015–2017) Revista Ciencia Reguladora. 2018;3:30–34.

Kenyon C. Positive association between the use of macrolides in food-producing animals and pneumococcal macrolide resistance: A global ecological analysis. Int. J. Infect. Dis. 2022;116:344–347. PubMed

Pospíšilová P, et al. Multi-locus sequence typing of Treponema pallidum subsp. pallidum present in clinical samples from France: Infecting treponemes are genetically diverse and belong to 18 allelic profiles. PLoS ONE. 2018;13:e0201068. PubMed PMC

Peng R-R, et al. Molecular typing of Treponema pallidum: A systematic review and meta-analysis. PLoS Negl. Trop. Dis. 2011;5:e1273. PubMed PMC

Edmondson DG, Hu B, Norris SJ. Long-term in vitro culture of the syphilis spirochete Treponema pallidum subsp. pallidum. MBio. 2018;9:e01153-18. PubMed PMC

Towns JM, et al. 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;21:1324–1331. PubMed

Heymans R, et al. Clinical value of Treponema pallidum real-time PCR for diagnosis of syphilis. J. Clin. Microbiol. 2010;48:497–502. PubMed PMC

Shields M, Guy RJ, Jeoffreys NJ, Finlayson RJ, Donovan B. A longitudinal evaluation of Treponema pallidum PCR testing in early syphilis. BMC Infect. Dis. 2012;12:353. PubMed PMC

World Health Organization . Sífilis. In: Unemo M, editor. Diagnóstico de laboratorio de las infecciones de transmisión sexual, incluida la infección por el virus de la inmunodeficiencia humana. World Health Organization; 2014. pp. 115–139.

Peeling RW, et al. Syphilis. Nat. Rev. Dis. Primers. 2017;3:17073. PubMed PMC

Vrbová E, et al. MLST typing of Treponema pallidum subsp. pallidum in the Czech Republic during 2004–2017: Clinical isolates belonged to 25 allelic profiles and harbored 8 novel allelic variants. PLoS ONE. 2019;14:e0217611. PubMed PMC

Kumar S, Stecher G, Li M, Knyaz C, Tamura K. MEGA X: Molecular evolutionary genetics analysis across computing platforms. Mol. Biol. Evol. 2018;35:1547–1549. PubMed PMC

Thompson JD, Higgins DG, Gibson TJ. CLUSTAL W: Improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994;22:4673–4680. PubMed PMC

Tamura K, Nei M, Kumar S. Prospects for inferring very large phylogenies by using the neighbor-joining method. Proc. Natl. Acad. Sci. U.S.A. 2004;101:11030–11035. PubMed PMC

Felsenstein J. Confidence limits on phylogenies: An Approach using the bootstrap. Evolution. 1985;39:783–791. PubMed

World Medical Association World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA. 2013;310:2191–2194. PubMed

Majority of Treponema pallidum ssp. pallidum MLST allelic profiles in the Czech Republic (2004-2022) belong to two SS14-like clusters