Diagnosis, molecular typing, and resistance profile of Treponema pallidum
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May 14, 2025
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Resumo
Objetivo: Analisar os fundamentos e a epidemiologia da sífilis, assim como discutir as abordagens moleculares que podem ser utilizadas para otimizar o diagnóstico precoce da infecção. Revisão bibliográfica: A incidência de sífilis tem aumentado globalmente, com cerca de 8,0 milhões de novos casos estimados em 2022, gerando preocupação em relação a essa infecção sexualmente transmissível (IST). Embora o diagnóstico atual é realizado com testes sorológicos, eles apresentam limitações, como baixa sensibilidade no início da infecção e dificuldade em diferenciar entre sífilis tratada e ativa. Isso ressalta a necessidade de desenvolvimento de novos métodos diagnósticos, que permitam a detecção de T. pallidum em estágios iniciais da infecção. Por outro lado, a tipagem molecular, incluindo o sistema Enhanced Centers for Disease Control and Prevention (ECDC), ajuda a entender a diversidade das cepas de T. pallidum globalmente. Apesar da relevância, há escassez de estudos sobre o perfil molecular e resistência do T. pallidum na América do Sul. Descrever todos os pontos metodológicos de forma sucinta, público, localização, coleta de dados e instrumento de pesquisa. Considerações finais: É fundamental que os esforços em saúde pública se concentrem não apenas na educação e conscientização sobre prevenção, mas também na pesquisa e no desenvolvimento de novas estratégias diagnósticas e terapêuticas.
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QueirozJ. H. F. de S., PaulaS. M. de, EcheverriaJ. E. S., & SimionattoS. (2025). Diagnosis, molecular typing, and resistance profile of Treponema pallidum. Revista Eletrônica Acervo Saúde, 25(5), e19553. https://doi.org/10.25248/reas.e19553.2025
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Revisão Bibliográfica
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Referências
1. BRASIL. Boletim Epidemiológico de Sífilis - Número Especial. Ministério da Saúde, 2023. Disponível em: https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/boletins/epidemiologicos/especiais/2023/boletim-epidemiologico-de-sifilis-numero-especial-out.2023/view. Acessado em: 6 de novembro de 2023.
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3. ECDC. European Centre for Disease Prevention and Control. Syphilis. Annual Epidemiological Report for 2022. Stockholm: ECDC; 2024. Disponível em: https://www.ecdc.europa.eu. Acessado em: 6 de novembro de 2023.
4. EDMONDSON DG, et al. Long-term in vitro culture of the syphilis spirochete Treponema pallidum subsp. pallidum. mBio, 2018; [s. l.], v. 9.
5. FERNÁNDEZ-NAVAL C, et al. Enhanced molecular typing and macrolide and tetracycline-resistance mutations of Treponema pallidum in Barcelona. Future Microbiology, 2019; [s. l.], v. 14, n. 13, p. 1099–1108.
6. FLORES JA, et al. Treponema pallidum subsp. pallidum genotypes and macrolide resistance status in syphilitic lesions among patients at 2 sexually transmitted infection clinics in Lima, Peru. Sexually Transmitted Diseases, 2016; [s. l.], v. 43.
7. FU B, et al. A comparison of genotyping tool in Treponema pallidum: Review and meta-analysis. Infection, Genetics and Evolution, 2020; [s. l.], v. 78, p. 104049.
8. GIACANI L, et al. Enhanced Molecular Typing of Treponema pallidum subspecies pallidum Strains From 4 Italian Hospitals Shows Geographical Differences in Strain Type Heterogeneity, Widespread Resistance to Macrolides, and Lack of Mutations Associated With Doxycycline Resistance. Sexually Transmitted Diseases, 2018; [s. l.], v. 45, n. 4, p. 237–242.
9. GRILLOVA L, et al. A public database for the new MLST scheme for Treponema pallidum subsp. pallidum: surveillance and epidemiology of the causative agent of syphilis. PeerJ, 2019; [s. l.], v. 6, p. e6182.
10. GRIMES M, et al. Two Mutations Associated With Macrolide Resistance in Treponema pallidum: Increasing Prevalence and Correlation With Molecular Strain Type in Seattle, Washington. Sexually Transmitted Diseases, 2012; [s. l.], v. 39, n. 12, p. 954.
11. KANAI M, et al. Molecular Typing and Macrolide Resistance Analyses of Treponema pallidum in Heterosexuals and Men Who Have Sex with Men in Japan, 2017. Journal of Clinical Microbiology, 2019; [s. l.], v. 57, n. 1, p. e01167-18.
12. KHAIRULLIN R, et al. Syphilis epidemiology in 1994–2013, molecular epidemiological strain typing and determination of macrolide resistance in Treponema pallidum in 2013–2014 in Tuva Republic, Russia. Journal of Pathology, Microbiology and Immunology, 2016; [s. l.], v. 124, n. 7, p. 595–602.
13. KOJIMA Y, et al. Circulation of Distinct Treponema pallidum Strains in Individuals with Heterosexual Orientation and Men Who Have Sex with Men. Journal of Clinical Microbiology, 2019; [s. l.], v. 57, n. 1, p. e01148-18.
14. KUBANOV AA, et al. Molecular epidemiology of Treponema pallidum in a Frontier region of the Russian Federation (Tuva Republic). Molecular Genetics, Microbiology and Virology, 2017; [s. l.], v. 32, n. 1, p. 29–34.
15. LIU D, et al. Molecular Characterization Based on MLST and ECDC Typing Schemes and Antibiotic Resistance Analyses of Treponema pallidum subsp. pallidum in Xiamen, China. Frontiers in Cellular and Infection Microbiology, 2021; [s. l.], v. 10.
16. LU Y, et al. Molecular epidemiological survey of Treponema pallidum in pregnant women in the Zhabei District of Shanghai. Journal of Medical Microbiology, 2017; [s. l.], v. 66, n. 4, p. 391–396.
17. MARRA CM, et al. Enhanced Molecular Typing of Treponema pallidum: Geographical Distribution of Strain Types and Association with Neurosyphilis. The Journal of Infectious Diseases, 2010; [s. l.], v. 202, n. 9, p. 1380–1388.
18. MIKALOVA L, et al. Comparison of CDC and sequence-based molecular typing of syphilis treponemes: tpr and arp loci are variable in multiple samples from the same patient. BMC Microbiology, 2013; [s. l.], v. 13.
19. MIKALOVÁ L, et al. Molecular Typing of Syphilis-Causing Strains Among Human Immunodeficiency Virus-Positive Patients in Antwerp, Belgium. Sexually Transmitted Diseases, 2017; [s. l.], v. 44, n. 6, p. 376.
20. ORGANIZAÇÃO MUNDIAL DA SAÚDE. Global progress report on HIV, viral hepatitis and sexually transmitted infections, 2021: Accountability for the global health sector strategies 2016–2021: actions for impact. Genebra: OMS, 2021. Disponível em: https://www.who.int. Acessado em: 6 de novembro de 2023.
21. PEELING RW, et al. Syphilis. The Lancet, 2023; [s. l.], v. 402, n. 10398, p. 336–346.
22. PENG R, et al. Molecular Typing of Treponema pallidum Causing Early Syphilis in China: A Cross-Sectional Study. Sexually Transmitted Diseases, 2012; [s. l.], v. 39, n. 1, p. 42.
23. PILLAY A, et al. Molecular subtyping of Treponema pallidum subspecies pallidum. Sexually Transmitted Diseases, 1998 [s. l.], v. 25.
24. READ P, et al. Treponema pallidum Strain Types and Association with Macrolide Resistance in Sydney, Australia: New TP0548 Gene Types Identified. Journal of Clinical Microbiology, 2016; [s. l.], v. 54, n. 8, p. 2172–2174.
25. SALADO-RASMUSSEN K, et al. Molecular Typing of Treponema pallidum in Denmark: A Nationwide Study of Syphilis. Acta Dermato-Venereologica, 2016; [s. l.], v. 96, n. 2, p. 202–206.
26. SALLE R, et al. Treponema pallidum resistance to azithromycin in France: A nationwide retrospective study from 2010 to 2022. Journal of the European Academy of Dermatology and Venereology: JEADV, 2024; [s. l.], v. 38, n. 1, p. e20–e21.
27. SATO NS, et al. P1.44 Molecular typing and detection of macrolide resistence in Treponema pallidum DNA from patients with primary syphilis in são paulo,brazil. Sexually Transmitted Infections, 2017; [s. l.], v. 93, n. Suppl 2, p. A60–A61.
28. SHUEL M, et al. Molecular typing and macrolide resistance of syphilis cases in Manitoba, Canada, from 2012 to 2016. Sexually Transmitted Diseases, 2018; [s. l.], v. 45.
29. TAOUK ML, et al. Characterisation of Treponema pallidum lineages within the contemporary syphilis outbreak in Australia: a genomic epidemiological analysis. The Lancet Microbe, 2022; [s. l.], v. 3, n. 6, p. e417–e426.
30. TIECCO G, et al. A 2021 Update on Syphilis: Taking Stock from Pathogenesis to Vaccines. Pathogens, 2021; [s. l.], v. 10, n. 11, p. 1364.
31. TUDDENHAM S, et al. Syphilis Laboratory Guidelines: Performance Characteristics of Nontreponemal Antibody Tests. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 2020; [s. l.], v. 71, n. Suppl 1, p. S21–S42.
32. TUDOR ME, et al. Syphilis. In: STATPEARLS. Treasure Island (FL): StatPearls Publishing, 2023. Disponível em: http://www.ncbi.nlm.nih.gov/books/NBK534780/. Acessado em: 13 nov. 2023.
33. VAULET LG, 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; [s. l.], v. 12, n. 2, p. e0172905.
34. VENTER JME, et al. Treponema pallidum Macrolide Resistance and Molecular Epidemiology in Southern Africa, 2008 to 2018. Journal of Clinical Microbiology, 2021; [s. l.], v. 59, n. 10, p. 10.1128/jcm.02385-20.
35. WANG C, et al. A New Specimen for Syphilis Diagnosis: Evidence by High Loads of Treponema pallidum DNA in Saliva. Clinical Infectious Diseases, 2021; [s. l.], v. 73, n. 9, p. e3250–e3258.
36. WANG X, et al. Molecular Characteristics of Macrolide Resistance in Treponema pallidum from Patients with Latent Syphilis in Xinjiang, China. Infection and Drug Resistance, 2023; [s. l.], v. 16, p. 1231–1236.
37. WU H, et al. Evaluation of macrolide resistance and enhanced molecular typing of Treponema pallidum in patients with syphilis in Taiwan: a prospective multicenter study. Journal of Clinical Microbiology, 2012; [s. l.], v. 50.
38. 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. Sexually Transmitted Diseases, 2016; [s. l.], v. 43, n. 5, p. 310–316.
39. YANG CJ, et al. Unexpectedly high prevalence of Treponema pallidum infection in the oral cavity of human immunodeficiency virus-infected patients with early syphilis who had engaged in unprotected sex practices. Clinical Microbiology and Infection, 2015; [s. l.], v. 21, n. 8, p. 787.e1-787.e7.
2. CHAUDHRY S, et al. Secondary Syphilis: Pathophysiology, Clinical Manifestations, and Diagnostic Testing. Venereology, 2023; v. 2, n. 2, p. 65–75.
3. ECDC. European Centre for Disease Prevention and Control. Syphilis. Annual Epidemiological Report for 2022. Stockholm: ECDC; 2024. Disponível em: https://www.ecdc.europa.eu. Acessado em: 6 de novembro de 2023.
4. EDMONDSON DG, et al. Long-term in vitro culture of the syphilis spirochete Treponema pallidum subsp. pallidum. mBio, 2018; [s. l.], v. 9.
5. FERNÁNDEZ-NAVAL C, et al. Enhanced molecular typing and macrolide and tetracycline-resistance mutations of Treponema pallidum in Barcelona. Future Microbiology, 2019; [s. l.], v. 14, n. 13, p. 1099–1108.
6. FLORES JA, et al. Treponema pallidum subsp. pallidum genotypes and macrolide resistance status in syphilitic lesions among patients at 2 sexually transmitted infection clinics in Lima, Peru. Sexually Transmitted Diseases, 2016; [s. l.], v. 43.
7. FU B, et al. A comparison of genotyping tool in Treponema pallidum: Review and meta-analysis. Infection, Genetics and Evolution, 2020; [s. l.], v. 78, p. 104049.
8. GIACANI L, et al. Enhanced Molecular Typing of Treponema pallidum subspecies pallidum Strains From 4 Italian Hospitals Shows Geographical Differences in Strain Type Heterogeneity, Widespread Resistance to Macrolides, and Lack of Mutations Associated With Doxycycline Resistance. Sexually Transmitted Diseases, 2018; [s. l.], v. 45, n. 4, p. 237–242.
9. GRILLOVA L, et al. A public database for the new MLST scheme for Treponema pallidum subsp. pallidum: surveillance and epidemiology of the causative agent of syphilis. PeerJ, 2019; [s. l.], v. 6, p. e6182.
10. GRIMES M, et al. Two Mutations Associated With Macrolide Resistance in Treponema pallidum: Increasing Prevalence and Correlation With Molecular Strain Type in Seattle, Washington. Sexually Transmitted Diseases, 2012; [s. l.], v. 39, n. 12, p. 954.
11. KANAI M, et al. Molecular Typing and Macrolide Resistance Analyses of Treponema pallidum in Heterosexuals and Men Who Have Sex with Men in Japan, 2017. Journal of Clinical Microbiology, 2019; [s. l.], v. 57, n. 1, p. e01167-18.
12. KHAIRULLIN R, et al. Syphilis epidemiology in 1994–2013, molecular epidemiological strain typing and determination of macrolide resistance in Treponema pallidum in 2013–2014 in Tuva Republic, Russia. Journal of Pathology, Microbiology and Immunology, 2016; [s. l.], v. 124, n. 7, p. 595–602.
13. KOJIMA Y, et al. Circulation of Distinct Treponema pallidum Strains in Individuals with Heterosexual Orientation and Men Who Have Sex with Men. Journal of Clinical Microbiology, 2019; [s. l.], v. 57, n. 1, p. e01148-18.
14. KUBANOV AA, et al. Molecular epidemiology of Treponema pallidum in a Frontier region of the Russian Federation (Tuva Republic). Molecular Genetics, Microbiology and Virology, 2017; [s. l.], v. 32, n. 1, p. 29–34.
15. LIU D, et al. Molecular Characterization Based on MLST and ECDC Typing Schemes and Antibiotic Resistance Analyses of Treponema pallidum subsp. pallidum in Xiamen, China. Frontiers in Cellular and Infection Microbiology, 2021; [s. l.], v. 10.
16. LU Y, et al. Molecular epidemiological survey of Treponema pallidum in pregnant women in the Zhabei District of Shanghai. Journal of Medical Microbiology, 2017; [s. l.], v. 66, n. 4, p. 391–396.
17. MARRA CM, et al. Enhanced Molecular Typing of Treponema pallidum: Geographical Distribution of Strain Types and Association with Neurosyphilis. The Journal of Infectious Diseases, 2010; [s. l.], v. 202, n. 9, p. 1380–1388.
18. MIKALOVA L, et al. Comparison of CDC and sequence-based molecular typing of syphilis treponemes: tpr and arp loci are variable in multiple samples from the same patient. BMC Microbiology, 2013; [s. l.], v. 13.
19. MIKALOVÁ L, et al. Molecular Typing of Syphilis-Causing Strains Among Human Immunodeficiency Virus-Positive Patients in Antwerp, Belgium. Sexually Transmitted Diseases, 2017; [s. l.], v. 44, n. 6, p. 376.
20. ORGANIZAÇÃO MUNDIAL DA SAÚDE. Global progress report on HIV, viral hepatitis and sexually transmitted infections, 2021: Accountability for the global health sector strategies 2016–2021: actions for impact. Genebra: OMS, 2021. Disponível em: https://www.who.int. Acessado em: 6 de novembro de 2023.
21. PEELING RW, et al. Syphilis. The Lancet, 2023; [s. l.], v. 402, n. 10398, p. 336–346.
22. PENG R, et al. Molecular Typing of Treponema pallidum Causing Early Syphilis in China: A Cross-Sectional Study. Sexually Transmitted Diseases, 2012; [s. l.], v. 39, n. 1, p. 42.
23. PILLAY A, et al. Molecular subtyping of Treponema pallidum subspecies pallidum. Sexually Transmitted Diseases, 1998 [s. l.], v. 25.
24. READ P, et al. Treponema pallidum Strain Types and Association with Macrolide Resistance in Sydney, Australia: New TP0548 Gene Types Identified. Journal of Clinical Microbiology, 2016; [s. l.], v. 54, n. 8, p. 2172–2174.
25. SALADO-RASMUSSEN K, et al. Molecular Typing of Treponema pallidum in Denmark: A Nationwide Study of Syphilis. Acta Dermato-Venereologica, 2016; [s. l.], v. 96, n. 2, p. 202–206.
26. SALLE R, et al. Treponema pallidum resistance to azithromycin in France: A nationwide retrospective study from 2010 to 2022. Journal of the European Academy of Dermatology and Venereology: JEADV, 2024; [s. l.], v. 38, n. 1, p. e20–e21.
27. SATO NS, et al. P1.44 Molecular typing and detection of macrolide resistence in Treponema pallidum DNA from patients with primary syphilis in são paulo,brazil. Sexually Transmitted Infections, 2017; [s. l.], v. 93, n. Suppl 2, p. A60–A61.
28. SHUEL M, et al. Molecular typing and macrolide resistance of syphilis cases in Manitoba, Canada, from 2012 to 2016. Sexually Transmitted Diseases, 2018; [s. l.], v. 45.
29. TAOUK ML, et al. Characterisation of Treponema pallidum lineages within the contemporary syphilis outbreak in Australia: a genomic epidemiological analysis. The Lancet Microbe, 2022; [s. l.], v. 3, n. 6, p. e417–e426.
30. TIECCO G, et al. A 2021 Update on Syphilis: Taking Stock from Pathogenesis to Vaccines. Pathogens, 2021; [s. l.], v. 10, n. 11, p. 1364.
31. TUDDENHAM S, et al. Syphilis Laboratory Guidelines: Performance Characteristics of Nontreponemal Antibody Tests. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 2020; [s. l.], v. 71, n. Suppl 1, p. S21–S42.
32. TUDOR ME, et al. Syphilis. In: STATPEARLS. Treasure Island (FL): StatPearls Publishing, 2023. Disponível em: http://www.ncbi.nlm.nih.gov/books/NBK534780/. Acessado em: 13 nov. 2023.
33. VAULET LG, 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; [s. l.], v. 12, n. 2, p. e0172905.
34. VENTER JME, et al. Treponema pallidum Macrolide Resistance and Molecular Epidemiology in Southern Africa, 2008 to 2018. Journal of Clinical Microbiology, 2021; [s. l.], v. 59, n. 10, p. 10.1128/jcm.02385-20.
35. WANG C, et al. A New Specimen for Syphilis Diagnosis: Evidence by High Loads of Treponema pallidum DNA in Saliva. Clinical Infectious Diseases, 2021; [s. l.], v. 73, n. 9, p. e3250–e3258.
36. WANG X, et al. Molecular Characteristics of Macrolide Resistance in Treponema pallidum from Patients with Latent Syphilis in Xinjiang, China. Infection and Drug Resistance, 2023; [s. l.], v. 16, p. 1231–1236.
37. WU H, et al. Evaluation of macrolide resistance and enhanced molecular typing of Treponema pallidum in patients with syphilis in Taiwan: a prospective multicenter study. Journal of Clinical Microbiology, 2012; [s. l.], v. 50.
38. 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. Sexually Transmitted Diseases, 2016; [s. l.], v. 43, n. 5, p. 310–316.
39. YANG CJ, et al. Unexpectedly high prevalence of Treponema pallidum infection in the oral cavity of human immunodeficiency virus-infected patients with early syphilis who had engaged in unprotected sex practices. Clinical Microbiology and Infection, 2015; [s. l.], v. 21, n. 8, p. 787.e1-787.e7.