New perspectives in the study of the congenital syphilis: A narrative review / Novas perspectivas no estudo da sífilis congênita: Uma revisão narrativa

Andrea Tatiana Durán- Rodriguez, Yolanda Cifuentes, Jeannette Navarrete Ospina, Liliana Muñoz Molina, Gladys Pinilla Bermudez

Abstract


Syphilis is still an infection of public health significance, particularly due to its impact during pregnancy and the possibility of mother-to-child transmission that may occur at any stage of pregnancy. Congenital syphilis can lead to miscarriage, stillbirth, perinatal death, premature birth, and clinical manifestations in the newborn. In prospective, the perinatal morbidity and mortality rates due to congenital syphilis are even greater than those due to HIV infection. Overall, both syphilis and congenital syphilis remain a serious public health issue mainly due to flaws both prenatal care systems and syphilis prevention and control programs. This review discusses vertical transmission of the syphilis agent the Treponema pallidum subsp. pallidum, the clinical manifestations of congenital syphilis, the current guidelines for the evaluation and treatment of infants born to mothers with gestational syphilis, the global epidemiology and ongoing research efforts to better understand the pathogenetic mechanisms employed by the syphilis agent to cross the placental barrier and cause congenital infection.

 

 


Keywords


Congenital syphilis, gestational syphilis, Treponema pallidum.

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References


Grillová L, Giacani L, Mikalová L, et al. Sequencing of Treponema pallidum subsp. pallidum from isolate UZ1974 using Anti-Treponemal Antibodies Enrichment: First complete whole genome sequence obtained directly from human clinical material. PLoS ONE. 2018; 13(8): e0202619.

Equipo Infecciones de Transmisión Sexual, grupo de transmisibles INS. Protocolo de vigilancia en salud publica, sifilis gestacional y sifilis congenita. INS. 2015 Feb; Version 02. (Ministerio de Salud de Colombia Web site). Available at: https://www.minsalud.gov.co/sites/rid/Lists/BibliotecaDigital/RIDE/IA/INS/protocolo-vigilancia-sifilis-gestacional.pdf. Accessed July27, 2019.

Newman L, Kamb M, Hawkes S, et al. Global Estimates of Syphilis in Pregnancy and Associated Adverse Outcomes: Analysis of Multinational Antenatal Surveillance Data. PLoS Med. 2013; 10(2): e1001396.

Grimprel E, Sanchez PJ, Wendel GD, et al. Use of polymerase chain reaction and rabbit infectivity testing to detect Treponema pallidum in amniotic fluid, fetal and neonatal sera, and cerebrospinal fluid. J Clin Microbiol. 1991; 29(8): 1711–1718.

The Lancet. Congenital syphilis in the USA. Lancet. 2018; 392 (10154): 1168.

European Centre for Disease Prevention and Control. Congenital syphilis. Annual epidemiological Report for 2017. (ECDC Web Side). Available at: https://www.ecdc.europa.eu/en/publications-data/congenital-syphilis-annual-epidemiological-report-2017. Accesed July30, 2019.

Furegato M, Fifer H, Mohammed H, et al. Factors associated with four atypical cases of congenital syphilis in England, 2016 to 2017: an ecological analysis. Euro Surveill. 2017;22(49):17-00750.

Herbert LJ, Middleton SI. An estimate of syphilis incidence in Eastern Europe. J Glob Health. 2012; 2(1):010402.

Peeling RW, Mabey D, Kamb ML, et al. Syphilis. Nat Rev Dis Primers. 2017;3:17073.

Molepo J, Pillay A, Weber B, et al. Molecular typing of Treponema pallidum strains from patients with neurosyphilis in Pretoria, South Africa. Sex Transm Infect. 2007; 83(3):189–92.

Lang R, Read R, Krentz HB, et al. Increasing incidence of syphilis among patients engaged in HIV care in Alberta, Canada: a retrospective clinic-based cohort study. BMC Infect Dis. 2018; 18(1): 125.

Olugbenga I, Taiwo O, Laverty M, et al. Clinic-based evaluation study of the diagnostic accuracy of a dual rapid test for the screening of HIV and syphilis in pregnant women in Nigeria. PLoS One. 2018; 13(8): e0202122.

Radolf JD, Deka RK, Anand A, et al. Treponema pallidum, the syphilis spirochete: making a living as a stealth pathogen. Nat Rev Microbiol. 2016; 14(12): 744-759.

Harter C, Benirschke K. Fetal syphilis in the first trimester. Am J Obstet Gynecol. 1976; 124(7): 705-711.

Nathan L, Bohman VR, Sanchez PJ, et al. In utero infection with Treponema pallidum in early pregnancy. Prenatal Diagnosis. 1997; 17(2): 119-123.

Ingraham NR JR. The value of penicillin alone in the prevention and treatment of congenital syphilis. Acta Derm Venereol Suppl (Stockh). 1950; 31(Suppl. 24): 60-87.

Klass PE, Brown ER, Pelton SI. The incidence of prenatal syphilis at the Boston City Hospital: a comparison across four decades. N Engl J Med. 1994; 94(1): 24-8.

De Santis M, De Luca C, Mappa I, et al. Syphilis Infection during pregnancy: fetal risks and clinical management. Infect Dis Obstet Gynecol. 2012; 2012: 430585.

Wahab AA, Ali UK, Mohammad M, et al. Syphilis in pregnancy. Pak J Med Sci. 2015; 31(1): 217-219.

Hussain SA, Vaidya R. Congenital Syphilis. In: StatPearls (Online) Feb 2019; Available from: https://www.ncbi.nlm.nih.gov/books/NBK537087/ Accessed August 10, 2019.

Herremans T, Kortbeek L, Notermans DW. A review of diagnostic tests for congenital syphilis in newborns. Eur J Clin Microbiol Infect Dis. 2010; 29(5): 495-501.

Carlson JA, Dabiri G, Cribier B, Sell S. The immunopathobiology of syphilis: the manifestations and course of syphilis are determined by the level of delayed-type hypersensitivity. Am J Dermatopathol. 2011; 33(5): 433–460.

Cherneskie, T. An Update and Review of the Diagnosis and Management of Syphilis. (The New York City STD/HIV Prevention Training Center Web Site). Available at: https://www.nycptc.org/x/Syphilis_Module_Online.pdf. Accessed August 12, 2019.

Kollmann T, Dobson S. Syphilis. Infectious Diseases of the Fetus and Newborn. Seventh Edition. Elsevier Inc; 2011: 524-563.

Tsimis ME, Sheffield JS. Update on syphilis and pregnancy. Birth Defects Res. 2017; 109: 347-352.

World Health Organization. Guideline on syphilis screening and treatment for pregnant women. (WHO Web Site). Available at: https://www.who.int/reproductivehealth/publications/rtis/syphilis-ANC-screenandtreat-guidelines/en/. Accessed August 15, 2019.

Arnold SR, Ford-Jones EL. Congenital syphilis: A guide to diagnosis and management. Paediatr Child Health. 2000; 5(8): 463-9.

Minnesota Department of Health. Guidance for syphilis during pregnancy and congenital syphilis, including infants and children. Clinical Guidelines for Syphilis. (MN Department of Health Web Site). Available at: https://www.health.state.mn.us/diseases/syphilis/hcp/healthcarewomen.html. Accessed August 20, 2019.

Centers for Disease Control and Prevention. Surveillance Case Definitions Congenital Syphilis. (CDC Web Site). Available from: https://wwwn.cdc.gov/nndss/conditions/congenital-syphilis/case-definition/2018/. Accessed August 20, 2019.

Queensland Clinical Guidelines. Syphilis in pregnancy. Queensland Clinical Guidelines. (Queensland Government Health Web Site). Available at: https://www.health.qld.gov.au/__data/assets/pdf_file/0035/736883/g-sip.pdf. Accessed August 20, 2019.

Sanguineti Cecilia. Pruebas de Laboratorio en el diagnóstico de la sífilis. Dermatologia peruana. 2000; 10(1): 1–6.

Morales-Múnera, CE, et al. Update on the Diagnosis and Treatment of Syphilis. Actas Dermosifiliogr. 2015; 106(1): 68-69.

Norris, S et al. Biology of Treponema pallidum: correlation of functional activities with genome sequence data. 2001; 3(1): 37-62.

Martin IE, Tsang RSW, Sutherland K, et al. Molecular Characterization of Syphilis in Patients in Canada: Azithromycin Resistance and Detection of Treponema pallidum DNA in Whole-Blood Samples versus Ulcerative Swabs. J Clin Microbiol. 2009; 47(6): 1668-1673.

Radolf JD, et al. Treponema pallidum and the quest for outer membrane proteins. Mol Microbiol. 2006; 16(6), 1067-1073.

Kubanov A, Runina A, Deryabin D. Novel Treponema pallidum Recombinant Antigens for Syphilis Diagnostics: Current Status and Future Prospects. Biomed Res Int. 2017; 2017:1436080.

Radolf JD, Kumar S. The Treponema pallidum Outer Membrane. Curr Top Microbiol Immunol. 2018; 415:1–38.

Lithgow K, Hof R, Wetherell C. et al. A defined syphilis vaccine candidate inhibits dissemination of Treponema pallidum subspecies pallidum. Nat Commun. 2017;8: 14273.

Runina AV, Starovoitova AS, Deryabin DG, Kubanov AA. Evaluation of the Recombinant Protein Tp0965 of Treponema Pallidum as Perspective Antigen for the Improved Serological Diagnosis of Syphilis. Vestn Ross Akad Med Nauk. 2016; (2): 109-113.

Sun R, Lai DH, Ren RX, et al. Treponema pallidum-specific antibody expression for the diagnosis of different stages of syphilis. Chin Med J (Engl). 2013; 126(2) :206-210.

Burstain JM, et al. Sensitive detection of Treponema pallidum by using the polymerase chain reaction. J Clin Microbiol. 1991; 29(1):62-69.

Chean R, Kwong JC, Ciciulla J, Leslie D. Confirmation of tertiary Treponema pallidum infection by polA polymerase chain reaction (PCR). Pathology. 2014; 46(3) :259-260.

Pinilla G, et al. Determinación de los genes, 16S ADNr, polA, y TpN47, en la detección de Treponema pallidum subsp. pallidum para el diagnóstico de sífilis congénita. NOVA. 2015; 13 (23): 17-25.

Giacani L, et al. Identification of the Treponema pallidum subsp. pallidum TP0092 (RpoE) regulon and its implications for pathogen persistence in the host and syphilis pathogenesis. J Bacteriol. 2013; 195(4), 896-907.

Ho EL, Lukehart SA. Syphilis: using modern approaches to understand an old disease. J Clin Invest. 2011; 121(12), 4584.

Brautigam CA, Deka RK, Liu WZ, Norgard MV. The Tp0684 (MglB-2) Lipoprotein of Treponema pallidum: A Glucose-Binding Protein with Divergent Topology. PLoS One. 2016; 11(8):e0161022.

Parsonage D, et al. Broad specificity AhpC-like peroxiredoxin and its thioredoxin reductant in the sparse antioxidant defense system of Treponema pallidum. Proc. Natl Acad. Sci. 2010; 107: 6240–6245.

Deka RK, et al. Structural evidence that the 32-kilodalton lipoprotein (Tp32) of Treponema pallidum is an L-methionine-binding protein. J Biol Chem. 2004; 279(53): 55644-50.

Lee YH, Deka RK, Norgard MV, Radolf JD, Hasemann CA. Treponema pallidum TroA is a periplasmic zinc-binding protein with a helical backbone. Nat Struct Biol. 1999; 6(7): 628-633.

Fraser CM, et al. Complete Genome Sequence of Treponema pallidum Syphilis Spirochete. Science. 1998; 281: 375-388.

Larsen SA, et al. Laboratory diagnosis and interpretation of tests for syphilis. Clin Microbiol Rev. 1995; 8(1):1-21.

Pětrošová H, et al. Resequencing of Treponema pallidum ssp. pallidum strains Nichols and SS14:correction of sequencing errors resulted in increased separation of syphilis treponeme subclusters. PLoS One. 2013; 10;8(9): e74319.

Arora N, Schuenemann VJ, Jäger G, et al. Origin of modern syphilis and emergence of a pandemic Treponema pallidum cluster. Nat Microbiol. 2016; 2: 16245.

LaFond R, Lukehart, SA. Biological basis for syphilis. Clin Microbiol Rev. 2006; 19(1): 29-49.

Knudsen A, et al. Cytokine expression during syphilis infection in HIV 1 infected individuals. Sex Transm Dis. 2009; 36(5): 300-304.

Engelkens HJ, Ten Kate FJ, Judanarso J, et al. The localisation of treponemes and characterisation of the inflammatory infiltrate in skin biopsies from patients with primary or secondary syphilis, or early infectious yaws [published correction appears in Genitourin Med 1993 Aug;69(4):327]. Genitourin Med. 1993;69(2):102-107.

Cruz AR, Ramirez LG, Zuluaga AV, et al. Immune evasion and recognition of the syphilis spirochete in blood and skin of secondary syphilis patients: two immunologically distinct compartments. PLoS Negl Trop Dis. 2012; 6(7): e1717.

Lee KH, Choi HJ, Lee MG, Lee JB. Virulent Treponema pallidum 47 kDa antigen regulates the expression of cell adhesion molecules and binding of T-lymphocytes to cultured human dermal microvascular endothelial cells. Yonsei Med J. 2000; 41(5):623-633.

Zhang RL, Wang QQ, Zhang JP, Yang LJ. Tp17 membrane protein of Treponema pallidum activates endothelial cells in vitro. Int Immunopharmacol. 2015; 25(2): 538-44.

Moraes M, Estevan M. Actualización en sífilis congénita temprana. Arch Pediatr Urug 2011; 83(1): 35-39.

Hossain M, Broutet N, Hawkes S. The elimination of congenital syphilis: a comparison of the proposed World Health Organization action plan for the elimination of congenital syphilis with existing national maternal and congenital syphilis polices. Sexually transmitted diseases. 2007; 34(7), S22-S30.

Peeling RW, Ye H. Diagnostic tools for preventing and managing maternal and congenital syphilis: an overview. Bull World Health Organ. 2004; 82(6): 439-446.

Woznicová V, et al. Detection of Treponema pallidum subsp. pallidum from skin lesions, serum, and cerebrospinal fluid in an infant with congenital syphilis after clindamycin treatment of the mother during pregnancy. J Clin Microbiol. 2007; 45(2): 659-661.

Ratnam S, et al. The laboratory diagnosis of syphilis. Can J Infect Dis Med Microbiol. 2005; 16:45-51.

Grange PA, Gressier L, Dion PL, et al. Evaluation of a PCR Test for Detection of Treponema pallidum in Swabs and Blood. J Clin Microbiol. 2012; 50(3): 546-552.

Centurion-Lara A, et al. Detection of Treponema pallidum by a sensitive reverse transcriptase PCR. J Clin Microbiol. 1997; 35(6): 1348-52.

Ham DC, Lin C, Newman L, Wijesooriya NS, Kamb M. Improving global estimates of syphilis in pregnancy by diagnostic test type: A systematic review and meta-analysis. Int J Gynaecol Obstet. 2015;130 Suppl 1(0 1): S10-S14.

Singh AE, Levett PN, Fonseca K, et al. Canadian Public Health Laboratory Network laboratory guidelines for congenital syphilis and syphilis screening in pregnant women in Canada. Can J Infect Dis Med Microbiol. 2015;26 Suppl A(Suppl A): 23A-8A.

Luu M, et al. Syphilis testing in antenatal care: Policies and practices among laboratories in the Americas. Int J Gynaecol Obstet. 2015; S0020-7292(15)00208-8.

Dassah ET, et al. Rollout of rapid point of care tests for antenatal syphilis screening in Ghana: healthcare provider perspectives and experiences. BMC Health Serv Res. 2018; 18(130).

Grimprel E, et al. Use of polymerase chain reaction and rabbit infectivity testing to detect Treponema pallidum in amniotic fluid, fetal and neonatal sera, and cerebrospinal fluid. J Clin Microbiol. 1991; 29(8):1711-1718.

Gama A, Carrillo-Casas EM, Hernández-Castro R, et al. Treponema pallidum ssp. pallidum identification by real-time PCR targetting the polA gene in paraffin-embedded samples positive by immunohistochemistry. Int J STD AIDS. 2017; 28(13):1299–304.

Pinilla G, Campos L, Durán A, et al. Detección de Treponema pallidum subespecie pallidum para el diagnóstico de sífilis congénita mediante reacción en cadena de la polimerasa anidada. Biomedica. 2018; 38(1): 128-135.

Chadha T, Trindade AA. Phylogenetic analysis of pbp genes in treponemes. Infect Ecol Epidemiol. 2013;3:10.3402/iee.v3i0.18636.

Pillay, A. In McKee IdFL. Filippis, Ivano, McKee, Marian L, Eds. Treponema. Molecular Typing in Bacterial Infections: Humana Press; 2013, 311-326.

Garza-Velasco R, Gómez-Pérez L, Manero-Brito S. La sífilis y los principales factores de virulencia de Treponema pallidum. México UNAM, Fac Química, Dep Biol. Available at: http://depa.fquim.unam.mx/bacteriologia/pdfs/ART%CDC-Tpallidum.pdf. Accessed September 10, 2019.

Cha J, et al. A novel β-lactamase activity from a penicillin-binding protein of Treponema pallidum and why syphilis is still treatable with penicillin. J Biol Chem. 2004; 279(15), 14917-14921.

Smith B, et al. New Proteins for a New Perspective on Syphilis Diagnosis. J Clin Microbiol. 2013; 51(1), 105-111.

Durán-Rodriguez A, et al. Detección molecular de sífilis gestacional y congenita. Infectio. 2020; 24(1): 15-19.

Vilela, L. S. C. A. L., et al. O pré-natal como ferramenta na prevenção da sífilis congênita: uma revisão integrativa da literature. Braz. J. Hea. Rev. 2019. v. 2, n. 3, p. 1609-1615.




DOI: https://doi.org/10.34119/bjhrv3n4-255

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