Syphilis reinfection is associated with an attenuated immune profile in the same individual: a prospective observational cohort study
Tóm tắt
Ascertaining if the clinical and immunological response to repeat syphilis differs from that in initial syphilis may assist in designing optimal syphilis screening strategies and vaccine design. We prospectively recruited 120 patients with a new diagnosis of (baseline) syphilis. During a 24-month follow-up period, 11 of these patients had a further diagnosis of (repeat) syphilis. We conducted a paired comparison of their plasma cyto-chemokines at baseline and repeat syphilis. Comparing to their baseline infection, paired analyses of the 11 individuals with repeat infections during follow-up revealed that these reinfections had lower concentrations of Interferon (IFN)α (0.8 [Interquartile range (IQR) 0.8–0.8 vs. 12.2 [IQR 1.6–24.2], P = 0.004) and Chemokine (C-C motif) ligand (CCL) 4 (0.9 [IQR 0.9–12.2 vs. 17.5 [IQR 4.9–32.8], P = 0.022]. In this small study of 11 individuals, repeat syphilis was found to present with an attenuated immune response. The relevance of these findings to the design of optimal syphilis screening programs is discussed.
Tài liệu tham khảo
Kenyon C, Lynen L, Florence E, Caluwaerts S, Vandenbruaene M, Apers L, Soentjens P, Van Esbroeck M, Bottieau E. Syphilis reinfections pose problems for syphilis diagnosis in Antwerp, Belgium - 1992 to 2012. Euro Surveill. 2014;19(45):20958.
Botham SJ, Ressler K-A, Maywood P, Hope KG, Bourne CP, Conaty SJ, Ferson MJ, Mayne DJ. Men who have sex with men, infectious syphilis and HIV coinfection in inner Sydney: results of enhanced surveillance. Sex Health. 2013;10(4):291–8.
Kenyon C, Osbak KK, Apers L. Repeat syphilis is more likely to be asymptomatic in HIV-infected individuals: a retrospective cohort analysis with important implications for screening. Open Forum Infect Dis. 2018;5(6):ofy096.
Kenyon C, Tsoumanis A, Osbak K, Van Esbroeck M, Crucitti T, Kestens L. Repeat syphilis has a different immune response compared to initial syphilis: an analysis of biomarker kinetics in two cohorts. Sex Transm Infect. 2017; Epub ahead of print.
Courjon J, Hubiche T, Dupin N, Grange PA, Del Giudice P. Clinical aspects of syphilis reinfection in HIV-infected patients. Dermatology. 2015;230(4):302–7.
Brewer TH, Peterman TA, Newman DR, Schmitt K. Reinfections during the Florida syphilis epidemic, 2000-2008. Sex Transm Dis. 2011;38(1):12–7.
Kerani R, Lukehart S, Stenger M, Marra C, Pedersen R, Golden M. Is early latent syphilis more likely in patients with a prior syphilis infection? British Society for Sexual Health and HIV. London: Presentation at 18th international society for STD research; 2009. 28 June-1 July
Magnuson HJ, Thomas EW, Olansky S, Kaplan BI, De Mello L, Cutler JC. Inoculation syphilis in human volunteers. Medicine (Baltimore). 1956;35(1):33–82.
Workowski KA, Berman SM, Centers for disease C, prevention. Sexually transmitted diseases treatment guidelines, 2010. Atlanta: Department of Health and Human Services, Centers for Disease Control and Prevention; 2010.
Chen CY, Chi KH, George RW, Cox DL, Srivastava A, Rui Silva M, Carneiro F, Lauwers GY, Ballard RC. Diagnosis of gastric syphilis by direct immunofluorescence staining and real-time PCR testing. J Clin Microbiol. 2006;44(9):3452–6.
Bernardeschi C, Grange PA, Janier M, Gressier L, Dion PL, Benhaddou N, Bianchi A, Lassau F, Avril MF, Batteux F, et al. Treponema pallidum induces systemic TH17 and TH1 cytokine responses. Eur J Dermatol. 2012;22(6):797–8.
Wicher V, Scarozza AM, Ramsingh AI, Wicher K. Cytokine gene expression in skin of susceptible Guinea-pig infected with Treponema pallidum. Immunology. 1998;95(2):242–7.
Salazar JC, Cruz AR, Pope CD, Valderrama L, Trujillo R, Saravia NG, Radolf JD. Treponema pallidum elicits innate and adaptive cellular immune responses in skin and blood during secondary syphilis: a flow-cytometric analysis. J Infect Dis. 2007;195(6):879–87.
Kojima N, Bristow CC, Maecker H, Rosenberg-Hasson Y, Leon SR, Vargas SK, Konda KA, Caceres CF, Klausner JD. Similarities in the markers of inflammation between men with syphilis and women with increased risk of HIV acquisition. Clin Infect Dis. 2016;62(2):265–6.
Cruz AR, Ramirez LG, Zuluaga AV, Pillay A, Abreu C, Valencia CA, La Vake C, Cervantes JL, Dunham-Ems S, Cartun R, 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.
Knudsen A, Benfield T, Kofoed K. Cytokine expression during syphilis infection in HIV-1-infected individuals. Sex Transm Dis. 2009;36(5):300–4.
Podwinska J, Lusiak M, Zaba R, Bowszyc J. The pattern and level of cytokines secreted by Th1 and Th2 lymphocytes of syphilitic patients correlate to the progression of the disease. FEMS Immunol Med Microbiol. 2000;28(1):1–14.
Pastuszczak M, Gozdzialska A, Jakiela B, Obtulowicz A, Jaskiewicz J, Wojas-Pelc A. Robust pro-inflammatory immune response is associated with serological cure in patients with syphilis: an observational study. Sex Transm Infect. 2017;93(1):11–14.
Fitzgerald TJ. The Th1/Th2-like switch in syphilitic infection: is it detrimental? Infect Immun. 1992;60(9):3475–9.
Kenyon C, Osbak KK, Crucitti T, Kestens L. The immunological response to syphilis differs by HIV status; a prospective observational cohort study. BMC Infect Dis. 2017;17(1):111.
Brown ST, Zaidi A, Larsen SA, Reynolds GH. Serological response to syphilis treatment. A new analysis of old data. JAMA. 1985;253(9):1296–9.
Romanowski B, Sutherland R, Fick GH, Mooney D, Love EJ. Serologic response to treatment of infectious syphilis. Ann Intern Med. 1991;114(12):1005–9.
Tramont E, In S, Mandell GL, Bennett JE, Dolin R. Principles and Practice of Infectious Diseases. 8th ed. Atlanta: Churchill Livingstone Inc; 2015.
Myint M, Bashiri H, Harrington RD, Marra CM. Relapse of secondary syphilis after benzathine penicillin G: molecular analysis. Sex Transm Dis. 2004;31(3):196–9.
Florindo C, Reigado V, Gomes JP, Azevedo J, Santo I, Borrego MJ. Molecular typing of treponema pallidum clinical strains from Lisbon, Portugal. J Clin Microbiol. 2008;46(11):3802–3.