The treatment outcome and predictors of serological response in syphilis in a sexually transmitted infections center,China

Abstract

Serology is the mainstay for syphilis treatment monitoring. Baseline rapid plasma reagin (RPR) titre, HIV status, and syphilis stage have been found to be associated with the time to serological response among syphilis patients. This study mainly aims to evaluate the time to serological response, and to identify factors affecting the serological outcome. Medical records of syphilis cases diagnosed in Peking Union Medical College Hospital (PUMCH) between 2008 and 2018 were retrospectively reviewed. Kaplan–Meier analysis was performed to evaluate the median time to serologic response and cumulative probability of serologic response over time according to different variables. Cox regression model was conducted to find factors associated with serological response. There were 984 patients diagnosed with primary, secondary, or latent syphilis cases and receiving injections of benzathine penicillin G (BPG) as initial treatment at the Peking Union Medical College Hospital (PUMCH) between 2008 and 2018. Finally, data on 571 patients, including 49 (8.6%) primary syphilis, 261 (45.7%) secondary syphilis, and 261 (45.7%) latent syphilis, were used for analysis. It took longer time to achieve serological response for subjects aged ≥45 years than younger individuals (89 days versus 58 days; p=0.008). Males achieved serological response more quickly than females (71 days versus 83 days; p = 0.011). There was a significant difference in the time to serological response according to different syphilis stages (p < 0.001), with 55 days (95% CI, 43–67 days) for primary, 57 days (95% CI, 51–63 days) for secondary, and 117 days for latent syphilis. In addition, patients with lower baseline RPR titre had longer period to achieve serological response (252 days [95% CI, 129–375 days] for RPR titre ≤1:8, 78 days [95% CI, 63–93 days] for RPR titres from 1:16 to 1:32, and 53 days [95% CI, 49–57 days] for RPR titres ≥1:64, respectively; p<0.001). However, no significant difference in time to serological response to treatment was found according to HIV coinfection status. The result of multivariate Cox regression analysis showed that being older than 45 years with latent syphilis, HIV coinfection, or with baseline RPR titre ≤1:8 was associated with slow response. Among patients followed for at least 1 year or seroreverted, 128 (36.9%) had seroreverted within a year, and 219 (63.1%) still had a positive RPR after 1 year. For multiple logistical regression, being female and HIV coinfection were significantly associated with the failure of seroreversion (OR, 0.42 [95% CI, 0.26–0.68]; p <0.001). This study revealed that younger age, higher initial RPR titre, early syphilis stage, and HIV-negative status were associated with faster serological cure. Female sex, individuals with HIV coinfection, and latent syphilis were significantly associated with the failure of seroreversion.

Keywords

syphilis (treponema pallidum) < bacterial disease treatment < other antibiotic < other HIV < viral disease

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References

O'Byrne

MacPherson

. Syphilis. BMJ 2019; 365: l4159.

Hook

. Syphilis. LANCET 2017; 389: 1550–1557.

Guidelines for the diagnosis and treatment of syphilis gonorrhea and genital chlamydia trachomatis. Chin J Dermatol. 2020; 2020(03):168–169.

Hook

Behets

Van Damme

, et al. A phase III equivalence trial of azithromycin versus benzathine penicillin for treatment of early syphilis. J Infect Dis 2010; 201: 1729–1735.

McMillan

Young

. Reactivity in the venereal diseases research laboratory test and the Mercia IgM enzyme immunoassay after treatment of early syphilis. Int J STD AIDS 2008; 19: 689–693.

Riedner

Rusizoka

Todd

, et al. Single-dose azithromycin versus penicillin G benzathine for the treatment of early syphilis. N Engl J Med 2005; 353: 1236–1244.

Seña

Zhang

, et al. A systematic review of syphilis serological treatment outcomes in HIV-infected and HIV-uninfected persons: Rethinking the significance of serological non-responsiveness and the serofast state after therapy. BMC Infect Dis 2015; 15: 479.

China NHCotPsRo . Diagnosis for Syphilis. National Health Commission of the People's Republic of China, 2018 (accessed on 2018, Aug 1).

Workowski

Bolan

. Sexually transmitted diseases treatment guidelines, 2015MMWR. Recommendations and reports: morbidity and mortality weekly report. MMWR Recomm Rep 2015; 64: 1–137.

10.

Knaute

Graf

Lautenschlager

, et al. Serological response to treatment of syphilis according to disease stage and HIV status. Clin Infect Dis 2012; 55: 1615–1622.

11.

Ghanem

Moore

Rompalo

, et al. Antiretroviral therapy is associated with reduced serologic failure rates for syphilis among HIV-infected patients. Clin Infect Dis 2008; 47(2): 258–265.

12.

Tong

Lin

Liu

, et al. Factors associated with serological cure and the serofast state of HIV-negative patients with primary, secondary, latent, and tertiary syphilis. PLoS One 2013; 8: e70102.

13.

Tittes

Aichelburg

Antoniewicz

, et al. Enhanced therapy for primary and secondary syphilis: A longitudinal retrospective analysis of cure rates and associated factors. Int J STD AIDS 2013; 24: 703–711.

14.

Seña

Wolff

Martin

, et al. Predictors of serological cure and serofast state after treatment in HIV-negative persons with early syphilis. Clin Infect Dis 2011; 53: 1092–1099.

15.

Jinno

Anker

Kaur

, et al. Predictors of serological failure after treatment in HIV-infected patients with early syphilis in the emerging era of universal antiretroviral therapy use. BMC Infect Dis 2013; 13: 605.

16.

Romanowski

Sutherland

Fick

, et al. Serologic response to treatment of infectious syphilis. Ann Intern Med 1991; 114: 1005–1009.

17.

Manavi

McMillan

. The outcome of treatment of early latent syphilis and syphilis with undetermined duration in HIV-infected and HIV-uninfected patients. Int J STD AIDS 2007; 18: 814–818.

18.

Dionne-Odom

Karita

Kilembe

, et al. Syphilis treatment response among HIV-discordant couples in Zambia and Rwanda. Clin Infect Dis 2013; 56: 1829–1837.

19.

Wang

Zheng

. Predictors of serological cure and serofast state after treatment in HIV-negative patients with early syphilis in China. Sex Transm Infect 2013; 89: 69.

20.

Rolfs

Joesoef

Hendershot

, et al. A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection. The Syphilis and HIV Study Group. N Engl J Med 1997; 337(5): 307–314.