IN THE PAST DECADE, in many cities in the western world a rising incidence of syphilis has been reported, especially among men who have sex with men (MSM).1–2
Because both syphilis and HIV are sexually transmitted diseases, coinfections are common. HIV seroprevalence among MSM having syphilis averages 40 to 50%.1 A significant proportion of syphilis infections in HIV infected persons is asymptomatic.3–4
Current guidelines published by the CDC, recommend at least yearly syphilis testing among HIV-positive patients.5 In this study, we investigated the yield of routine syphilis screening in HIV-patients. The incidence of symptomatic and asymptomatic syphilis infections in patients visiting the HIV-outpatient clinic of a large university hospital in Amsterdam, the Netherlands, was determined both retrospectively and prospectively.
Materials and Methods
Syphilis serology was performed in all HIV-infected patients who visited our outpatient clinic from March through June 2003. It was repeated from September through December 2003. Serology was performed using the Treponema pallidum particle agglutination assay (TPPA; Fujirebio Inc, Tokyo, Japan) and, when positive, followed by the non-treponemal rapid plasma reagin assay (RPR; Biomerieux, Boxtel, The Netherlands). A newly positive TPPA-test or a fourfold or greater rise in RPR-titre was considered diagnostic of syphilis infection. If patients had evidence of a new infection during the first episode of screening, TPPA/RPR tests were performed on historical sera in order to narrow down the moment of seroconversion. For prospective analyses, test results of the first and second screening episode were compared. Clinical data were retrieved from case records, to assess whether the episode of syphilis had been recognized by the clinician (primary and secondary syphilis), respectively whether the testing had been done because of risk contacts with syphilis cases; all other cases were considered asymptomatic (early and late latent syphilis, latent syphilis of unknown duration). For both the retrospective and prospective analysis we calculated the number of person years (PY) of follow-up in the cohort.
From March through June 2003, syphilis serology was performed in 1351 patients. Of those, 246 patients had no historical syphilis test results and they were therefore excluded from further analyses. The remaining 1,105 patients had been followed at our clinic for a median of 5.7 (range 0.5–20) years. In this cohort, 81 episodes of syphilis were identified in 68 patients. All episodes were in male patients, mostly MSM (94%). One patient had 3 episodes of syphilis, and 11 patients had 2 episodes. 27/81 (33%) of the syphilis infections were asymptomatic.
Additional tests performed on historical sera showed that only 1 episode of syphilis occurred in the period 1994–1997 and 3 between 1997 and 2000. The remaining 77 infections were acquired between January 2000 and June 2003. For the latter period, the total follow-up was 2818 PY, resulting in a calculated event rate of 2.7/100 PY, and 0.9/100 PY for asymptomatic disease (Table 1). 74 of 77 new cases of syphilis in this period occurred in MSM, resulting in a total incidence in this subgroup of 4.6/100 PY, and 1.5/100 PY for asymptomatic disease.
Serology was repeated in 1010 patients from September through December 2003. In 17 patients, a new (N = 9) or recurrent (N = 8) syphilis infection was found. The total follow-up time was 5,840 months, resulting in an event rate of 3.5/100 PY of follow-up (Table 1). Disease was asymptomatic in 4/17 (24%) subjects, and therefore detected merely by routine serology testing. All events occurred among MSM (N = 571), with a corresponding incidence of 6.2/100 PY and an event rate for asymptomatic disease of 1.4/100 PY.
In this study, we show an increasing incidence of syphilis infections among HIV-infected MSM over a 10-year period. Especially in the retrospective analysis we may have missed a number of successfully treated cases, so the real incidence was probably even higher. Importantly, 31% of the infections were asymptomatic and detected only through routine serology testing. We found, retrospectively and prospectively, an incidence of asymptomatic disease in MSM of 1.4 to 1.5/100 PY. To our knowledge, this is the highest incidence reported so far.3–4,6–9 The highest previously reported incidence is an incidence of 2.9/100 PY of follow up among HIV+ MSM visiting an HIV outpatient clinic in London.9 An ongoing study in our outpatient clinic shows similar incidence figures (unpublished data), consistent with a trend rather than an outbreak. Several factors may explain this trend, among which the introduction of HAART resulting in increased survival and quality of life with resumption of sexual activities, increased risky sexual behaviour, and serosorting with other HIV-infected MSM.10–11
Untreated syphilis can have serious sequelae with significant morbidity. In addition, syphilic ulcers facilitate HIV transmission.12 Finally, immune activation caused by syphilis infection stimulates HIV replication, resulting in a higher viral load and lower CD4+ lymphocyte numbers.13 These are all valid arguments for routine screening. Our data endorse current CDC guidelines advising at least annual routine syphilis testing in HIV-infected MSM.5
1. Dougan S, Evans BG, Elford J. Sexually transmitted infections in Western Europe among HIV-positive men who have sex with men. Sex Transm Dis 2007; 34:783–790.
2. Centers for Disease Control and Prevention. Primary and secondary syphilis – United States, 2003–2004. MMWR 2006; 55:269–273.
3. Winston A, Hawkins D, Mandalia S, et al. Is increased surveillance for asymptomatic syphilis in a HIV outpatient department worthwhile? Sex Transm Infect 2003; 79:257–259.
4. Cohen CE, Winston A, Asboe D, et al. Increasing detection of asymptomatic syphilis in HIV patients. Sex Transm Infect 2005; 81:217–219.
5. Centers for Disease Control, Prevention, Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep 2006; 55:1–94.
6. Hopkins S, Lyons F, Coleman C, et al. Resurgence in infectious syphilis in Ireland. An epidemiological study. Sex Transm Dis 2004; 31:317–321.
7. Kerani RP, Handsfield HH, Stenger MS, et al. Rising rates of syphilis in the era of syphilis elimination. Sex Transm Dis 2007; 34:154–161.
8. Chesson HW, Heffelfinger JD, Voigt RF, et al. Estimates of primary and secondary syphilis rates in persons with HIV in the United States, 2002. Sex Transm Dis 2005; 32:265–269.
9. Ivens D, Patel M. Incidence and presentation of early syphilis diagnosed in HIV-positive gay men attending a central London outpatients’ department. Int J STD AIDS 2005; 16:201–202.
10. Bachmann LH, Grimley DM, Waithaka Y, et al. Sexually transmitted disease/HIV transmission risk behaviors and sexually transmitted disease prevalence among HIV-positive men receiving continuing care. Sex Transm Dis 2005; 32:20–26.
11. Dodds JP, Johnson AM, Parry JV, et al. A tale of three cities: persisting high HIV prevalence, risk behaviour and undiagnosed infection in community samples of men who have sex with men. Sex Transm Infect 2007; 3:392–396.
12. Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect 1999; 75:3–17.
13. Buchasz K, Patel P, Taylor M, et al. Syphilis increases HIV viral load and decreases CD4 cell counts in HIV-infected patients with new syphilis infections. Aids 2004; 18:2075–2079.