Prevalence of antibodies against Treponema pallidum among HIV-positive patients in a tertiary care hospital in Mexico

Abstract

Our objective was to determine the seroprevalence of syphilis among HIV-infected patients in a tertiary care hospital in Mexico City. A cross-sectional study was developed, and 318 HIV-positive patients were evaluated from January to February 2013 at Hospital de Infectología, National Medical Center ‘La Raza’ (a tertiary care hospital specialising in infectious diseases in Mexico City). Laboratory data were screened for the detection of antibodies against Treponema pallidum. Patients completed a questionnaire relating to socio-demographic data and factors associated with syphilis. Of the 318 patients, 83% were men. The mean age ± SD was 36 ± 11 years; 52% were men who have sex with men and 47% had undertaken higher education. The overall seroprevalence of syphilis among these patients was 25% (95% confidence interval 21%, 30%). Men who have sex with men had a significantly higher seroprevalence (30% vs. 15%, p = 0.009). We conclude that, in Mexico, there is a high seroprevalence of syphilis antibodies in HIV-infected patients and that men who have sex with men are the group most affected.

Keywords

HIV AIDS sexually transmitted infection epidemiology prevalence syphilis clinical features socio-demographic

Introduction

Syphilis is a global public health problem. About 12 million new infections occur annually worldwide,¹ of which 3 million occur in Latin America.² This sexually transmitted infection (STI) increases the transmissibility of human immunodeficiency virus (HIV), in part because of damage to the mucous membranes and natural epithelial barriers.³ Every patient who has an STI diagnosis should also be tested for HIV antibodies using an enzyme-linked immunosorbent assay, and similarly, every patient diagnosed with HIV infection should be screened for syphilis.^4,5

Similar to the HIV epidemic, the current syphilis epidemic affects primarily three groups: men who have sex with men (MSM), injecting drug users and people who engage in sex for money or drugs. A lower proportion of other groups, such as pregnant women and heterosexuals with low sexual risk behaviour, is also affected by the syphilis epidemic. In most countries, the association between HIV and other STIs including syphilis has been well described, and the frequency of acquisition of any of these STIs is directly related to the number of sexual partners, other sexual risk practices and sexual identity, among other factors.³ In 2011, the US Centers for Disease Control and Prevention reported that 70% of patients with primary or secondary syphilis in the United States are MSM and that, although the prevalence in women was much lower, it has increased in the past 10 years.⁶

In Latin America, the syphilis prevalence in MSM varies between 5% and 29%; Argentina and Peru are the countries with the highest prevalence (17% and 29%, respectively). Reinfection has also been shown to be frequent.⁷ In Mexico, the trend in the number of syphilis infections showed a slight increase from 2000 to 2007. In 2009, 2191 new cases of acquired syphilis were reported with a national rate of 2.0 per 100,000 inhabitants. Of these cases, 56.8% were in women, and the highest prevalence was in the 20–24-year-old age group.⁸ Of 111,030 blood donors, 471 (0.42%) had positive results when analysed by the Venereal Disease Research Laboratory or the unheated serum reagin tests. One hundred ninety-six were confirmed positive (0.17%) with the fluorescent treponemal antibody absorption test.⁸ Thus, the seroprevalence in blood donors is about 0.20%. The seroprevalence in the Mexican adult population is 3.1%, with a higher frequency of antibodies in men, people who had sex at an early age, and people who do not use a condom.⁹

In Tijuana, Mexico, a study showed that HIV-positive clients of female sex workers were more likely to test positive for syphilis (odds ratio 7.53; 95% confidence interval [CI] 1.43, 39.59).¹⁰ To our knowledge, there are no published studies that determined the syphilis seroprevalence in HIV-infected patients in Mexico. Given the importance of this disease in HIV-infected people, it is necessary to establish the seroprevalence of syphilis in our population of HIV-infected patients.

Patients and methods

Design

We conducted a cross-sectional study at the Hospital de Infectología, ‘La Raza’ Medical Center; this is an infectious diseases tertiary hospital in Mexico City. This hospital receives naïve and treatment-experienced HIV patients. We assess the clinical and immunological status of the naïve patients and determine their eligibility for antiretroviral therapy. During the first visit, all outpatients are screened for syphilis antibodies, CD4⁺ T-cell count, plasma HIV-1 RNA, hepatitis B and C, blood chemistry, liver function tests and blood cell count. The HIV clinic has around 1000 HIV-infected patients.

Patients

The institutional review board and ethics committee at Hospital de Infectología ‘La Raza’ National Medical Center reviewed and approved this study (number 35021, with reference number for approval R-2013-35021-6). All included patients provided written informed consent to complete a socio-demographic questionnaire.

Over a two-month period from 3 December 2012 to 31 January 2013, we randomly selected 334 HIV-positive treatment-naïve outpatients who were tested for syphilis antibodies (Liaison® Treponema Screen [310840], DiaSorin S.p.A, Saluggia, Italy). Patients were asked to complete a questionnaire to provide epidemiological data; there was a 95.5% response rate (n = 318).

A level of anti-Treponema pallidum antibody ≥1.1 was considered positive; the test sensitivity was 99.4% (95% CI 96.73, 99.98) and specificity was 99.91% (95% CI 99.75, 98.98). Clinical data and laboratory information were obtained from the patients’ records. This information comprised the immunological and virological status at the time of HIV diagnosis and at the time of the data collection. Patients had neither been treated previously for syphilis nor had a previous diagnosis of this disease. Patients completed a questionnaire to identify socio-demographic variables including educational level, Mexico state origin, kind of activity, educational level and place of birth.

Statistical analysis

Data entry and analysis were performed using SPSS. The results were summarised using descriptive statistics; medians with interquartile ranges of 25–75% (IQR 25.75) were used for the variables without a normal distribution. The Kolmogorov–Smirnov test was used to determine the integrity of the sampling distributions for the quantitative variables. The Mann–Whitney U and χ² tests were used to compare between patients who were positive and negative for syphilis antibodies.

We estimated syphilis seroprevalence in patients with HIV (and 95% CI) with significant p-values <0.05. A χ² test was used to evaluate differences between percentages according to the presence or absence of antibodies after stratifying by age group, gender, sexual orientation, number of sexual partners, schooling, place of birth, current address, CD4⁺ cell count and HIV-1 RNA viral load.

Results

Of a total of 318 HIV-infected patients included in the study, 83% were men. The mean age (±SD) was 36 (±11) years. Most of the patients (62%) were Mexico City residents. Sixty-one per cent of the patients were diagnosed in stage C3. In terms of their sexual orientation, 52% were MSM. The median number of sexual partners since the beginning of sexual life was 5 (IQR 3–15). The median age for onset of sexual activity was 18 years (IQR 16–19 years) (Table 1). The median CD4⁺ cell count at the time of the survey was 328 cells/µL (IQR 190–516). The prevalence of syphilis antibodies was 25% (95% CI 21%, 30%). The distribution of syphilis seropositivity was associated with the number of sexual partners (p = 0.001) but was not significantly associated with educational level (p = 0.278).

Table 1.

Characteristics of the subjects (n = 318).

	Patients positive for anti-Treponema pallidum antibodies	Patients negative for anti-Treponema pallidum antibodies	p
Age (years)	37 (± 9)	36 (± 11)	0.507
Gender (M/F)	76/4	190/48	0.001
Age of starting sexual activity	18 (15–19)	17 (16–20)	0.353
Number of sexual partners (persons)	8 (4–30)	5 (3–10)	0.001
Men who have sex with men/heterosexual (persons)	64/16	154/84	0.001
CD4⁺ (cells/µL)	283 (180–448)	352 (198–536)	0.04

Statistical methods used: the Mann–Whitney U-test and χ² test.

The rate of syphilis seropositivity differed significantly between the genders; only four (5%) of the syphilis-positive HIV-positive patients were women. The rate of seropositivity was also higher in MSM (30%) compared with heterosexual HIV-infected individuals (15%) (p = 0.009). The frequency of antibodies against T. pallidum was highest (45%) in patients aged 30–39 years, and an analysis of the linear trend shows a significant difference between age groups (p = 0.03) (Figure 1). There was no difference regarding educational level (Figure 2).

Figure 1.

Anti-treponema antibody seroprevalence by age group.

Figure 2.

Seropositivity by educational level.

Discussion

This study showed that the overall prevalence of syphilis seropositivity in HIV-infected patients was 25%. These results indicate that clinicians should consider testing for syphilis in all HIV-infected patients. We also found that MSM and a higher number of sexual partners increase the likelihood of acquiring syphilis. We found no significant relationship between syphilis seropositivity and educational level or age of onset of sexual activity.

Our results are consistent with those of a meta-analysis performed in Europe,¹¹ which reported a rate of seropositivity in the range of 14–59% depending on the region. MSM also had the highest rate of seropositivity in the European study.

In our study, gender was significantly associated with seropositivity because men had a higher seroprevalence than women.^12–14 We also found that the highest rate of seropositivity was in the 30–39-year-old age group (45%) followed by the 40–49-year-old age group (25%). This high syphilis seroprevalence in certain age groups is consistent with the findings of other studies and probably reflects the increased risk of exposure to syphilis over time.^15–17

The rate of syphilis and HIV coinfection varies in relation to the prevalence of each of these diseases in the population analysed and to individual risk factors. A meta-analysis of 30 studies that analysed HIV infection rates in patients diagnosed with syphilis in the United States found that the HIV seroprevalence was 15.7% (25.7% in men and 12.4% in women) and reached 22.5–70.6% in intravenous drug users and 68–90% in MSM.¹⁶ The risk that these behaviours influence syphilis prevalence has been corroborated in multiple scenarios, including in Mexico. Having more than two sexual partners increases the probability of acquiring syphilis six times compared with not being sexually active.¹³ Our study showed a direct relationship between the number of sexual partners and syphilis seroprevalence.

Other countries have similar prevalence rates as in Mexico. For example, in Spain, Pérez et al.¹⁸ found a syphilis prevalence of 21% in HIV-infected patients. Schuelter-Trevisol et al.¹⁹ found a syphilis prevalence of 19% in HIV-infected sex workers in southern Brazil. Callegari et al.²⁰ found that the treponemal test was positive in 18.9% of HIV outpatients in Vitoria, Brazil.

The findings of our study should be interpreted in the context of the methodological limitations of a cross-sectional study.

In conclusion, this study describes a high syphilis seroprevalence in HIV-infected patients in Mexico; the rate was similar to those reported in many parts of the world. This knowledge is crucial for helping prevent syphilis transmission in HIV-infected patients. Syphilis screening as a part of HIV patient screening is required. There is a need for more longitudinal studies to investigate further the interaction between these two infections.

Footnotes

Acknowledgements

We thank all patients who kindly gave consent to participate in this study.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

References

Karp

Schlaeffer

Jotkowitz

. Syphilis and HIV coinfection. Eur J Intern Med 2009; 20: 9–13.

WHO, UNAIDS and UNICEF. Epidemic update and health sector progress towards universal access. Progress Report 2011. Geneva: World Health Organization, 2011, http://www.unicef.es/sites/www.unicef.es/files/VIH.SIDA_.Informe.pdf (2011, accessed February 2013).

World Health Organization. Introduction to HIV, AIDS and sexually transmitted infection surveillance module 3: surveillance of most-at-risk and vulnerable populations/World Health Organization. Regional Office for the Eastern Mediterranean, UNAIDS 2011, http://applications.emro.who.int/dsaf/EMRPUB_2011_EN_1361.pdf (2011, accessed February 2013).

Perez-Brumer

Konda

Salvatierra

. Prevalence of HIV, STIs, and risk behaviors in a cross-sectional community- and clinic-based sample of men who have sex with men (MSM) in Lima, Peru. PLoS One 2013; 8: e59072–e59072.

Galban

Benzaken

. Situation of syphilis in 20 countries in Latin America and the Caribbean: year 2006. DST – J Bras Doenças Sex Transm 2007; 19: 166–172.

Zoni

Alonso-González

Werin-Sjögren

. Syphilis in the most at-risk populations in Latin America and the Caribbean: a systematic review. Int J Infect Dis 2013; 17: e84–e92.

Pan American Health Organization. Challenges posed by the HIV epidemic in Latin America and the Caribbean 2009. Priority interventions: HIV/AIDS, Universal access, Latin America. Lima, Peru, http://new.paho.org/hq/dmdocuments/2010/CHALLENGES-hiv-epidemic-INGLES-2010.pdf (2009, accessed February 2013).

Rivera-López

Arenas-Esqueda

Ambriz-Fernández

. SINAVE/DGE/SALUD/Description and behavior of weekly reportable diseases, epidemiological synthesis 2009. June 2011. Rev Med Inst Mex Seguro Soc 2009; 47: 65–68.

Conde-González

Valdespino

Juárez-Figuero

. Treponemal antibody prevalence and sociodemographic characteristics of the adult Mexican population in 2000. Salud Pública Méx 2007; 49 suppl 3: s412–s420.

10.

Patterson

Goldenberg

Gallardo

. Correlates of HIV, sexually transmitted infections, and associated high-risk behaviors among male clients of female sex workers in Tijuana, Mexico. AIDS 2009; 23: 1765–1771.

11.

Dougan

Evans

Elford

. Sexually transmitted infections in Western Europe among HIV-positive men who have sex with men. Sex Transm Dis 2007; 34: 783–790.

12.

Moges

Kebede

Kassu

. Seroprevalence of HIV, HBV infections and syphilis among street dwellers in Gondar city, northwest Ethiopia. Ethiop J Health Dev 2006; 20: 160–165.

13.

Uneke

Ogbu

Alo

. Syphilis serology in HIV-positive and HIV-negative Nigerians: the public health significance. Online J Health Allied Sci 2006; 5: 1–8.

14.

Bremer

Marcus

Hamouda

. Syphilis on the rise again in Germany—results from surveillance data for 2011. Euro Surveill 2012; 17: 1–6.

15.

Tessema

Yismaw

Kassu

. Seroprevalence of HIV, HBV, HCV and syphilis infections among blood donors at Gondar University Teaching Hospital, northwest Ethiopia: declining trends over a period of five years. BMC Infect Dis 2010; 10: 111–111.

16.

Bernstein

Stephens

Strona

. Epidemiologic characteristics of an ongoing syphilis epidemic among men who have sex with men, San Francisco. Sex Transm Dis 2013; 40: 11–17.

17.

Blocker

Levine

St Louis

. HIV prevalence in patients with syphilis, United States. Sex Transm Dis 2000; 27: 53–59.

18.

Pérez

Cerón

Fuentes

. Hepatitis B, C, Treponema pallidum and Toxoplasma gondii co-infections in HIV infected patients. Rev Med Chil 2009; 137: 641–648.

19.

Schuelter-Trevison

Custódio

Silva

. HIV, hepatitis B and C, and syphilis prevalence and coinfection among sex workers in Southern Brazil. Rev Soc Bras Med Trop 2013; 46: 493–497.

20.

Callegari

Pinto-Neto

Medeiros

. Syphilis and HIV co-infection in patients who attend an AIDS outpatient clinic in Vitoria, Brazil. AIDS Behav 2014; 18(Suppl 1): 104–109.