Article Text

Download PDFPDF

Original article
Risk factors for syphilis infection in men who have sex with men: results of a case–control study in Lille, France
  1. Karen Champenois1,2,
  2. Anthony Cousien2,
  3. Bakhao Ndiaye3,
  4. Yougoudou Soukouna3,
  5. Véronique Baclet4,
  6. Isabelle Alcaraz4,
  7. Philippe Choisy4,
  8. Pascal Chaud3,
  9. Annie Velter5,
  10. Anne Gallay5,
  11. Yazdan Yazdanpanah1,4,6,7
  1. 1ATIP-Avenir Inserm: “Modélisation, Aide à la Décision, et Coût-Efficacité en Maladies Infectieuses”, Lille, France
  2. 2EA2694, Faculté Lille-Nord de France, Lille, France
  3. 3Institut de Veille Sanitaire, Lille, France
  4. 4Service Universitaire des Maladies Infectieuses et du Voyageur, Centre Hospitalier de Tourcoing, Tourcoing, France
  5. 5Institut de Veille Sanitaire, Saint-Maurice, France
  6. 6Service des Maladies Infectieuses et Tropicales, Hôpital Bichat Claude Bernard, Paris, France
  7. 7Université Denis Diderot, Paris, France
  1. Correspondence to Karen Champenois, ATIP-Avenir, Inserm U995, Parc Eurasanté, 152 rue du Professeur Yersin, 59120 Lille, France; karen.champenois{at}


Background Substantial increases in syphilis have been reported since the early 2000s in northern countries, particularly among men who have sex with men (MSM). The authors aimed to identify risk factors for early syphilis in MSM in Lille, a large urban area of northern France.

Methods A matched case–control study was conducted in MSM aged ≥18 years. Cases were diagnosed with primary, secondary or early latent syphilis between April 2008 and June 2010. Controls sought care in STIs clinics or were followed in an HIV clinic. Controls had no history of and no current syphilis. They were matched to cases for age and HIV status. Multivariate conditional logistic regression models were used to identify risk factors for early syphilis.

Results 53 patients with early syphilis were enrolled. Average age was 37 years, and 47% were HIV-infected. For analysis, they were matched to 90 controls. Factors associated with syphilis were: low educational attainment (OR=5.38, 95% CI 1.94 to 14.94; p=0.001), receptive oral sex with casual male partners without a condom (OR=4.86, 95% CI 1.63 to 14.48; p=0.005) and anal sex toy use with casual male partners (OR=2.72, 95% CI 1.01 to 7.32; p=0.05). Seeking of sex partners online (OR=5.17, 95% CI 1.33 to 20.11), use of poppers (OR=2.2, 95% CI 1.1 to 4.3) and erectile dysfunction drugs (OR=1.9, 95% CI 1.0 to 13.2) were associated with syphilis only in the univariate analysis.

Conclusions Receptive oral sex without a condom and use of anal sex toys were identified as presenting a major risk of syphilis infection. Although these practices have been shown to present low risk of HIV transmission, the general public is unaware of their impact on transmission of other STIs.

  • Syphilis
  • STI
  • MSM
  • case–control study
  • HIV
  • epidemiology
  • gay men
  • AIDS
  • infectious diseases
  • public health
  • clinical trials
  • sexual behaviour
  • social
  • sexual practices
  • homosexual

Statistics from


Resurgence of syphilis has been observed in North America1 ,2 and Western Europe3–5 since the late 1990s. It is concentrated mainly in urban areas and affects men who have sex with men (MSM). In France, a syphilis outbreak has been observed since 2000; MSM account for 80% of syphilis cases, and half of them is infected with HIV.6 In 2007, the French STI sentinel surveillance system recorded 570 cases of syphilis in France, of whom 86 (15%) in northern France, that is, a sevenfold increase since 2001.6

The resurgence of sexually transmitted infections (STIs) in MSM is related to an increase in sexual risk-taking that may also increase the HIV incidence.5 Furthermore, like other ulcerative STIs, syphilis increases the risk of transmission and acquisition of HIV by two- to threefold each.7

Since the recent outbreaks, several studies have identified risk factors for syphilis infection, involving sexual behaviour and venues frequented for meeting sex partners.1 ,2 ,5 ,8–12 In France, little is known about the role of these venues in the spread of syphilis infection, and no study has been conducted to measure the risk of sexual behaviour in syphilis infection. With the aim of better understanding the high incidence of syphilis and implementing preventive policies, the purpose of this study was to assess risk factors for early syphilis infection, including venues and sexual behaviour, in MSM of a large urban area in northern France.


Study population

A case–control study was conducted from April 2008 to June 2010. Eligible participants were men aged ≥18 years living and/or working during the previous 6 months within a 20 km radius from the city of Lille, the largest urban area in northern France (around 1 million of inhabitants). They had to be MSM. A case was defined as a man with a diagnosis of early syphilis (primary, secondary or latent syphilis that can be dated ≤1 year13) based on clinical examination and serological evaluation (Treponema pallidum haemaglutination assay/Veneral Disease Research Laboratory; TPHA/VDRL). History of clinical signs consistent with primary or secondary syphilis, or negative results of syphilis testing documented in the previous 12 months attested to early latent syphilis. A control was a man not infected with syphilis at enrolment (VDRL=0) and with no history of syphilis infection. People with a history or current diagnosis of other STIs were included. Controls were recruited in the study when they sought care for: (1) clinical signs suggesting STIs, (2) HIV testing after taking sexual risks or (3) HIV disease follow-up if they were HIV-infected. HIV serostatus was checked for all the non-HIV-positive participants.

Cases were recruited at the time of syphilis diagnosis from an STIs clinic, an HIV/infectious diseases outpatient clinic, and dermatology departments of urban area hospitals, as well as from two general practitioners engaged in HIV care and in the Lille voluntary counselling and testing centre. For each case, two controls were consecutively selected among eligible patients who sought care within 6 months of the corresponding case enrolment, with a maximum of three controls for certain cases.

Since sexual behaviour may differ according age, and in light of the known association between HIV and syphilis,7 ,12 ,14 controls were matched to cases for age (18–29, 30–49, ≥50 years old) and HIV status (positive, negative).

Assuming an exposure rate of 50% among controls (ie, for oral sex with sperm exposure in MSM, as reported in a French study on MSM15), a two-tailed significance level of 5% and a power level of 80%, enrolment of 49 cases and 98 controls was expected to detect a minimal OR of 3.

Written informed consent was obtained from all eligible participants, and the study received ethical approval from the French data protection authority (CCTIRS/CNIL).

Data collection

Data were collected using two standardised questionnaires. The first was completed by the practitioner and included clinical and serological data on syphilis, HIV and other STIs (histories and coinfections). The second was completed by participants and included socio-demographic characteristics, venues frequented for meeting sex partners and sexual behaviour during the 6 months prior to inclusion.

Venues for meeting sex partners were classified as: (1) internet venues: websites and chat rooms, and phone sex lines; (2) venues with sex: sex clubs, bathhouses, commercial venues with backrooms and public cruising areas and (3) venues without sex: bars, dance clubs without place to have sex and private parties. Geographic location of frequented venues was requested and classified as follows for analysis: France only, Belgium (close to Lille) and other countries.

Data on sexual behaviour in the last 6 months included information on sex partners; sexual practices with casual partners: oral sex (receptive/insertive, condom use), anal sex (receptive/insertive, condom use) and use of sex toys. A sexual practice was considered unprotected when a condom was not used.

Statistical analysis

First, cases of syphilis and controls were described. To test for trend, we used the Cochran–Armitage test. Next, univariate conditional logistic regression was used to determine crude disease ‘exposure’ associations by estimating the OR and its 95% CI based on the matched design. Variables with p values <0.20 were submitted to a multivariate conditional logistic regression model. Backward stepwise regression procedures were used to identify the final multivariate model with factors associated significantly and independently with syphilis diagnosis. p Values ≤0.05 (two-tailed) were considered significant. Analyses were performed with SAS software V.9.2 (SAS Institute).

Initially, regression analysis was performed only for patients without missing data (complete case analysis). Here, missing data for each variable ranged 0%–10%. This may decrease the precision of CIs around OR point estimates. Therefore, a second analysis was performed in which missing data were estimated from observed data using the multiple imputation technique.16 Five complete data sets were created, and ORs were the means of five distinct analyses. Multiple imputations were performed with R software V.2.8, MICE package ( We presented here results of the analysis conducted with the multiple imputation technique.


Description of syphilis cases

During the study period, 74 patients with syphilis were enrolled (table 1). Seventeen cases were excluded because they did not fulfil study criteria: eight men had late latent syphilis (>1 year or undetermined duration), one had tertiary syphilis, two were exclusively heterosexual and six were not living or working in the study area. Among the remaining 57 men with early syphilis, two cases did not complete the self-questionnaire. For two cases >50 years of age, we found no matched controls. Finally, 53 cases were enrolled (table 1): 64% were 30–49 years old and 48% were infected with HIV. Ten (19%) were diagnosed at the primary stage of syphilis, 28 (54%) at the secondary stage and 15 (27%) at the early latent stage. One-third of patients had a history of syphilis. Controls had no history of syphilis; however, 19 (21%) had a history of STIs (vs 45% of cases, p=0.0005).

Table 1

Socio-demographic and clinical characteristics of cases (MSM with early syphilis, n=53) and controls (MSM with no current and no history of syphilis, n=90)

Identification of risk factors, univariate analysis

Etiologic analysis was conducted in 53 cases and 90 controls. Distributions of matched variables did not differ between cases and controls (table 1).

Compared with controls, cases had a lower educational attainment (51% had a high school level or below vs 28% of controls, OR=2.63, p=0.009; table 2) and used more often internet venues for meeting sex partners (62% vs 43% of controls, OR=5.17, p=0.05). We found a trend towards greater risk of syphilis according to venues localisation: cases were less likely to use French venues only than Belgian venues than other countries venues (p=0.09). Compared with controls, cases were more likely to consume poppers (53% vs 30% of controls, OR=2.17, p=0.02) and erectile dysfunction drugs (21% vs 6% of controls, OR=1.94, p=0.06). However, cases less often drank alcohol before or during sex (51% vs 66% of controls, OR=0.36, p<0.0001).

Table 2

Selected characteristics and behaviour in the 6 months prior to inclusion associated with early syphilis, by univariate analysis

Overall, 81% of MSM stated that they had had at least one casual male partner in the 6 months prior to enrolment (median number of casual partners: 5 (IQR, 2–10)). Compared with controls, cases had more often casual partners (92% vs 74% of controls, OR=5.06, p=0.01). They also had more frequent unprotected receptive oral sex (85% vs 62% of controls, OR=3.32, p=0.009), unprotected insertive or receptive anal sex (60% vs 41% of controls, OR=3.04, p=0.06) and more often used anal sex toys (38% vs 18% of controls, OR=2.88, p=0.01).

Identification of risk factors, multivariate analysis

A low educational attainment was associated with higher risk of syphilis (OR=5.24, p=0.001) (table 3). Alcohol consumption before or during sex was lower in syphilis cases (OR=0.32, p=0.01). We observed a higher risk of syphilis for unprotected receptive oral sex with casual partners (OR=4.86, p=0.005) and anal sex toy use (OR=2.72, p=0.05).

Table 3

Characteristics associated with early syphilis in multivariate analysis

It is noteworthy that internet venues, and poppers and erectile dysfunction drug consumption were not associated with syphilis in multivariate analysis. These variables are associated with high-risk sexual practices. Indeed, 89% of men who recruited sex partners by internet websites reported unprotected oral sex versus 71% of men who did not go on such websites (p=0.01). Likewise, 93% and 100% of men using poppers or erectile dysfunction drugs before or during sex reported unprotected oral sex versus 67% (p=0.0004) and 73% (p=0.03) of men who did not use such drugs, respectively.


In this case–control study conducted in MSM of an urban area in northern France, independent risk factors for early syphilis infection include low educational attainment and unprotected receptive oral sex, along with anal sex toy use with casual partners.

Our study had several strengths and limitations. The matched case–control study design allowed a better identification of risk factors than in a cross-sectional study. However, the challenge in case–control studies is to select the appropriate control group. Recruiting controls from same medical settings is the most feasible method for finding sexually active MSM. However, in this population, the prevalence of at-risk sexual behaviour may be high, thus leading to an underestimate of the association between risk factors and syphilis infection. Furthermore, a lack of contrast in the sexual behaviours of participating men creates feasibility issues when attempting to evaluate the impact of specific variables, such as anal sex in syphilis transmission. Nevertheless, most risk factors identified in our study were consistent with those reported in the literature.1 ,2 ,8 ,11

The target number of controls was not achieved (90/98) because of issues related to matching criteria. This may lead to a loss of statistical power that was, however, balanced by the higher number of cases enrolled and matched to at least one control (53/49). Indeed with patients actually enrolled, a two-tailed significance level of 5% and an OR of 3, the a posteriori calculated statistical power was estimated at 85%. Sample size of some reference groups of categorical variables targeting sexual behaviour was small. This may lead to a lack of precision in the estimate points and CIs.

In this study, data were collected within a retrospective period of 6 months to limit recall bias. However, recall bias cannot be excluded. Moreover, we were not able to collect data on sexual behaviour of steady partners outside the couple. The analysis of risk to acquire syphilis was therefore limited to sexual behaviour with casual partners.

Finally, to deal with missing data and improve statistical power, multiple imputations were used.16 Associations found in complete case analysis (data not shown) were the same as those using multiple imputations. The proportion of missing data was low (<10%), and with the five complete data sets created in our analysis, the relative efficiency calculated for every variable of the final logistic model was >98%.16 This indicates that our results are reliable. In addition, the proportion of missing data was no different between cases and controls for each variable, and the non-response bias may be negligible (missing at random condition).

A low educational attainment as a risk factor for syphilis is consistent with the literature.11 Several studies identified unprotected oral sex as a risk factor for syphilis infection.8 ,10 Because the risk of HIV transmission is lower with oral sex than anal sex,17 MSM consider oral sex as safe. Nevertheless, syphilis transmission was attributed to oral sex in 20% and 46% of cases in MSM in studies conducted in Chicago8 and Northern Ireland,5 respectively.

In our study, in addition to receptive oral sex, anal sex toy use was independently associated with syphilis infection. Sex toys are often used by MSM during solo and partnered sexual activities to enhance the sexual experience.18 Seen as a way to reduce HIV risk acquisition by many MSM,19 sex toy use has been described in the past as a risk factor for hepatitis C,20 lymphogranuloma venereum proctitis21 and HIV22 infections. To our knowledge, this is the first study identifying use of anal sex toys as a risk factor for syphilis infection. Heiligenberg et al 23 found in HIV-infected MSM that use of same sex toys with any partners is associated with having any STI but not with syphilis specifically. Although data on the transmission of syphilis through infected items are rare, it is physiopathologically possible.24 It has been stated that Treponema pallidum can survive until 24 h in blood at room temperature.25 Moreover, given the relatively short time during which infected toys could be exchanged during sexual intercourse with use and sharing of sex toys, T pallidum transmission is likely through sex toys.

Studies on syphilis in MSM reported unprotected anal sex at high frequency.2 ,11 ,26 Imrie et al 11 showed an association between syphilis infection and inconsistent condom use during receptive anal sex. In our study, practice of anal sex, protected or not, when adjusted for unprotected receptive oral sex with casual partners and anal sex toys use was no longer a risk factor for syphilis infection. Most MSM who reported unprotected anal sex reported unprotected oral sex too; consequently, we were unable to assess the specific association between unprotected anal intercourse and syphilis infection.

In the present study, poppers and erectile dysfunction drugs consumption, and use of the internet to meet sex partners were associated with syphilis in univariate analysis. However, these factors were associated with high-risk sexual behaviour and increased syphilis infection risk through such behaviour. Several studies reported the use of these recreational drugs as risk factors for unsafe sex, HIV and STIs.27–29 Likewise, the association between internet use and syphilis infection has been demonstrated in the past1 ,9 ,11; contact with sex partners online is associated with anonymous encounters, substance use and unprotected sex.30 ,31

Surprisingly, alcohol use before and during sex was found to be significantly lower in syphilis cases. Such an association has been described, though not in detail, in few studies.1 ,2 ,27 On the contrary, other studies found an association between excessive alcohol use and syphilis infection.12 ,32 In our study, this association was not related to a negative association between alcohol and other recreational drugs consumption (ie, alcohol and recreational drugs were not associated), and heavy drinking remained protective (data not shown). This association should be further evaluated.

In MSM in northern France, main risk factors for early syphilis infection include practice of unprotected receptive oral sex and use of anal sex toys with casual partners. Risks factors identified were sexual behaviour shown to have low risk of HIV transmission. Thus, intensive health promotion and education is needed when addressing sexual risk behaviour and route of transmission, not only of HIV, but also of STIs. The internet is largely used to meet sex partners and might be an excellent tool of information and education. The present study adds to our knowledge of transmission of syphilis in MSM and suggests the need for innovative prevention programmes specifically aimed at limiting expansion of syphilis in this community.

Key messages

  • In MSM in northern France, risk factors for early syphilis infection were sexual behaviour shown to have low risk of HIV transmission.

  • Sexual practices associated with early syphilis were unprotected receptive oral sex and use of anal sex toys with casual male partners.

  • Poppers and erectile dysfunction drugs consumption and use of the internet to meet sex partners were actually associated with high-risk sexual behaviour.


We thank the organisations AIDES, Sida-Info-Service, SNEG and Spiritek for their implication in the prevention and testing campaign conducted in parallel with this study and the anonymous and free testing centre (Ciddist) of Lille and all physicians who participated in the study. We also thank Clémence de Baudoin for her help at the beginning of the study and Alain Duhamel for statistical advice.



  • Funding This work was supported by the Groupe Régional de Santé Publique (GRSP) Nord-Pas de Calais, France. Funders had no role in the conduction of the study or in the preparation of the manuscript.

  • Competing interests YY had received travel grants, honoraria for presentation at workshops and consultancy honoraria from Bristol-Myers Squibb, Gilead, Glaxo-SmithKline, Merck, Pfizer, Roche and Tibotec. Other authors report no conflict of interest.

  • Ethics approval Ethics approval was provided by CCTIRS and CNIL (French authorities).

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.