Prevalence of Neisseria gonorrhoeae and Chlamydia trachomatis infection in men attending STD clinics in Brazil

Introduction: The study aimed to assess the prevalence of Neisseria gonorrhoeae and Chlamydia trachomatis infections and identify demographic, behavioral and clinical factors correlated with such infections in men attending six sexually transmitted disease clinics in Brazil. Methods: Multicentric, cross-sectional study performed among men attending STD clinics in Brazil. The study included STD clinics in six cities distributed throughout the five geographic regions of Brazil in 2005. Patients provided 20 ml of first catch urine for testing for NG and CT by DNA-PCR. Results: A total of 767 (92.9%) men were included in the study. The mean age was 26.5 (SD 8.3) years-old. Prevalence of Chlamydia infection was 13.1% (95%CI 10.7%-15.5%) and gonorrhea was 18.4% (95%CI 15.7%21.1%). Coinfection prevalence was 4.4% (95%CI 2.95%-5.85%) in men who sought attendance in STI clinics. Factors identified as associated with C. trachomatis were younger age (15-24) [OR=1.4 (95%CI 1.01-1.91)], present urethral discharge [OR=4.8 (95%CI 1.52-15.05)], genital warts [OR=3.0 (95%CI 1.49-5.92)] and previous history of urethral discharge [OR=2.4 (95%CI 1.11-5.18)]. Variables associated with gonorrhea were younger age (15 to 24) [OR=1.5 (95%CI 1.09-2.05)], presence of urethral discharge [OR=9.9 (95%CI 5.53-17.79)], genital warts [OR=18.3 (95%CI 8.03-41.60)] and ulcer present upon clinical examination [OR=4.9 (95%CI 1.06-22.73)]. Conclusions: These findings have important implications for education and prevention actions directed toward men at risk of HIV/STD. A venue-based approach to offer routine screening for young men in STD clinics should be stimulated. Key-words: Chlamydia trachomatis. Neisseria gonorrhoeae. Risk factors. Multicentric study. STD clinic. PCR. RESUMO Introdução: Nosso objetivo foi acessar a prevalência de Neisseria gonorrhoeae e Chlamydia trachomatis e identificar fatores demográficos, comportamentais e clínicos correlacionados a essas infecções em homens atendidos em clínicas de doenças sexualmente transmissíveis no Brasil. Métodos: Estudo multicêntrico, transversal conduzido em homens que procuraram atendimento em clínicas de DST. O estudo incluiu clínicas de DST em seis cidades distribuídas nas cinco regiões geográficas do Brasil em 2005. Pacientes coletaram 20ml do primeiro jato de urina para testar NG e CT por DNA-PCR. Resultados: Um total de 767 (92,9%) homens foi incluído no estudo. A média de idade foi 26,5 (DP 8,3) anos. A prevalência de infecção por CT foi 13,1% (IC95% 10,7%-15,5%) e NG de 18,4% (IC95% 15,7%-21,1%). A prevalência de co-infecção foi 4,4% (IC95% 2,95%-5,85%). Os fatores identificados como sendo associados com a infecção pela CT foram ser jovem (15-24) [OR=1,4 (IC95% 1,01-1,91)], apresentar corrimento uretral ao exame [OR=4.8 (IC95% 1,52-15,05)], verrugas genitais [OR=3,0 (IC95% 1,49-5,92)] e história prévia de corrimento uretral [OR=2,4 (IC95% 1,11-5,18)]. As variáveis associadas com a gonorréia foram ser jovem (15 to 24) [OR=1,5 (IC95% 1,09-2,05)], apresentar corrimento uretral [OR=9,9 (IC95% 5,53-17,79)], verrugas genitais [OR=18,3 (IC95% 8,03-41,60)] e úlcera ao exame clínico [OR=4,9 (IC95% 1,06-22,73)]. Conclusões: Estes resultados têm implicações importantes para medidas de educação e prevenção direcionadas aos homens com risco acrescido de HIV/DST. A abordagem no serviço para oferecer testes de rotina para homens jovens atendidos em clínica de DST deve ser estimulada. Palavras-chaves: Chlamydia trachomatis. Neisseria gonorrhoeae. Fatores de risco. Estudo multicêntrico. Clínicas DST. PCR. The importance of understanding and addressing Chlamydia trachomatis (CT)infections and gonorrhea among men is being recognized in several studies1,2. The role of identifying and treating male infections in preventing adverse outcomes among women has prompted some researchers to call for Chlamydia trachomatis and gonorrhea screening guidelines directed at detecting male infections3,4. Untreated infections may have direct adverse outcomes among men, including epididymitis, prostatitis and proctitis4,5. Currently, males are opportunistically tested for C. trachomatis infection and/or gonorrhea; recommendations for routinely screening males for these infections are discouraged1. Although several existing studies have examined Chlamydia and gonorrhea infections in men, these studies are geographically limited, targeted to a certain portion of the population6-9. Sexually transmitted disease (STD) Treatment Guidelines of the Centers for Disease Control and Prevention (CDC) recommend empirical treatment for C. trachomatis when treating a diagnosed gonococcal infection, because Chlamydia coinfection is frequent among individuals diagnosed with gonorrhea4. Frequently, coinfection data are derived from STI clinic settings, where patients are likely to present with symptoms of, or suspected exposure to, an STD10. National published data regarding C. trachomatis infections and gonorrhea among men in Brazil is not available, while prevalence date for these infections are available only in local studies11,12. In this study, the prevalence of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis infection and the coinfection rate were assessed and correlated demographic, behavioral and clinical factors were identified in an at-risk population during a multicentric study among men attending STD clinics in six cities in Brazil distributed among the five geographical regions. The information will be used for planning prevention and assistance programs to reach this population.


The importance of understanding and addressing
Chlamydia trachomatis (CT)infections and gonorrhea among men is being recognized in several studies 1,2 .The role of identifying and treating male infections in preventing adverse outcomes among women has prompted some researchers to call for Chlamydia trachomatis and gonorrhea screening guidelines directed at detecting male infections 3,4 .
Untreated infections may have direct adverse outcomes among men, including epididymitis, prostatitis and proctitis 4,5 .Currently, males are opportunistically tested for C. trachomatis infection and/or gonorrhea; recommendations for routinely screening males for these infections are discouraged 1 .Although several existing studies have examined Chlamydia and gonorrhea infections in men, these studies are geographically limited, targeted to a certain portion of the population [6][7][8][9] .
Sexually transmitted disease (STD) Treatment Guidelines of the Centers for Disease Control and Prevention (CDC) recommend empirical treatment for C. trachomatis when treating a diagnosed gonococcal infection, because Chlamydia coinfection is frequent among individuals diagnosed with gonorrhea 4 .Frequently, coinfection data are derived from STI clinic settings, where patients are likely to present with symptoms of, or suspected exposure to, an STD 10 .
National published data regarding C. trachomatis infections and gonorrhea among men in Brazil is not available, while prevalence date for these infections are available only in local studies 11,12 .In this study, the prevalence of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis infection and the coinfection rate were assessed and correlated demographic, behavioral and clinical factors were identified in an at-risk population during a multicentric study among men attending STD clinics in six cities in Brazil distributed among the five geographical regions.The information will be used for planning prevention and assistance programs to reach this population.A multicentric, cross-sectional study conducted among men attending STD clinics in Brazil.The study included STD clinics in six geographically diverse cities in Brazil (São Paulo, Rio de Janeiro, Porto Alegre, Goiânia, Fortaleza and Manaus) in 2005.

Population
Men seeking care during their first visit to a STD clinic and with no history of antibiotic therapy in the preceding 15 days were invited to take part in the study.HIV positive men were excluded.

Sample size
Based on a priori power calculations, the study required the enrollment of 750 men to provide 80% power to estimate a point prevalence of Chlamydia and gonorrhea coinfection at 5% 11 with a 95% confidence interval of (3.5%-6.5%).Considering a refusal rate of 10%, 825 men were required.All men sampled who met the eligibility criteria were invited to participate.

Subject selection and eligibility criteria
Health professionals invited men attending STD clinics for the first time to take part in the study.At the time of screening, all men in the multicentric study were asked to complete a standard questionnaire involving demographic, behavioral and clinical data, including STD symptoms.Those who accepted screening provided a urine specimen.Gonorrhea and/or Chlamydia infected men were notified and treated according to the Brazilian National STD guidelines 13 .Patients received counseling to advise all their sexual partners in order to provide testing and treatment.Determination of research-exempt status or human subjects review and approval was obtained from all participating institutions.Free, informed consent was obtained and patient confidentiality was maintained, as required by law.

laboratory specimens
Patients provided 20ml of first catch urine to test for Neisseria gonorrhoeae and Chlamydia trachomatis by DNA detection using Polymerase Chain Reaction (PCR; Cobas Amplicor CT/NG, Roche Diagnostics Systems, USA).These tests are the most sensitive available.

Statistical analysis
Standard descriptive statistical analyses were performed, including frequency distributions for categorical data and calculation of means and standard deviations for continuous variables.Prevalence of coinfection was defined as the detection of both Neisseria gonorrhoeae and Chlamydia trachomatis in a single urine specimen.It was calculated to reflect its relative frequency, with corresponding 95% confidence intervals (95%CI).Odds ratios and 95%CI were calculated in bivariate analyses to estimate the strength of the association between infections and each potential risk factor.Independent risk factors for each infection were assessed using stepwise logistic regression: variables significant at P 0.05 in bivariate analysis were entered into the model and additional variables were entered into the multivariate model based on known a priori associations (for instance, age and number of sex partners).

Ethical
The Ethics in Research National Committee approved the protocol for the study.Written, informed consent was obtained by all participants and their parents or guardians (if <18 years), in accordance with Brazilian legal guidelines.
Table 1 shows the correlations between demographic characteristics and STD prevalence: 52.4% of men were 15 to 24 years-old, 55.4% had nine or more years of education, 59.8% were single and 73.5% earned a monthly income of four or less Brazilian minimum wages (1 Brazilian minimum wage = US$ 150 in 2005).The only correlation was between C. trachomatis infection and age from 25 to 34 years-old.
Regarding risk behaviors, 339 participants reported first sex intercourse at ≤ 14 years of age, 85.4% reported one partner in the preceding 12 months, 20.1% reported regular use of condoms and 13.4% reported injecting drug use.Having one sexual partner in the preceding 12 months had a negative correlation with a diagnosis of gonorrhea (Table 2).

DISCUSSION
This study sought to investigate the prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections and assess associated risk exposures in men attending STD clinics in Brazil.Analysis of the results verified that 4.4% of men had both infections.The coinfection rate obtained was consistent with the results of previous studies conducted among the male population in Brazil 11,12 and other countries 8,14 .
The isolated frequency of each infection reported in this study was high, as expected in an STD clinic, 13.1% and 18.4% of Chlamydia trachomatis and Neisseria gonorrhoeae, respectively.Since male gonococcal infections are largely symptomatic 15 , diagnostic testing, rather than routine screening, has been the recommended disease control strategy, and national disease rates in men reflect mainly symptomatic infection.Although there is evidence that asymptomatic gonococcal infections in heterosexual men may contribute disproportionately to disease transmission to women 14 , relatively few studies have measured the prevalence of Neisseria gonorrhoeae infection among asymptomatic men 9,16,17 .Regarding C. trachomatis infection, the rate of asymptomatic infection is higher 18 .
The main risk factors reported in the literature as associated with C. trachomatis infections are age below 25 years-old, inconsistent condom use, multiple sexual partners, a new partner in the preceding 60 days and a history of STD 11,19,20 .In this study, an association among younger men (15-24 years-old) with infections was identified, but no association with reporting more than one partner in the preceding 12 months, inconsistent condom use and previous STD was included in the final model.
There is a lack of current evidence-based data for clinical symptoms and coinfection diagnosis in male populations 4,8 .An association between C. trachomatis infection and gonorrhea with urethral discharge was verified in this study.This it was an expected result even when considering that these infections can be asymptomatic in numerous cases 18 .An association between genital ulcer and genital vesicles and gonorrhea upon clinical examination

TABlE 1 -Prevalence of Neisseria gonorrhoeae and Chlamydia trachomatis infections and their correlation with demographic factors among men attending STD clinics in six cities in Brazil, 2005 (n=767).
*OneBrazilian minimal wage in 2005 = US$150.CT: Chlamydia trachomatis, GC: Neisseria gonorrhoeae.

Table 3
describes clinical symptoms; previous history of genital warts was correlated with Chlamydia trachomatis and Neisseria gonorrhoeae and having a sexual partner with a genital ulcer was correlated with gonorrhea.In clinical examinations, presenting urethral discharge, genital ulcers and genital vesicles were associated with Chlamydia trachomatis and Neisseria gonorrhoeae infections.

TABlE 3 -Prevalence of Neisseria gonorrhoeae and Chlamydia trachomatis infections and their correlation with clinical factors among men attending STI clinics in six cities in Brazil, 2005 (N=767).
CT: Chlamydia trachomatis, GC: Neisseria gonorrhoeae.