La circoncisione non riduce il rischio di malattie sessualmente trasmissibili
La circoncisione maschile non ha ridotto il rischio di contrarre infezioni trasmesse sessualmente (IST) - quelli che causano la gonorrea, clamidia e la tricomoniasi - tra gli uomini in uno studio in Kenya (Journal of Infectious Diseases , Ottobre 2010). L'analisi dei dati sulle malattie sessualmente trasmissibili negli studi di circoncisione maschile condotti in in Sud Africa, Kenya e Uganda (New England Journal of Medicine and Study of Aids -Maggio 2011) ha mostrato che la circoncisione inoltre non offre protezione neppure contro il papillomavirus umano, anche se potrebbe offrire una protezione parziale dall'herpes genitale.
Adult Male Circumcision Does Not Reduce the Risk of Incident Neisseria gonorrhoeae, Chlamydia trachomatis, or Trichomonas vaginalis Infection: Results from a Randomized, Controlled Trial in Kenya e Sud Africa.
Effect of circumcision status on incidence of nonulcerative STI
The incidences of nonulcerative STIs, individually or combined, did not differ by circumcision status as a time-dependent variable or as a fixed variable based on assignment (table 1). Incidence rate ratios for circumcised versus uncircumcised men (time-dependent circumcision status) were 0.95 for N. gonorrhoeae infection (95% CI, 0.68–1.34; P p.781 ), 0.87 for C. trachomatis infection (95% CI, 0.65–1.16; P = .325), 0.89 for N. gonorrhoeae and/or C. trachomatis infection combined (95% CI, 0.70–1.12; P = .305), and 0.77 for T. vaginalis infection (95% CI, 0.44–1.36; P = .346).
Incidence of nonulcerative STI by sociodemographic and behavioral characteristics and baseline infection status
The incidences of N. gonorrhoeae and C. trachomatis infection were increased among men with lower educational attainment, baseline N. gonorrhoeae or C. trachomatis infection, multiple sex partners reported in the 30 days previous to the visit at which infection was detected, and a history of having sex with a woman during her menses in the 6 months before infection was detected (table 1). For both N. gonorrhoeae and C. trachomatis infection, the incidence rates were highest among men who reported having sex during a woman's menses (N. gonorrhoeae and C. trachomatis, 8.0 and 9.3 cases per 100 person-years, respectively) and among those who had baseline N. gonorrhoeae and/or C. trachomatis infection (N. gonorrhoeae and C. trachomatis, 9.8 and 9.3 cases per 100 person-years, respectively; data not shown). The incidence of T. vaginalis infection was low, and few baseline factors distinguished men with infection at follow-up from those who were not infected (table 1). Men who reported a preference for dry vaginal sex had an increased incidence of T. vaginalis infection but not of N. gonorrhoeae or C. trachomatis infection, compared with men who preferred wet vaginal sex. The incidence rate of each infection was lower by 35%–50% among men reporting condom use at their last sexual intercourse. Marital status and herpes simplex virus type 2 infection at baseline were not significantly associated with increased incidence of nonulcerative STI. Only 7 HIV seroconversions occurred among men who also had incident nonulcerative STI; HIV seroconversion was detected in the same follow-up interval as was STI for 6 of the men. Thus, HIV seroconversion was not examined as a predictor of STI.
Cox proportional hazards regression: risks for infection
In multivariate regression, risks for N. gonorrhoeae and C. trachomatis infection were similar (table 2) and included N. gonorrhoeae or C. trachomatis infection at baseline, multiple recent sex partners, and sexual intercourse with a woman during menses. Condom use at last intercourse remained significantly protective against N. gonorrhoeae infection (HR, 0.50) and T. vaginalis infection (HR, 0.52) in multivariate analysis but not against C. trachomatis infection. The only other significant risk factors for T. vaginalis infection were baseline infection with C. trachomatis or T. vaginalis. Men who reported that their penis had been abraded or felt sore during intercourse in the 6 months before infection was detected had an increased risk for N. gonorrhoeae infection (HR, 1.61). There was no statistically significant or meaningful 2-way interaction term in any model. Examination of Schoenfeld residuals identified no violation of the assumption of proportionality for each independent variable or for the global test of each model.
Background We examined the effect of male circumcision on the acquisition of 3 nonulcerative sexually transmitted infections (STIs).
Methods We evaluated the incidence of STI among men aged 18–24 years enrolled in a randomized trial of circumcision to prevent human immunodeficiency virus (HIV) infection in Kisumu, Kenya. The outcome was first incident nonulcerative STI during 2 years of follow-up. STIs examined were laboratory-detected Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis infection.
Results There were 342 incident infections among 2655 men followed up. The incidences of infection due to N. gonorrhoeae, C. trachomatis, and T. vaginalis were 3.48, 4.55, and 1.32 cases per 100 person-years, respectively. The combined incidence of N. gonorrhoeae and C. trachomatis infection was 7.26 cases per 100 person-years (95% confidence interval, 6.49–8.13 cases per 100 person-years). The incidences of these STIs, individually or combined, did not differ by circumcision status as a time-dependent variable or a fixed variable based on assignment. Risks for incident STIs in multivariate analysis included an STI at enrollment, multiple sex partners within <30 days, and sexual intercourse during menses in the previous 6 months; condom use was protective.
Conclusions: Circumcision of men in this population did not reduce their risk of acquiring these nonulcerative STIs. Improved STI control will require more-effective STI management, including partner treatment and behavioral risk reduction counseling.
Cox proportional hazards regression: risks for infection with N. gonorrhoeae and/or C. trachomatis
We combined N. gonorrhoeae and C. trachomatis infection at follow-up into a single outcome, owing to similarities in stratified models and to increase our power to detect significant associations (table 3). In a multivariate Cox regression analysis, N. gonorrhoeae or C. trachomatis infection at enrollment (HR, 2.31 [95% CI, 1.64–3.26]), multiple sex partners in the previous 30 days (HR, 2.15 [95% CI, 1.42–3.27]), and sexual intercourse during a woman's menstruation (HR, 1.67 [95% CI, 1.19–2.33]) remained significant predictors of N. gonorrhoeae and/or C. trachomatis infection (table 3). Conversely, higher education (HR, 0.67 [95% CI, 0.50–0.88]) and reported condom use at last intercourse (HR, 0.64 [95% CI, 0.50–0.82]) were protective against infection. There was no statistically significant or meaningful 2-way interaction term and no violation of the assumption of proportionality for each independent variable or for the global test of the model.
DiscussionWe did not find that adult male circumcision had a protective effect against any of the nonulcerative STIs examined (N. gonorrhoeae, C. trachomatis, or T. vaginalis infection) in these sexually active young men in Kisumu, Kenya. Multiple differences in organism pathogenesis and host immunogenicity may explain why circumcision may confer protection against HIV infection but not against these STIs. Specific HIV-1 target cells may be protected through increased keratinization resulting from circumcision; HIV-1 must attach to the CD4 receptor for cell entry. Bacterial STIs, such as N. gonorrhoeae, C. trachomatis, and T. vaginalis infection, however, may bind through multiple ligands and host receptors [18]. Unlike the chlamydia organism, gonococci are not obligate intracellular organisms, and T. vaginalis has complex and multiple methods of adhering to and entering host cells. The preferred host cell site is cuboidal or columnar epithelium (internal to the urethra) for both N. gonorrhoeae and C. trachomatis; thus, it is very unlikely that intact foreskin would provide protection against these infections. The suggestion of a protective effect stemmed from analysis of non-experimental study designs [19] rather than from a biological rationale. The findings of our randomized, controlled trial showing no association between circumcision status and these STIs confirm findings from several other studies with nonexperimental designs [11–14]. It is not likely that a longer observation period would have been necessary to demonstrate any potential protective effects; graphical inspection of the estimated cumulative hazard rate appears constant, and biological protective effects would be expected to appear shortly after circumcision. However, as demonstrated by statistical modeling, the effectiveness of circumcision in reducing the burden of HIV infection in the population varies by prevalence of circumcision, prevalence of HIV infection, and sexual behavior [20]; thus, adult male circumcision may have different effects on the risk of nonulcerative STIs at the population level, varying with population-level sexual practices and the prevalence of STIs and circumcision.
Despite the lack of protection against infection with N. gonorrhoeae, C. trachomatis, or T. vaginalis, adult male circumcision may have other beneficial effects on STIs, such as reduced transmission to sexual partners or decreased acuity or sequelae of infection. Among women enrolled as control subjects in a cervical cancer study in 5 countries, self-reported circumcision in male sex partners was strongly protective against C. trachomatis infection in the women [21]. Conversely, a cohort study examining hormonal contraception and the risk of HIV infection among women in 3 countries found that male sex partners' self-reported circumcision status was not associated with incident N. gonorrhoeae, C. trachomatis, or T. vaginalis infections in women [22]. However, few studies have examined this issue, and none were specifically designed to assess the association between male circumcision and the risk of STIs in female partners. Prospective studies comparing STI incidence among sexual partners and the course of infection among circumcised and uncircumcised men are necessary to determine a broader range of potential benefits of adult male circumcision.
Data on the incidence of nonulcerative STI among adolescent men in sub-Saharan Africa are limited, but the rates that we observed (combined incidence of N. gonorrhoeae and/or C. trachomatis infection, 7.26 cases per 100 person-years) seem to be relatively high. Among trucker drivers aged 16–62 years from Mombasa, Kenya, who were enrolled in a cohort study during 1993–1994, the incidence of N. gonorrhoeae infection was 12.6 cases per 100 person-years and the incidence of nongonococcal urethritis was 7.5 cases per 100 person-years [23]. As part of a 1997–1998 cross-sectional study in 4 sub-Saharan African cities, the prevalences of N. gonorrhoeae and C. trachomatis infection were 0% and 2.6%, respectively, among a representative sample of Kisumu men aged 15–49 years [24]. Beyond comparison with other populations, the incidence that we observed seems to be high contextually; the young men were enrolled in a study that provided ongoing testing and treatment for STIs, and men received risk-reduction counseling and unlimited numbers of free condoms. Men with baseline N. gonorrhoeae and C. trachomatis infection were at increased risk of reinfection. This suggests that men may become reinfected by infected partners. Infected men in the trial were given coupons for their sex partners to receive free treatment at a nearby clinic, but we do not know how many partners sought treatment. Our results suggest that more-aggressive partner tracing and treatment might be warranted.
Sexual intercourse with a woman during her menses was a risk factor for N. gonorrhoeae and C. trachomatis infection in stratified and combined analyses. In a previous analysis of our data, among men who were excluded from the trial because they were HIV infected at baseline, sexual intercourse with a woman during her menses was a risk factor for prevalent HIV infection in multivariate analysis [25]. Some studies have demonstrated increased HIV load during the menstrual phase of the menstrual cycle [26, 27]. In 1 study, sex partners of men with a diagnosis of gonorrhea were more likely to test positive for gonorrhea if they were tested during the menstrual phase rather than during other phases of the menstrual cycle [28], possibly because of increased organism shedding. There are limited published data quantifying STI organism load and transmission throughout the menstrual cycle. Individual studies suggest that mechanisms may include increased organism load or increased pathogenicity of organisms during menses as a result of altered genital flora [29]. Although further study is necessary to elucidate female-to-male transmission of STIs during the menstrual cycle, current counseling and prevention efforts could emphasize avoiding sexual intercourse during a woman's menses and using condoms.
Men who reported coital injuries (penis cut, scratched, or abraded during sexual intercourse in the 6 months before detected infection) had an increased risk of N. gonorrhoeae infection. The nature of these injuries and the mechanism by which they may increase the risk of infection are unknown. Use of condoms reduced the risk of infection by more than one-third, emphasizing the importance of promoting condom use.
The incidence (1.32 cases per 100 person-years) and baseline prevalence (2.1%) of T. vaginalis infection in our population was low, compared with prevalences detected in cross-sectional studies in other sub-Saharan countries. The prevalence of trichomoniasis was 11% among men aged 15–54 years in rural Tanzania [30] and 6.3% among male sex partners of a community-based sample of women in Moshi, Tanzania [31]. Because the epidemiological mechanism of T. vaginalis infection among African men is largely unknown, specific behaviors and sexual practices that increase risk may not have been measured in our study.
Limitations of the original trial have been reviewed elsewhere [3]; thus, our discussion of limitations is confined to the current analysis. If a large proportion of infected men sought treatment outside the study clinic, those infections would not be accounted for in this analysis, which would potentially lead to an underestimation of incidence and, thus, bias the results toward the null. Some participants did not attend all scheduled follow-up visits, but <5% of enrolled men did not have any follow-up testing for STIs. These men were significantly less likely than men with STI testing at follow-up to report coital injuries (results not shown). However, their baseline characteristics did not differ from those of men who received follow-up with regard to the number of sex partners in the previous 30 days; baseline infection with N. gonorrhoeae, C. trachomatis, or T. vaginalis; sexual intercourse during a woman's menses, condom use at last intercourse, age, educational attainment, or treatment assignment. Finally, behavioral risks were self-reported and were therefore subject to limitations of recall and socially desirable reporting.
Data on the incidence of nonulcerative STI among adolescent men in sub-Saharan Africa are limited, but the rates that we observed (combined incidence of N. gonorrhoeae and/or C. trachomatis infection, 7.26 cases per 100 person-years) seem to be relatively high. Among trucker drivers aged 16–62 years from Mombasa, Kenya, who were enrolled in a cohort study during 1993–1994, the incidence of N. gonorrhoeae infection was 12.6 cases per 100 person-years and the incidence of nongonococcal urethritis was 7.5 cases per 100 person-years [23]. As part of a 1997–1998 cross-sectional study in 4 sub-Saharan African cities, the prevalences of N. gonorrhoeae and C. trachomatis infection were 0% and 2.6%, respectively, among a representative sample of Kisumu men aged 15–49 years [24]. Beyond comparison with other populations, the incidence that we observed seems to be high contextually; the young men were enrolled in a study that provided ongoing testing and treatment for STIs, and men received risk-reduction counseling and unlimited numbers of free condoms. Men with baseline N. gonorrhoeae and C. trachomatis infection were at increased risk of reinfection. This suggests that men may become reinfected by infected partners. Infected men in the trial were given coupons for their sex partners to receive free treatment at a nearby clinic, but we do not know how many partners sought treatment. Our results suggest that more-aggressive partner tracing and treatment might be warranted.
Sexual intercourse with a woman during her menses was a risk factor for N. gonorrhoeae and C. trachomatis infection in stratified and combined analyses. In a previous analysis of our data, among men who were excluded from the trial because they were HIV infected at baseline, sexual intercourse with a woman during her menses was a risk factor for prevalent HIV infection in multivariate analysis [25]. Some studies have demonstrated increased HIV load during the menstrual phase of the menstrual cycle [26, 27]. In 1 study, sex partners of men with a diagnosis of gonorrhea were more likely to test positive for gonorrhea if they were tested during the menstrual phase rather than during other phases of the menstrual cycle [28], possibly because of increased organism shedding. There are limited published data quantifying STI organism load and transmission throughout the menstrual cycle. Individual studies suggest that mechanisms may include increased organism load or increased pathogenicity of organisms during menses as a result of altered genital flora [29]. Although further study is necessary to elucidate female-to-male transmission of STIs during the menstrual cycle, current counseling and prevention efforts could emphasize avoiding sexual intercourse during a woman's menses and using condoms.
Men who reported coital injuries (penis cut, scratched, or abraded during sexual intercourse in the 6 months before detected infection) had an increased risk of N. gonorrhoeae infection. The nature of these injuries and the mechanism by which they may increase the risk of infection are unknown. Use of condoms reduced the risk of infection by more than one-third, emphasizing the importance of promoting condom use.
The incidence (1.32 cases per 100 person-years) and baseline prevalence (2.1%) of T. vaginalis infection in our population was low, compared with prevalences detected in cross-sectional studies in other sub-Saharan countries. The prevalence of trichomoniasis was 11% among men aged 15–54 years in rural Tanzania [30] and 6.3% among male sex partners of a community-based sample of women in Moshi, Tanzania [31]. Because the epidemiological mechanism of T. vaginalis infection among African men is largely unknown, specific behaviors and sexual practices that increase risk may not have been measured in our study.
Limitations of the original trial have been reviewed elsewhere [3]; thus, our discussion of limitations is confined to the current analysis. If a large proportion of infected men sought treatment outside the study clinic, those infections would not be accounted for in this analysis, which would potentially lead to an underestimation of incidence and, thus, bias the results toward the null. Some participants did not attend all scheduled follow-up visits, but <5% of enrolled men did not have any follow-up testing for STIs. These men were significantly less likely than men with STI testing at follow-up to report coital injuries (results not shown). However, their baseline characteristics did not differ from those of men who received follow-up with regard to the number of sex partners in the previous 30 days; baseline infection with N. gonorrhoeae, C. trachomatis, or T. vaginalis; sexual intercourse during a woman's menses, condom use at last intercourse, age, educational attainment, or treatment assignment. Finally, behavioral risks were self-reported and were therefore subject to limitations of recall and socially desirable reporting.
We did not find that adult male circumcision had a protective effect against any of the nonulcerative STIs examined (N. gonorrhoeae, C. trachomatis, or T. vaginalis infection) in these sexually active young men in Kisumu, Kenya e in Uganda.
Potential conflicts of interest: none reported.
Financial support: Family Health International, supported by the US Government and the Bill and Melinda Gates Foundation (to R.C.B.); Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health (AI50440); and Canadian Institutes of Health Research (HCT 44180; investigator award to S.M.).
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(da Journal of Africa & Journal of Infectious Diseases)
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