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      Male circumcision for the prevention of HSV-2 and HPV infections and syphilis.

      The New England journal of medicine
      Adolescent, Adult, Circumcision, Male, Condoms, utilization, Confounding Factors (Epidemiology), Genotype, Herpes Genitalis, epidemiology, prevention & control, Herpesvirus 2, Human, isolation & purification, Humans, Incidence, Kaplan-Meier Estimate, Male, Papillomaviridae, genetics, Papillomavirus Infections, Prevalence, Sexual Behavior, Syphilis, Treponema pallidum, Young Adult

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          Abstract

          Male circumcision significantly reduced the incidence of human immunodeficiency virus (HIV) infection among men in three clinical trials. We assessed the efficacy of male circumcision for the prevention of herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) infections and syphilis in HIV-negative adolescent boys and men. We enrolled 5534 HIV-negative, uncircumcised male subjects between the ages of 15 and 49 years in two trials of male circumcision for the prevention of HIV and other sexually transmitted infections. Of these subjects, 3393 (61.3%) were HSV-2-seronegative at enrollment. Of the seronegative subjects, 1684 had been randomly assigned to undergo immediate circumcision (intervention group) and 1709 to undergo circumcision after 24 months (control group). At baseline and at 6, 12, and 24 months, we tested subjects for HSV-2 and HIV infection and syphilis, along with performing physical examinations and conducting interviews. In addition, we evaluated a subgroup of subjects for HPV infection at baseline and at 24 months. At 24 months, the cumulative probability of HSV-2 seroconversion was 7.8% in the intervention group and 10.3% in the control group (adjusted hazard ratio in the intervention group, 0.72; 95% confidence interval [CI], 0.56 to 0.92; P=0.008). The prevalence of high-risk HPV genotypes was 18.0% in the intervention group and 27.9% in the control group (adjusted risk ratio, 0.65; 95% CI, 0.46 to 0.90; P=0.009). However, no significant difference between the two study groups was observed in the incidence of syphilis (adjusted hazard ratio, 1.10; 95% CI, 0.75 to 1.65; P=0.44). In addition to decreasing the incidence of HIV infection, male circumcision significantly reduced the incidence of HSV-2 infection and the prevalence of HPV infection, findings that underscore the potential public health benefits of the procedure. (ClinicalTrials.gov numbers, NCT00425984 and NCT00124878.) 2009 Massachusetts Medical Society

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          Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta-analysis.

          We set out to estimate the age and genotype-specific prevalence of cervical human papillomavirus (HPV) DNA in women with normal cervical cytology worldwide by meta-analysis of a systematic literature review. Reports on HPV prevalence published between January, 1995, and January, 2005, were retrieved. To be included, studies required information on cervical cytology, plus detailed descriptions of study populations, methods used to collect cervical samples, and assays used for HPV DNA detection and typing. Final analyses included 78 studies that could be separated into women with normal cytology, and of which subsets of 44 and 48 studies had data on age and type-specific HPV prevalence, respectively. Overall HPV prevalence in 157 879 women with normal cervical cytology was estimated to be 10.4% (95% CI 10.2-10.7). Corresponding estimates by region were Africa 22.1% (20.9-23.4), Central America and Mexico 20.4% (19.3-21.4), northern America 11.3% (10.6-12.1), Europe 8.1% (7.8-8.4), and Asia 8.0% (7.5-8.4). In all world regions, HPV prevalence was highest in women younger than 35 years of age, decreasing in women of older age. In Africa, the Americas, and Europe, a clear second peak of HPV prevalence was observed in women aged 45 years or older. On the basis of these estimates, around 291 million women worldwide are carriers of HPV DNA, of whom 32% are infected with HPV16 or HPV18, or both. The HPV types most commonly detected are similar to those most commonly described in pre-neoplastic and cancer cases, although the relative contribution of HPV16 and HPV18 is substantially lower in cytologically normal women.
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            Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda.

            The probability of HIV-1 transmission per coital act in representative African populations is unknown. We aimed to calculate this probability overall, and to estimate how it is affected by various factors thought to influence infectivity. 174 monogamous couples, in which one partner was HIV-1 positive, were retrospectively identified from a population cohort in Rakai, Uganda. Frequency of intercourse and reliability of reporting within couples was assessed prospectively. HIV-1 seroconversion was determined in the uninfected partners, and HIV-1 viral load was measured in the infected partners. Adjusted rate ratios of transmission per coital act were estimated by Poisson regression. Probabilities of transmission per act were estimated by log-log binomial regression for quartiles of age and HIV-1 viral load, and for symptoms or diagnoses of sexually transmitted diseases (STDs) in the HIV-1-infected partners. The mean frequency of intercourse was 8.9 per month, which declined with age and HIV-1 viral load. Members of couples reported similar frequencies of intercourse. The overall unadjusted probability of HIV-1 transmission per coital act was 0.0011 (95% CI 0.0008-0.0015). Transmission probabilities increased from 0.0001 per act at viral loads of less than 1700 copies/mL to 0.0023 per act at 38 500 copies/mL or more (p=0.002), and were 0.0041 with genital ulceration versus 0.0011 without (p=0.02). Transmission probabilities per act did not differ significantly by HIV-1 subtypes A and D, sex, STDs, or symptoms of discharge or dysuria in the HIV-1-positive partner. Higher viral load and genital ulceration are the main determinants of HIV-1 transmission per coital act in this Ugandan population.
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              Genital herpes.

              Genital herpes is the main cause of genital ulcers worldwide; the prevalence of herpes simplex virus (HSV) type 2 infections in the general population ranges from 10% to 60%. Most genital herpes is caused by HSV-2, although HSV-1 accounts for about half of new cases in developed countries. The risk of HIV acquisition is three times higher in people with HSV-2. Neonatal herpes is an uncommon but serious complication of genital herpes. Most genital HSV-2 infections are unrecognised and undiagnosed; infected individuals, even with mild symptoms, shed HSV, and can infect sexual partners. Since clinical diagnosis is neither sensitive nor specific, virological and type-specific serological tests should be used routinely. Oral antiviral drugs for HSV infections are safe and effective and can be used both to treat episodes and to prevent recurrences. Antiviral treatment of the infected partners and condom use reduce the risk of sexual transmission of HSV-2.
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