Topical penile microbicide use by men to prevent recurrent bacterial vaginosis in sex partners: a randomized clinical trial.

BACKGROUND: Bacterial vaginosis (BV) recurs frequently after metronidazole treatment. This randomized, single-masked clinical trial evaluated the efficacy of topical application of 62% ethyl alcohol in emollient gel (gel) to the penis by male partners of women diagnosed with BV for preventing post-treatment BV recurrence. METHODS: Among 587 Kenyan women presenting with vulvovaginal symptoms, 236 had BV (vaginal Gram stain Nugent score >=7), of whom 223 (94.3%) agreed, along with their partners, to be randomized: 115 to the intervention and 108 to the control arm. In the intervention arm, male partners agreed to apply gel each morning, and before and after sexual intercourse. All couples received counseling, condoms, and syndromic treatment of sexually transmitted infection symptoms. Follow-up visits were scheduled 1 week, 1 month, and 2 months postenrollment, with vaginal Gram stains at every visit and culture for H2O2-producing lactobacilli at the 2-month visit. The primary outcome was time to diagnosis of BV during follow-up. RESULTS: In the primary intent-to-treat analysis, diagnosis of BV was significantly more frequent in the intervention arm (hazard ratio: 1.44, 95% confidence interval: 1.01­2.04). After adjustment for baseline covariates, the hazard ratio was 1.39 (95% confidence interval: 0.98­1.99). At the 2-month visit, prevalences of any vaginal lactobacilli or of H2O2-producing lactobacilli did not differ appreciably in the 2 study arms (P = 0.81 and 0.32, respectively). CONCLUSION: Daily use of the 62% ethyl alcohol gel by men before and after sex significantly increased persistence or early recurrence of BV in their partners through 2 months after metronidazole treatment. However, no difference was observed in prevalences of vaginal lactobacilli within this same period.

The association of HIV counseling and testing with HIV risk behaviors in a random population-based survey in Kisumu, Kenya.

HIV testing has been promoted as a key HIV prevention strategy in low-resource settings, despite studies showing variable impact on risk behavior. We sought to examine rates of HIV testing and the association between testing and sexual risk behaviors in Kisumu, Kenya. Participants were interviewed about HIV testing and sexual risk behaviors. They then underwent HIV serologic testing. We found that 47% of women and 36% of men reported prior testing. Two-thirds of participants who tested HIV-positive in this study reported no prior HIV test. Women who had undergone recent testing were less likely to report high-risk behaviors than women who had never been tested; this was not seen among men. Although rates of HIV testing were higher than seen in previous studies, the majority of HIV-infected people were unaware of their status. Efforts should be made to increase HIV testing among this population.

Endometrial histopathology in patients with laparoscopic proven salpingitis and HIV-1 infection.

STUDY OBJECTIVE: To identify sensitive and specific histological criteria for endometritis in women with laparoscopically-confirmed acute salpingitis. METHODS: Women, age 18-40 years of age presenting with complaints of lower abdominal pain ≤2 weeks and no antibiotics use in past two weeks, were enrolled. They underwent clinical examination, screening for HIV; other sexually transmitted infections plus endometrial biopsy sampling for histopathology. Diagnostic laparoscopy confirmed the diagnosis of acute salpingitis. Controls were women undergoing tubal ligation and HIV-1 infected women asymptomatic for genital tract infection. RESULTS: Of 125 women with laparoscopically-confirmed salpingitis, 38% were HIV-1 seropositive. Nineteen HIV-1 negative controls were recruited. For the diagnosis of endometritis, ≥1 plasma cells (PC) and ≥3 polymorphonuclear lymphocytes (PMN) per HPF in the endometrium had a sensitivity of 74% for HIV-1-seropositive, 63% for HIV-1-seronegative women with a specificity of 75% and positive predictive value of 85% regardless of HIV-1-infection for predicting moderate to severe salpingitis. For HIV-1-seronegative women with mild salpingitis, ≥1 PC and ≥3 PMN had a sensitivity of 16% and a PPV of 57%. CONCLUSION: Endometrial histology, did not perform well as a surrogate marker for moderate to severe salpingitis, and failed as a surrogate marker for mild salpingitis.

Intravaginal practices among female sex workers in Kibera, Kenya.

OBJECTIVES: To assess vaginal cleansing and lubricant use among female sex workers (FSW) in Kenya participating in a 6-month, prospective study of the acceptability of the use of the diaphragm. METHODS: The study is based on 140 FSW in Nairobi, who completed 140 baseline visits and 390 bi-monthly follow-up visits. Participants were instructed to wear the diaphragm for all coital acts during follow-up and to refrain from vaginal cleansing while wearing the diaphragm. Logistic regression was used to identify predictors of recent vaginal cleansing to 'tighten' the vagina reported at baseline; recent vaginal cleansing to prevent infection reported at baseline; recent vaginal cleansing with the diaphragm in place reported during follow-up; and recent use of oil-based lubricant during coitus reported at baseline. RESULTS: At baseline, 99% of women reported vaginal cleansing in the previous 2 weeks for purposes of hygiene or to remove evidence of past coitus. Approximately 41% of women also reported cleansing in the past 2 weeks to 'tighten' the vagina. Women reported vaginal cleansing with the diaphragm in place in the past 2 weeks at 14% of follow-up visits in which the diaphragm was used. Predictors of such cleansing included young age, 6-month study visit, being divorced or widowed and higher educational level. CONCLUSIONS: While vaginal cleansing is a modifiable behaviour, given that cleansing for hygiene was almost universal among this study population at baseline and that more women reported cleansing while wearing the diaphragm as the study progressed, the complete eradication of the practice would probably be difficult.

Diaphragm for STI and HIV prevention: is it a safe method for women at high risk?

Female sex workers (n = 140) were enrolled in a 6-month acceptability trial of the diaphragm. We randomized a subset (n = 40) to receive colposcopies after 1 month of diaphragm use or after 1 month of observation before commencing diaphragm use. Adverse events were mild in nature. Frequency of colposcopic findings did not differ between women randomized to immediate versus delayed diaphragm use (P = 0.25).

Adherence to diaphragm use for infection prevention: a prospective study of female sex workers in Kenya.

OBJECTIVE: To assess adherence to and acceptability of the diaphragm among 140 female sex workers in Kenya in a 6-month prospective study. METHODS: At baseline and bimonthly visits, participants were interviewed on diaphragm knowledge, attitude, and practices. We used principal component analysis and logistic regression to identify predictors of consistent use. RESULTS: At 50% of 386 bimonthly visits, women reported consistently using a diaphragm with all partners during the preceding 2 weeks. Consistent use was significantly higher at the 6-month than the 2-month visit. Women reported less covert use with "helping" (regular sex partners to whom she could go for help or support) than with "other" partners. Perceptions that diaphragms are easier to use than condoms and that their lack of coital interruption is important were associated with consistent diaphragm use with both partner types. Partner support of diaphragm use is correlated with consistent use with "helping" partners only while higher parity, consistent condom use, and perceived lack of need of condoms as a benefit of diaphragms were associated with consistent use with "other" partners. CONCLUSIONS: Diaphragm acceptance among female sex workers in Nairobi was high. Future studies should distinguish between partner types when evaluating diaphragm adherence.

Infectious correlates of HIV-1 shedding in the female upper and lower genital tracts.

OBJECTIVES: To determine the effects of vaginal, cervical, and endometrial infections on shedding of HIV-1 RNA in the female genital tract. DESIGN: Cross-sectional. METHODS: Antiretroviral-naive women from Nairobi, Kenya with CD4 cell counts >or= 350 cells/mul had plasma and endocervical wick samples collected for HIV quantification by real-time RNA reverse transcriptase-polymerase chain reaction. Vaginal and cervical Gram stains and endometrial biopsies were obtained. Vaginal Gram stain was used to diagnose bacterial vaginosis and to quantify Lactobacillus levels. RESULTS: Twenty-six of 50 (52%) women had detectable endocervical HIV-1 RNA with a median endocervical viral load of 1760 copies/ml (range: undetectable to 1 1,030,000 copies/ml). Women with decreased Lactobacillus had 15.8-fold [95% confidence interval (CI), 2.0-123] greater endocervical HIV-1 RNA than women with normal Lactobacillus levels. Women with plasma cell (PC) endometritis [>or= 1 PC/high-power field (hpf)] had a 15.8-fold (95% CI, 2.0-120) higher endocervical HIV RNA level than women without PC endometritis. Both these associations remained after controlling for plasma viral load. Cervicitis (>or= 30 polymorphonuclear leukocytes/hpf), however, was not associated with endocervical HIV-1 RNA shedding (P = 0.81). CONCLUSIONS: In HIV-1-infected, antiretroviral-naive women without symptoms of pelvic inflammatory disease infection, abnormal vaginal flora and inflammatory cells in the endometrium affected HIV-1 shedding from the lower genital tract. These data suggest that both the upper and lower genital tracts contribute to female HIV-1 genital shedding.

Effect of human immunodeficiency virus-1 infection on treatment outcome of acute salpingitis.

OBJECTIVE: To examine the effect of human immunodeficiency virus (HIV)-1 infection on treatment outcome of laparoscopically verified acute salpingitis. METHODS: Women aged 18-40 years with laparoscopically verified acute salpingitis received antibiotic therapy that included cefotetan 2 g intravenously and doxycycline 100 mg orally every 12 hours and laparoscopically guided drainage of tuboovarian abscesses of 4 cm or more. Clinical investigators blinded to HIV-1 serostatus used predetermined clinical criteria, including calculation of a clinical severity score and a standard treatment protocol to assess response to therapy. RESULTS: Of the 140 women with laparoscopically confirmed acute salpingitis, 61 (44%) women had mild, 38 (27%) had moderate, and 41 (29%) had severe disease (ie, pyosalpinx, tuboovarian abscesses, or both). Fifty-three (38%) were HIV-1-infected. Severe disease was more common in HIV-1-infected in comparison with HIV-1-uninfected women (20 [38%] compared with 21 [24%], P = .02). Defined as time of hospital discharge or 75% or more reduction in baseline clinical severity score, HIV-1-infected women with severe (6 days [4-16] compared with 5 days [3-9], P = .09) but not those with either mild (4 days [2-6] compared with 4 days [2-6] P = .4) or moderate salpingitis (4 days [3-7] compared with 4 days [3-6] P = .32) tended to take longer to meet criteria for clinical improvement. The need for intravenous clindamycin or additional surgery was not different in HIV-1-infected and uninfected cases (15 [28%] compared with 18 [21%], P = .3). CONCLUSION: Although HIV-1 infection may prolong hospitalization in women with severe salpingitis, all women hospitalized with acute salpingitis responded promptly to antibiotic therapy and surgical drainage regardless of HIV-1 infection status. LEVEL OF EVIDENCE: II-2.

Association of attitudes and beliefs towards antiretroviral therapy with HIV-seroprevalence in the general population of Kisumu, Kenya.

BACKGROUND: Since antiretroviral therapy (ART) became available in the developed world, the prevalence of unprotected sex and the incidence of sexually transmitted infections (STIs) and HIV have increased. We hypothesized that a similar phenomenon may be occurring in sub-Saharan Africa concomitant with the scale-up of HIV treatment. METHODS: We conducted a general population-based survey in Kisumu, Kenya. Participants completed an interview that included demographics as well as ART-related attitudes and beliefs (AB) and then underwent HIV serological testing. Exploratory and confirmatory factor analyses of AB about ART indicated two factors: 1) ART-related risk compensation (increased sexual risk taking now that ART is available); and 2) a perception that HIV is more controllable now that ART is available. Logistic regression was used to determine associations of these factors with HIV-seroprevalence after controlling for age. FINDINGS: 1,655 (90%) of 1,844 people aged 15-49 contacted, including 749 men and 906 women, consented to participate in the study. Most participants (n = 1164; 71%) had heard of ART. Of those who had heard of ART, 23% believed ART was a cure for HIV. ART-related risk compensation (Adjusted (A)OR = 1.45, 95% CI 1.16-1.81), and a belief that ART cures HIV (AOR = 2.14, 95% CI 1.22-3.76) were associated with an increased HIV seroprevalence in men but not women after controlling for age. In particular, ART-related risk compensation was associated with an increased HIV-seroprevalence in young (aged 15-24 years) men (OR = 1.56; 95% CI 1.12-2.19). CONCLUSIONS: ART-related risk compensation and a belief that ART cures HIV were associated with an increased HIV seroprevalence among men but not women. HIV prevention programs in sub-Saharan Africa that target the general population should include educational messages about ART and address the changing beliefs about HIV in the era of greater ART availability.

Cesarean delivery outcomes from the WHO global survey on maternal and perinatal health in Africa.

OBJECTIVE: To assess the association between cesarean delivery rates and pregnancy outcomes in African health facilities. METHODS: Data were obtained from all births over 2-3 months in 131 facilities. Outcomes included maternal deaths, severe maternal morbidity, fresh stillbirths, and neonatal deaths and morbidity. RESULTS: Median cesarean delivery rate was 8.8% among 83439 births. Cesarean deliveries were performed in only 95 (73%) facilities. Facility-specific cesarean delivery rates were influenced by previous cesarean, pre-eclampsia, induced labor, referral status, and higher health facility classification scores. Pre-eclampsia increased the risks of maternal death, fresh stillbirths, and severe neonatal morbidity. Adjusted emergency cesarean delivery rate was associated with more fresh stillbirths, neonatal deaths, and severe neonatal morbidity--probably related to prolonged labor, asphyxia, and sepsis. Adjusted elective cesarean delivery rate was associated with fewer perinatal deaths. CONCLUSION: Use of cesarean delivery is limited in the African health facilities surveyed. Emergency cesareans, when performed, are often too late to reduce perinatal deaths.

The HAART cell phone adherence trial (WelTel Kenya1): a randomized controlled trial protocol.

BACKGROUND: The objectives are to compare the effectiveness of cell phone-supported SMS messaging to standard care on adherence, quality of life, retention, and mortality in a population receiving antiretroviral therapy (ART) in Nairobi, Kenya. METHODS AND DESIGN: A multi-site randomized controlled open-label trial. A central randomization centre provided opaque envelopes to allocate treatments. Patients initiating ART at three comprehensive care clinics in Kenya will be randomized to receive either a structured weekly SMS ('short message system' or text message) slogan (the intervention) or current standard of care support mechanisms alone (the control). Our hypothesis is that using a structured mobile phone protocol to keep in touch with patients will improve adherence to ART and other patient outcomes. Participants are evaluated at baseline, and then at six and twelve months after initiating ART. The care providers keep a weekly study log of all phone based communications with study participants. Primary outcomes are self-reported adherence to ART and suppression of HIV viral load at twelve months scheduled follow-up. Secondary outcomes are improvements in health, quality of life, social and economic factors, and retention on ART. Primary analysis is by 'intention-to-treat'. Sensitivity analysis will be used to assess per-protocol effects. Analysis of covariates will be undertaken to determine factors that contribute or deter from expected and determined outcomes. DISCUSSION: This study protocol tests whether a novel structured mobile phone intervention can positively contribute to ART management in a resource-limited setting.

Safety, acceptability, and tolerability of 3 topical microbicides among heterosexual Kenyan men.

OBJECTIVES: To compare the acceptability, tolerability, and safety of 3 topical microbicide formulations (62% ethyl alcohol in emollient gel and 0.1% and 0.4% benzalkonium chloride on a sanitary wipe) for use on male genitalia. DESIGN: This triple-randomized crossover study among men attending a sexually transmitted disease (STD) clinic in Nairobi, Kenya assigned individuals without clinical evidence of an STD to apply products to the penis in a predetermined random order, each for a 2-week period with a 1-week washout period between each product. Men recorded side effects and were examined for adverse events. RESULTS: Of 39 participants, 33 (84%) completed 6 clinic visits plus 3 home visits by community health workers. Participants reported use of 62% ethanol gel and 0.1% and 0.4% benzalkonium on 99%, 99%, and 96% of daily scheduled applications; 99%, 98%, and 97% of preintercourse applications, and 99%, 94%, and 98% of postintercourse applications. All participants said they would recommend all 3 products to a friend; 72% preferred the 62% ethanol gel, 17% the 0.1% benzalkonium, and 11% the 0.4% benzalkonium. One person developed objective signs of a genital ulcer after 14 days of 0.4% benzalkonium wipe use. CONCLUSIONS: Two of the 3 topical microbicides had minimal reported adverse effects, and no adverse effects were observed during use of the ethanol gel, which was preferred by most men.

Bacterial vaginosis: risk factors among Kenyan women and their male partners.

OBJECTIVES: To simultaneously examine associations of bacterial vaginosis (BV) with potential risk factors in both the female and her male partner. STUDY DESIGN: We recruited women 18-45 years of age and their male partners from clinics in Nairobi, Kenya. All underwent face-to-face standardized interview physical examination, human immunodeficiency virus (HIV)-1 and syphilis serologic testing, endocervical cultures for Neisseria gonorrhoeae, and vaginal swabs for diagnosis of BV by Gram stain and trichomoniasis by culture. RESULTS: Of 219 women, 97 (44%) had BV. BV was significantly associated by univariate analyses with women's own risk factors (young age, being unmarried, early sexual debut, more than 1 sexual partner, lifetime, rectal sex, trichomoniasis, HIV infection, and by principal components analysis, with low socioeconomic status [SES]) and also with male partners' characteristics (HIV infection, and by principal components analysis, low SES, and poor hygiene). In multivariate analysis including risk factors from both genders, the odds of having BV was 5.7 times higher if either partner was HIV seropositive, 13.2 times higher if the female had trichomoniasis, 2.5 times higher if the female had more than 1 sex partner ever, and decreased with increasing age of the female. CONCLUSION: In this population, characteristics of males and of females were independently associated with BV. Close association of male hygiene and male HIV status precluded distinguishing the influence of male hygiene on partner's BV.

Joint modelling of repeated measurements and event time: application to performance traits and survival of lambs bred in sub-humid tropics.

We considered the analysis of a study for Dorper, Red Maasai and crossbred lambs born over a period of 6 years at the Diani Estate, Kenya. The study was designed to compare survival and performance traits of genotypes with differing susceptibilities to helminthiasis. The available data include information on time to death and repeated measurements of body weight, packed cell volume (PCV) and faecal egg count (FEC) of the animals. In the paper, we consider joint modelling of the survival time and the repeated measurements. Such an approach allows to account for the possible association between the survival and repeated measurement processes. The advantages and limitations of the joint modelling are discussed and illustrated using the Diani Estate study data.

Immunoepidemiologic profile of Chlamydia trachomatis infection: importance of heat-shock protein 60 and interferon- gamma.

Epidemiological, animal, and in vitro investigations suggest that Chlamydia trachomatis infection engenders acquired immunity, the basis for which is incompletely defined, especially in humans. In a prospective cohort study of women at high risk for C. trachomatis infection, we found that, at baseline and after adjustment for age and other potential confounding variables, production of interferon- gamma by peripheral-blood mononuclear cells (PBMCs) stimulated with chlamydia heat-shock protein 60 strongly correlated with protection against incident C. trachomatis infection. This investigation supports a direct role for C. trachomatis-specific immune responses in altering the risk of infection and suggests immune correlates of protection that are potentially useful in vaccine development.