Kathy Baisley

Effect of Herpes Simplex Suppression on Incidence of HIV among Women in Tanzania

BACKGROUND Infection with herpes simplex virus type 2 (HSV-2) is associated with an increased risk of acquiring infection with the human immunodeficiency virus (HIV). This study tested the hypothesis that HSV-2 suppressive therapy reduces the risk of HIV acquisition. METHODS Female workers at recreational facilities in northwestern Tanzania who were 16 to 35 years of age were interviewed and underwent serologic testing for HIV and HSV-2. We enrolled female workers who were HIV-seronegative and HSV-2-seropositive in a randomized, double-blind, placebo-controlled trial of suppressive treatment with acyclovir (400 mg twice daily). Participants attended mobile clinics every 3 months for a follow-up period of 12 to 30 months, depending on enrollment date. The primary outcome was the incidence of infection with HIV. We used a modified intention-to-treat analysis; data for participants who became pregnant were censored. Adherence to treatment was estimated by a tablet count at each visit. RESULTS A total of 821 participants were randomly assigned to receive acyclovir (400 participants) or placebo (421 participants); 679 (83%) completed follow-up. Mean follow-up for the acyclovir and placebo groups was 1.52 and 1.62 years, respectively. The incidence of HIV infection was 4.27 per 100 person-years (27 participants in the acyclovir group and 28 in the placebo group), and there was no overall effect of acyclovir on the incidence of HIV (rate ratio for the acyclovir group, 1.08; 95% confidence interval, 0.64 to 1.83). The estimated median adherence was 90%. Genital HSV was detected in a similar proportion of participants in the two study groups at 6, 12, and 24 months. No serious adverse events were attributable to treatment with acyclovir. CONCLUSIONS These data show no evidence that acyclovir (400 mg twice daily) as HSV suppressive therapy decreases the incidence of infection with HIV. (Current Controlled Trials number, ISRCTN35385041 [controlled-trials.com].).

Distribution and diversity of Wolbachia infections in Southeast Asian mosquitoes (Diptera: Culicidae).

Abstract Wolbachia are a group of intracellular inherited bacteria that infect a wide range of arthropods. They are associated with a variety of reproductive alterations in their hosts, the best known being cytoplasmic incompatability. The Wolbachia pipientis assemblage has been divided into two major groups (A and B) and 12 subgroups. We report herein the first systematic survey of Wolbachia in mosquitoes, and the first survey classifying Wolbachia infections by subgroup. Wolbachia were detected in 28.1% of 89 wild-caught mosquito species, based on a polymerase chain reaction assay using ftsZ and wsp gene primers. Infections were found in all major disease vector genera except Anopheles. Nine of the 12 Wolbachia subgroups were represented. Group B Wolbachia strains showed more phylogenetic concordance with their host taxa than group A strains. Of the 25 positive mosquito species, five were superinfected with group A bacteria strains (AA), eight were superinfected with A and B strains (AB), and one was superinfected with group B strains (BB). The widespread distribution of Wolbachia among mosquito species further supports their potential importance in the genetic control of disease vectors.

Distribution of hyperglycaemia and related cardiovascular disease risk factors in low-income countries: a cross-sectional population-based survey in rural Uganda

Background Data on non-communicable disease (NCD) burden are often limited in developing countries in Africa but crucial for planning and implementation of prevention and control strategies. We assessed the prevalence of related cardiovascular disease risk factors (hyperglycaemia, high blood pressure and obesity) in a longstanding population cohort in rural Uganda. Methods Trained field staff conducted a cross-sectional population-based survey of cardiovascular disease risk indicators using a questionnaire and simple measurements of body mass index (BMI), waist and hip circumference, waist/hip ratio (WHR), blood pressure and random plasma glucose. All members of the population cohort aged ≥13 years were eligible to participate in the survey. Results Of the 4801 males and 5372 females who were eligible, 2719 (56.6%) males and 3959 (73.7%) females participated in the survey. Male and female participants had a mean standard deviation (SD) age of 31.8 (18.4) years and 33.7 (17.6) years, respectively. The observed prevalences of probable diabetes (glucose >11.0 mmol/l) and probable hyperglycaemia (7.0–11.0 mmol/l) were 0.4 and 2.9%, respectively. Less than 1% of males and 4% of females were obese (BMI ≥30 kg/m2), with 3.6% of males and 14.5% of females being overweight (BMI 25.0–29.9 kg/m2). However, in women, the prevalence of abdominal obesity was high (71.3% as measured by WHR and 31.2% as measured by waist circumference). The proportions of male and female current regular smokers were low (13.7 and 0.9%, respectively). The commonest cardiovascular disease risk factor was high blood pressure, with an observed prevalence of 22.5% in both sexes. Conclusions Population-based data on the burden of related cardiovascular disease risk factors can aid in the planning and implementation of an effective response to the double burden of communicable diseases and NCDs in this rural population of a low-income country undergoing epidemiological transition.

Effects of rabeprazole, 20 mg, or esomeprazole, 20 mg, on 24-h intragastric pH and serum gastrin in healthy subjects.

Aim : To compare the antisecretory effects of rabeprazole and esomeprazole in an open, randomized, two‐way crossover, clinical pharmacology study.

Human Papillomavirus Vaccination in Tanzanian Schoolgirls: Cluster-Randomized Trial Comparing 2 Vaccine-Delivery Strategies

Background.We compared vaccine coverage achieved by 2 different delivery strategies for the quadrivalent human papillomavirus (HPV) vaccine in Tanzanian schoolgirls. Methods.In a cluster-randomized trial of HPV vaccination conducted in Tanzania, 134 primary schools were randomly assigned to class-based (girls enrolled in primary school grade [class] 6) or age-based (girls born in 1998; 67 schools per arm) vaccine delivery. The primary outcome was coverage by dose. Results.There were 3352 and 2180 eligible girls in schools randomized to class-based and age-based delivery, respectively. HPV vaccine coverage was 84.7% for dose 1, 81.4% for dose 2, and 76.1% for dose 3. For each dose, coverage was higher in class-based schools than in age-based schools (dose 1: 86.4% vs 82.0% [P = .30]; dose 2: 83.8% vs 77.8% [P = .05]; and dose 3: 78.7% vs 72.1% [P = .04]). Vaccine-related adverse events were rare. Reasons for not vaccinating included absenteeism (6.3%) and parent refusal (6.7%). School absenteeism rates prior to vaccination ranged from 8.1% to 23.5%. Conclusions.HPV vaccine can be delivered with high coverage in schools in sub-Saharan Africa. Compared with age-based vaccination, class-based vaccination located more eligible pupils and achieved higher coverage. HPV vaccination did not increase absenteeism rates in selected schools. Innovative strategies will be needed to reach out-of-school girls. Clinical Trials Registration. NCT01173900.

Epidemiology of hypertension in low-income countries: a cross-sectional population-based survey in rural Uganda

Objective Population-based data on burden of hypertension are crucial for planning and implementation of prevention and control strategies but are often limited in developing countries in Africa. We assessed the prevalence of hypertension and related risk factors in a population cohort in rural Uganda initially established for HIV surveys. Methods In a cross-sectional population-based survey of hypertension and related risk factors in 2009, trained field staff administered a questionnaire and obtained a single measurement of blood pressure, BMI, waist and hip circumference, waist/hip ratio (WHR) and random plasma glucose. All members of the population cohort aged 13 years and above were eligible for survey participation. Logistic regression was used to evaluate factors associated with high blood pressure, defined as SBP (mmHg) ≥140 or DBP ≥90. Results Of the 4801 men and 5372 women who were eligible, 2719 (56.6%) men and 3959 (73.7%) women participated in the survey. The prevalence of high blood pressure was 22.0%, age standardized to the local population. Factors that were independently associated with high blood pressure were increasing age, BMI and elevated glucose in both sexes, extremes of education level (none and secondary or above) among men, and being unmarried and waist circumference ≥80 cm among women. Levels of reported hypertension were very low, with nine out 10 people unaware of their condition. Conclusion The use of established research infrastructure, for example, community HIV surveys, can help to generate the population-based data on the prevalence of hypertension and related risk factors needed to inform planning and implementation of effective prevention and control strategies in low-income countries. There is an urgent need to strengthen health services in responding effectively to the large burden of undetected hypertension.

Correlates of HIV-1 genital shedding in Tanzanian women.

Background Understanding the correlates of HIV shedding is important to inform strategies to reduce HIV infectiousness. We examined correlates of genital HIV-1 RNA in women who were seropositive for both herpes simplex virus (HSV)-2 and HIV-1 and who were enrolled in a randomised controlled trial of HSV suppressive therapy (aciclovir 400 mg b.i.d vs. placebo) in Tanzania. Methodology Samples, including a cervico-vaginal lavage, were collected and tested for genital HIV-1 and HSV and reproductive tract infections (RTIs) at randomisation and 6, 12 and 24 months follow-up. Data from all women at randomisation and women in the placebo arm during follow-up were analysed using generalised estimating equations to determine the correlates of cervico-vaginal HIV-1 RNA detection and load. Principal Findings Cervico-vaginal HIV-1 RNA was detected at 52.0% of 971 visits among 482 women, and was independently associated with plasma viral load, presence of genital ulcers, pregnancy, bloody cervical or vaginal discharge, abnormal vaginal discharge, cervical ectopy, Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, an intermediate bacterial vaginosis score and HSV DNA detection. Similar factors were associated with genital HIV-1 RNA load. Conclusions RTIs were associated with increased presence and quantity of genital HIV-1 RNA in this population. These results highlight the importance of integrating effective RTI treatment into HIV care services.

Risk factors for herpes simplex virus type 2 and HIV among women at high risk in northwestern Tanzania - Preparing for an HSV-2 intervention trial

Objectives:To determine prevalence of and risk factors for herpes simplex virus type 2 (HSV-2) and HIV among women being screened for a randomized, controlled trial of HSV suppressive therapy in northwestern Tanzania. Methods:Two thousand seven hundred nineteen female facility workers aged 16 to 35 were interviewed and underwent serological testing for HIV and HSV-2. Factors associated with HSV-2 and HIV in women aged 16 to 24 were examined using logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). Results:HSV-2 seroprevalence was 80%, and HIV seroprevalence was 30%. Among women aged 16 to 24, both infections were significantly and independently associated with older age, being a bar worker, working at a truck stop, and having more lifetime sexual partners. HSV-2 infection was also associated with lower socioeconomic status, increased alcohol intake, younger age at first sex, inconsistent condom use, and vaginal douching. There was a strong association between the 2 infections after adjustment for other factors (OR = 4.22, 95% CI: 2.6 to 6.9). Conclusions:Female facility workers in northwestern Tanzania are vulnerable to HSV-2 and HIV infections. Programs designed to increase safer sexual behavior and reduce alcohol use could be effective in reducing HSV-2 incidence and, in turn, HIV infection. This is a suitable population for an HSV suppressive therapy trial.

Pharmacokinetic interaction between domperidone and ketoconazole leads to QT prolongation in healthy volunteers: a randomized, placebo-controlled, double- blind, crossover study

AIMS To assess the steady-state pharmacokinetic and QT(c) effects of domperidone and ketoconazole, given alone and together. METHODS A randomized, placebo-controlled, double-blind, crossover study was carried out. Healthy subjects (14 men, 10 women; age 18-39 years; mean weight 73.5kg, range 53.8-98.8kg; 23 Europid, 1 Afro-Caribbean) received orally, for 7 days each, placebo, domperidone 10mg, four doses daily, at 4h intervals, ketoconazole 200mg 12-hourly and domperidone and ketoconazole together. The washout period was 15 days. Pharmacokinetics and serial 12-lead ECGs were assessed on day 7, and serial ECGs on day -1 and at follow-up. Two subjects withdrew before the third treatment period, so data were available for 22-24 subjects. RESULTS Ketoconazole tripled domperidone concentrations at steady-state. Domperidone, ketoconazole and their combination significantly increased QT(c) F in men. Overall adjusted mean differences from placebo were 4.20 (95% CI 0.77, 7.63), 9.24 (95% CI 5.85, 12.63) and 15.90 (95% CI 12.47, 19.33) ms, respectively. In women, QT(c) F was not significantly different from placebo on either domperidone or ketoconazole alone, or in combination. However, QT(c) was positively correlated with plasma drug concentrations, in both men and women. ΔQT(c) F increased by about 2ms per 10ngml(-1) rise in domperidone concentration, and per 1µgml(-1) rise in ketoconazole concentration. CONCLUSIONS Ketoconazole tripled the plasma concentrations of domperidone. Domperidone and ketoconazole increased QT(c) F in men, whether given together or separately. The effect of domperidone alone was below the level of clinical importance. The negative result in women is unexplained.

Assessing Water Filtration and Safe Storage in Households with Young Children of HIV-Positive Mothers: A Randomized, Controlled Trial in Zambia

Background Unsafe drinking water presents a particular threat to people living with HIV/AIDS (PLHIV) due to the increased risk of opportunistic infections, diarrhea-associated malabsorption of essential nutrients, and increased exposure to untreated water for children of HIV-positive mothers who use replacement feeding to reduce the risk of HIV transmission. This population may particularly benefit from an intervention to improve water quality in the home. Methods and Findings We conducted a 12-month randomized, controlled field trial in Zambia among 120 households with children <2 years (100 with HIV-positive mothers and 20 with HIV-negative mothers to reduce stigma of participation) to assess a high-performance water filter and jerry cans for safe storage. Households were followed up monthly to assess use, drinking water quality (thermotolerant coliforms (TTC), an indicator of fecal contamination) and reported diarrhea (7-day recall) among children <2 years and all members of the household. Because previous attempts to blind the filter have been unsuccessful, we also assessed weight-for-age Z-scores (WAZ) as an objective measure of diarrhea impact. Filter use was high, with 96% (596/620) of household visits meeting the criteria for users. The quality of water stored in intervention households was significantly better than in control households (3 vs. 181 TTC/100 mL, respectively, p<0.001). The intervention was associated with reductions in the longitudinal prevalence of reported diarrhea of 53% among children <2 years (LPR = 0.47, 95% CI: 0.30–0.73, p = 0.001) and 54% among all household members (LPR = 0.46, 95% CI: 0.30–0.70, p<0.001). While reduced WAZ was associated with reported diarrhea (−0.26; 95% CI: −0.37 to −0.14, p<0.001), there was no difference in WAZ between intervention and control groups. Conclusion In this population living with HIV/AIDS, a water filter combined with safe storage was used correctly and consistently, was highly effective in improving drinking water quality, and was protective against diarrhea. Trial Registration Clinicaltrials.gov NCT01116908