Deborah Watson-Jones

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].).

Mortality risk in preterm and small-for-gestational-age infants in low-income and middle-income countries: a pooled country analysis

BACKGROUND Babies with low birthweight (<2500 g) are at increased risk of early mortality. However, low birthweight includes babies born preterm and with fetal growth restriction, and not all these infants have a birthweight less than 2500 g. We estimated the neonatal and infant mortality associated with these two characteristics in low-income and middle-income countries. METHODS For this pooled analysis, we searched all available studies and identified 20 cohorts (providing data for 2,015,019 livebirths) from Asia, Africa, and Latin America that recorded data for birthweight, gestational age, and vital statistics through 28 days of life. Study dates ranged from 1982 through to 2010. We calculated relative risks (RR) and risk differences (RD) for mortality associated with preterm birth (<32 weeks, 32 weeks to <34 weeks, 34 weeks to <37 weeks), small-for-gestational-age (SGA; babies with birthweight in the lowest third percentile and between the third and tenth percentile of a US reference population), and preterm and SGA combinations. FINDINGS Pooled overall RRs for preterm were 6·82 (95% CI 3·56-13·07) for neonatal mortality and 2·50 (1·48-4·22) for post-neonatal mortality. Pooled RRs for babies who were SGA (with birthweight in the lowest tenth percentile of the reference population) were 1·83 (95% CI 1·34-2·50) for neonatal mortality and 1·90 (1·32-2·73) for post-neonatal mortality. The neonatal mortality risk of babies who were both preterm and SGA was higher than that of babies with either characteristic alone (15·42; 9·11-26·12). INTERPRETATION Many babies in low-income and middle-income countries are SGA. Preterm birth affects a smaller number of neonates than does SGA, but is associated with a higher mortality risk. The mortality risks associated with both characteristics extend beyond the neonatal period. Differentiation of the burden and risk of babies born preterm and SGA rather than with low birthweight could guide prevention and management strategies to speed progress towards Millennium Development Goal 4--the reduction of child mortality. FUNDING Bill & Melinda Gates Foundation.

Syphilis in Pregnancy in Tanzania. I. Impact of Maternal Syphilis on Outcome of Pregnancy

To measure the impact of maternal syphilis on pregnancy outcome in the Mwanza Region of Tanzania, 380 previously unscreened pregnant women were recruited into a retrospective cohort at delivery and tested for syphilis. Stillbirth was observed in 18 (25%) of 73 women with high-titer active syphilis (i.e., women with a rapid plasma reagin titer > or = 1 :8 and a positive Treponema pallidum hemagglutination assay or indirect fluorescent treponemal antibody test result), compared with 3 (1%) of 233 uninfected women (risk ratio [RR], 18.1; P<.001). Women with high-titer active syphilis were also at the greatest risk of having low-birth-weight or preterm live births (RR, 3.0 and 6.1, respectively), compared with women with other serological stages of syphilis. Among unscreened women, 51% of stillbirths, 24% of preterm live births, and 17% of all adverse pregnancy outcomes were attributable to maternal syphilis. Syphilis continues to be a major cause of pregnancy loss and adverse pregnancy outcome among women who do not receive antenatal syphilis screening and treatment.

Hormonal Contraception and the Risk of HIV Acquisition: An Individual Participant Data Meta-analysis:

In a meta-analysis of individual participant data, Charles Morrison and colleagues explore the association between hormonal contraception use and risk of HIV infection in sub-Saharan Africa.

Intravaginal Practices, Bacterial Vaginosis, and HIV Infection in Women: Individual Participant Data Meta-analysis

Pooling of data from 14,874 women in an individual participant data meta-analysis by Nicola Low and colleagues reveals that some intravaginal practices increase the risk of HIV acquisition.

Sexually transmitted infections in pregnancy: prevalence, impact on pregnancy outcomes, and approach to treatment in developing countries

Sexually transmitted infections (STIs) are common in the developing world. Management of STIs in pregnancy in many developing countries has, however, been complicated by the lack of simple and affordable diagnostic tests. This review examines the prevalence and impact on pregnancy outcome of STIs in developing countries and recommends approaches to management of STIs in pregnancy for resource poor settings.

Syphilis in Pregnancy in Tanzania. II. The Effectiveness of Antenatal Syphilis Screening and Single-Dose Benzathine Penicillin Treatment for the Prevention of Adverse Pregnancy Outcomes

Treatment for maternal syphilis with single-dose benzathine penicillin (2.4 million units intramuscularly) is being implemented in many parts of sub-Saharan Africa. To examine the effectiveness of this regimen, a prospective cohort of 1688 pregnant women was recruited in Tanzania. Birth outcomes were compared among women treated for high-titer (n=133; rapid plasma reagin [RPR] titer > or = 1:8 and Treponema pallidum hemagglutination assay [TPHA]/fluorescent treponemal antibody [FTA] positive) and low-titer (n=249; RPR titer <1:8 and TPHA/FTA positive) active syphilis and 950 uninfected women. Stillbirth or low-birth-weight live births were observed in 2.3% and 6.3%, respectively, of women treated for high-titer active syphilis and in 2.5% and 9.2%, respectively, of seronegative women. There was no increased risk for adverse pregnancy outcome for women treated for high-titer active syphilis (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.4-1.4) or low-titer active syphilis (OR, 0.95; 95% CI, 0.6-1.5), compared with seronegative women. Single-dose treatment is effective in preventing adverse pregnancy outcomes attributable to maternal syphilis.

Is antenatal syphilis screening still cost effective in sub-Saharan Africa

Objectives: To estimate the cost effectiveness of on-site antenatal syphilis screening and treatment in Mwanza, Tanzania. To compare this intervention with other antenatal and child health interventions, specifically the prevention of mother to child transmission of HIV (PMTCT). Methods: The economic costs of adding the intervention to routine antenatal care were assessed. Cost effectiveness (CE) ratios of the intervention were obtained for low birth weight (LBW) live births and stillbirths averted and cost per DALY saved. Cost per DALY saved was also estimated for previous CE studies of syphilis screening. The CE of the intervention at different syphilis prevalence rates was modelled. Results: The economic cost of the intervention is

Human papillomavirus infection and increased risk of HIV acquisition. A systematic review and meta-analysis

1.44 per woman screened,

Treatment of sexually transmitted infections for HIV prevention: end of the road or new beginning?

20 per woman treated, and