Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Negative Women: A Multicentre Randomized Controlled Trial

Background

Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by WHO to prevent malaria in African pregnant women. The spread of SP parasite resistance has raised concerns regarding long-term use for IPT. Mefloquine (MQ) is the most promising of available alternatives to SP based on safety profile, long half-life, and high efficacy in Africa. We evaluated the safety and efficacy of MQ for IPTp compared to those of SP in HIV-negative women.

Methods and Findings

A total of 4,749 pregnant women were enrolled in an open-label randomized clinical trial conducted in Benin, Gabon, Mozambique, and Tanzania comparing two-dose MQ or SP for IPTp and MQ tolerability of two different regimens. The study arms were: (1) SP, (2) single dose MQ (15 mg/kg), and (3) split-dose MQ in the context of long lasting insecticide treated nets. There was no difference on low birth weight prevalence (primary study outcome) between groups (360/2,778 [13.0%]) for MQ group and 177/1,398 (12.7%) for SP group; risk ratio [RR], 1.02 (95% CI 0.86–1.22; p = 0.80 in the ITT analysis). Women receiving MQ had reduced risks of parasitemia (63/1,372 [4.6%] in the SP group and 88/2,737 [3.2%] in the MQ group; RR, 0.70 [95% CI 0.51–0.96]; p = 0.03) and anemia at delivery (609/1,380 [44.1%] in the SP group and 1,110/2743 [40.5%] in the MQ group; RR, 0.92 [95% CI 0.85–0.99]; p = 0.03), and reduced incidence of clinical malaria (96/551.8 malaria episodes person/year [PYAR] in the SP group and 130/1,103.2 episodes PYAR in the MQ group; RR, 0.67 [95% CI 0.52–0.88]; p = 0.004) and all-cause outpatient attendances during pregnancy (850/557.8 outpatients visits PYAR in the SP group and 1,480/1,110.1 visits PYAR in the MQ group; RR, 0.86 [0.78–0.95]; p = 0.003). There were no differences in the prevalence of placental infection and adverse pregnancy outcomes between groups. Tolerability was poorer in the two MQ groups compared to SP. The most frequently reported related adverse events were dizziness (ranging from 33.9% to 35.5% after dose 1; and 16.0% to 20.8% after dose 2) and vomiting (30.2% to 31.7%, after dose 1 and 15.3% to 17.4% after dose 2) with similar proportions in the full and split MQ arms. The open-label design is a limitation of the study that affects mainly the safety assessment.

Conclusions

Women taking MQ IPTp (15 mg/kg) in the context of long lasting insecticide treated nets had similar prevalence rates of low birth weight as those taking SP IPTp. MQ recipients had less clinical malaria than SP recipients, and the pregnancy outcomes and safety profile were similar. MQ had poorer tolerability even when splitting the dose over two days. These results do not support a change in the current IPTp policy.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT 00811421","term_id":"NCT00811421"}}NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001429343 Please see later in the article for the Editors'' Summary     

Urogenital schistosomiasis during pregnancy is associated with low birth weight delivery: analysis of a prospective cohort of pregnant women and their offspring in Gabon

An estimated 40 million women of childbearing age suffer from schistosomiasis. Animal models indicate a deleterious effect of maternal schistosomiasis on pregnancy outcomes. To date there is a lack of epidemiological evidence evaluating schistosomiasis-related morbidity in pregnancy. This study was designed to describe the impact of urogenital schistosomiasis on pregnancy outcomes in a highly endemic region of central Africa. Pregnant women attending antenatal clinics in Fougamou and Lambaréné, Gabon, were consecutively screened for the presence of Schistosoma haematobium eggs in diurnal urine samples. Maternal and newborn characteristics assessed at delivery were compared between infected and uninfected mothers. The impact of maternal schistosomiasis on low birth weight and preterm delivery was assessed using logistic regression analysis. Urogenital schistosomiasis was diagnosed in 103 (9%) of 1115 pregnant women. Maternal age was inversely associated with the prevalence of urogenital schistosomiasis, with a higher burden amongst nulliparous women. Low birth weight was more common amongst infants of S. haematobium-infected mothers. This association was unaffected by controlling for demographic characteristics, gestational age and Plasmodium infection status (adjusted Odds Ratio 1.93; 95% confidence interval: 1.08–3.42). Other risk factors associated with low birth weight delivery were underweight mothers (adjusted Odds Ratio 2.34; 95% confidence interval: 1.12–4.92), peripheral or placental Plasmodium falciparum infection (adjusted Odds Ratio 2.04; 95% confidence interval: 1.18–3.53) and preterm birth (adjusted Odds Ratio 3.12; 95% confidence interval: 1.97–4.96). Preterm delivery was not associated with S. haematobium infection (adjusted Odds Ratio 1.07 95% confidence interval: 0.57–1.98). In conclusion, this study indicates that pregnant women with urogenital schistosomiasis are at an increased risk for low birth weight deliveries. Further studies evaluating targeted treatment and prevention programmes for urogenital schistosomiasis in pregnant women and their impact on delivery outcomes are warranted.