Search

Background Malaria infections during pregnancy lead to sequestration of parasite infected red blood cells in the placenta. Placental infection can result in adverse outcomes for mothers and infants. Despite many studies, it remains unclear which peripheral blood infections during pregnancy lead to development of placental malaria. Understanding the timing of peripheral infections that lead to placental malaria and the ability of intermittent preventive treatment with sulfadoxine–pyrimethamine (SP-IPT) and artemisinin-based combination therapy to clear infections will enable the rational design of new interventions to decrease the burden of malaria in pregnancy. Methods Microsatellite markers were used to genotype peripheral and placental malaria infections in an observational cohort in Blantyre, Malawi. Genotypes were compared to determine the timing of infections that sequester in the placenta. The effects of SP-IPT and artemether–lumefantrine as curative treatment were also evaluated by assessing the occurrence of peripheral infections or matching genotypes between peripheral and placental parasites following treatment. Results Genotypes from 92 peripheral samples prior to delivery, 26 peripheral samples at delivery, and 29 placental samples were compared. Thirty percent of women with genotyped parasites in their placentas that had peripheral infections detected during pregnancy had matching peripheral-placental genotypes. Matching genotypes were not associated with gestational age and occurred from 13 to 39 weeks. Among women with more than one genotyped peripheral infection during pregnancy, 80 % had persistent infection with the same genotype while the remaining were new infections. Among infections treated with SP or artemether–lumefantrine, 28/84 (33 %) and 9/56 (16 %) had infection detected after treatment, respectively. Recrudescent infections were detected after both treatments and occurred up to 76 days after treatment. Women treated with SP-IPT and artemether–lumefantrine had genotypes matching treated infections detected in the placenta. Conclusions Placental malaria can occur at any time during pregnancy. In the context of late enrollment in antenatal care, interventions that protect all women of childbearing age and throughout pregnancy are needed. Currently used medications do not always clear peripheral or placental infections. The ability of anti-malarial drugs to prevent or clear placental infections should be considered in the development of future interventions.

Background Preventing malaria during pregnancy is important for the health of mothers and newborns. Interventions, which include distribution of bed nets and administration of intermittent preventive treatment (IPT), typically occur at the first antenatal visit, usually in the second or third trimester of pregnancy. In 2012, during the course of ongoing clinical studies of malaria among pregnant women in Malawi, a universal bed net campaign was implemented by the Government. This study tested the hypothesis that a universal bed net campaign would decrease the prevalence of malaria among pregnant women at their first antenatal visit. Methods Some 1661 women were recruited for two studies from 2009 to 2014. Quantitative PCR (qPCR) was conducted from dried blood spots collected at the first antenatal care visit (prior to administration of IPT or any study interventions) from women who were in their first or second pregnancy and less than 28 weeks gestation by clinical assessment. Results Overall, 320 of 1629 (19.6 %) women tested for malaria at their first antenatal visit were infected. Malaria infection rates declined from 28.4 % before the universal bed net campaign, to 18.5 % in 2012, to 15.0 % in the years following the universal bed net campaign. The odds of malaria infection at the time of first antenatal visit in 2012 and the years following the bed net campaign were significantly lower than in the years prior to the intervention (OR 0.6, 95 % CI 0.4–0.8; and OR 0.4, 95 % CI 0.3–0.6, respectively). A similar pattern was observed for the prevalence of clinical malaria. The inverse trend was observed for reported bed net use. However bed net use and malaria infection were not significantly associated on the individual level. Conclusions Malaria infection in pregnant women is common even after a bed net campaign in Malawi, though prevalence rates declined. These early infections may cause maternal anaemia and placental malaria resulting in adverse maternal and fetal outcomes. Infection early in pregnancy may also contribute to malaria transmission as pregnant women represent a significant untreated reservoir of parasites. Universal bed net distribution appears to have moderate success in preventing malaria early in pregnancy and these findings support continued efforts to target women early in pregnancy and all women of childbearing age.

Background Missing outcomes can seriously impair the ability to make correct inferences from randomized controlled trials (RCTs). Complete case (CC) analysis is commonly used, but it reduces sample size and is perceived to lead to reduced statistical efficiency of estimates while increasing the potential for bias. As multiple imputation (MI) methods preserve sample size, they are generally viewed as the preferred analytical approach. We examined this assumption, comparing the performance of CC and MI methods to determine risk difference (RD) estimates in the presence of missing binary outcomes. We conducted simulation studies of 5000 simulated data sets with 50 imputations of RCTs with one primary follow-up endpoint at different underlying levels of RD (3–25 %) and missing outcomes (5–30 %). Results For missing at random (MAR) or missing completely at random (MCAR) outcomes, CC method estimates generally remained unbiased and achieved precision similar to or better than MI methods, and high statistical coverage. Missing not at random (MNAR) scenarios yielded invalid inferences with both methods. Effect size estimate bias was reduced in MI methods by always including group membership even if this was unrelated to missingness. Surprisingly, under MAR and MCAR conditions in the assessed scenarios, MI offered no statistical advantage over CC methods. Conclusions While MI must inherently accompany CC methods for intention-to-treat analyses, these findings endorse CC methods for per protocol risk difference analyses in these conditions. These findings provide an argument for the use of the CC approach to always complement MI analyses, with the usual caveat that the validity of the mechanism for missingness be thoroughly discussed. More importantly, researchers should strive to collect as much data as possible.