Prevention of malaria in pregnancy

Although the World Health Organization (WHO) has established recommendations for prevention of malaria, it remains one of the most preventable causes of adverse birth outcomes. The WHO recommends intermittent preventive treatment in pregnancy (IPTp) with for women who are HIV-negative, or co-trimoxazole prophylaxis for women who are HIV-positive. However, parasite resistance to sulfadoxine pyrimethamine in sub-Saharan Africa has led researchers to pursue other screen-and-treat approaches. This analysis reviews the effect of sulfadoxine-pyrimethamine on IPTp efficacy and summarizes trials focused on the prevention of malaria in pregnancy in areas where malaria is endemic. A total of 65 efficacy-related articles were included. Sulfadoxine-pyrimethamine as IPTp in pregnant women reduces the risk of comorbidities including anemia, antenatal and placental parasitemia, spontaneous abortions, and low birthweight. Reviews of this regimen have found it to be highly costeffective when combined with existing antenatal services. A meta-analysis conducted in Africa found that 3-course or monthly IPTp with sulfadoxine-pyrimethamine was much more effective in reducing adverse birth outcomes than the standard 2-course regimen, leading the WHO to update its guidelines in 2012. Observational studies have shown that resistance to sulfadoxine-pyrimethamine reduces the parasitological efficacy of IPTp and duration of prophylaxis. High resistance is found in regions where prevalence of parasites with quintuple Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthetase (Pfdhps) mutations is greater than 90%. Even in such locations, sulfadoxine-pyrimethamine regimens continue to have beneficial effects on low birthweight. Research into alternative IPTp therapies are ongoing, yet many proposed alternatives thus far have found that they are tolerated poorly by patients. Two trials of IPTp using dihydroartemisinin-piperaquine show that it was well tolerated compared with sulfadoxine-pyrimethamine and associated with greater reductions in malaria and fetal loss. Four studies examined intermittent screening and treatment in pregnancy (ISTp) as an alternative to IPTp in areas of high resistance and high sensitivity to sulfadoxine-pyrimethamine. Meta-analysis of these trials, which involve rapid diagnostic testing and artemisinin-based combination therapy, revealed ISTp was associated with a 25-g decrease in mean birthweight (95% confidence interval, 7-44; P = 0.0088, n = 8659). There is a gap in the research on pharmacokinetic and dynamic drug interactions between antiretroviral and antimalarial drugs in pregnancy. Research in sub-Saharan Africa revealed lack of education targeting women on care of malaria in pregnancy. Studies related to operational feasibility revealed confusion over IPTp guidelines for providers and a lack of interventional studies to improve professional delivery of IPTp and ISTp. Modeling analysis concluded that the burden ofmalaria in pregnancy will saturate atmoderate-to-high levels of transmission, and in areas of sustained transmission, a high proportion of the burden is caused by infected-women becoming pregnant rather than pregnant women becoming infected. Improved funding over the past decade has led to an increase in the literature on research gaps in the prevention of malaria in pregnancy. Confirmatory trials are indicated for the safety, efficacy, and feasibility of dihydroartemisinin-piperaquine as an alternative to sulfadoxine-pyrimethamine for IPTp. More research is needed on many avenues reported here, including the interaction of HIVand malaria during pregnancy, RDT in point-of-care settings, and improving uptake of the WHOs updated policy on IPTp with sulfadoxine-pyrimethamine and insecticide-treated nets.