Abstract
SummaryBackgroundMalaria in pregnancy affects both the mother and the fetus. However, evidence supporting treatment guidelines for uncomplicated (including asymptomatic) falciparum malaria in pregnant women is scarce and assessed in varied ways. We did a systematic literature review and individual patient data (IPD) meta-analysis to compare the efficacy and tolerability of different artemisinin-based or quinine-based treatments for malaria in pregnant women.MethodsWe did a systematic review of interventional or observational cohort studies assessing the efficacy of artemisinin-based or quinine-based treatments in pregnancy. Seven databases (MEDLINE, Embase, Global Health, Cochrane Library, Scopus, Web of Science, and Literatura Latino Americana em Ciencias da Saude) and two clinical trial registries (International Clinical Trials Registry Platform and ClinicalTrials.gov) were searched. The final search was done on April 26, 2019. Studies that assessed PCR-corrected treatment efficacy in pregnancy with follow-up of 28 days or more were included. Investigators of identified studies were invited to share data from individual patients. The outcomes assessed included PCR-corrected efficacy, PCR-uncorrected efficacy, parasite clearance, fever clearance, gametocyte development, and acute adverse events. One-stage IPD meta-analysis using Cox and logistic regression with random-effects was done to estimate the risk factors associated with PCR-corrected treatment failure, using artemether-lumefantrine as the reference. This study is registered with PROSPERO, CRD42018104013.FindingsOf the 30 studies assessed, 19 were included, representing 92% of patients in the literature (4968 of 5360 episodes). Risk of PCR-corrected treatment failure was higher for the quinine monotherapy (n=244, adjusted hazard ratio [aHR] 6·11, 95% CI 2·57–14·54, p<0·0001) but lower for artesunate-amodiaquine (n=840, 0·27, 95% 0·14–0·52, p<0·0001), artesunate-mefloquine (n=1028, 0·56, 95% 0·34–0·94, p=0·03), and dihydroartemisinin-piperaquine (n=872, 0·35, 95% CI 0·18–0·68, p=0·002) than artemether-lumefantrine (n=1278) after adjustment for baseline asexual parasitaemia and parity. The risk of gametocyte carriage on day 7 was higher after quinine-based therapy than artemisinin-based treatment (adjusted odds ratio [OR] 7·38, 95% CI 2·29–23·82).InterpretationEfficacy and tolerability of artemisinin-based combination therapies (ACTs) in pregnant women are better than quinine. The lower efficacy of artemether-lumefantrine compared with other ACTs might require dose optimisation.FundingThe Bill & Melinda Gates Foundation, ExxonMobil Foundation, and the University of Oxford Clarendon Fund.
Highlights
The physiological changes that occur during pregnancy mean that pregnant women are more susceptible to malaria than women who are not pregnant
By including single-arm studies and more studies done after the release of the treatment guidelines, this study aims to contribute to the body of evidence by pooling individual patient data from studies to assess the efficacy of recommended antimalarial drugs for uncomplicated falciparum malaria during pregnancy, including patients who were asymptomatic
Search strategy and selection criteria We did a systematic review on the efficacy of artemisinin-based treatm ents (ABT) and quinine-based treatments (QBT) on uncomplicated falciparum malaria, including asymptomatic parasitaemia in pregnancy without any restrictions on language or publication year, and this was published elsewhere.[6]
Summary
The physiological changes that occur during pregnancy mean that pregnant women are more susceptible to malaria than women who are not pregnant. Symptomatic and asymptomatic infections affect both mother and fetus.[1,2] Around 60% of pregnant women in the world live in malaria-endemic regions, with an estimated 125 million pregnant women at risk of malaria every year.[3] Efficacious prevention and treatment are required to limit maternal mortality and the cumulative adverse effects of malaria episodes during pregnancy. This susceptible population nurturing future generations is understudied.[4] Pregnant women are often excluded from clinical trials and antimalarial studies are no exception.[5]
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