Parasitological efficacy of antimalarials in the treatment and prevention of falciparum malaria in pregnancy 1998 to 2009: a systematic review

Background Pregnant women are at increased risk from malaria. Resistance to all classes of antimalarials has affected the treatment and prevention of malaria in pregnancy. Objectives To review the therapeutic efficacy of antimalarials used for treatment and intermittent preventive treatment (IPT) in pregnancy. Search strategy We searched MEDLINE and the Cochrane Library between January 1998 and December 2009 for publications using the medical subject headings: efficacy, antimalarials, malaria, pregnancy, pharmacokinetics, treatment, IPT and placenta positive. In May 2010 we searched the register of clinical trials (http://clinicaltrials.gov/) and of WHO (http://apps.who.int/trialsearch/) using 'malaria', and 'pregnancy' and 'treatment'. Selection criteria We identified 233 abstracts, reviewed 83 full text articles and included 60 studies. Data collection and analysis Two authors entered extracted data to an excel spreadsheet. Main results Parasitological failure rates, placenta positivity rates (assessed by microscopy) or both were reported in 44% (21/48), 46% (22/48) and 10% (5/48) of articles, respectively. Most pharmacokinetic studies (9/12) suggested dose optimisation. In 23 treatment studies 17 different antimalarial drugs were delivered in 53 study arms; 43.4% (23/53) reported a failure rate of < 5%; 83.3% of sulphadoxine-pyrimethamine (SP) arms and 9% of artemisinin combination therapy (ACT) arms had failure rates >= 10%. Placenta-positive rates (mostly reported in the context of IPT in pregnancy) were > 10% in 68% (23/34) of SP trial arms and > 15% in all seven chloroquine arms. The ACT provided lower parasitological failure and gametocyte carriage rates. Author's conclusions Drugs used in pregnancy should aim for 95% efficacy but many currently deployed regimens are associated with much lower cure rates.