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Lancet Infect Dis. 2018 Apr;18(4):e119-e132. doi: 10.1016/S1473-3099(18)30064-1. Epub 2018 Jan 31.

Prevention of malaria in pregnancy.

Author information

Malaria Branch, US Centers for Diseases Control and Prevention, Atlanta, GA, USA. Electronic address:
Liverpool School of Tropical Medicine, Liverpool, UK.
London School of Hygiene & Tropical Medicine, London, UK.
Faculty of Medicine, School of Public Health, Imperial College London, London, UK.
Centre for Social Science and Global Health, University of Amsterdam, Amsterdam, Netherlands.
Malaria Branch, US Centers for Diseases Control and Prevention, Atlanta, GA, USA.
Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Dentistry, University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali.
ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
Mère et Enfant Face aux Infections Tropicales (UMR216), Institut de Recherche pour le Développement, Laboratoire de Parasitologie, Faculté de Pharmacie, Paris, France.


Malaria remains one of the most preventable causes of adverse birth outcomes. Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine is used to prevent malaria, but resistance to this drug combination has decreased its efficacy and new alternatives are needed. In Africa, a meta-analysis showed three-course or monthly IPTp with sulfadoxine-pyrimethamine to be safe and more effective than the original two-course sulfadoxine-pyrimethamine strategy, prompting WHO to update its policy in 2012. Although resistance to sulfadoxine-pyrimethamine reduces the parasitological efficacy of IPTp, this drug combination remains associated with reduced incidence of low birthweight in areas where prevalence of parasites with quintuple Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthetase (Pfdhps) mutations is greater than 90%. Nevertheless, its effectiveness is compromised in women infected with sextuple mutant parasites. Six trials of IPTp showed that neither amodiaquine, mefloquine, nor chloroquine-azithromycin are suitable replacements for sulfadoxine-pyrimethamine because of poor tolerability. Furthermore, four trials showed that intermittent screening and treatment with the current generation of malaria rapid diagnostic tests was not a suitable alternative strategy to IPTp with sulfadoxine-pyrimethamine, even in areas with high prevalence of quintuple mutations. Two trials showed that IPTp with dihydroartemisinin-piperaquine was well tolerated, effective, and acceptable for IPTp, with monthly regimens being the most effective. Coverage of IPTp and insecticide-treated nets continues to lag behind targets. The key barriers to uptake are well documented, and many are open to intervention. Outside of Africa, a single trial suggests a potential role for integrated approaches that combine sulfadoxine-pyrimethamine with azithromycin for IPTp in areas of Papua New Guinea where malaria transmission is high. Modelling analysis suggests the importance of the prevention of malaria early in pregnancy and the need to protect pregnant women declines more slowly than the rate at which transmission declines. Improved funding has led to an increase in the number of prevention trials in the past decade, showing the value of more sustained protection with monthly IPTp regimens. There is a need for confirmatory trials of the safety, efficacy, and feasibility of IPTp with dihydroartemisinin-piperaquine, for studies of intermittent screening and treatment with more sensitive rapid diagnostic tests, for studies of integrated strategies for malaria and other co-infections, and for studies of prevention strategies for malaria in pregnant women who are HIV-positive and living outside of Africa. Additional research is required on how to improve uptake of WHO's updated policy on IPTp with sulfadoxine-pyrimethamine and insecticide-treated nets.

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