Malaria in pregnancy - IMPROVE project
Malaria in pregnancy is estimated to be responsible for 35% of newborns with preventable low birth weight. Low birth weight is a strong predictor of infant mortality, childhood morbidity and productivity in adult life. WHO recommends sulphadoxine-pyrimethamine (SP) for women without malaria symptoms as preventive treatment in pregnancy (IPTp). However, its efficacy is threatened by increasing SP resistance, while there are no acceptable alternatives. Over the last decade, several IPTp trials showed that neither amodiaquine, nor mefloquine, nor chloroquine-azithromycin is a suitable replacement for SP because of their poor tolerability for pregnant women. Furthermore, intermittent screening for malaria and treatment with artemisinin-based combination therapies has shown to be non-superior to IPTp-SP even in areas with very high SP resistance.
The IMPROVE project, led by Professor Feiko ter Kuile (Liverpool School of Tropical Medicine, United Kingdom), aims to address this clear and urgent need for alternative drugs for malaria prevention in pregnancy. Two earlier exploratory trials from Kenya and Uganda showed that dihydroartemisinin-piperaquine (DP) has the potential to replace SP for malaria prevention in pregnancy. It was more effective than SP in reducing malaria infection and clinical malaria. As both trials were small and not powered to assess birth outcomes, WHO concluded in 2015 that definitive multi-centre trials were needed before IPTp-DP can be recommended for health care use.
Therefore, IMPROVE will evaluate the use of DP (with and without azithromycin), as an alternative to SP for intermittent preventive treatment (IPTp) for control of malaria in pregnancy. The project received a €7.4 million grant from EDCTP and is a collaboration of partners from Denmark, Finland, Kenya, Malawi, Norway, Tanzania and the United Kingdom. Additional funding of £2.7 million was provided by the Joint Global Health Trials, a partnership of the UK Department for International Development, the UK medical Research Council, the National Istitute for Health research and the Wellcome Trust. The grant made it possible to include a trial with HIV-infected pregnant women alongside the main study with HIV-uninfected participants. The project aims to provide WHO with definitive evidence to determine whether IPTp with DP (with or without AZ), is a viable alternative to the IPTp with SP. A positive result would improve the outcome of pregnancies in areas of the world with moderate to high malaria transmission and high parasite resistance to SP.