Over 30 million pregnant women in malaria-endemic regions in Africa are exposed to malaria infection annually. Malaria in pregnancy is associated with pregnancy loss, preterm birth, low birth weight (LBW), fetal growth restriction, and infant and maternal anemia and maternal clinical illness; resulting in an estimated >10,000 maternal deaths and 75.000 – 200.000 infant deaths per year. The risk of malaria is higher in pregnant than in non-pregnant women, possibly due to immunological and hormonal changes occurring during pregnancy combined with the unique ability of a subset of red blood cells (erythrocytes) infected with the malaria parasite (Plasmodium) to hide away in the placenta. Considering its harmful effects on mother and her developing baby (foetus), malaria must always be adequately treated.
In principle malaria can nowadays be effectively treated with artemisinin-based combination therapy (ACT). However, concerns on the potential harm that new antimalarial treatments, including ACTs, may have on pregnant women or their unborn baby has led to their systematic exclusion from clinical trials, resulting in few human studies on the pharmacokinetics, safety and efficacy of ACTs in pregnancy. There is a need to increase the therapeutic options to treat malaria during the 2nd and 3rd trimester of pregnancy in the advent of reduction of efficacy of the existing antimalarials due to the spread of drug resistance. Recently a new ACT drug has become available to treat malaria, but this new combination, Pyronaridine-Artesunate -PYRAMAX® (PA), has not yet been extensively evaluated in pregnant women. The need for a novel therapeutic option to treat malaria during the 2nd and 3rd trimester of pregnancy as well, as the data on safety and efficacy of PA has led to the development and implementation of the PYRAPREG project; “Efficacy and Safety of a newly registered Artemisinin-Based Combination (Pyronaridine-Artesunate -PYRAMAX®) for the treatment of uncomplicated malaria in African pregnant women [2nd and 3rd trimester]”.
Although the PYRAPREG project made very good progress, its completion was halted due to the Covid19 pandemic. In particular follow up of children (1 year infant follow-up) and the corresponding data cleaning and analysis, including the pharmacokinetics research. Consequently, this important safety information could not be delivered and disseminated and this compromised achieving the safety objectives of the trial, mostly criticized by the malaria scientific community, as usually, trials do not plan to have infant safety outcomes. Furthermore, PhD students who were working in the context of PYRAPREG were not able to complete their studies. To circumvent these issues, PYRAPREG-extended project was designed as a1 year follow-up project that enabled us to complete our trial activities including a one year infant follow-up; data processing, entry, and cleaning; PK analysis; data analysis and write-up of the trial report; and completion of PhD studies.
