Cost-effectiveness of interventions preventing malaria during pregnancy

Background: Malaria remains a major threat during pregnancy, contributing to a wide range of adverse maternal and infant outcomes including severe clinical malaria infection, maternal anaemia, low birth weight and perinatal mortality. It was estimated that in 2020 there were 46.1 million pregnancies at risk of Plasmodium falciparum infection in the WHO AFRO region. Current preventive strategies rely primarily on insecticide-treated nets and intermittent preventive treatment with sulfadoxine–pyrimethamine (IPTp-SP) or daily cotrimoxazole (CTX) for women living with HIV. Growing resistance to SP in many settings threatens IPTp-SP efficacy and underscores the need to evaluate alternative approaches for protecting pregnant women and their infants. Methods: This thesis brings together several analytical components to strengthen the evidence base for interventions to prevent malaria during pregnancy. First, I conducted two cost-effectiveness analyses (CEAs) assessing potential replacements for IPTp-SP: a strategy of intermittent screening followed by treatment (ISTp), and the use of an alternative antimalarial drug regimen for IPTp. Second, I led a Delphi consultation with international experts to co-develop a comprehensive disease policy model for malaria in pregnancy, capturing a broad set of maternal and child health outcomes and key sources of heterogeneity. Finally, I applied the disease policy model, together with insights from the earlier analyses, to evaluate the cost-effectiveness of IPTp with dihydroartemisinin–piperaquine (DP) combined with CTX compared to CTX alone among pregnant women living with HIV in Kenya and Malawi, using data from the IMPROVE-2 trial. Results: The cost-effectiveness analysis of ISTp versus IPTp-SP showed that at current levels of drug resistance in West Africa, this strategy incurred additional costs without measurable health gains, indicating that it is unlikely to be cost-effective. The analysis provided crucial evidence presented in 2015 at a WHO evidence review group meeting. The economic evaluation of IPTp-DP using data pooled across three trials suggested promising results over IPTp-SP; however, more recent evidence has highlighted important uncertainties, including possible negative effects on child health outcomes outweighing the superior antimalarial efficacy of IPTp-DP. The Delphi process produced the first structured, expert-informed disease policy model of malaria in pregnancy, reflecting the complexity of its consequences across both maternal and infant populations. It also was the first formal attempt to co-develop a disease model of this kind in a disease area predominantly prevalent in low- and middle income countries. Applying the expert-informed conceptual model to the cost-effectiveness of IPTp-DP in addition to CTX in HIV positive pregnant women revealed that a substantial proportion of malaria exposure occurs before women typically make their first antenatal care visit, limiting interventions’ ability to influence miscarriage, stillbirth, and other health outcomes. Despite these constraints, IPTp-DP plus CTX was cost-effective in Kenya across most cost-effectiveness thresholds, with modest but meaningful reductions in malaria exposure and DALYs, and producing cost-savings for households. Conclusions: Together, this multi-component PhD research project brings together empirical evidence and methodological contributions to support decision-making on prevention of malaria in pregnancy, particularly in the context of rising drug resistance and emerging alternative regimens. Collectively, these contributions strengthen the evidence base for interventions to prevent malaria in pregnancy, and present a methodological approach that demonstrates a transferrable way to co-develop disease models with experts across a wide range of health conditions. Lastly, the model’s ability to capture accumulated exposure from conception highlights that earlier initiation of malaria prevention - ideally in the first trimester - is likely essential to achieve larger and measurable health gains in this highly vulnerable population.