Two international scientific studies published in 2025, with the prominent involvement of GHTM | IHMT-NOVA, reveal concerning signs that the malaria parasite, Plasmodium falciparum, is developing resistance to two of the main drugs used in Africa.
The studies, published in the journals Nature Communications and The Journal of Infectious Diseases, were led by José Pedro Gil, a researcher at GHTM and at the Karolinska Institute in Stockholm, heading a network of collaborations with African and European institutions.
One of the studies, conducted in Mali and funded by EDCTP and the Foundation for Science and Technology (FCT), analysed the effectiveness of treatment with dihydroartemisinin-piperaquine (DHA-PPQ), one of the most promising drugs for malaria prevention in children and pregnant women. The researchers monitored hundreds of children treated with DHA-PPQ over two years and observed that protection against new infections significantly decreased over time. The main cause identified was the selection of parasites with multiple copies of the pfpm3 gene, associated with piperaquine resistance. These parasites became more frequent following repeated use of the drug, compromising its preventive effectiveness. This phenomenon raises concerns about the future of chemoprevention strategies in Africa, such as intermittent preventive treatment in pregnant women and seasonal malaria chemoprevention in children, both of which rely on the prolonged efficacy of this drug.
The other study, supported by the Aga Khan Development Network (AKD), FCT, and the Calouste Gulbenkian Foundation, was conducted in Angola and evaluated the effectiveness of treatment with artemether-lumefantrine (AL), the most widely used antimalarial in Africa. The clinical trial involved 100 children with uncomplicated malaria, treated under direct supervision. The results showed that around 35% of the children were infected with parasites carrying additional copies of the pfmdr1 gene, a genetic marker associated with lumefantrine resistance. These children had a significantly lower cure rate after 42 days. The study also demonstrated that even a small proportion of resistant parasites within an infection can compromise treatment success, highlighting the need for ongoing genomic surveillance.
The involvement of GHTM | IHMT-NOVA was decisive for the development of these studies, resulting from a long-established collaboration with the Karolinska Institute in the field of malaria research, contributing to specialised expertise in the molecular characterisation of parasites and the integrated analysis of the data obtained. This involvement reinforces the institute’s commitment to research applied to public health and highlights its leading position on the international stage of tropical disease research. The results now published demonstrate the importance of scientific collaboration between institutions from different regions of the world to address emerging challenges such as antimalarial drug resistance.