Neutrophil levels and artemisinin-based combination therapy efficacy in the treatment of Plasmodium falciparum infections in vulnerable populations in Mali

Reducing the burden of malaria among pregnant women and children remains a major public health challenge in many African countries. Beside malaria, undernourishment (low weight) in children is also a major cause of morbidity and mortality in low-income countries. Neutrophils, the most abundant white blood cells of our immune system, play a fundamental role in the innate immune defense. Artemisinin-based combination therapies (ACTs) are drugs recommended by the World Health Organization for the treatment of uncomplicated malaria. In this thesis, the effect of neutropenia or weight deficiency in the efficacy of these drugs in eliminating current Plasmodium falciparum (parasite causing malaria) infection and preventing reinfection after treatment was investigated.
We have conducted clinical trials in which malaria-infected pregnant women and children were treated with various ACTs: artemether - lumefantrine (AL), dihydroartemisinin - piperaquine (DP), artesunate-amodiaquine (ASAQ) or pyronaridine – artesunate (PA) and followed for 42 to 63 days after treatment (according to studies). Based on neutrophil levels in peripheral blood, patients were classified as neutropenic or non-neutropenic.
Our data show that pregnancy may induce the production of neutrophils that are subsequently continuously released into the circulation. It’s also suggested that neutropenia may decrease the prophylactic efficacy of AL in pregnant women as well as in children. Contrary to neutropenia, this thesis shows that weight deficiency does not reduce the efficacy of ACTs.
The results presented in this thesis elucidate the need to consider patient’s neutrophil levels in the choice of ACTs recommended to treat malaria in pregnant women and children.