Neutropenia and its possible effect on the effectiveness of artemisinin-based combination therapy in pregnant women in Mali

Background Reducing the burden of malaria in pregnant women remains a serious challenge for control programmes. A possible waning in immunity makes pregnant women more vulnerable to infectious diseases, including malaria. In this study, the effect of neutropenia on artemisinin-based combination therapy (ACTs) effectiveness in clearing current Plasmodium falciparum infection and preventing reinfection after treatment was investigated. Methods Data for this study were obtained within the context of a clinical trial evaluating the efficacy of pyronaridine-artesunate compared to other ACTs to treat malaria infection in African pregnant women (PYRAPREG). Participants were treated with either artemether-lumefantrine (AL, n1 = 188), dihydroartemisinin-piperaquine (DP, n2 = 183), or pyronaridine-artesunate (PA, n3 = 174) and were followed for 63 days after treatment. Dynamics of neutrophil levels in the peripheral blood of the participants were measured during the 63-day follow-up. Based on the neutrophil counts, the pregnant women were classified as either neutropenic or non-neutropenic. A chi-square test was used to compare adequate clinical and parasitological response (ACPR) rate according to neutrophil status. Results Without molecular correction at Day 28, the rate of ACPR was higher in the non-neutropenic pregnant women 96.6% (54/56) compared to neutropenic pregnant women 87.0% (114/131) in the AL arm; p = 0.038. However, ACPR did not vary according to neutrophil status in DP and PA treatment arms. In the DP treatment arm, ACPR was 97.2% (105/108) versus 98.6% (73/74) respectively in neutropenic and non-neutropenic pregnant women (p = 0.463). In the PA treatment arm, it was 99.1% (105/106) versus 98.5% (66/67) respectively in neutropenic and non-neutropenic pregnant women (p = 0.851). Molecular analysis revealed that there was no recrudescence during the 28-day follow-up, regardless of the treatment arm. Conclusion The findings suggest that lower peripheral blood neutrophil levels may decrease the prophylactic effectiveness of AL but not of DP or PA in pregnant women.