Possible effect of neutropenia on the efficacy of artemisinin-based combination therapy in pregnant women in Mali

Reducing the burden of malaria in pregnant women remains a major challenge for control programmes. Decreasing immunity may increase the vulnerability of pregnant women to infectious diseases, including malaria. In this study, the effects of neutropenia on the effectiveness of artemisinin-based combination therapy (ACTs) in clearing current Plasmodium falciparum infections and preventing reinfection after treatment were investigated. Data for this study were obtained within the context of a clinical trial evaluating the efficacy of pyronaridine-artesunate compared with other ACTs for treating malaria infection in pregnant African women. The participants were treated with artemether-lumefantrine (AL, n = 188), dihydroartemisinin-piperaquine (DP, n = 183), or pyronaridine-artesunate (PA, n = 174) and were followed for 63 days after treatment. The dynamics of neutrophil percentages in the peripheral blood of participants were measured during the 63-day follow-up. Pregnant women were classified as either neutropenic or nonneutropenic on the basis of their neutrophil counts at enrolment. A chi-square test was used to compare adequate clinical and parasitological response (ACPR) on Day 28 in the different treatment groups according to neutrophil status. Without molecular correction on Day 28, the rate of ACPR was significantly greater in nonneutropenic pregnant women (96.6%; 54/56) than in neutropenic pregnant women (87.0%; 114/131) in the AL arm (p = 0.038). In contrast, ACPR did not vary significantly according to neutrophil status in the DP or PA treatment arms. In the DP treatment arm, ACPR was 97.2% (105/108) and 98.6% (73/74) in neutropenic and nonneutropenic pregnant women, respectively (p = 0.463). In the PA treatment arm, it was 99.1% (105/106) versus 98.5% (66/67) in neutropenic and nonneutropenic pregnant women, respectively (p = 0.851). Molecular analysis revealed that there was no recrudescence during the 28-day follow-up, regardless of the treatment arm. The findings suggest that the prophylactic efficacy of AL, but not of DP or PA, is decreased in neutropenic pregnant women. The study was registered with the Pan African Clinical Trial Registry (PACTR202011812241529) on 30 November 2020.