Variation in Neutrophil Levels and Artemisinin-Based Combination Therapy Efficacy in West-africa

Background White blood cells, including abundant neutrophils, constitute the first line of innate defence against pathogens. Neutrophils are involved in pathogen clearance by phagocytosis. However, their role on malaria parasite clearance and on the efficacy of Artemisinin-based Combination Therapy (ACT) are poorly understood.MethodsIn a prospective longitudinal in vivo study, conducted from 2010 to 2014 in Mali, Burkina Faso and Guinea, in which 5360 malaria cases were enrolled, neutrophil rates were compared with malaria carriage after treatment with different ACTs. i.e. Artemether - lumefantrine (AL), Artesunate - amodiaquine (ASAQ), Dihydroartemisinin - piperaquine (DHAPQ) or Pyronaridine artesunate (PA). Depending on the level of neutrophils in the blood, study cases were classified as having neutropenia, normal neutrophils level or neutrophilia. A secondary analysis on data of 4845 cases was performed using R ggplot2 statistical package to compare the post treatment neutrophil levels means and standard deviation between different treatment arms at subsequent malaria episodes.ResultsMicroscopy showed that at day 7 only 4 patients in the neutropenia group and treated with AL had a malaria positive blood smear. At Day 28, rate of recurrent parasitemia in the AL arm was significantly higher in cases with neutropenia (50.9%) versus in cases with normal rates of neutrophils (43.1%) and in patients with neutrophilia (6%) (p<0.001). For patients treated with ASAQ, the rate of recurrent parasitemia was 58.8% in the neutropenia group versus 29.4% in patients with normal rates of neutrophils and 11.8% in patients with neutrophilia (p<0.001). No patient treated with DHAPQ with normal neutrophil counts or neutrophilia was carrying malaria parasites at Day 28. Compared to adults, under 5 years old children were shown to be at risk of malaria parasite reappearance at post treatment Day 28 (OR = 5.64, p = 0.04). Regardless of the ACT used in this study, we observed a significant decrease of neutrophil levels at day 3 post-treatment. Furthermore, regardless the ACT used, an increase in the prevalence of gametocytemia was found in the neutropenic group.ConclusionPatients with neutropenia had higher rates of recurrent parasitemia after artemisinin-based combination therapy. Parasite recurrence in patients with neutropenia was faster after treatment with AL.