Assessment of the impact of pregnancy and malaria infection on the variation of neutrophil levels in women from San, Mali.

BACKGROUND: In patients with severe neutropenia, infections can rapidly become serious and life-threatening. It is essential to understand whether pregnancy induces changes in neutrophil levels thereby posing an increased threat to the health of gravidae. METHODOLOGY: This cross-sectional study was conducted in San Health District (Mali) and involved pregnant women infected or not by malaria parasites and non-pregnant healthy volunteers. Subjects were categorized as having neutropenia, normal neutrophil levels, and neutrophilia regarding their neutrophil levels. A logistic regression analysis was performed to determine factors associated with neutrophil level variation in pregnant women. RESULTS: Whether or not the pregnant women were infected with malaria, 98 of the 202 cases (48.5%) showed neutrophilia. Surprisingly, 67 of the 71 cases of neutropenia (94.4%) observed in this study concerned healthy people who were not pregnant. The mean percentage of neutrophil levels was significantly (p < 0.001) lower (49.9%) in the first trimester compared to the second trimester of pregnancy (62.0%). A logistic regression model showed that compared to early pregnancy, the second (OR = 12.9, 95% CI 2.2-248.1, p = 0.018) and the third trimesters (OR = 13.7, 95% CI 2.3-257.5, p = 0.016) were strongly associated with the increase of neutrophil levels. CONCLUSIONS: Pregnancy can induce the production of mature neutrophils that are continually released into circulation. Neutrophil levels were lower during the first trimester of the pregnancy compared to the second and third trimesters, but not affected by the presence or absence of malaria infection.

Efficacy and safety of pyronaridine-artesunate (PYRAMAX) for the treatment of P. falciparum uncomplicated malaria in African pregnant women (PYRAPREG): study protocol for a phase 3, non-inferiority, randomised open-label clinical trial.

INTRODUCTION: Malaria infection during pregnancy increases the risk of low birth weight and infant mortality and should be prevented and treated. Artemisinin-based combination treatments are generally well tolerated, safe and effective; the most used being artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP). Pyronaridine-artesunate (PA) is a new artemisinin-based combination. The main objective of this study is to determine the efficacy and safety of PA versus AL or DP when administered to pregnant women with confirmed Plasmodium falciparum infection in the second or third trimester. The primary hypothesis is the pairwise non-inferiority of PA as compared with either AL or DP. METHODS AND ANALYSIS: A phase 3, non-inferiority, randomised, open-label clinical trial to determine the safety and efficacy of AL, DP and PA in pregnant women with malaria in five sub-Saharan, malaria-endemic countries (Burkina Faso, Democratic Republic of the Congo, Mali, Mozambique and the Gambia). A total of 1875 pregnant women will be randomised to one of the treatment arms. Women will be actively monitored until Day 63 post-treatment, at delivery and 4-6 weeks after delivery, and infants' health will be checked on their first birthday. The primary endpoint is the PCR-adjusted rate of adequate clinical and parasitological response at Day 42 in the per-protocol population. ETHICS AND DISSEMINATION: This protocol has been approved by the Ethics Committee for Health Research in Burkina Faso, the National Health Ethics Committee in the Democratic Republic of Congo, the Ethics Committee of the Faculty of Medicine and Odontostomatology/Faculty of Pharmacy in Mali, the Gambia Government/MRCG Joint Ethics Committee and the National Bioethics Committee for Health in Mozambique. Written informed consent will be obtained from each individual prior to her participation in the study. The results will be published in peer-reviewed open access journals and presented at (inter)national conferences and meetings. TRIAL REGISTRATION NUMBER: PACTR202011812241529.

Differential Incidence of Malaria in Neighboring Villages in a High-Transmission Setting of Southern Mali.

Throughout a phase IIIb/IV efficacy study of repeated treatment with four artemisinin-based combination therapies, significant heterogeneity was found in the number of clinical episodes experienced by individuals during the 2-year follow-up. Several factors, including host, parasite, and environmental factors, may contribute to the differential malaria incidence. We aimed to identify risk factors of malaria incidence in the context of a longitudinal study of the efficacy of different artemisinin-based combination therapy regimens in Bougoula-Hameau, a high-transmission setting in Mali. Risk factors including age, residence, and treatment regimen were compared among individuals experiencing eight or more clinical episodes of malaria ("high-incidence group") and individuals experiencing up to three clinical episodes ("low-incidence group"). Consistent with the known association between age and malaria risk in high-transmission settings, individuals in the high incidence group were significantly younger than individuals in the low-risk group (mean age, 7.0 years versus 10.6 years, respectively; t-test, P < 0.0001). Compared with individuals receiving artemether-lumefantrine, those receiving artesunate-amodiaquine had greater odds of being in the high-incidence group (odds ratio [OR], 2.24; 95% CI, 1.03 - 4.83, P = 0.041), while individuals receiving dihydroartemisinin-piperaquine had a lower odds of being in high incidence group (OR: 0.30, 95% CI, 0.11-0.85; P = 0.024). Individuals residing in the forested areas of Sokourani and Karamogobougou had significantly greater odds of being in the high-incidence group compared with individuals residing in the semi-urban area of Bougoula-Hameau 1 (Karamogobougou: OR, 3.68; 95% CI, 1.46-9.31; P = 0.0059; Sokourani: OR, 11.46; 95% CI, 4.49-29.2; P < 0.0001). This study highlights the importance of fine-mapping malaria risks even at sub-district levels for targeted and customized interventions.