Higher platelet counts and platelet factors are associated with a reduction in Plasmodium falciparum parasite density in young Malian children.

OBJECTIVES: The association between thrombocytopenia and parasite density or disease severity is described in numerous studies. In recent years, several studies described the protective role of platelets in directly killing Plasmodium parasites, mediated by platelet factor 4 (PF4) binding to Duffy antigen. This study aimed to evaluate the protective role of platelets in young children who are Duffy antigen-negative, such as those in sub-Saharan Africa. METHODS: A zero-inflated negative binomial model was used to relate platelet count and parasite density data collected in a longitudinal birth cohort. Platelet factors were measured by enzyme-linked immunosorbent assay in samples collected from malaria-infected children who participated in a cross-sectional study. RESULTS: We described that an increase of 10,000 platelets/µl was associated with a 2.76% reduction in parasite count. Increasing levels of PF4 and CXCL7 levels were also significantly associated with a reduction in parasite count. CONCLUSIONS: Platelets play a protective role in reducing parasite burden in Duffy-negative children, possibly mediated through activation of the innate immune system.

Acquisition of antibodies that block Plasmodium falciparum adhesion to placental receptor chondroitin sulfate A with increasing gravidity in Malian women.

In malaria-endemic areas, pregnant women are more susceptible to Plasmodium falciparum infection, especially primigravidae. During pregnancy, parasites sequester in the placenta and bind to the receptor chondroitin sulfate (CSA). This unique adhesion is mediated by the parasite protein VAR2CSA expressed on the surface of infected erythrocytes (IE). Placental malaria is associated with poor pregnancy outcomes including perinatal mortality, preterm delivery, small for gestational age (SGA) and low birthweight deliveries. Over successive pregnancies, women acquire functional antibodies that inhibit IE adhesion to CSA. Here, we examine the development of anti-adhesion activity and the breadth of anti-adhesion activity as a function of number of previous pregnancies, using samples collected from pregnant women living in an area with high seasonal malaria transmission. Women reached plateau levels of anti-adhesion activity and breadth of anti-adhesion activity after 5 pregnancies. We related the level of anti-adhesion activity and reactivity with surface IE to SGA 19/232 pregnancies resulted in SGA, and report that an increase of 10% in median anti-adhesion activity reduced the odds of SGA by 13% and this relationship approached significance. Further, at an anti-adhesion activity level of 43.7%, an increase of 10% in the breadth of activity significantly reduced the odds of SGA by 21.5%. Antibodies that recognize IE surface increased over successive pregnancies, but were not associated with a reduction in SGA. These results can serve as a guideline for assessing vaccine candidates aiming to reduce poor pregnancy outcomes associated with placental malaria.

Effect of seasonal malaria chemoprevention on the acquisition of antibodies to Plasmodium falciparum antigens in Ouelessebougou, Mali.

BACKGROUND: Seasonal malaria chemoprevention (SMC) is a new strategy to reduce malaria burden in young children in Sahelian countries. It consists of the administration of full treatment courses of sulfadoxine-pyrimethamine plus amodiaquine to children at monthly intervals during the malaria season. However, it is not clear if there is a cumulative effect of SMC over time on acquisition of antibodies to malaria antigens. METHODS: A cross-sectional serosurvey was carried out 1 month after the last dose of SMC in 2016. Children aged 3-4 years were randomly selected from areas where SMC was given for 1, 2 or 3 years during the malaria season. Children in the areas where SMC had been implemented for 1 year but who failed to receive SMC were used as comparison group. Antibody extracted from dry blood spots was used to measure IgG levels to CSP, MSP-142 and AMA1. RESULTS: The prevalence of antibodies to AMA-1 were high and similar in children who received SMC for 1, 2 or 3 years and also when compared to those who never received SMC (96.3 vs 97.5%, adjusted OR = 0.99, 95% CI 0.33-2.97, p = 0.99). The prevalence of antibodies to MSP-142 and to CSP were similar in children that received SMC for 1, 2 or 3 years, but were lower in these children compared to those who did not receive SMC (87.1 vs 91.2%, adjusted OR = 0.55, 95% CI 0.29-1.01, p = 0.05 for MSP-142; 79.8 vs 89.2%, adjusted OR = 0.52, 95% CI 0.30-0.90, p = 0.019 for CSP). CONCLUSIONS: SMC reduced seropositivity to MSP-142 and CSP, but the duration of SMC did not further reduce seropositivity. Exposure to SMC did not reduce the seropositivity to AMA1.