Effect of Seasonal Malaria Chemoprevention on Immune Markers of Exhaustion and Regulation

Abstract

Background Seasonal malaria chemoprevention (SMC) is a novel strategy to reduce malaria infections in children. Infection with Plasmodium falciparum results in immune dysfunction characterized by elevated expression of markers associated with exhaustion, such as PD1 and LAG3, and regulatory CD4+FOXP3+ T cells. Methods In the current study, the impact of seasonal malaria chemoprevention on malaria-induced immune dysfunction, as measured by markers associated with exhaustion and regulatory T cells, was explored by flow cytometry. Results Children that received seasonal malaria chemoprevention had fewer malaria episodes and showed significantly lower fold changes in CD4+PD1+ and CD4+PD1+LAG3+ compared to those that did not receive SMC. Seasonal malaria chemoprevention had no observable effect on fold changes in CD8 T cells expressing PD1 or CD160. However, children receiving SMC showed greater increases in CD4+FOXP3+ T regulatory cells compared to children not receiving SMC. Conclusions These results provide important insights into the dynamics of malaria-induced changes in the CD4 T-cell compartment of the immune system and suggest that the reduction of infections due to seasonal malaria chemoprevention may also prevent immune dysfunction. Clinical Trials Registration NCT02504918.

Evolution of Malaria Incidence in Five Health Districts, in the Context of the Scaling up of Seasonal Malaria Chemoprevention, 2016 to 2018, in Mali

“…After the administration of SMC, the authors of a study in Ouessebougou in central Mali measured the level of IgG-type antibodies against specific malaria antigens. These results show the presence of the antibodies [ 10 ]. However, the IgG amount was not proportional to the number of passages received by the child but was higher compared to children who did not receive SMC [ 16 ].…”

“…This strategy consists of administering a single dose of SP and a dose of Amodiaquine for three days, in four rounds, to children aged 3–59 months and, recently, 5 to 10 years old [ 10 , 11 ]. SMC pilot studies showed encouraging results, with a reduction in the number of malaria and anemia cases in children aged 6–59 months.…”

“…SMC has been recommended by the WHO since 2012 in Sahelian countries, where more than 60% of clinical malaria cases occur within a maximum of four months [5,8,9]. This strategy consists of administering a single dose of SP and a dose of Amodiaquine for three days, in four rounds, to children aged 3-59 months and, recently, 5 to 10 years old [10,11]. SMC pilot studies showed encouraging results, with a reduction in the number of malaria and anemia cases in children aged 6-59 months.…”

Seasonal Malaria Chemoprevention Implementation: Effect on Malaria Incidence and Immunity in a Context of Expansion of P. falciparum Resistant Genotypes with Potential Reduction of the Effectiveness in Sub-Saharan Africa

“…Mali was one of the first countries in the Sahel region to implement SMC in 2012, which has now been gradually rolled out to cover the entire country. 8 As of 2020, 13 countries have adopted SMC (Benin, Burkina Faso, Cameroon, Chad, Gambia, Ghana, Guinea, Guinea Bissau, Mali, Niger, Nigeria, Senegal, and Togo) at different scales of implementation. 9 Several studies in Africa have shown that this intervention is cost-effective, safe, and feasible for the prevention of malaria among children in areas with highly seasonal malaria transmission.…”