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Donate today to support women in science at Burnet and their work to unlock the vaginal microbiome and reduce risk of HIV infection and preterm birth for women around the world.
BACKGROUND: Antibodies to the blood-stages of malaria enhance parasite-clearance and antimalarial efficacy. The antibody subclass and functions that contribute to parasite-clearance during anti-malarial treatment and their relationship with malaria transmission intensity have not been characterised. METHODS: IgG subclasses and C1q-fixation in response to P. falciparum merozoite antigens (EBA-175RIII-V, MSP-2 and MSP-142), and opsonic-phagocytosis of merozoites were measured in a multinational trial assessing the efficacy of artesunate across 11 South-East Asian sites. Regression analyses assessed the effects of antibody seropositivity on parasite-clearance half-life (hours)(PC(½)), PC(½)>/=5 hours, and day-3 parasitemia. RESULTS: IgG3, followed by IgG1, was the predominant IgG subclass detected (seroprevalence range IgG1: 5%-35% and IgG3: 27%-41%), varied across study-sites, and was lowest in study-sites with the lowest transmission intensity, and slowest mean PC(½). IgG3, C1q-fixation and opsonic-phagocytosis seropositivity were associated with faster PC(½) (mean reduction in PC(½) range 0.47-1.16 (hours), p-range: 0.001-0.03) and reduced odds of PC(½)>/=5 hours and day-3 parasitemia. CONCLUSIONS: Prevalence of IgG3, complement-fixing antibodies and merozoite phagocytosis vary according to transmission intensity, are associated with faster parasite-clearance and may be a sensitive surrogate of augmented clearance capacity of infected-erythrocytes. Determining the functional immune mechanisms associated with parasite-clearance will improve characterisation of artemisinin resistance.