The complex relationship of exposure to new infections and incidence of clinical malaria in Papua New Guinea.

Unlabelled: The molecular force of blood-stage infection (FOB) is a quantitative surrogate metric for malaria transmission at population level and for exposure at individual level. Relationships between FOB, parasite prevalence and clinical incidence were assessed in a treatment-to-reinfection cohort, where () hypnozoites were eliminated in half the children by primaquine (PQ). Discounting relapses, children acquired equal numbers of new () and blood-stage infections/year (FOB = 0-18, FOB = 0-23) resulting in comparable spatial and temporal patterns in incidence and prevalence of infections. Including relapses, FOB increased >3 fold (relative to PQ-treated children) showing greater heterogeneity at individual (FOB = 0-36) and village levels. and FOB were strongly associated with clinical episode risk. Yearly clinical incidence rate (IR = 0.28) was higher than for (IR = 0.12) despite lower FOB. These relationships between FOB, clinical incidence and parasite prevalence reveal a comparable decline in and transmission that is normally hidden by the high burden of relapses.

Clinical Trial Registration: ClinicalTrials.gov NCT02143934.