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

The molecular force of blood-stage infection ((mol)FOB) is a quantitative surrogate metric for malaria transmission at population level and for exposure at individual level. Relationships between (mol)FOB, parasite prevalence and clinical incidence were assessed in a treatment-to-reinfection cohort, where P.vivax (Pv) hypnozoites were eliminated in half the children by primaquine (PQ). Discounting relapses, children acquired equal numbers of new P. falciparum (Pf) and Pv blood-stage infections/year (Pf-(mol)FOB = 0–18, Pv-(mol)FOB = 0–23) resulting in comparable spatial and temporal patterns in incidence and prevalence of infections. Including relapses, Pv-(mol)FOB increased >3 fold (relative to PQ-treated children) showing greater heterogeneity at individual (Pv-(mol)FOB = 0–36) and village levels. Pf- and Pv-(mol)FOB were strongly associated with clinical episode risk. Yearly Pf clinical incidence rate (IR = 0.28) was higher than for Pv (IR = 0.12) despite lower Pf-(mol)FOB. These relationships between (mol)FOB, clinical incidence and parasite prevalence reveal a comparable decline in Pf and Pv transmission that is normally hidden by the high burden of Pv relapses. Clinical trial registration: ClinicalTrials.gov NCT02143934