Persistent Plasmodium falciparum infections enhance transmission-reducing immunity development

Subclinical infections that serve as reservoir populations to drive transmission remain a hurdle to malaria control. Data on infection dynamics in a geographical area is required to strategically design and implement malaria interventions. In a longitudinal cohort, we monitored Plasmodium falciparum infection prevalence and persistence, and anti-parasite immunity to gametocyte and asexual antigens for 10 weeks. Of the 100 participants, only 11 were never infected, whilst 16 had persistent infections detected by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), and one participant had microscopic parasites at all visits. Over 70% of the participants were infected three or more times, and submicroscopic gametocyte prevalence was high, >= 48% of the parasite carriers. Naturally induced responses against recombinant Pfs48/45.6C, Pfs230proC, and EBA175RIII-V antigens were not associated with either infection status or gametocyte carriage, but the antigen-specific IgG titers inversely correlated with parasite and gametocyte densities consistent with partial immunity. Longitudinal analysis of gametocyte diversity indicated at least four distinct clones circulated throughout the study period. The high prevalence of children infected with distinct gametocyte clones coupled with marked variation in infection status at the individual level suggests ongoing transmission and should be targeted in malaria control programs.

Automated summary

Subclinical infections continue to pose a challenge to malaria control efforts, as reservoir populations contribute to ongoing transmission. Data on infection dynamics in specific geographical areas is important for designing and implementing strategic interventions. In a longitudinal cohort study, it was found that the majority of participants were infected multiple times with Plasmodium falciparum, and there was a high prevalence of submicroscopic gametocytes. Immune responses to specific antigens did not correlate with infection status or gametocyte carriage, but antibody levels were inversely related to parasite and gametocyte densities, suggesting partial immunity. Longitudinal analysis revealed the circulation of at least four distinct gametocyte clones over the study period. The findings indicate the need to target ongoing transmission, particularly in children, in malaria control programs.