Identification of the asymptomatic Plasmodium falciparum and Plasmodium vivax gametocyte reservoir under different transmission intensities

Background Understanding epidemiological variables affecting gametocyte carriage and density is essential to design interventions that most effectively reduce malaria human-to-mosquito transmission. Methodology/Principal findings Plasmodium falciparum and P. vivax parasites and gametocytes were quantified by qPCR and RT-qPCR assays using the same methodologies in 5 cross-sectional surveys involving 16,493 individuals in Brazil, Thailand, Papua New Guinea, and Solomon Islands. The proportion of infections with detectable gametocytes per survey ranged from 44-94% for P. falciparum and from 23-72% for P. vivax. Blood-stage parasite density was the most important predictor of the probability to detect gametocytes. In moderate transmission settings (prevalence by qPCR>5%), parasite density decreased with age and the majority of gametocyte carriers were children. In low transmission settings (prevalence<5%), >65% of gametocyte carriers were adults. Per survey, 37-100% of all individuals positive for gametocytes by RT-qPCR were positive by light microscopy for asexual stages or gametocytes (overall: P. falciparum 178/348, P. vivax 235/398). Conclusions/Significance Interventions to reduce human-to-mosquito malaria transmission in moderate-high endemicity settings will have the greatest impact when children are targeted. In contrast, all age groups need to be included in control activities in low endemicity settings to achieve elimination. Detection of infections by light microscopy is a valuable tool to identify asymptomatic blood stage infections that likely contribute most to ongoing transmission at the time of sampling. Author summary Plasmodium vivax and Plasmodium falciparum cause the vast majority of all human malaria cases. Across all transmission settings, a large proportion of infections of the two species remain asymptomatic. These infections are not diagnosed and treated by control programs focusing on clinical cases. They can carry gametocytes, the sexual stage of the parasite that establishes infections in mosquitos, thus asymptomatic infections contribute to transmission. In order to determine who is likely to contribute to transmission, gametocyte densities were measured by sensitive molecular methods in afebrile individuals in four countries. The proportion of infections with gametocytes varied greatly among surveys, and was higher in regions that had experienced low transmission for extended periods of time. In moderate-high transmission settings, gametocyte densities were particularly high in children below six years, highlighting the importance that interventions to reduce transmission include this age group. The majority of gametocyte carriers was positive by light microscopy. The comprehensive data on gametocyte carriage presented here lays the foundation for the development of more effective screen and treat activities to reduce malaria transmission.