Modelling the epidemiology of residual Plasmodium vivax malaria in a heterogeneous host population: A case study in the Amazon Basin.

The overall malaria burden in the Americas has decreased dramatically over the past two decades, but residual transmission pockets persist across the Amazon Basin, where Plasmodium vivax is the predominant infecting species. Current elimination efforts require a better quantitative understanding of malaria transmission dynamics for planning, monitoring, and evaluating interventions at the community level. This can be achieved with mathematical models that properly account for risk heterogeneity in communities approaching elimination, where few individuals disproportionately contribute to overall malaria prevalence, morbidity, and onwards transmission. Here we analyse demographic information combined with routinely collected malaria morbidity data from the town of Mâncio Lima, the main urban transmission hotspot of Brazil. We estimate the proportion of high-risk subjects in the host population by fitting compartmental susceptible-infected-susceptible (SIS) transmission models simultaneously to age-stratified vivax malaria incidence densities and the frequency distribution of P. vivax malaria attacks experienced by each individual over 12 months. Simulations with the best-fitting SIS model indicate that 20% of the hosts contribute 86% of the overall vivax malaria burden. Despite the low overall force of infection typically found in the Amazon, about one order of magnitude lower than that in rural Africa, high-risk individuals gradually develop clinical immunity following repeated infections and eventually constitute a substantial infectious reservoir comprised of asymptomatic parasite carriers that is overlooked by routine surveillance but likely fuels onwards malaria transmission. High-risk individuals therefore represent a priority target for more intensive and effective interventions that may not be readily delivered to the entire community. Author summary: Malaria transmission models that disregard risk heterogeneity at the community level, classifying individuals as uniformly susceptible or infected, may not properly recapitulate the epidemiology of malaria in real-life settings. Here we fit a compartmental susceptible-infected-susceptible model to malaria morbidity data from Mâncio Lima, the main urban transmission hotspot of Brazil, and estimate that 20% of the urban residents contribute 86% of the overall vivax malaria burden in the town. Despite the low average force of infection, one order of magnitude lower that in rural Africa, high-risk individuals experience enough repeated infections to develop clinical immunity and constitute an asymptomatic reservoir that fuels onwards malaria transmission. Therefore, these high-risk subjects account for the paradoxical finding of clinical immunity and frequent asymptomatic parasite carriage in low-endemicity Amazonian communities. We argue that mathematical models accounting for risk heterogeneity are crucial to plan and evaluate malaria control and elimination interventions targeted to high-risk groups in communities, municipalities, and regions. [ABSTRACT FROM AUTHOR]