Population heterogeneity in Plasmodium vivax relapse risk.

A key characteristic of Plasmodium vivax parasites is their ability to adopt a latent liver-stage form called hypnozoites, able to cause relapse of infection months or years after a primary infection. Relapses of infection through hypnozoite activation are a major contributor to blood-stage infections in P vivax endemic regions and are thought to be influenced by factors such as febrile infections which may cause temporary changes in hypnozoite activation leading to 'temporal heterogeneity' in reactivation risk. In addition, immunity and variation in exposure to infection may be longer-term characteristics of individuals that lead to 'population heterogeneity' in hypnozoite activation. We analyze data on risk of P vivax in two previously published data sets from Papua New Guinea and the Thailand-Myanmar border region. Modeling different mechanisms of reactivation risk, we find strong evidence for population heterogeneity, with 30% of patients having almost 70% of all P vivax infections. Model fitting and data analysis indicates that individual variation in relapse risk is a primary source of heterogeneity of P vivax risk of recurrences. Trial Registration: ClinicalTrials.gov NCT01640574, NCT01074905, NCT02143934. Author summary: Despite elimination efforts, malaria continues to be a public health burden world-wide. Partially due to its ability to remain dormant in the liver for weeks or months, the malaria parasite Plasmodium vivax has not responded well to elimination efforts. These dormant parasites may reactivate and thereby cause disease and contribute to further transmission of the disease. Though it is often assumed that reactivations of dormant P vivax parasites occur at a constant rate, it has also been proposed that there is a time of increased risk of reactivation ('temporal heterogeneity') and there may be differences in individual's reactivation risks ('population heterogeneity'). We created models for constant reactivations, temporal heterogeneity, and population heterogeneity which we use to analyse data of P vivax malaria events from the Thailand-Myanmar border region and Papua New Guinea. We find strong evidence for population heterogeneity as a major determinant of reactivation patterns. Further analysis of the data suggests that spatial heterogeneity in exposure to infectious mosquito bites is a potential contributor to this heterogeneity. Thus, we find that population heterogeneity plays an important role in the overall epidemiology of P vivax recurrences. [ABSTRACT FROM AUTHOR]