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Plasmodium vivax has the ability to relapse from dormant parasites in the liver weeks or months after inoculation, causing further blood-stage infection and potential onward transmission. Estimates of the force of blood-stage infections arising from primary infections and relapses are important for designing intervention strategies. However, in endemic settings their relative contributions are unclear. Infections are frequently asymptomatic, many individuals harbor multiple infections, and while high-resolution genotyping of blood samples enables individual infections to be distinguished, primary infections and relapses cannot be identified. We develop a model and fit it to longitudinal genotyping data from children in Papua New Guinea to estimate the incidence and seasonality of P vivax primary infection and relapse. The children, aged one to three years at enrolment, were followed up over 16 months with routine surveys every two months. Blood samples were taken at the routine visits and at other times if the child was ill. Samples positive by microscopy or a molecular method for species detection were genotyped using high-resolution capillary electrophoresis for P vivax MS16 and msp1F3, and P falciparum msp2. The data were summarized as longitudinal patterns of success or failure to detect a genotype at each routine time-point (eg 001000001). We assume that the seasonality of P vivax primary infection is similar to that of P falciparum since they are transmitted by the same vectors and, because P falciparum does not have the ability to relapse, the seasonality can be estimated. Relapses occurring during the study period can be a consequence of infections occurring prior to the study: we assume that the seasonal pattern of primary infections repeats over time. We incorporate information from parasitological and entomology studies to gain leverage for estimating the parameters, and take imperfect detection into account. We estimate the force of P vivax primary infections to be 11.5 (10.5, 12.3) for a three-year old child per year and the mean number of relapses per infection to be 4.3 (4.0, 4.6) over 16 months. The peak incidence of relapses occurred in the two month interval following the peak interval for primary infections: the contribution to the force of blood-stage infection from relapses is between 71% and 90% depending on the season. Our estimates contribute to knowledge of the P vivax epidemiology and have implications for the timing of intervention strategies targeting different stages of the life cycle., Author Summary Plasmodium vivax is the most widespread of the malaria species affecting humans. It has the ability for parasites to lie dormant in liver cells and then to relapse weeks or months later, causing further blood-stage infections and onward transmission. Relapses present a challenge to control and elimination programs. The contribution of relapses to the force of blood-stage infection is not well established. While genotyping can distinguish individual infections, the difficulty lies in the inability to distinguish primary infections (occurring shortly after an infectious mosquito bite) and relapses. This is a gap in the knowledge of the epidemiology of P vivax. We develop a statistical model to tease out and estimate the contributions of primary infections and relapses to the force of blood-stage infection. We use data from a cohort of children in Papua New Guinea with genotyped routine blood samples. The study area has both P vivax and P falciparum malaria: we use the seasonality of P falciparum to estimate the seasonality of P vivax primary infections. We also take into account infections occurring prior to the study period and their subsequent relapses during the study period. We find that approximately 80% of the force of blood-stage infection l is contributed by relapses and that primary infections and relapses have different seasonal patterns. The findings are important to the epidemiology of P vivax and for designing intervention strategies targeting different stages of the parasite life cycle.

INTRODUCTION: The importance of Plasmodium vivax in malaria elimination is increasingly being recognized yet little is known about its population size and population genetic structure in the South Pacific an area that is the focus of intensified malaria control. METHODS: We have genotyped 13 microsatellite markers in 295 P. vivax isolates from four geographically distinct sites in Papua New Guinea (PNG) and one site from Solomon Islands representing different transmission intensities. RESULTS: Diversity was very high with expected heterozygosity values ranging from 0.62 to 0.98 for the different markers. Effective population size was high (12'872 to 19'533 per site). In PNG population structuring was limited with moderate levels of genetic differentiation. F ST values (adjusted for high diversity of markers) were 0.14 0.15. Slightly higher levels were observed between PNG populations and Solomon Islands (F ST?=?0.16). CONCLUSIONS: Low levels of population structure despite geographical barriers to transmission are in sharp contrast to results from regions of low P. vivax endemicity. Prior to intensification of malaria control programs in the study area parasite diversity and effective population size remained high.