Abstract
BackgroundIn malaria endemic populations, complex patterns of Plasmodium vivax and Plasmodium falciparum blood-stage infection dynamics may be observed. Genotyping samples from longitudinal cohort studies for merozoite surface protein (msp) variants increases the information available in the data, allowing multiple infecting parasite clones in a single individual to be identified. msp genotyped samples from two longitudinal cohorts in Papua New Guinea (PNG) and Thailand were analysed using a statistical model where the times of acquisition and clearance of each clone in every individual were estimated using a process of data augmentation.ResultsFor the populations analysed, the duration of blood-stage P. falciparum infection was estimated as 36 (95% Credible Interval (CrI): 29, 44) days in PNG, and 135 (95% CrI 94, 191) days in Thailand. Experiments on simulated data indicated that it was not possible to accurately estimate the duration of blood-stage P. vivax infections due to the lack of identifiability between a single blood-stage infection and multiple, sequential blood-stage infections caused by relapses. Despite this limitation, the method and data point towards short duration of blood-stage P. vivax infection with a lower bound of 24 days in PNG, and 29 days in Thailand. On an individual level, P. vivax recurrences cannot be definitively classified into re-infections, recrudescences or relapses, but a probabilistic relapse phenotype can be assigned to each P. vivax sample, allowing investigation of the association between epidemiological covariates and the incidence of relapses.ConclusionThe statistical model developed here provides a useful new tool for in-depth analysis of malaria data from longitudinal cohort studies, and future application to data sets with multi-locus genotyping will allow more detailed investigation of infection dynamics.
Highlights
In malaria endemic populations, complex patterns of Plasmodium vivax and Plasmodium falciparum blood-stage infection dynamics may be observed
Assessment of model performance with simulated datasets The statistical methods were applied to simulated data sets with known values of the population-level parameters describing the infection dynamics of P. falciparum and P. vivax, to investigate whether it was possible to accurately estimate these parameters
Low genotype detectability leads to positive samples being missed, causing long sequences of consecutive samples to be split into several shorter sequences. dBS was underestimated for small values of κWB—the shape parameter of the Weibull distribution
Summary
Complex patterns of Plasmodium vivax and Plasmodium falciparum blood-stage infection dynamics may be observed. Genotyping samples from longitudinal cohort studies for merozoite surface protein (msp) variants increases the information available in the data, allowing multiple infecting parasite clones in a single individual to be identified. Plasmodium falciparum and Plasmodium vivax malaria parasites cause persistent blood-stage infections in humans lasting for weeks, months, and occasionally years [1]. A P. falciparum recurrence can be due to: (i) re-infection from a new mosquito bite; or (ii) recrudescence, where blood-stage parasites originating from a previous infection persist at sub-patent densities where the probability of detection is low, before increasing in density to become detectable. Recrudescences can be excluded with high-sensitivity testing for blood-stage parasites, for example if prior to a positive blood sample an individual tested negative by qPCR, it’s unlikely that the positive sample was due to a recrudescence
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