The temporal dynamics and infectiousness of subpatent Plasmodium falciparum infections in relation to parasite density.
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ABSTRACT:
SUBMITTER: Slater HC
PROVIDER: S-EPMC6440965 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundNatural immunity to Plasmodium falciparum has been widely studied, but its effects on parasite dynamics are poorly understood. Acquisition and clearance rates of untreated infections are key elements of the dynamics of malaria, but estimating these parameters is challenging because of frequent super-infection and imperfect detectability of parasites. Consequently, information on effects of host immune status or age on infection dynamics is fragmentary.MethodsAn age-stratified cohort of 347 individuals from Northern Ghana was sampled six times at 2 month intervals. High-throughput capillary electrophoresis was used to genotype the msp-2 locus of all P. falciparum infections detected by PCR. Force of infection (FOI) and duration were estimated for each age group using an immigration-death model that allows for imperfect detection of circulating parasites.ResultsAllowing for imperfect detection substantially increased estimates of FOI and duration. Effects of naturally acquired immunity on the FOI and duration would be reflected in age dependence in these indices, but in our cohort data FOI tended to increase with age in children. Persistence of individual parasite clones was characteristic of all age-groups. Duration peaked in 5-9 year old children (average duration 319 days, 95% confidence interval 318;320).ConclusionsThe main age-dependence is on parasite densities, with only small age-variations in the FOI and persistence of infections. This supports the hypothesis that acquired immunity controls transmission mainly by limiting blood-stage parasite densities rather than changing rates of acquisition or clearance of infections.
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Project description:Background:Afebrile Plasmodium falciparum infections usually remain undetected and untreated in the community and could potentially contribute to sustaining local malaria transmission in areas aiming for malaria elimination. Methods:Thirty-two men with afebrile P. falciparum infections detected with rapid diagnostic test (RDTs) were followed for 28 days. Kaplan-Meier estimates were computed to estimate probability of parasite positivity and of reducing parasitemia by half of its initial level by day 28. Trends of parasite densities quantified by microscopy and real-time quantitative polymerase chain reaction (qPCR) were assessed using Poisson regression models, and the microscopy-to-qPCR positivity ratio was calculated at each time point. Three survival distributions (Gompertz, Weibull, and gamma) were used to evaluate their strength of fit to the data and to predict the median lifetime of infection. Results:The cumulative probability of parasite qPCR positivity by day 28 was 81% (95% confidence interval [CI], 60.2-91.6). Geometric mean parasitemia at recruitment was 516.1 parasites/?L and fell to <100 parasites/?L by day 3, reaching 56.7 parasites/?L on day 28 (P < .001). The ratio of P. falciparum-positive samples by microscopy to qPCR decreased from 0.9 to 0.52 from recruitment to day 28. The best model fit to the data was obtained assuming a Gompertz distribution. Conclusions:Afebrile P. falciparum infections detectable by RDT in semi-immune adults fall and stabilize at low-density levels during the first 4 days after detection, suggesting a rapid decline of potential transmissibility in this hidden parasite reservoir. Clincial trials registration:NCT02698748.
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