The dynamics of natural Plasmodium falciparum infections

Abstract

Background: Natural 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.

Methods: An 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.

Results: Allowing 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).

Conclusions: The 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.

Figure 1. Mean multiplicity of infection (MOI) and prevalence by PCR.

(a) by age and (b) by survey. Mean multiplicity is calculated from PCR positive samples only. Error bars correspond to approximate 95% confidence intervals.

Figure 2. Sampling intervals and rainfall in Navrongo during the study period.

Blue triangles represent weekly rainfall, the black line shows the 5 weeks moving average of rainfall. Grey bars represent the six sampling periods.

Figure 3. Transition types observed between two consecutive survey rounds by age group.

Transitions are gains or losses of parasite clones.

Figure 4. Age dependence of parameter estimates.

a. Estimated detectability by age (Model A and triplet model), and Williams mean parasite densities by age group assessed by microscopy. The grey area is the 95% confidence envelope for the detectability. (The Williams mean of N observed densities y is calculated as ). b. Observed mean multiplicity of infection (MOI) by age group in northern Ghana and estimated MOI allowing for imperfect detection. MOI was determined from PCR positive blood samples only. c. Estimated average duration of an infection by age group (Model A). Error bars are approximate 95% confidence intervals. d. Estimated force of infection by age group (Model B). Estimates are rates expressed relative to that in the oldest age group. Error bars are approximate 95% confidence intervals.