Dynamics of Afebrile Plasmodium falciparum Infections in Mozambican Men

Beatriz Galatas, Helena Martí-Soler, Lidia Nhamussua, Pau Cisteró, Pedro Aide, Francisco Saute, Clara Menéndez, N Regina Rabinovich, Pedro L Alonso, Quique Bassat, Alfredo Mayor, Beatriz Galatas, Helena Martí-Soler, Lidia Nhamussua, Pau Cisteró, Pedro Aide, Francisco Saute, Clara Menéndez, N Regina Rabinovich, Pedro L Alonso, Quique Bassat, Alfredo Mayor

Abstract

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/μL and fell to <100 parasites/μL by day 3, reaching 56.7 parasites/μL 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.

Figures

Figure 1.
Figure 1.
Kaplan–Meier estimates of the cumulative probability of parasite positivity by day 28 measured by quantitative polymerase chain reaction.
Figure 2.
Figure 2.
Distributions of individual-level parasite densities observed for each day of follow-up of 32 afebrile Plasmodium falciparum–infected individuals over 28 days. 100 parasites/μL represents the threshold below which infections are considered submicroscopic. Abbreviation: p/μL, parasites per microliter.
Figure 3.
Figure 3.
Kaplan–Meier estimates of the cumulative probability of failure to reduce parasitemia levels by at least 50% of their initial value—or half-life probability measured by quantitative polymerase chain reaction.
Figure 4.
Figure 4.
Proportion of positive samples by real-time quantitative polymerase chain reaction and microscopy per follow-up observation (bars, left y axis), and ratio of samples detected by polymerase chain reaction and microscopy through time (line, right y axis) during the follow-up of 32 afebrile Plasmodium falciparum–infected individuals at baseline. Abbreviation: qPCR, quantitative polymerase chain-reaction.

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