Emergence of Nonfalciparum Plasmodium Infection Despite Regular Artemisinin Combination Therapy in an 18-Month Longitudinal Study of Ugandan Children and Their Mothers

Abstract

As part of a longitudinal cohort investigation of intestinal schistosomiasis and malaria in Ugandan children and their mothers on the shorelines of Lakes Victoria and Albert, we documented risk factors and morbidity associated with nonfalciparum Plasmodium infections and the longitudinal dynamics of Plasmodium species in children. Host age, household location, and Plasmodium falciparum infection were strongly associated with nonfalciparum Plasmodium infections, and Plasmodium malariae infection was associated with splenomegaly. Despite regular artemisinin combination therapy treatment, there was a 3-fold rise in P. malariae prevalence, which was not accountable for by increasing age of the child. Worryingly, our findings reveal the consistent emergence of nonfalciparum infections in children, highlighting the complex dynamics underlying multispecies infections here. Given the growing body of evidence that nonfalciparum malaria infections cause significant morbidity, we encourage better surveillance for nonfalciparum Plasmodium infections, particularly in children, with more sensitive DNA detection methods and improved field-based diagnostics.

Figure 1.

Plasmodium infection prevalence in Ugandan lakeshore communities varies with host age. A, Plasmodium infection prevalence at baseline in children enrolled in the Schistosomiasis in Mothers and Infants (SIMI) study. B, Plasmodium infection prevalence at baseline in mothers enrolled in the SIMI study. “PCR” refers to infection status determined by real-time polymerse chain reaction performed on DNA extracted from dried blood spots. “Microscopy” refers to presence of parasites in peripheral blood as determined by microscopy on Giemsa-stained blood smears. Error bars represent 95% confidence intervals. Abbreviations: P. falciparum, Plasmodium falciparum; P. malariae, Plasmodium malariae; P. ovale, Plasmodium ovale; PCR, polymerse chain reaction.

Figure 2.

Plasmodium infection prevalence in children in Bukoba village at different survey time points. Infection status was determined by real-time polymerase chain reaction performed on DNA extracted from dried blood spots. Error bars represent 95% confidence intervals. Abbreviations: P. falciparum, Plasmodium falciparum; P. malariae, Plasmodium malariae; P. ovale, Plasmodium ovale.

Figure 3.

Areas of Bukoba with significant log-transformed relative risk of malaria at baseline, determined using a Monte Carlo simulation envelope approach for Plasmodium falciparum infections (A), P. falciparum and Plasmodium malariae infections (B), and P. falciparum and Plasmodium ovale (C) infections. Each individual, infected (red) nor not-infected (black), is represented by a dot corresponding to their household. Yellow areas indicate more infections than expected, whereas purple areas indicate fewer infections than expected. Abbreviations: Pf, Plasmodium falciparum; Pm, Plasmodium malariae; Po, Plasmodium ovale; RR, relative risk.