Abstract
BackgroundThe widespread presence of low-density asymptomatic infections with concurrent gametocytes may be a stumbling block for malaria elimination. This study investigated the asymptomatic reservoir of Plasmodium falciparum and Plasmodium vivax infections in schoolchildren from five settings in northwest Ethiopia.MethodsTwo cross-sectional surveys were conducted in June and November 2015, enrolling 551 students from five schools and 294 students from three schools, respectively. Finger prick whole blood and plasma samples were collected. The prevalence and density of P. falciparum and P. vivax parasitaemia and gametocytaemia were determined by 18S rRNA quantitative PCR (qPCR) and pfs25 and pvs25 reverse transcriptase qPCR. Antibodies against blood stage antigens apical membrane antigen-1 (AMA-1) and merozoite surface protein-1 (MSP-119) were measured for both species.ResultsWhilst only 6 infections were detected by microscopy in 881 slides (0.7%), 107 of 845 blood samples (12.7%) were parasite positive by (DNA-based) qPCR. qPCR parasite prevalence between sites and surveys ranged from 3.8 to 19.0% for P. falciparum and 0.0 to 9.0% for P. vivax. The median density of P. falciparum infections (n = 85) was 24.4 parasites/µL (IQR 18.0–34.0) and the median density of P. vivax infections (n = 28) was 16.4 parasites/µL (IQR 8.8–55.1). Gametocyte densities by (mRNA-based) qRT-PCR were strongly associated with total parasite densities for both P. falciparum (correlation coefficient = 0.83, p = 0.010) and P. vivax (correlation coefficient = 0.58, p = 0.010). Antibody titers against P. falciparum AMA-1 and MSP-119 were higher in individuals who were P. falciparum parasite positive in both surveys (p < 0.001 for both comparisons).DiscussionThis study adds to the available evidence on the wide-scale presence of submicroscopic parasitaemia by quantifying submicroscopic parasite densities and concurrent gametocyte densities. There was considerable heterogeneity in the occurrence of P. falciparum and P. vivax infections and serological markers of parasite exposure between the examined low endemic settings in Ethiopia.
Highlights
The widespread presence of low-density asymptomatic infections with concurrent gametocytes may be a stumbling block for malaria elimination
Non-linear, the likelihood of mosquito infections increases with increasing gametocyte density [12] and microscopically detectable gametocytes are more likely to result in mosquito infections than submicroscopic gametocyte densities [4, 13]
Parasite and gametocyte prevalence by microscopy and quantitative PCR (qPCR) During the first cross-sectional survey (June 2015), 551 students were enrolled from 5 elementary schools
Summary
The widespread presence of low-density asymptomatic infections with concurrent gametocytes may be a stumbling block for malaria elimination. In settings where recent malaria control efforts have been successful, submicroscopic infections frequently outnumber microscopically detectable infections [3,4,5]. Whilst the clinical consequences of apparently asymptomatic submicroscopic infections are unknown [6, 7], infections may last for several months [8] and are associated with gametocyte production [9,10,11]. Gametocytes are essential for onward malaria transmission to mosquitoes. Submicroscopic infections may contribute considerably to malaria transmission because of their relative abundance in populations [10, 14]
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