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Predominance of asymptomatic and sub-microscopic infections characterize the Plasmodium vivax gametocyte reservoir in the Peruvian Amazon

Juan Jose Contreras-Mancilla 1 ; Eduard Rovira-Vallbona 2 ; Roberson Ramirez 3 ; Mitchel Guzman 3 ; Gabriel Carrasco-Escobar 2 ; Alejandro Llanos-Cuentas 4 ; Joseph M. Vinetz 5 ; Dionicia Gamboa 6 ; Anna Rosanas-Urgell 1
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Background: Malaria transmission requires that Anopheles mosquitoes ingest Plasmodiumgametocyte stages circulating in human bloodstream. In the context of malaria elimination, understanding the epidemiology of gametocytes relative to all Plasmodium infections and the contribution of asymptomatic and sub-microscopic infections to the gametocyte reservoir is necessary, especially in low endemic settings with predominance of P.vivax. Material and Method: A longitudinal study (n=1935 individuals) was conducted in two communities of Loreto Department, Peru, between 2013 and 2014, with active trimestral screenings for Plasmodiuminfections and gametocyte stages by quantitative PCR (qPCR) and reverse transcription (RT)-qPCR, respectively. Results: Parasite prevalence by qPCR was 7.2% for P.vivax(n=520/7235; range by survey 6.0-8.1%) and 3.2% for P.falciparum (n=235/7235; range by survey 0.4-7.7%). Sub-microscopic infections accounted for 73.5% of P.vivax (range by survey 60%-89%) and almost the totality of P.falciparum cases. Gametocytes were found in 28.4% P.vivax infections (range by survey 18.7%-34.1%), with a peak of 61.5% in one community at the start of transmission season. About 59.8% of all P.vivax gametocyte carriers were asymptomatic and 31.9% were sub-microscopic. Age patterns for gametocyte prevalence paralleled asexual infections and peaked among 15-25 year old individuals. Asexual parasite density was found to be the strongest predictor for P.vivax gametocyte presence in longitudinal multivariate analysis (odds ratio 2.33 [95% confidence interval: 1.96, 2.78]; P<0.001). Conclusions:Despite significant differences in seasonality patterns and P.vivax prevalence found at the local scale, sub-microscopic and asymptomatic infections predominate and contribute significantly to the gametocyte reservoir in different communities of the Peruvian Amazon. Control and elimination campaigns need sensitive tools to detect all infections that escape routine malaria surveillance, which may contribute to maintain transmission in the region.