Epidemiology of Disappearing Plasmodium vivax Malaria: A Case Study in Rural Amazonia

Abstract

BackgroundNew frontier settlements across the Amazon Basin pose a major challenge for malaria elimination in Brazil. Here we describe the epidemiology of malaria during the early phases of occupation of farming settlements in Remansinho area, Brazilian Amazonia. We examine the relative contribution of low-density and asymptomatic parasitemias to the overall Plasmodium vivax burden over a period of declining transmission and discuss potential hurdles for malaria elimination in Remansinho and similar settings.MethodsEight community-wide cross-sectional surveys, involving 584 subjects, were carried out in Remansinho over 3 years and complemented by active and passive surveillance of febrile illnesses between the surveys. We used quantitative PCR to detect low-density asexual parasitemias and gametocytemias missed by conventional microscopy. Mixed-effects multiple logistic regression models were used to characterize independent risk factors for P. vivax infection and disease.Principal Findings/Conclusions P. vivax prevalence decreased from 23.8% (March–April 2010) to 3.0% (April–May 2013), with no P. falciparum infections diagnosed after March–April 2011. Although migrants from malaria-free areas were at increased risk of malaria, their odds of having P. vivax infection and disease decreased by 2–3% with each year of residence in Amazonia. Several findings indicate that low-density and asymptomatic P. vivax parasitemias may complicate residual malaria elimination in Remansinho: (a) the proportion of subpatent infections (i.e. missed by microscopy) increased from 43.8% to 73.1% as P. vivax transmission declined; (b) most (56.6%) P. vivax infections were asymptomatic and 32.8% of them were both subpatent and asymptomatic; (c) asymptomatic parasite carriers accounted for 54.4% of the total P. vivax biomass in the host population; (d) over 90% subpatent and asymptomatic P. vivax had PCR-detectable gametocytemias; and (e) few (17.0%) asymptomatic and subpatent P. vivax infections that were left untreated progressed to clinical disease over 6 weeks of follow-up and became detectable by routine malaria surveillance.

Basic sanitation, socioeconomic conditions, and degree of risk for the presence and maintenance of malaria in a low-transmission area in the Brazilian Amazon

“…This prevalence underscores the fact that the dynamics of malaria transmission in Ananindeua are similar to those reported in other areas of the country (6) (19) (20) (21) , where this species of Plasmodium is responsible for most detected cases. In addition, the State of Pará has an API ≥ 50, classifying it as a high-risk area for malaria, due to the high number of reported cases.…”

“…The other possibility may be related to a lack of preparation and/or neglect of health agents in fi lling out the epidemiological forms. However, we must consider that the occurrence of a malaria outbreak in this case could also be a consequence of the autochthonous transmission of P. vivax or relapses (old malaria profi le) (19) (25) and may not necessarily be related to recent introduction of the disease to this area. Furthermore, asymptomatic carriers of P. vivax could have some epidemiological importance as a source of infection for vectors (16) (19) , since they are able to maintain the parasite transmission.…”

Development of vaccines for Plasmodium vivax malaria

“…Most if not all of these infections produce gametocytes [11] and likely contribute substantially to maintaining P. vivax transmission [12]. These infections will not be efficiently cleared unless specifically targeted with active case detection and/or mass drug administration, which is logistically challenging and would again require treating large numbers of individuals with asymptomatic infections or even those without blood stage infections with primaquine to clear hypnozoites.…”

Uncovering the transmission dynamics ofPlasmodium vivaxusing population genetics

“…4 ) and that these proportions may increase with decreasing transmission. 5 Genotyping approaches that distinguish between different parasite clones within an infection to estimate the multiplicity of infection (MOI) have provided some insight into the intensity of transmission in different endemic areas. However, proportions of polyclonal infections remain relatively high despite seemingly low transmission.…”