Reactive Case Detection for Plasmodium vivax Malaria Elimination in Rural Amazonia

Abstract

BackgroundMalaria burden in Brazil has reached its lowest levels in 35 years and Plasmodium vivax now accounts for 84% of cases countrywide. Targeting residual malaria transmission entrenched in the Amazon is the next major challenge for ongoing elimination efforts. Better strategies are urgently needed to address the vast reservoir of asymptomatic P. vivax carriers in this and other areas approaching malaria elimination.MethodsWe evaluated a reactive case detection (RCD) strategy tailored for P. vivax transmission in farming settlements in the Amazon Basin of Brazil. Over six months, 41 cases detected by passive surveillance triggered four rounds of RCD (0, 30, 60, and 180 days after index case enrollment), using microscopy- and quantitative real-time polymerase chain reaction (qPCR)-based diagnosis, comprising subjects sharing the household (HH) with the index case (n = 163), those living in the 5 nearest HHs within 3 km (n = 878), and individuals from 5 randomly chosen control HHs located > 5 km away from index cases (n = 841). Correlates of infection were identified with mixed-effects logistic regression models. Molecular genotyping was used to infer local parasite transmission networks.Principal findings/ConclusionsSubjects in index and neighbor HHs were significantly more likely to be parasitemic than control HH members, after adjusting for potential confounders, and together harbored > 90% of the P. vivax biomass in study subjects. Clustering patterns were temporally stable. Four rounds of microscopy-based RCD would identify only 49.5% of the infections diagnosed by qPCR, but 76.8% of the total parasite biomass circulating in the proximity of index HHs. However, control HHs accounted for 27.6% of qPCR-positive samples, 92.6% of them from asymptomatic carriers beyond the reach of RCD. Molecular genotyping revealed high P. vivax diversity, consistent with complex transmission networks and multiple sources of infection within clusters, potentially complicating malaria elimination efforts.

Apical membrane protein 1‐specific antibody profile and temporal changes in peripheral blood B‐cell populations in Plasmodium vivax malaria

“…All study subjects lived in farming settlements in the Amazon Basin of Brazil, close to the border with Bolivia (Figure ). This area receives most rainfall between November and March (annual average, 2318 mm), but low‐level P vivax transmission occurs year‐round., with no P falciparum infections diagnosed since early 2012 …”

“…This area receives most rainfall between November and March (annual average, 2318 mm), but low-level P vivax transmission occurs year-round., with no P falciparum infections diagnosed since early 2012. 28,29…”

Improving the efficiency of reactive case detection for malaria elimination in southern Zambia: a cross-sectional study

“…Many studies evaluating the efficiency of RCD highlight its inability to halt infections in areas of low transmission due to the use of less sensitive RDTs, travel-related infections, and large budgetary requirements [2,18]. A major concern for RCD-based strategies is that asymptomatic individuals will be missed if no clinical cases report to CHWs [42]. A survey in coastal Kenya found that asymptomatic and symptomatic infections do not necessarily overlap spatially, and that clusters of symptomatic infections have greater temporal stability over more than ten years [42].…”

“…A major concern for RCD-based strategies is that asymptomatic individuals will be missed if no clinical cases report to CHWs [42]. A survey in coastal Kenya found that asymptomatic and symptomatic infections do not necessarily overlap spatially, and that clusters of symptomatic infections have greater temporal stability over more than ten years [42]. Another issue often highlighted is the different criteria and screening radii employed by countries to define and recruit neighbouring households [42] For example, RCD data from four villages in the Myanmar-Thailand border determined that RCD would only be successful at a radius of 150 metres, and any screening occurring beyond this radius would not perform better than random screening [2].…”

Improving the efficiency of reactive case detection for malaria elimination in southern Zambia: A cross-sectional study

“…2,18 A major concern for RCD-based strategies is that asymptomatic individuals will be missed if no clinical cases report to CHWs. 42 A survey in coastal Kenya found that asymptomatic and symptomatic infections do not necessarily overlap spatially, and that clusters of symptomatic infections have greater temporal stability over >10 years. 42 Another issue often highlighted is the different criteria and screening radii employed by countries to define and recruit neighboring households.…”