title: Reactive Case Detection for Plasmodium vivax Malaria Elimination in Rural Amazonia.
abstract: Malaria 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.
  
  
  
  We 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.
  
  
  
  Subjects 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.
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Pablo S
authors.initials: PS
authors.lastname: Fontoura
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Bruna F
authors.initials: BF
authors.lastname: Finco
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Nathália F
authors.initials: NF
authors.lastname: Lima
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Jaques F
authors.initials: JF
authors.lastname: de Carvalho
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, CA, United States of America.|Alexander von Humboldt Institute of Tropical Medicine and Faculty of Sciences, Department of Cellular and Molecular Sciences, Laboratory of Research and Development, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Vinetz
authors.affiliation: Department of Global Health and Population, Harvard T. H. Chan School of Public Health, Boston, MA, United States of America.
authors.forename: Márcia C
authors.initials: MC
authors.lastname: Castro
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Marcelo U
authors.initials: MU
authors.lastname: Ferreira
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058345:Asymptomatic Infections / Q000453:epidemiology; D001938:Brazil / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D017281:Cost of Illness; D060740:Disease Eradication / Q000379:methods*; D005191:Family Characteristics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D016780:Malaria, Vivax / Q000175:diagnosis* / Q000453:epidemiology / Q000517:prevention & control* / Q000635:transmission; D008297:Male; D008875:Middle Aged; D010966:Plasmodium vivax / Q000302:isolation & purification; D012423:Rural Health; D055815:Young Adult