title: Epidemiology of disappearing Plasmodium vivax malaria: a case study in rural Amazonia.
abstract: BACKGROUND
  New 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.
  
  
  METHODS
  Eight 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.
  
  
  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.
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Susana
authors.initials: S
authors.lastname: Barbosa
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Gozze
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, 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, São Paulo, Brazil.
authors.forename: Camilla L
authors.initials: CL
authors.lastname: Batista
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Melissa da Silva
authors.initials: Mda S
authors.lastname: Bastos
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Vanessa C
authors.initials: VC
authors.lastname: Nicolete
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, 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, São Paulo, Brazil.
authors.forename: Raquel M
authors.initials: RM
authors.lastname: Gonçalves
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Susana Ariane S
authors.initials: SA
authors.lastname: Viana
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Menezes
authors.affiliation: Department of Parasitology, Microbiology and Immunology, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil.
authors.forename: Kézia Katiani G
authors.initials: KK
authors.lastname: Scopel
authors.affiliation: Department of Dermatologic, Infectious and Parasitic Diseases, Faculty of Medicine of São José do Rio Preto, São José do Rio Preto, São Paulo, Brazil.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Cavasini
authors.affiliation: Institute of Tropical Medicine of São Paulo, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Rosely dos Santos
authors.initials: Rdos S
authors.lastname: Malafronte
authors.affiliation: Center of Health Sciences and Sports, Federal University of Acre, Rio Branco, Acre, Brazil.
authors.forename: Mônica
authors.initials: M
authors.lastname: da Silva-Nunes
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, California, 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 School of Public Health, Boston, Massachusetts, 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, São Paulo, Brazil.
authors.forename: Marcelo U
authors.initials: MU
authors.lastname: Ferreira
mesh_terms: D000328:Adult; D001938:Brazil / Q000453:epidemiology; D005260:Female; D006801:Humans; D016780:Malaria, Vivax / Q000453:epidemiology* / Q000469:parasitology / Q000635:transmission; D008297:Male; D018512:Parasitemia / Q000453:epidemiology / Q000469:parasitology; D010966:Plasmodium vivax / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012424:Rural Population / Q000706:statistics & numerical data; D055815:Young Adult