title: Declining malaria transmission in rural Amazon: changing epidemiology and challenges to achieve elimination.
abstract: In recent years, considerable success in reducing its incidence has been achieved in Brazil, leading to a relative increase in the proportion of cases caused by Plasmodium vivax, considered a harder-to-eliminate parasite. This study aim is to describe the transmission dynamics and associated risk factors in a rural settlement area in the Western Brazilian Amazon.
  
  
  
  A prospective cohort was established in a rural settlement area for 3 years. Follow-up included continuous passive case detection and monthly active case detection for a period of 6 months. Demographic, clinical and transmission control practices data were collected. Malaria diagnosis was performed through thick blood smear. Univariable and multivariable analyses of factors associated with malaria incidence were performed using negative binomial regression models. Factors associated with recurrence of P. vivax and Plasmodium falciparum malaria within 90 days of a previous episode were analysed using univariable and multivariable Cox-Proportional Hazard models.
  
  
  
  Malaria prevalence decreased from 7 % at the study beginning to 0.6 % at month 24, with P. vivax predominating and P. falciparum disappearing after 1 year of follow-up. Malaria incidence was significantly higher in the dry season [IRR (95 % CI) 1.4 (1.1-1.6); p < 0.001)]. Use of ITN was associated to malaria protection in the localities [IRR (95 % CI) 0.7 (0.6-0.8); p = 0.001)]. A recurrent P. vivax episode within 90 days was observed in 29.4 % of individuals after an initial diagnosis. A previous P. vivax [IRR (95 % CI) 2.3 (1.3-4.0); p = 0.006)] or mixed P. vivax + P. falciparum [IRR (95 % CI) 2.9 (1.5-5.7); p = 0.002)] infections were significantly associated to a vivax malaria episode within 90 days of follow-up.
  
  
  
  In an area of P. falciparum and P. vivax co-endemicity, a virtual disappearance of P. falciparum was observed with P. vivax increasing its relative contribution, with a large proportion of recurring episodes. This finding reinforces the perception of P. falciparum being more responsive to early diagnosis and treatment and ITN use and the contribution of relapsing P. vivax to maintain this species' transmission. In areas of P. vivax endemicity, antihypnozoite treatment effectiveness assessment in different transmission intensity may be a fundamental activity for malaria control and elimination.
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Av. Pedro Teixeira, 25, Dom Pedro, Manaus, AM, 69040-000, Brazil.|Universidade do Estado do Amazonas, Av. Pedro Teixeira, 25, Dom Pedro, Manaus, AM, 69040-000, Brazil.
authors.forename: Sheila
authors.initials: S
authors.lastname: Vitor-Silva
authors.affiliation: Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Av. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 21040-360, Brazil.
authors.forename: André Machado
authors.initials: AM
authors.lastname: Siqueira
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Av. Pedro Teixeira, 25, Dom Pedro, Manaus, AM, 69040-000, Brazil.|Universidade do Estado do Amazonas, Av. Pedro Teixeira, 25, Dom Pedro, Manaus, AM, 69040-000, Brazil.
authors.forename: Vanderson
authors.initials: V
authors.lastname: de Souza Sampaio
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic-Universitat de Barcelona, Rosselló 132, 4°, 08036, Barcelona, Spain.
authors.forename: Caterina
authors.initials: C
authors.lastname: Guinovart
authors.affiliation: Secretaria de Vigilância em Saúde, Ministério da Saúde, Lotes 5/6 Bloco F, SAF Sul Trecho 2, Brasília, DF, 70070-600, Brazil.
authors.forename: Roberto Carlos
authors.initials: RC
authors.lastname: Reyes-Lecca
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Av. Pedro Teixeira, 25, Dom Pedro, Manaus, AM, 69040-000, Brazil.|Universidade do Estado do Amazonas, Av. Pedro Teixeira, 25, Dom Pedro, Manaus, AM, 69040-000, Brazil.
authors.forename: Gisely Cardoso
authors.initials: GC
authors.lastname: de Melo
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Av. Pedro Teixeira, 25, Dom Pedro, Manaus, AM, 69040-000, Brazil.|Universidade do Estado do Amazonas, Av. Pedro Teixeira, 25, Dom Pedro, Manaus, AM, 69040-000, Brazil.
authors.forename: Wuelton Marcelo
authors.initials: WM
authors.lastname: Monteiro
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic-Universitat de Barcelona, Rosselló 132, 4°, 08036, Barcelona, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Hernando A
authors.initials: HA
authors.lastname: Del Portillo
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic-Universitat de Barcelona, Rosselló 132, 4°, 08036, Barcelona, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Alonso
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic-Universitat de Barcelona, Rosselló 132, 4°, 08036, Barcelona, Spain.|Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique.
authors.forename: Quique
authors.initials: Q
authors.lastname: Bassat
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Av. Pedro Teixeira, 25, Dom Pedro, Manaus, AM, 69040-000, Brazil. marcuslacerda.br@gmail.com.|Universidade do Estado do Amazonas, Av. Pedro Teixeira, 25, Dom Pedro, Manaus, AM, 69040-000, Brazil. marcuslacerda.br@gmail.com.|Instituto de Pesquisas Leônidas & Maria Deane, Fundação Oswaldo Cruz, Rua Terezina, 476, Adrianópolis, Manaus, AM, 69057-070, Brazil. marcuslacerda.br@gmail.com.
authors.forename: Marcus Vinícius Guimarães
authors.initials: MV
authors.lastname: Lacerda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D003140:Communicable Disease Control / Q000379:methods*; D018562:Disease Transmission, Infectious; D005260:Female; D006302:Health Services Research; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology* / Q000635:transmission*; D016780:Malaria, Vivax / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology* / Q000635:transmission*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011446:Prospective Studies; D012424:Rural Population; D055815:Young Adult
keywords: Amazon; Elimination; Health Surveillance; Malaria; Plasmodium falciparum; Plasmodium vivax