title: Plasmodium vivax sub-patent infections after radical treatment are common in Peruvian patients: results of a 1-year prospective cohort study.
abstract: BACKGROUND
  There is an increasing body of literature reporting treatment failure of the currently recommended radical treatment of Plasmodium vivax infections. As P. vivax is the main malaria species outside the African continent, emerging tolerance to its radical treatment regime could have major consequences in countries like Peru, where 80% of malaria cases are due to P. vivax. Here we describe the results of a 1-year longitudinal follow up of 51 confirmed P. vivax patients living around Iquitos, Peruvian Amazon, and treated according to the Peruvian national guidelines.
  
  
  METHODS
  Each month a blood sample for microscopy and later genotyping was systematically collected. Recent exposure to infection was estimated by detecting antibodies against the P. vivax circumsporozoite protein (CSP) and all PCR confirmed P. vivax infections were genotyped with 16 polymorphic microsatellites.
  
  
  RESULTS
  During a 1-year period, 84 recurrent infections, 22 positive also by microscopy, were identified, with a median survival time to first recurrent infection of 203 days. Most of them (71%) were asymptomatic; in 13 patients the infection persisted undetected by microscopy for several consecutive months. The genotype of mostly recurrent infections differed from that at day 0 while fewer differences were seen between the recurrent infections. The average expected heterozygosity was 0.56. There was strong linkage disequilibrium (I(A)(s) = 0.29, p<1.10(-4)) that remained also when analyzing only the unique haplotypes, suggesting common inbreeding.
  
  
  CONCLUSIONS
  In Peru, the P. vivax recurrent infections were common and displayed a high turnover of parasite genotypes compared to day 0. Plasmodium vivax patients, even when treated according to the national guidelines, may still represent an important parasite reservoir that can maintain transmission. Any elimination effort should consider such a hidden reservoir.
authors.affiliation: Department of Parasitology, Institute of Tropical Medicine, Antwerp, Belgium. pvandeneede@itg.be
authors.forename: Peter
authors.initials: P
authors.lastname: Van den Eede
authors.forename: Veronica E
authors.initials: VE
authors.lastname: Soto-Calle
authors.forename: Christopher
authors.initials: C
authors.lastname: Delgado
authors.forename: Dionicia
authors.initials: D
authors.lastname: Gamboa
authors.forename: Tanilu
authors.initials: T
authors.lastname: Grande
authors.forename: Hugo
authors.initials: H
authors.lastname: Rodriguez
authors.forename: Alejandro
authors.initials: A
authors.lastname: Llanos-Cuentas
authors.forename: Jozef
authors.initials: J
authors.lastname: Anné
authors.forename: Umberto
authors.initials: U
authors.lastname: D'Alessandro
authors.forename: Annette
authors.initials: A
authors.lastname: Erhart
mesh_terms: D000913:Antibodies, Protozoan / Q000097:blood; D015331:Cohort Studies; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D016780:Malaria, Vivax / Q000453:epidemiology* / Q000628:therapy* / Q000635:transmission; D010568:Peru / Q000453:epidemiology; D010966:Plasmodium vivax / Q000235:genetics; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012008:Recurrence
chemical_list: D000913:Antibodies, Protozoan