title: Relapses of Plasmodium vivax infection usually result from activation of heterologous hypnozoites.
abstract: BACKGROUND
  Relapses originating from hypnozoites are characteristic of Plasmodium vivax infections. Thus, reappearance of parasitemia after treatment can result from relapse, recrudescence, or reinfection. It has been assumed that parasites causing relapse would be a subset of the parasites that caused the primary infection.
  
  
  METHODS
  Paired samples were collected before initiation of antimalarial treatment and at recurrence of parasitemia from 149 patients with vivax malaria in Thailand (n=36), where reinfection could be excluded, and during field studies in Myanmar (n=75) and India (n=38).
  
  
  RESULTS
  Combined genetic data from 2 genotyping approaches showed that novel P. vivax populations were present in the majority of patients with recurrent infection (107 [72%] of 149 patients overall [78% of patients in Thailand, 75% of patients in Myanmar {Burma}, and 63% of patients in India]). In 61% of the Thai and Burmese patients and in 55% of the Indian patients, the recurrent infections contained none of the parasite genotypes that caused the acute infection.
  
  
  CONCLUSIONS
  The P. vivax populations emerging from hypnozoites commonly differ from the populations that caused the acute episode. Activation of heterologous hypnozoite populations is the most common cause of first relapse in patients with vivax malaria.
authors.affiliation: Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Mallika
authors.initials: M
authors.lastname: Imwong
authors.forename: Georges
authors.initials: G
authors.lastname: Snounou
authors.forename: Sasithon
authors.initials: S
authors.lastname: Pukrittayakamee
authors.forename: Naowarat
authors.initials: N
authors.lastname: Tanomsing
authors.forename: Jung Ryong
authors.initials: JR
authors.lastname: Kim
authors.forename: Amitab
authors.initials: A
authors.lastname: Nandy
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Guthmann
authors.forename: Francois
authors.initials: F
authors.lastname: Nosten
authors.forename: Jane
authors.initials: J
authors.lastname: Carlton
authors.forename: Sornchai
authors.initials: S
authors.lastname: Looareesuwan
authors.forename: Shalini
authors.initials: S
authors.lastname: Nair
authors.forename: Daniel
authors.initials: D
authors.lastname: Sudimack
authors.forename: Nicholas P J
authors.initials: NP
authors.lastname: Day
authors.forename: Timothy J C
authors.initials: TJ
authors.lastname: Anderson
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002738:Chloroquine / Q000008:administration & dosage / Q000627:therapeutic use; D017931:DNA Primers; D006801:Humans; D007194:India / Q000453:epidemiology; D016780:Malaria, Vivax / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology*; D002052:Myanmar / Q000453:epidemiology; D010966:Plasmodium vivax / Q000235:genetics* / Q000472:pathogenicity; D012150:Polymorphism, Restriction Fragment Length; D011319:Primaquine / Q000008:administration & dosage / Q000627:therapeutic use; D015800:Protozoan Proteins / Q000235:genetics; D012008:Recurrence; D013785:Thailand / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D017931:DNA Primers; D015800:Protozoan Proteins; D002738:Chloroquine; D011319:Primaquine