title: An intensive longitudinal cohort study of Malian children and adults reveals no evidence of acquired immunity to Plasmodium falciparum infection.
abstract: BACKGROUND
  In experimental models of human and mouse malaria, sterilizing liver stage immunity that blocks progression of Plasmodium infection to the symptomatic blood stage can be readily demonstrated. However, it remains unclear whether individuals in malaria-endemic areas acquire such immunity.
  
  
  METHODS
  In Mali, 251 healthy children and adults aged 4-25 years who were free of blood-stage Plasmodium infection by polymerase chain reaction (PCR) were enrolled in a longitudinal study just prior to an intense 6-month malaria season. Subsequent clinical malaria episodes were detected by weekly active surveillance and self-referral. Asymptomatic P. falciparum infections were detected by blood-smear microscopy and PCR analysis of dried blood spots that had been collected every 2 weeks for 7 months.
  
  
  RESULTS
  As expected, the risk of clinical malaria decreased with increasing age (log-rank test, P = .0038). However, analysis of PCR data showed no age-related differences in P. falciparum infection risk (log-rank test, P = .37).
  
  
  CONCLUSIONS
  Despite years of exposure to intense P. falciparum transmission, there is no evidence of acquired, sterile immunity to P. falciparum infection in this population, even as clinical immunity to blood-stage malaria is clearly acquired. Understanding why repeated P. falciparum infections do not induce sterile protection may lead to insights for developing vaccines that target the liver stage in malaria-endemic populations.
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
authors.forename: Tuan M
authors.initials: TM
authors.lastname: Tran
authors.forename: Shanping
authors.initials: S
authors.lastname: Li
authors.forename: Safiatou
authors.initials: S
authors.lastname: Doumbo
authors.forename: Didier
authors.initials: D
authors.lastname: Doumtabe
authors.forename: Chiung-Yu
authors.initials: CY
authors.lastname: Huang
authors.forename: Seydou
authors.initials: S
authors.lastname: Dia
authors.forename: Aboudramane
authors.initials: A
authors.lastname: Bathily
authors.forename: Jules
authors.initials: J
authors.lastname: Sangala
authors.forename: Younoussou
authors.initials: Y
authors.lastname: Kone
authors.forename: Abdrahamane
authors.initials: A
authors.lastname: Traore
authors.forename: Moussa
authors.initials: M
authors.lastname: Niangaly
authors.forename: Charles
authors.initials: C
authors.lastname: Dara
authors.forename: Kassoum
authors.initials: K
authors.lastname: Kayentao
authors.forename: Aissata
authors.initials: A
authors.lastname: Ongoiba
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
authors.forename: Boubacar
authors.initials: B
authors.lastname: Traore
authors.forename: Peter D
authors.initials: PD
authors.lastname: Crompton
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D002648:Child; D015331:Cohort Studies; D006801:Humans; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000276:immunology* / Q000517:prevention & control; D008302:Mali / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000276:immunology*
keywords: Plasmodium falciparum; endemic population; infection risk; malaria; preerythrocytic immunity