An intensive longitudinal cohort study of malian children and adults reveals no evidence of acquired immunity to plasmodium falciparum infection

Tuan  Tran, Shanping Li, Safiatou Doumbo, Didier Doumtabe, Chiung Yu Huang, Seydou Dia, Aboudramane Bathily, Jules Sangala, Younoussou Kone, Abdrahamane Traore, Moussa Niangaly, Charles Dara, Kassoum Kayentao, Aissata Ongoiba, Ogobara K. Doumbo, Boubacar Traore, Peter D. Crompton

Research output: Contribution to journalArticle

92 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)40-47
Number of pages8
JournalClinical Infectious Diseases
Volume57
Issue number1
DOIs
StatePublished - Jul 2013
Externally publishedYes

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Adaptive Immunity
Plasmodium falciparum
Malaria
Longitudinal Studies
Cohort Studies
Immunity
Polymerase Chain Reaction
Dried Blood Spot Testing
Mali
Liver
Population
Microscopy
Theoretical Models
Referral and Consultation
Vaccines

Keywords

  • endemic population
  • infection risk
  • malaria
  • Plasmodium falciparum
  • preerythrocytic immunity

ASJC Scopus subject areas

  • Infectious Diseases
  • Microbiology (medical)

Cite this

An intensive longitudinal cohort study of malian children and adults reveals no evidence of acquired immunity to plasmodium falciparum infection. / Tran, Tuan ; Li, Shanping; Doumbo, Safiatou; Doumtabe, Didier; Huang, Chiung Yu; Dia, Seydou; Bathily, Aboudramane; Sangala, Jules; Kone, Younoussou; Traore, Abdrahamane; Niangaly, Moussa; Dara, Charles; Kayentao, Kassoum; Ongoiba, Aissata; Doumbo, Ogobara K.; Traore, Boubacar; Crompton, Peter D.

In: Clinical Infectious Diseases, Vol. 57, No. 1, 07.2013, p. 40-47.

Research output: Contribution to journalArticle

Tran, T, Li, S, Doumbo, S, Doumtabe, D, Huang, CY, Dia, S, Bathily, A, Sangala, J, Kone, Y, Traore, A, Niangaly, M, Dara, C, Kayentao, K, Ongoiba, A, Doumbo, OK, Traore, B & Crompton, PD 2013, 'An intensive longitudinal cohort study of malian children and adults reveals no evidence of acquired immunity to plasmodium falciparum infection', Clinical Infectious Diseases, vol. 57, no. 1, pp. 40-47. https://doi.org/10.1093/cid/cit174
Tran, Tuan  ; Li, Shanping ; Doumbo, Safiatou ; Doumtabe, Didier ; Huang, Chiung Yu ; Dia, Seydou ; Bathily, Aboudramane ; Sangala, Jules ; Kone, Younoussou ; Traore, Abdrahamane ; Niangaly, Moussa ; Dara, Charles ; Kayentao, Kassoum ; Ongoiba, Aissata ; Doumbo, Ogobara K. ; Traore, Boubacar ; Crompton, Peter D. / An intensive longitudinal cohort study of malian children and adults reveals no evidence of acquired immunity to plasmodium falciparum infection. In: Clinical Infectious Diseases. 2013 ; Vol. 57, No. 1. pp. 40-47.
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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.",
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AU - Li, Shanping

AU - Doumbo, Safiatou

AU - Doumtabe, Didier

AU - Huang, Chiung Yu

AU - Dia, Seydou

AU - Bathily, Aboudramane

AU - Sangala, Jules

AU - Kone, Younoussou

AU - Traore, Abdrahamane

AU - Niangaly, Moussa

AU - Dara, Charles

AU - Kayentao, Kassoum

AU - Ongoiba, Aissata

AU - Doumbo, Ogobara K.

AU - Traore, Boubacar

AU - Crompton, Peter D.

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N2 - 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.

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