A Longitudinal Systems Biological Analysis of Naturally Acquired Malaria Immunity in Mali
Condition: Malaria
MeSH terms: Malaria
Study type: Observational

Summary: 
      Plasmodium falciparum (Pf) malaria remains a major cause of morbidity and mortality
      worldwide. A malaria vaccine would contribute towards efforts to control and eliminate
      malaria. Optimism that an effective malaria vaccine can be developed is derived in part from
      the observation that repeated Pf infections can induce protective immunity; however, the
      mechanisms underlying acquired malaria immunity remain unclear. The goal of the current study
      is to apply systems biological tools to an observational cohort in an area of intense
      seasonal Pf transmission to gain insight into the mechanisms underlying naturally acquired
      malaria immunity. This year-long observational-cohort study of 700 individuals (3 months and
      25 years of age) will be conducted in the rural village of Kalifabougou, Mali, where Pf
      transmission is intense and seasonal. Asymptomatic Pf infection and malaria episodes will be
      detected by passive and active surveillance. Immune parameters of malaria-protected and
      -susceptible individuals will be assayed from blood samples collected at strategic time
      points relative to the malaria season. The primary objective is to identify genome-wide
      expression profiles induced by Pf infection that are associated with protection from malaria.
      Secondary objectives include identifying age-related (surrogate for cumulative Pf exposure)
      changes in Pf-induced gene-expression and serum cytokine profiles, and examining Pf-specific
      antibody profiles that are associated with protection from malaria using a protein microarray
      representing 2000 Pf proteins (40 percent of the Pf proteome). Exploratory objectives for
      this study are to compare the magnitude and quality of the Pf-specific CD4 plus T cell
      response in malaria-protected and -susceptible individuals and determine how this response
      varies with age and among individuals before, during, and after malaria season, as well as
      compare various immune parameters in Pf-infected and uninfected individuals at the end of the
      dry season to investigate host immune factors associated with chronic asymptomatic Pf
      infection....
    

Detailed description: 
      Plasmodium falciparum (Pf) malaria remains a major cause of morbidity and mortality
      worldwide. A malaria vaccine would contribute towards efforts to control and eliminate
      malaria. Optimism that an effective malaria vaccine can be developed is derived in part from
      the observation that repeated Pf infections can induce protective immunity; however, the
      mechanisms underlying acquired malaria immunity remain unclear. The goal of the current study
      is to apply systems biological tools to an observational cohort in an area of intense
      seasonal Pf transmission to gain insight into the mechanisms underlying naturally acquired
      malaria immunity. This observational-cohort study of individuals (3 months and 40 years of
      age) will be conducted in the rural village of Kalifabougou, Mali, where Pf transmission is
      intense and seasonal. Asymptomatic Pf infection and malaria episodes will be detected by
      passive and active surveillance. Immune parameters of malaria-protected and -susceptible
      individuals will be assayed from blood samples collected at strategic time points relative to
      the malaria season. The primary objective is to identify genome-wide expression profiles
      induced by Pf infection that are associated with protection from malaria. Secondary
      objectives include identifying age-related (surrogate for cumulative Pf exposure) changes in
      Pf-induced gene-expression and serum cytokine profiles, and examining Pf-specific antibody
      profiles that are associated with protection from malaria using a protein microarray
      representing 2000 Pf proteins (approximately 40% of the Pf proteome). Exploratory objectives
      for this study are to compare the magnitude and quality of the Pf-specific CD4+ T cell
      response in malaria-protected and -susceptible individuals and determine how this response
      varies with age and among individuals before, during, and after malaria season, as well as
      compare various immune parameters in Pf-infected and uninfected individuals at the end of the
      dry season to investigate host immune factors associated with chronic asymptomatic Pf
      infection.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        All study subjects will be selected from the village of Kalifabougou, Mali. Male and female
        volunteers 3 months to 40 years of age will be included. This age range captures the period
        over which immunity to malaria is acquired in areas of intense Pf transmission like Mali.
        There is no exclusion based on race, ethnicity, or gender.@@@
      
Keywords: Plasmodium; PBMC; Natural History; Malaria