Analysis of the Immune Response to the Malaria Parasite in Mali, West Africa
Condition: Malaria
MeSH terms: Malaria
Study type: Observational

Summary: 
      This study will examine the immune response to the malaria parasite at the cellular level to
      better understand why people achieve natural immunity to the parasite only after multiple
      infections and why immunity diminishes rapidly in the absence of ongoing infection. The
      results of this study may provide insight into whether and how natural immunity can be
      improved upon by vaccination.

      Healthy people 2-4 and 18-25 years of age who live in the village of Kambila, Mali, may be
      eligible for this 1-year study. Participants have a small blood sample collected from a vein
      in the arm and also from two finger pricks at the beginning of the study, then every 2 months
      for 6 months and at the end of the study (for a total of five samples). People who become ill
      with malaria are evaluated and treated by a physician. Those recovering from their first
      episode of malaria during the study period have another blood sample collection and two
      finger pricks (bringing to six the total number of samples collected).
    

Detailed description: 
      Malaria remains an important public health threat, responsible for over one million deaths
      annually, the majority among African children. The development of a safe and effective
      vaccine is widely regarded as a crucial step forward in the control of this disease. However,
      vaccines tested in clinical trials to date have resulted in very short-lived protection at
      best. This appears to mirror the kinetics of naturally acquired immunity to Plasmodium
      falciparum, in that multiple infections are required over many years before clinical immunity
      is achieved, and then appears to diminish relatively rapidly in the absence of ongoing
      infection. The mechanisms underlying the delayed acquisition and presumably rapid loss of
      humoral immunity are poorly understood. A more detailed understanding of these processes on
      the cellular level may provide insight into whether and how natural immunity can be improved
      upon by vaccination. This longitudinal cohort study in a P. falciparum endemic village of
      Mali proposes to test the hypothesis that resistance to malaria is associated with
      acquisition of P. falciparum specific memory B cells. The 52 week study will cover an entire
      malaria transmission season and will enroll 224 healthy persons ages 2 to 10 and 18 to 25.
      After informed consent is obtained from the participant, or the participant's parent or
      guardian, an age appropriate volume of venous blood will be drawn at baseline, and at 2, 4,
      6, and 12 months thereafter; and serum and peripheral blood mononuclear cells (PBMC) will be
      frozen and stored. One convalescent blood sample per participant will also be drawn within
      two weeks of their first symptomatic P. falciparum infection. Clinical data, including the
      frequency and severity of malaria infections, will be collected during the study period by
      passive surveillance. After 52 weeks, serum and PBMC will be thawed and analyzed to determine
      antibody titers to malaria antigens and to enumerate relevant B cell subpopulations,
      including total and antigen-specific naive, memory, and plasma cells by ELISPOT assays and
      flow cytometry.
    

Keywords: Immunity; Memory; ELISPOT; Malaria; Prospective