Markers of T Cell Suppression: Associations With Malaria Infection and Antimalarial Treatment in Malian Children
Condition: Malaria
MeSH terms: Malaria
Study type: Observational

Summary: 
      Background:

      - The disease malaria can cause very serious health problems. Researchers want to see if
      malaria affects the way T cells and vaccines work in the body. If it does, they may need to
      give malaria treatments before vaccines. They want to check the T cells in children who do or
      do not get antimalarial treatment.

      Objectives:

      - To study the effect of blood stage malaria on T cell suppression and vaccine responses. To
      describe markers of T cell suppression in children who do or do not receive antimalarial
      treatment.

      Eligibility:

      - Children ages 12 59 months living near Ouelessebougou in Mali. They must have no serious
      illness.

      Design:

        -  Participants will be screened with medical history and physical exam.

        -  Some participants will get a course of antimalarial tablets. Some will not. This will be
           decided at random.

        -  Participants will have monthly visits for up to a year. They will have blood tests at
           each visit.
    

Detailed description: 
      Malaria caused by Plasmodium falciparum continues to be a global problem with devastating
      consequences. New interventions are needed to combat malaria, and progress is being made in
      development of vaccines: a subunit vaccine called RTSS confers partial protection against
      clinical malaria in children and is nearing licensure; a whole organism product called PfSPZ
      Vaccine can confer sterile protection against infection, and is now undergoing field trials.
      NIAID is involved in field trials of PfSPZ Vaccine and other vaccines, and a key question in
      vaccine trial design has been whether concurrent parasitemia will impair vaccine responses.
      The primary hypothesis in this study is that T cell suppression and regulation will decrease
      following antimalarial treatment that clears blood stage parasites for an extended period of
      time.

      Up to 200 children will be recruited into longitudinal studies that will be conducted in
      Ouelessebougou and neighboring villages in Mali. In August 2015, up to 50 children presenting
      for Seasonal Malaria Chemoprevention (SMC) in a village where the government has implemented
      SMC will be enrolled, as well as up to 50 age-matched children residing in an adjacent
      village where SMC has not been implemented by the government of Mali; and then followed
      through the rainy season. In January 2016, up to 100 healthy children in Ouelessebougou
      village area will be enrolled and randomized to receive or not receive a course of
      artemether-lumefantrine, and then followed for the duration of the dry season (Jan-Jun 2016)
      and the subsequent rainy season (Jul-Dec 2016). Samples in both cohort studies (age-matched
      SMC study; randomized artemether-lumefantrine study) will be collected from the children at
      the time of monthly visits and assessed in ex vivo assays for markers of T cell suppression
      as the primary outcome of this study. For our secondary outcomes, we will examine levels of
      regulatory T cells, measure T cell responses in stimulation assays, and survey parasitemia by
      blood smear and by polymerase chain reaction (PCR) assays. We expect that levels of T cell
      suppression and regulatory T cells will be similar between groups before antimalarial
      treatment or malaria infection, but after treatment or in those subjects that remain
      uninfected these levels will be significantly lower as compared to the untreated and or
      infected subjects.
    

Observational model: Cohort
Time perspective: Prospective
Keywords: Plasmodium Falciparum; Regulatory; Chemoprevention; Coartem; Parasitemia