Plasmodium Resistance in A. Gambiae
Condition: Malaria; Plasmodium Falciparum Malaria
MeSH terms: Malaria; Malaria, Falciparum
Study type: Observational

Summary: 
      The purpose of this study is to find new ways to control malaria by looking at mosquitoes
      infected with the disease. Knowledge of the genetics that affect the spread of malaria by
      mosquitoes will help in developing control strategies. A small amount of blood from infected
      humans will be used to infect the mosquitoes. No contact will occur between the human subject
      and the mosquito. Study participants will be divided into 2 groups of 20, for a total of 40
      children, ages 5-10, in Burkina Faso, West Africa. Each subject will be screened by
      finger-prick once per month, from June through October, until they reach a maximum age of 10.
      Two positive subjects of the 40 screened will be asked to donate about 1 teaspoon of blood,
      which will be used to feed and infect the mosquitoes. Study participants will be involved in
      study related procedures for a maximum of 5 years.
    

Detailed description: 
      Malaria is a blood-borne human disease, and is transmitted to mosquitoes in the bloodmeal, an
      obligatory step in human malaria transmission. This is a study of malaria parasites in the
      major mosquito vector of human malaria in Africa, Anopheles gambiae. The intent of the study
      is to develop modern forms of vector control that would specifically decrease disease
      transmission by targeting the vector. Genetic linkage mapping of the mosquito vector
      (Anopheles gambiae) in Africa has identified a small genomic region in the mosquito that
      controls most of the natural genetic variation for resistance to mosquito infection with the
      human malaria parasite (Plasmodium falciparum). In order to study the influence of mosquito
      vector genetics on transmission of malaria parasites, mosquitoes are exposed to malaria
      parasites and then the efficiency of parasite development within the mosquito is measured.
      The goal of the study is to promote and expand this non-transmitting subset of the vector
      population in order to decrease or interrupt human malaria transmission. The study focuses on
      the mosquito vector, not the human subjects infected with malaria. The reason for the use of
      human subjects is that 5cc of blood from human subjects naturally infected with malaria will
      be used to infect the mosquitoes by an indirect feeding method that involves a membrane
      feeding device. There will be no contact of human subjects with the mosquitoes. The blood-fed
      mosquitoes are the primary focus of this study, not human subjects. DNA extracted from
      mosquitoes that fed on the blood of human study subjects will be analyzed genetically by
      microsatellites and single-nucleotide polymorphisms (SNPs) to identify mosquito genes that
      control mosquito resistance to malaria parasites. The genetic analysis is of mosquito DNA,
      not DNA of the human subjects. At the time mosquitoes are analyzed, one week after the
      bloodmeal, there is no residual genetic, DNA, cellular, or any material of the human subject
      remaining within the mosquito, and thus no genetic or other information can derive from the
      human source, even accidentally. A secondary objective will be to identify
      naturally-occurring mechanisms of mosquito resistance to malaria infection in Burkina Faso.
      Mosquitoes that are not infected by malaria parasites do not transmit malaria. Research that
      identifies these genes for resistance may lead to a method for blocking the transmission of
      malaria. A total enrollment of 40 healthy volunteers, 5-10 years old, is planned at one site
      in Burkina Faso, West Africa. Malaria transmission occurs during the rainy season (June
      through October). There will be 2 experimental cycles per month from June through October (10
      cycles per year). There will be two such groups of 20, for a total study size of 40. Each
      group of 20 will be screened for malaria in an alternating pattern, so each group of 20 is
      screened no more frequently than once per month during the malaria transmission season, for a
      total study duration of 5 years. One human subject with mature malaria gametocytes (the
      transmission stage infective to mosquitoes) will be identified the day before the projected
      experimental infection of mosquitoes. Blood (5 cc) will be drawn from the subject, which will
      occur no more frequently than once per month. Twenty subjects are screened for malaria
      parasites (by standard diagnosis) to insure finding at least one positive donor per cycle.
      The 5cc of blood is used to feed and infect mosquitoes, which are the subject of this study.
      Subject participation is approximately 5 months per year, for the total study duration of 5
      years. A target sample size of 200 mosquitoes with a set of 150 markers will be analyzed in
      this study. A successful outcome of this study is genetic identification of mosquito genes
      controlling resistance and susceptibility to P. falciparum infection of the mosquitoes.
    

Time perspective: Prospective
Keywords: Malaria, Plasmodium falciparum, mosquito, Africa, Anopheles