Chemoprophylaxis and Plasmodium Falciparum NF54 Sporozoite Immunization Challenged by Heterologous Infection
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional

Summary: 
      Malaria, a disease caused by the parasite Plasmodium, is one of the world's major infectious
      diseases. With approximately 627.000 deaths a year, it is both a chief cause of morbidity and
      mortality as well as a significant contribution to ongoing poverty in endemic countries.
      Ultimately, the key to malaria control, and hopefully eradication, would be an effective
      vaccine. Though a number of vaccine-candidates have entered the pipeline of pre-clinical and
      clinical development, they have yet to achieve the level of efficacy necessary for effective
      malaria prevention. It has been shown previously that if healthy human volunteers taking
      chloroquine chemoprophylaxis are repeatedly exposed to Plasmodium parasites through the bites
      of infected mosquitoes, they are fully protected against a later challenge infection with a
      'homologous' (genetically similar) Plasmodium parasite. This process is known as
      ChemoProphylaxis and Sporozoites, or CPS-immunization. One of the obstacles to developing an
      effective vaccine is the genetic heterogeneity of malaria parasites. To further consider the
      development of whole-parasite based vaccines against malaria and in order to better
      understand the protective immunity induced by CPS-immunization, it is essential to
      investigate whether heterologous protection against genetically diverse (heterologous) P.
      falciparum clones can be induced.

      This is a single center, randomized, double-blind study to determine whether healthy
      volunteers immunized with P. falciparum NF54 parasites under chloroquine prophylaxis are
      protected against a challenge infection with the genetically distinct NF135.C10 or NF166.C8
      P. falciparum clones.
    


Intervention name(s): CPS-immunization; malaria challenge infection, P. falciparum NF135.C10; malaria challenge infection, P. falciparum NF166.C8; malaria challenge infection, P. falciparum NF54; atovaquone/proguanil
Intervention type(s): Biological; Biological; Biological; Biological; Drug
Intervention description(s): Subjects will be exposed 3 times to bites from 15 NF54 Plasmodium infected mosquitoes during each immunization, while taking chloroquin prophylaxis.; Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites.; Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF166.C8 sporozoites.; Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF54 sporozoites.; All participants will be treated with atovaquone/proguanil when they develop a malaria infection or on day 28 after malaria challenge infection.
Other intervention name(s): chloroquin; Plasmodium falciparum NF54 sporozoites; Plasmodium falciparum NF135.C10 sporozoites; Plasmodium falciparum NF166.C8 sporozoites; Plasmodium falciparum NF54 sporozoites; Malarone
Intervention MeSH terms: Chloroquine; Atovaquone; Proguanil; Atovaquone, proguanil drug combination
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Malaria; Plasmodium falciparum