Immunization With Different Doses of Plasmodium Falciparum Sporozoites Under Chloroquine Prophylaxis
Condition: Plasmodium Falciparum Malaria
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional

Summary: 
      Malaria is one of the major infectious diseases in the world with a tremendous impact on the
      quality of life significantly contributing to the ongoing poverty in endemic countries. It
      causes almost one million deaths per year, the majority of which are children under the age
      of five. The malaria parasite enters the human body through the skin, by the bite of an
      infected mosquito. Subsequently, it invades the liver and develops and multiplies inside the
      hepatocytes. After a week, the hepatocytes burst open and the parasites are released in the
      blood stream, causing the clinical phase of the disease.

      As a unique opportunity to study malaria immunology and efficacy of immunisation strategies,
      a protocol has been developed in the past to conduct experimental human malaria infections
      (EHMIs). EHMIs generally involve small groups of malaria-naïve volunteers infected via the
      bites of P. falciparum infected laboratory-reared Anopheline mosquitoes. Although potentially
      serious or even lethal, P. falciparum malaria can be radically cured at the earliest stages
      of blood infection where risks of complications are virtually absent.

      The investigators have shown previously that healthy human volunteers can be protected from a
      malaria mosquito (sporozoite) challenge by immunization with sporozoites (by mosquito bites)
      under chloroquine prophylaxis (CPS immunization). However, it is unknown how many mosquito
      bites are necessary to confer protection. Moreover, as all volunteers were protected in this
      study, no correlates of protection could be established. For future development of vaccines
      and understanding of protective immunity to malaria, it is important to investigate the
      lowest dose of CPS immunization that confers 100% protection and to find correlates of
      protection. Therefore, the present study aims to make the CPS immunization protocol more
      sensitive by lowering the number of infected mosquito bites, in order to study the underlying
      mechanisms of protection.
    


Intervention name(s): Chloroquine prophylaxis; Immunization; Plasmodium falciparum challenge; Malarone treatment
Intervention type(s): Drug; Biological; Biological; Drug
Intervention description(s): The chloroquine dose used will be 300mg for the first two days, followed by 300mg per week, for 13 weeks.; All groups will be immunised with mosquitobites. The number of infected mosquitoes differs per group, as clarified in group description.; Exposure to the bites of 5 Plasmodium falciparum infected mosquitoes.; When thick smear positive, of ar day 21 after challenge, all volunteers will be treated with malarone.
Other intervention name(s): atovaquon/proguanil
Intervention MeSH terms: Chloroquine; Proguanil; Atovaquone, proguanil drug combination
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science