Experimental Human Malaria Infection After Immunization With 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, Plasmodium falciparum (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 challenge by immunization with mosquito-bites under chloroquine
      prophylaxis (CPS immunization). However, it is unknown whether this protection is based on
      immunity directed towards the liver- or the blood stage of the disease. For future
      development of vaccines and understanding of protective immunity to malaria, it is important
      to investigate at which level protective immunity is generated by CPS immunization.
      Therefore, we aim to investigate whether CPS immunization confers protection to a blood-stage
      challenge.
    


Intervention name(s): Chloroquine prophylaxis; Immunization; Plasmodium falciparum Bloodstage challenge; Plasmodium falciparum mosquito challenge; Malarone treatment
Intervention type(s): Drug; Biological; 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.; Groups 1 and 2 will be immunized with 3 times 15 bites of Pf infected mosquitoes under chloroquine prophylaxis.; Groups 1 and 3 will be challenged by intravenous administration of Plasmodium falciparum infected erythrocytes.; Groups 2 and 4 will be challenged by 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: Single (Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Plasmodium; falciparum; malaria; chloroquine; immunity