Immunization With Different Doses of Plasmodium Falciparum Sporozoites Under Chloroquine Prophylaxis
Status:
Completed
Trial end date:
2012-03-01
Target enrollment:
Participant gender:
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.
Phase:
N/A
Details
Lead Sponsor:
Radboud University
Treatments:
Atovaquone, proguanil drug combination Chloroquine Chloroquine diphosphate Proguanil Vaccines