Immunization With Plasmodium Falciparum Sporozoites Under Chloroquine Versus Mefloquine Prophylaxis
Status:
Completed
Trial end date:
2013-04-01
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 800.000 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 controlled human malaria infections
(CHMIs). CHMIs 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 when 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). Interestingly, sterile protection in 100%
of the human CPS immunized volunteers was achieved by a relatively miniscule dose, i.e. a
total of 45 infectious mosquito bites, strikingly 20-fold more potent than the 1000 bites
needed in a model using irradiated mosquitoes. One possible explanation for this efficient
induction of protective immunity, is the immune modulating effect of chloroquine. The
investigators aim to assess this possible immune modulating effect in CPS immunization by
comparing immunization with P. falciparum sporozoites under chloroquine with immunization
under mefloquine prophylaxis, which has the same antimalarial effect, but not the immune
modulating effects known from chloroquine.
Phase:
N/A
Details
Lead Sponsor:
Radboud University
Collaborator:
ZonMw: The Netherlands Organisation for Health Research and Development
Treatments:
Atovaquone, proguanil drug combination Chloroquine Chloroquine diphosphate Mefloquine Proguanil Vaccines