Immunization With Different Doses of Plasmodium Falciparum Sporozoites Under Chloroquine Prophylaxis

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.

Conditions

• Plasmodium Falciparum Malaria

Interventions

DRUG

Chloroquine prophylaxis

The chloroquine dose used will be 300mg for the first two days, followed by 300mg per week, for 13 weeks.

BIOLOGICAL

Immunization

All groups will be immunised with mosquitobites. The number of infected mosquitoes differs per group, as clarified in group description.

BIOLOGICAL

Plasmodium falciparum challenge

Exposure to the bites of 5 Plasmodium falciparum infected mosquitoes.

DRUG

Malarone treatment

When thick smear positive, of ar day 21 after challenge, all volunteers will be treated with malarone.

Sponsors & Collaborators

• Radboud University Medical Center

  lead OTHER

Principal Investigators

• Leo G Visser, MD, PhD · Leiden University Medical Centre

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

35 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2011-04-30

Primary Completion

2012-01-31

Completion

2012-03-31

Countries

• Netherlands

Study Locations