Infectious Diseases

In the mid 1990s it had been established that malarone, a combination of atoquaone and proguanil is highly effective and safe for the treatment of Plasmodium falciparium malaria. The drug company has an interest in establishing whether this drug is also effective at preventing malaria. They therefore propose the following study.

Around 300 children, ages 4-16 from a Public School in an African country will be recruited. Written informed consent from the parents will be sought. The recruited group will be randomized to a treatment group or to a placebo group. Children who sleep under bed nets will be excluded from the study. Because of the expected high rate of parasitaemia in these children, they will receive an initial curative regimen with malarone for the first three days of the study. After this curative phase they will be given malarone or placebo for 12 weeks. Tablets will be given once a day with a fatty meal by a field worker. Body temperature and thick blood smears will be taken weakly, and assessment for adverse event done daily. Blood smears will alos be done within 24 hours in case malaria is suspected. In case of a positive blood smear a second one will be done and assessed independently of the first by at least two medical investigators.

After the initial 12 weeks, the participants will be followed up for another 4 weeks, and thick blood smears and reporting of adverse events done weekly.

The primary endpoint of the study will be a positive blood smear.

Children diagnosed with malaria will be promptly treated by available antimalarial drugs and withdrawn from the study.

Critics of the study argue that this trial is unethical because the population will not benefit from the results of the study: They live in a malaria endemic area where drug prophylaxis is not medically indicated. The primary beneficiaries of this study will be travelers from rich countries visiting developing countries.

The trial sponsors point out that the trial represents no risks to the participants because of the safeguards. In a similar trial in another country, no serious adverse events have been recorded. Furthermore, the children in the trial will received better care than is otherwise available to them.

The local government strongly supports the trial, and in fact does not understand why the local research ethics committee has any reservations.