Malaria chemoprophylaxis: when should we use it and what are the options?

Abstract

Malaria chemoprophylaxis concerns prescribing healthy individuals medication for an infection they have an unknown chance of getting. Sensible use of malaria chemoprophylaxis is a balance between the risk of infection and death, and the risk of side effects. The risk of infection can be broken down into the risk of being bitten by a malaria-infected mosquito and the risk of the malaria parasites being resistant to the drug used for prophylaxis. Our knowledge of these parameters is patchy. The risk of infection is not uniform at a given location and the standard of living will greatly influence risk. It is suggested that chemoprophylaxis should not be recommended in areas with less than ten reported cases of P. falciparum malaria per 1000 inhabitants per year. The resistance pattern is known to a certain extent but, for instance, diverging opinion of how much resistance to chloroquine there is in West Africa illustrates the lack of data. There is much debate on rare adverse events, which usually escape Phase III studies prior to registration and are only picked up by passive, postmarketing surveillance. The lessons over the past 20 years with the introduction of amodiaquine, pyrimethamine/dapsone (Maloprim, GlaxoSmithKline) and pyrimethamine/sulfadoxine (Fansidar, Roche), which were all withdrawn for prophylaxis after a few years, show how sensitive drugs for chemoprophylaxis are to side effects. Three levels of chemoprophylaxis are used: chloroquine in areas with sensitive P. falciparum, chloroquine plus proguanil in areas with low level chloroquine resistance, and atovaquone/proguanil (Malarone, GlaxoSmithKline), doxycycline or mefloquine (Lariam, Roche) in areas with extensive resistance against chloroquine and proguanil. Primaquine and the primaquone analog tafenoquine may be future alternatives but otherwise there are few new drugs for chemoprophylaxis on the horizon.