Chemoprophylaxis of malaria: underlying principles and their realization

Drug prophylaxis of malaria, first practised with quinine, became safer and simpler after the introduction of mepacrine and later chloroquine. The occurrence and spread of chloroquine resistance in Plasmodium falciparum rendered prophylaxis more difficult as it necessitated the use of alternative drugs, some of which were associated with major adverse reactions. The presence of resistance to sulfadoxine-pyrimethamine in some areas compounded the problem. The current repertoire of prophylactic drugs for routine use includes chloroquine, proguanil and mefloquine. The indications for which depend on the local sensitivity pattern of the malaria parasites, especially Plasmodium falciparum, duration of exposure, special risk factors and immune status. A closed look at these drugs, especially proguanil, suggests that their efficacy or safety can be increased by following sound pharmacokinetic principles. Chlorproguanil has so far not been used in keeping with its pharmacological characteristics. This drug holds considerable promise for improving the drug prophylaxis of malaria, particularly if it can be associated with a well, tolerated synergist.