Malaria chemoprophylaxis in the age of drug resistance. II. Drugs that maybe available in the future

All current regimens of malaria chemoprophylaxis have serious drawbacks as a result of either suboptimal efficacy, difficulty with medication complian ce, or adverse events. Two 8-aminoquinolines may be approaching registratio n, with primaquine having completed its prophylactic field testing and tafe noquine having begun advanced field testing at the end of 2000. Primaquine has long been used for management of relapses of malaria, but in the past d ecade, it has been reexamined for use in malaria prevention in order to sto p infection in the liver. In field trials performed in Indonesia and Colomb ia, the efficacy of primaquine for malaria prevention was similar to 90%, c ompared with that of placebo. Because of its short half-life, primaquine re quires daily administration. For adults, the prevention regimen is 30 mg ba se daily (0.5 mg base/kg/day), and it can probably be discontinued soon aft er departure from an area where malaria is endemic. To kill parasites that already exist in the liver, terminal prophylaxis is given after exposure to relapses of malaria infection; for adults, such prophylaxis usually consis ts of 15 mg base (0.3 mg base/kg/day) given daily for 2 weeks. Primaquine-i nduced gastrointestinal disturbances can be minimized if the drug is taken with food. Neither primaquine nor tafenoquine should be given to persons wi th glucose-6-phosphate dehydrogenase deficiency, to avoid the development o f potentially severe drug-induced hemolysis. Tafenoquine is an analogue of primaquine that is more potent than the parent drug. Field trials in Kenya, Ghana, Gabon, and Southeast Asia have demonstrated an efficacy rate of sim ilar to 90% for tafenoquine. Its long half-life allows for infrequent dosin g (currently tested at 200 mg base/week), and its effect on parasites at th e liver stage may allow for drug discontinuation at the time of departure f rom the area of endemicity.