One hundred thirty nonimmune subjects living in Yaounde, Cameroon, completed an 18-month prospective study on the efficacy and safety of weekly chloroquine and daily proguanil (chloroguanide) (Ch-P) in malaria prevention. A total of 9 of 78 Ch-P-treated subjects and 26 of 52 subjects who received no prophylaxis contracted Plasmodium falciarum infection during this period (P < 0.00005). These two groups were comparable for demographic parameters and degree of exposure. Clinical manifestations were of similar severities in the two groups, but parasite counts were significantly higher in the subjects who received no prophylaxis (P < 0.00005). Side effects of prophylaxis were frequent (31%), minor, and related to chloroquine, and they usually resolved within 4 to 6 weeks. Prolonged administration of Ch-P is safe and effectively prevents P. fakciparum malaria in an endemic area with a high prevalence of chloroquine resistance.

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Fifty subjects with acute uncomplicated falciparum malaria were treated orally with a new micronized formulation of halofantrine. The dose given corresponded to one-half the normal dose for the standard formulation. Parasitemia cleared in all subjects within 78 h. There was recrudescence of falciparum malaria in seven subjects after day 14. The mean standard deviation clearance times of parasitemia and fever were 49.0 14.2 and 24.3 13.2 h, respectively. Other clinical symptoms related to malaria cleared within the first 3 days. Pruritus occurred in two subjects, back pain occurred in one subject, and diarrhea occurred in one subject; all of these symptoms were mild. Hematological and biochemical indices were not adversely affected by treatment except in five subjects in whom minor and transitory increases in aspartate aminotransferase and alanine aminotransferase were observed. Micronized halofantrine appears to be a safe, well-tolerated, and effective treatment for acute falciparum malaria in semiimmune patients.The spread of chloroquine-resistant Plasmodium falciparum to most countries in Africa has prompted the development of alternative drugs for the treatment of malaria. Halofantrine has been used since 1988 in France and some West and Central African countries and was demonstrated to be effective in treating resistant falciparum malaria (5, 10, 17). However, a major drawback of halofantrine is its poor and variable absorption and bioavailability between subjects; these have been responsible for a number of treatment failures (3,11,12,15,18 greater, respectively. These doses correspond to one-half the normal dose for the standard formulation of halofantrine (25 mg/kg of body weight). The drug was administered to patients without a specific food regimen. Patients were followed at home, and the intake of the doses was supervised. Investigations including clinical examination, temperature, symptom recording, and blood smears were performed twice daily for the first 4 days and on days 7, 14, 21, and 28 posttreatment. Parasite counts on blood smears were determined twice daily until two successive thick blood smears were negative.Routine blood examinations (hematocrit, hemoglobin, erythrocyte count, total leukocyte count, and platelet count) were performed before treatment and on days 3, 7, 14, 21, and 28 posttreatment.Aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase, bilirubin, and creatinine were measured before treatment and on days 3, 7, and 28 posttreatment.In vitro antimalarial drug susceptibilities (chloroquine, quinine, and halofantrine) were assessed before treatment by an isotopic semimicrotest (13). Briefly, a suspension (700 ,ul per well) of parasitized erythrocytes (1.5% hematocrit, 0.2 to 0.5% initial parasitemia) in RPMI 1640 medium supplemented with 10% human serum and buffered with 25 mmol of N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) per liter and 25 mmol of NaHCO3 per liter was distributed in predosed 24-well plates. The plates were incu...