Halofantrine resistance in African countries [letter]

A comment is made on the study of Brasseur and colleagues who accounted for the rapid emergence of Plasmodium falciparum resistance to halofantrine by high drug-pressure from halofantrine in contrast with the absence of resistance to mefloquine in the Congo. The same micro-isotopic test with results expressed in IC50 (the concentration inhibiting 3H-hypoxanthine uptake by 50%) was employed to investigate malaria drug resistance in Brazzaville city during March-April 1990. In 1990 it was demonstrated that 6 strains of P falciparum of 67 tested had a mefloquine IC50 >30 nmol/L. The findings of these 2 studies were contradictory for halofantrine while for chloroquine quinine and mefloquine they were similar. Methodological difficulties with halofantrine could be implicated but the Brasseur in-vivo study seemed to confirm high resistance. None of the 8 Congolese strains nor 15 strains from Cameroon tested showed in vitro resistance to halofantrine (threshold 5 nmol/L). The hypothesis of Brasseur concerning drug pressure is surprising because it implies: 1) no cross-resistance between mefloquine and halofantrine; 2) high pressure from a drug which unlike mefloquine is not used chemoprophylactically and which has a shorter half-life; and 3) the high consumption of halofantrine in Djoumouna. At the end of 1989 a questionnaire administered to 600 mothers of Brazzaville on antimalarials used to treat malaria in children indicated: chloroquine 47% quinine 28% amodiaquine 18% sulphadoxine plus pyrimethamine 3.5% and others 3-5%. Halofantrine was mentioned in less than .5% of cases. The reduced sensitivity towards aminoalcohols in Central Africa because of drug pressure could be explained by cross-resistance with quinine taken in large quantities by the population since the emergence of chloroquine resistance. 4-aminoquinolines continue to be effective in the Congo in the Central Africa Republic and in Gabon.