Chloroquine resistant Plasmodium falciparum in indigenous residents of Cameroon.
Thirty-nine percent (36 of 92) of children in Limbe, Cameroon, treated with chloroquine (10 mg/kg body weight on days 1 and 2, and 5 mg/kg on day 3) for falciparum malaria failed to respond within 7 d of treatment. Twenty-two of these children with chloroquine-resistant malaria were successfully treated with Fansidar [one-half tablet (250 mg sulfadoxine and 25 mg pyrimethamine) per 10 kg body weight], while the other 14 children were cured with mefloquine (25 mg/kg body weight). In vitro, a combination of verapamil at 1.0 x 10(-6) M with chloroquine or desethylchloroquine reversed resistance to the antimalarial drug and its primary metabolite in each of the 2 isolates successfully adapted and maintained in continuous culture. Similar combinations had no effect on susceptibilities of a sensitive reference clone, D6, used as control. Both chloroquine-resistant isolates from Cameroon were significantly more susceptible to mefloquine and halofantrine in vitro than the chloroquine-sensitive reference clone. Clinical observation, and in vitro confirmation, of chloroquine-resistant falciparum malaria in these indigenous children from Cameroon, and the current socio-economic condition in West Africa, underscore the need for pragmatic health management policies for efficient use of alternative antimalarial drugs in controlling drug resistant Plasmodium falciparum in the region. This observation of reversal of chloroquine resistance in isolates of P. falciparum obtained from West Africa, and a previous report on clones obtained from south-east Asia and South America, suggest that the mechanism(s) of resistance to chloroquine may be identical in resistant parasites from the 3 continents.
Oduola
A M
AM
Department of Parasitology, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Moyou-Somo
R S
RS
Kyle
D E
DE
Martin
S K
SK
Gerena
L
L
Milhous
W K
WK
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D002163:Cameroon; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D004338:Drug Combinations / Q000627:therapeutic use; D004351:Drug Resistance; D006801:Humans; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology*; D015767:Mefloquine / Q000494:pharmacology; D010616:Phenanthrenes / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects*; D011739:Pyrimethamine / Q000627:therapeutic use; D013413:Sulfadoxine / Q000627:therapeutic use; D014700:Verapamil / Q000494:pharmacology
D000962:Antimalarials; D004338:Drug Combinations; D010616:Phenanthrenes; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002738:Chloroquine; D014700:Verapamil; C023768:halofantrine; D015767:Mefloquine; D011739:Pyrimethamine; C007278:desethylchloroquine