Enhanced efficacy of chloroquine-chlorpheniramine combination in acute uncomplicated falciparum malaria in children.
Chlorpheniramine, a histamine H1 receptor antagonist, reverse chloroquine resistance in Plasmodium falciparum in vitro. However, the clinical significance of this remains unclear. We have evaluated the efficacy of chloroquine and a chloroquine-chlorpheniramine combination in 112 consecutive children with acute symptomatic uncomplicated falciparum malaria. There was no significant difference in the parasite and fever clearance times in the 2 treatment groups. However, the proportion of patients in whom parasitaemia increased 24 h after commencement of treatment was significantly higher in the chloroquine group than in the chloroquine-chlorpheniramine group (28.5% vs. 8.3%, chi 2 = 6.61, P < 0.01). There was also a higher proportion of children with RII and RIII responses to treatment in the chloroquine than in the chloroquine-chlorpheniramine group but the difference was not statistically significant. The cure rate on day 14 was higher in the chloroquine-chlorpheniramine group than in the chloroquine group. Chloroquine and its combination with chlorpheniramine were well tolerated, the only prominent adverse effect being pruritus, with equal incidence in both groups. Chlorpheniramine reversed chloroquine resistance in vitro in a similar manner to verapamil in isolates of P. falciparum obtained from the patients. Failure of a response in vivo to chloroquine correlated with resistance in vitro in patients treated with this drug. In contrast, all but one patient with isolates which were chloroquine resistant in vitro were successfully treated with chloroquine-chlorpheniramine combination. These data suggest the enhanced efficacy of chloroquine-chlorpheniramine combination in treating acute uncomplicated P. falciparum infection in children from an endemic area of Nigeria.
Sowunmi
A
A
Department of Pharmacology and Therapeutics, University of Ibadan, Nigeria.
Oduola
A M
AM
Ogundahunsi
O A
OA
Falade
C O
CO
Gbotosho
G O
GO
Salako
L A
LA
D000208:Acute Disease; D000818:Animals; D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000009:adverse effects / Q000627:therapeutic use*; D002744:Chlorpheniramine / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D006634:Histamine H1 Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D018512:Parasitemia / Q000188:drug therapy*; D010963:Plasmodium falciparum / Q000187:drug effects; D011537:Pruritus / Q000139:chemically induced; D016896:Treatment Outcome
D000962:Antimalarials; D006634:Histamine H1 Antagonists; D002744:Chlorpheniramine; D002738:Chloroquine