ENHANCED EFFICACY OF CHLOROQUINE-CHLORPHENIRAMINE COMBINATION IN ACUTE UNCOMPLICATED FALCIPARUM-MALARIA IN CHILDREN

Chlorpheniramine, a histamine H-1 receptor antagonist, reverses chloro quine resistance in Plasmodium falciparum in vitro. However, the clini cal significance of this remains unclear. We have evaluated the effica cy of chloroquine and a chloroquine-chlorpheniramine combination in 11 2 consecutive children with acute symptomatic uncomplicated falciparum malaria. There was no significant difference in the parasite and feve r clearance times in the 2 treatment groups. However, the proportion o f patients in whom parasitaemia increased 24 h after commencement of t reatment 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-chlo rpheniramine group but the difference was not statistically significan t. The cure rate on day 14 was higher in the chloroquine-chlorpheniram ine group than in the chloroquine group. Chloroquine and its combinati on with chlorpheniramine were well tolerated, the only prominent adver se effect being pruritus, with equal incidence in both groups. Chlorph eniramine 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 resistan ce in vitro in patients treated with this drug. In contrast, all but o ne patient with isolates which were chloroquine resistant in vitro wer e successfully treated with chloroquine-chlorpheniramine combination. These data suggest the enhanced efficacy of chloroquine-chlorphenirami ne combination in treating acute uncomplicated P. falciparum infection in children from an endemic area of Nigeria.