Comparative cardiac effects of halofantrine and chloroquine plus chlorpheniramine in children with acute uncomplicated falciparum malaria

The cardiac effects of halofantrine (HF) and chloroquine plus chlorpheniramine (CQ-CP), a histamine I-Il antagonist which reverses chloroquine insensitivity in Plasmodium falciparum in vitro and in vivo, were assessed in 41 children with acute symptomatic uncomplicated P. falciparum malaria by electrocardiographic and clinical monitoring over a period of 14 days. In addition, the cardiac effects of chloroquine (CQ) alone and CQ-CP were compared in 10 age- and sex-marched children. HF produced a significantly higher proportion of abnormally prolonged P-R interval (8 abnormally prolonged out of 132 total P-R events) than CQ-CP (1 of 133 P-R events) (P = 0.03): but a similar proportion of prolonged Q-Tc interval to that of CQ-CP (46 of 149 versus 29 of 134 events, P = 0.07). Compared with pre-treatment Q-Tc, HF significantly prolonged this interval from 6 to 96 h post treatment with a maximum effect at 24 h after commencing HF treatment. CQ-CP by contrast produced significant changes in Q-Tc values from 6 to only 48 h with a maximum effect at 48 h. HF-induced Q-Tc prolongations were significantly higher than those of CQ-CP only at 24 h. The cardiac effects of CQ-CP were similar to those of CQ alone. Despite the electrocardiogram abnormalities, rhythm disturbance was rare and there was no clinical symptom in any of the treatment groups. Compared with HF, CQ-CP produced cardiac effects that were less severe and in fewer children with acute falciparum malaria. The addition of CP to CQ does not significantly amplify the cardiac effects of CQ in children with acute uncomplicated falciparum malaria.