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 chlorpheniram ine (CQ-CP), a histamine I-Il antagonist which reverses chloroquine insensi tivity in Plasmodium falciparum in vitro and in vivo, were assessed in 41 c hildren with acute symptomatic uncomplicated P. falciparum malaria by elect rocardiographic and clinical monitoring over a period of 14 days. In additi on, the cardiac effects of chloroquine (CQ) alone and CQ-CP were compared i n 10 age- and sex-marched children. HF produced a significantly higher prop ortion 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 si milar proportion of prolonged Q-Tc interval to that of CQ-CP (46 of 149 ver sus 29 of 134 events, P = 0.07). Compared with pre-treatment Q-Tc, HF signi ficantly prolonged this interval from 6 to 96 h post treatment with a maxim um 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 effe ct at 48 h. HF-induced Q-Tc prolongations were significantly higher than th ose of CQ-CP only at 24 h. The cardiac effects of CQ-CP were similar to tho se of CQ alone. Despite the electrocardiogram abnormalities, rhythm disturb ance was rare and there was no clinical symptom in any of the treatment gro ups. 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 wi th acute uncomplicated falciparum malaria.