High-dose chloroquine for uncomplicated Plasmodium falciparum malaria is well tolerated and causes similar QT prolongation as standard dose chloroquine in children
Ursing J., Rombo L., Eksborg S., Larson L., Bruvoll A., Tarning J., Rodrigues A., Kofoed P-E.
<jats:p><jats:bold>Background.</jats:bold> Higher chloroquine doses can effectively treat up to 93-96% of malaria infections caused by <jats:italic>P. falciparum</jats:italic> carrying the resistance conferring chloroquine resistance transporter (<jats:italic>pfcrt</jats:italic>) 76T allele. The tolerability of 50 (double standard dose) and 70 mg/kg total chloroquine doses were assessed in this study.</jats:p> <jats:p><jats:bold>Methods.</jats:bold> Fifteen, 4-8 year old children, with uncomplicated malaria were given 10 mg/kg of chloroquine twice daily for two days and 5 mg/kg twice daily on the third day. Fifteen additional children were given 5 mg/kg twice daily for two more days. Chloroquine concentrations, blood pressure, ECG, parasite density and adverse events were assessed until day 28.</jats:p> <jats:p><jats:bold>Results.</jats:bold> Both dosages were well tolerated and symptoms resolved by day three in parallel with increasing chloroquine concentrations. The median QTc interval was 12-26 milliseconds higher at expected peak concentrations compared to day 0 (p<0.001). <jats:italic>Pfcrt</jats:italic> 76T was associated with delayed parasite clearance. Day 28 clinical and parasitological responses against <jats:italic>P. falciparum</jats:italic> with <jats:italic>pfcrt</jats:italic> 76T were 57% (4/7) and 67% (4/6) after treatment with 50 and 70 mg/kg, respectively</jats:p> <jats:p><jats:bold>Conclusions.</jats:bold> Dosages were well tolerated and no severe cardiac adverse events occurred. QTc interval increase was similar to that found in adults taking 25 mg/kg of chloroquine.</jats:p>