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<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&lt;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>

Original publication

DOI

10.1128/aac.01846-19

Type

Journal article

Journal

Antimicrobial Agents and Chemotherapy

Publisher

American Society for Microbiology

Publication Date

06/01/2020