High-dose chloroquine for uncomplicated plasmodium falciparum malaria is well tolerated and causes similar QT interval prolongation as standard-dose chloroquine in children

Johan Ursing*, Lars Rombo, Staffan Eksborg, Lena Larson, Anita Bruvoll, Joel Tarning, Amabelia Rodrigues, Poul Erik Kofoed

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Higher chloroquine doses can effectively treat up to 93 to 96% of malaria infections caused by Plasmodium falciparum carrying the resistance-conferring chloroquine resistance transporter (pfcrt) 76T allele. The tolerability of 50 (double the standard dose) and 70 mg/kg total chloroquine doses were assessed in this study. Fifteen 4- to 8-year-old children with uncomplicated malaria were given 10 mg/kg of chloroquine twice daily for 2 days and 5 mg/kg twice daily on the third day. Fifteen additional children were given 5 mg/kg twice daily for 2 more days. Chloroquine concentrations, blood pressure, electrocardiograms (ECGs), parasite density, and adverse events were assessed until day 28. Both dosages were well tolerated, and symptoms resolved by day 3 in parallel with increasing chloroquine concentrations. The median corrected QT (QTc) interval was 12 to 26 ms higher at expected peak concentrations than at day 0 (P < 0.001). Pfcrt 76T was associated with delayed parasite clearance. Day 28 clinical and parasitological responses against P. falciparum with pfcrt 76T were 57% (4/7) and 67% (4/6) after treatment with 50 and 70 mg/kg, respectively. Dosages were well tolerated, and no severe cardiac adverse events occurred. The QTc interval increase was similar to that found in adults taking 25 mg/kg of chloroquine.

Original languageEnglish
Article numbere01846
JournalAntimicrobial Agents and Chemotherapy
Volume64
Issue number3
Number of pages12
ISSN0066-4804
DOIs
Publication statusPublished - Mar 2020

Keywords

  • Cardiac safety
  • Chloroquine
  • Guinea-Bissau
  • Pfcrt
  • Pharmacokinetics
  • Plasmodium falciparum
  • Tolerability
  • Treatment

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