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Chloroquine is grossly under dosed in young children with malaria: implications for drug resistance

Johan Ursing1, Staffan Eksborg2, Lars Rombo3

  • 1Projecto de Saúde de Bandim, Indepth Network, Bissau, Guinea-Bissau ; Malaria Research Laboratory, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.

Plos One
|January 28, 2014
PubMed

Insights

Chloroquine (CQ) is under-dosed in children, especially those under two years old. Dosing based on body surface area (BSA) ensures therapeutic CQ concentrations and may overcome drug resistance in malaria treatment.

Area of Science:

  • Pharmacology
  • Pediatrics
  • Infectious Diseases

Background:

  • Plasmodium falciparum malaria treatment typically uses a fixed chloroquine (CQ) dose (25 mg/kg) regardless of patient age.
  • Theoretical dosing by body surface area (BSA) suggests current protocols may be suboptimal.
  • Previous studies indicated doubling the CQ dose per kilogram improved efficacy in African children with resistant malaria.

Purpose of the Study:

  • To investigate the impact of age on chloroquine (CQ) concentrations in children.
  • To determine if current weight-based dosing adequately achieves therapeutic CQ levels across different pediatric age groups.

Main Methods:

  • Analysis of whole blood CQ concentrations from 150 children receiving 25 mg/kg and 302 children receiving 50 mg/kg in prior clinical trials.
  • CQ concentrations were normalized for dose administered per kilogram (mg/kg) and per square meter (mg/m²).
  • Statistical analysis to assess the relationship between age and normalized CQ concentrations.

Main Results:

  • CQ concentrations normalized for mg/kg dose decreased significantly with decreasing age (p<0.001).
  • CQ concentrations normalized for mg/m² dose were independent of age.
  • Younger children (<2 years) required approximately double the mg/kg dose of older children (10-14 years) to achieve similar CQ concentrations.

Conclusions:

  • Current weight-based chloroquine (CQ) dosing is inadequate for pediatric malaria treatment, leading to under-dosing in younger children.
  • Dosing CQ according to body surface area (BSA) is recommended to achieve consistent therapeutic concentrations across all pediatric ages.
  • Adjusted dosing, potentially increasing by up to three-fold for the youngest children, may be safely administered and could help overcome CQ resistance in malaria-endemic regions like Africa.
Abstract

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