Early parasite clearance following artemisinin-based combination therapy among Ugandan children with uncomplicated Plasmodium falciparum malaria

Malar J. 2014 Jan 28;13:32. doi: 10.1186/1475-2875-13-32.

Abstract

Background: Artemisinin-based combination therapy (ACT) is widely recommended as first-line therapy for uncomplicated Plasmodium falciparum malaria worldwide. Artemisinin resistance has now been reported in Southeast Asia with a clinical phenotype manifested by slow parasite clearance. Although there are no reliable reports of artemisinin resistance in Africa, there is a need to better understand the dynamics of parasite clearance in African children treated with ACT in order to better detect the emergence of artemisinin resistance.

Methods: Data from a cohort of Ugandan children four to five years old, enrolled in a longitudinal, randomized, clinical trial comparing two leading ACT, artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP), were analysed. For all episodes of uncomplicated P. falciparum malaria over a 14-month period, daily blood smears were performed for three days following the initiation of therapy. Associations between pre-treatment variables of interest and persistent parasitaemia were estimated using multivariate, generalized, estimating equations with adjustment for repeated measures in the same patient.

Results: A total of 202 children were included, resulting in 416 episodes of malaria treated with AL and 354 episodes treated with DP. The prevalence of parasitaemia on days 1, 2, and 3 following initiation of therapy was 67.6, 5.6 and 0% in those treated with AL, and 52.2, 5.7 and 0.3% in those treated with DP. Independent risk factors for persistent parasitaemia on day 1 included treatment with AL vs DP (RR = 1.34, 95% CI 1.20-1.50, p < 0.001), having a temperature ≥38.0°C vs < 37.0°C (RR = 1.19, 95% CI 1.05-1.35, p = 0.007) and having a parasite density >20,000/μL vs <4,000/μL (RR = 3.37, 95% CI 2.44-4.49, p < 0.001). Independent risk factors for having persistent parasitaemia on day 2 included elevated temperature, higher parasite density, and being HIV infected.

Conclusions: Among Ugandan children, parasite clearance following treatment with AL or DP was excellent with only one of 752 patients tested having a positive blood slide three days after initiation of therapy. The type of ACT given, pre-treatment temperature, pre-treatment parasite density and HIV status were associated with differences in persistent parasitaemia, one or two days following therapy.

Trial registration: Current Controlled Trials Identifier NCT00527800.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antimalarials / administration & dosage
  • Antimalarials / pharmacology*
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins / administration & dosage
  • Artemisinins / pharmacology*
  • Child, Preschool
  • Drug Combinations
  • Drug Resistance
  • Ethanolamines / administration & dosage
  • Ethanolamines / pharmacology*
  • Fluorenes / administration & dosage
  • Fluorenes / pharmacology*
  • Humans
  • Kinetics
  • Longitudinal Studies
  • Malaria, Falciparum / drug therapy*
  • Malaria, Falciparum / parasitology
  • Parasitemia / drug therapy*
  • Parasitemia / parasitology
  • Plasmodium falciparum / drug effects*
  • Quinolines / administration & dosage
  • Quinolines / pharmacology*
  • Risk Factors
  • Uganda

Substances

  • Antimalarials
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins
  • Drug Combinations
  • Ethanolamines
  • Fluorenes
  • Quinolines
  • dihydroartemisinin
  • piperaquine

Associated data

  • ClinicalTrials.gov/NCT00527800