Anaemia following Artemisinin-Based Combination Treatments of Uncomplicated Plasmodium falciparum Malaria in Children: Temporal Patterns of Haematocrit and the Use of Uncomplicated Hyperparasitaemia as a Model for Evaluating Late-Appearing Anaemia

Chemotherapy. 2017;62(4):231-238. doi: 10.1159/000449366. Epub 2017 Apr 28.

Abstract

Background: In severe malaria, intravenous artesunate may cause delayed haemolytic anaemia but there has been little evaluation of the propensity of oral artemisinin-based combination treatments (ACTs) to cause late-appearing anaemia.

Methods: The frequency of anaemia (haematocrit <30%), and temporal changes in haematocrit were evaluated in 1,191 malarious children following ACTs. "Haematocrit conservation" was evaluated by using the fall in haematocrit/1,000 asexual parasites cleared from the peripheral blood (FIH/1,000 asexual parasites cpb), and the ratio of the average haematocrit (on the first 3 days of starting treatment):total parasitaemia cleared.

Results: The frequency of anaemia decreased significantly following treatment. FIH/1,000 asexual parasites cpb, average haematocrit:total parasitaemia cleared, and mean haematocrit 5 weeks after treatment began were significantly lower in hyperparasitaemic children than in children without hyperparasitaemia, suggesting haematocrit conservation during treatment followed later by a loss of haematocrit. Asymptomatic late-appearing anaemia occurred in 6% of the children.

Conclusion: Artesunate-amodiaquine and artemether-lumefantrine contribute to haematocrit conservation at high parasitaemias but may cause late-appearing anaemia.

Keywords: Anaemia; Artemisinin-based combination treatments; Children; Nigeria; Uncomplicated hyperparasitaemia.

MeSH terms

  • Amodiaquine / adverse effects*
  • Amodiaquine / therapeutic use
  • Anemia / etiology*
  • Antimalarials / adverse effects*
  • Antimalarials / therapeutic use
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins / adverse effects*
  • Artemisinins / therapeutic use
  • Child
  • Child, Preschool
  • Drug Combinations
  • Ethanolamines / adverse effects*
  • Ethanolamines / therapeutic use
  • Female
  • Fluorenes / adverse effects*
  • Fluorenes / therapeutic use
  • Hematocrit
  • Humans
  • Infant
  • Malaria, Falciparum / complications
  • Malaria, Falciparum / drug therapy*
  • Male
  • Parasitemia / complications

Substances

  • Antimalarials
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins
  • Drug Combinations
  • Ethanolamines
  • Fluorenes
  • amodiaquine, artesunate drug combination
  • Amodiaquine