Post-treatment haemolysis in African children with hyperparasitaemic falciparum malaria; a randomized comparison of artesunate and quinine

C Fanello, M Onyamboko, S J Lee, C Woodrow, S Setaphan, K Chotivanich, P Buffet, S Jauréguiberry, K Rockett, K Stepniewska, N P J Day, N J White, A M Dondorp, C Fanello, M Onyamboko, S J Lee, C Woodrow, S Setaphan, K Chotivanich, P Buffet, S Jauréguiberry, K Rockett, K Stepniewska, N P J Day, N J White, A M Dondorp

Abstract

Background: Parenteral artesunate is the treatment of choice for severe malaria. Recently, haemolytic anaemia occurring 1 to 3 weeks after artesunate treatment of falciparum malaria has been reported in returning travellers in temperate countries.

Methods: To assess these potential safety concerns in African children, in whom most deaths from malaria occur, an open-labelled, randomized controlled trial was conducted in Kinshasa, Democratic Republic of Congo. 217 children aged between 6 months and 14 years with acute uncomplicated falciparum malaria and parasite densities over 100,000/μL were randomly allocated to intravenous artesunate or quinine, hospitalized for 3 days and then followed for 42 days.

Results: The immediate reduction in haemoglobin was less with artesunate than with quinine: median (IQR) fall at 72 h 1.4 g/dL (0.90-1.95) vs. 1.7 g/dL (1.10-2.40) (p = 0.009). This was explained by greater pitting then recirculation of once infected erythrocytes. Only 5% of patients (in both groups) had a ≥ 10% reduction in haemoglobin after day 7 (p = 0.1). One artesunate treated patient with suspected concomitant sepsis had a protracted clinical course and required a blood transfusion on day 14.

Conclusions: Clinically significant delayed haemolysis following parenteral artesunate is uncommon in African children hospitalised with acute falciparum malaria and high parasitaemias.

Trial registration: ClinicalTrials.gov ; Identifier: NCT02092766 (18/03/2014).

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the Oxford Tropical Medicine Ethics Committee and the University of Kinshasa, School of Public Health institutional review board. The study was explained to caregivers in French or Lingala and they were requested to sign a consent form to allow their child’s participation in the study. The intervention was assigned by the study nurse, after the doctor confirmed eligibility and the caregivers had signed the informed consent.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Study flowchart
Fig. 2
Fig. 2
Mean haemoglobin a, median oi-RBCs b, reticulocyte counts c and LDH d, by treatment, over time

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