Clinical and laboratory characteristics of children with sickle cell disease on hydroxyurea treated with artemether-lumefantrine for acute uncomplicated malaria

Catherine Segbefia; Seth Kwabena Amponsah; Adwoa K A Afrane; Mame Yaa Nyarko; Yvonne Brew; Nihad Salifu; Samuel Yao Ahorhorlu; Abdul Malik Sulley; Lars Hviid; Michael Fokuo Ofori; George Obeng Adjei

doi:10.3389/fmed.2023.1291330

Clinical and laboratory characteristics of children with sickle cell disease on hydroxyurea treated with artemether-lumefantrine for acute uncomplicated malaria

Front Med (Lausanne). 2023 Nov 23:10:1291330. doi: 10.3389/fmed.2023.1291330. eCollection 2023.

Authors

Affiliations

¹ Department of Child Health, University of Ghana Medical School, Accra, Ghana.
² Department of Medical Pharmacology, University of Ghana Medical School, Accra, Ghana.
³ Princess Marie Louise Hospital, Accra, Ghana.
⁴ Department of Paediatrics, Greater Accra Regional Hospital, Accra, Ghana.
⁵ Centre for Tropical Clinical Pharmacology and Therapeutics, University of Ghana Medical School, Accra, Ghana.
⁶ Centre for Medical Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁷ Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
⁸ Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.

^# Contributed equally.

Abstract

Introduction: Limited information exists on any interactions between hydroxyurea (HU) and antimalarials in sickle cell disease (SCD). We evaluated changes in clinical and laboratory parameters among children with SCD on HU therapy treated with artemether-lumefantrine (AL) for acute uncomplicated malaria (UM).

Methods: A prospective, non-randomized, pilot study of 127 children with SCD (23, UM; 104, steady state) were recruited from three hospitals in Accra. UM participants were treated with standard doses of AL and followed up, on days 1, 2, 3, 7, 14, and 28. Venous blood was collected at baseline and follow-up days in participants with UM for determination of malaria parasitaemia, full blood count, reticulocytes, and clinical chemistry. Further, Plasmodium falciparum identification of rapid diagnostic test (RDT) positive samples was done using nested polymerase chain reaction (PCR).

Results: Among SCD participants with UM, admission temperature, neutrophils, alanine-aminotransferase, gamma-glutamyl-transferase, and haemoglobin significantly differed between HU recipients (HU+) and steady state, while white blood cell, neutrophils, reticulocytes, bilirubin, urea, and temperature differed significantly between non-HU recipients (no-HU), and steady state. Mean parasitaemia (HU+, 2930.3 vs. no-HU, 1,060, p = 0.74) and adverse events (HU+, 13.9% vs. no-HU, 14.3%), were comparable (p = 0.94). Day 28 reticulocyte count was higher in the HU+ (0.24) (0.17 to 0.37) vs. no-HU, [0.15 (0.09 to 0.27), p = 0.022]. Significant differences in lymphocyte [HU+ 2.74 95% CI (-5.38 to 58.57) vs. no-HU -0.34 (-3.19 to 4.44), p = 0.024]; bilirubin [HU+, -4.44 (-16.36 to 20.74) vs. no-HU -18.37 (-108.79 to -7.16)]; and alanine aminotransferase, [HU+, -4.00 (-48.55 to 6.00) vs. no-HU, 7.00 (-22.00 to 22.00)] were observed during follow up.

Conclusion: Parasite clearance and adverse event occurrence were comparable between SCD children treated with AL irrespective of HU status. However, distinct patterns of changes in laboratory indices suggest the need for larger, more focused studies.

Keywords: artemether-lumefantrine; children; hydroxyurea; malaria; sickle cell disease.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Funding for the study was provided by DANIDA/DFC through the Building Stronger Universities phase 3 project. The sponsors had no role in the study design, collection, analysis, or interpretation of the data; in the writing of the report and in the decision to submit the article for publication.