Short-course, high-dose primaquine regimens for the treatment of liver-stage vivax malaria in children

Brioni R Moore; Sam Salman; Roselyn Tobe; John Benjamin; Gumul Yadi; Bernadine Kasian; Moses Laman; Leanne J Robinson; Madhu Page-Sharp; Inoni Betuela; Kevin T Batty; Laurens Manning; Ivo Mueller; Timothy M E Davis

doi:10.1016/j.ijid.2023.05.063

Short-course, high-dose primaquine regimens for the treatment of liver-stage vivax malaria in children

Int J Infect Dis. 2023 Sep:134:114-122. doi: 10.1016/j.ijid.2023.05.063. Epub 2023 Jun 1.

Authors

Affiliations

¹ Curtin Medical School, Curtin University, Perth, Australia; Curtin Health Innovation Research Institute, Curtin University, Perth, Australia; Medical School, The University of Western Australia, Perth, Australia; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Australia. Electronic address: brioni.moore@curtin.edu.au.
² Medical School, The University of Western Australia, Perth, Australia; Clinical Pharmacology and Toxicology Unit, PathWest, Perth, Australia.
³ Vector Borne Disease Unit, Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
⁴ Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Australia; Burnet Institute, Melbourne, Australia.
⁵ Curtin Medical School, Curtin University, Perth, Australia.
⁶ Curtin Medical School, Curtin University, Perth, Australia; Curtin Health Innovation Research Institute, Curtin University, Perth, Australia.
⁷ Medical School, The University of Western Australia, Perth, Australia; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Australia.
⁸ Department of Medical Biology, University of Melbourne, Melbourne, Australia; Burnet Institute, Melbourne, Australia.
⁹ Medical School, The University of Western Australia, Perth, Australia.

PMID: 37269941
DOI: 10.1016/j.ijid.2023.05.063

Abstract

Objectives: To assess the pharmacokinetics, safety, and tolerability of two high-dose, short-course primaquine (PQ) regimens compared with standard care in children with Plasmodium vivax infections.

Methods: We performed an open-label pediatric dose-escalation study in Madang, Papua New Guinea (Clinicaltrials.gov NCT02364583). Children aged 5-10 years with confirmed blood-stage vivax malaria and normal glucose-6-phosphate dehydrogenase activity were allocated to one of three PQ treatment regimens in a stepwise design (group A: 0.5 mg/kg once daily for 14 days, group B: 1 mg/kg once daily for 7 days, and group C: 1 mg/kg twice daily for 3.5-days). The study assessments were completed at each treatment time point and fortnightly for 2 months after PQ administration.

Results: Between August 2013 and May 2018, 707 children were screened and 73 met the eligibility criteria (15, 40, and 16 allocated to groups A, B, and C, respectively). All children completed the study procedures. The three regimens were safe and generally well tolerated. The pharmacokinetic analysis indicated that an additional weight adjustment of the conventionally recommended milligram per kilogram PQ doses is not necessary to ensure the therapeutic plasma concentrations in pediatric patients.

Conclusions: A novel, ultra-short 3.5-day PQ regimen has potential benefits for improving the treatment outcomes in children with vivax malaria that warrants further investigation in a large-scale clinical trial.

Keywords: Children; Pharmacokinetics; Primaquine; Safety; Short-course regimen; Vivax malaria.

MeSH terms

Antimalarials* / adverse effects
Child
Humans
Liver
Malaria, Vivax* / drug therapy
Plasmodium vivax
Primaquine / adverse effects
Treatment Outcome

Substances

Primaquine
Antimalarials

Associated data

ClinicalTrials.gov/NCT02364583