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Modelling the therapeutic dose range of single low dose primaquine to reduce malaria transmission through age-based dosing

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Hayes, Daniel, Banda, Cliffor, Chipasula-Teleka, Alexandra and Terlouw, Anja ORCID: https://orcid.org/0000-0001-5327-8995 (2017) 'Modelling the therapeutic dose range of single low dose primaquine to reduce malaria transmission through age-based dosing'. BMC Infectious Diseases, Vol 17, Issue 1, p. 254.

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Abstract

Background

Low-dose primaquine is a key candidate for use in malaria transmission reduction and elimination campaigns such as mass drug administration (MDA). Uncertainty about the therapeutic dose range (TDR) required for general and paediatric populations challenge the implementation of the World Health Organisation’s recommendation to add 0.25 mg/kg to current standard antimalarial treatment in such settings. Modelling work shows that for low-dose primaquine to have an impact, high efficacy and extensive population coverage are needed. In practice, age-based dose regimens, often used in MDA, could lead to safety concerns and a different effectiveness profile. We aimed to define TDRs for primaquine and to assess dosing accuracy of age-based dose regimens.

Methods

Optimised regional age-based dosing regimens for low-dose primaquine were developed in steps. First, we identified potential TDR options based on suggested published efficacy and safety thresholds (i.e. 0.1–0.4, 0.125–0.375, 0.15–0.35 mg/kg). We then used our previously defined weight-for-age growth references and age-based dose optimisation tool to model predicted regimen accuracies for Africa, Asia and Latin America based on low-dose primaquine tablets (3.75 mg and 7.5 mg) currently under development by Sanofi while employing the identified dose range options and pre-specified regimen characteristics.

Results

Dose regimens employing TDRs of 0.1–0.4 and 0.125–0.375 mg/kg had the highest average predicted dose accuracies in all regions with the widest dose range of 0.1–0.4 mg/kg resulting in ≥99% dose accuracy in all three regions. The narrower 0.15–0.35 mg/kg range was on average predicted to correctly dose 91.4% of the population in Africa, 93.2% in Asia and 92.6% in Latin America. This range would prescribe ≥20% of 3-year-olds doses below 0.15 mg/kg and ≥20% of 11-year-olds doses above 0.35 mg/kg. Widening the TDR from 0.15–0.35 to 0.1–0.4 mg/kg increased the dose accuracy by ≥20% in Africa, ≥15% in Asia and ≥10% in Latin America.

Conclusion

Optimised age-based dose regimens derived from wider TDRs are predicted to attain the dose accuracies required for effective MDA in malaria transmission reduction and elimination settings. We highlight the need for a clearly defined TDR and for safety and efficacy trials to focus on doses compatible with age-based dosing often employed in such settings.

Item Type: Article
Subjects: QV Pharmacology > Drug Standardization. Pharmacognosy. Medicinal Plants > QV 748 Prescription writing. Dosage. Dosage calculations
WA Public Health > Preventive Medicine > WA 110 Prevention and control of communicable diseases. Transmission of infectious diseases
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 765 Prevention and control
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1186/s12879-017-2378-9
Depositing User: Helen Wong
Date Deposited: 13 Apr 2017 12:03
Last Modified: 13 Sep 2019 13:10
URI: https://archive.lstmed.ac.uk/id/eprint/6984

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