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Model-based assessment of the safety of community interventions with primaquine in sub-Saharan Africa

van Beek, Stijn W., Svensson, Elin M., Tiono, Alfred B., Okebe, Joseph ORCID:, D’Alessandro, Umberto, Gonçalves, Bronner P., Bousema, Teun, Drakeley, Chris and ter Heine, Rob (2021) 'Model-based assessment of the safety of community interventions with primaquine in sub-Saharan Africa'. Parasites & Vectors, Vol 14, Issue 524.

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Single low-dose primaquine (SLD-PQ) is recommended in combination with artemisinin-based combination therapy to reduce Plasmodium falciparum transmission in areas threatened by artemisinin resistance or aiming for malaria elimination. SLD-PQ may be beneficial in mass drug administration (MDA) campaigns to prevent malaria transmission but uptake is limited by concerns of hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. The aim of this study was to improve the evidence on the safety of MDA with SLD-PQ in a sub-Saharan African setting.

A nonlinear mixed-effects model describing the pharmacokinetics and treatment-induced hemolysis of primaquine was developed using data from an adult (n = 16, G6PD deficient) and pediatric study (n = 38, G6PD normal). The relationship between primaquine pharmacokinetics and hemolysis was modeled using an established erythrocyte lifespan model. The safety of MDA with SLD-PQ was explored through Monte Carlo simulations for SLD-PQ at 0.25 or 0.4 mg/kg using baseline data from a Tanzanian setting with detailed information on hemoglobin concentrations and G6PD status.

The predicted reduction in hemoglobin levels following SLD-PQ was small and returned to pre-treatment levels after 25 days. G6PD deficiency (African A- variant) was associated with a 2.5-fold (95% CI 1.2–8.2) larger reduction in hemoglobin levels. In the Tanzanian setting where 43% of the population had at least mild anemia (hemoglobin < 11–13 g/dl depending on age and sex) and 2.73% had severe anemia (hemoglobin < 7–8 g/dl depending on age and sex), an additional 3.7% and 6.0% of the population were predicted to develop at least mild anemia and 0.25% and 0.41% to develop severe anemia after 0.25 and 0.4 mg/kg SLD-PQ, respectively. Children < 5 years of age and women ≥ 15 years of age were found to have a higher chance to have low pre-treatment hemoglobin.

This study supports the feasibility of MDA with SLD-PQ in a sub-Saharan African setting by predicting small and transient reductions in hemoglobin levels. In a setting where a substantial proportion of the population had low hemoglobin concentrations, our simulations suggest treatment with SLD-PQ would result in small increases in the prevalence of anemia which would most likely be transient.

Item Type: Article
Subjects: QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 258 Primaquine. Quinacrine
WA Public Health > Preventive Medicine > WA 108 Preventive health services. Preventive medicine. Travel Medicine.
WA Public Health > Preventive Medicine > WA 110 Prevention and control of communicable diseases. Transmission of infectious diseases
WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries
Faculty: Department: Clinical Sciences & International Health > International Public Health Department
Digital Object Identifer (DOI):
Depositing User: Rachel Dominguez
Date Deposited: 05 Nov 2021 15:30
Last Modified: 05 Nov 2021 15:30


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