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Model-based assessm...
Model-based assessment of the safety of community interventions with primaquine in sub-Saharan Africa
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- van Beek, Stijn W. (författare)
- Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Nijmegen, Netherlands.
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- Svensson, Elin, 1985- (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Institutionen för farmaci,Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Nijmegen, Netherlands.;Uppsala Univ, Dept Pharm, Uppsala, Sweden.
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- Tiono, Alfred B. (författare)
- Natl Ctr Res & Training Malaria CNRFP, Ouagadougou, Burkina Faso.
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- Okebe, Joseph (författare)
- Univ Liverpool Liverpool Sch Trop Med, Dept Int Publ Hlth, Liverpool, Merseyside, England.
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- D'Alessandro, Umberto (författare)
- Gambia London Sch Hyg & Trop Med, Med Res Council Unit, Faraja, Gambia.
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- Goncalves, Bronner P. (författare)
- London Sch Hyg & Trop Med, London, England.
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- Bousema, Teun (författare)
- Radboud Univ Nijmegen, Dept Med Microbiol, Med Ctr, Nijmegen, Netherlands.
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- Drakeley, Chris (författare)
- London Sch Hyg & Trop Med, London, England.
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- ter Heine, Rob (författare)
- Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Nijmegen, Netherlands.
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Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Nijmegen, Netherlands Institutionen för farmaceutisk biovetenskap (creator_code:org_t)
- 2021-10-09
- 2021
- Engelska.
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Ingår i: Parasites & Vectors. - : BioMed Central (BMC). - 1756-3305. ; 14:1
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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Abstract
Ämnesord
Stäng
- Background 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. Methods 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. Results 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. Conclusions 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Nyckelord
- Primaquine
- Malaria
- Plasmodium falciparum
- Mass Drug Administration
- Modeling
- G6PD
- Anemia
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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van Beek, Stijn ...
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Svensson, Elin, ...
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Tiono, Alfred B.
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Okebe, Joseph
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D'Alessandro, Um ...
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Goncalves, Bronn ...
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visa fler...
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Bousema, Teun
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Drakeley, Chris
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ter Heine, Rob
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