Single-Dose Primaquine in a Preclinical Model of Glucose-6-Phosphate Dehydrogenase Deficiency: Implications for Use in Malaria Transmission-Blocking Programs
| Autor: | Gregory A. Reichard, Sean R. Marcsisin, Rosemary Rochford, Paul C. Baresel, Jason C. Sousa, Larry A. Walker, Chau T. Vuong, Kristina S. Wickham, Brice Campo, Babu L. Tekwani |
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| Rok vydání: | 2016 |
| Předmět: |
Drug
Hemolytic anemia Erythrocytes Primaquine media_common.quotation_subject 030231 tropical medicine Mice SCID Nod Pharmacology Antimalarials 03 medical and health sciences 0302 clinical medicine Animals Humans Medicine Experimental Therapeutics Pharmacology (medical) 030212 general & internal medicine media_common business.industry medicine.disease Malaria Disease Models Animal Glucosephosphate Dehydrogenase Deficiency Infectious Diseases Toxicity Erythrocyte Transfusion business Glucose-6-phosphate dehydrogenase deficiency medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 60:5906-5913 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.00600-16 |
| Popis: | Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd) are at risk for developing hemolytic anemia when given the antimalarial drug primaquine (PQ). The WHO Evidence Review Group released a report suggesting that mass administration of a single dose of PQ at 0.25 mg of base/kg of body weight (mpk) (mouse equivalent of 3.125 mpk) could potentially reduce malaria transmission based on its gametocytocidal activity and could be safely administered to G6PD-deficient individuals, but there are limited safety data available confirming the optimum single dose of PQ. A single-dose administration of PQ was therefore assessed in our huRBC-SCID mouse model used to predict hemolytic toxicity with respect to G6PD deficiency. In this model, nonobese diabetic (NOD)/SCID mice are engrafted with human red blood cells (huRBC) from donors with the African or Mediterranean variant of G6PDd (A-G6PDd or Med-G6PDd, respectively) and demonstrate dose-dependent sensitivity to PQ. In mice engrafted with A-G6PD-deficient huRBC, single-dose PQ at 3.125, 6.25, or 12.5 mpk had no significant loss of huRBC compared to the vehicle control group. In contrast, in mice engrafted with Med-G6PDd huRBC, a single dose of PQ at 3.125, 6.25, or 12.5 mpk resulted in a significant, dose-dependent loss of huRBC compared to the value for the vehicle control group. Our data suggest that administration of a single low dose of 0.25 mpk of PQ could induce hemolytic anemia in Med-G6PDd individuals but that use of single-dose PQ at 0.25 mpk as a gametocytocidal drug to block transmission would be safe in areas where A-G6PDd predominates. |
| Databáze: | OpenAIRE |
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