8-Aminoquinoline Therapy for Latent Malaria: G6PD Testing Remains the Critical Bottleneck
This comprehensive review traces the century-long history of 8-aminoquinoline antimalarials from plasmochin through primaquine to tafenoquine, all limited by hemolytic toxicity in G6PD-deficient patients. Despite FDA approval of tafenoquine in 2018, the absence of widely available point-of-care G6PD testing continues to impede deployment in endemic regions. For diagnostics professionals, the review highlights an urgent unmet need for rapid, affordable G6PD assays to unlock the potential of radical cure for relapsing malaria.
The original study
8-Aminoquinoline Therapy for Latent Malaria.
- Authors
- Baird JK
- Journal
- Clinical microbiology reviews
- Type
- Journal Article, Research Support, Non-U.S. Gov't, Review
- PMID
- 31366609
Original abstract
The technical genesis and practice of 8-aminoquinoline therapy of latent malaria offer singular scientific, clinical, and public health insights. The 8-aminoquinolines brought revolutionary scientific discoveries, dogmatic practices, benign neglect, and, finally, enduring promise against endemic malaria. The clinical use of plasmochin-the first rationally synthesized blood schizontocide and the first gametocytocide, tissue schizontocide, and hypnozoitocide of any kind-commenced in 1926. Plasmochin became known to sometimes provoke fatal hemolytic crises. World War II delivered a newer 8-aminoquinoline, primaquine, and the discovery of glucose-6-phosphate dehydrogenase (G6PD) deficiency as the basis of its hemolytic toxicity came in 1956. Primaquine nonetheless became the sole therapeutic option against latent malaria. After 40 years of fitful development, in 2018 the U.S. Food and Drug Administration registered the 8-aminoquinoline called tafenoquine for the prevention of all malarias and the treatment of those that relapse. Tafenoquine also cannot be used in G6PD-unknown or -deficient patients. The hemolytic toxicity of the 8-aminoquinolines impedes their great potential, but this problem has not been a research priority. This review explores the complex technical dimensions of the history of 8-aminoquinolines. The therapeutic principles thus examined may be leveraged in improved practice and in understanding the bright prospect of discovery of newer drugs that cannot harm G6PD-deficient patients.