Tafenoquine for travelers' malaria: evidence, rationale and recommendations

Abstract

BackgroundEndemic malaria occurring across much of the globe threatens millions of exposed travelers. While unknown numbers of them suffer acute attacks while traveling, each year thousands return from travel and become stricken in the weeks and months following exposure. This represents perhaps the most serious, prevalent and complex problem faced by providers of travel medicine services. Since before World War II, travel medicine practice has relied on synthetic suppressive blood schizontocidal drugs to prevent malaria during exposure, and has applied primaquine for presumptive anti-relapse therapy (post-travel or post-diagnosis of Plasmodium vivax) since 1952. In 2018, the US Food and Drug Administration approved the uses of a new hepatic schizontocidal and hypnozoitocidal 8-aminoquinoline called tafenoquine for the respective prevention of all malarias and for the treatment of those that relapse (P. vivax and Plasmodium ovale).MethodsThe evidence and rationale for tafenoquine for the prevention and treatment of malaria was gathered by means of a standard search of the medical literature along with the package inserts for the tafenoquine products Arakoda™ and Krintafel™ for the prevention of all malarias and the treatment of relapsing malarias, respectively.ResultsThe development of tafenoquine—an endeavor of 40 years—at last brings two powerful advantages to travel medicine practice against the malaria threat: (i) a weekly regimen of causal prophylaxis; and (ii) a single-dose radical cure for patients infected by vivax or ovale malarias.ConclusionsAlthough broad clinical experience remains to be gathered, tafenoquine appears to promise more practical and effective prevention and treatment of malaria. Tafenoquine thus applied includes important biological and clinical complexities explained in this review, with particular regard to the problem of hemolytic toxicity in G6PD-deficient patients.

Molecular Docking suggests repurposing of Brincidofovir as a potential drug targeting SARS-CoV-2 "COVID-19" ACE2 receptor and main protease

“…The second top-ranked drug is Tafenoquine which is an orally-active 8-aminoquinoline, a long-acting analog of primaquine, anti-malarial medicine developed by GlaxoSmithKline and 60 Degrees Pharmaceuticals [23,24]. The drug was FDA-approved for the radical cure of Plasmodium vivax (P. vivax) malaria and the prophylaxis of malaria in 2018.…”

“…The drug was FDA-approved for the radical cure of Plasmodium vivax (P. vivax) malaria and the prophylaxis of malaria in 2018. The drug is active against pre-erythrocytic, erythrocytic forms and the gametocytes of Plasmodium species that include P. falciparum and P. vivax [23,24]. Clinical trials for this drug may be also recommended.…”

Synthesis and Antibacterial Activity of New N‐Substituted Hexahydroquinolinone Derivatives and X‐Ray Crystallographic Studies

“…During the last few years, exploration of N-heterocycles, particularly quinolone molecules, is a rapidly emerging area due to their wide applications [1,2] in pharmaceuticals, clinically used drugs and agrochemicals. [3][4][5][6][7] Quinoline based molecules like albaconazole has been used for its antibacterial and antifungal activity, [8][9][10] tafenoquin as an antimalarial drug, [11,12] afloqualone as an anticancer and muscle relaxant drug [13,14] and cliquinol for its antiprotozoal activity [15,16] (Figure 1).…”

Tafenoquine for the radical cure and prevention of malaria: the importance of testing for G6 PD deficiency

“…However, in 2018, the Therapeutic Goods Administration in Australia and the Food and Drug Administration in the United States granted licences for tafenoquine for the radical cure of P. vivax malaria and for malaria chemoprophylaxis. Both primaquine and tafenoquine are 8‐aminoquinoline antimalarial drugs that can cause severe haemolysis in individuals with glucose‐6‐phosphate dehydrogenase (G6PD) deficiency . Primaquine is rapidly metabolised and eliminated from the body, with a half‐life of 6 hours .…”

“…Both primaquine and tafenoquine are 8‐aminoquinoline antimalarial drugs that can cause severe haemolysis in individuals with glucose‐6‐phosphate dehydrogenase (G6PD) deficiency . Primaquine is rapidly metabolised and eliminated from the body, with a half‐life of 6 hours . Radical cure of latent infection is achieved with daily administration, the total dose spread over 14 days to improve tolerability.…”