Tafenoquine for travelers' malaria: evidence, rationale and recommendations.
Background: Endemic 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). Methods: The 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. Results: The 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. Conclusions: Although 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.