Tafenoquine: A Breakthrough Drug for Radical Cure and Elimination of Malaria

Abstract

Forty percent of the world's population is at risk of Plasmodium vivax infection. Relapse is a feature of malaria caused by P. vivax and P. ovale due to the presence of the parasite's hypnozoite stage that allows it to stay dormant in the human liver. The associated morbidity and economic burden is high, as P. vivax causes severe anemia, miscarriage among pregnant women, malnutrition, and developmental delay in young children due to its chronic relapsing nature. Till recently, for more than 60 years the only licensed antimalarial with proven hypnozoitocidal activity was primaquine. The World Health Organization recommends a regimen of 3-day chloroquine plus 14 days of primaquine for radical cure. Poor adherence to the primaquine course limits its public health benefit on a large scale. Tafenoquine is an 8-aminoquinoline with slower elimination rate, hence a single dose of it is sufficient for hypnozoitocidal activity. Additionally, the schizontocidal activity of tafenoquine makes it a superior drug to the currently available antimalarials, which are mostly single stage specific. Recently, tafenoquine was approved in the USA and Australia for the radical cure of P. vivax malaria in patients aged ≥16 years who are receiving appropriate antimalarial therapy for acute P. vivax malaria, and for the prophylaxis of malaria in patients aged ≥18 years. We have reviewed the available literature of tafenoquine here, and this article explores the possibility of tafenoquine as a key tool for control and elimination of malaria.

Plasmodium vivax: the potential obstacles it presents to malaria elimination and eradication

“…This is because the drug's delayed clearance (terminal half-life of approximately 15 days) makes single-dose treatment possible [ 101 ]. This orally active, 8-aminoquinoline drug is eliminated much slower than PQ (14 to 28 days versus 4 to 6 h) [ 76 ]. Tafenoquine solves the potentially important problem of poor adherence to daily primaquine by providing a radical cure in a single dose [ 85 ].…”

Gametocytogenesis-enhancing drug combinations can facilitate artemisinin resistance despite better clinical outcomes

“…Hence, gametocidal drugs such as primaquine (PQ) are used in combination with artemisinin, not only for better clinical results, but also to prevent transmission [22,23]. PQ and tafenoquine (TQ) are the only approved antimalarials that efficiently act on gametocytes [24]. PQ is administered with ACTs as a single dose in some regions for treatment of falciparum malaria [25], whereas it is used for radical cure in P. vivax for 14 days [24].…”

“…PQ and tafenoquine (TQ) are the only approved antimalarials that efficiently act on gametocytes [24]. PQ is administered with ACTs as a single dose in some regions for treatment of falciparum malaria [25], whereas it is used for radical cure in P. vivax for 14 days [24]. Notably, PQ and TQ are contraindicated in individuals suffering from G6PD deficiency [24,26].…”