Advances 5: Tafenoquine
For over 60 years primaquine has been the only widely available drug in the 8-aminoquinoline class. In the past year, after a long and difficult gestation, the slowly eliminated 8-AQ tafenoquine was registered and launched. Tafenoquine is a well tolerated single dose treatment which solves the problem of potentially poor adherence (51,52). Like the other 8-aminoquinolines tafenoquine also causes oxidant haemolysis in G6PD deficiency. However the rapidly eliminated primaquine can be stopped in case of haemolysis in a G6PD deficient patient, thereby limiting the consequent anaemia – whereas tafenoquine continues to cause haemolysis for weeks. Thus tafenoquine has the advantage of simplicity and reliability of dosing, but at the expense of an increased risk of serious haemolysis. Currently available rapid screening tests identify individuals who have 30-40% of normal erythrocyte G6PD activity which identifies all male hemizygotes and female homozygotes, but they do not identify the majority of female heterozygotes (whose blood contains a mixture of G6PD deficient and normal erythrocytes). Safe use of tafenoquine therefore requires development and deployment of simple quantitative G6PD screening tests which can identify individuals with <70% of normal red G6PD activity in blood samples. These are under development, but they are not yet ready for roll out. In East Asia and Oceania relapse is the main cause of vivax illness, a major contributor to morbidity and mortality, and a major obstacle to elimination. The dose of tafenoquine currently recommended (300mg adult dose) is too low for this populous region, where a large proportion of the world’s relapses occur. In the pre-registration clinical trials tafenoquine 300mg proved inferior to a sub-optimal dose of primaquine (52) (Figure 5). Unfortunately there are no plans currently to rectify this.