Obstacles 3: Underuse of primaquine
Primaquine is a very important antimalarial as both a single dose gametocytocide in falciparum malaria, and in multiple dose “radical cure” regimens to prevent relapse in vivax and ovale malaria (1), but it is underused. This is because of concerns over haemolytic toxicity in glucose-6-phosphate dehydrogenase (G6PD) deficiency (43). Gene frequencies for X-linked G6PD deficiency average 8-10% in tropical areas (although prevalences are lower in vivax malaria), but screening tests to identify G6PD deficient patients are not widely available. Relapses are recurrences of malaria which follow complete cure of the blood stage infection. They derive from dormant parasite forms (hypnozoites) which persist in the liver. Hypnozoites are resistant to all current antimalarial drugs except the 8-aminoquinolines (8-AQ) (1). Without radical cure relapse rates vary between 20% and 80%. Relapse is a major cause of morbidity and mortality in higher transmission settings (44). Primaquine has usually been given in 7 or 14 day “radical cure” courses. As these cause predictable haemolysis in G6PD deficient patients, G6PD testing is recommended (1,43). The recent development of rapid screening tests is a significant advance which should enable wider safe use of primaquine for radical cure, and thereby make elimination a more achievable target. Recent very large studies confirm that the treatment courses even for the higher dose primaquine regimens (total 7mg/kg) can be condensed into a one week course. With G6PD testing to exclude deficient patients these are well tolerated , and if these adhered to, radical curative efficacy is very high (>95%) (45, 46).
Until recently primaquine was used in a single 0.75mg base/kg dose (45mg adult dose) as a P. falciparum gametocytocide to reduce transmissibility of the treated infection. This was given in addition to the standard three day ACT for treatment. Re-evaluation of the transmission blocking dose-response relationship for primaquine indicates that the same gametocytocidal effect is obtained with a dose three times lower (0.25mg base/kg) with obviously less haemolytic risk. This obviates the need for G6PD testing- so this has now become the recommended dose (1,47).