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).