Biology Reference
In-Depth Information
Health Organization, 2010
). The exact rationale for this age cutoff is not
clear. In most endemic settings, young patients are at greatest risk of recur-
rent
P. vivax
infections and have the highest rates of morbidity and mortality,
particularly with regard to anaemia (
Douglas et al., 2011
,
2012
;
Phimpraphi
et al., 2008
;
Poespoprodjo et al., 2009
). A recent review of the literature
revealed 11 clinical studies of primaquine therapy that recruited patients
under 4 years of age. Although age-stratified tolerability was not reported,
the overall safety profile of primaquine in G6PD normal individuals was
excellent and no worse than for other anti-malarial drugs (
John et al., 2012
).
Some policymakers, recognising the importance of providing anti-relapse
therapy, have opted to recommend prescription of primaquine in children
as young as 1 year of age. As far as we are aware, no national malaria control
guidelines advocate primaquine for those <1-year old. The lack of provision
of radical cure for infants represents not only a failure to reduce morbidity
in the most vulnerable population but also a lost opportunity to impact on
P. vivax
transmission.
In view of the high rates of
P. vivax
relapse following treatment of falci-
parum malaria in co-endemic regions, there is a rationale for administering
terminal prophylaxis in patients presenting without peripheral
P. vivax
para-
sitaemia. The proposition of giving hypnozoitocidal doses of primaquine to
those with falciparum malaria raises several ethical issues (
Baird, 2011
;
Baird
and Surjadjaja, 2010
;
Price and Douglas, 2010
). There is currently no test to
determine the presence of
P. vivax
hypnozoites and, therefore, a proportion
of patients with
P. falciparum
malaria would receive primaquine without any
individual benefit. Unlike other anti-malarials in use today, primaquine has
activity against all stages of
P. falciparum
gametocytes (
White, 2008
). A single
dose has been associated with a significant reduction in gametocyte carriage
when compared with artemisinin combination therapy alone and the same
will be true of a full curative course provided for the purpose of eradicat-
ing liver stages of
P. vivax
(
Smithuis et al., 2010
;
Price and Douglas, 2010
).
Whether the chance of individual benefit from preventing
P. vivax
relapses
and the population benefit of reduced transmissibility of both
P. vivax
and
P. falciparum
outweigh the individual risks of primaquine in those with fal-
ciparum malaria requires further study.
The only potential hypnozoitocidal alternatives to primaquine on the
horizon are tafenoquine, bulaquine and NPC1161B. Tafenoquine is a syn-
thetic analogue of primaquine with a half-life of approximately 14 days
(compared to 4-6 h for primaquine) (
Brueckner et al., 1998
). A total dose
of 1200 mg over 3 days has been shown to be as efficacious at preventing
