Biology Reference
In-Depth Information
essential to provide evidence-based advice from which to optimise cur-
rent policies and practices. Given the wide variation in relapse patterns
both within the same geographic location and between different locations,
follow-up of patients in all clinical studies of anti-relapse therapies must be
prolonged (
John et al., 2012
).
Several practical issues limit the effectiveness of primaquine for pre-
venting
P. vivax
relapses. First, adherence to the standard 2-week prima-
quine regimen is poor (
Baird and Rieckmann, 2003
). A small number of
clinical trials have shown that direct supervision of primaquine treatment
is associated with a significant benefit over unsupervised therapy (
Grietens
et al., 2010
;
Maneeboonyang et al., 2011
;
Takeuchi et al., 2010
;
Leslie et al.,
2004
). These studies are likely to underestimate the benefit of supervision
since even the unsupervised patients in these trials were more likely to have
been compliant than those in the community, purely by virtue of their
study participation (the Hawthorne effect). Compressing a 14-day course
of primaquine into 7 days (still much longer than typical blood schizonto-
cide courses) may help to improve patient adherence without compromis-
ing efficacy (
Krudsood et al., 2008
;
Clyde and McCarthy, 1977
). The same
total dose over 3 days has not been shown to be as efficacious and if the
drug is not taken with food can cause excessive gastrointestinal side effects
(
Carmona-Fonseca and Maestre, 2009
). Routine direct observation of long
courses of primaquine is unlikely to be practicable in most malaria-endemic
settings. Alternative approaches to improving adherence such as education
and poster campaigns warrant further exploration.
A second practical concern is that primaquine can cause significant
haemolysis in patients with G6PD deficiency (
Nkhoma et al., 2009
). At
least 140 mutations in the gene coding for G6PD have been described,
each conferring varying degrees of enzyme inactivation (
Beutler and
Vulliamy, 2002
). Patients with severe deficiency are at risk of life-threatening
haemolysis after one dose of primaquine, whereas those with mild deficiency
will only experience a minor, self-limiting drop in haemoglobin (
Baird and
Hoffman, 2004
;
Reeve et al., 1992
). It is not known what threshold level of
G6PD deficiency confers an unacceptable risk of haemolysis. Furthermore,
there is currently no rapid test for reliably identifying and grading patients
with G6PD deficiency. Safety studies in those with G6PD deficiency and
development of rapid, affordable and accurate tests for G6PD activity are
arguably the highest priorities in the field of vivax-malaria research today.
The 2010 World Health Organization guidelines recommend that
children under the age of 4 years should not receive primaquine (
World
