Biology Reference
In-Depth Information
relatively recent well-controlled trials demonstrated the 5-day regimen to
be almost completely inefficacious against relapse (
Gogtay et al., 1999
;
Yadav
and Ghosh, 2002
). Moreover, the inadequacy of the 15 mg/14 days regi-
men against strains like Chesson has been a long-acknowledged problem.
Studies consistently show high risk of relapse after such therapy in patients
infected in Southeast Asia or, especially, the island of New Guinea (
Elliott
et al., 2004
;
Jelinek et al., 1995
). Authorities now recommend the 30 mg
regimen, with G6PDd screening, as first-line treatment regardless of geo-
graphic origin.
The radical cure of
P. vivax
in patients known to be G6PDd is difficult.
Current WHO guidelines recommend for patients with >10% residual
G6PD enzyme activity (WHO Class III or IV G6PDd variant), a weekly
dose of 0.75 mg/kg for 8 weeks to reduce the risk of haemolysis whilst
retaining efficacy (
Alving et al., 1960
;
Leslie et al., 2008
). The weekly
dosing schedule was derived from studies in the USA in a small number
of adults with the mildly primaquine-sensitive African A-G6PDd variant
(
Alving et al., 1960
). Since host vulnerability to haemolysis varies between
over 100 different G6PDd variants (
Clyde, 1981
), the available evidence
is inadequate to ensure the universal safety of a 0.75 mg/kg dose either
as a single dose, as advocated for reducing the transmission of falciparum
malaria, or a weekly dose for the radical cure of vivax malaria (
Baird and
Surjadjaja, 2011
).
There are as yet no reliable bedside tests for G6PDd. Hence, many health
care providers elect to administer primaquine without G6PD testing or,
probably more often, simply adopt a blanket policy to omit the prescription
of anti-relapse therapy altogether. Clinicians may initiate low-dose treat-
ment with primaquine with instructions to stop medication should the
patient notice signs of haematuria.
The most recent WHO malaria treatment guidelines suggest that prima-
quine should be avoided in children <4 years of age and in pregnant women
(
World Health Organization, 2010
). The rationale behind the 4-year-old
cut off is unclear and unreferenced, but may reflect caution in the face of
inadequate data rather than overt toxicity. However, the consequences of
denying young children anti-relapse therapy also need to be factored into
such decisions that profoundly shape policy and practice since the adverse
consequences of recurrent vivax malaria in early life may be very con-
siderable (
Poespoprodjo et al., 2009
). In practice, national malaria control
programs often advocate deployment of 14 days primaquine in children as
young as 1-year old, but studies are urgently needed to examine the risk vs.
