Biology Reference
In-Depth Information
likely to remain the sole option for at least the next few years (
Medicines
for MalariaVenture, 2011
;
Anthony et al., 2012
). Although primaquine was
first approved over 50 years ago, there are many areas of uncertainty sur-
rounding its toxicity profile, optimal dosing and mechanism of action. Its
efficacy is hard to gauge since geographical differences in recurrence rates
may reflect acquired resistance, inherent differences in strain susceptibility
or simply differences in relapse patterns.
Early work by Alving et al. showed that concurrent administration
of primaquine with either chloroquine or quinine was associated with
greater efficacy than serial administration of quinine followed by prima-
quine (
Alving et al., 1955
). It is currently not known whether other blood
schizontocides, such as the artemisinin combination therapies, also have this
potentiating effect. Several trials have shown good efficacy of artemisinin
derivatives either in combination with or closely followed by primaquine
for preventing
P. vivax
recurrences up to day 28 (
Krudsood et al., 2007, 2008
;
Hamedi et al., 2004
;
Dao et al., 2007
;
Silachamroon et al., 2003
;
Wilairatana
et al., 1999
). The short duration of follow-up in these trials precludes an
assessment of the risk of late relapse.
The efficacy of primaquine is determined by the total dose of drug
received as opposed to the concentrations achieved in the blood (
Leslie
et al., 2008
;
Clyde and McCarthy, 1977
;
Alving et al., 1960
). A weekly pri-
maquine dosing regimen given over 8 weeks after effective blood schizon-
tocidal treatment is as efficacious as the same total dose of primaquine given
over 2 weeks (
Leslie et al., 2008
). The optimal total dose required to prevent
future relapses is uncertain but appears to differ by geographic location
(
Goller et al., 2007
). A dose of 210 mg over 14 days (∼3.5 mg/kg) has been
associated with close to 100% protection against future relapse in patients
with
P. vivax
infection acquired in parts of South Korea, South and Central
America and India (
Alving et al., 1953
;
Coatney et al., 1953
;
Gogtay et al.,
1999
;
Miller et al., 1974
). Twice that total dose (∼7 mg/kg) may be required
to reliably prevent relapses in those with the frequently relapsing Chesson
strain, known to be prevalent in Papua New Guinea and Papua, Indone-
sia (
Baird, 2009
;
Clyde and McCarthy, 1977
;
Goller et al., 2007
;
Coatney
and Getz, 1962
;
Collins and Jeffery, 1996
). Based on the limited available
evidence, the expert committees of the World Health Organization recom-
mend 0.25 mg/kg primaquine daily over 14 days except in Oceania and
Southeast Asia, where a dose of 0.5 mg/kg/day is recommended (
World
Health Organization, 2010
). Further work to clarify relapse patterns and
the efficacy of different doses of primaquine in vivax-endemic regions is
