Biology Reference
In-Depth Information
P. vivax
infections and, therefore, this potentially translates to a shorter period
free from gametocytaemia. Early chloroquine resistance might explain the
greater parasitological cure rate observed with DHA + PIP relative to CQ
in Afghanistan despite the longer terminal elimination half-life and greater
potency of chloroquine against sensitive
P. vivax
strains when compared with
piperaquine (
Lu et al., 2011
;
Awab et al., 2010
;
Krishna and White, 1996
).
Assessments of the effectiveness of artesunate + amodiaquine (half-life
1-3 weeks (
Krishna and White, 1996
)) in regions where chloroquine resis-
tance has emerged demonstrate that the post-treatment prophylactic effect
of this combination has also been truncated in some regions (
Ratcliff et al.,
2007
;
Karunajeewa et al., 2008
), presumably because of cross-resistance to
amodiaquine.
The risk of relapse and potential benefits of post-treatment prophylaxis
are not restricted to patients with acute
P. vivax
monoinfection. Use of
slowly eliminated anti-malarials, such as mefloquine or piperaquine, mark-
edly reduces the risk of early heterologous
P. vivax
relapses in patients
presenting initially with pure
P. falciparum
infection (
Douglas et al., 2011
).
The benefits of post-treatment prophylaxis are generally short-lived, with
almost all anti-malarial drugs reduced to sub-therapeutic concentrations
within 63 days. Although reducing early recurrent
P. vivax
infections may
impact upon early gametocyte carriage and transmission potential (
Phyo
et al., 2011
), the long-term benefits of prolonged post-exposure prophylaxis
are unknown. It is not clear whether suppressing the first relapse reduces
the total number of relapses, and hence total parasitaemia, associated with
a single inoculation, or simply delays the occurrence of the first one. In
regions where reinoculation of
P. vivax
occurs frequently, this is an aca-
demic question as the liver will continue to be seeded with new hypnozo-
ites throughout life. Chemotherapeutic suppression of any relapses in these
regions should reduce the life-time burden of parasitaemia and, therefore,
should be associated with reduced transmission of
P. vivax
. This proposition
remains speculative. Proof would best be achieved by conducting long-
term, cluster-randomised studies of repeated treatment with either a rapidly
or a slowly eliminated artemisinin combination therapy.
3.3. Eradicating Hypnozoites
Primaquine, an 8-aminoquinoline, is the only licensed drug with activity
against hypnozoites and, therefore, the only means of preventing all future
relapses from previously acquired hypnozoites. Given the dearth of new
candidates in the hypnozoitocidal drug discovery pipeline, primaquine is
