Biology Reference
In-Depth Information
with intravenous artesunate or quinine. This is particularly important in
co-endemic regions where mixed infections may often be missed by the
microscopist.
8. EVALUATING DRUG RESISTANCE IN VIVAX
MALARIA
Following an initial period of drug development in the 1940s and
1950s, the emphasis on drug evaluation of
P. vivax
declined and between
1966 and 2002, only 11% (47/435) of published antimalarial drug trials
assessed antimalarial efficacy in patients with vivax malaria (
Myint et al.,
2004
). Studies of antimalarial efficacy focused primarily on
P. falciparum
through the second half of the twentieth century. WHO protocols for
the evaluation of
P. falciparum
have undergone extensive revision over that
period; in general, these methodologies have been extended to include the
study of
P. vivax
rather than specifically being adapted to the idiosyncracies
of this parasite. The
in vivo
and
ex vivo
assessment of
P. vivax
drug suscepti-
bility are far more challenging than
P. falciparum
(
Price et al., 2009
;
Baird,
2004
), reflecting fundamental differences in the biology of these two species
that need to be specifically addressed. Indeed when the
in vivo
and
in vitro
methods for evaluating
P. falciparum
drug resistance are applied to
P. vivax
,
they yield misleading or ambiguous findings.
8.1.
In vivo
Assessment of Schizontocidal Therapy
Assessment of the acute response to drug treatment of
P. vivax
is the same as
that for
P. falciparum
. However, the interpretation of late parasitological out-
come is confounded by the occurrence of relapses (as well as reinfection).
Recurrent
P. vivax
parasitemia following initial treatment can arise from
reinfection, relapse, or recrudescence. Molecular analysis, which has been so
valuable in quantifying true recrudescence in clinical trials of
P. falciparum
, is
not helpful in
P. vivax
studies since it is currently not possible to distinguish
between recrudescence and relapse of the same parasite strain.
Plasmodium
vivax
genotyping methodologies have been developed (
Koepfli et al., 2009
)
but their application to clinical trials is not straightforward. A recurrent
infection with a parasite with an identical
P. vivax
genotype can represent
either a recrudescence or relapse from a brood of hypnozoites originating
from the same inoculation with sporozoites (
Chen et al., 2007
;
Imwong
et al., 2007
). Likewise, a mismatched genotype may be either a reinfec-
tion or a relapse. This problem can significantly confound clinical efficacy
