Biology Reference
In-Depth Information
and this was manifest by lower
in vitro
susceptibility in parasites with the
mutation. These observations are supported by work from Papua New
Guinea where theY976F mutation was correlated with the
in vivo
response
(
Marfurt et al., 2008
).
However, since chloroquine resistance can occur in isolates with wild-
type
pvmdr1
(
Suwanarusk et al., 2007
;
Sa et al., 2005
;
Kim et al., 2011b
),
and cure can be achieved in the presence of the 976 mutation (
Barnadas
et al., 2008
),
pvmdr1
mutations are likely to be at best only minor determi-
nants of resistance. Whereas the
pvmdr1
976 mutation was found at greater
prevalence in Papuan isolates,
pvmdr1
amplification had a greater prevalence
in Thailand (21%) compared to Indonesian (0%), and was associated with
a twofold reduction in
in vitro
susceptibility to mefloquine (
Suwanarusk
et al., 2008
).
Imwong et al. (2008)
found amplification of
pvmdr1
in
P. vivax
isolates, and proposed that this represented parasite selection associated with
greater use of mefloquine in Thailand and Myanmar.
The roles of
DHFR
and
DHPS
have been well characterized in
P. fal-
ciparum
and the relationship with clinical and
in vitro
drug susceptibility
established. Sequential acquisition of mutations in
pvdhfr
and
pvdhps
has
also observed where
P. vivax
has been exposed to intense antifolate pressure
(
Tjitra et al., 2002
;
Karunajeewa et al., 2008b
;
Fernandez-Becerra et al.,
2009
;
Rungsihirunrat et al., 2008
;
Zakeri et al., 2009
). However, in view of
the lack of antifolate efficacy against most
P. vivax
and logistical difficulties in
anti-folate
in vitro
testing, no studies to date have addressed phenotypic cor-
relation with prevalent genotypes. Studies with limited numbers of patients
with
P. vivax
and erroneously treated with sulfadoxine plus pyrimethamine,
however, suggested uniform sensitivity of strains having wild-type DHFR
and DHPS (
Hastings et al., 2004
;
Hastings et al., 2005
).
8.2.3. Non-human primates
8.2.3.1. Human parasites
A means of assessing the therapeutic response to chloroquine and other
drugs by human strains of
P. vivax
in owl monkeys (
Aotus trivirgatus
) was
detailed by
Rossan et al. (1975)
and
Schmidt (1978)
. Several other species
of owl monkey were proven receptive to hosting
P. vivax
:
Aotus lemurinus
griseimembra
,
A. vociferans
,
A. nancymai
and
A. azarae boliviensis
. One species
of squirrel money,
Saimiri boliviensis
, also hosts blood-stage
P. vivax
. A variety
of other New and Old World monkeys (tamrin, spider monkey, gibbon,
and white-faced monkey) have proven more or less receptive to
P. vivax
infection (
Coatney, 1971
), but the owl and squirrel monkeys have proven
