Biology Reference
In-Depth Information
the most durable with respect to reliability of the infection and suitability
to humane captivity. Chimpanzees (
Pan troglodytes
), unlike monkey hosts,
experience both the acute attack and relapses (
Krotoski et al., 1986
), but
high cost of humane captivity and large size, apart from the ethical chal-
lenges of experimentation on sentient animals, makes chimpanzees unsuit-
able for this purpose.
With the lone exception of chimpanzees, adapting
P. vivax
to these animals
is laborious and often fails. Use of splenectomized animals greatly improves
the likelihood of success. However, in experiments involving
Aotus lemurinus
griseimembra
, investigators found no difference in susceptibility between spleen
intact and splenectomized monkeys (
Jordan-Villegas et al., 2005
). Moreover,
they found no differences in infection success between the adapted Salvador I
strain of
P. vivax
and two isolates from Colombia. The unnatural host-parasite
relationship, the absence of a spleen, and possible confounding or bias in
selection for monkey-adapted strains of human parasites need all to be con-
sidered in interpreting experimentation with chemotherapeutics.
Tables 4.8 and 4.9
list the therapeutic responses of several strains of
P.
vivax
established long before onset of clinical resistance to chloroquine
(
Rossan et al., 1975
;
Schmidt, 1978
). These may thus be considered standard
responses of chloroquine-sensitive parasites to chloroquine therapy in these
animals. Investigators using owl or squirrel monkeys tend to report total
dose of drug rather than mg/kg (see rhesus monkey data in earlier tables),
because these adult monkeys typically weigh at or near 1 kg. The effective-
ness of an approximately 10 mg dose ranged from none to complete by
strain, whereas a 25 mg dose of chloroquine proved uniformly effective
(also see references
Collins et al., 2005
,
1998
;
Sullivan et al., 2001
). Thus,
Collins et al. (2000)
considered failure of a 30 mg dose definitive evidence
of resistance to chloroquine by
P. vivax
in
Aotus
or
Saimiri
monkeys.
Table 4.8
Cure Rates of Various Doses of Chloroquine against Chloroquine-Sensitive
Strains of
Plasmodium vivax
in Blood stage-Challenged
Aotus trivirgatus
Total Chloroquine
Dose (mg)
Strain
Monkeys
Cure rate ($)
New Guinea Chesson
9
2
0
18
4
100
36
2
100
Vietnam Palo Alto
9
4
0
18
5
80
36
4
100
Adapted from
Schmidt (1978)
