Biology Reference
In-Depth Information
Table 4.9
Cure Rates of 10 mg or 25 mg Doses of Chloroquine against
Chloroquine-Sensitive Achiote Strain of
Plasmodium vivax
in Blood stage-Challenged
Aotus trivirgatus
or
Saimiri sciureus
()
Animal
Number
Dose (mg)
Cure rate (%)
Aotus trivirgatus
6
25
100
Saimiri sciureus
10
25
100
4
10
100
Adapted from
Rossan et al. (1975)
A sufficient knowledge base informs the usual range of effective doses for
chloroquine-sensitive
P. vivax
in the
Aotus
or
Saimiri
models. Clinically phe-
notyped isolates from travellers infected in Papua New Guinea (AMRU-1)
and Sumatra, Indonesia (Indonesia I/CDC) often recrudesced with 30 mg
or 15 mg, respectively (
Rieckmann et al., 1989
;
Collins et al., 1992
;
Sullivan
et al., 1999
;
Obaldia et al., 1997
). Later, the Indonesia XIX/CDC strain
from patients in Indonesian Papua (clinically phenotyped as chloroquine-
resistant) was inoculated into 11 monkeys and either failed to clear parasit-
emia (1 animal) or recrudesced (8 animals) following 30 mg treatments of
chloroquine (
Collins et al., 2000
). Tafenoquine has been evaluated against
blood stages of chloroquine-resistant AMRU-1 strain in splenectomized
Aotus
monkeys (
Obaldia et al., 1997
;
Cooper et al., 1994
). Tafenoquine,
though apparently slow-acting on the AMRU-1 strain blood stages, was
nonetheless more rapidly acting that chloroquine against the chloroquine-
sensitive Chesson strain in
Aotus
monkeys (
Cooper et al., 1994
).
8.2.3.2.
Plasmodium cynomolgi
Although not directly useful in assessing clinical resistance of human par-
asite isolates, the therapeutic responses of
P. cynomolgi
to various blood
schizontocides provides a frame of reference for relative potency of the
drugs against a parasite very close to
P. vivax
but in its natural host.
Schmidt
et al. (1982)
reported hundreds of experimental infections of three distinct
strains of
P. cynomolgi
(M, B, and R
0
) in rhesus macaques treated by a wide
variety of blood schizontocides. The investigators evaluated several impor-
tant variables, including route of challenge, size of inoculum, anopheline
species, source and preparation of inoculum, route of drug administration
and duration of dosing. The report represents an appeal for and technical
foundation supporting standardization in the evaluation of chemotherapies
aimed at
P. vivax
in humans. The drugs evaluated include quinine, atabrine,
amodiaquine, chloroguanide and pyrimethamine blood schizontocides,