Biology Reference
In-Depth Information
Table 4.5
Definitive Evidence for Quinine Synergizing Primaquine against Relapse of
Chesson Strain Vivax Malaria Reported in 1955
Total dose
primaquine
Drug administration
Number of subjects
% relapse
240
Quinine consecutive
19
79
240
Quinine concurrent
19
5
240
Chloroquine concurrent
19
26
Adapted from
Alving et al. (1955)
et al. (1955)
concluded, '
Evidence is presented which indicates that either quinine
or chloroquine, when administered concurrently with primaquine during the treat-
ment of clinical attacks of mosquito-induced Chesson strain vivax malaria, potenti-
ates the curative action of primaquine'
. This critically important observation and
conclusion seems to have been lost to malariology during the 60-year hiatus
from technical consideration of the problem.
Unpublished data from
Alving et al. (1949)
were described in a 1949
semi-annual report to their US NIH sponsors (the BMCS dissolved in
1946) showing synergistic effects against relapse between isopentaquine,
quinine, and, remarkably, methylene blue. Nine of 10 subjects given isopen-
taquine alone (60 mg daily for 14 days) relapsed (or possibly recrudesced).
Among 15 other subjects given the same dose of isopentaquine but with
quinine, only five relapsed. Adding 0.5 g methylene blue daily in lieu of
quinine in nine subjects resulted in just three relapses. And three subjects
given methylene blue, a 60 mg regimen of isopentaquine (30 mg doses of
this drug were also used but all relapsed regardless of adjunctive therapy),
and quinine did not relapse. In the same report, Alving also describes one
subject who haemolysed severely when given the 60 mg regimen of pen-
taquine, and again did so with a 30 mg daily regimen of pamaquine. When
that subject was again treated with the 60 mg pentaquine regimen in com-
bination with methylene blue, he suffered no haemolysis during the 14 days
of dosing. This observation, viewed in the context of the severe limitations
imposed by primaquine therapy in unscreened G6PDd patients, commands
attention.
Later studies of the treatment of
P. cynomolgi
infections of rhesus
monkeys (a superb model for
P. vivax
in humans) documented distinct
therapeutic responses to primaquine when administered with quinine or
chloroquine.
Tables 4.6 and 4.7
summarize those findings for the M and
B strains of that parasite, i.e. combining chloroquine with primaquine
provided consistently superior efficacy to primaquine against relapse
