Biology Reference
In-Depth Information
recurrence rate (including reinfection) among patients given the standard
14-day regimen vs. 57% in patients given the same total dose over just 3 days
(
Carmona-Fonseca and Maestre, 2009
). Controlled studies are needed to
affirm short-duration, high-dose primaquine regimens, along with better
G6PD diagnostics to protect patients from risk of harm from this approach.
3.5. Hypnozoitocidal Co-drug Synergy
Co-drug synergy represents a vital consideration in the safety, efficacy and
effectiveness of primaquine, and in seeking new means of radical cure. The
data demonstrating co-drug synergy thus merits deeper examination, espe-
cially because many workers today presume primaquine acts alone in killing
hypnozoites. The effect of the blood schizontocidal partner on the effi-
cacy of primaquine becomes decisively important with the encroaching
loss of chloroquine efficacy against the acute attack. Replacing chloroquine
in radical cure is not simply exchange of blood schizontocide for use with
primaquine, but development of a pair of drugs, each impacting the safety
and efficacy of the other.
In their approach to assessing 8-aminoquinolines, Alving et al. set out
to standardise the prisoner volunteer challenge model (
Alving et al., 1948
;
Craige et al., 1947a
,
1947b
). They selected the Chesson strain of
P. vivax
, a
rapid and frequent relapsing strain isolated from an American soldier named
Chesson who was infected in New Guinea during 1944 (
Ehrman et al.,
1945
). In these challenge studies, they controlled for possible confound-
ing by recrudescence by demonstrating complete efficacy of quinine alone
against blood stage challenge with Chesson strain. They also carefully char-
acterized pamaquine efficacy against relapse as the benchmark for discov-
ery of drugs superior to it. In this work, they noted, similar to Sinton and
colleagues had 20 years before them (
Sinton and Bird, 1928
;
Sinton et al.,
1930
), distinct differences in efficacy when quinine and pamaquine were
administered together.
Tables 4.2-4.4
list the data from Alving's group (
Ruhe et al., 1949
;
Berliner et al., 1948b
).
Alving et al. (1955)
referred to these findings in
explaining the rationale for a clinical trial designed to test the hypoth-
esis of potentiation of primaquine activity against relapse by drugs having
no known effect on relapse when administered without primaquine. They
wrote, '
These experiments, however, cannot be considered definitive because the indi-
vidual groups treated were either too small or the different test groups lacked adequate
controls. The possibility of potentiation of the action of any 8-aminoquinoline against
