Biology Reference
In-Depth Information
Sinton et al., 1930
). Widely used in the 1920s and 1930s, plasmoquine
was not well tolerated at the doses required for anti-malarial effects. Dur-
ing and after the Second World War, the enormous allied research effort
to find new anti-malarial drugs gave new more effective and less toxic
8-aminoquinolines (
Alving et al., 1948
;
Edgcomb et al., 1950
;
Cooper
et al., 1953
;
Coatney et al., 1953
). Pentaquine, isopentaquine, and then pri-
maquine were developed and evaluated between 1944 and 1955 (
Coatney
et al., 1953
;
Robinson et al., 1953
;
Di Lorenzo et al., 1953
). Primaquine
took over as the standard radical treatment of vivax malaria (except in
the USSR where the positional isomer quinocide was preferred initially).
The 8-aminoquinolines also have significant blood-stage activity against
P. vivax
(and
Plasmodium knowlesi
) although resistance in the blood-stage
infection can be induced experimentally (
Arnold et al., 1961
). The widely
used chloroquine-primaquine regimen should, therefore, be considered
a combination treatment for vivax malaria. The dose of primaquine rec-
ommended globally for radical cure (0.25 mg base/kg/day for 2 weeks)
was chosen largely as a result of studies on the relatively drug-sensitive
Korean
P. vivax
(
Coatney et al., 1953
;
Robinson et al., 1953
;
Di Lorenzo
et al., 1953
)
.
The Chesson strain had been shown to be more 'resistant' to
8-aminoquinolines (
Cooper et al., 1953
), but recommendations for a
higher dose of primaquine (adult dose: 22.5 mg base/day) were applied
initially only in Oceania. Sinton's work in India had suggested that quinine
and plasmoquine were synergistic in the prevention of relapse in vivax
malaria (
Sinton and Bird, 1928
;
Sinton et al., 1930
). Ruhe et al. showed that
concurrent quinine and pamaquine (plasmoquine) were more effective in
prevention of relapse with the St. Elizabeth strain than sequential adminis-
tration (
Ruhe et al., 1949
). In the 1950s, Alving et al. conducted a formal
interaction study, which provided evidence of marked synergy between
both quinine and chloroquine and primaquine (
Alving et al., 1955
). The
reason for this synergy, and whether it extends to other quinolines or
related compounds, has not been explored further. Most countries adopted
the 15 mg base/day primaquine radical curative regimen usually given for
14 days. Five-day regimens of primaquine (total adult dose 75 mg base) were
recommended in the Indian sub-continent and some other areas; although
there was no evidence, they were effective (
Goller et al. 2007
). It has been
suggested that resistance to the radical curative activity of primaquine has
emerged (
Baird, 2009
;
Collins and Jeffery, 1996
) - but it is not at all clear
if there has been any significant change in susceptibility. As the tropical
phenotype is usually associated with a greater number of relapses than the
