Biology Reference
In-Depth Information
'Chesson strain' isolated from a soldier who had fought in New Guinea
(
Whorton et al., 1947
;
Craige et al., 1947
;
Jeffery, 1956
). In volunteers
infected with the Chesson strain, 80% of relapses occurred within 30 days
of initial treatment with quinine.
2.2. Discovery of the Liver Stages
In 1947, Garnham identified the pre-erythrocytic development of
Hepa-
tocystis
(then
Plasmodium
)
kochi
in the hepatocytes of African monkeys
(
Garnham, 1947
). Shortly afterwards, in England, definitive studies by
Shortt and Garnham identified the site of pre-erythrocytic development in
primate malarias as the liver, first in
P. cynomolgi
-infected Rhesus monkeys
(
Shortt and Garnham, 1948a, 1948b
), and then in a very heavily infected
volunteer who underwent open liver biopsy (
Shortt et al., 1948a, 1948b
;
Garnham, 1967
). This classic work still did not identify the persistent stage
(
Garnham, 1967
;
Shortt and Garnham, 1948c
). Forty years later, Krotoski,
working with Garnham et al. at Imperial College, finally identified the
dormant stages or 'hypnozoites' of
P. cynomolgi
and
P. vivax
responsible for
relapses in the liver (
Krotoski et al., 1980
;
Krotoski et al., 1982
;
Krotoski,
1985
;
Garnham, 1988
;
Bray and Garnham, 1982
). Although parasite bod-
ies, which are probably hypnozoites, have since been demonstrated in liver
cell cultures (
Dembele et al., 2011
), remarkably little is known of their
biology. The term
relapse
is now used specifically to describe recurrences
of malaria derived from persistent liver stages of the parasite (hypnozoites),
whereas
recrudescence
refers to a recurrence of malaria derived from persis-
tence of the blood-stage infection. The relapse arises after the 'awakening'
of these hypnozoites and the subsequent intrahepatic schizogony followed
by blood-stage multiplication.
3. PHENOTYPIC VARIATION IN
P.VIVAX
Today, there is a tendency to regard all
P. vivax
together as a sin-
gle homogenous species, indeed the temperate strains seem to have been
all but forgotten, but the human malaria therapy and volunteer studies
showed that there was substantial phenotypic variation between
P. vivax
'strains'. Studies conducted over 50 years ago indicated that incubation
periods, numbers of merozoites per blood schizont, antigenic relationships,
intrinsic drug susceptibility, virulence, and relapse intervals all differed
between 'strains'. At this time, the
P. vivax
with infection phenotypes sim-
ilar to those of the 'Madagascar' and 'St Elizabeth' strains, which were
