Biology Reference
In-Depth Information
genotype (homologous immunity). In the studies of the St. Elizabeth strain,
there was clear evidence that late relapses were attenuated if there was an
early infection, but this did not affect the interval to latency, whereas the
greater the sporozoite inoculum, the shorter was the interval (
Coatney
et al., 1950a
). These observations suggest that the size of the inoculum is
more important than immunity in determining the duration of latency or
the inter-relapse interval. Blood-stage immunity against homologous strains
of
P. vivax
, which persists for many months, was a consistent observation in
malaria therapy and challenge studies. Boyd noted that if the initial infec-
tion was allowed to run its natural course, then relapse did not occur and
reinfection with the homologous strain was not possible (
Boyd, 1947
).
4.2. Artificial versus Natural Infections
Artificial infections were very informative but they differed from natural
infections in several important respects (
Swellengrebel and De Buck, 1938
;
Winckel, 1941
). The artificial infections were only in non-immune adults,
whereas the burden of vivax disease in endemic areas was in children. Adults
in the malaria endemic areas have received multiple inoculations in their
lifetime, and so have usually developed significant immunity to a broad range
of local parasites, which controls symptoms and reduces parasite densities.
The artificial infections in the majority of volunteer studies and in malaria
therapy followed the bites of 5-10 infected anopheline mosquitoes selected
for maximal infectivity based on salivary gland sporozoite loads. The opti-
misation of infectivity in malaria therapy and experimental studies contrasts
with the natural setting where anopheline mosquitoes typically display a
wide range of infectivities depending on sporozoite age and other factors.
In artificial infection studies, mosquito mid guts often contained multiple
oocyts, whereas in trapped wild anopheline vectors, oocyst numbers are
typically low (median 2-3). Median sporozoite inocula in natural infections
are estimated to be <10 sporozoites (
Ponnudurai et al., 1991
;
Rosenburg
and Wirtz, 1990
;
Beier et al., 1991
). If Garnham's estimates (50:50 ratio
of immediately developing parasites to hypnozoites) are correct, this cor-
responds to a median of five hypnozoites in tropical
P. vivax
infections. The
inocula in artificial infections were therefore usually 'supranormal', which
did not bring out the important stochastic component of
P. vivax
epidemi-
ology resulting from low-sporozoite inocula in areas of low seasonal trans-
mission. The 'strains' of
P. vivax
used in malaria therapy were likely to have
been of a single genotype or very closely related interbreeding genotypes,
which were passaged over many years. It is likely that with multiple passages
