Biology Reference
In-Depth Information
6 months. The maximum documented interval was 397 days). This proves
that long latency can and does occur with the tropical frequent-relapse
phenotype.
These patterns of relapse are also illustrated well in the primate model;
the Rhesus monkey infected with
P. cynomolgi
(the primate malaria 'equiva-
lent' of
P. vivax
) (
Schmidt, 1986
). In Schmidt's detailed longitudinal monkey
experiments, where different sporozoite inocula were evaluated, there was
no clear difference in the number of relapses between monkeys inoculated
with 5 × 10
2
sporozoites up to 5 × 10
6
sporozoites, although 'the intervals
between relapses were related to size of inoculum, being distinctly shorter
in monkeys inoculated with 5 × 10
6
sporozoites than in those challenged
with 5 × 10
2
sporozoites, with recipients of 5 × 10
4
sporozoites occu-
pying an intermediary position'. Taken together with the absence of any
relapses following an inoculum of only five sporozoites in three monkeys,
this argues for activation of a proportion of hypnozoites per relapse, and
is consistent with the earlier observations in soldiers and malaria therapy
patients of a fixed fraction of relapses following each illness episode in vivax
malaria (
Fig. 2.5
).
9.1. Theories to Explain the Periodicity of Relapse
Any theory seeking to explain the remarkable biology of
P. vivax
relapse
must accommodate the following (
White, 2011
):
1.
Relapses show remarkable periodicity.
2.
Early relapses reach patency around 3 weeks after starting treatment,
which suggests emergence from the liver at least 1 week earlier.
3.
Not all
P. vivax
primary infections are followed by a relapse. In Thailand,
approximately 50% of infections are followed by a subsequent relapse
within 28 days if a rapidly eliminated anti-malarial drug (artesunate)
is given for treatment of the primary infection and primaquine is not
given (
Silachamroon et al., 2003
). Elsewhere, the probability of relapse
generally varies between 20% and 80%. Animal experiments, the malaria
therapy experience, and volunteer studies all suggest this proportion is a
function of sporozoite inoculum.
4.
Multiple relapses are common, particularly in young children, even
though sporozoite inocula are thought to be relatively small (median
6-10 sporozoites). It is not uncommon in tropical areas for children to
have 4-6 relapses at 4-6 week intervals and sometimes more following
an incident infection. Even larger numbers of relapses were observed in
soldiers following intense exposure and in Rhesus monkeys receiving
