Relapse - Advances in Parasitology - page 133

very large sporozoite inocula ( Schmidt, 1986 ). Importantly, the fraction
of people experiencing a relapse after each illness episode in a particular
location appears constant ( Fig. 2.5 ).
5. In long-latency phenotypes, there is commonly a period of 8-9 months
either before the first symptomatic infection or between the first symp-
tomatic infection and the first relapse. This long-latency interval appears
to be normally distributed (mode 28 weeks for the Madagascar strain)
( Fig. 2.2 ). Sometimes, there are several short interval relapses followed by
a long interval. Conversely, long latencies may also occur after multiple
relapses in the tropical frequent-relapse phenotype ( Fig. 2.3 ).
6. If there are further relapses after the long-latent period, then they occur
frequently with short intervals, which are very similar to those observed
in the tropical 'strains' ( Fig. 2.3 ).
7. The relapses in clinical studies conducted in endemic areas are com-
monly with a genotype which is different to that identified in the primary
infection (48% in Columbian isolates, 55% in Indian isolates, 61% in
Thai and Burmese isolates, and 71% in East Timor isolates) ( Imwong
et al., 2007 ; Chen et al., 2007 ; Restrepo et al., 2011 ).
8. A remarkably high proportion of acute infections with P. falciparum are
followed by an episode of P. vivax infection. The proportion is cur-
rently 30% in Thailand ( Looareesuwan et al., 1987 ; Mayxay et al., 2004 ;
Douglas et al., 2011 ) and 50% in Myanmar ( Smithuis et al., 2010 ). The
intervals between the acute P. falciparum malaria illness and the subse-
quent P. vivax malaria are similar to those between acute P. vivax malaria
and the subsequent P. vivax relapse ( White, 2011 ). The epidemiological
characteristics suggest that these are all relapses.
It is also interesting and probably relevant that in endemic areas, despite
very low seasonal transmission, P. vivax maintains a high degree of genetic
diversity.
9.2. Relapses of Vivax Malaria Arise from Activation of Latent
Hypnozoites (ALH)
The combined evidence suggests that in endemic areas, a high proportion of the
population have latent P. vivax hypnozoites, which can be activated by a sufficient
stimulus (White, 2011).
Four lines of evidence support this ALH hypothesis.
1. Mixed species infections
Mixed blood-stage infections with P. falciparum and P. vivax are underes-
timated by microscopy, but, even with sensitive PCR techniques, this