Relapse - Advances in Parasitology - page 134

proportion does not explain the 30-50% of patients in South East Asia who
experience vivax malaria following falciparum malaria ( Douglas et al., 2011 ).
The interval between the primary P. falciparum infection and the subsequent
P. vivax malaria strongly suggests that this is a relapse ( White, 2011 ). Support-
ing evidence that these are P. vivax relapses and not simultaneously acquired
infections comes from entomology studies, in which single anopheline
mosquitoes have been examined for both species ( Imwong et al., 2011 ). If
these mixed species infections resulted from simultaneous inoculation, then
30-50% of anopheline vectors carrying one species should also carry the
other. In fact, finding vectors with both P. falciparum and P. vivax sporozoites
is relatively uncommon (overall in Asia, 6.6% of P. falciparum -sporozoite-
positive mosquitoes (17 of 258) also contained P. vivax ). In the published
literature, not one of the 45 individually examined malaria-positive wild-
anopheline vectors trapped in Thailand contained both malaria species
( Imwong et al., 2011 ). This is also supported by the rarity of finding patients
or healthy subjects with gametocytes of both species in the blood at the
same time. Development rates in the mosquito are also slightly different
( P. vivax being more rapid). Although space-time clustering of infections
may occur in low-transmission areas, it is implausible that over 20% of
P. falciparum inoculations would be associated with a separate P. vivax inocu-
lation within 1 or 2 days, particularly when individuals living in these areas
receive on average less than one infectious bite per year. There is other
supporting anecdotal evidence from travellers and from soldiers with brief
periods of exposure in South EastAsia.These groups have much lower rates of
P. vivax following P. falciparum presumably because they do not have a'bank' of
activatable hypnozoites acquired from earlier inoculations. The most plausi-
ble explanation for these findings is that the majority of these P. vivax episodes
arise from hypnozoites, which were latent in the liver of the patient at the
time of acquiring P. falciparum (ALH). The remarkable similarity of both the
timing of the P. vivax recurrences and their variance strongly suggest that latent
P. vivax hypnozoites are activated by acute falciparum malaria.
2. Heterologous genotypes
If P. falciparum malaria activates latent P. vivax hypnozoites, then P. vivax
malaria should do the same. This explains the finding of heterologous geno-
types in one-half to two-thirds of P. vivax relapses ( Imwong et al., 2007 ;
Chen et al., 2007 ; Restrepo et al., 2011 ). In these cases, where the origi-
nal genotype was not detected in the malaria recurrence, then either the
inoculated infection did not relapse or its hypnozoite(s) were activated but
their progeny was outcompeted by the earlier activation or more rapid