Relapse - Advances in Parasitology - page 141

10. IMPLICATIONS FOR EPIDEMIOLOGICAL
ASSESSMENT
If this ALH theory is correct, it explains why relapse phenotypes may
be difficult to characterize in malaria endemic areas, and why in areas with
long-latency P. vivax frequent-relapse patterns may still be observed. This is
because a primary illness with long-latency P. vivax of the 'Madagascar' or
'St. Elizabeth' phenotype may activate previously acquired latent hypno-
zoites (of similar phenotype) - giving an early relapse. The illness caused
by the relapse may then activate further latent homologous or heterolo-
gous hypnozoites. Thus, several relapses may follow at short intervals even
though all the parasites are of the long-latency type. The net result would
be indistinguishable from the epidemiological pattern of frequent-relapse
vivax malaria [for further explanation see White, 2011 ]. The converse may
also occur; for example, long latency with the tropical frequent-relapse
phenotypes was demonstrated clearly in the studies of the Chesson strain
following single mosquito bites ( Coatney et al., 1950b ) ( Fig. 2.3 ). If both
short- and long-latency types are prevalent in the same area, then identify-
ing phenotypes from illness patterns become even more difficult, and it may
be impossible to discern the long-latency phenotypes amongst the frequent
relapses. The presence of long-latency phenotypes may only be evident in
travellers and soldiers who spend a brief period in the endemic area, do
not receive primaquine, and then return to a non-endemic area and relapse
many months later without re-exposure ( Warwick et al., 1980 ; Walker, 1983 ;
Kopel et al., 2010 ; Eichenlaub et al., 1979 ; Smoak et al., 1997 ; Jiang et al.,
1982 ). There is uncertainty over the true epidemiology of relapse patterns
over a large proportion of the P. vivax endemic world. This large knowl-
edge gap seems to have gone unnoticed. Long-latency phenotypes may be
present in many tropical areas ( Fig. 2.6 ). Identifying the relapse phenotypes
is an essential prerequisite for therapeutic assessments, control and elimina-
tion planning, and the evaluation of novel interventions such as vaccines.
There is an additional point in biological interest. Activation of hyp-
nozoites from different preceding inoculations will commonly result in
two or more genotypes reaching patent parasitaemia at similar times. As
gametocytogenesis in P. vivax occurs simultaneously with asexual stage
development, this provides an effective method of ensuring that a mos-
quito will ingest gametocytes of different genotypes, thereby facilitating
meiotic recombination between genetically unrelated P. vivax parasites.