Relapse - Advances in Parasitology - page 142

This must be an important contributor to the relatively high degree of
genetic diversity in P. vivax often found in areas with very low seasonal
transmission.
10.1. Practical Implications
If long-latency P. vivax still contributes a significant proportion of vivax
malaria in the Indian sub-continent and further west, then current methods
of assessing drugs and vaccines may need reconsideration.
In therapeutic assessments, a follow-up period of 6 months or less may
miss a significant proportion of the relapses. If the majority of relapses in
endemic areas derive from heterologous latent hypnozoites, then malaria
control interventions, which are effective, will not prevent relapses emerg-
ing for months or years, although the number of relapses will decline as the
reduced transmission will result in less illness and, therefore, less-hypnozoite
activation. Mass drug administration with radical curative regimens (cur-
rently primaquine is the only option) would be the only way to eliminate
this reservoir of infection quickly. Epidemiological assessments in older
children and adults in endemic areas may underestimate the burden of
vivax malaria as partial immunity (and premunition) will ameliorate disease
severity and may lead to reduced activation of relapses. This would result
in relatively low relapse rates. The proportion of acute falciparum malaria
infections, which are followed by P. vivax , may be a better indicator of the
prevalence of latent hypnozoite carriage.
It is possible that much of the variance in responses to radical curative
primaquine regimens is explained by differences in rates and burdens of
latent hypnozoite carriage, and degree of immunity, and not to variation
in intrinsic drug susceptibility. The same factors, which affect therapeutic
responses in the blood-stage infection, affect the responses to hypnozoito-
cidal treatment, i.e. organism load and immunity. We should take a quantita-
tive approach to assessing 8-aminoquinoline radical curative activity based
on hypnozoite burdens. Patients with very large liver burdens of hypno-
zoites from either a very heavy inoculation or multiple inoculations and
little or no immunity (such as soldiers) would be expected to have a larger
number of relapses than travellers who have a brief period of exposure.
The apparent radical curative activity of primaquine would be expected
to improve as malaria transmission falls. Long-term follow-up (minimum
1 year) of well-characterised patients with parasite genotyping in low-trans-
mission settings should help to dissect the contributions of pre-existing
versus recently inoculated hypnozoites to relapse.