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antimalarial drugs can often manifest up to 63 days after treatment, and
such a response would not be detected if follow-up is limited to 28 days.
Furthermore, treatment failure reflects the ability of the recurrent para-
site to grow in blood concentrations above a sensitive MIC, but this does
not necessarily equate to the initial parasite biomass being CQR. Hence,
caution is needed when attempting to extrapolate the initial biomarkers
of resistance with subsequent treatment failure. In other words, the initial
parasitemia may have been completely sensitive to treatment but was fol-
lowed by relapse of a drug-resistant strain. The genotype and phenotype
of parasites appearing in the primary parasitaemia remains ambiguous,
except in the instance of therapeutic success and a classification as drug
sensitive. The resistant phenotype and genotype may only be applied to
the parasite populations later emerging in the presence of ordinarily effec-
tive concentrations of chloroquine.
Clinical trials of other blood schizontocidal agents add another layer
of complexity to the interpretation. Most recent studies have adapted a
pragmatic approach comparing the overall risk of recurrent P. vivax infec-
tion within a defined period of time. Such in vivo assessments have a pub-
lic health merit, reflecting both blood schizontocidal and PTP. However,
they do not permit the true efficacy to be gauged. Instead, the unadjusted
risk of recurrence needs to be interpreted in light of the concomitant use
of primaquine, the timing of recurrence, available molecular data, blood
schizontocidal drug concentrations, entomological inoculation rates, and
the epidemiology of relapse in the study area.
8.2. Ex vivo Assessment of Schizontocidal Therapy
8.2.1. Ex vivo drug susceptibility testing
Ex vivo drug susceptibility assays provide an alternative means of quantifying
drug resistance of Plasmodium sp. free from the confounders of adherence to
therapy and its absorption or metabolism, host immunity, relapse, and rein-
fection. In P. falciparum , a multitude of methods has been used to quantify
drug activity, and significant difficulties persist in comparing results between
laboratories and methodologies ( Bacon et al., 2007 ). The analysis of P. vivax
is complicated by its preferential invasion of young red blood cells, which
limits its reproductive capacity and the ability to culture the parasite ex vivo
( Udomsangpetch et al., 2007 ). To date, P. vivax cannot be sustained in ex vivo
culture or grown from cryopreserved isolates for more than 1-2 cycles of
asexual growth. To overcome this, ex vivo studies of P. vivax have focused on
techniques evaluating the inhibitory effect of blood schizontocides on fresh
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