Predictors of relapse
Several different factors determine whether vivax or ovale malarias will
relapse. The hypnozoite burden, geographic origin (i.e. “strain”), and
degree of immunity are all important determinants. Liver stage immunity
may affect hepatic schizont development and blood stage immunity
suppresses the relapse parasitaemia to an extent that it is
asymptomatic, subpatent, or both (13, 14). Although there is no evidence
of acquired 8-aminoquinoline resistance in hypnozoites, parasites do
differ in intrinsic susceptibility. For example, the long latencyP. vivax “strains” prevalent in temperate regions are more
susceptible to 8-aminoquinolines than tropical frequent relapse strains,
and P. vivax parasites in SE Asia and Oceania appear to be less
susceptible (i.e. require a larger primaquine dosage) than other
tropical “strains” (15).
From a therapeutic perspective exposure to the biologically active
metabolites of the 8-aminoquinoline is the critical factor determining
relapse prevention (radical cure) efficacy (16, 17). This exposure
results from the total dose absorbed, and the degree of
biotransformation. Patients with cytochrome P450 2D6 polymorphisms
conferring reduced function have reduced production of primaquine’s
bioactive metabolite(s) and correspondingly reduced radical curative
efficacy (18,19). The oxidative activity of the 8-aminoquinoline
treatment is also reflected in the intraerythrocytic concentrations of
methaemoglobin. The association of methaemoglobinaemia with radical
curative efficacy of 8-aminoquinolines is discussed.