Another difficulty in assessing the therapeutic response to primaquine
is the highly variable natural rate of relapse among strains of P. vivax (see
Chapter 2). If local strains relapse in only 10% of infections (as in India),
for example, a 10% relapse rate among treated patients is not 90% efficacy,
but no efficacy at all. In contrast, a 10% relapse rate in patients infected in
Southeast Asia or Oceania, where most strains relapse at least once, may
well approach 90% real efficacy. The natural relapse rate must be known to
estimate therapeutic efficacy.
The conduct of studies in non-endemic zones eliminates confound-
ing by reinfection, but nonetheless requires knowledge of relapse risk
(without primaquine) in order to estimate the efficacy of primaquine in
treated patients. Studies in non-endemic zones typically involve a series
of patients infected at various locations abroad. Unless all of the patients
were infected at the same location, efforts to estimate primaquine effi-
cacy in infected travellers may be considered untenable. The value of such
study populations may be limited to compelling case demonstrations of
resistance to primaquine in individual patients. The approach to assess-
ing primaquine resistance thus differs greatly depending upon endemic
vs. non-endemic settings. In brief, endemic settings may yield estimates
of primaquine efficacy in populations but cannot demonstrate a prima-
quine-resistant strain in any given patient; and the converse is true in
The two sections that follow each expresses analytical approaches that
could perhaps be applied in assessing therapeutic responses to primaquine.
Neither has been assessed in practice, much less validated. These should not
be construed as recommended for implementation. Instead, the exercise
of considering the problem provides useful insights, principally regarding
the obstacles, pitfalls, and gaps in understanding precisely what makes such
assessments so challenging.
220.127.116.11. Primaquine resistance in endemic zones
Assessing the therapeutic response to primaquine in endemic zones, where
reinfection likely occurs, requires two essential features:
(1) Data that estimate the natural rate of relapse in the study population.
(2) Data that estimate the natural rate of reinfection in the study popula-
tion, or have confidence that reinfection is either highly unlikely, or
accept reinfection as equally distributed among treatment groups.
Meeting both of these requirements permits assessment of the therapeu-
tic response in populations of patients. In other words, patients require