Diagnosis and Treatment of Plasmodium vivax Malaria - Advances in Parasitology - page 202

9. Research and Development Urgencies 252

9.1. Proof of Efficacy 253

9.2. Proof of Safety 253

9.3. Proof of Effectiveness 254

9.4. Minimizing Risk of Harm 254

9.5. New Drug Discovery 255

10. Summary 257

Abstract
Infection by Plasmodium vivax poses unique challenges for diagnosis and treat-
ment. Relatively low numbers of parasites in peripheral circulation may be difficult
to confirm, and patients infected by dormant liver stages cannot be diagnosed
before activation and the ensuing relapse. Radical cure thus requires therapy aimed
at both the blood stages of the parasite (blood schizontocidal) and prevention of
subsequent relapses (hypnozoitocidal). Chloroquine and primaquine have been the
companion therapies of choice for the treatment of vivax malaria since the 1950s.
Confirmed resistance to chloroquine occurs in much of the vivax endemic world
and demands the investigation of alternative blood schizontocidal companions
in radical cure. Such a shift in practice necessitates investigation of the safety and
efficacy of primaquine when administered with those therapies, and the toxicity
profile of such combination treatments, particularly in patients with glucose-6-
phosphate dehydrogenase deficiency. These clinical studies are confounded by
the frequency and timing of relapse among strains of P. vivax , and potentially by
differing susceptibilities to primaquine. The inability to maintain this parasite in
continuous in vitro culture greatly hinders new drug discovery. Development of safe
and effective chemotherapies for vivax malaria for the coming decades requires
overcoming these challenges.

1. INTRODUCTION
Accurate diagnosis and targeted treatment of vivax malaria consti-
tutes the front line of defence against this infection. Indeed in the absence
of a vaccine and the relative ineffectiveness of vector control to prevent
it, diagnosis and treatment may be the only effective response available.
Given the burdens of risk and disease detailed in Chapter 1, and the
daunting challenges to effective diagnosis and treatment detailed in this
chapter, Plasmodium vivax can be appreciated as very serious threat to
human health.
Treatment of infection by P. vivax imposes far greater complexity, nuance,
and risk to the patient relative to treatment of uncomplicated falciparum
malaria. Treating both liver and blood stages, as opposed to blood stages