Treatment, Prophylaxis and Resistance in P. vivax Malaria

Abstract

The burden of malaria caused by Plasmodium vivax remains under-appreciated to a great extent, both in terms of its clinical spectrum and incidence of disease. Control measures are hampered by both the emergence of chloroquine (CQ) resistance and the presence of dormant hypnozoite stages in the liver, which result in relapse infections weeks after the cure of the initial episode. Although CQ remains the first line of treatment for patients with vivax malaria in most of the world, CQ monotherapy is now virtually ineffective in Papua Indonesia with significant clinical resistance apparent throughout the Indonesian archipelago. Sporadic cases have been reported from South America and Asia. Unfortunately, the mechanism of P. vivax CQ resistance is largely unknown and as yet no genetic markers have been identified. Since clinical studies are difficult to carry out in this species due to factors such as individual variations in patient immune status, reinfections and frequent relapses, and in vitro susceptibility assays applicability is limited by lack of culture methods, the global prevalence of CQ resistance to P. vivax continues to be poorly defined. Primaquine, an 8-aminoquinoline compound, is the only commercially available drug with hypnozoitocidal activity against P. vivax and is widely used for terminal prophylaxis; yet, little is known about how the drug works, if it works, or how it fails. Reports of true PQ failure and subsequent P. vivax relapse are unusual. Most suspected cases can be ascribed to poor patient adherence. The lack of effective alternatives to PQ against hypnozoites represents an important drawback in clinical practice and may be as operationally crippling to control efforts against P. vivax, as having no access to insecticides, bed nets, reliable diagnostics, or chemoprophylaxis. Plasmodium vivax malaria will linger as a persistent and severe challenge to public health as long as our drug armamentarium remains limited and substantial areas of our knowledge on its biology, epidemiology, genetics, metabolism, and mechanisms of resistance to antimalarials, remain obscure. Abstracts for SupplementInternational Journal of Infectious DiseasesVol. 14Preview Full-Text PDF Open Archive