Prevention and treatment of vivax malaria

Abstract

Plasmodium vivax is a significant public health threat throughout most of the tropics and to travelers to these regions. The infection causes a debilitating febrile syndrome that often recurs and in rare cases ends in death. The complex life cycle of the parasite compounds the difficulty of prevention and treatment, principally due to the phenomenon of relapse. Most commonly used drugs for preventing malaria fail to prevent late relapses by this parasite. Treatment requires dealing with both blood and liver stages. Since 1950, primaquine has been the only drug available for treatment of liver stages, and important clinical questions surround its appropriate use (ie, dosing, efficacy, safety, and tolerability). Likewise, chloroquine has been first-line therapy for vivax malaria since 1946, and the emergence of resistance to the drug further complicates therapeutic management decisions.

The Global Public Health Significance of Plasmodium vivax

“…One theory is that the mechanism is an adaptive trait of the parasite to sequester or 'hibernate' during times when climatic conditions would be inhospitable to the Anopheles vector of the disease (Shute et al, 1976;Baird and Rieckmann, 2003;White, 2011). This theory is supported by observations that temperate strains of the parasite tend to exhibit longer relapse intervals than tropical strains (Garnham et al, 1975;Shute et al, 1976;Cogswell, 1992;Collins and Jeffery, 1996;Adak et al, 1998;Baird et al, 2007;Imwong et al, 2007). Primaquine is currently the only widely available drug with activity on the hypnozoite stage capable of preventing relapse (Baird and Hoffman, 2004;Galappaththy et al, 2007), but is associated with haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency (Beutler, 1994;Baird and Hoffman, 2004;Cappellini and Fiorelli, 2008).…”

Clinical Proteomics of the Neglected Human Malarial Parasite Plasmodium vivax

“…As with P. falciparum , drug resistance poses a severe problem in the treatment of vivax -malaria. Drug resistant strains of P. vivax have evolved against commonly used anti-malarials such as chloroquine, primaquine and sulphadoxine-pyrimethamine [37]–[39]. Notwithstanding the recent advances in global studies of P. vivax by transcriptomics and next generation sequencing [5], [6], [40], the amount of knowledge that exists about P. vivax is insufficient to understand its biology that will enable discovery of newer drug targets against the parasite.…”

Prophylaxis of Malaria

“…They demonstrated 100% protective efficacy. 41 Since these drugs have no activity against liver stages and development of hypnozoites, they actually prevent only primary infection and not late relapses. In fact in recent years, with the increase of travel to the tropics, it has become more evident that using recommended prophylaxis, which is almost exclusively blood stage prophylaxis, only postpones the first clinical attack of malaria to several months after return.…”