The Epidemiology of Plasmodium Vivax: History, Hiatus and Hubris

Shanks, G. Dennis, G. Dennis Shanks

Plasmodium vivax represents a special challenge to malaria control because of the ability of a single infection to relapse over months to years. P. vivax is more tolerant of low temperatures than P. falciparum, which spreads its potential range far beyond the tropics into sub-Arctic areas. Ordinary malaria control measures such as residual insecticide spraying and impregnated bed nets are effective for P. vivax, but long-lasting (up to 3 years) residual hepatic parasites (hypnozoites) mean that even well-executed malaria control programs must maintain maximal efforts for an extended period in order to eliminate indigenous infections. Hypnozoites are only eliminated by using an 8-aminoquinoline (currently only primaquine), which requires compliance with a long regimen as well as care to avoid those at risk of haemolysis due to the common genetic polymorphism, glucose-6-phosphate dehydrogenase deficiency. Risk of reintroduction of P. vivax into areas without malaria but still containing competent Anopheles vectors is enhanced as persons carrying hypnozoites are undetectable until they become symptomatic from activation of the quiescent liver parasite. Mass drug administration using drug combinations including primaquine have successfully eliminated malaria from small islands demonstrating proof of principal as a potential elimination method. It will be very difficult to maintain adequate malaria surveillance measures for years after malaria has ceased to be a public health problem, which will clearly be required to eliminate relapsing malaria such as P. vivax. New interventions will likely be required to eliminate vivax malaria; highly desirable new products include transmission-blocking vaccines, new drug combinations to treat chloroquine resistant strains and a safe, long-lasting 8-aminoquinoline.