Evidence and implications of mortality associated with acute Plasmodium vivax malaria

Abstract

Vivax malaria threatens patients despite relatively low-grade parasitemias in peripheral blood. The tenet of death as a rare outcome, derived from antiquated and flawed clinical classifications, disregarded key clinical evidence, including (i) high rates of mortality in neurosyphilis patients treated with vivax malaria; (ii) significant mortality from zones of endemicity; and (iii) the physiological threat inherent in repeated, very severe paroxysms in any patient, healthy or otherwise. The very well-documented course of this infection, with the exception of parasitemia, carries all of the attributes of "perniciousness" historically linked to falciparum malaria, including severe disease and fatal outcomes. A systematic analysis of the parasite biomass in severely ill patients that includes blood, marrow, and spleen may ultimately explain this historic misunderstanding. Regardless of how this parasite is pernicious, recent data demonstrate that the infection comes with a significant burden of morbidity and associated mortality. The extraordinary burden of malaria is not heavily weighted upon any single continent by a single species of parasite-it is a complex problem for the entire endemic world, and both species are of fundamental importance. Humanity must rally substantial resources, intellect, and energy to counter this daunting but profound threat.

Fig 1

Global map illustrating prevalence of Plasmodium vivax in 2010. (Reproduced from reference , which was published under a Creative Commons license.)

Fig 2

(Top) Typical course of repeated daily paroxysms in a neurosyphilis patient treated with P. vivax (body temperature is given in degrees Fahrenheit). (Bottom) Course of a single 14-hour paroxysm. (Reprinted from reference with permission from BMJ Publishing Group Ltd.)

Fig 3

(Top) Graph illustrating citations in books for Plasmodium falciparum and Plasmodium vivax from 1900 to 2008, generated by use of the tool at http://books.google.com/ngrams. (Bottom) Citation data from PubMed since 1960. (Reproduced from reference, which was published under a Creative Commons license.)

Fig 4

Proportions of patients with not serious, serious, or fatal disease with a diagnosis of P. falciparum or P. vivax infection and having parasitemias of >6,000/μl among patients hospitalized with a primary diagnosis of malaria at a hospital in Sumba, Indonesia. (Reproduced from reference with permission.)

Fig 5

Mature trophozoite of P. vivax in a Giemsa-stained thin blood film under oil-immersion magnification. (Photomicrograph by Lenny Ekawati, Jakarta, Indonesia.)