The global burden of Plasmodium vivax malaria is obscure and insidious

Abstract

Estimates of the global burdens of morbidity attributable to acute attacks of Plasmodium falciparum malaria typically dwarf those of Plasmodium vivax, i.e., hundreds of millions versus tens of millions of cases. Global burden estimates take no account of latent and subpatent reservoirs of infections carrying more subtle burdens of illness and death in impoverished settings of malnutrition, coendemic infections, and limited access to quality healthcare. Impacts of chronic malaria on human health may be substantial and are excluded from estimates of burdens of acute malaria. Compartments of human infection by P. vivax beyond vascular patency-vascular subpatency, extravascular subpatency, sexual latency, and hepatic latency-obscure endemic transmission and burdens of infection and illness. Long thought to be absent from most of sub-Saharan Africa due to the high prevalence of the Duffy-negative phenotype among residents, recent investigations suggest that widespread reservoirs of transmission may occur across that region. Human glucose-6-phosphate dehydrogenase (G6PD) deficiency may also affect susceptibility to infection and directly impact access to effective antirelapse therapy of P. vivax using 8-aminoquinolines that are dangerous to those patients. Natural polymorphisms of the human cytochrome P-450 2D6 gene impact parasite susceptibility to primaquine antirelapse therapy at population levels. All these factors impose great complexity in considering estimates of burdens of P. vivax and access to effective mitigation of the harm caused. The conventional diagnostics underpinning epidemiological and clinical understanding of vivax malaria may be inadequate to the biology of this parasite.