Battle KE, Baird JK, et al. - Typically smaller estimates were generated for the global burdens of morbidity attributable to acute attacks of Plasmodium falciparum malaria vs Plasmodium vivax, ie, hundreds of millions vs tens of millions of cases.

• Latent and subpatent reservoirs of infections are not accounted in global burden estimates which carry more subtle burdens of illness and death in impoverished settings of malnutrition, coendemic infections, and limited access to quality healthcare.

• Possibly there are substantial impacts of chronic malaria on human health that are excluded from estimates of burdens of acute malaria.

• Endemic transmission and burdens of infection and illness are obscured because of compartments of human infection by P. vivax beyond vascular patency—vascular subpatency, extravascular subpatency, sexual latency, and hepatic latency.

• Due to the high prevalence of the Duffy-negative phenotype among residents, there was a misconception of their absence from most of sub-Saharan Africa for a long time, recent investigations however suggest a possible presence of widespread reservoirs of transmission across that region.

• Possibly the susceptibility to infection is influenced by the deficiency of human glucose-6-phosphate dehydrogenase (G6PD) which may directly affect access to effective antirelapse therapy of P. vivax using 8-aminoquinolines that are dangerous to those patients.

• Parasite susceptibility to primaquine antirelapse therapy is impacted at population levels by the natural polymorphisms of the human cytochrome P-450 2D6 gene.

• Because of all these factors, great complexity is encountered in determining 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.