The overwhelming dominance of Duffy blood group negativity among most people living in sub-Saharan Africa has been considered the basis of their protection from endemic Plasmodium vivax malaria. New evidence demonstrates widespread transmission of P. vivax in Duffy-negative Africa, though currently of unknown distribution, magnitude, or consequences. Other new evidence from outside of Africa demonstrates marked tropisms of P. vivax for extravascular tissues of bone marrow and spleen. Those establish states of proliferative infection with low-grade or undetectable parasitemia of peripheral blood causing acute and chronic disease. This review examines the plausibility of those infectious processes also operating in Duffy-negative Africans and causing harm of unrecognized origin.