Malaria is an ancient affliction of humanity, and over deep time malaria parasites and human beings coevolved. Some human populations developed genetic mutations to mitigate the burden of malaria. In tropical Africa, an early genetic mutation to vivax infections known as Duffy antigen negativity was dominantly successful: It dramatically reduced the incidence of vivax malaria and produced no deleterious health consequences for those who carried it. By contrast, a later genetic mutation to falciparum infections known as sickle cell hemoglobin reduced morbidity and mortality for those who inherited the sickle cell gene from only one parent but caused early death for those who inherited the sickle cell gene from both. Both Duffy negativity and sickle cell are molecular testimonies to humanity's struggle to expand our domain in early tropical Africa. They constitute the first chapter in the history of human infectious disease, and they unveil the profound depth of our African past, dissolving the artificial boundary between the supposed timelessness of “prehistory” and the chronology of “history.”

Our immune systems also responded to the burden of malaria. Few individuals infected by vivax parasites achieved immunities, even after extensive suffering, probably because the rates of vivax transmission with less efficient vectors were low compared to those in the falciparum zone. By contrast, most falciparum sufferers in areas of intense transmission, who survived their early childhood infections, remained parasitized but achieved partially or fully functional immunities.