Malaria and Human Polymorphisms

Malaria has probably killed more human beings than any other single disease (Garnham 1) . In 1952 Russell (2) estimated that there were about 350 million cases of malaria per year with an estimated 1 percent mortality. More recently Bruce-Chwatt (3) has estimated that 1741 million people now live in areas that were once malarious; of that numher 381 million are still subjected to endemic malaria, and 710 million inhabit areas where malaria is only partially controlled. As a leading cause of human morbidity and mortality, malaria has undoubtedly been a major agent of natural se­ lection and consequently a determinant of man's genetic evolution. Haldane (4-6) was primarily responsible for directing the attention of geneticists to the importance of infectious disease including malaria in man's recent evolution. Although man undoubtedly has had many parasites during his long history as a hunter and collector, the domestication of animals and plants about 9000 years ago increased the number and severity of parasitic infections, since it enormously increased the population density of the human species and made it one of the most available hosts for parasites. The effects of either epidemic or endemic malaria are also so disruptive to human affairs that malaria has often been considered a major cause of historical events from the declines of Greece and Rome to the failure of the Crusades and the Gallipoli campaign of World War I (Jones 7 , Hackett 8, Garnham 1). Shortt (9) has discussed the economic importance of malaria and given examples of its disastrous effects. He also points out that this disease may have prevented the settling of some areas of India. Because of its distinctive symptoms, malaria can be traced more pre­ cisely than most infectious diseases in the writings of antiquity. References on papyri of the 16th century B. C. to splenomegaly, and hieroglyphic inscriptions referring to intermittent fever seem to indicate the presence of malaria in ancient Egypt (Hoeppli 10, Garnham 1) . But the characteristic symptoms of malaria, tertian or quartan fever and an enlarged spleen, were specifically recorded in Greece by Hippocrates in the 4th century B . C. and were also known in Roman times in Italy (Boyd 1 1 , Russell 12). Pre­ Christian written records from China and India also refer to the same symptoms (Gwei-Djen so we know that malaria was present throughout the civilizations of antiquity.