The history of malaria stretches from its prehistoric origin as a zoonotic disease in the primates of Africa through to the 21st century. A widespread and potentially lethal human infectious disease, at its peak malaria infested every continent, except Antarctica.[1] Its prevention and treatment have been targeted in science and medicine for hundreds of years. Since the discovery of the parasites which cause it, research attention has focused on their biology, as well as that of the mosquitoes which transmit the parasites.

References to its unique, periodic fevers are found throughout recorded history beginning in the first millennium BC in Greece and China.[2][3]

For thousands of years, traditional herbal remedies have been used to treat malaria.[4] The first effective treatment for malaria came from the bark of the cinchona tree, which contains quinine. After the link to mosquitos and their parasites were identified in the early twentieth century, mosquito control measures such as widespread use of the insecticide DDT, swamp drainage, covering or oiling the surface of open water sources, indoor residual spraying and use of insecticide treated nets was initiated. Prophylactic quinine was prescribed in malaria endemic areas, and new therapeutic drugs, including chloroquine and artemisinins, were used to resist the scourge. Today, artemisinin is present in every remedy applied in treatment of malaria. After introducing artemisinin as a cure administered together with other remedies, the mortality in Africa went down by a half.[5]

Malaria researchers have won multiple Nobel Prizes for their achievements, although the disease continues to afflict some 200 million patients each year, killing more than 600,000.

Malaria was the most important health hazard encountered by U.S. troops in the South Pacific during World War II, where about 500,000 men were infected.[6] According to Joseph Patrick Byrne, "Sixty thousand American soldiers died of malaria during the African and South Pacific campaigns."[7]

At the close of the 20th century, malaria remained endemic in more than 100 countries throughout the tropical and subtropical zones, including large areas of Central and South America, Hispaniola (Haiti and the Dominican Republic), Africa, the Middle East, the Indian subcontinent, Southeast Asia, and Oceania. Resistance of Plasmodium to anti-malaria drugs, as well as resistance of mosquitos to insecticides and the discovery of zoonotic species of the parasite have complicated control measures.

Origin and prehistoric period

The first evidence of malaria parasites was found in mosquitoes preserved in amber from the Palaeogene period that are approximately 30 million years old.[8] Human malaria likely originated in Africa and coevolved with its hosts, mosquitoes and non-human primates. Malaria protozoa are diversified into primate, rodent, bird, and reptile host lineages.[9][10] Humans may have originally caught Plasmodium falciparum from gorillas.[11] P. vivax, another malarial Plasmodium species among the six that infect humans, also likely originated in African gorillas and chimpanzees.[12] Another malarial species recently discovered to be transmissible to humans, P. knowlesi, originated in Asian macaque monkeys.[13] While P. malariae is highly host specific to humans, there is some evidence that low level non-symptomatic infection persists among wild chimpanzees.[14]

About 10,000 years ago, malaria started having a major impact on human survival, coinciding with the start of agriculture in the Neolithic revolution. Consequences included natural selection for sickle-cell disease, thalassaemias, glucose-6-phosphate dehydrogenase deficiency, Southeast Asian ovalocytosis, elliptocytosis and loss of the Gerbich antigen (glycophorin C) and the Duffy antigen on the erythrocytes, because such blood disorders confer a selective advantage against malaria infection (balancing selection).[15] The three major types of inherited genetic resistance (sickle-cell disease, thalassaemias, and glucose-6-phosphate dehydrogenase deficiency) were present in the Mediterranean world by the time of the Roman Empire, about 2000 years ago.[16]

Molecular methods have confirmed the high prevalence of P. falciparum malaria in ancient Egypt.[17] The Ancient Greek historian Herodotus wrote that the builders of the Egyptian pyramids (circa 2700–1700 BCE) were given large amounts of garlic,[18] probably to protect them against malaria. The Pharaoh Sneferu, the founder of the Fourth dynasty of Egypt, who reigned from around 2613–2589 BCE, used bed-nets as protection against mosquitoes. Cleopatra VII, the last Pharaoh of Ancient Egypt, similarly slept under a mosquito net.[19] However, whether the mosquito nets were used for the purpose of malaria prevention, or for more mundane purpose of avoiding the discomfort of mosquito bites, is unknown. The presence of malaria in Egypt from circa 800 BCE onwards has been confirmed using DNA-based methods.

Human genetic resistance to malaria

Human genetic resistance to malaria refers to inherited changes in the DNA of humans which increase resistance to malaria and result in increased survival of individuals with those genetic changes. The existence of these genotypes is likely due to evolutionary pressure exerted by parasites of the genus Plasmodium which cause malaria. Since malaria infects red blood cells, these genetic changes are most commonly alterations to molecules essential for red blood cell function (and therefore parasite survival), such as hemoglobin or other cellular proteins or enzymes of red blood cells. These alterations generally protect red blood cells from invasion by Plasmodium parasites or replication of parasites within the red blood cell.

These inherited changes to hemoglobin or other characteristic proteins, which are critical and rather invariant features of mammalian biochemistry, usually cause some kind of inherited disease. Therefore, they are commonly referred to by the names of the blood disorders associated with them, including sickle-cell disease, thalassemia, glucose-6-phosphate dehydrogenase deficiency, and others. These blood disorders cause increased morbidity and mortality in areas of the world where malaria is less prevalent.

So human malaria originated in Africa, .... so at some point Africa was called "White man's grave". Hmm!