Malaria or a disease resembling malaria has been noted for more than 4,000 years. From the Italian for “bad air,” mal’aria has probably influenced to a great extent human populations and human history.

Ancient History (2700 BCE-340 CE)

The symptoms of malaria were described in ancient Chinese medical writings. In 2700 BC, several characteristic symptoms of what would later be named malaria were described in the Nei Ching, The Canon of Medicine). Nei Ching was edited by Emperor Huang Ti. Malaria became widely recognized in Greece by the 4th century BCE, and it was responsible for the decline of many of the city-state populations. Hippocrates noted the principal symptoms. By the age of Pericles, there were extensive references to malaria in the literature and depopulation of rural areas was recorded. In the Susruta, a Sanskrit medical treatise, the symptoms of malarial fever were described and attributed to the bites of certain insects. A number of Roman writers attributed malarial diseases to the swamps.

In China, during the second century BCE, the Qinghao plant (Artemisia annua) was described in the medical treatise, 52 Remedies, found in the Mawangdui Tomb. In the United States, this plant is known as the annual or sweet wormwood. In 340 CE, the antifever properties of Qinghao were first described by Ge Hong of the East Yin Dynasty. The active ingredient of Qinghao, known as artemisinin, was isolated by Chinese scientists in 1971. Derivatives of this extract, known collectively as artemisinins, are today very potent and effective antimalarial drugs, especially in combination with other medicines.

Quinine (Early 17th Century)

Following their arrival in the New World, Spanish Jesuit missionaries learned from indigenous Indian tribes of a medicinal bark used for the treatment of fevers. With this bark, the Countess of Chinchón, the wife of the Viceroy of Peru, was cured of her fever. The bark from the tree was then called Peruvian bark and the tree was named Cinchona after the countess. The medicine from the bark is now known as the antimalarial, quinine. Along with artemisinins, quinine is one of the most effective antimalarial drugs available today.

Discovery of the Malaria Parasite (1880)

Charles Louis Alphonse Laveran, a French army surgeon stationed in Constantine, Algeria, was the first to notice parasites in the blood of a patient suffering from malaria. This occurred on the 6th of November 1880. For his discovery, Laveran was awarded the Nobel Prize in 1907.

Differentiation of Species of Malaria (1886)

Camillo Golgi, an Italian neurophysiologist, established that there were at least two forms of the disease, one with tertian periodicity (fever every other day) and one with quartan periodicity (fever every third day). He also observed that the forms produced differing numbers of merozoites (new parasites) upon maturity and that fever coincided with the rupture and release of merozoites into the blood stream. He was awarded a Nobel Prize in Medicine for his discoveries in neurophysiology in 1906.

Portrait of Laveran

Alphonse Laveran was the first to notice parasites in the blood of a patient suffering from malaria.

Naming of Human Malaria Parasites (1890, 1897)

The Italian investigators Giovanni Batista Grassi and Raimondo Filetti first introduced the names Plasmodium vivax and P. malariae for two of the malaria parasites that affect humans in 1890. Laveran had believed that there was only one species, Oscillaria malariae. An American, William H. Welch, reviewed the subject and, in 1897, he named the malignant tertian malaria parasite P. falciparum. There were many arguments against the use of this name; however, the use was so extensive in the literature that a change back to the name given by Laveran was no longer thought possible. In 1922, John William Watson Stephens described the fourth human malaria parasite, P. ovale. P. knowlesi was first described by Robert Knowles and Biraj Mohan Das Gupta in 1931 in a long-tailed macaque. The first documented human infection with P. knowlesi was in 1965.

Discovery That Mosquitoes Transmit Malaria Parasites (1897-1898)

On August 20th, 1897, Ronald Ross, a British officer in the Indian Medical Service, was the first to demonstrate that malaria parasites could be transmitted from infected patients to mosquitoes. In further work with bird malaria, Ross showed that mosquitoes could transmit malaria parasites from bird to bird. This necessitated a sporogonic cycle (the time interval during which the parasite developed in the mosquito). Thus, the problem of malaria transmission was solved. For his discovery, Ross was awarded the Nobel Prize in 1902.

Discovery of the Transmission of the Human Malaria Parasites Plasmodium (1898-1899)

Led by Giovanni Batista Grassi, a team of Italian investigators, which included Amico Bignami and Giuseppe Bastianelli, collected Anopheles claviger mosquitoes and fed them on malarial patients. The complete sporogonic cycle of Plasmodium falciparum, P. vivax, and P. malariae was demonstrated. In 1899, mosquitoes infected by feeding on a patient in Rome were sent to London where they fed on two volunteers, both of whom developed malaria.

The Panama Canal (1905-1910)

The construction of the Panama Canal was made possible only after yellow fever and malaria were controlled in the area. These two diseases were a major cause of death and disease among workers in the area. In 1906, there were over 26,000 employees working on the Canal. Of these, over 21,000 were hospitalized for malaria at some time during their work. By 1912, there were over 50,000 employees, and the number of hospitalized workers had decreased to approximately 5,600. Through the leadership and efforts of William Crawford Gorgas, Joseph Augustin LePrince, and Samuel Taylor Darling, yellow fever was eliminated and malaria incidence markedly reduced through an integrated program of insect and malaria control.

Chloroquine (Resochin) (1934, 1946)

Chloroquine was discovered by a German, Hans Andersag, in 1934 at Bayer I.G. Farbenindustrie A.G. laboratories in Eberfeld, Germany. He named his compound resochin. Through a series of lapses and confusion brought about during the war, chloroquine was finally recognized and established as an effective and safe antimalarial in 1946 by British and U.S. scientists.

Dichloro-diphenyl-trichloroethane (DDT) (1939)

A German chemistry student, Othmer Zeidler, synthesized DDT in 1874, for his thesis. The insecticidal property of DDT was not discovered until 1939 by Paul Müller in Switzerland. Various militaries in WWII utilized the new insecticide initially for control of louse-borne typhus. DDT was used for malaria control at the end of WWII after it had proven effective against malaria-carrying mosquitoes by British, Italian, and American scientists. Müller won the Nobel Prize for Medicine in 1948.