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Eradication of malaria

Elimination of the mosquito-borne infectious disease

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malaria death rate
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The World Health Organization (WHO) defines "elimination" (or "malaria-free") as having no domestic transmission (indigenous cases) for the past three years. They also define "pre-elimination" and "elimination" stages when a country has fewer than 5 or 1, respectively, cases per 1000 people at risk per year. In 2021, the total of international and national funding for malaria control and elimination was $3.5 billion—only half of what is estimated to be needed. According to UNICEF, to achieve the goal of a malaria-free world, annual funding would need to more than double to reach the US$6.8 billion target.

In parts of the world with rising living standards, the elimination of malaria was often a collateral benefit of the introduction of window screens and improved sanitation. A variety of usually simultaneous interventions represents best practice. These include antimalarial drugs to prevent or treat infection; improvements in public health infrastructure to diagnose, sequester and treat infected individuals; bednets and other methods intended to keep mosquitoes from biting humans; and vector control strategies such as larvaciding with insecticides, ecological controls such as draining mosquito breeding grounds or introducing fish to eat larvae and indoor residual spraying (IRS) with insecticides.

Development of malaria control

Pre-modern epidemiology

Malaria has majorly affected humans since the Neolithic Revolution, approximately 10,000 years before the present. Ancient societies including the Egyptians and Greeks were affected by the disease, and by the 4th century BCE it was widely known as a killer in Greece, though its cause was not yet understood. Malaria was prevalent in the Roman Empire, and the Roman scholars associated the disease with the marshy or swampy lands where the disease was particularly rampant. It was from those Romans the name "malaria" originated. They called it malaria (literally meaning "bad air") as they believed that the disease was a kind of miasma that was spread in the air, as originally conceived by ancient Greeks. Since then, it was a medical consensus for centuries that malaria was spread due to miasma, the bad air. However, in medieval West Africa, specifically at Djenné, the people were able to relate mosquitos with malaria.

Spanish missionaries in the 16th–19th-century Americas observed Amerindians near Loxa (Ecuador) treating fever with powder from "Peruvian bark" (later established to be from any of several trees of genus Cinchona). It was used by the Quechua Indians of Ecuador to reduce the shaking effects caused by severe chills. Jesuit Brother Agostino Salumbrino (1561–1642), who lived in Lima and was an apothecary by training, observed the Quechua using the bark of the cinchona tree for that purpose. While its effect in treating malaria (and hence malaria-induced shivering) was unrelated to its effect in controlling shivering from cold, it was nevertheless effective for malaria. The use of the "fever tree" bark was introduced into European medicine by Jesuit missionaries (Jesuit's bark). Jesuit Bernabé de Cobo (1582–1657), who explored Mexico and Peru, is credited with taking cinchona bark to Europe. He brought the bark from Lima to Spain, and then to Rome and other parts of Italy, in 1632. Francesco Torti wrote in 1712 that only "intermittent fever" was amenable to the fever tree bark. This work finally established the specific nature of cinchona bark and brought about its general use in medicine.

19th–early 20th centuries

Quinine

In the 19th century, the first drugs were developed to treat malaria, and parasites were first identified as its source. French chemist Pierre Joseph Pelletier and French pharmacist Joseph Bienaimé Caventou separated in 1820 the alkaloids cinchonine and quinine from powdered fever tree bark, allowing for the creation of standardized doses of the active ingredients. Prior to 1820, the bark was simply dried, ground to a fine powder and mixed into a liquid (commonly wine) for drinking.

Native Bolivian Manuel Incra Mamani spent four years collecting cinchona seeds in the Andes in Bolivia, highly prized for their quinine but forbidden from export. He provided them to an English trader, Charles Ledger, who sent the seeds to his brother in England to sell. He sold them to the Dutch government, which cultivated 20,000 trees of the Cinchona ledgeriana in Java (Indonesia). By the end of the 19th century, the Dutch had established a world monopoly over its supply.

Isolation and identification of malarial parasites

In 1834, in British Guiana, a German physician, Carl Warburg, invented an antipyretic medicine: 'Warburg's Tincture'. This secret, proprietary remedy contained quinine and a number of herbs. Trials were held in Europe in the 1840s and 1850s. It was officially adopted by the Austrian Empire in 1847. It was considered by many eminent medical professionals to be a more efficacious antimalarial than quinine. It was also more economical. The British government supplied Warburg's Tincture to troops in India and other colonies.

In 1880, French physician Charles Louis Alphonse Laveran, working in the military hospital of Constantine, Algeria, observed pigmented parasites inside the red blood cells of people afflicted with malaria. He witnessed the release of flagellated microgametes from the parasites, and became convinced that the moving flagella were parasitic microorganisms. He noted that quinine removed the parasites from the blood. Laveran called this microscopic organism Oscillaria malariae and proposed that malaria was caused by this protozoan. This discovery remained controversial until the development of the oil immersion lens in 1884 and of superior staining methods in 1890–1891. Laveran was awarded the 1907 Nobel Prize for Physiology or Medicine "in recognition of his work on the role played by protozoa in causing diseases".

Mosquito-malaria theory and early attempts at control

The notion of malaria as being caused by "bad air", or miasma, was accepted by medicine until the 19th century. The theory that the disease was in fact transmitted by mosquitoes was developed in the latter half of the century, at first received with controversy until it was proven correct in 1897.

In 1882, English-American physician Albert Freeman Africanus King proposed eradicating malaria from Washington, DC by encircling the city with a wire screen as high as the Washington Monument. Many people took this as a jest, partly because the link between malaria and mosquitoes had, at that time, been hypothesized by only a few physicians.

In 1896, an outbreak of malaria in Uxbridge, Massachusetts prompted health officer Dr. Leonard White to write a report to the State Board of Health, which led to a study of mosquito-malaria links and the first efforts for malaria prevention. Massachusetts state pathologist Theobald Smith asked that White's son collect mosquito specimens for further analysis, and that citizens add screens to windows and drain collections of water.

Britain's Sir Ronald Ross, an army surgeon working in Secunderabad, India, proved in 1897 that malaria is transmitted by mosquitoes, an event now commemorated by World Mosquito Day. He was able to find pigmented malaria parasites in a mosquito that he artificially fed on a malaria patient who had crescents in his blood. He continued his research into malaria by showing that certain mosquito species (Culex fatigans) transmit malaria to sparrows and he isolated malaria parasites from the salivary glands of mosquitoes that had fed on infected birds. He reported this to the British Medical Association in Edinburgh in 1898.

Ross' scientific evidences were soon fortified by Italian biologists including Giovanni Battista Grassi, Amico Bignami, and Giuseppe Bastianelli, who discovered that human malarial parasite was transmitted by the bite of a female mosquito. In 1899 they reported the infection of Plasmodium falciparum with the mosquito Anopheles claviger However the practical importance of validating the theory, i.e. control of mosquito vector should be an effective management strategy for malaria, was not realised by the medical community and the public. Hence in 1900 Patrick Manson clinically demonstrated that the bite of infected anopheline mosquitoes invariably resulted in malaria. He acquired carefully reared infected mosquitoes from Bignami and Bastianelli in Rome. Manson infected his own son, P. Thurburn Manson, with malaria, and P. Thurburn gave a detailed account of his malarial fevers and treatment at the London School of Tropical Medicine. As he summarised, Manson's clinical trial showed that the practical solution to malaria infection was to avoid areas where mosquitoes are abundant, to destroy the habitats of mosquitoes, and to protect from mosquito bites.

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