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Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria
Quinine background and historical perspective
The discovery of quinine is considered the most serendipitous medical discovery of the 17th century [1] and malaria treatment with quinine marked the first successful use of a chemical compound to treat an infectious disease[2]. Quinine, as a component of the bark of the cinchona (quina-quina) tree, was used to treat malaria from as early as the 1600s, when it was referred to as the ''Jesuits' bark'' "cardinal's bark," or "sacred bark." These names stem from its use in 1630 by Jesuit missionaries in South America, though a legend suggests earlier use by the native population[2]. According to this legend, an Indian with a high fever was lost in an Andean jungle. Thirsty, he drank from a pool of stagnant water and found that it tasted bitter. Realizing that the water had been contaminated by the surrounding quina-quina trees he thought he was poisoned. Surprisingly, his fever soon abated, and he shared this accidental discovery with fellow villagers, who thereafter used extracts from the quina-quina bark to treat fever [3]. The legend of quinine's discovery accepted in Europe differs though, and involves the Spanish Countess of Chinchon who, while in Peru, contracted a fever that was cured by the bark of a tree. Returning to Spain with the bark, she introduced quinine to Europe in 1638 and, in 1742, botanist Carl Linnaeus called the tree "Cinchona" in her honour [4].
Before 1820, the bark of the cinchona tree was first dried, ground to a fine powder, and then mixed into a liquid (commonly wine) before being drunk. In 1820, quinine was extracted from the bark, isolated and named by Pierre Joseph Pelletier and Joseph Caventou. Purified quinine then replaced the bark as the standard treatment for malaria [5]. Quinine and other cinchona alkaloids including quinidine, cinchonine and cinchonidine are all effective against malaria. The efficacies of these four alkaloids were evaluated in one of the earliest clinical trials, conducted from 1866 to 1868 in 3600 patients using prepared sulfates of the alkaloids. With the main outcome measure of "cessation of febrile paroxysms", all four alkaloids were found to be comparable, with cure rates of >98%[6]. However, after 1890 quinine became the predominantly used alkaloid, mainly due to a change in supply from South American to Javan cinchona bark, which contained a higher proportion of quinine [7]. Quinine remained the mainstay of malaria treatment until the 1920s, when more effective synthetic anti-malarials became available. The most important of these drugs was chloroquine, which was extensively used, especially beginning in the 1940s [6]. With heavy use, chloroquine resistance developed slowly. Resistance of Plasmodium falciparum to chloroquine was seen in parts of Southeast Asia and South America by the late 1950s, and was widespread in almost all areas with falciparum malaria by the 1980s. With increasing resistance to chloroquine, quinine again played a key role, particularly in the treatment of severe malaria [6].
https://malariajournal.biomedcentral.com/articles/10.1186/1475-2875-10-144