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Quinine remains an important anti-malarial drug almost 400 years after its effectiveness was first documented. However, its continued use is challenged by its poor tolerability, poor compliance with complex dosing regimens, and the availability of more efficacious anti-malarial drugs. This article reviews the historical role of quinine, considers its current usage and provides insight into its appropriate future use in the treatment of malaria. In light of recent research findings intravenous artesunate should be the first-line drug for severe malaria, with quinine as an alternative. The role of rectal quinine as pre-referral treatment for severe malaria has not been fully explored, but it remains a promising intervention. In pregnancy, quinine continues to play a critical role in the management of malaria, especially in the first trimester, and it will remain a mainstay of treatment until safer alternatives become available. For uncomplicated malaria, artemisinin-based combination therapy (ACT) offers a better option than quinine though the difficulty of maintaining a steady supply of ACT in resource-limited settings renders the rapid withdrawal of quinine for uncomplicated malaria cases risky. The best approach would be to identify solutions to ACT stock-outs, maintain quinine in case of ACT stock-outs, and evaluate strategies for improving quinine treatment outcomes by combining it with antibiotics. In HIV and TB infected populations, concerns about potential interactions between quinine and antiretroviral and anti-tuberculosis drugs exist, and these will need further research and pharmacovigilance.
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 . 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%. 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 . 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 . 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 . To-date quinine continues to play a significant role in the management of malaria. This review, discusses the historical role of quinine, considers its current usage, and provides insight into the appropriate future use of quinine for the treatment of malaria. Information was obtained by searching published literature in the National Library of Medicine via Pub Med and MEDLINE search engines for research articles, reviews, books, and other reports. Identification of published reports was done using key word searches such as quinine and malaria treatment, quinine and drug resistance, quinine in pregnancy, quinine and antibiotic combinations, and quinine and HIV/TB infected populations.
In the near future, quinine will continue to play a significant role in the management of malaria, particularly in resource limited settings. Following the results of the SEAQUAMAT and AQUAMAT trials, artesunate is now recommended as the treatment of choice for severe malaria patients, with quinine only acting as an alternative when artesunate is not available. The role of rectal quinine as pre-referral treatment for severe malaria has not been fully explored, but this remains a promising intervention given the limited availability of rectal artemisinin preparations in resource limited settings. Quinine continues to play a critical role in the management of malaria in the first trimester of pregnancy, and will remain so until safer alternatives become available. The continued use of quinine in the management of uncomplicated malaria is a concern. Clearly, the seven day duration of therapy and thrice daily administration of quinine present a major challenge to completion of therapy, leading to sub-optimal treatment outcomes. In these situations, ACT is a better option given the simplicity of dosing and shorter treatment duration. However, because of the frequent ACT stock outs, the rapid withdrawal of quinine as a treatment option for uncomplicated malaria cases is risky. The best approach would be, besides improving the supply system, to maintain quinine as a fall-back drug in case of ACT stock-outs.