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      Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria

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          Abstract

          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.

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          Most cited references112

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          Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial.

          In the treatment of severe malaria, intravenous artesunate is more rapidly acting than intravenous quinine in terms of parasite clearance, is safer, and is simpler to administer, but whether it can reduce mortality is uncertain. We did an open-label randomised controlled trial in patients admitted to hospital with severe falciparum malaria in Bangladesh, India, Indonesia, and Myanmar. We assigned individuals intravenous artesunate 2.4 mg/kg bodyweight given as a bolus (n=730) at 0, 12, and 24 h, and then daily, or intravenous quinine (20 mg salt per kg loading dose infused over 4 h then 10 mg/kg infused over 2-8 h three times a day; n=731). Oral medication was substituted when possible to complete treatment. Our primary endpoint was death from severe malaria, and analysis was by intention to treat. We assessed all patients randomised for the primary endpoint. Mortality in artesunate recipients was 15% (107 of 730) compared with 22% (164 of 731) in quinine recipients; an absolute reduction of 34.7% (95% CI 18.5-47.6%; p=0.0002). Treatment with artesunate was well tolerated, whereas quinine was associated with hypoglycaemia (relative risk 3.2, 1.3-7.8; p=0.009). Artesunate should become the treatment of choice for severe falciparum malaria in adults.
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            Vertical transmission of HIV-1 infection.

            M-L Newell (2015)
            Vertical transmission is the dominant mode of acquisition of infection for HIV infection in children, and about 1600 infants are newly infected each day worldwide. Without interventions the risk of transmission is between 15% and 35%, and associated with maternal disease progression, prematurity, duration of rupture of membranes, length of labour, and vaginal delivery. Breastfeeding approximately doubles the risk of vertical transmission; the additional risk of transmission through breastfeeding is approximately 15-20%, with about one-third of this accounted for by late postnatal transmission after 3 months of age. Current strategies to reduce the risk of transmission include a short course of anti-retroviral therapy, avoidance of breastfeeding and Caesarean section delivery. However, even if interventions late in pregnancy or around the time of delivery are highly effective in preventing perinatal infection, it is likely that as a public health policy they are of interest only if alternatives to breastfeeding are feasible, affordable, safe and available.
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              Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial

              Summary Background Severe malaria is a major cause of childhood death and often the main reason for paediatric hospital admission in sub-Saharan Africa. Quinine is still the established treatment of choice, although evidence from Asia suggests that artesunate is associated with a lower mortality. We compared parenteral treatment with either artesunate or quinine in African children with severe malaria. Methods This open-label, randomised trial was undertaken in 11 centres in nine African countries. Children (<15 years) with severe falciparum malaria were randomly assigned to parenteral artesunate or parenteral quinine. Randomisation was in blocks of 20, with study numbers corresponding to treatment allocations kept inside opaque sealed paper envelopes. The trial was open label at each site, and none of the investigators or trialists, apart from for the trial statistician, had access to the summaries of treatment allocations. The primary outcome measure was in-hospital mortality, analysed by intention to treat. This trial is registered, number ISRCTN50258054. Findings 5425 children were enrolled; 2712 were assigned to artesunate and 2713 to quinine. All patients were analysed for the primary outcome. 230 (8·5%) patients assigned to artesunate treatment died compared with 297 (10·9%) assigned to quinine treatment (odds ratio [OR] stratified for study site 0·75, 95% CI 0·63–0·90; relative reduction 22·5%, 95% CI 8·1–36·9; p=0·0022). Incidence of neurological sequelae did not differ significantly between groups, but the development of coma (65/1832 [3·5%] with artesunate vs 91/1768 [5·1%] with quinine; OR 0·69 95% CI 0·49–0·95; p=0·0231), convulsions (224/2712 [8·3%] vs 273/2713 [10·1%]; OR 0·80, 0·66–0·97; p=0·0199), and deterioration of the coma score (166/2712 [6·1%] vs 208/2713 [7·7%]; OR 0·78, 0·64–0·97; p=0·0245) were all significantly less frequent in artesunate recipients than in quinine recipients. Post-treatment hypoglycaemia was also less frequent in patients assigned to artesunate than in those assigned to quinine (48/2712 [1·8%] vs 75/2713 [2·8%]; OR 0·63, 0·43–0·91; p=0·0134). Artesunate was well tolerated, with no serious drug-related adverse effects. Interpretation Artesunate substantially reduces mortality in African children with severe malaria. These data, together with a meta-analysis of all trials comparing artesunate and quinine, strongly suggest that parenteral artesunate should replace quinine as the treatment of choice for severe falciparum malaria worldwide. Funding The Wellcome Trust.
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                Author and article information

                Journal
                Malar J
                Malaria Journal
                BioMed Central
                1475-2875
                2011
                24 May 2011
                : 10
                : 144
                Affiliations
                [1 ]Department of Pediatrics and Child Health, Makerere University College of Health Sciences, P.O. Box 7475, Kampala, Uganda
                [2 ]Department of Epidemiology and Biostatistics, Makerere University School of Public Health, P.O Box 7072, Kampala, Uganda
                [3 ]Department of Parasitology, Institute of Tropical Medicine, Nationalestraat 155, 2000 Antwerp, Belgium
                [4 ]Epidemiology Unit, Uganda Malaria Surveillance Project, P.O Box 7475, Kampala, Uganda
                [5 ]Communicable Diseases Control Department, Malaria Consortium Africa, P.O Box 8045, Kampala, Uganda
                [6 ]Department of Medicine, University of California San Francisco, 1001 Potrero Ave, SFGH 30, San Francisco, CA, 94143, USA
                Article
                1475-2875-10-144
                10.1186/1475-2875-10-144
                3121651
                21609473
                22943d03-2c85-4602-8734-391b42b4789e
                Copyright ©2011 Achan et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 31 January 2011
                : 24 May 2011
                Categories
                Review

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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