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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... Full description

Journal Title: Lancet 2010, Vol.376 (9753), p.1647-1657
Main Author: Dondorp, Arjen M, MD
Other Authors: Fanello, Caterina I, PhD , Hendriksen, Ilse CE, MD , Gomes, Ermelinda, MD , Seni, Amir, MD , Chhaganlal, Kajal D, MD , Bojang, Kalifa, FRCP , Olaosebikan, Rasaq, FWACP , Anunobi, Nkechinyere, FMCpaed , Maitland, Kathryn, Prof , Kivaya, Esther, MSc , Agbenyega, Tsiri, Prof , Nguah, Samuel Blay, FWACPCH , Evans, Jennifer, MRCPCH , Gesase, Samwel, MD , Kahabuka, Catherine, MD , Mtove, George, MD , Nadjm, Behzad, MD , Deen, Jacqueline, MD , Mwanga-Amumpaire, Juliet, MD , Nansumba, Margaret, MD , Karema, Corine, MD , Umulisa, Noella, MD , Uwimana, Aline, MD , Mokuolu, Olugbenga A, FWACP , Adedoyin, Olanrewaju T, FWACP , Johnson, Wahab BR, Prof , Tshefu, Antoinette K, Prof , Onyamboko, Marie A, MB , Sakulthaew, Tharisara, BNS , Ngum, Wirichada Pan, PhD , Silamut, Kamolrat, PhD , Stepniewska, Kasia, PhD , Woodrow, Charles J, MRCP , Bethell, Delia, MRCPCH , Wills, Bridget, FRCPCH , Oneko, Martina, MD , Peto, Tim E, Prof , von Seidlein, Lorenz, PhD , Day, Nicholas PJ, Prof , White, Nicholas J, Prof
Format: Electronic Article Electronic Article
Language: English
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Quelle: Alma/SFX Local Collection
Publisher: Kidlington: Elsevier Ltd
ID: ISSN: 0140-6736
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title: Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial
format: Article
creator:
  • Dondorp, Arjen M, MD
  • Fanello, Caterina I, PhD
  • Hendriksen, Ilse CE, MD
  • Gomes, Ermelinda, MD
  • Seni, Amir, MD
  • Chhaganlal, Kajal D, MD
  • Bojang, Kalifa, FRCP
  • Olaosebikan, Rasaq, FWACP
  • Anunobi, Nkechinyere, FMCpaed
  • Maitland, Kathryn, Prof
  • Kivaya, Esther, MSc
  • Agbenyega, Tsiri, Prof
  • Nguah, Samuel Blay, FWACPCH
  • Evans, Jennifer, MRCPCH
  • Gesase, Samwel, MD
  • Kahabuka, Catherine, MD
  • Mtove, George, MD
  • Nadjm, Behzad, MD
  • Deen, Jacqueline, MD
  • Mwanga-Amumpaire, Juliet, MD
  • Nansumba, Margaret, MD
  • Karema, Corine, MD
  • Umulisa, Noella, MD
  • Uwimana, Aline, MD
  • Mokuolu, Olugbenga A, FWACP
  • Adedoyin, Olanrewaju T, FWACP
  • Johnson, Wahab BR, Prof
  • Tshefu, Antoinette K, Prof
  • Onyamboko, Marie A, MB
  • Sakulthaew, Tharisara, BNS
  • Ngum, Wirichada Pan, PhD
  • Silamut, Kamolrat, PhD
  • Stepniewska, Kasia, PhD
  • Woodrow, Charles J, MRCP
  • Bethell, Delia, MRCPCH
  • Wills, Bridget, FRCPCH
  • Oneko, Martina, MD
  • Peto, Tim E, Prof
  • von Seidlein, Lorenz, PhD
  • Day, Nicholas PJ, Prof
  • White, Nicholas J, Prof
subjects:
  • Africa South of the Sahara
  • Antibiotics. Antiinfectious agents. Antiparasitic agents
  • Antimalarials
  • Antimalarials - adverse effects
  • Antimalarials - therapeutic use
  • Antiparasitic agents
  • Artemisinins
  • Artemisinins - adverse effects
  • Artemisinins - therapeutic use
  • Biological and medical sciences
  • Biomedical research
  • Child
  • Child, Preschool
  • Complications and side effects
  • Dosage and administration
  • Drug therapy
  • Falciparum
  • Fast track
  • Fast track — Articles
  • Female
  • General aspects
  • Hospitals
  • Human protozoal diseases
  • Humans
  • Infant
  • Infectious diseases
  • Internal Medicine
  • Kaplan
  • Kaplan-Meier Estimate
  • Malaria
  • Malaria, Falciparum - complications
  • Malaria, Falciparum - drug therapy
  • Malaria, Falciparum - mortality
  • Male
  • Medical research
  • Medical sciences
  • Medicine
  • Meier Estimate
  • Mortality
  • Parasitic diseases
  • Pharmacology. Drug treatments
  • Preschool
  • Protozoal diseases
  • Quinine
  • Quinine - adverse effects
  • Quinine - therapeutic use
  • Survival Rate
  • Systematic review
ispartof: Lancet, 2010, Vol.376 (9753), p.1647-1657
description: 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 (
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0140-6736
fulltext: fulltext
issn:
  • 0140-6736
  • 1474-547X
  • 1474-547X
url: Link


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titleArtesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial
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creatorDondorp, Arjen M, MD ; Fanello, Caterina I, PhD ; Hendriksen, Ilse CE, MD ; Gomes, Ermelinda, MD ; Seni, Amir, MD ; Chhaganlal, Kajal D, MD ; Bojang, Kalifa, FRCP ; Olaosebikan, Rasaq, FWACP ; Anunobi, Nkechinyere, FMCpaed ; Maitland, Kathryn, Prof ; Kivaya, Esther, MSc ; Agbenyega, Tsiri, Prof ; Nguah, Samuel Blay, FWACPCH ; Evans, Jennifer, MRCPCH ; Gesase, Samwel, MD ; Kahabuka, Catherine, MD ; Mtove, George, MD ; Nadjm, Behzad, MD ; Deen, Jacqueline, MD ; Mwanga-Amumpaire, Juliet, MD ; Nansumba, Margaret, MD ; Karema, Corine, MD ; Umulisa, Noella, MD ; Uwimana, Aline, MD ; Mokuolu, Olugbenga A, FWACP ; Adedoyin, Olanrewaju T, FWACP ; Johnson, Wahab BR, Prof ; Tshefu, Antoinette K, Prof ; Onyamboko, Marie A, MB ; Sakulthaew, Tharisara, BNS ; Ngum, Wirichada Pan, PhD ; Silamut, Kamolrat, PhD ; Stepniewska, Kasia, PhD ; Woodrow, Charles J, MRCP ; Bethell, Delia, MRCPCH ; Wills, Bridget, FRCPCH ; Oneko, Martina, MD ; Peto, Tim E, Prof ; von Seidlein, Lorenz, PhD ; Day, Nicholas PJ, Prof ; White, Nicholas J, Prof
creatorcontribDondorp, Arjen M, MD ; Fanello, Caterina I, PhD ; Hendriksen, Ilse CE, MD ; Gomes, Ermelinda, MD ; Seni, Amir, MD ; Chhaganlal, Kajal D, MD ; Bojang, Kalifa, FRCP ; Olaosebikan, Rasaq, FWACP ; Anunobi, Nkechinyere, FMCpaed ; Maitland, Kathryn, Prof ; Kivaya, Esther, MSc ; Agbenyega, Tsiri, Prof ; Nguah, Samuel Blay, FWACPCH ; Evans, Jennifer, MRCPCH ; Gesase, Samwel, MD ; Kahabuka, Catherine, MD ; Mtove, George, MD ; Nadjm, Behzad, MD ; Deen, Jacqueline, MD ; Mwanga-Amumpaire, Juliet, MD ; Nansumba, Margaret, MD ; Karema, Corine, MD ; Umulisa, Noella, MD ; Uwimana, Aline, MD ; Mokuolu, Olugbenga A, FWACP ; Adedoyin, Olanrewaju T, FWACP ; Johnson, Wahab BR, Prof ; Tshefu, Antoinette K, Prof ; Onyamboko, Marie A, MB ; Sakulthaew, Tharisara, BNS ; Ngum, Wirichada Pan, PhD ; Silamut, Kamolrat, PhD ; Stepniewska, Kasia, PhD ; Woodrow, Charles J, MRCP ; Bethell, Delia, MRCPCH ; Wills, Bridget, FRCPCH ; Oneko, Martina, MD ; Peto, Tim E, Prof ; von Seidlein, Lorenz, PhD ; Day, Nicholas PJ, Prof ; White, Nicholas J, Prof ; for the AQUAMAT group ; AQUAMAT group
descriptionSummary 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.
identifier
0ISSN: 0140-6736
1ISSN: 1474-547X
2EISSN: 1474-547X
3DOI: 10.1016/S0140-6736(10)61924-1
4PMID: 21062666
5CODEN: LANCAO
languageeng
publisherKidlington: Elsevier Ltd
subjectAfrica South of the Sahara ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antimalarials ; Antimalarials - adverse effects ; Antimalarials - therapeutic use ; Antiparasitic agents ; Artemisinins ; Artemisinins - adverse effects ; Artemisinins - therapeutic use ; Biological and medical sciences ; Biomedical research ; Child ; Child, Preschool ; Complications and side effects ; Dosage and administration ; Drug therapy ; Falciparum ; Fast track ; Fast track — Articles ; Female ; General aspects ; Hospitals ; Human protozoal diseases ; Humans ; Infant ; Infectious diseases ; Internal Medicine ; Kaplan ; Kaplan-Meier Estimate ; Malaria ; Malaria, Falciparum - complications ; Malaria, Falciparum - drug therapy ; Malaria, Falciparum - mortality ; Male ; Medical research ; Medical sciences ; Medicine ; Meier Estimate ; Mortality ; Parasitic diseases ; Pharmacology. Drug treatments ; Preschool ; Protozoal diseases ; Quinine ; Quinine - adverse effects ; Quinine - therapeutic use ; Survival Rate ; Systematic review
ispartofLancet, 2010, Vol.376 (9753), p.1647-1657
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5Copyright Elsevier Limited Nov 13-Nov 19, 2010
62010 Elsevier Ltd. All rights reserved. 2010 Elsevier Ltd
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0Dondorp, Arjen M, MD
1Fanello, Caterina I, PhD
2Hendriksen, Ilse CE, MD
3Gomes, Ermelinda, MD
4Seni, Amir, MD
5Chhaganlal, Kajal D, MD
6Bojang, Kalifa, FRCP
7Olaosebikan, Rasaq, FWACP
8Anunobi, Nkechinyere, FMCpaed
9Maitland, Kathryn, Prof
10Kivaya, Esther, MSc
11Agbenyega, Tsiri, Prof
12Nguah, Samuel Blay, FWACPCH
13Evans, Jennifer, MRCPCH
14Gesase, Samwel, MD
15Kahabuka, Catherine, MD
16Mtove, George, MD
17Nadjm, Behzad, MD
18Deen, Jacqueline, MD
19Mwanga-Amumpaire, Juliet, MD
20Nansumba, Margaret, MD
21Karema, Corine, MD
22Umulisa, Noella, MD
23Uwimana, Aline, MD
24Mokuolu, Olugbenga A, FWACP
25Adedoyin, Olanrewaju T, FWACP
26Johnson, Wahab BR, Prof
27Tshefu, Antoinette K, Prof
28Onyamboko, Marie A, MB
29Sakulthaew, Tharisara, BNS
30Ngum, Wirichada Pan, PhD
31Silamut, Kamolrat, PhD
32Stepniewska, Kasia, PhD
33Woodrow, Charles J, MRCP
34Bethell, Delia, MRCPCH
35Wills, Bridget, FRCPCH
36Oneko, Martina, MD
37Peto, Tim E, Prof
38von Seidlein, Lorenz, PhD
39Day, Nicholas PJ, Prof
40White, Nicholas J, Prof
41for the AQUAMAT group
42AQUAMAT group
title
0Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial
1Lancet
addtitleLancet
descriptionSummary 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.
subject
0Africa South of the Sahara
1Antibiotics. Antiinfectious agents. Antiparasitic agents
2Antimalarials
3Antimalarials - adverse effects
4Antimalarials - therapeutic use
5Antiparasitic agents
6Artemisinins
7Artemisinins - adverse effects
8Artemisinins - therapeutic use
9Biological and medical sciences
10Biomedical research
11Child
12Child, Preschool
13Complications and side effects
14Dosage and administration
15Drug therapy
16Falciparum
17Fast track
18Fast track — Articles
19Female
20General aspects
21Hospitals
22Human protozoal diseases
23Humans
24Infant
25Infectious diseases
26Internal Medicine
27Kaplan
28Kaplan-Meier Estimate
29Malaria
30Malaria, Falciparum - complications
31Malaria, Falciparum - drug therapy
32Malaria, Falciparum - mortality
33Male
34Medical research
35Medical sciences
36Medicine
37Meier Estimate
38Mortality
39Parasitic diseases
40Pharmacology. Drug treatments
41Preschool
42Protozoal diseases
43Quinine
44Quinine - adverse effects
45Quinine - therapeutic use
46Survival Rate
47Systematic review
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7Olaosebikan, Rasaq, FWACP
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11Agbenyega, Tsiri, Prof
12Nguah, Samuel Blay, FWACPCH
13Evans, Jennifer, MRCPCH
14Gesase, Samwel, MD
15Kahabuka, Catherine, MD
16Mtove, George, MD
17Nadjm, Behzad, MD
18Deen, Jacqueline, MD
19Mwanga-Amumpaire, Juliet, MD
20Nansumba, Margaret, MD
21Karema, Corine, MD
22Umulisa, Noella, MD
23Uwimana, Aline, MD
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25Adedoyin, Olanrewaju T, FWACP
26Johnson, Wahab BR, Prof
27Tshefu, Antoinette K, Prof
28Onyamboko, Marie A, MB
29Sakulthaew, Tharisara, BNS
30Ngum, Wirichada Pan, PhD
31Silamut, Kamolrat, PhD
32Stepniewska, Kasia, PhD
33Woodrow, Charles J, MRCP
34Bethell, Delia, MRCPCH
35Wills, Bridget, FRCPCH
36Oneko, Martina, MD
37Peto, Tim E, Prof
38von Seidlein, Lorenz, PhD
39Day, Nicholas PJ, Prof
40White, Nicholas J, Prof
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titleArtesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial
authorDondorp, Arjen M, MD ; Fanello, Caterina I, PhD ; Hendriksen, Ilse CE, MD ; Gomes, Ermelinda, MD ; Seni, Amir, MD ; Chhaganlal, Kajal D, MD ; Bojang, Kalifa, FRCP ; Olaosebikan, Rasaq, FWACP ; Anunobi, Nkechinyere, FMCpaed ; Maitland, Kathryn, Prof ; Kivaya, Esther, MSc ; Agbenyega, Tsiri, Prof ; Nguah, Samuel Blay, FWACPCH ; Evans, Jennifer, MRCPCH ; Gesase, Samwel, MD ; Kahabuka, Catherine, MD ; Mtove, George, MD ; Nadjm, Behzad, MD ; Deen, Jacqueline, MD ; Mwanga-Amumpaire, Juliet, MD ; Nansumba, Margaret, MD ; Karema, Corine, MD ; Umulisa, Noella, MD ; Uwimana, Aline, MD ; Mokuolu, Olugbenga A, FWACP ; Adedoyin, Olanrewaju T, FWACP ; Johnson, Wahab BR, Prof ; Tshefu, Antoinette K, Prof ; Onyamboko, Marie A, MB ; Sakulthaew, Tharisara, BNS ; Ngum, Wirichada Pan, PhD ; Silamut, Kamolrat, PhD ; Stepniewska, Kasia, PhD ; Woodrow, Charles J, MRCP ; Bethell, Delia, MRCPCH ; Wills, Bridget, FRCPCH ; Oneko, Martina, MD ; Peto, Tim E, Prof ; von Seidlein, Lorenz, PhD ; Day, Nicholas PJ, Prof ; White, Nicholas J, Prof
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languageeng
creationdate2010
topic
0Africa South of the Sahara
1Antibiotics. Antiinfectious agents. Antiparasitic agents
2Antimalarials
3Antimalarials - adverse effects
4Antimalarials - therapeutic use
5Antiparasitic agents
6Artemisinins
7Artemisinins - adverse effects
8Artemisinins - therapeutic use
9Biological and medical sciences
10Biomedical research
11Child
12Child, Preschool
13Complications and side effects
14Dosage and administration
15Drug therapy
16Falciparum
17Fast track
18Fast track — Articles
19Female
20General aspects
21Hospitals
22Human protozoal diseases
23Humans
24Infant
25Infectious diseases
26Internal Medicine
27Kaplan
28Kaplan-Meier Estimate
29Malaria
30Malaria, Falciparum - complications
31Malaria, Falciparum - drug therapy
32Malaria, Falciparum - mortality
33Male
34Medical research
35Medical sciences
36Medicine
37Meier Estimate
38Mortality
39Parasitic diseases
40Pharmacology. Drug treatments
41Preschool
42Protozoal diseases
43Quinine
44Quinine - adverse effects
45Quinine - therapeutic use
46Survival Rate
47Systematic review
toplevel
0peer_reviewed
1online_resources
creatorcontrib
0Dondorp, Arjen M, MD
1Fanello, Caterina I, PhD
2Hendriksen, Ilse CE, MD
3Gomes, Ermelinda, MD
4Seni, Amir, MD
5Chhaganlal, Kajal D, MD
6Bojang, Kalifa, FRCP
7Olaosebikan, Rasaq, FWACP
8Anunobi, Nkechinyere, FMCpaed
9Maitland, Kathryn, Prof
10Kivaya, Esther, MSc
11Agbenyega, Tsiri, Prof
12Nguah, Samuel Blay, FWACPCH
13Evans, Jennifer, MRCPCH
14Gesase, Samwel, MD
15Kahabuka, Catherine, MD
16Mtove, George, MD
17Nadjm, Behzad, MD
18Deen, Jacqueline, MD
19Mwanga-Amumpaire, Juliet, MD
20Nansumba, Margaret, MD
21Karema, Corine, MD
22Umulisa, Noella, MD
23Uwimana, Aline, MD
24Mokuolu, Olugbenga A, FWACP
25Adedoyin, Olanrewaju T, FWACP
26Johnson, Wahab BR, Prof
27Tshefu, Antoinette K, Prof
28Onyamboko, Marie A, MB
29Sakulthaew, Tharisara, BNS
30Ngum, Wirichada Pan, PhD
31Silamut, Kamolrat, PhD
32Stepniewska, Kasia, PhD
33Woodrow, Charles J, MRCP
34Bethell, Delia, MRCPCH
35Wills, Bridget, FRCPCH
36Oneko, Martina, MD
37Peto, Tim E, Prof
38von Seidlein, Lorenz, PhD
39Day, Nicholas PJ, Prof
40White, Nicholas J, Prof
41for the AQUAMAT group
42AQUAMAT group
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0ScienceDirect Open Access Titles
1Elsevier:ScienceDirect:Open Access
2Pascal-Francis
3Medline
4MEDLINE
5MEDLINE (Ovid)
6MEDLINE
7MEDLINE
8PubMed
9CrossRef
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13Global News & ABI/Inform Professional
14ProQuest Central (Corporate)
15Bacteriology Abstracts (Microbiology B)
16Calcium & Calcified Tissue Abstracts
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18Neurosciences Abstracts
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20Virology and AIDS Abstracts
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29ProQuest Pharma Collection
30Public Health Database
31Lancet Titles
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33ProQuest Natural Science Collection
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35Hospital Premium Collection (Alumni Edition)
36ProQuest Central (Alumni) (purchase pre-March 2016)
37Research Library (Alumni Edition)
38ProQuest Central (Alumni Edition)
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40British Nursing Index
41ProQuest Central Essentials
42Biological Science Collection
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46Environmental Sciences and Pollution Management
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62Health & Medical Collection (Alumni Edition)
63Healthcare Administration Database
64Medical Database
65Psychology Database
66Research Library
67Science Database
68Algology Mycology and Protozoology Abstracts (Microbiology C)
69Biological Science Database
70Research Library (Corporate)
71Nursing & Allied Health Premium
72ProQuest One Academic Eastern Edition
73ProQuest One Academic
74ProQuest One Academic UKI Edition
75ProQuest Central Basic
76SIRS Editorial
77OpenAIRE (Open Access)
78OpenAIRE
79PubMed Central (Full Participant titles)
jtitleLancet
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
au
0Dondorp, Arjen M, MD
1Fanello, Caterina I, PhD
2Hendriksen, Ilse CE, MD
3Gomes, Ermelinda, MD
4Seni, Amir, MD
5Chhaganlal, Kajal D, MD
6Bojang, Kalifa, FRCP
7Olaosebikan, Rasaq, FWACP
8Anunobi, Nkechinyere, FMCpaed
9Maitland, Kathryn, Prof
10Kivaya, Esther, MSc
11Agbenyega, Tsiri, Prof
12Nguah, Samuel Blay, FWACPCH
13Evans, Jennifer, MRCPCH
14Gesase, Samwel, MD
15Kahabuka, Catherine, MD
16Mtove, George, MD
17Nadjm, Behzad, MD
18Deen, Jacqueline, MD
19Mwanga-Amumpaire, Juliet, MD
20Nansumba, Margaret, MD
21Karema, Corine, MD
22Umulisa, Noella, MD
23Uwimana, Aline, MD
24Mokuolu, Olugbenga A, FWACP
25Adedoyin, Olanrewaju T, FWACP
26Johnson, Wahab BR, Prof
27Tshefu, Antoinette K, Prof
28Onyamboko, Marie A, MB
29Sakulthaew, Tharisara, BNS
30Ngum, Wirichada Pan, PhD
31Silamut, Kamolrat, PhD
32Stepniewska, Kasia, PhD
33Woodrow, Charles J, MRCP
34Bethell, Delia, MRCPCH
35Wills, Bridget, FRCPCH
36Oneko, Martina, MD
37Peto, Tim E, Prof
38von Seidlein, Lorenz, PhD
39Day, Nicholas PJ, Prof
40White, Nicholas J, Prof
aucorp
0for the AQUAMAT group
1AQUAMAT group
formatjournal
genrearticle
ristypeJOUR
atitleArtesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial
jtitleLancet
addtitleLancet
date2010
risdate2010
volume376
issue9753
spage1647
epage1657
pages1647-1657
issn
00140-6736
11474-547X
eissn1474-547X
codenLANCAO
notesMembers listed at end of paper.
abstractSummary 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.
copKidlington
pubElsevier Ltd
pmid21062666
doi10.1016/S0140-6736(10)61924-1
oafree_for_read