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-
1
Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ, 1992. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 101 :1644–1655.
-
2
Annane D, Aegerter P, Jars-Guincestre MC, Guidet B, 2003. Current epidemiology of septic shock: the CUB-Rea Network. Am J Respir Crit Care Med 168 :165–172.
-
3
Ssali FN, Kamya MR, Wabwire-Mangen F, Kasasa S, Joloba M, Williams D, Mugerwa RD, Ellner JJ, Johnson JL, 1998. A prospective study of community-acquired bloodstream infections among febrile adults admitted to Mulago Hospital in Kampala, Uganda. J Acquir Immune Defic Syndr Hum Retrovirol 19 :484–489.
-
4
Reyburn H, Mbakilwa H, Mwangi R, Mwerinde O, Olomi R, Drakeley C, Whitty CJ, 2007. Rapid diagnostic tests compared with malaria microscopy for guiding outpatient treatment of febrile illness in Tanzania: randomised trial. BMJ 334 :403.
-
5
Hamer DH, Ndhlovu M, Zurovac D, Fox M, Yeboah-Antwi K, Chanda P, Sipilinyambe N, Simon JL, Snow RW, 2007. Improved diagnostic testing and malaria treatment practices in Zambia. JAMA 297 :2227–2231.
-
6
Hill PC, Onyeama CO, Ikumapayi UN, Secka O, Ameyaw S, Simmonds N, Donkor SA, Howie SR, Tapgun M, Corrah T, Adegbola RA, 2007. Bacteraemia in patients admitted to an urban hospital in West Africa. BMC Infect Dis 7 :2.
-
7
Evans JA, Adusei A, Timmann C, May J, Mack D, Agbenyega T, Horstmann RD, Frimpong E, 2004. High mortality of infant bacteraemia clinically indistinguishable from severe malaria. QJM 97 :591–597.
-
8
Bronzan RN, Taylor TE, Mwenechanya J, Tembo M, Kayira K, Bwanaisa L, Njobvu A, Kondowe W, Chalira C, Walsh AL, Phiri A, Wilson LK, Molyneux ME, Graham SM, 2007. Bacteremia in Malawian children with severe malaria: prevalence, etiology, HIV coinfection, and outcome. J Infect Dis 195 :895–904.
-
9
Berkley J, Mwarumba S, Bramham K, Lowe B, Marsh K, 1999. Bacteraemia complicating severe malaria in children. Trans R Soc Trop Med Hyg 93 :283–286.
-
10
WHO, 2006. Guidelines for the Treatment of Malaria/World Health Organization.
-
11
Zongo I, Dorsey G, Rouamba N, Dokomajilar C, Sere Y, Rosenthal PJ, Ouedraogo JB, 2007. Randomized comparison of amodiaquine plus sulfadoxine-pyrimethamine, artemether-lumefantrine, and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Burkina Faso. Clin Infect Dis 45 :1453–1461.
-
12
Rulisa S, Gatarayiha JP, Kabarisa T, Ndayisaba G, 2007. Comparison of different artemisinin-based combinations for the treatment of Plasmodium falciparum malaria in children in Kigali, Rwanda, an area of resistance to sulfadoxine-pyrimethamine: artesunate plus sulfadoxine/pyrimethamine versus artesunate plus sulfamethoxypyrazine/pyrimethamine. Am J Trop Med Hyg 77 :612–616.
-
13
Dorsey G, Staedke S, Clark TD, Njama-Meya D, Nzarubara B, Maiteki-Sebuguzi C, Dokomajilar C, Kamya MR, Rosenthal PJ, 2007. Combination therapy for uncomplicated falciparum malaria in Ugandan children: a randomized trial. JAMA 297 :2210–2219.
-
14
Pareek A, Nandy A, Kochar D, Patel KH, Mishra SK, Mathur PC, 2006. Efficacy and safety of beta-arteether and alpha/ beta-arteether for treatment of acute Plasmodium falciparum malaria. Am J Trop Med Hyg 75 :139–142.
-
15
Health UMo, 2005. National Policy on Malaria Treatment. Available at: http://www.health.go.ug/mcp/mt.html.
-
16
Wang J, Zhou H, Zheng J, Cheng J, Liu W, Ding G, Wang L, Luo P, Lu Y, Cao H, Yu S, Li B, Zhang L, 2006. The antima-larial artemisinin synergizes with antibiotics to protect against lethal live Escherichia coli challenge by decreasing proinflammatory cytokine release. Antimicrob Agents Chemother 50 :2420–2427.
-
17
Xu H, He Y, Yang X, Liang L, Zhan Z, Ye Y, Lian F, Sun L, 2007. Anti-malarial agent artesunate inhibits TNF-alpha-induced production of proinflammatory cytokines via inhibition of NF-kappaB and PI3 kinase/Akt signal pathway in human rheumatoid arthritis fibroblast-like synoviocytes. Rheumatology (Oxford) 46 :920–926.
-
18
Bozza FA, Salluh JI, Japiassu AM, Soares M, Assis EF, Gomes RN, Bozza MT, Castro-Faria-Neto HC, Bozza PT, 2007. Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis. Crit Care 11 :R49.
-
19
Clark IA, Budd AC, Alleva LM, Cowden WB, 2006. Human malarial disease: a consequence of inflammatory cytokine release. Malar J 5 :85.
-
20
Zeni F, Freeman B, Natanson C, 1997. Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. Crit Care Med 25 :1095–1100.
-
21
van Hensbroek MB, Palmer A, Onyiorah E, Schneider G, Jaffar S, Dolan G, Memming H, Frenkel J, Enwere G, Bennett S, Kwiatkowski D, Greenwood B, 1996. The effect of a monoclonal antibody to tumor necrosis factor on survival from childhood cerebral malaria. J Infect Dis 174 :1091–1097.
-
22
Aldieri E, Atragene D, Bergandi L, Riganti C, Costamagna C, Bosia A, Ghigo D, 2003. Artemisinin inhibits inducible nitric oxide synthase and nuclear factor NF-kB activation. FEBS Lett 552 :141–144.
-
23
Dondorp AM, Lee SJ, Faiz MA, Mishra S, Price R, Tjitra E, Than M, Htut Y, Mohanty S, Yunus EB, Rahman R, Nosten F, Anstey NM, Day NP, White NJ, 2008. The relationship between age and the manifestations of and mortality associated with severe malaria. Clin Infect Dis 47 :151–157.
-
24
Zurovac D, Midia B, Ochola SA, English M, Snow RW, 2006. Microscopy and outpatient malaria case management among older children and adults in Kenya. Trop Med Int Health 11 :432–440.
-
25
Amexo M, Tolhurst R, Barnish G, Bates I, 2004. Malaria misdiagnosis: effects on the poor and vulnerable. Lancet 364 :1896–1898.
-
26
Cheng AC, West TE, Limmathurotsakul D, Peacock SJ, 2008. Strategies to reduce mortality from bacterial sepsis in adults in developing countries. PLoS Med 5 :e175.
-
27
Petti CA, Polage CR, Quinn TC, Ronald AR, Sande MA, 2006. Laboratory medicine in Africa: a barrier to effective health care. Clin Infect Dis 42 :377–382.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 33 | 33 | 13 |
| Full Text Views | 343 | 142 | 0 |
| PDF Downloads | 116 | 37 | 0 |
Treatment of Severe Sepsis with Artemether-Lumefantrine Is Associated with Decreased Mortality in Ugandan Patients without Malaria
Christopher C. Moore
Christopher C. Moore
Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia; Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington; Department of Internal Medicine, Masaka Regional Referral Hospital, Masaka, Uganda; Faculty of Medicine, Infectious Diseases Institute, Makerere University, Kampala, Uganda; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Johns Hopkins University School of Medicine, Baltimore, Maryland
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Shevin T. Jacob
Shevin T. Jacob
Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia; Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington; Department of Internal Medicine, Masaka Regional Referral Hospital, Masaka, Uganda; Faculty of Medicine, Infectious Diseases Institute, Makerere University, Kampala, Uganda; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Johns Hopkins University School of Medicine, Baltimore, Maryland
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Relana Pinkerton
Relana Pinkerton
Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia; Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington; Department of Internal Medicine, Masaka Regional Referral Hospital, Masaka, Uganda; Faculty of Medicine, Infectious Diseases Institute, Makerere University, Kampala, Uganda; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Johns Hopkins University School of Medicine, Baltimore, Maryland
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Patrick Banura
Patrick Banura
Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia; Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington; Department of Internal Medicine, Masaka Regional Referral Hospital, Masaka, Uganda; Faculty of Medicine, Infectious Diseases Institute, Makerere University, Kampala, Uganda; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Johns Hopkins University School of Medicine, Baltimore, Maryland
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David B. Meya
David B. Meya
Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia; Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington; Department of Internal Medicine, Masaka Regional Referral Hospital, Masaka, Uganda; Faculty of Medicine, Infectious Diseases Institute, Makerere University, Kampala, Uganda; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Johns Hopkins University School of Medicine, Baltimore, Maryland
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Steven J. Reynolds
Steven J. Reynolds
Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia; Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington; Department of Internal Medicine, Masaka Regional Referral Hospital, Masaka, Uganda; Faculty of Medicine, Infectious Diseases Institute, Makerere University, Kampala, Uganda; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Johns Hopkins University School of Medicine, Baltimore, Maryland
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Nathan Kenya-Mugisha
Nathan Kenya-Mugisha
Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia; Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington; Department of Internal Medicine, Masaka Regional Referral Hospital, Masaka, Uganda; Faculty of Medicine, Infectious Diseases Institute, Makerere University, Kampala, Uganda; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Johns Hopkins University School of Medicine, Baltimore, Maryland
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Harriet Mayanja-Kizza
Harriet Mayanja-Kizza
Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia; Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington; Department of Internal Medicine, Masaka Regional Referral Hospital, Masaka, Uganda; Faculty of Medicine, Infectious Diseases Institute, Makerere University, Kampala, Uganda; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Johns Hopkins University School of Medicine, Baltimore, Maryland
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We enrolled 382 patients at two hospitals in Uganda in a prospective observational study of severe sepsis. Because artemisinins improve survival in murine sepsis models, we performed a post hoc analysis of the association between the use of artemether-lumefantrine (A-L) and mortality in patients with or without malaria. In patients with negative malaria smears (N = 328 of 379), Kaplan–Meier curves revealed decreased combined inpatient and 30-day mortality among patients receiving A-L versus those who did not (20.6%, SE = 10.6 versus 48.8%, SE = 3.2; Log rank χ2 = 3.93, P = 0.048). The decrease in mortality associated with A-L was maintained in the most clinically ill patients determined by Karnofsky Performance Scores ≤ 50 (16.7%, SE = 15.2 versus 58.3%, SE = 3.7; Log rank χ2 3.94, P = 0.041). Research into the properties of A-L is needed to improve treatment of sepsis without compromising malarial susceptibility.
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-
1
Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ, 1992. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 101 :1644–1655.
-
2
Annane D, Aegerter P, Jars-Guincestre MC, Guidet B, 2003. Current epidemiology of septic shock: the CUB-Rea Network. Am J Respir Crit Care Med 168 :165–172.
-
3
Ssali FN, Kamya MR, Wabwire-Mangen F, Kasasa S, Joloba M, Williams D, Mugerwa RD, Ellner JJ, Johnson JL, 1998. A prospective study of community-acquired bloodstream infections among febrile adults admitted to Mulago Hospital in Kampala, Uganda. J Acquir Immune Defic Syndr Hum Retrovirol 19 :484–489.
-
4
Reyburn H, Mbakilwa H, Mwangi R, Mwerinde O, Olomi R, Drakeley C, Whitty CJ, 2007. Rapid diagnostic tests compared with malaria microscopy for guiding outpatient treatment of febrile illness in Tanzania: randomised trial. BMJ 334 :403.
-
5
Hamer DH, Ndhlovu M, Zurovac D, Fox M, Yeboah-Antwi K, Chanda P, Sipilinyambe N, Simon JL, Snow RW, 2007. Improved diagnostic testing and malaria treatment practices in Zambia. JAMA 297 :2227–2231.
-
6
Hill PC, Onyeama CO, Ikumapayi UN, Secka O, Ameyaw S, Simmonds N, Donkor SA, Howie SR, Tapgun M, Corrah T, Adegbola RA, 2007. Bacteraemia in patients admitted to an urban hospital in West Africa. BMC Infect Dis 7 :2.
-
7
Evans JA, Adusei A, Timmann C, May J, Mack D, Agbenyega T, Horstmann RD, Frimpong E, 2004. High mortality of infant bacteraemia clinically indistinguishable from severe malaria. QJM 97 :591–597.
-
8
Bronzan RN, Taylor TE, Mwenechanya J, Tembo M, Kayira K, Bwanaisa L, Njobvu A, Kondowe W, Chalira C, Walsh AL, Phiri A, Wilson LK, Molyneux ME, Graham SM, 2007. Bacteremia in Malawian children with severe malaria: prevalence, etiology, HIV coinfection, and outcome. J Infect Dis 195 :895–904.
-
9
Berkley J, Mwarumba S, Bramham K, Lowe B, Marsh K, 1999. Bacteraemia complicating severe malaria in children. Trans R Soc Trop Med Hyg 93 :283–286.
-
10
WHO, 2006. Guidelines for the Treatment of Malaria/World Health Organization.
-
11
Zongo I, Dorsey G, Rouamba N, Dokomajilar C, Sere Y, Rosenthal PJ, Ouedraogo JB, 2007. Randomized comparison of amodiaquine plus sulfadoxine-pyrimethamine, artemether-lumefantrine, and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Burkina Faso. Clin Infect Dis 45 :1453–1461.
-
12
Rulisa S, Gatarayiha JP, Kabarisa T, Ndayisaba G, 2007. Comparison of different artemisinin-based combinations for the treatment of Plasmodium falciparum malaria in children in Kigali, Rwanda, an area of resistance to sulfadoxine-pyrimethamine: artesunate plus sulfadoxine/pyrimethamine versus artesunate plus sulfamethoxypyrazine/pyrimethamine. Am J Trop Med Hyg 77 :612–616.
-
13
Dorsey G, Staedke S, Clark TD, Njama-Meya D, Nzarubara B, Maiteki-Sebuguzi C, Dokomajilar C, Kamya MR, Rosenthal PJ, 2007. Combination therapy for uncomplicated falciparum malaria in Ugandan children: a randomized trial. JAMA 297 :2210–2219.
-
14
Pareek A, Nandy A, Kochar D, Patel KH, Mishra SK, Mathur PC, 2006. Efficacy and safety of beta-arteether and alpha/ beta-arteether for treatment of acute Plasmodium falciparum malaria. Am J Trop Med Hyg 75 :139–142.
-
15
Health UMo, 2005. National Policy on Malaria Treatment. Available at: http://www.health.go.ug/mcp/mt.html.
-
16
Wang J, Zhou H, Zheng J, Cheng J, Liu W, Ding G, Wang L, Luo P, Lu Y, Cao H, Yu S, Li B, Zhang L, 2006. The antima-larial artemisinin synergizes with antibiotics to protect against lethal live Escherichia coli challenge by decreasing proinflammatory cytokine release. Antimicrob Agents Chemother 50 :2420–2427.
-
17
Xu H, He Y, Yang X, Liang L, Zhan Z, Ye Y, Lian F, Sun L, 2007. Anti-malarial agent artesunate inhibits TNF-alpha-induced production of proinflammatory cytokines via inhibition of NF-kappaB and PI3 kinase/Akt signal pathway in human rheumatoid arthritis fibroblast-like synoviocytes. Rheumatology (Oxford) 46 :920–926.
-
18
Bozza FA, Salluh JI, Japiassu AM, Soares M, Assis EF, Gomes RN, Bozza MT, Castro-Faria-Neto HC, Bozza PT, 2007. Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis. Crit Care 11 :R49.
-
19
Clark IA, Budd AC, Alleva LM, Cowden WB, 2006. Human malarial disease: a consequence of inflammatory cytokine release. Malar J 5 :85.
-
20
Zeni F, Freeman B, Natanson C, 1997. Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. Crit Care Med 25 :1095–1100.
-
21
van Hensbroek MB, Palmer A, Onyiorah E, Schneider G, Jaffar S, Dolan G, Memming H, Frenkel J, Enwere G, Bennett S, Kwiatkowski D, Greenwood B, 1996. The effect of a monoclonal antibody to tumor necrosis factor on survival from childhood cerebral malaria. J Infect Dis 174 :1091–1097.
-
22
Aldieri E, Atragene D, Bergandi L, Riganti C, Costamagna C, Bosia A, Ghigo D, 2003. Artemisinin inhibits inducible nitric oxide synthase and nuclear factor NF-kB activation. FEBS Lett 552 :141–144.
-
23
Dondorp AM, Lee SJ, Faiz MA, Mishra S, Price R, Tjitra E, Than M, Htut Y, Mohanty S, Yunus EB, Rahman R, Nosten F, Anstey NM, Day NP, White NJ, 2008. The relationship between age and the manifestations of and mortality associated with severe malaria. Clin Infect Dis 47 :151–157.
-
24
Zurovac D, Midia B, Ochola SA, English M, Snow RW, 2006. Microscopy and outpatient malaria case management among older children and adults in Kenya. Trop Med Int Health 11 :432–440.
-
25
Amexo M, Tolhurst R, Barnish G, Bates I, 2004. Malaria misdiagnosis: effects on the poor and vulnerable. Lancet 364 :1896–1898.
-
26
Cheng AC, West TE, Limmathurotsakul D, Peacock SJ, 2008. Strategies to reduce mortality from bacterial sepsis in adults in developing countries. PLoS Med 5 :e175.
-
27
Petti CA, Polage CR, Quinn TC, Ronald AR, Sande MA, 2006. Laboratory medicine in Africa: a barrier to effective health care. Clin Infect Dis 42 :377–382.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 33 | 33 | 13 |
| Full Text Views | 343 | 142 | 0 |
| PDF Downloads | 116 | 37 | 0 |