Nila J. Dharan, MD; Larisa V. Gubareva, PhD; John J. Meyer, MPH; Margaret Okomo-Adhiambo, PhD; Reginald C. McClinton, MPH; Steven A. Marshall, MS; Kirsten St. George, MAppSc, PhD; Scott Epperson, MPH; Lynnette Brammer, MPH; Alexander I. Klimov, PhD; Joseph S. Bresee, MD; Alicia M. Fry, MD, MPH; for the Oseltamivir-Resistance Working Group
JAMA. 2009;301(10):1034-1041. Published online March 2, 2009 (doi:10.1001/jama.2009.294).
Context During the 2007-2008 influenza season, oseltamivir resistance among influenza A(H1N1) viruses increased significantly for the first time worldwide. Early surveillance data suggest that the prevalence of oseltamivir resistance among A(H1N1) viruses will most likely be higher during the 2008-2009 season.
Objectives To describe patients infected with oseltamivir-resistant influenza A(H1N1) virus and to determine whether there were any differences between these patients and patients infected with oseltamivir-susceptible A(H1N1) virus in demographic or epidemiological characteristics, clinical symptoms, severity of illness, or clinical outcomes.
Design, Setting, and Patients Influenza A(H1N1) viruses that were identified and submitted to the Centers for Disease Control and Prevention by US public health laboratories between September 30, 2007, and May 17, 2008, and between September 28, 2008, and February 19, 2009, were tested as part of ongoing surveillance. Oseltamivir resistance was determined by neuraminidase inhibition assay and pyrosequencing analysis. Information was collected using a standardized case form from patients with oseltamivir-resistant A(H1N1) infections and a comparison group of patients with oseltamivir-susceptible A(H1N1) infections during 2007-2008.
Main Outcome Measures Demographic and epidemiological information as well as clinical information, including symptoms, severity of illness, and clinical outcomes.
Results During the 2007-2008 season, influenza A(H1N1) accounted for an estimated 19% of circulating influenza viruses in the United States. Among 1155 influenza A(H1N1) viruses tested from 45 states, 142 (12.3%) from 24 states were resistant to oseltamivir. Data were available for 99 oseltamivir-resistant cases and 182 oseltamivir-susceptible cases from this period. Among resistant cases, median age was 19 years (range, 1 month to 62 years), 5 patients (5%) were hospitalized, and 4 patients (4%) died. None reported oseltamivir exposure before influenza diagnostic sample collection. No significant differences were found between cases of oseltamivir-resistant and oseltamivir-susceptible influenza in demographic characteristics, underlying medical illness, or clinical symptoms. Preliminary data from the 2008-2009 influenza season identified resistance to oseltamivir among 264 of 268 influenza A(H1N1) viruses (98.5%) tested.
Conclusions Oseltamivir-resistant A(H1N1) viruses circulated widely in the United States during the 2007-2008 influenza season, appeared to be unrelated to oseltamivir use, and appeared to cause illness similar to oseltamivir-susceptible A(H1N1) viruses. Circulation of oseltamivir-resistant A(H1N1) viruses will continue, with a higher prevalence of resistance, during the 2008-2009 season.
In January 2006, the US Centers for Disease Control and Prevention (CDC) recommended against the use of adamantanes due to a significant increase in resistance among circulating influenza A(H3N2) viruses.1 As a result, neuraminidase inhibitors (NAIs) became the only class of antiviral agents recommended for the treatment and prophylaxis of influenza virus infections in the United States.1–2 Since their introduction in 1999, the proportion of influenza viruses resistant to NAIs among circulating influenza viruses has been low, generally less than 1% of isolates tested worldwide.3–5
1. Centers for Disease Control and Prevention (CDC). High levels of adamantane resistance among influenza A (H3N2) viruses and interim guidelines for use of antiviral agents—United States, 2005-06 influenza season. MMWR Morb Mortal Wkly Rep. 2006;55(2):44-46. PUBMED
- Bright RA, Shay DK, Shu B, Cox NJ, Klimov AI. Adamantane resistance among influenza A viruses isolated early during the 2005-2006 influenza season in the United States. JAMA. 2006;295(8):891-894. FREE FULL
- Monto AS, McKimm-Breschkin JL, Macken C; et al. Detection of influenza viruses resistant to neuraminidase inhibitors in global surveillance during the first 3 years of their use. Antimicrob Agents Chemother. 2006;50(7):2395-2402. FREE FULL TEXT
- Sheu TG, Deyde VM, Okomo-Adhiambo M; et al. Surveillance for neuraminidase inhibitor resistance among human influenza A and B viruses circulating worldwide from 2004 to 2008. Antimicrob Agents Chemother. 2008;52(9):3284-3292. FREE FULL TEXT
- Mungall BA, Xu X, Klimov A. Surveillance of influenza isolates for susceptibility to neuraminidase inhibitors during the 2000-2002 influenza seasons. Virus Res. 2004;103(1-2):195-197. FULL TEXT | ISI | PUBMED
- World Health Organization. Influenza A(H1N1) virus resistance to oseltamivir; last quarter 2007 to first quarter 2008. http://www.who.int/csr/disease/influenza/oseltamivir_summary/en/index.html. Accessed January 2, 2009.
- Centers for Disease Control and Prevention (CDC). Influenza activity—United States and worldwide, 2007-08 season. MMWR Morb Mortal Wkly Rep. 2008;57(25):692-697. PUBMED
- Centers for Disease Control and Prevention (CDC). Update: influenza activity—United States, September 28-November 29, 2008. MMWR Morb Mortal Wkly Rep. 2008;57(49):1329-1332. PUBMED
- Ward P, Small I, Smith J, Suter P, Dutkowski R. Oseltamivir (Tamiflu) and its potential for use in the event of an influenza pandemic. J Antimicrob Chemother. 2005;55(suppl 1):i5-i21. FREE FULL TEXT
- Weinstock DM, Gubareva LV, Zuccotti G. Prolonged shedding of multidrug-resistant influenza A virus in an immunocompromised patient. N Engl J Med. 2003;348(9):867-868. FREE FULL TEXT
- Gubareva LV, Kaiser L, Matrosovich MN, Soo-Hoo Y, Hayden FG. Selection of influenza virus mutants in experimentally infected volunteers treated with oseltamivir. J Infect Dis. 2001;183(4):523-531. FULL TEXT | ISI | PUBMED
- Whitley RJ, Hayden FG, Reisinger KS; et al. Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J. 2001;20(2):127-133. ISI | PUBMED
- Kiso M, Mitamura K, Sakai-Tagawa Y; et al. Resistant influenza A viruses in children treated with oseltamivir: descriptive study. Lancet. 2004;364(9436):759-765. FULL TEXT | ISI | PUBMED
- Moscona A. Neuraminidase inhibitors for influenza. N Engl J Med. 2005;353(13):1363-1373. FREE FULL TEXT
- Aoki FY, Boivin G, Roberts N. Influenza virus susceptibility and resistance to oseltamivir. Antivir Ther. 2007;12(4 pt B)(4 pt B):603-616. ISI | PUBMED
- Ives JA, Carr JA, Mendel DB; et al. The H274Y mutation in the influenza A/H1N1 neuraminidase active site following oseltamivir phosphate treatment leave virus severely compromised both in vitro and in vivo. Antiviral Res. 2002;55(2):307-317. FULL TEXT | ISI | PUBMED
- Roberts NA. Treatment of influenza with neuraminidase inhibitors: virological implications. Philos Trans R Soc Lond B Biol Sci. 2001;356(1416):1895-1897. FREE FULL TEXT
- Herlocher ML, Truscon R, Elias S; et al. Influenza viruses resistant to the antiviral drug oseltamivir: transmission studies in ferrets. J Infect Dis. 2004;190(9):1627-1630. FULL TEXT | ISI | PUBMED
- Deyde VM, Okomo-Adhiambo M, Sheu TG; et al. Pyrosequencing as a tool to detect molecular markers of resistance to neuraminidase inhibitors in seasonal influenza A viruses. Antiviral Res. 2009;81(1):16-24. FULL TEXT | ISI | PUBMED
- Bright RA, Medina MJ, Xu X; et al. Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern. Lancet. 2005;366(9492):1175-1181. FULL TEXT | ISI | PUBMED
- Laplante J, Marshall SA, Van T; et al. Surveillance of antiviral resistant influenza from 2006-2008 by a network of U.S. state public health laboratories. Presented at: 24th Annual Clinical Virology Symposium; April 27-30, 2008; Daytona Beach, FL.
- Loonsk JW. BioSense: a national initiative for early detection and quantification of public health emergencies. MMWR Morb Mortal Wkly Rep. 2004;53(suppl):53-55. PUBMED
- RelayHealth. http://www.relayhealth.com/ Accessed January 2, 2009.
- Centers for Disease Control and Prevention (CDC). Update: influenza activity—United States, September 30-December 1, 2007. MMWR Morb Mortal Wkly Rep. 2007;56(49):1287-1291. PUBMED
- Centers for Disease Control and Prevention (CDC). Update: influenza activity—United States, September 30, 2007-February 9, 2008. MMWR Morb Mortal Wkly Rep. 2008;57(7):179-183. PUBMED
- Fluview. A weekly influenza surveillance report prepared by the Influenza Division. http://www.cdc.gov/flu/weekly. Accessed February 3, 2009.
- Centers for Disease Control and Prevention. Issues Interim Recommendations for the Use of Influenza Antiviral Medications in the Setting of Oseltamivir Resistance among Circulating Influenza A (H1N1) Viruses, 2008-09 Influenza Season. http://www2a.cdc.gov/HAN/ArchiveSys/ViewMsgV.asp?AlertNum=00279. Accessed January 2, 2009.
- Hauge SH, Dudman S, Borgen K, Lackenby A, Hungnes O. Oseltamivir-resistant influenza viruses A (H1N1), Norway, 2007-08. Emerg Infect Dis. 2009;15(2):155-162. FULL TEXT | PUBMED
- World Health Organization. Influenza A (H1N1) virus resistance to oseltamivir; 14 October 2008. http://www.who.int/csr/disease/influenza/H1N1200801013.pdf. Accessed January 2, 2009.
- World Health Organization. Influenza A (H1N1) virus resistance to oseltamivir; 20 August, 2008. http://www.who.int/csr/disease/influenza/H1N1webupdate20082008_kf.pdf. Accessed January 2, 2009.
- Lackenby A, Thompson CI, Democratis J. The potential impact of neuraminidase inhibitor resistant influenza. Curr Opin Infect Dis. 2008;21(6):626-638. FULL TEXT | ISI | PUBMED
- van der Vries E, van den Berg B, Schutten M. Fatal oseltamivir-resistant influenza virus infection. N Engl J Med. 2008;359(10):1074-1076. FREE FULL TEXT
CLINIC FOR CHILDREN
JL Taman Bendungan Asahan 5 Jakarta Indonesia 102010
phone : 62(021) 70081995 – 5703646
Clinical and Editor in Chief :
DR WIDODO JUDARWANTO
email : email@example.com
Copyright © 2009, Clinic For Children Information Education Network. All rights reserved.