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Volume 17, Number 4—April 2011
CME ACTIVITY - Research

H275Y Mutant Pandemic (H1N1) 2009 Virus in Immunocompromised Patients

Christian Renaud, Alexandre A. Boudreault, Jane Kuypers, Kathryn H. Lofy, Lawrence Corey, Michael J. Boeckh, and Janet A. EnglundComments to Author 
Author affiliations: Author affiliations: Fred Hutchinson Cancer Research Center, Seattle, Washington, USA (C. Renaud, A.A. Boudreault, L. Corey, M.J. Boeckh, J.A. Englund); Seattle Children’s Hospital, Seattle (C. Renaud, J.A. Englund); University of Washington, Seattle (J. Kuypers, L. Corey, M.J. Boeckh, J.A. Englund); Washington State Department of Health, Shoreline, Washington, USA (K.H. Lofy)

Main Article

Table 1

Demographic characteristics and underlying conditions in 8 patients with H275Y mutation of pandemic (H1N1) 2009 virus, Seattle Cancer Care Alliance, Seattle, Washington, USA, May 1, 2009–April 30, 2010*

Patient no. Age, y/sex BMI Underlying disease State of disease HCT Recent immunosuppressive therapy Concurrent illness Lymphocytes, × 103 cells/L
1†
 51/M
 20.5
 AML
 Remission
 2 y post–allo-HCT
 MMF, tacrolimus
 GVHD, renal failure
 110
2†
 47/F
 22.9
 AML
 Relapse
 3 y post–allo-HCT
 Chemotherapy 1 mo before influenza dx and 1 d after-dx
 None
 540
3
 50/M
 23.3
 CML
 Remission
 9 mo post–allo-HCT
 TBI, cyclophosphamide,
tacrolimus
 GVHD
 1,470
4
 7/F
 18.9
 ALL
 Relapse
 NA
 Chemotherapy 2 d after influenza diagnosis; prednisone 1.5 mg/kg/d
 None
 1,440
5
 34/F
 38.8
 Hogkin lymphoma
 Refractory
 2 d pre–allo-HCT
 TBI, fludarabine, cyclophosphamide
 Renal failure
 0
6†
 17/M
 19.5
 ALL (T cell)
 Remission
 3 wk post–allo-HCT
 TBI, fludarabine, cyclophosphamide,
MMF, CSA, prednisone 0.5 mg/kg/d
 CMV, GVHD
 154
7
 17/M
 22.4
 Osteosarcoma
 Relapse
 NA
 Chemotherapy 1 d before influenza diagnosis
 Lung metastasis, thoracotomy, restrictive syndrome
 366
8 8/F 14.5 Aplastic anemia Treatment NA ATG, CSA maintenance None 1,145

*BMI, body mass index; HCT, hemopoietic cell transplant; AML, acute myeloblastic leukemia; allo, allogenic; MMF, mycophenolate mofetil; GVHD, graft-versus-host disease; NA, not applicable; CML, chronic myeloblastic leukemia; TBI, total body irradiation; ALL, acute lymphoblastic leukemia; CSA, cyclosporine; CMV, cytomegalovirus; ATG, antithymocyte globuline.
†Patients previously reported in references (5,13).

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References
  1. Lackenby  A, Thompson  CI, Democratis  J. The potential impact of neuraminidase inhibitor resistant influenza. Curr Opin Infect Dis. 2008;21:626–38. DOIPubMedGoogle Scholar
  2. World Health Organization. Weekly update on oseltamivir resistance to pandemic influenza A (H1N1) 2009 viruses [cited 2010 Jul 14]. http://www.who.int/csr/disease/swineflu/laboratory16_07_2010/en/index.html
  3. Memoli  MJ, Hrabal  RJ, Hassantoufighi  A, Eichelberger  MC, Taubenberger  JK. Rapid selection of oseltamivir- and peramivir-resistant pandemic H1N1 virus during therapy in 2 immunocompromised hosts. Clin Infect Dis. 2010;50:1252–5. DOIPubMedGoogle Scholar
  4. Gulland  A. First cases of spread of oseltamivir resistant swine flu between patients are reported in Wales. BMJ. 2009;339:b4975. DOIPubMedGoogle Scholar
  5. Centers for Disease Control and Prevention. Oseltamivir-resistant novel influenza A (H1N1) virus infection in two immunosuppressed patients—Seattle, Washington, 2009. MMWR Morb Mortal Wkly Rep. 2009;58:893–6.PubMedGoogle Scholar
  6. Balicer  RD, Huerta  M, Davidovitch  N, Grotto  I. Cost-benefit of stockpiling drugs for influenza pandemic. Emerg Infect Dis. 2005;11:1280–2.PubMedGoogle Scholar
  7. Lee  VJ, Yap  J, Cook  AR, Chen  MI, Tay  JK, Tan  BH, Oseltamivir ring prophylaxis for containment of 2009 H1N1 influenza outbreaks. N Engl J Med. 2010;362:2166–74. DOIPubMedGoogle Scholar
  8. Moscona  A. Global transmission of oseltamivir-resistant influenza. N Engl J Med. 2009;360:953–6. DOIPubMedGoogle Scholar
  9. Renaud  C, Kuypers  J, Corey  L. Diagnostic accuracy of an allele-specific reverse transcriptase–PCR assay targeting the H275Y oseltamivir resistant mutation in 2009 pandemic influenza A/H1N1 virus. J Clin Virol. 2010;49:21–5. DOIPubMedGoogle Scholar
  10. Kuypers  J, Wright  N, Ferrenberg  J, Huang  ML, Cent  A, Corey  L, Comparison of real-time PCR assays with fluorescent-antibody assays for diagnosis of respiratory virus infections in children. J Clin Microbiol. 2006;44:2382–8. DOIPubMedGoogle Scholar
  11. Liu  CM, Driebe  EM, Schupp  J, Kelley  E, Nguyen  JT, McSharry  JJ, Rapid quantification of single-nucleotide mutations in mixed influenza A viral populations using allele-specific mixture analysis. J Virol Methods. 2010;163:109–15. DOIPubMedGoogle Scholar
  12. Kuypers  J, Wright  N, Morrow  R. Evaluation of quantitative and type-specific real-time RT-PCR assays for detection of respiratory syncytial virus in respiratory specimens from children. J Clin Virol. 2004;31:123–9. DOIPubMedGoogle Scholar
  13. Renaud  C, Pergam  SA, Polyak  C, Jain  R, Kuypers  J, Englund  JA, Early emergence of an H275Y mutation in a hematopoietic cell transplant recipient treated with intravenous peramivir. Transpl Infect Dis. 2010;12:513–7. DOIPubMedGoogle Scholar
  14. Harvala  H, Gunson  R, Simmonds  P, Hardie  A, Bennett  S, Scott  F, The emergence of oseltamivir-resistant pandemic influenza A(H1N1) 2009 virus amongst hospitalised immunocompromised patients in Scotland, November–December, 2009. Euro Surveill. 2010;15: pii: 19536.
  15. Tramontana  AR, George  B, Hurt  AC, Doyle  JS, Langan  K, Reid  AB, Oseltamivir resistance in adult oncology and hematology patients infected with pandemic (H1N1) 2009 virus, Australia. Emerg Infect Dis. 2010;16:1068–75. DOIPubMedGoogle Scholar
  16. Campanini  G, Piralla  A, Rovida  F, Puzelli  S, Facchini  M, Locatelli  F, First case in Italy of acquired resistance to oseltamivir in an immunocompromised patient with influenza A/H1N1v infection. J Clin Virol. 2010;48:220–2. DOIPubMedGoogle Scholar
  17. Baz  M, Abed  Y, Simon  P, Hamelin  ME, Boivin  G. Effect of the neuraminidase mutation H274Y conferring resistance to oseltamivir on the replicative capacity and virulence of old and recent human influenza A(H1N1) viruses. J Infect Dis. 2010;201:740–5. DOIPubMedGoogle Scholar
  18. Bloom  JD, Gong  LI, Baltimore  D. Permissive secondary mutations enable the evolution of influenza oseltamivir resistance. Science. 2010;328:1272–5. DOIPubMedGoogle Scholar
  19. Wagner  R, Matrosovich  M, Klenk  HD. Functional balance between haemagglutinin and neuraminidase in influenza virus infections. Rev Med Virol. 2002;12:159–66. DOIPubMedGoogle Scholar
  20. Chen  H, Wen  X, To  KK, Wang  P, Tse  H, Chan  JF, Quasispecies of the D225G substitution in the hemagglutinin of pandemic influenza A(H1N1) 2009 virus from patients with severe disease in Hong Kong, China. J Infect Dis. 2010;201:1517–21. DOIPubMedGoogle Scholar
  21. Baz  M, Abed  Y, Boivin  G. Characterization of drug-resistant recombinant influenza A/H1N1 viruses selected in vitro with peramivir and zanamivir. Antiviral Res. 2007;74:159–62. DOIPubMedGoogle Scholar
  22. Nguyen  JT, Hoopes  JD, Smee  DF, Prichard  MN, Driebe  EM, Engelthaler  DM, Triple combination of oseltamivir, amantadine, and ribavirin displays synergistic activity against multiple influenza virus strains in vitro. Antimicrob Agents Chemother. 2009;53:4115–26. DOIPubMedGoogle Scholar
  23. Nguyen  JT, Hoopes  JD, Le  MH, Smee  DF, Patick  AK, Faix  DJ, Triple combination of amantadine, ribavirin, and oseltamivir is highly active and synergistic against drug resistant influenza virus strains in vitro. PLoS ONE. 2010;5:e9332. DOIPubMedGoogle Scholar
  24. Nguyen  HT, Fry  AM, Loveless  PA, Klimov  AI, Gubareva  LV. Recovery of a multidrug-resistant strain of pandemic influenza A 2009 (H1N1) virus carrying a dual H275Y/I223R mutation from a child after prolonged treatment with oseltamivir. Clin Infect Dis. 2010;51:983–4. DOIPubMedGoogle Scholar
  25. van der Vries  E, Stelma  FF, Boucher  CA. Emergence of a multidrug-resistant pandemic influenza A (H1N1) virus. N Engl J Med. 2010;363:1381–2. DOIPubMedGoogle Scholar

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Page updated: September 01, 2011
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