Volume 17, Number 4—April 2011
CME ACTIVITY - Research
H275Y Mutant Pandemic (H1N1) 2009 Virus in Immunocompromised Patients
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).
References
- Lackenby A, Thompson CI, Democratis J. The potential impact of neuraminidase inhibitor resistant influenza. Curr Opin Infect Dis. 2008;21:626–38. DOIPubMedGoogle Scholar
- 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
- 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
- Gulland A. First cases of spread of oseltamivir resistant swine flu between patients are reported in Wales. BMJ. 2009;339:b4975. DOIPubMedGoogle Scholar
- 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
- 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
- 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
- Moscona A. Global transmission of oseltamivir-resistant influenza. N Engl J Med. 2009;360:953–6. DOIPubMedGoogle Scholar
- 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
- 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
- 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
- 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
- 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
- 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.
- 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
- 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
- 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
- Bloom JD, Gong LI, Baltimore D. Permissive secondary mutations enable the evolution of influenza oseltamivir resistance. Science. 2010;328:1272–5. DOIPubMedGoogle Scholar
- 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
- 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
- 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
- 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
- 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
- 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
- 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
Page created: September 01, 2011
Page updated: September 01, 2011
Page reviewed: September 01, 2011
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.