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Volume 18, Number 7—July 2012
CME ACTIVITY - Dispatch

Low Pathogenic Avian Influenza A (H7N2) Virus Infection in Immunocompromised Adult, New York, USA, 2003

Author affiliations: Westchester County Department of Health, New Rochelle, New York, USA (B. Ostrowsky, A. Huang, W. Terry); Westchester County Department of Laboratories and Research, Valhalla, New York, USA (D. Anton, B. Brunagel, L. Traynor, S. Abid); New York State Department of Health, Albany, New York, USA (G. Johnson, M. Kacica); and Centers for Disease Control and Prevention, Atlanta, Georgia, USA (J. Katz, L. Edwards, S. Lindstrom, A. Klimov, T.M. Uyeki)

Cite This Article

Introduction

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MEDSCAPE CME

Medscape, LLC is pleased to provide online continuing medical education (CME) for this journal article, allowing clinicians the opportunity to earn CME credit.

This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Medscape, LLC and Emerging Infectious Diseases. Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians.

Medscape, LLC designates this Journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit(s)TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 70% minimum passing score and complete the evaluation at www.medscape.org/journal/eid; (4) view/print certificate.

Release date: June 14, 2012; Expiration date: June 14, 2013

Learning Objectives

Upon completion of this activity, participants will be able to:

• Distinguish the usual severity of infections with LPAI

• Analyze the differential diagnosis for patients presenting with LPAI infection

• Evaluate the epidemiology of LPAI

• Assess other clinical characteristics of LPAI infection

CME Editor

P. Lynne Stockton, VMD, MS, ELS(D), Technical Writer/Editor, Emerging Infectious Diseases. Disclosure: P. Lynne Stockton, VMD, MS, ELS(D), has disclosed no relevant financial relationships.

CME AUTHOR

Charles P. Vega, MD, Health Sciences Clinical Professor; Residency Director, Department of Family Medicine, University of California, Irvine. Disclosure: Charles P. Vega, MD, has disclosed no relevant financial relationships.

AUTHORS

Disclosures: Belinda Ostrowsky, MD, MPH; William Terry, MD, MPH; Diane Anton, MS, M(ASCP); Barbara Brunagel, MS; Lorraine Traynor, BS; Syed Abid, PhD; Geraldine Johnson, MS; Marilyn Kacica, MD, MPH; Stephen Lindstrom, PhD; Alexander Klimov, PhD; and Timothy M. Uyeki, MD, MPH, MPP, have disclosed no relevant financial relationships. Ada Huang, MD, has disclosed the following relevant financial relationships: owns stock, stock options, or bonds from Merck, Pfizer. Jacqueline Katz, PhD, has disclosed the following relevant financial relationships: received grants for clinical research from GlaxoSmithKline for research not related to the current study; received grants for preclinical research from Colby Pharmaceuticals (formerly Juvaris Bio Therapeutics) for research not related to the current study. Lindsay Edwards has disclosed the following relevant financial relationships: spouse owns GlaxoSmithKline stock.

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Abstract

In 2003, infection with low pathogenic avian influenza A (H7N2) virus was identified in an immunocompromised man with fever and community-acquired pneumonia in New York, USA. The patient recovered. Although the source of the virus was not identified, this case indicates the usefulness of virus culture for detecting novel influenza A viruses.

Limited numbers of human infections with low pathogenic avian influenza A, subtype H7, viruses have been reported and attributed to recent exposure to infected poultry (16). Such infections generally resulted in clinically mild illness. We report a case of low pathogenic avian influenza (LPAI) A (H7N2) virus infection in an immunocompromised adult.

The Study

On November 3, 2003, a 48-year-old man from the Caribbean sought care at an emergency department in Westchester County, New York, USA, after an episode of near syncopy; a 2–4 week history of feverishness, cough, fatigue, and myalgia; and a 10-pound weight loss over 2 months. He had lived in the United States since 1987 and had no known medical conditions. A month earlier, he had been evaluated at a clinic, and an oral antimicrobial drug was prescribed for possible pneumonia. Eight days before the emergency department admission reported here, he had sought emergency care for unilateral conjunctivitis, eye pain, and blurred vision; the diagnosis was corneal abrasion.

Physical examination on November 3, 2003, found that the patient was afebrile, weak, and mildly tachypneic (respiratory rate 18–26 breaths/minute, room air oxygenation saturation 98%) with bibasilar inspiratory rales. Pertinent laboratory findings included mild anemia and thrombocytopenia (hemoglobin 11.9 g/dL, platelets 107 × 109/L, leukocytes 8.0 × 109 cells/L [52% lymphocytes]), mildly elevated hepatic transaminases (aspartate aminotransferase 116 U/L, alanine aminotransferase 87 U/L), and elevated creatine kinase (1,844 U/L). A chest radiograph showed a right hilar density and left lower lobe infiltrates; computed tomographic scan of the chest and abdomen showed bilateral micronodular opacities with right perihilar infiltrates and lymphadenopathy. The patient was admitted for community-acquired pneumonia and received intravenous gatifloxicin.

A tuberculin skin test was reactive (20-mm induration). HIV ELISA/Western blot test results were positive (HIV test result from 3 years earlier was reportedly negative), and CD4 count was 300 cells/μL. Treatment was switched to rifampin, isoniazid, pyrazinamide, ethambutol, and pyridoxine. Bronchoalveolar lavage (BAL) performed on November 7 yielded influenza A virus by tissue cell culture at the Westchester County Department of Laboratories and Research and was negative for Pneumocystis spp., Legionella spp., and other bacterial or viral pathogens. A second BAL and biopsy performed later during hospitalization to evaluate adenopathy indicated inflammation without definitive pathology. The lower respiratory tract disease improved after 13 days, and the patient was empirically prescribed tuberculosis treatment (directly observed therapy) and discharged while mycobacterial culture results were pending. After 8 weeks, mycobacterial culture of the BAL specimen was negative for Mycobacterium tuberculosis but yielded M. avium complex.

The patient lived in an apartment with his wife and 4 children, none of whom were sick during his illness. He denied recent travel and had not traveled outside the United States for 4 years. He worked in a cafeteria as a dishwasher and handled food and garbage until 1 month before hospitalization. He denied any known risk factors for HIV infection.

The influenza A virus isolate was difficult to grow in culture, reacted minimally with antiserum to hemagglutinin H1, and was sent to the Centers for Disease Control and Prevention (CDC) for further characterization. On March 19, 2004, CDC reported that the influenza isolate, designated A/New York/107/2003, was an LPAI A (H7N2), not subtype H1N1, virus.

An epidemiologic investigation was initiated by the Westchester County Department of Health. During 3 interviews (with a Creole interpreter), the patient denied any exposure to live or dead poultry, wild birds, or bird feces. No live poultry markets or poultry were found on the surrounding property or in the neighborhood.

Serum samples obtained during the patient’s hospitalization on November 5, 2003, and on April 4, 2004, were tested at CDC by microneutralization assay with the LPAI A (H7N2) virus from the patient. The acute-phase serum sample was negative (titer 10), but the convalescent-phase serum sample was positive (influenza [H7N2] virus neutralizing antibody titer 80), indicating seroconversion and evidence of infection with LPAI A (H7N2) virus. A confirmatory Western blot assay detected H7 hemagglutinin-specific antibody in the convalescent-phase serum sample. Testing of paired serum samples by ELISA demonstrated a 16-fold rise in H7 hemagglutinin-specific IgG. Serum samples collected from the patient’s wife and 3 of the children on April 4, 2004, were seronegative for influenza A (H7N2) neutralizing antibodies.

Conclusions

In this immunocompromised man with pneumonia, the contribution of influenza A (H7N2) virus infection to his lower respiratory tract disease is unclear. The diagnosis of influenza A (H7N2) virus infection was not made until long after the patient had been discharged, and no influenza antiviral treatment was administered. The patient’s history and clinical findings were consistent with HIV and community-acquired pneumonia with possible clinical response to the antimicrobial drug therapy or improvement of self-limiting viral pneumonia. In patients with HIV infection, M. avium complex is often detected as an indolent pathogen, especially associated with disseminated disease in patients with advanced AIDS; clinical resolution usually requires prolonged multidrug treatment (7). Isolation of influenza A (H7N2) virus from a BAL specimen and resolution of lower respiratory tract disease during hospitalization suggest that this infection might have contributed to the pulmonary disease. The clinical spectrum of human infection with LPAI viruses, including subtype H7, is generally mild, ranging from conjunctivitis to influenza-like illness (16), although hospitalization of patients with influenza A (H7N2) virus infection has been reported (6).

Conjunctival infection with influenza A subtype H7 viruses in persons with conjunctivitis has been confirmed by reverse transcription PCR or virus isolation (13,5). The patient initially reported ophthalmologic symptoms. Because conjunctival specimens were not available for virus testing, the role of influenza A (H7N2) virus in the conjunctivitis is unknown. However, intraocular inoculation of mice with the influenza A (H7N2) virus from the patient (A/New York/107/2003) did not result in infection, and the virus replicated at relatively low levels in murine corneal epithelial cells ex vivo (8,9). Intranasal inoculation with the LPAI A (H7N2) virus caused respiratory symptoms, elevated mean lung titers, and cytokine increases in mice; among ferrets, the virus replicated efficiently in the upper respiratory tract and was transmissible through direct contact (8,10).

The source of the patient’s infection with influenza A (H7N2) virus was not determined, although exposure to poultry was suspected. A limitation is that the investigations were conducted 5 months after the patient was hospitalized, after the influenza A isolate was identified as an LPAI A (H7N2) virus. LPAI A (H7N2) viruses have been documented among birds in live poultry markets in the northeastern United States, including New York (1113). Such viruses have receptor-binding properties consistent with receptors found in the human upper respiratory tract (10).

This case of LPAI A (H7N2) virus infection was detected through influenza virus surveillance of specimens submitted from outpatients and hospitalized patients to the Westchester County Department of Laboratories and Research and illustrates the value of virus culture for detection of human infections with novel influenza A viruses, which are nationally notifiable. For the patient reported here, neither seasonal influenza nor zoonotic influenza was suspected. Whether HIV infection might have made the patient more susceptible to lower respiratory tract infection with LPAI A (H7N2) virus is unknown, but a case of pulmonary infection with LPAI A (H9N2) virus in an immunosuppressed adult has been reported (14). A serologically confirmed case of LPAI A (H7N2) virus infection in the United States was associated with upper respiratory tract illness (4). Although information about the frequency of human infection with LPAI A H7 viruses is limited, 1 study reported antibody detection in 3.8% of exposed poultry workers after an outbreak of LPAI A (H7N3) virus infection among poultry in Italy (15). More information is needed to clarify the risk for LPAI A H7 virus infections among immunocompetent and immunocompromised persons.

Dr Ostrowsky was director of communicable and sexually transmitted diseases at the Westchester County Department of Health when the case reported here was investigated. She is currently director of the antimicrobial stewardship program at Montefiore Medical Center of Albert Einstein College of Medicine. Her research interests include antimicrobial drug resistance, health care–associated infections, and public health.

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Acknowledgment

We thank the many colleagues who helped with the epidemiologic and laboratory investigations, including Ralph Bernard , who assisted with interviews and translation; the public health nursing staff who arranged for the serologic testing and directly observed therapy; the staff at the Westchester Medical Center, where the case-patient received medical care; and Perry Smith, Barbara Wallace, Bryan Cherry, and Amanda Balish.

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References

  1. Kurtz  J, Manvell  RJ, Banks  J. Avian influenza virus isolated from a woman with conjunctivitis. Lancet. 1996;348:9012. DOIPubMedGoogle Scholar
  2. Tweed  SA, Skowronski  DM, David  ST, Larder  A, Petric  M, Lees  W, Human illness from avian influenza H7N3, British Columbia. Emerg Infect Dis. 2004;10:21969. DOIPubMedGoogle Scholar
  3. Skowronski  DM, Tweed  SA, Petric  M, Booth  T, Li  Y, Tam  T. Human illness and isolation of low-pathogenicity avian influenza virus of the H7N3 subtype in British Columbia, Canada. J Infect Dis. 2006;193:899900. DOIPubMedGoogle Scholar
  4. Edwards  LE, Terebuh  P, Adija  A, Rowe  T, Kleene  J, Hu-Primmer  J. Serological diagnosis of human infection with avian influenza A (H7N2) virus. Presented at the International Conference on Emerging Infectious Diseases 2004, Atlanta, Georgia, February 22–March 3, 2004. Abstract 60, Session 44.
  5. Nguyen-Van-Tam  JS, Nair  P, Acheson  P, Baker  A, Barker  M, Bracebridge  S, ; Incident Response Team. Outbreak of low pathogenicity H7N3 avian influenza in UK, including associated case of human conjunctivitis. Euro Surveill. 2006;11:E060504.2 PubMedGoogle Scholar
  6. Avian influenza A/(H7N2) outbreak in the United Kingdom. Euro Surveill. 2007;12:E070531.2.
  7. Karakousis  PC, Moore  RD, Chaisson  RE. Mycobacterium avium complex in patients with HIV infection in the era of highly active antiretroviral therapy. Lancet Infect Dis. 2004;4:55765. DOIPubMedGoogle Scholar
  8. Belser  JA, Lu  X, Maines  TR, Smith  C, Li  Y, Donis  RO, Pathogenesis of avian influenza (H7) virus infection in mice and ferrets: enhanced virulence of Eurasian H7N7 viruses isolated from humans. J Virol. 2007;81:1113947. DOIPubMedGoogle Scholar
  9. Belser  JA, Wadford  DA, Xu  J, Katz  JM, Tumpey  TM. Ocular infection of mice with influenza A (H7) viruses: a site of primary replication and spread to the respiratory tract. J Virol. 2009;83:707584. DOIPubMedGoogle Scholar
  10. Belser  JA, Blixt  O, Chen  LM, Pappas  C, Maines  TR, Van Hoeven  N, Contemporary North American influenza H7 viruses possess human receptor specificity: implications for virus transmissibility. Proc Natl Acad Sci U S A. 2008;105:755863. DOIPubMedGoogle Scholar
  11. Suarez  DL, Spackman  E, Senne  DA. Update on molecular epidemiology of H1, H5, and H7 influenza virus infections in poultry in North America. Avian Dis. 2003;47(Suppl):88897. DOIPubMedGoogle Scholar
  12. Senne  DA, Suarez  DL, Pedersen  JC, Panigrahy  B. Molecular and biological characteristics of H5 and H7 avian influenza viruses in live-bird markets of the northeastern United States, 1994–2001. Avian Dis. 2003;47(Suppl):898904. DOIPubMedGoogle Scholar
  13. Bulaga  LL, Garber  L, Senne  D, Myers  TJ, Good  R, Wainwright  S, Descriptive and surveillance studies of suppliers to New York and New Jersey retail live-bird markets. Avian Dis. 2003;47(Suppl):116976. DOIPubMedGoogle Scholar
  14. Cheng  VC, Chan  JF, Wen  X, Wu  WL, Que  TL, Chen  H, Infection of immunocompromised patients by avian H9N2 influenza A virus. J Infect. 2011. Epub ahead of print. DOIPubMedGoogle Scholar
  15. Puzelli  S, Di Trani  L, Fabiani  C, Campitelli  L, De Marco  MA, Capua  I, Serological analysis of serum samples from humans exposed to avian H7 influenza viruses in Italy between 1999 and 2003. J Infect Dis. 2005;192:131822. DOIPubMedGoogle Scholar

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Follow Up

Earning CME Credit

To obtain credit, you should first read the journal article. After reading the article, you should be able to answer the following, related, multiple-choice questions. To complete the questions (with a minimum 70% passing score) and earn continuing medical education (CME) credit, please go to www.medscape.org/journal/eid. Credit cannot be obtained for tests completed on paper, although you may use the worksheet below to keep a record of your answers. You must be a registered user on Medscape.org. If you are not registered on Medscape.org, please click on the New Users: Free Registration link on the left hand side of the website to register. Only one answer is correct for each question. Once you successfully answer all post-test questions you will be able to view and/or print your certificate. For questions regarding the content of this activity, contact the accredited provider, CME@medscape.net. For technical assistance, contact CME@webmd.net. American Medical Association’s Physician’s Recognition Award (AMA PRA) credits are accepted in the US as evidence of participation in CME activities. For further information on this award, please refer to http://www.ama-assn.org/ama/pub/category/2922.html. The AMA has determined that physicians not licensed in the US who participate in this CME activity are eligible for AMA PRA Category 1 Credits™. Through agreements that the AMA has made with agencies in some countries, AMA PRA credit may be acceptable as evidence of participation in CME activities. If you are not licensed in the US, please complete the questions online, print the certificate and present it to your national medical association for review.

Article Title: Low Pathogenic Avian Influenza A (H7N2) Virus Infection in Immunocompromised Adult, New York, USA, 2003

CME Questions

1. You are seeing a 48-year-old man who complains of 2 weeks of severe malaise, tactile fever, cough, and weight loss.

You consider whether this patient has influenza. Which of the following statements best characterizes the majority of low pathogenic avian influenza (LPAI) viral infections?

A.        The mortality rate approaches 50%

B.        Almost all cases are diagnosed in the hospital

C.        Most infections are mild in nature

D.        They are characterized by higher rates of secondary pneumonia compared with other influenza infections

2. You want to offer targeted antimicrobial therapy for this patient. What was the patient in the current case study treated for originally?

A.        Community-acquired pneumonia

B.        Primary influenza infection

C.        Primary HIV infection

D.        Tuberculosis

3. The patient is confirmed to have infection with LPAI. How did the patient in the current case study acquire LPAI?

A.        Keeping pigeons above his home

B.        Working in a poultry processing plant

C.        Direct contact with infected coworkers

D.        Unknown

4. What else should you consider regarding the current case study as you treat this patient with LPAI infection?

A.        The presence of conjunctivitis suggests something different from infection with H7 subtype viruses

B.        Concomitant HIV infection has been definitively associated with an increased risk of lower respiratory tract infection with H7N2 virus

C.        The case patient recovered without specific treatment for influenza

D.        The influenza A isolate grew rapidly in culture

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Cite This Article

DOI: 10.3201/eid1807.111913

1Current affiliation: Montefiore Medical Center, the University Hospital for the Albert Einstein College of Medicine, Bronx, New York, USA.

2Current affiliation: The State University of New York School of Medicine, Buffalo, New York, USA.

3Current affiliation: University of Colorado School of Medicine, Denver, Colorado, USA.

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Comments

Please use the form below to submit correspondence to the authors or contact them at the following address:

Belinda Ostrowsky, Montefiore Medical Center, Albert Einstein College of Medicine, 111 E 210 St, Bronx, NY 10467, USA

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Page created: June 15, 2012
Page updated: June 22, 2012
Page reviewed: June 22, 2012
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.
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