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Brief Communication: Fatal Human Metapneumovirus Infection in Stem-Cell Transplant Recipients

Janet A. Englund, MD; Michael Boeckh, MD; Jane Kuypers, PhD; W. Garrett Nichols, MD, MS; Robert C. Hackman, MD; Rhoda A. Morrow, PhD; David N. Fredricks, MD; and Lawrence Corey, MD
[+] Article and Author Information

From the Children's Hospital and Regional Medical Center, University of Washington, and Fred Hutchinson Cancer Research Center, Seattle, Washington.


The paper was presented in part at the American Society of Hematology 46th Annual Meeting, San Diego, California, 4–7 December 2004.

Note: Drs. Englund and Boeckh contributed equally to the manuscript.

Acknowledgments: The authors acknowledge the immunohistochemical studies in lung tissue performed by Dr. Thijs Kuiken, Erasmus University. They thank Kristen White for specimen processing and Nancy Wright for laboratory assistance with PCR testing.

Grant Support: In part by National Institutes of Health (grants CA 18029, CA 15704, and PO1 AI 30731), the Fred Hutchinson Cancer Research Center (support grant P30 CA015704), and Adult Leukemia Research Center (grant P01 CA18029).

Potential Financial Conflicts of Interest: Consultancies: J.A. Englund (MedImmune Inc., Wyeth Vaccines); Grants received: J.A. Englund (MedImmune Inc.), R.A. Morrow (GlaxoSmithKline); Grants pending: J.A. Englund (National Institutes of Health).

Requests for Single Reprints: Janet A. Englund, MD, Children's Hospital and Regional Medical Center, 4800 Sand Point Way NE, Mail Stop W-8851, Seattle, WA 98105; e-mail, janet.englund@seattlechildrens.org.

Current Author Addresses: Dr. Englund: Children's Hospital and Regional Medical Center, 4800 Sand Point Way NE, Mail Stop W-8851, Seattle, WA 98105.

Drs. Boeckh, Fredricks, and Corey: Program in Infectious Diseases, D3-100, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, P.O. Box 19024, Seattle, WA 98109-1024.

Dr. Kuypers: Department of Laboratory Medicine, University of Washington Clinical Virology Laboratory, Children's Hospital and Regional Medical Center, 4800 Sand Point Way NE, Mailstop 8G-3, Seattle, WA 98105.

Dr. Nichols: 5 Moore Drive, 17.1354B, Research Triangle Park, NC 27709.

Dr. Hackman: Department of Pathology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, P.O. Box 19024, Seattle, WA 98109-1024.

Dr. Morrow: Department of Laboratory Medicine, University of Washington Clinical Virology Laboratory, Children's Hospital and Regional Medical Center, 4800 Sand Point Way NE, Mail Stop G 815, Seattle, WA 98105.

Author Contributions: Conception and design: J.A. Englund, M. Boeckh, W.G. Nichols, L. Corey.

Analysis and interpretation of the data: J.A. Englund, M. Boeckh, J. Kuypers, W.G. Nichols, R.C. Hackman, R.A. Morrow, D.N. Fredricks, L. Corey.

Drafting of the article: J.A. Englund, M. Boeckh, W.G. Nichols, R.C. Hackman, R.A. Morrow, L. Corey.

Critical revision of the article for important intellectual content: J.A. Englund, M. Boeckh, J. Kuypers, W.G. Nichols, L. Corey.

Final approval of the article: J.A. Englund, M. Boeckh, W.G. Nichols, R.A. Morrow, D.N. Fredricks, L. Corey.

Provision of study materials or patients: J.A. Englund, M. Boeckh, R.C. Hackman, L. Corey.

Obtaining of funding: M. Boeckh, L. Corey.

Administrative, technical, or logistic support: R.A. Morrow, L. Corey.

Collection and assembly of data: J.A. Englund, M. Boeckh, W.G. Nichols, R.C. Hackman, R.A. Morrow, D.N. Fredricks.


Ann Intern Med. 2006;144(5):344-349. doi:10.7326/0003-4819-144-5-200603070-00010
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Patients undergoing HCT who underwent BAL between 1995 to 1999 for evaluation of respiratory disease were eligible for inclusion if they had previously consented to diagnostic studies on their tissue and if residual specimens were available and were in good condition. We retrospectively reviewed clinical and laboratory records, biopsy specimens, and autopsy specimens of all patients with detected hMPV. We also evaluated stored BAL samples in 19 HCT recipients who were enrolled in a separate prospective study evaluating BAL after transplantation.

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Figure.
Computed tomography scan of chest in a patient with fatal human metapneumovirus infection after transplantation (top) and lung histologic study in a patient with human metapneumovirus pneumonia (bottom). Top.Bottom.insetarrowarrow

Computed tomography scan of chest from case 2 on day 29 after transplantation revealing right pleural effusion, with bilateral nodular infiltrates and bilateral infiltrates with extensive consolidation. Lung tissue (case 2) obtained at autopsy. Human metapneumovirus was detected by polymerase chain reaction but not by immunohistochemical staining in this sample. Histologic examination of the lung shows both diffuse alveolar damage and alterations in the bronchial and alveolar epithelium suggestive of viral infection ( ). In the larger photomicrograph, distended bronchioles and alveolar ducts are lined by hyaline membranes ( ), with infiltration of the interstitium by mononuclear inflammatory cells. (Hematoxylin–eosin staining; original magnification, ×90.) In the inset, the nuclei of the atypical bronchiolar epithelial cells are pleomorphic and hyperchromatic, and some display chromatin margination ( ). Definite viral inclusions are not apparent. (Hematoxylin–eosin staining; original magnification, ×360.)

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