Hantavirus pulmonary syndrome: Pathogenesis of an emerging infectious disease

S. R. Zaki, P. W. Greer, L. M. Coffield, C. S. Goldsmith, K. B. Nolte, K. Foucar, R. M. Feddersen, R. E. Zumwalt, G. L. Miller, A. S. Khan, P. E. Rollin, Thomas Ksiazek, S. T. Nichol, B. W J Mahy, C. J. Peters

Research output: Contribution to journalArticle

481 Citations (Scopus)

Abstract

A recent outbreak of a severe pulmonary disease in the southwestern United States was etiologically linked to a previously unrecognized hantavirus. The virus has been isolated from its major reservoir, the deer mouse, Peromyscus maniculatus, and recently named Sin Nombre virus. Clinically, the disease has become known as the hantavirus pulmonary syndrome (HPS). Since May 1993, 44 fatal cases of HPS have been identified through clinicopathological review and immunohistochemical (IHC) testing of tissues from 273 patients who died of an unexplained noncardiogenic pulmonary edema. In 158 cases for which suitable specimens were available, serological testing and/or reverse transcription-polymerase chain reaction (RT-PCR) amplification of extracted RNA was also performed. IHC, serological, and PCR results were concordant for virtually all HPS and non-HPS patients when more than one assay was performed. The prodromal illness of HPS is similar to that of many other viral diseases. Consistent hematological features include thrombocytopenia, hemoconcentration, neutrophilic leukocytosis with a left shift, and reactive lymphocytes. Pulmonary histopathological features were similar in most of the fatal HPS cases (40/44) and consisted of an interstitial pneumonitis with a variable mononuclear cell infiltrate, edema, and focal hyaline membranes. In four cases, however, pulmonary features were significantly different and included diffuse alveolar damage and variable degrees of severe air space disorganization IHC analysis showed widespread presence of hantaviral antigens in endothelial cells of the microvasculature, particularly in the lung. Hantaviral antigens were also observed within follicular dendritic cells, macrophages, and lymphocytes. Hantaviral inclusions were observed in endothelial cells of lungs by thin-section electron microscopy, and their identity was verified by immunogold labeling. Virus-like particles were seen in pulmonary endothelial cells and macrophages. HPS is a newly recognized, of ten fatal disease, with a spectrum of microscopic morphological changes, which may be an important cause of severe and fatal illness presenting as adult respiratory distress syndrome.

Original languageEnglish (US)
Pages (from-to)552-579
Number of pages28
JournalAmerican Journal of Pathology
Volume146
Issue number3
StatePublished - 1995
Externally publishedYes

Fingerprint

Hantavirus Pulmonary Syndrome
Emerging Communicable Diseases
Lung
Peromyscus
Endothelial Cells
Sin Nombre virus
Macrophages
Southwestern United States
Lymphocytes
Follicular Dendritic Cells
Hantavirus
Antigens
Polymerase Chain Reaction
Hyalin
Interstitial Lung Diseases
Leukocytosis
Adult Respiratory Distress Syndrome
Virus Diseases
Pulmonary Edema
Microvessels

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Zaki, S. R., Greer, P. W., Coffield, L. M., Goldsmith, C. S., Nolte, K. B., Foucar, K., ... Peters, C. J. (1995). Hantavirus pulmonary syndrome: Pathogenesis of an emerging infectious disease. American Journal of Pathology, 146(3), 552-579.

Hantavirus pulmonary syndrome : Pathogenesis of an emerging infectious disease. / Zaki, S. R.; Greer, P. W.; Coffield, L. M.; Goldsmith, C. S.; Nolte, K. B.; Foucar, K.; Feddersen, R. M.; Zumwalt, R. E.; Miller, G. L.; Khan, A. S.; Rollin, P. E.; Ksiazek, Thomas; Nichol, S. T.; Mahy, B. W J; Peters, C. J.

In: American Journal of Pathology, Vol. 146, No. 3, 1995, p. 552-579.

Research output: Contribution to journalArticle

Zaki, SR, Greer, PW, Coffield, LM, Goldsmith, CS, Nolte, KB, Foucar, K, Feddersen, RM, Zumwalt, RE, Miller, GL, Khan, AS, Rollin, PE, Ksiazek, T, Nichol, ST, Mahy, BWJ & Peters, CJ 1995, 'Hantavirus pulmonary syndrome: Pathogenesis of an emerging infectious disease', American Journal of Pathology, vol. 146, no. 3, pp. 552-579.
Zaki SR, Greer PW, Coffield LM, Goldsmith CS, Nolte KB, Foucar K et al. Hantavirus pulmonary syndrome: Pathogenesis of an emerging infectious disease. American Journal of Pathology. 1995;146(3):552-579.
Zaki, S. R. ; Greer, P. W. ; Coffield, L. M. ; Goldsmith, C. S. ; Nolte, K. B. ; Foucar, K. ; Feddersen, R. M. ; Zumwalt, R. E. ; Miller, G. L. ; Khan, A. S. ; Rollin, P. E. ; Ksiazek, Thomas ; Nichol, S. T. ; Mahy, B. W J ; Peters, C. J. / Hantavirus pulmonary syndrome : Pathogenesis of an emerging infectious disease. In: American Journal of Pathology. 1995 ; Vol. 146, No. 3. pp. 552-579.
@article{3ee5361b947d4eb4b7b01dff500a0bca,
title = "Hantavirus pulmonary syndrome: Pathogenesis of an emerging infectious disease",
abstract = "A recent outbreak of a severe pulmonary disease in the southwestern United States was etiologically linked to a previously unrecognized hantavirus. The virus has been isolated from its major reservoir, the deer mouse, Peromyscus maniculatus, and recently named Sin Nombre virus. Clinically, the disease has become known as the hantavirus pulmonary syndrome (HPS). Since May 1993, 44 fatal cases of HPS have been identified through clinicopathological review and immunohistochemical (IHC) testing of tissues from 273 patients who died of an unexplained noncardiogenic pulmonary edema. In 158 cases for which suitable specimens were available, serological testing and/or reverse transcription-polymerase chain reaction (RT-PCR) amplification of extracted RNA was also performed. IHC, serological, and PCR results were concordant for virtually all HPS and non-HPS patients when more than one assay was performed. The prodromal illness of HPS is similar to that of many other viral diseases. Consistent hematological features include thrombocytopenia, hemoconcentration, neutrophilic leukocytosis with a left shift, and reactive lymphocytes. Pulmonary histopathological features were similar in most of the fatal HPS cases (40/44) and consisted of an interstitial pneumonitis with a variable mononuclear cell infiltrate, edema, and focal hyaline membranes. In four cases, however, pulmonary features were significantly different and included diffuse alveolar damage and variable degrees of severe air space disorganization IHC analysis showed widespread presence of hantaviral antigens in endothelial cells of the microvasculature, particularly in the lung. Hantaviral antigens were also observed within follicular dendritic cells, macrophages, and lymphocytes. Hantaviral inclusions were observed in endothelial cells of lungs by thin-section electron microscopy, and their identity was verified by immunogold labeling. Virus-like particles were seen in pulmonary endothelial cells and macrophages. HPS is a newly recognized, of ten fatal disease, with a spectrum of microscopic morphological changes, which may be an important cause of severe and fatal illness presenting as adult respiratory distress syndrome.",
author = "Zaki, {S. R.} and Greer, {P. W.} and Coffield, {L. M.} and Goldsmith, {C. S.} and Nolte, {K. B.} and K. Foucar and Feddersen, {R. M.} and Zumwalt, {R. E.} and Miller, {G. L.} and Khan, {A. S.} and Rollin, {P. E.} and Thomas Ksiazek and Nichol, {S. T.} and Mahy, {B. W J} and Peters, {C. J.}",
year = "1995",
language = "English (US)",
volume = "146",
pages = "552--579",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Hantavirus pulmonary syndrome

T2 - Pathogenesis of an emerging infectious disease

AU - Zaki, S. R.

AU - Greer, P. W.

AU - Coffield, L. M.

AU - Goldsmith, C. S.

AU - Nolte, K. B.

AU - Foucar, K.

AU - Feddersen, R. M.

AU - Zumwalt, R. E.

AU - Miller, G. L.

AU - Khan, A. S.

AU - Rollin, P. E.

AU - Ksiazek, Thomas

AU - Nichol, S. T.

AU - Mahy, B. W J

AU - Peters, C. J.

PY - 1995

Y1 - 1995

N2 - A recent outbreak of a severe pulmonary disease in the southwestern United States was etiologically linked to a previously unrecognized hantavirus. The virus has been isolated from its major reservoir, the deer mouse, Peromyscus maniculatus, and recently named Sin Nombre virus. Clinically, the disease has become known as the hantavirus pulmonary syndrome (HPS). Since May 1993, 44 fatal cases of HPS have been identified through clinicopathological review and immunohistochemical (IHC) testing of tissues from 273 patients who died of an unexplained noncardiogenic pulmonary edema. In 158 cases for which suitable specimens were available, serological testing and/or reverse transcription-polymerase chain reaction (RT-PCR) amplification of extracted RNA was also performed. IHC, serological, and PCR results were concordant for virtually all HPS and non-HPS patients when more than one assay was performed. The prodromal illness of HPS is similar to that of many other viral diseases. Consistent hematological features include thrombocytopenia, hemoconcentration, neutrophilic leukocytosis with a left shift, and reactive lymphocytes. Pulmonary histopathological features were similar in most of the fatal HPS cases (40/44) and consisted of an interstitial pneumonitis with a variable mononuclear cell infiltrate, edema, and focal hyaline membranes. In four cases, however, pulmonary features were significantly different and included diffuse alveolar damage and variable degrees of severe air space disorganization IHC analysis showed widespread presence of hantaviral antigens in endothelial cells of the microvasculature, particularly in the lung. Hantaviral antigens were also observed within follicular dendritic cells, macrophages, and lymphocytes. Hantaviral inclusions were observed in endothelial cells of lungs by thin-section electron microscopy, and their identity was verified by immunogold labeling. Virus-like particles were seen in pulmonary endothelial cells and macrophages. HPS is a newly recognized, of ten fatal disease, with a spectrum of microscopic morphological changes, which may be an important cause of severe and fatal illness presenting as adult respiratory distress syndrome.

AB - A recent outbreak of a severe pulmonary disease in the southwestern United States was etiologically linked to a previously unrecognized hantavirus. The virus has been isolated from its major reservoir, the deer mouse, Peromyscus maniculatus, and recently named Sin Nombre virus. Clinically, the disease has become known as the hantavirus pulmonary syndrome (HPS). Since May 1993, 44 fatal cases of HPS have been identified through clinicopathological review and immunohistochemical (IHC) testing of tissues from 273 patients who died of an unexplained noncardiogenic pulmonary edema. In 158 cases for which suitable specimens were available, serological testing and/or reverse transcription-polymerase chain reaction (RT-PCR) amplification of extracted RNA was also performed. IHC, serological, and PCR results were concordant for virtually all HPS and non-HPS patients when more than one assay was performed. The prodromal illness of HPS is similar to that of many other viral diseases. Consistent hematological features include thrombocytopenia, hemoconcentration, neutrophilic leukocytosis with a left shift, and reactive lymphocytes. Pulmonary histopathological features were similar in most of the fatal HPS cases (40/44) and consisted of an interstitial pneumonitis with a variable mononuclear cell infiltrate, edema, and focal hyaline membranes. In four cases, however, pulmonary features were significantly different and included diffuse alveolar damage and variable degrees of severe air space disorganization IHC analysis showed widespread presence of hantaviral antigens in endothelial cells of the microvasculature, particularly in the lung. Hantaviral antigens were also observed within follicular dendritic cells, macrophages, and lymphocytes. Hantaviral inclusions were observed in endothelial cells of lungs by thin-section electron microscopy, and their identity was verified by immunogold labeling. Virus-like particles were seen in pulmonary endothelial cells and macrophages. HPS is a newly recognized, of ten fatal disease, with a spectrum of microscopic morphological changes, which may be an important cause of severe and fatal illness presenting as adult respiratory distress syndrome.

UR - http://www.scopus.com/inward/record.url?scp=0028954686&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028954686&partnerID=8YFLogxK

M3 - Article

C2 - 7887439

AN - SCOPUS:0028954686

VL - 146

SP - 552

EP - 579

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 3

ER -