eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Hantavirus Pulmonary Syndrome: Differential Diagnoses & Workup

Author: Vinod K Dhawan, MD, FACP, FRCP(C), Professor, Department of Clinical Medicine, University of California at Los Angeles; Professor of Medicine, Charles R Drew University of Medicine and Science; Chief, Division of Infectious Diseases, MLK-Harbor Hospital
Coauthor(s): Veronica A Mas Casullo, MD, Assistant Professor, Department of Pediatric Infectious Diseases, Mount Sinai School of Medicine
Contributor Information and Disclosures

Updated: Aug 11, 2008

Differential Diagnoses

Leptospirosis
Meningococcal Infections
Neonatal Sepsis
Plague
Rickettsial Infection
Tularemia

Other Problems to Be Considered

Influenza

Workup

Laboratory Studies

  • Several laboratory tests are useful in the diagnosis of Hantavirus pulmonary syndrome (HPS).
    • Thrombocytopenia is noted early in the disease.
    • Leukocytosis is noted with a left shift.
    • Abnormal lymphocytes and immunoblasts are present in the peripheral smear.
    • The hematocrit level is elevated because of the ultrafiltration of fluid into the lungs.
    • Activated partial thromboplastin time (aPTT) is prolonged.
    • Aspartate aminotransferase (AST) and lactic dehydrogenase (LDH) may be mildly elevated.
    • ABG measurement reveals desaturation.
  • The tetrad of thrombocytopenia, leukocytosis (often with left shift), elevated hematocrit levels, and presence of immunoblasts in peripheral blood smear is a sensitive and specific early clue to the underlying disease. These findings in a patient with rapid onset of respiratory insufficiency should suggest the diagnosis.
  • Serologic methods are useful in the diagnosis of Hantavirus infection. Most patients have both immunoglobulin M (IgM) and immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) antibodies upon admission to the hospital.
  • Hantavirus can be detected in the tissue by the RT-PCR.
  • Immunohistochemical staining of tissue reveals Hantaviral antigen.

Imaging Studies

  • Chest radiographs usually reveal marked peribronchial cuffing and Kerley B lines early in the disease.
  • Rapid progression of bilateral interstitial and alveolar infiltrates is observed in patients with full-blown Hantavirus pulmonary syndrome.

Procedures

  • Catheterization of the pulmonary artery in patients with profound Hantavirus pulmonary syndrome generally reveals decreased stroke volume index (SVI) and a low to low-normal cardiac index (CI).
  • The pulmonary vascular resistance index is elevated.
  • Increased systemic vascular resistance, along with the failure of correction of lowered CI and SVI by volume replacement, distinguishes Hantavirus pulmonary syndrome from septic shock.

Histologic Findings

  • Histopathology of the lungs in patients with Hantavirus pulmonary syndrome is depicted in Media file 6. Under light microscopy, the lungs of these patients reveal interstitial and alveolar edema, alveolar hemorrhage, and a mononuclear interstitial pneumonitis composed of macrophages and T lymphocytes.
  • Unlike the acute respiratory distress syndrome (ARDS) due to other causes, no marked necrosis, polymorphonuclear leukocyte infiltration, type II pneumocyte hyperplasia, or dense hyalinization is observed.
  • Electron microscopy of lung tissue reveals intact and somewhat swollen vascular endothelium. Inflammatory cell infiltration of capillaries, interstitium, and alveoli is evident. The cytoplasm of endothelial cells contains viral inclusions. No evidence of necrosis or a structural cellular defect responsible for the capillary leak is observed.
  • Examination of other tissues may reveal infiltration by immunoblasts, such as in lymph nodes, spleen, liver, and blood vessels of other organs.

More on Hantavirus Pulmonary Syndrome

Overview: Hantavirus Pulmonary Syndrome
Differential Diagnoses & Workup: Hantavirus Pulmonary Syndrome
Treatment & Medication: Hantavirus Pulmonary Syndrome
Follow-up: Hantavirus Pulmonary Syndrome
Multimedia: Hantavirus Pulmonary Syndrome
References
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References

  1. CDC. Update: hantavirus pulmonary syndrome--United States, 1993. MMWR Morb Mortal Wkly Rep. Oct 29 1993;42(42):816-20. [Medline].

  2. Mori M, Rothman AL, Kurane I, et al. High levels of cytokine-producing cells in the lung tissues of patients with fatal hantavirus pulmonary syndrome. J Infect Dis. Feb 1999;179(2):295-302. [Medline].

  3. Kilpatrick ED, Terajima M, Koster FT, et al. Role of specific CD8+ T cells in the severity of a fulminant zoonotic viral hemorrhagic fever, hantavirus pulmonary syndrome. J Immunol. Mar 1 2004;172(5):3297-304. [Medline]. [Full Text].

  4. Mills JN, Ksiazek TG, Ellis BA, et al. Patterns of association with host and habitat: antibody reactive with Sin Nombre virus in small mammals in the major biotic communities of the southwestern United States. Am J Trop Med Hyg. Mar 1997;56(3):273-84. [Medline].

  5. Kuenzi AJ, Douglass RJ, Bond CW. Sin nombre virus in deer mice captured inside homes, southwestern Montana. Emerg Infect Dis. Jul-Aug 2000;6(4):386-8. [Medline].

  6. Armstrong LR, Zaki SR, Goldoft MJ, et al. Hantavirus pulmonary syndrome associated with entering or cleaning rarely used, rodent-infested structures. J Infect Dis. Oct 1995;172(4):1166. [Medline].

  7. Dietl CA, Wernly JA, Pett SB, et al. Extracorporeal membrane oxygenation support improves survival of patients with severe Hantavirus cardiopulmonary syndrome. J Thorac Cardiovasc Surg. Mar 2008;135(3):579-84. [Medline].

  8. Jonsson CB, Hooper J, Mertz G. Treatment of hantavirus pulmonary syndrome. Antiviral Res. Apr 2008;78(1):162-9. [Medline].

  9. Cho HW, Howard CR. Antibody responses in humans to an inactivated hantavirus vaccine (Hantavax). Vaccine. Jun 4 1999;17(20-21):2569-75. [Medline].

  10. Abbott KD, Ksiazek TG, Mills JN. Long-term hantavirus persistence in rodent populations in central Arizona. Emerg Infect Dis. Jan-Feb 1999;5(1):102-12. [Medline].

  11. Abel Borges A, Figueiredo LT. Mechanisms of shock in hantavirus pulmonary syndrome. Curr Opin Infect Dis. Jun 2008;21(3):293-7. [Medline].

  12. Bartholomew DM, Hansen LA, Frank JJ, Farver DK. Case report of hantavirus pulmonary syndrome and review. S D Med. May 2007;60(5):189-91, 193-5. [Medline].

  13. Bennett SG, Webb JP Jr, Madon MB, et al. Hantavirus (Bunyaviridae) infections in rodents from Orange and San Diego counties, California. Am J Trop Med Hyg. Jan 1999;60(1):75-84. [Medline].

  14. Brillman J, Talan DA, Moran GJ, Pinner R. Update on emerging infections from the Centers for Disease Control and Prevention. Hantavirus pulmonary syndrome--five states, 2006. Ann Emerg Med. Nov 2006;48(5):593-4; discussion 594-5. [Medline].

  15. CDC. From the Centers for Disease Control and Prevention. Hantavirus pulmonary syndrome--Panama, 1999-2000. JAMA. May 3 2000;283(17):2232-3. [Medline].

  16. CDC. Update: hantavirus pulmonary syndrome--United States, 1999. MMWR Morb Mortal Wkly Rep. Jun 25 1999;48(24):521-5. [Medline].

  17. Chang B, Crowley M, Campen M, Koster F. Hantavirus cardiopulmonary syndrome. Semin Respir Crit Care Med. Apr 2007;28(2):193-200. [Medline].

  18. Cheney PR. Update on emerging infections from the Centers for Disease Control and Prevention. Hantavirus pulmonary syndrome--Colorado and New Mexico, 1998. Ann Emerg Med. Jan 1999;33(1):121-3. [Medline].

  19. Chin C, Chiueh TS, Yang WC, et al. Hantavirus infection in Taiwan: the experience of a geographically unique area. J Med Virol. Feb 2000;60(2):237-47. [Medline].

  20. Douglass RJ, Calisher CH, Bradley KC. State-by-state incidences of hantavirus pulmonary syndrome in the United States, 1993-2004. Vector Borne Zoonotic Dis. Summer 2005;5(2):189-92. [Medline].

  21. Drebot MA, Artsob H, Werker D. Hantavirus pulmonary syndrome in Canada, 1989-1999. Can Commun Dis Rep. Apr 15 2000;26(8):65-9. [Medline].

  22. Duchin JS, Koster FT, Peters CJ, et al. Hantavirus pulmonary syndrome: a clinical description of 17 patients with a newly recognized disease. The Hantavirus Study Group. N Engl J Med. Apr 7 1994;330(14):949-55. [Medline].

  23. Ferreira MS, Nishioka Sd, Santos TL, et al. Hantavirus pulmonary syndrome in Brazil: clinical aspects of three new cases. Rev Inst Med Trop Sao Paulo. Jan-Feb 2000;42(1):41-6. [Medline].

  24. Hallin GW, Simpson SQ, Crowell RE, et al. Cardiopulmonary manifestations of hantavirus pulmonary syndrome. Crit Care Med. Feb 1996;24(2):252-8. [Medline].

  25. Hantavirus pulmonary syndrome--five states, 2006. MMWR Morb Mortal Wkly Rep. Jun 9 2006;55(22):627-9. [Medline].

  26. Hjelle B, Glass GE. Outbreak of hantavirus infection in the Four Corners region of the United States in the wake of the 1997-1998 El Nino-southern oscillation. J Infect Dis. May 2000;181(5):1569-73. [Medline].

  27. Khan AS, Gaviria M, Rollin PE, et al. Hantavirus pulmonary syndrome in Florida: association with the newly identified Black Creek Canal virus. Am J Med. Jan 1996;100(1):46-8. [Medline].

  28. Khan AS, Khabbaz RF, Armstrong LR, et al. Hantavirus pulmonary syndrome: the first 100 US cases. J Infect Dis. Jun 1996;173(6):1297-303. [Medline].

  29. Klein SL, Calisher CH. Emergence and persistence of hantaviruses. Curr Top Microbiol Immunol. 2007;315:217-52. [Medline].

  30. Koraka P, Avsic-Zupanc T, Osterhaus AD, Groen J. Evaluation of two commercially available immunoassays for the detection of hantavirus antibodies in serum samples. J Clin Virol. Sep 1 2000;17(3):189-96. [Medline].

  31. Maeda K, West K, Toyosaki-Maeda T, et al. Identification and analysis for cross-reactivity among hantaviruses of H-2b-restricted cytotoxic T-lymphocyte epitopes in Sin Nombre virus nucleocapsid protein. J Gen Virol. Jul 2004;85(Pt 7):1909-19. [Medline].

  32. Maes P, Clement J, Gavrilovskaya I, Van Ranst M. Hantaviruses: immunology, treatment, and prevention. Viral Immunol. 2004;17(4):481-97. [Medline].

  33. Mertz GJ, Hjelle B, Crowley M, Iwamoto G, Tomicic V, Vial PA. Diagnosis and treatment of new world hantavirus infections. Curr Opin Infect Dis. Oct 2006;19(5):437-42. [Medline].

  34. Mills JN, Corneli A, Young JC, et al. Hantavirus pulmonary syndrome--United States: updated recommendations for risk reduction. Centers for Disease Control and Prevention. MMWR Recomm Rep. Jul 26 2002;51(RR-9):1-12. [Medline].

  35. Saggioro FP, Rossi MA, Duarte MI, et al. Hantavirus infection induces a typical myocarditis that may be responsible for myocardial depression and shock in hantavirus pulmonary syndrome. J Infect Dis. May 15 2007;195(10):1541-9. [Medline].

  36. Seitsonen E, Hynninen M, Kolho E, et al. Corticosteroids combined with continuous veno-venous hemodiafiltration for treatment of hantavirus pulmonary syndrome caused by Puumala virus infection. Eur J Clin Microbiol Infect Dis. Mar 21 2006;[Medline].

  37. Shope RE. A midcourse assessment of hantavirus pulmonary syndrome. Emerg Infect Dis. Jan-Feb 1999;5(1):172-4. [Medline].

  38. Terajima M, Hayasaka D, Maeda K, Ennis FA. Immunopathogenesis of hantavirus pulmonary syndrome and hemorrhagic fever with renal syndrome: Do CD8+ T cells trigger capillary leakage in viral hemorrhagic fevers?. Immunol Lett. Nov 15 2007;113(2):117-20. [Medline].

  39. Wells RM, Sosa Estani S, Yadon ZE, et al. An unusual hantavirus outbreak in southern Argentina: person-to-person transmission? Hantavirus Pulmonary Syndrome Study Group for Patagonia. Emerg Infect Dis. Apr-Jun 1997;3(2):171-4. [Medline].

  40. Zaki SR, Greer PW, Coffield LM, et al. Hantavirus pulmonary syndrome. Pathogenesis of an emerging infectious disease. Am J Pathol. Mar 1995;146(3):552-79. [Medline].

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Further Reading

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Keywords

Hantavirus pulmonary syndrome, Hantavirus, HPS, HPS disease, hemorrhagic fever with renal syndrome, HFRS, Sin Nombre virus, nameless virus, Peromyscus maniculatus, infectious rodent, pulmonary capillary permeability, severe pulmonary edema, viremia, atypical myocarditis, Hantavirus pulmonary syndrome shock, viral upper respiratory tract infections, rhinorrhea, pharyngitis

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Contributor Information and Disclosures

Author

Vinod K Dhawan, MD, FACP, FRCP(C), Professor, Department of Clinical Medicine, University of California at Los Angeles; Professor of Medicine, Charles R Drew University of Medicine and Science; Chief, Division of Infectious Diseases, MLK-Harbor Hospital
Vinod K Dhawan, MD, FACP, FRCP(C) is a member of the following medical societies: American College of Physicians, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, and Royal College of Physicians and Surgeons of Canada
Disclosure: Pfizer Inc None None

Coauthor(s)

Veronica A Mas Casullo, MD, Assistant Professor, Department of Pediatric Infectious Diseases, Mount Sinai School of Medicine
Disclosure: Nothing to disclose.

Medical Editor

Rosemary Johann-Liang, MD, Medical Officer, Infectious Diseases and Pediatrics, Division of Special Pathogens and Immunological Drug Products, Center for Drug Evaluation and Research, Food and Drug Administration
Rosemary Johann-Liang, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Mark R Schleiss, MD, American Legion Chair of Pediatrics, Professor of Pediatrics, Division Director, Division of Infectious Diseases and Immunology, Department of Pediatrics, University of Minnesota School of Medicine
Mark R Schleiss, MD is a member of the following medical societies: American Pediatric Society, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Consulting; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; Novartis Honoraria Speaking and teaching; sanofi pasteur Grant/research funds Unrestricted research grant; sanofi pasteur  Consulting; sanofi pasteur Honoraria Speaking and teaching; Tap Honoraria Speaking and teaching

Chief Editor

Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: None None None

 
 
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