Diagnostic Considerations

Drug-induced noncardiac pulmonary edema

An appropriate ingestion history of medications that are associated with noncardiac pulmonary edema may differentiate drug-induced noncardiac pulmonary edema from Hantavirus pulmonary syndrome (HPS).

Patients with cardiac pulmonary edema usually have a left ventricular S₃ gallop rhythm and often have cardiomegaly upon physical examination, which is not the case with HPS.

Acute respiratory distress syndrome

In contrast to HPS, the distribution of the infiltrates associated with acute respiratory distress syndrome (ARDS) observed on chest radiographs is peripheral rather than central. In addition, pleural effusions are common in HPS but are not a feature of ARDS.

HPS is accompanied by perihilar cuffing, earlier appearance of interstitial edema (Kerley B lines), and pericardiac haziness (fuzzy heart sign), which are characteristic of HPS and are not found with ARDS.

Pneumonic plague

Patients with pneumonic plague are critically ill with hemoptysis, which is not a feature of HPS. Pneumonic plague occurs in the setting of an outbreak of antecedent bubonic plague. Patients with HPS are less ill and have no adenopathy suggesting preceding or concomitant pneumonic plague.

Atypical community-acquired pneumonias

Among the nonzoonotic atypical pneumonias, Legionnaires disease may resemble HPS. Levels of serum transaminases may be mildly elevated in patients with Legionnaires disease and in those with HPS. Relative bradycardia uniformly accompanies Legionnaires disease but not HPS. Gastrointestinal symptoms, particularly diarrhea, may be observed in both. Severe renal insufficiency is uncommon in HPS and is unusual in Legionnaires disease. Cardiopulmonary collapse frequently occurs in HPS and seldom complicates Legionnaires disease, except in the terminal stages.

Tularemia and Q fever are zoonotic atypical pneumonias that are in the differential diagnoses of HPS. However, the vectors are different for these zoonotic infections. Contact with sheep or parturient cats is the usual epidemiological antecedent for Q fever pneumonia. Similarly, contact with deer, rabbits, or deer flies is the usual history suggesting tularemia. Symptoms common to Q fever, tularemia, and HPS are headache and myalgias. Q fever may feature splenomegaly and relative bradycardia, which are findings not observed in HPS. Bilateral hilar adenopathy and bloody pleural effusion characterize tularemic pneumonia and are not associated with HPS.

Viral influenza

Influenza begins abruptly, with patients often recalling the exact minute and/or hour they became acutely ill. A dry nonproductive cough and a sore throat, usually accompanied by rhinorrhea, characterize influenza. These are not features of HPS. Headache and myalgias are common in both infections.

Workup

Rubin R. Pet Rats Infect Daughter, Mother With Hantavirus. JAMA. 2017 Nov 28. 318 (20):1969. [QxMD MEDLINE Link].
Enria D, Padula P, Segura EL, et al. Hantavirus pulmonary syndrome in Argentina. Possibility of person to person transmission. Medicina (B Aires). 1996. 56(6):709-11. [QxMD MEDLINE Link].
Padula PJ, Edelstein A, Miguel SD, et al. Hantavirus pulmonary syndrome outbreak in Argentina: molecular evidence for person-to-person transmission of Andes virus. Virology. 1998 Feb 15. 241(2):323-30. [QxMD MEDLINE Link].
Martinez VP, Bellomo CM, Cacace ML, Suarez P, Bogni L, Padula PJ. Hantavirus pulmonary syndrome in Argentina, 1995-2008. Emerg Infect Dis. 2010 Dec. 16(12):1853-60. [QxMD MEDLINE Link].
Rasmuson J, Andersson C, Norrman E, Haney M, Evander M, Ahlm C. Time to revise the paradigm of hantavirus syndromes? Hantavirus pulmonary syndrome caused by European hantavirus. Eur J Clin Microbiol Infect Dis. 2011 May. 30(5):685-90. [QxMD MEDLINE Link]. [Full Text].
Rozental T, Silva ASVD, Oliveira RC, Favacho ARM, Oliveira MLA, Bastos FI, et al. Seroprevalence of Bartonella spp., Coxiella burnetii, and Hantavirus among people who inject drugs in Rio de Janeiro, Brazil: a retrospective assessment of a biobank. Rev Inst Med Trop Sao Paulo. 2018 Jul 19. 60:e31. [QxMD MEDLINE Link].
Fonseca LX, Oliveira SV, Duarte EC. Magnitude and distribution of deaths due to hantavirus in Brazil, 2007-2015. Epidemiol Serv Saude. 2018 Jun 28. 27 (2):e2017221. [QxMD MEDLINE Link].
Burns JE, Metzger ME, Messenger S, Fritz CL, Vilcins IE, Enge B, et al. Novel Focus of Sin Nombre Virus in Peromyscus eremicus Mice, Death Valley National Park, California, USA. Emerg Infect Dis. 2018 Jun. 24 (6):1112-1115. [QxMD MEDLINE Link].
Kuenzli AB, Marschall J, Schefold JC, Schafer M, Engler OB, Ackermann-Gäumann R, et al. Hantavirus Cardiopulmonary Syndrome Due to Imported Andes Hantavirus Infection in Switzerland: A Multidisciplinary Challenge, Two Cases and a Literature Review. Clin Infect Dis. 2018 May 22. [QxMD MEDLINE Link].
Moreli ML, Marques-Silva AC, Pimentel VA, da Costa VG. Effectiveness of the ribavirin in treatment of hantavirus infections in the Americas and Eurasia: a meta-analysis. Virusdisease. 2014. 25 (3):385-9. [QxMD MEDLINE Link].
Crowley MR, Katz RW, Kessler R, et al. Successful treatment of adults with severe Hantavirus pulmonary syndrome with extracorporeal membrane oxygenation. Crit Care Med. 1998 Feb. 26(2):409-14. [QxMD MEDLINE Link].
Wernly JA, Dietl CA, Tabe CE, Pett SB, Crandall C, Milligan K, et al. Extracorporeal membrane oxygenation support improves survival of patients with Hantavirus cardiopulmonary syndrome refractory to medical treatment. Eur J Cardiothorac Surg. 2011 Dec. 40 (6):1334-40. [QxMD MEDLINE Link].
Alkharsah KR. VEGF Upregulation in Viral Infections and Its Possible Therapeutic Implications. Int J Mol Sci. 2018 Jun 1. 19 (6):[QxMD MEDLINE Link].
Vial PA, Valdivieso F, Ferres M, Riquelme R, Rioseco ML, Calvo M, et al. High-dose intravenous methylprednisolone for hantavirus cardiopulmonary syndrome in Chile: a double-blind, randomized controlled clinical trial. Clin Infect Dis. 2013 Oct. 57 (7):943-51. [QxMD MEDLINE Link].
Jung J, Ko SJ, Oh HS, Moon SM, Song JW, Huh K. Protective Effectiveness of Inactivated Hantavirus Vaccine Against Hemorrhagic Fever With Renal Syndrome. J Infect Dis. 2018 Apr 11. 217 (9):1417-1420. [QxMD MEDLINE Link].
Boroja M, Barrie JR, Raymond GS. Radiographic findings in 20 patients with Hantavirus pulmonary syndrome correlated with clinical outcome. AJR Am J Roentgenol. 2002 Jan. 178(1):159-63. [QxMD MEDLINE Link].
Butler JC, Peters CJ. Hantaviruses and hantavirus pulmonary syndrome. Clin Infect Dis. 1994 Sep. 19(3):387-94; quiz 395. [QxMD MEDLINE Link].
Carneiro M, Koch BE, Krummenauer EC, Machado JA. Hantavirus pulmonary syndrome: when should you consider this diagnosis?. Braz J Infect Dis. 2011 May-Jun. 15(3):298-9. [QxMD MEDLINE Link].
Castillo C, Naranjo J, Sepúlveda A, et al. Hantavirus pulmonary syndrome due to Andes virus in Temuco, Chile: clinical experience with 16 adults. Chest. 2001 Aug. 120(2):548-54. [QxMD MEDLINE Link].
Castillo C, Nicklas C, Mardones J, et al. Andes Hantavirus as possible cause of disease in travellers to South America. Travel Med Infect Dis. 2007 Jan. 5(1):30-4. [QxMD MEDLINE Link].
Centers for Disease Control and Prevention. Hantavirus pulmonary syndrome--Northeastern United States, 1994. MMWR Morb Mortal Wkly Rep. 1994 Aug 5. 43(30):548-9, 555-6. [QxMD MEDLINE Link].
Centers for Disease Control and Prevention. Hantavirus pulmonary syndrome--Vermont, 2000. JAMA. 2001 Aug 22-29. 286(8):912-3. [QxMD MEDLINE Link].
Chang B, Crowley M, Campen M, et al. Hantavirus cardiopulmonary syndrome. Semin Respir Crit Care Med. 2007 Apr. 28(2):193-200. [QxMD MEDLINE Link].
Chaparro J, Vega J, Terry W, et al. Assessment of person-to-person transmission of hantavirus pulmonary syndrome in a Chilean hospital setting. J Hosp Infect. 1998 Dec. 40(4):281-5. [QxMD MEDLINE Link].
Chapman LE, Khabbaz RF. Etiology and epidemiology of the Four Corners hantavirus outbreak. Infect Agents Dis. 1994 Oct. 3(5):234-44. [QxMD MEDLINE Link].
Christensen PJ, Armstrong LR, Fak JJ, et al. Regulation of rat pulmonary dendritic cell immunostimulatory activity by alveolar epithelial cell-derived granulocyte macrophage colony-stimulating factor. Am J Respir Cell Mol Biol. 1995 Oct. 13(4):426-33. [QxMD MEDLINE Link].
da Rosa Elkhoury M, da Silva Mendes W, Waldman EA, et al. Hantavirus pulmonary syndrome: prognostic factors for death in reported cases in Brazil. Trans R Soc Trop Med Hyg. 2012 May. 106(5):298-302. [QxMD MEDLINE Link].
da Silva MV, Vasconcelos MJ, Hidalgo NT, et al. Hantavirus pulmonary syndrome. Report of the first three cases in São Paulo, Brazil. Rev Inst Med Trop Sao Paulo. 1997 Jul-Aug. 39(4):231-4. [QxMD MEDLINE Link].
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. 1994 Apr 7. 330(14):949-55. [QxMD MEDLINE Link].
Engelthaler DM, Mosley DG, Cheek JE, et al. Climatic and environmental patterns associated with hantavirus pulmonary syndrome, Four Corners region, United States. Emerg Infect Dis. 1999 Jan-Feb. 5(1):87-94. [QxMD MEDLINE Link].
Fulhorst CF, Milazzo ML, Armstrong LR, et al. Hantavirus and arenavirus antibodies in persons with occupational rodent exposure. Emerg Infect Dis. 2007 Apr. 13(4):532-8. [QxMD MEDLINE Link].
Hallin GW, Simpson SQ, Crowell RE, et al. Cardiopulmonary manifestations of hantavirus pulmonary syndrome. Crit Care Med. 1996 Feb. 24(2):252-8. [QxMD MEDLINE Link].
Jenison S, Hjelle B, Simpson S, et al. Hantavirus pulmonary syndrome: clinical, diagnostic, and virologic aspects. Semin Respir Infect. 1995 Dec. 10(4):259-269. [QxMD MEDLINE Link].
Ketai LH, Kelsey CA, Jordan K, et al. Distinguishing hantavirus pulmonary syndrome from acute respiratory distress syndrome by chest radiography: are there different radiographic manifestations of increased alveolar permeability?. J Thorac Imaging. 1998 Jul. 13(3):172-7. [QxMD MEDLINE Link].
Ketai LH, Williamson MR, Telepak RJ, et al. Hantavirus pulmonary syndrome: radiographic findings in 16 patients. Radiology. 1994 Jun. 191(3):665-8. [QxMD MEDLINE Link].
Khan AS, Khabbaz RF, Armstrong LR, et al. Hantavirus pulmonary syndrome: the first 100 US cases. J Infect Dis. 1996 Jun. 173(6):1297-303. [QxMD MEDLINE Link].
Khan AS, Kitsutani PT, Corneli AL. Hantavirus pulmonary syndrome in the Americas: the early years. Semin Respir Crit Care Med. 2000. 21(4):313-22. [QxMD MEDLINE Link].
Klein SL, Calisher CH. Emergence and persistence of hantaviruses. Curr Top Microbiol Immunol. 2007. 315:217-52. [QxMD MEDLINE Link].
Koch J, Brockmann SO, Winter C, et al. Significant increase of hantavirus infections in Germany since the beginning of 2007. Euro Surveill. 2007 May 3. 12(5):E070503.1. [QxMD MEDLINE Link].
Koster F, Foucar K, Hjelle B, et al. Rapid presumptive diagnosis of hantavirus cardiopulmonary syndrome by peripheral blood smear review. Am J Clin Pathol. 2001 Nov. 116(5):665-72. [QxMD MEDLINE Link].
Ksiazek TG, Peters CJ, Rollin PE, et al. Identification of a new North American hantavirus that causes acute pulmonary insufficiency. Am J Trop Med Hyg. 1995 Feb. 52(2):117-23. [QxMD MEDLINE Link].
Lazaro ME, Cantoni GE, Calanni LM, et al. Clusters of hantavirus infection, southern Argentina. Emerg Infect Dis. 2007 Jan. 13(1):104-10. [QxMD MEDLINE Link].
Levy H, Simpson SQ. Hantavirus pulmonary syndrome. Am J Respir Crit Care Med. 1994 Jun. 149(6):1710-3. [QxMD MEDLINE Link].
Macneil A, Nichol ST, Spiropoulou CF. Hantavirus pulmonary syndrome. Virus Res. 2011 Dec. 162(1-2):138-47. [QxMD MEDLINE Link].
Mehta S, Jiandani P. Ocular features of hantavirus infection. Indian J Ophthalmol. 2007 Sep-Oct. 55(5):378-80. [QxMD MEDLINE Link].
Mertz GJ, Hjelle BL, Bryan RT. Hantavirus infection. Adv Intern Med. 1997. 42:369-421. [QxMD MEDLINE Link].
Miedzinski L. Community-acquired pneumonia: new facets of an old disease--Hantavirus pulmonary syndrome. Respir Care Clin N Am. 2005 Mar. 11(1):45-58. [QxMD MEDLINE Link].
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. 2002 Jul 26. 51:1-12. [QxMD MEDLINE Link].
Montgomery JM, Ksiazek TG, Khan AS. Hantavirus pulmonary syndrome: the sound of a mouse roaring. J Infect Dis. 2007 Jun 1. 195(11):1553-5. [QxMD MEDLINE Link].
Moolenaar RL, Dalton C, Lipman HB, et al. Clinical features that differentiate hantavirus pulmonary syndrome from three other acute respiratory illnesses. Clin Infect Dis. 1995 Sep. 21(3):643-9. [QxMD MEDLINE Link].
Murgue B, Domart Y, Coudrier D, et al. First reported case of imported hantavirus pulmonary syndrome in europe. Emerg Infect Dis. 2002 Jan. 8(1):106-7. [QxMD MEDLINE Link].
Outbreak news. Hantavirus pulmonary syndrome, Yosemite National Park, United States of America. Wkly Epidemiol Rec. 2012 Sep 14. 87(37):345-6. [QxMD MEDLINE Link].
Padula P, Martinez VP, Bellomo C, et al. Pathogenic hantaviruses, northeastern Argentina and eastern Paraguay. Emerg Infect Dis. 2007 Aug. 13(8):1211-4. [QxMD MEDLINE Link].
Passaro DJ, Shieh WJ, Hacker JK, et al. Predominant kidney involvement in a fatal case of hantavirus pulmonary syndrome caused by Sin Nombre virus. Clin Infect Dis. 2001 Jul 15. 33(2):263-4. [QxMD MEDLINE Link].
Peters CJ, Khan AS. Hantavirus pulmonary syndrome: the new American hemorrhagic fever. Clin Infect Dis. 2002 May 1. 34(9):1224-31. [QxMD MEDLINE Link].
Pini NC, Resa A, del Jesús Laime G, et al. Hantavirus infection in children in Argentina. Emerg Infect Dis. 1998 Jan-Mar. 4(1):85-7. [QxMD MEDLINE Link].
Ramos MM, Overturf GD, Crowley MR, et al. Infection with Sin Nombre hantavirus: clinical presentation and outcome in children and adolescents. Pediatrics. 2001 Aug. 108(2):E27. [QxMD MEDLINE Link].
Rasmuson J, Andersson C, Norrman E, et al. Time to revise the paradigm of hantavirus syndromes? Hantavirus pulmonary syndrome caused by European hantavirus. Eur J Clin Microbiol Infect Dis. 2011 May. 30(5):685-90. [QxMD MEDLINE Link]. [Full Text].
Rosenberg RB, Waagner DC, Romano MJ, et al. Hantavirus pulmonary syndrome treated with inhaled nitric oxide. Pediatr Infect Dis J. 1998 Aug. 17(8):749-52. [QxMD MEDLINE Link].
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. 2007 May 15. 195(10):1541-9. [QxMD MEDLINE Link].
Shefer AM, Tappero JW, Bresee JS, et al. Hantavirus pulmonary syndrome in California: report of two cases and investigation. Clin Infect Dis. 1994 Dec. 19(6):1105-9. [QxMD MEDLINE Link].
Simpson SQ, Spikes L, Patel S, Faruqi I. Hantavirus pulmonary syndrome. Infect Dis Clin North Am. 2010 Mar. 24(1):159-73. [QxMD MEDLINE Link].
Slama TG, Zon R. Fatal hantavirus pulmonary syndrome in Indiana. N Engl J Med. 1994 Apr 7. 330(14):1010. [QxMD MEDLINE Link].
Smithee L, Bos J, Mallonee S, et al. Update on hantavirus in Oklahoma: are we missing cases?. J Okla State Med Assoc. 2007 May. 100(5):145-8. [QxMD MEDLINE Link].
Tahirkheli NK, Greipp PR. Treatment of the systemic capillary leak syndrome with terbutaline and theophylline. A case series. Ann Intern Med. 1999 Jun 1. 130(11):905-9. [QxMD MEDLINE Link].
Verity R, Prasad E, Grimsrud K, et al. Hantavirus pulmonary syndrome in northern Alberta, Canada: clinical and laboratory findings for 19 cases. Clin Infect Dis. 2000 Oct. 31(4):942-6. [QxMD MEDLINE Link].
Vinh DC, Embil JM. Hantavirus pulmonary syndrome: a concise clinical review. South Med J. 2009 Jun. 102(6):620-5. [QxMD MEDLINE Link].
Werker DH, Artsob H. Of mice and mostly men--hantavirus pulmonary syndrome. CMAJ. 1998 Apr 7. 158(7):912-5. [QxMD MEDLINE Link].
Young JC, Hansen GR, Graves TK, et al. The incubation period of hantavirus pulmonary syndrome. Am J Trop Med Hyg. 2000 Jun. 62(6):714-7. [QxMD MEDLINE Link].
Zaki SR, Greer PW, Coffield LM, et al. Hantavirus pulmonary syndrome. Pathogenesis of an emerging infectious disease. Am J Pathol. 1995 Mar. 146(3):552-79. [QxMD MEDLINE Link].
Zavasky DM, Hjelle B, Peterson MC, et al. Acute infection with Sin Nombre hantavirus without pulmonary edema. Clin Infect Dis. 1999 Sep. 29(3):664-6. [QxMD MEDLINE Link].

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Author

David J Cennimo, MD, FAAP, FACP, FIDSA, AAHIVS Associate Professor of Medicine and Pediatrics, Adult and Pediatric Infectious Diseases, Rutgers New Jersey Medical School

David J Cennimo, MD, FAAP, FACP, FIDSA, AAHIVS is a member of the following medical societies: American Academy of HIV Medicine, American Academy of Pediatrics, American College of Physicians, American Medical Association, HIV Medicine Association, Infectious Diseases Society of America, Medical Society of New Jersey, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Coauthor(s)

Zachariah E Hale, MD Resident Physician, Departments of Internal Medicine and Pediatrics, Rutgers New Jersey Medical School

Zachariah E Hale, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

John L Brusch, MD, FACP Corresponding Faculty Member, Harvard Medical School

John L Brusch, MD, FACP is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

Burke A Cunha, MD Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Acknowledgements

Kenneth C Earhart, MD Deputy Head, Disease Surveillance Program, United States Naval Medical Research Unit #3

Kenneth C Earhart, MD is a member of the following medical societies: American College of Physicians, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, and Undersea and Hyperbaric Medical Society

Disclosure: Nothing to disclose.