Hantavirus Pulmonary Syndrome

Disease Overview

Hantavirus pulmonary syndrome (HPS) is a rare infectious disease caused by hantaviruses, primarily the Sin Nombre hantavirus (SNV) in most of the United States.¹

The average age of onset for HPS is 38, although individuals of all ages may encounter and develop the disease.²

Transmission most often occurs through direct or indirect (airborne) contact with the saliva or waste products of infected rodents that carry the virus, most commonly deer mice.² Rural populations, in addition to those who work in construction, janitorial, agricultural and pest control jobs, have increased risk for HPS as they have high potential exposure to wild rodents.³

Initial symptoms commonly present three to four weeks (range 1-8 weeks post-hantavirus exposure, and may include fevers, muscle aches (myalgias) and headaches.⁴ Around 3-6 days after this initial phase, the disease may progress rapidly to respiratory distress characterized by cough, shortness of breath,  low blood pressure (hypotension), shock, fluid in the lungs (pulmonary edema) and respiratory failure.^5,6

HPS caused by SNV is rare and there are only around 30 affected individuals per year.¹ The disease is very severe and has a very poor prognosis. There are currently no specific treatments to combat HPS, but supportive care methods targeting the severity of symptoms may help improve the outcome for affected people. For example, oxygen therapy may be used to treat respiratory compromise, while hypotension can be managed with medications similar to dopamine and norepinephrine.⁷ In severely affected individuals, extracorporeal membrane oxygenation (ECMO) may be used as a life-saving measure.⁶

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Synonyms

• HCPS (hantavirus cardiopulmonary syndrome)
• HPS

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Signs & Symptoms

HPS primarily affects adults with the mean age of onset being 38 years.² Common initial  symptoms of HPS are non-specific and include fever, muscle aches, fatigue and headache.⁴ These are likely followed by shortness of breath, rapid breathing (tachypnea) and rapid heart rate (tachycardia).⁴ Additional symptoms such as chills, abdominal pain, dizziness, diarrhea, malaise joint pain (arthralgia), back or chest pain and sweating may also be present.⁴

Hantavirus primarily affects the lungs and kidneys which contributes to respiratory distress, hypotension and shock as the disease advances to the “cardiopulmonary phase”.⁶ Coughing and shortness of breath may occur 4-10 days after initial disease onset, which is characteristic of the more severe cardiopulmonary phase of HPS. Additionally, excess fluid (edema) may accumulate in the lungs leading to low oxygen levels in the blood (hypoxemia).^5,8 HPS, once progressed into the cardiopulmonary phase, carries a 40% mortality rate overall.⁹ One-third of affected people die within the first 48 hours of hospital admission.⁹

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Causes

HPS is caused by viruses of the family Hantaviridae and the genus Orthohantavirus.⁹  In viruses, a family is a broad group of viruses sharing similar characteristics, while a genus is a smaller, more specific group within a family. HPS in the U.S. is primarily caused by the “Sin Nombre hantavirus (SNV)”, a virus within the Orthohantavirus genus and carried primarily by the deer mice (Peromyscus maniculatus).^10,11 The deer mouse is found throughout most of the U.S. except the southeast, with most SNV infections occurring west of the Mississippi river.¹¹

Not all deer mice carry the virus, but those that do not have symptoms.¹¹ People are infected  through indirect or direct contact with an infected rodent’s saliva, feces, urine, or by inhalation of viral-containing aerosol particles.¹² Other hantaviruses known to cause human disease in the U.S. include the New York virus, transmitted by the eastern white-footed mouse, Black Creek Canal virus from the cotton rat in Florida and Bayou virus from the rice field mouse in Texas and Louisiana.¹¹

Additionally, several other hantaviruses have been found in other rodent species in the U.S., though these strains have not yet been detected in humans. In South America, the Andes virus causes severe HPS in Argentina and Chile.² Additionally, Andes virus can spread through human-to-human contact instead of just rodent-to-human transmission.¹³

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Affected populations

HPS caused by SNV is very rare. There were only 850 people identified in the United States between 1993 and 2021 and an average of  around  30 affected individuals per year.¹ In North America, HPS affects males slightly more than females with a little over 60% of reports involving males.^1,2 In the United States, around 74-78% of affected individuals are Caucasian, while around 17-20% of the documented reports involving American Indian Alaskan Native populations.^1,2 Children are affected less frequently, yet experience a briefer timeframe between symptom onset and death.¹⁴ Fewer diagnoses in children may be related to misdiagnosis rather than actual disease incidence.¹⁴ Geographic exposure to rodent droppings appears to be the primary risk factor, as many reports were initially concentrated in the southwestern U.S.¹⁵ Rural populations, in addition to those who work in construction, janitorial, agricultural and pest control jobs, have increased risk due to potential exposure to wild rodents.^3,16

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Disorders with Similar Symptoms

Symptoms of several disorders, particularly forms of pneumonia, can mimic those of HPS. Laboratory tests are essential to differentiate HPS from these disorders.⁸

• Interstitial pneumonia, for example, involves increased interstitial tissue in the lungs and decreased lung function, and often leads to shortness of breath and coughing.⁸
• Eosinophilic pneumonia, which involves inflammation and an increase in a type of white blood cell (eosinophils) in the lungs and blood, presents symptoms such as weight loss, fever, cough and labored breathing. These symptoms can range from mild to severe depending on the extent of lung involvement.¹⁷

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Diagnosis

Hantavirus pulmonary syndrome (HPS) can be difficult to detect early because its symptoms are similar to other respiratory infections like the flu or Q fever. To diagnose HPS, doctors look at symptoms, history of rodent exposure and specific lab tests. These tests can show blood changes like low platelets (thrombocytopenia) and unusual white blood cells such as atypical lymphocytes.⁵

Early symptoms of HPS include sudden high fever (over 101°F), chills and stomach issues.¹⁸ However, as commented above, since these symptoms are not unique, lab tests are needed to confirm the presence of Hantavirus.^18,19,20

The Centers for Disease Control and Prevention (CDC) defines an HPS diagnosis based on: ^18,19

• Symptoms of severe lung disease, such as acute respiratory distress syndrome or ARDS), a condition that occurs when the lungs fill with fluid, making it hard to breathe.
• Lab tests confirming Hantavirus infection, including one of the following:

1. • Hantavirus-specific antibodies (IgM), which are proteins that the body makes to fight infection
   • Rising IgM levels over time to show that the antibodies are actively fighting Hantavirus
   • Hantavirus genetic material (RNA) in blood or tissue samples, because finding the Hantavirus’s RNA, which is the virus’s genetic code, confirms an active infection
   • Hantavirus antigens in lung tissue, because finding antigens (parts of the virus) taken during a biopsy or autopsy confirms the diagnosis

The CDC mentions the use of different tests to detect the virus:²¹

• ELISA (enzyme-linked immunosorbent assay): A test that detects IgM antibodies in the blood
• PCR (polymerase chain reaction): A method that amplifies small amounts of the virus’s RNA to make it easier to find
• Immunohistochemistry (IHC): A process that uses special dyes to highlight viral antigens in tissue samples

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Standard Therapies

There are currently no specific antiviral drugs or vaccines for HPS, so treatment focuses on managing symptoms. Because HPS affects multiple organs, affected people need to be seen by many different specialists that should work together as a team in a coordinated way. Among others, the team of specialists should include experts in infectious disease, pulmonology, hematology, intensive care and neurology.⁹

 Since fluid can quickly build up in the lungs, careful monitoring of fluids, electrolytes and blood pressure is critical. ²² In severe cases, patients may need oxygen therapy or mechanical ventilation. ⁹ A treatment called extracorporeal membrane oxygenation (ECMO) can help in life-threatening cases with a 70% success rate when used early.⁶

Preventive measures include avoiding areas where deer mice leave droppings such as storage sheds, basements and wood piles.¹⁸ People cleaning such areas should wear a fit-tested N95 face mask and rubber gloves and sanitize the area with bleach solution to prevent contact with infectious dust.²³ People having symptoms such as fever, muscle or back pain and headache one to eight weeks after exposure to mouse droppings should  seek immediate medical attention, as HPS can progress rapidly within hours.^2,11

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Clinical Trials and Studies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]

Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/

For information about clinical trials sponsored by private sources, in the main, contact: www.centerwatch.com

For more information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/

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References

1. Reported cases of hantavirus disease. Centers for Disease Control and Prevention. Last edited 06/26/2024. Available at: https://www.cdc.gov/hantavirus/data-research/cases/index.html Accessed April 1, 2025.
2. MacNeil A, Ksiazek TG, Rollin PE. Hantavirus pulmonary syndrome, United States,1993-2009. Emerging infectious diseases. 2011;17(7):1195–1201. doi:https://doi.org/10.3201/eid1707.101306
3. “Hantavirus Pulmonary Syndrome (HPS) Symptoms, Causes and Risk Factors.” Edited by American Lung Association Scientific and Medical Editorial Review Panel, American Lung Association. Available at: www.lung.org/lung-health-diseases/lung-disease-lookup/hantavirus-pulmonary-syndrome/treatment. Accessed April 1, 2025.
4. Hallin GW, Simpson SQ, Crowell RE, et al. Cardiopulmonary manifestations of hantavirus pulmonary syndrome. Crit Care Med. 1996;24(2):252-258. doi:10.1097/00003246-199602000-00012
5. Koster F, Mackow E. Pathogenesis of the hantavirus pulmonary syndrome. Future Virology. 2011;7(1):41-51. doi:10.2217/fvl.11.138
6. Wernly JA, Dietl CA, Tabe CE, et al. Extracorporeal membrane oxygenation support improves survival of patients with Hantavirus cardiopulmonary syndrome refractory to medical treatment. Eur J Cardiothorac Surg. 2011;40(6):1334-1340. doi:10.1016/j.ejcts.2011.01.089
7. Jonsson CB, Hooper J, Mertz G. Treatment of hantavirus pulmonary syndrome. Antiviral Res. 2008;78(1):162-169. doi:10.1016/j.antiviral.2007.10.012
8. 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;13(3):172-177. doi:10.1097/00005382-199807000-00002
9. Moore RA, Griffen D. Hantavirus Pulmonary Syndrome. [Updated 2024 Apr 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513243/ Accessed April 1, 2025.
10. 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;52(2):117-123. doi:10.4269/ajtmh.1995.52.117
11. Mills JN, Amman BR, Glass GE. Ecology of hantaviruses and their hosts in North America. Vector Borne Zoonotic Dis. 2010;10(6):563-574. doi:10.1089/vbz.2009.0018
12. Ulloa-Morrison R, Pavez N, Parra E, et al. Critical care management of hantavirus cardiopulmonary syndrome. A narrative review. Journal of Critical Care. 2024;84:154867. doi:10.1016/j.jcrc.2024.154867
13. Toledo J, Haby MM, Reveiz L, Sosa Leon L, Angerami R, Aldighieri S. Evidence for human-to-human transmission of Hantavirus: A systematic review. The Journal of Infectious Diseases. 2021;226(8). doi:10.1093/infdis/jiab461
14. Thorp L, Fullerton L, Whitesell A, Dehority W. Hantavirus pulmonary syndrome: 1993–2018. Pediatrics. 2023;151(4) doi:10.1542/peds.2022-059352
15. Knust B, Rollin PE. Twenty-year summary of surveillance for human hantavirus infections, United States. Emerg Infect Dis. 2013;19(12):1934-1937. doi:10.3201/eid1912.131217
16. Jonsson CB, Figueiredo LT, Vapalahti O. A global perspective on hantavirus ecology, epidemiology, and disease. Clin Microbiol Rev. 2010;23(2):412-441. doi:10.1128/CMR.00062-09
17. Mertz GJ, Hjelle B, Crowley M, Iwamoto G, Tomicic V, Vial PA. Diagnosis and treatment of new world hantavirus infections. Curr Opin Infect Dis. 2006;19(5):437-442. doi:10.1097/01.qco.0000244048.38758.1f
18. CDC. Clinician Brief: Hantavirus Pulmonary Syndrome (HPS). Published 05/23/2024. Available at: https://www.cdc.gov/hantavirus/hcp/clinical-overview/hps.html Accessed April 1, 2025.
19. Hantavirus Pulmonary Syndrome (HPS) 2015 Case Definition | CDC. National Notifiable Diseases Surveillance System (NNDSS). Published 4/16/2021.Available at: https://ndc.services.cdc.gov/case-definitions/hantavirus-pulmonary-syndrome-2015/. Accessed April 1, 2025.
20. Vial PA, Ferrés M, Vial C, et al. Hantavirus in humans: a review of clinical aspects and management. Lancet Infectious Diseases. 2023;23(9). doi:10.1016/s1473-3099(23)00128-7
21. Munir N, Jahangeer M, Hussain S, et al. Hantavirus diseases pathophysiology, their diagnostic strategies and therapeutic approaches: A review. Clinical and Experimental Pharmacology and Physiology. 2020;48(1):20-34. doi:10.1111/1440-1681.13403
22. Akram SM, Mangat R, Huang B. Hantavirus cardiopulmonary syndrome (Archived). In: StatPearls. Treasure Island (FL): StatPearls Publishing; February 25, 2023.
23. “Spring Cleaning? Protect Yourself against Hantavirus.” San Juan County, WA. 05/06/2024. Available at:  www.sanjuancountywa.gov/CivicAlerts. Accessed April 1, 2025.

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