Hantavirus Pulmonary Syndrome

Updated: Oct 27, 2015
  • Author: Burke A Cunha, MD; Chief Editor: Michael Stuart Bronze, MD  more...
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Hantaviruses are RNA zoonotic viruses that are transmitted to humans from rodent hosts. They are members of the family Bunyaviridae that are generally spherical in shape (70-100 nm in diameter). The lipid envelope contains 2 major glycoproteins. On electron microscopy, characteristic inclusion bodies and a distinctive gridlike pattern can be seen. Examples are distributed worldwide. Hantaan virus, Seoul Hantavirus, Dobrava/Belgrade Hantavirus, and Puumala virus produce the syndrome of hemorrhagic fever with renal failure syndrome (HFRS).

In 1993, an unusual cluster of deaths occurred in the southwest United States. The outbreak was characterized by a febrile prodrome that was followed by acute respiratory failure and finally death due to circulatory collapse. This outbreak was initially named Four Corners disease because it seemed to be focused at the juncture of the borders of 4 states. Physicians from the Indian Health Service and the Centers for Disease Control and Prevention determined that a rodent vector was responsible for this infection. This disease was subsequently renamed Hantavirus pulmonary syndrome (HPS).

The Sin Nombre virus (SNV) is the Hantavirus species primarily responsible for HPS. However, closely related strains (Bayou and Black Creek Canal viruses), found in the southeastern United States, may produce a variant of the syndrome that is characterized by a greater degree of renal failure. The New York virus is the cause of cases of HPS in New York and Rhode Island. Retrospective analyses indicate that HPS has been present in North America since as early as 1959.

Hantavirus has now been reported in more than 24 states in the continental United States, Canada, and South America.



The basic pathophysiological lesion of HPS, and indeed of all Hantavirus infections, is a generalized increase in capillary permeability that results from endothelial damage. This injury appears to be a consequence of the host's immunological response to viral antigens that have penetrated the endothelium by means of the cells' own integrins. The onset of clinical symptoms is correlated with the development of specific antibodies to the virus. The increased capillary permeability gives rise to widespread protein-rich edema. The particular organs affected are related to the specific species of Hantavirus. In HFRS, a large outpouring of edema fluid flows into the retroperitoneum and is associated with hemorrhage and necrosis. Individuals with HPS have edema concentrated in the pleura and lungs.

The endothelial cells appear swollen. Lung examination findings reveal an interstitial pneumonitis made up of edema fluid, mononuclear cells, and lymphocytes with polymorphonuclear leukocytes. Hyaline membranes appear along with a proliferation of type 2 alveolar lining cells. As the disease progresses, the alveolar septa become increasingly fibrotic. The spleen in patients with HPS shows infiltration of immunocompetent cells within the red pulp and the periarteriolar sheaths.

Severe cases of HPS present clinically as noncardiogenic pulmonary edema. The pathophysiology of the pulmonary findings is that of a pulmonary capillary leak syndrome. The heart is not directly affected. The pulmonary capillary leak syndrome is the primary underlying pathophysiological defect responsible for both cardiopulmonary and renal dysfunction. Prerenal azotemia is due to the inadequate intravascular volume of the hypotensive patient and not to direct infection. Hantavirus particles are not found within the renal tubular cells of patients with HPS. Hypoxia also contributes to the state of shock.




United States

HPS occurs primarily in the fall, when small rodents (eg, field mice) inhabit human dwellings to protect themselves from the cold weather. In the wild, many small rodents (eg, voles, white-footed deer mice) also transmit the virus. Inhalation of infected aerosolized rodent urine or dried excreta can lead to infection with HPS. Human-to-human transmission of HPS has not been reported in the United States, nor have nosocomial infections been reported. HPS is a zoonosis and parallels the distribution of the associated rodent vectors. The climactic conditions of El Niño promote the transmission of the causative virus.


Hantavirus infections occur in eastern Asia, Latin America, and North America, including Canada. However, HPS seems to be restricted to North and South America. While human-to-human transmission has not been reported in the United States, outbreaks of HPS reported from Argentina were possibly associated with human-to-human transmission. [1, 2, 3]

One report suggests clinical and pathological findings in 3 cases of severe European Puumala hantavirus infection were similar to those found in American hantavirus patients and met the case definition of HPS. [4]


Initially, HPS was thought to be uniformly lethal. Current experience indicates that HPS represents a wide spectrum of clinical disease, from mild infection in ambulatory patients to severe infection requiring mechanical ventilation. The fatality rate is approximately 50%.


HPS has no race predilection.


HPS has no sex predilection; however, because of cultural sex roles, males are more likely than females to encounter small rodents in hunting and/or field exposures.


HPS is conspicuously absent among very young persons and very elderly persons. This absence may reflect their relative lack of contact with rodents in the outdoor setting.



The small rodent vectors of Hantavirus are thought to be lifelong carriers of the virus and are not subject to infection by the virus. The deer mouse is the reservoir for SNV in the western United States. The white-footed mouse serves that role for SNV and the New York virus in the northeastern United States.