eMedicine Specialties > Infectious Diseases > Lower Respiratory Tract Infections

Hantavirus Pulmonary Syndrome

Author: 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
Contributor Information and Disclosures

Updated: Jun 25, 2008

Introduction

Background

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 BlackCreekCanal 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.

Pathophysiology

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.

Frequency

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.

International

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, an outbreak of HPS reported from Argentina was possibly associated with human-to-human transmission.1,2

Mortality/Morbidity

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%.

Race

HPS has no race predilection.

Sex

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.

Age

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.

Breed

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.

Clinical

History

  • The incubation period of Hantavirus pulmonary syndrome (HPS) ranges from 1-4 weeks. HPS has been divided into 3 clinical phases: (1) the prodromal phase, (2) the cardiopulmonary phase, and (3) the convalescent phase.
    • Prodromal symptoms resemble those of many viral illnesses, including fever, headache, and myalgias. Vomiting, diarrhea, and abdominal pain are common. Because symptoms initially referable to the respiratory tract are minimal or absent, the physician may conclude that the patient has viral gastroenteritis. Neurologic symptoms, except dizziness, are uncommon. This phase lasts 3-5 days.
    • The cardiopulmonary phase is initiated by dyspnea, nonproductive cough, and circulatory collapse. This stage lasts only 24-48 hours. Seventy-five percent of patients with pulmonary edema require mechanical ventilation. Oliguric renal failure is uncommon. When it does occur, it is due to acute tubular necrosis (ATN), as compared to the renal tubular cell damage caused by the endotheliosis observed in hemorrhagic fever with renal failure syndrome (HFRS).
    • Resolution of the cardiopulmonary stage of HPS is heralded by the onset of the significant diuresis. After this occurs, the patient improves quite rapidly (ie, convalescent phase). The chronic sequelae of HPS are minimal.

Physical

  • Physical findings, reported in 80-90% of patients, include fever, tachypnea, tachycardia, and rales.
  • Upon presentation, hypotension is found in only one third of patients.
  • Rash is quite uncommon.

Causes

  • Sin Nombre virus (SNV) is thought to cause most cases of HPS in the United States.

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
References
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Further Reading

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Keywords

hantavirus pulmonary syndrome, hantaviruses, Bunyaviridae, bunyaviruses, Sin Nombre virus, SNV, HPS, lung infection, lung disease, rodent infestation, zoonotic, zoonoses, Bayou virus, Black Creek Canal virus, New York virus, viral infection, acute respiratory failure, circulatory collapse, Hantaan virus, Seoul Hantavirus, Dobrava/Belgrade Hantavirus, Puumala virus, hemorrhagic fever with renal syndrome, HFRS, hemorrhagic fever with renal failure syndrome, Four Corners disease

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Contributor Information and Disclosures

Author

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, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Medical Editor

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.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

John L Brusch, MD, FACP, Assistant Professor of Medicine, Harvard Medical School; Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health Alliance
John L Brusch, MD, FACP is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD, Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center
Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, Association of Professors of Medicine, Association of Program Directors in Internal Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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