Hantavirus Pulmonary Syndrome

Updated: Oct 01, 2018
  • Author: David J Cennimo, MD, FAAP, FACP, AAHIVS; Chief Editor: Michael Stuart Bronze, MD  more...
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Overview

Background

In May 1993, an unusual cluster of deaths occurred in the southwestern United States. The deaths were characterized by a febrile prodrome that preceded acute respiratory failure and shock. Physicians from the Indian Health Service and the Centers for Disease Control and Prevention (CDC) determined that a rodent vector was responsible for the infection and identified the responsible virus as a member of the Hantavirus family.

Sin Nombre virus (SNV), as it is now known, is the primary agent responsible for Hantavirus pulmonary syndrome (HPS) and the deadliest member of the Hantavirus family. However, there are numerous other pathogenic hantaviruses. The New York virus has been identified as the cause of HPS in New York and Rhode Island, and the Bayou and Black Creek Canal viruses, found in the southeastern United States, produce a variant of the syndrome that includes a greater degree of renal failure. The more distantly related Hantaan, Seoul, Dobrava/Belgrade, and Puumala hantaviruses produce a distinct syndrome of hemorrhagic fever and renal failure (HFRS).

The hantaviruses are RNA zoonotic viruses that are generally spherical in shape, measuring 70-100 nm in diameter, and can be identified by inclusion bodies and distinctive gridlike patterns on electron microscopy. They are transmitted to humans from rodent hosts, including possibly from pet rets, [1] but, except for the Andes hantavirus, have not been shown to be capable of human-to-human transmission.

Retrospective analyses indicate that HPS has been present in North America since as early as 1959, and Hantavirus infections have now been reported in at least 32 states in the United States, as well as in Canada and South America.

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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.

HPS can 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.

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Epidemiology

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, outbreaks of HPS reported from Argentina were possibly associated with human-to-human transmission. [2, 3, 4]

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. [5]

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 for the complete syndrome is approximately 50%.

Recent studies have suggested that asymptomatic Hantavirus infection may be quite common, with some populations showing up to 4% seropositivity for anti-Hantavirus antibodies. [6]

Race

HPS has no racial predilection.

Sex

HPS has no sexual 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. However, infections in these age groups appear to be more deadly. [7]

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Breed

The small rodent vectors of Hantavirus are thought to be lifelong carriers of the virus and are not subject to symptomatic infection by the virus. The deer mouse (Peromyscus maniculatus) is the primary reservoir for SNV in the western United States. Some attention has also been given to the cactus mouse (Peromyscus eremicus) in this region. The white-footed mouse (Peromyscus leucopus) serves that role for SNV and the New York virus in the northeastern United States. [8]

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Prognosis

The prognosis of HPS varies, although it appears to correlate with the severity of disease. It does not appear to correlate with viral load.

Mild cases of HPS are typically nonfatal, and patients can be expected to make a full recovery. Most patients who recover from near-fatal HPS do not have any residual cardiopulmonary disease, although recovery time may be substantially longer. Superinfection has been observed in more severe cases.

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Patient Education

The CDC has provided patient education materials for the prevention of Hantavirus pulmonary syndrome in hikers and campers.

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