HANTAVIRUS PULMONARY SYNDROME

General Goal: To know the major cause(s) of  Hantavirus Pulmonary Syndrome, how it is transmitted, and the major manifestations of the disease.

Specific Educational Objectives: The student should be able to:

1. describe the common means of transmission of these diseases in general and for HPS.

3. describe the major manifestations of these diseases and for HPS.

4. describe the clinical case definition of HPS.

4. describe how you diagnose, treat and prevent HPS.

Reading: MEDICAL MICROBIOLOGY by P.R. Murray, K.S. Rosenthal, and M.A. Pfaller, 6th Edition. pp. 622-623.

Lecture: Dr. Neal R. Chamberlain

Overview

Hantavirus pulmonary syndrome is a relatively new disease reported in the U.S. The first cases of hantavirus pulmonary syndrome occurred in 1993 and were in the four- corner region of the United States in Arizona, Utah, Colorado, and New Mexico. This viral infection can cause significant pulmonary edema, and although relatively rare has a high mortality rate (35%).

Etiology

The virus responsible for hantavirus pulmonary syndrome is a new-world hantavirus called Sin Nombre virus.

Manifestations

Sin Nombre virus causes cardiopulmonary signs and symptoms that have been called hantavirus pulmonary syndrome (Table Endo-2).

Table Endo-2. Signs and Symptoms of Hantavirus Pulmonary Syndrome
Stage or Phase of Disease	Signs and Symptoms	Comments
Prodrome	Fever, myalgias, headache, chills, dizziness, nausea, and vomiting	Respiratory tract symptoms are minimal or absent and, thus, the physician may conclude that the patient has viral gastroenteritis. This phase lasts 3–5 days
Late or cardiopulmonary phase (lasts only 24–48 hours)	Shortness of breath, cough, fever, tachypnea, tachycardia, and rales; chest radiographs usually show a pattern of noncardiac pulmonary edema: The cardiac silhouette is not enlarged Perihilar haziness (“shaggy heart” sign) is characteristic Interstitial edema due to pulmonary capillary leak, which manifests as peribronchial cuffing or Kerley B lines	Cough and tachypnea generally do not develop until about day 7. Most patients with pulmonary edema require mechanical ventilation
Convalescence	Resolution of the cardiopulmonary stage is heralded by the onset of the significant diuresis	After diuresis, the patient improves quite rapidly

Epidemiology

• Cases of hantavirus pulmonary syndrome have been reported in 31 different states in the United States.
• A total of 465 cases of the disease were reported in the United States from 1993 to March 2007. Around 30-40 cases of hantavirus pulmonary syndrome are
• Sin Nombre virus is present in animal urine or feces from mice. The virus is transmitted to humans following aerosolization of murine urine or feces.

Pathogenesis

Portals of entry for the Sin Nombre virus include the respiratory and digestive tracts. Viral multiplication occurs in the endothelial cells. Viremia and fever occur 2–14 days after infection.

Viral antigens can be seen within the endothelium of capillaries throughout various tissues of the patient with hantavirus pulmonary syndrome. High concentrations of hantaviral antigens are seen in the pulmonary microvasculature and in follicular dendritic cells within the lymphoid follicles of the spleen and lymph nodes. Typical hantaviral inclusions are seen frequently in pulmonary endothelial cells. Antibodies produced to the hantaviral antigens damage the endothelial cells and increase capillary permeability. The increased capillary permeability in the lungs results in leakage of protein-rich plasma from the capillaries into the lungs and the pleura. This leakage causes the cardiopulmonary signs and symptoms detailed in Table Endo-2.

Diagnosis

A clinical case definition has been developed for diagnosis of patients with hantavirus pulmonary syndrome and is described in Table Endo-3. The white blood cell count of patients with hantavirus pulmonary syndrome is usually elevated, with a marked left shift (bandemia). White blood cell precursors (band cells) may be as high as 50%, and atypical lymphocytes are frequently present. Atypical lymphocytes usually are observed at the onset of pulmonary edema. The platelet count in about 80% of individuals with hantavirus pulmonary syndrome is below 150,000. A dramatic decrease in the platelet count indicates a transition from the prodrome to the pulmonary edema phase (cardiopulmonary phase) of the illness. Early in the disease, chest radiographs show interstitial pulmonary edema, which progresses to alveolar edema with severe bilateral involvement. Pleural effusions are common and can be large enough to be observed in chest radiographs.

Table 27-3. Clinical Definition of Hantavirus Pulmonary Syndrome

Hantavirus pulmonary syndrome is an illness characterized by one or more of the following clinical features:

A febrile illness (> 38.3°C) with bilateral diffuse interstitial edema that may radiographically resemble adult respiratory distress syndrome, with respiratory compromise requiring supplemental oxygen, developing within 72 hours of hospitalization, and occurring in a previously healthy person.

An unexplained respiratory illness resulting in death, with an autopsy examination demonstrating noncardiogenic pulmonary edema without an identifiable cause.

Laboratory criteria for diagnosis include detection of hantavirus-specific IgM or rising titers of hantavirus-specific IgG, or detection of hantavirus-specific RNA sequence by PCR in clinical specimens, or detection of hantavirus antigen by immunohistochemistry.

IgM, immunoglobulin M; IgG, immunoglobulin G; RNA, ribonucleic acid; PCR, polymerase chain reaction.

Therapy and Prevention

Treatment of hantavirus pulmonary syndrome involves supportive care. Improved sanitation standards and control of the rodent populations is important in preventing this disease.

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