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Symptoms and Clinical Findings

Symptoms in the human host

Hantavirus Pulmonary Syndrome (HPS)

Hantavirus infection produces two distinctly different clinical manifestations in people.  The form of the disease that occurs in North America is called Hantavirus Pulmonary Syndrome (HPS).  It is associated with infection by certain species of Hantavirus, in particular Sin Nombre virus.  The disease is uncommon in Canada, averaging approximately 3 cases per year.  The majority of Canadian cases have occurred in Alberta. (12, 26)Cough - courtesy of bisolvon.com

HPS initially presents as a flu-like illness, characterized by fever, myalgia and fatigue.  Half of patients will also experience other symptoms early in the disease, such as headache, chills, dizziness, abdominal pain, vomiting, diarrhea and nausea.  The second stage of the illness, the cardiopulmonary phase, occurs four to ten days after initial signs are observed.   The lungs begin to fill with fluid and the patient will experience coughing and shortness of breath. Once this phase is reached, the disease progresses rapidly.  Most patients require hospitalization and placement on a ventilator within 24 hours of first experiencing respiratory signs. (12, 25)

Although morbidity is low, mortality is high, with up to 50% of affected people succumbing to the disease.  Recovery from the illness is prolonged and symptoms can take weeks to months to completely resolve.  Due to the severity of the illness and its zoonotic origin, HPS has been named a notifiable disease in Canada.  If you experience flu-like symptoms or shortness of breath, especially if you have been exposed to rodents or their droppings in the last month, seek medical attention immediately. (12, 26)

Hemorrhagic Fever with Renal Syndrome (HFRS)

The second manifestation of Hantavirus infection is Hemorrhagic Fever with Renal Syndrome (HFRS).  This form of the disease is found in Europe and Asia and is associated with infection by the majority of Hantavirus species.  HFRS is extremely rare in the United States, and has not yet been documented in Canada.   It commonly causes shock and Disseminated Intravascular Coagulation (DIC), as well as kidney dysfunction.  HFRS has a mortality rate of approximately 10%, which is significantly less than what is seen with the pulmonary form of the disease (HPS). (28)

Clinical findings with HPS in humans

There are several pathological developments that are routinely seen in people with Hantavirus Pulmonary Syndrome.  Blood work commonly shows an increase in PCV and reduced albumin.  This is due to the loss of fluid and small proteins from virus-damaged capillaries in the lungs.  Thrombocytopenia is seen in 80% of HPS patients, and it is common to see proliferation of band cells aHistology section pulmonary edema - courtesy of cdc.govs well as atypical lymphocytes. (25)

Pulmonary edema is the most consistent finding.  Mild interstitial pulmonary edema will be seen on radiographs early in the disease, which then progresses to a bilateral alveolar pattern. Pleural effusions commonly occur.  Atypical presentations have been seen in the United States, involving fever and renal insufficiency, rather than pulmonary edema.  These cases were likely caused by Seoul virus, however, which causes HFRS rather than HPS. (25)

On necropsy, the main findings for HPS are pulmonary.  On gross examination, the lungs will be dense, rubbery, and heavier than normal.  There is often yellow, transparent fluid in the pleural cavity.  Histology of the organs will show vascular lesions, with the most common finding being edema and dilation of capillaries.  This is most prominent in the lung, but can also be found in the spleen, liver and lymph nodes.  On histologic section of the lungs, proteinaceous edema in the alveoli and a mild interstitial pneumonia can be seen (see photo at right). (25)

Symptoms and pathology in the rodent hostDeer Mouse - courtesy of stikine.org

Hantavirus infection does not make rodents obviously sick.  For several species of Hantavirus, rodents have been shown to be true asymptomatic hosts.  This means that although viral antigen can be found in several host tissues, including lung, liver, spleen and kidney, pathology resulting from the virus cannot be demonstrated.  These animals are persistently infected, and secrete viral particles in the urine, feces and saliva. Viral antigen can be demonstrated in host tissues for up to a year after infection occurred. (14, 28)

There is evidence, however, that in some species of rodent, Hantavirus infection is associated with demonstrable pathology.  In deer mice infected with Sin Nombre Virus, viral antigen deposition in the pulmonary alveoli is associated with septal edema.  Mononuclear cell infiltration can also be found around the portal tracts in the liver.  Both of these findings are similar to the response seen in people infected with Sin Nombre Virus.  So it appears that at least in deer mice, Hantavirus infection is not truly asymptomatic. (14)