Hantavirus Pulmonary Syndrome (HPS) : Treatment

by CDC

(Page 10 of 17)

There is no specific treatment or cure for hantavirus infection. Treatment of patients with HPS remains supportive in nature. Patients should receive appropriate, broad-spectrum antibiotic therapy while awaiting confirmation of a diagnosis of HPS. Care during the initial stages of the disease should include antipyretics and analgesia as needed.

If there is a high degree of suspicion of HPS, patients should be immediately transferred to an emergency department or intensive care unit (ICU) for close monitoring and care. Patients presenting with fulminant illness due to HPS have a poor prognosis despite ICU care. ICU management should include careful assessment, monitoring and adjustment of volume status and cardiac function, including inotropic and vasopressor support if needed. Fluids should be administered carefully due to the potential for capillary leakage. Supplemental oxygen should be administered if patients become hypoxic. Equipment and materials for intubation and mechanical ventilation should be readily available since onset of respiratory failure may be precipitous.

Intravenous ribavirin, a guanosine analogue, has not been shown to be effective for treatment of HPS despite its effects on a related disease, hemorrhagic fever with renal syndrome (HFRS), which is caused by Old World hantaviruses. Controlled trials showed a reduction in case-fatality for HFRS patients treated with ribavirin. However, despite in vitro activity of ribavirin against SNV, neither an open-label trial conducted during the 1993 outbreak nor an attempted placebo-controlled trial demonstrated clinical benefit for HPS. Ribavirin is not recommended for treatment of HPS and is not available for this use under any existing research protocol.

Histopathology

No single pathognomonic lesion is found that would permit certain histopathologic diagnosis of HPS. In fact, the incipient stages of ARDS can create a picture of pulmonary edema similar to HPS. However, the total picture is rather distinctive. Pathology in HPS patients is characterized mainly by pulmonary findings, as well as findings in the spleen, liver, and lymph nodes.

Grossly, the lungs are dense, rubbery and heavy, usually weighing twice as much as the average lung. They are often found floating in a pool of yellow serous fluid within the pleural cavity.

The pathologic lesions are primarily vascular with variable degrees of generalized capillary dilation and edema. Morphologic changes of the endothelium are uncommon and, when present, consist of prominent and swollen endothelial cells. Histopathologic lesions are mainly seen in the lung and spleen. In most cases, the lungs reveal a mild to moderate interstitial pneumonitis with variable degrees of congestion, edema, and mononuclear cell infiltration. The cellular infiltrate is composed of small and enlarged mononuclear cells with the appearance of immunoblasts. Focal hyalin membranes are observed, as well as extensive intraalveolar edema and fibrin. Neutrophils are scanty, and the respiratory epithelium is intact in typical cases, with no evidence of cellular debris, nuclear fragmentation, or type II pneumocyte hyperplasia.

Among patients who die after a longer-than-average course of the disease, and in lung biopsy specimens from survivors, the histopathologic changes are more characteristic of exudative and proliferative stages of diffuse alveolar damage. In these cases, proliferation of reparative type II pneumocytes, severe edematous and fibroblastic thickening of the alveolar septa with severe airspace disorganization, and distortion of lung architecture can be seen.

Other typical histopathologic findings are seen in lymphoid tissues of HPS patients. These include the presence of immunoblasts within the red pulp and periarteriolar sheaths of the spleen and paracortex, within sinuses of lymph nodes, and in the peripheral blood.

Pathology and Pathogenesis

Immunohistochemistry analysis has shown that viral antigens are distributed primarily within the endothelium of capillaries throughout various tissues from patients with HPS. Marked accumulations of hantaviral antigens are seen in the pulmonary microvasculature and in follicular dendritic cells within the lymphoid follicles of spleen and lymph nodes. Hantaviral nucleic acids can also be localized to endothelial and inflammatory cells in tissues from HPS cases by using in situ hybridization. Electron micrographic studies confirm the infection of endothelial cells and macrophages in the lungs of HPS patients. Typical hantaviral inclusions are seen frequently in pulmonary endothelial cells, and their identity can be confirmed by immunolabeling. In the heart, endothelial staining is mainly in the capillaries of the myocardium and varies from focal immunostaining in some cases to diffuse and extensive staining in others. Occasionally, staining of endothelial cells lining the endocardium is observed.

Functional impairment of vascular endothelium is central to the pathogenesis of HPS. However, the pathogenesis of HPS is complex, and a myocardial depressant may contribute significantly to the mortality of this disease. It is unclear how the shock syndrome relates to factors such as viral distribution and immunologic and pharmacological mediators of capillary permeability. There appears to be compartmentalization of a selective immune response in the lungs of HPS patients in combination with extremely high levels of viral antigens in the pulmonary vasculature. This feature suggests that the mechanism of inflammatory cell recruitment in the lungs of HPS patients may result from specific attraction and adherence of a selective population of inflammatory cells to an activated pulmonary microvascular endothelium.

About the Author

www.cdc.gov
The Centers for Disease Control and Prevention (CDC) is one of the 13 major operating components of the Department of Health and Human Services (HHS), which is the principal agency in the United States government for protecting the health and safety of all Americans and for providing essential human services, especially for those people who are least able to help themselves.