The person presenting this package may have been exposed to Hantavirus (Sin Nombre virus) during field research on ______________ (date) in Robinson Forest, Kentucky This research involved carrying traps containing small mammals, including rodents. Participants were trained in the proper methods and precautions to be taken (protective gloves, handwashing, not contaminating clothing) and were informed that should they develop a fever or respiratory illness within 45 days of this field research, they should seek medical care due to the potentially serious nature of hanta pulmonary syndrome (HPS)

GENERAL DESCRIPTION OF AGENT: Hantavirus is a zoonotic agent transmitted to humans by exposure by excreta of infected rodents. Incubation period is 1-5 weeks, and cases have been reported throughout the United States, though it is more prevalent in the western USA. There were 2 cases in Randolph County, West Virginia in 2004. Reported in MMWR:
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5346a3.htm

More information may be accessed at:
http://www.cdc.gov/ncidod/diseases/hanta/hps/noframes/phys/printtechsection.htm

SYMPTOMS: Prodrome of fever, chills, Myalgia, headache, cough and gastrointestinal symptoms. Rapid progression after the prodrome to pulmonary edema and nonischemic, cardiogenic shock.

MORTALITY: in the USA: 37%

CLINICAL MANIFESTATIONS: Presentation and First Evaluation: Patients with HPS typically present in a very nonspecific way with a relatively short febrile prodrome lasting 3-5 days. In addition to fever and myalgias, early symptoms include headache, chills, dizziness, non-productive cough, nausea, vomiting, and other gastrointestinal symptoms. Malaise, diarrhea, and lightheadedness are reported by approximately half of all patients, with less frequent reports of arthralgias, back pain, and abdominal pain. Patients may report shortness of breath, (respiratory rate usually 26 - 30 times per minute). Typical findings on initial presentation include fever, tachypnea and tachycardia. The physical examination is usually otherwise normal.

HPS CLINICAL PRESENTATION

The diagnosis is seldom made at this stage, as cough and tachypnea generally do not develop until approximately day seven. Once the cardiopulmonary phase begins, however, the disease progresses rapidly, necessitating hospitalization and often ventilation within 24 hours.

Signs that make a diagnosis of HPS unlikely include rashes, conjunctival or other hemorrhages, throat or conjunctival erythema, petechiae, and peripheral or periorbital edema.

CLINICAL CASE DEFINITION: An illness characterized by one or more of the following clinical features:
A febrile illness (i.e., temperature greater than 101.0° F {greater than 38.3° C}) characterized by bilateral diffuse interstitial edema that may radiographically resemble ARDS, 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 FINDINGS: Acute respiratory distress syndrome on chest radiograph

Thrombocytopenia and hemoconcentration, left shift in WBC, neutrophilic leukocytosis, thrombocytopenia, circulating immunoblasts

Confirmation by serology

Additional confirmation by immunohistochemistry or reverse transcriptase-polymerase chain reaction

LABORATORY CRITERIA FOR DIAGNOSIS: Detection of hantavirus-specific immunoglobulin M or rising titers of hantavirus-specific immunoglobulin G, or

Detection of hantavirus-specific ribonucleic acid sequence by polymerase chain reaction in clinical specimens, or

Detection of hantavirus antigen by immunohistochemistry.

CLINICAL ASSESSMENT: If a hantavirus infection is suspected, a CBC and blood chemistry should be repeated every 8 to 12 hours. A fall in the serum albumin and a rise in the hematocrit may indicate a fluid shift from the patient's circulation into the lungs. The white blood cell count tends to be raised with a marked left shift. The percentage of white blood cells precursors may be as high as 50% and atypical lymphocytes are frequently present, usually at the time of onset of pulmonary edema. In about 80% of individuals with HPS, the platelet count is below 150,000 units. A dramatic fall in the platelet count may herald a transition from the prodrome to the pulmonary edema phase of the illness.

The most severe cases of HPS develop disseminated intravenous coagulation (DIC), but, unlike the hantavirus-related hemorrhagic fevers (HFRS) seen in Asia, this is uncommon.

PROPHYLATIC TREATMENT: There is no vaccine or specific antiviral treatment

TREATMENT: 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.

TAKE-HOME MESSAGE FOR CARE PROVIDERS:
Rapid transfer to ICU
Careful monitoring
Fluid balance
Electrolyte balance
Blood pressure

To obtain health care advice if you develop a fever or respiratory problems within 45 days of your field research:

Students should first try to reach University Health Service (UHS) by phone:

References:
1. All About Hantaviruses, CDC, Special Pathogens Branch, http://www.cdc.gov/ncidod/diseases/hanta/hps/noframes/phys/printtechsection.htm

2. Two Cases of Hantavirus Pulmonary Syndrome: Randolph County, West Virginia, July, 2004.Morbidity and Mortality Weekly Review, November 26, 2004, 53(46): 1086-1089.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5346a3.htm

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