Hantavirus

Background

• Enveloped, single-stranded RNA virus within the order Bunyavirales, family Hantaviridae
• Acquired by inhalation of contaminated rodent urine or feces, and possibly by bites
  • In North America, it is carried by the deer mouse (most common in NA, transmits Sin Nombre), meadow vole (also present, transmits Prospect Hill), and white-footed mouse (also present, transmits New York); also cotton rat, rice rat, shrew, and mole
• Essentially worldwide, though New World viruses tend to cause hantavirus pulmonary syndrome and Old World viruses tend to cause hemorrhagic fever with renal syndrome
  • In Canada, no cases have been described east of Manitoba
  • No cases of HPS have been described in Ontario since it became reportable in 2001
  • About 4 or 5 new cases annually from southern rural parts of BC, Alberta, Saskatchewan, and Manitoba
• Incidence of HPS peaks in summer months (in North America)

Clinical Manifestations

• Incubation period of 14 days (range 5 to 42 days)

Hemorrhagic Fever With Renal Syndrome (HFRS)

• Caused by Old World hantaviruses, such as Hantaan, Dobrava, Seoul, Puumala, and other Old World hantaviruses
• Fever, thrombocytopenia, and AKI caused by acute interstitial nephritis
• Also headache, abdominal pain, low back pain, dizziness, and blurred vision
• Can have conjunctival injection and petechiae on upper trunk and soft palate
• Febrile phase lasts 4 to 7 days of acute, severe illness, followed by hypotensive, oliguric, and polyuric phases
• Leukocytosis and thrombocytopenia seen on CBC
• Mortality up to 5%

Hantavirus Pulmonary Syndrome (HPS)

• Caused by New World hantaviruses such as Sin Nombre, Bayou, and Black Creek Canal
• Incubation for 2 to 3 weeks
• Prodromal phase
  • Lasts 2 to 8 days
  • Nonspecific syndrome of fevers, chills, myalgias (including severe myalgias)
  • Continues to develop, with headache, vomiting, weakness, abdominal pain (can be severe), and sometimes diarrhea
  • Typically does not include upper respiratory symptoms, except cough and, in children, pharyngitis
  • Some strains can cause conjunctivitis, facial flushing, and a petechial rash
  • Thrombocytopenia is common, and can see elevated LDH
• Cardiopulmonary phase
  • Characterized by capillary leak
  • Usually characterized by non-productive cough, with rapid onset of shock, coagulopathy, pulmonary edema (including ARDS), bronchorrhea, and arrhythmias
  • Chest x-ray almost always shows bilateral infiltrates suggestive of ARDS
  • Elevated hematocrit (from third-spacing), leukocytosis, atypical lymphocytes, thrombocytopenia (with severity predicting mortality), prolonged PTT, and mild elevations in AST and LDH
    • Triad of a left shift, lymphoid blasts >10%, and thrombocytopenia, is a helpful diagnostic triad
• Oliguric and diuretic phases
  • Oliguria can last 3 to 7 days, followed by diuresis of variable duration
  • Creatinine may be elevated, but not as severe as HFRS
• Convalescent phase
  • Initial recovery can be dramatically fast (over days), but complete recovery can be slow
• Case fatality rate is about 35%

Differential Diagnosis

• HPS: other causes of unexplained pulmonary edema

Diagnosis

• Serology usually positive by presentation (both IgM and IgG)
• PCR or immunohistochemical staining are both possible
• Viral culture is difficult
• Of note, it is a biosafety risk group 3 pathogen, which requires special precautions in the lab

HPS Case Definition (CDC)

• Clinical criteria
  • Fever greater than 38.3°C with prodrome of fever, chills, myalgia, headache, and GI symptoms, with one or more of:
    • Bilateral diffuse interstitial edema
    • Clinical diagnosis of ARDS
    • Unexplained respiratory illness resulting in death where autopsy demonstrates noncardiogenic pulmonary edema
    • Healthcare documentation listing a diagnosis of hantavirus pulmonary syndrome
    • Death certificate listing hantavirus pulmonary syndrome
• Laboratory criteria requires one of:
  • Reactive IgM, or rising titres of IgG
  • PCR/NAAT
  • Antigen by immunohistochemistry on biopsy
• A confirmed case requires both clinical and laboratory criteria

Management

• Supportive