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)

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%

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%

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

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