Diagnosis of hantavirus infection in humans

Abstract

Rodent-borne hantaviruses (family Bunyaviridae, genus Hantavirus) cause hantavirus pulmonary syndrome in the Americas and hemorrhagic fever with renal syndrome in Europe and Asia. The viruses are transmitted to humans mainly by inhalation of virus-contaminated aerosols of rodent excreta and secreta. Classic clinical hemorrhagic fever with renal syndrome occurs in five phases: fever, hypotension, oliguria, polyuria, and convalescence. Hantavirus pulmonary syndrome is a severe acute disease that is associated with respiratory failure, pulmonary edema and cardiogenic shock. The diagnosis of hantavirus infections in humans is based on clinical and epidemiological information as well as laboratory tests. We review diagnosis for hantavirus infections based on serology, PCR, immunochemistry and virus culture.

Keywords:

• differential diagnosis
• epidemiology
• hantavirus
• reservoir
• symptoms

Acknowledgements

The authors would like to thank JN Mills for critical review of the manuscript.

Financial and competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Hantaviruses are transmitted by rodents, humans become infected by inhaling aerosols of excreta and urine.

• Hantaviruses cause hemorrhagic fever with renal syndrome in Europe and Asia and with cardiopulmonary syndrome in the Americas.

• The clinical course of HPS can be basically divided into three periods: a febrile prodrome, a cardiopulmonary stage and the convalescence. There is 14–17 days incubation period after exposure, which is followed by the prodrome phase, which usually lasts for 3–6 days with myalgia, malaise and fever of abrupt onset in the absence of cough and coryza. Additional symptoms seen at early stages could include mainly gastrointestinal manifestations, headache and chills.

• Laboratory abnormalities include increased hematocrit, thrombocytopenia with neutrophilia and relative lymphopenia. The first to appear is thrombocytopenia, which can anticipate the respiratory failure of 1 or 2 days. Leukocytosis is later and more specific for progression to severe cases. There are changes in blood chemistry, increased lactate dehydrogenase and transaminases.

• Detection of antigens or virus RNA is essential for early diagnosis in patients with hantavirus. Hantaviruses N-protein is the most abundant and conserved structural protein in infected cells and virions and it is the target commonly selected for the detection of IgG or IgM antibodies. Therefore, hantaviruses N-protein is more suitable for the development of monoclonal antibodies in acute or convalescent patients.

• Detection of RNA viral by RT-PCR is required to confirm clinical or post-mortem cases.

• Viral isolation is difficult and requires biosafety 3 and 4 laboratories (BSL-3/4).

• The differential diagnosis of this syndrome in tropical countries include several atypical pneumonia, influenza, heart failure, malaria, dengue, arenavirus, leptospirosis and rikettsia.