Hantavirus

Two major groups of hantaviruses are recognized based on their clinical presentation. The first group includes Sin Nombre Virus (SNV), which causes hantavirus pulmonary syndrome. A second group of hantaviruses includes Seoul, Hantaan, Dobrava, and Puumala viruses. This group of hantaviruses causes hemorrhagic fever with renal syndrome, which is not commonly seen in the United States. Sin Nombre virus causes the majority of infections in the United States.

Hantavirus pulmonary syndrome was first described in 1993 during an outbreak of unexplained fever and the acute respiratory distress syndrome among members of the Navajo tribe at the northern border between New Mexico and Arizona. Hantavirus infection in humans is extremely rate. In 2024, only 15 cases were reported in the United States to the CDC. Most cases have occurred in the Western United States. 

Hantavirus pulmonary syndrome (HPS) is an acute, zoonotic viral disease that is spread by contact with infected rodents, including deer mice (Peromyscus maniculatus), White Footed Mice (Peromyscus leucopus), Rice rats (Orysomys palustris), and Cotton Rats (Sigmodon hispidus). Most persons with HPS are infected by inhaling small airborne particles of urine, saliva or droppings that have been excreted by infected rodents. Other modes of transmission include: touching contaminated droppings or nesting materials, being bitten or scratched by an infected rodent, and eating food contaminated by urine, saliva, or droppings from an infected rodent. The majority of HPS cases occur in spring and summer; however, the seasonality of HPS can vary by elevation, location, and biome. Hantavirus is not spread between humans.

The incubation period for HPS is typically 2 to 4 weeks after exposure, with a range of a few days up to 6 weeks. Hantavirus pulmonary syndrome (HPS) typically begins as severe headache, high-grade fever, chills, myalgia, cough and gastrointestinal symptoms in a previously healthy person. Characteristic laboratory abnormalities include thrombocytopenia, leukocytosis, hemoconcentration, hypoalbuminemia, and elevated serum lactate dehydrogenase. The prodromal phase is followed by an abrupt progression to the cardiopulmonary phase, which is characterized by productive cough with nonpurulent secretions and dyspnea with severe respiratory distress. Chest radiographs reveal bilateral diffuse interstitial pulmonary edema which can resemble acute respiratory distress syndrome. There is no specific treatment available, but early recognition and administration of supportive care greatly increase the chance of survival. Fatality rate is 30 to 40%. 

The symptoms of hemorrhagic fever with renal syndrome usually develop within 1 to 2 weeks after exposure. They include intense headaches, fever and chills, back and abdominal pain, and blurred vision. Patients may progress to internal bleeding, hypotension, acute kidney failure, and shock. The severity of the illness depends on the virus causing the infection. Hantaan and Dobrava viruses cause severe symptoms with a 5 to 15% fatality rate. Seoul, Saaremaa, and Puumala virus infections are usually more moderate with a 1% fatality rate. 

Laboratory testing of patients with symptoms consistent with HPS is required to confirm the diagnosis. Sera are initially screened for IgG and IgM antibodies that recognize the nucleocapsid protein common to all hantaviruses. Samples from the United States that test positive for Hantavirus IgM are forwarded to a public health laboratory for Sin Nombre Virus-specific IgM testing. A positive result indicates an acute infection with Sin Nombre virus. A positive Hantavirus IgM result but a negative Sin Nombre-specific IgM antibody result may indicate either reactivity to a hantavirus other than Sin Nombre or a false positive reaction..

Hantavirus-specific IgG is often also present in the blood shortly after the onset of illness and can persist for months to years after the acute illness has occurred. Samples that are Hantavirus IgG positive but IgM negative are not forwarded for Sin Nombre-specific IgM testing, since the lack of IgM antibody rules out an acute Sin Nombre infection. 

Rarely, a sample that tests positive for Sin Nonbre IgM antibody but negative for Hantavirus IgG antibody may represent a false positive reaction associated with acute cytomegalovirus (CMV) or Epstein Barr virus (EBV) infection.

Because it is a reportable disease in the United States, clinicians suspecting HPS should notify their state health department.

References

CDC, Hantavirus, http://www.cdc.gov/hantavirus/technical/hps/index.html.

Ulloa-Morrison R, et al. Critical care management of hantavirus cardiopulmonary syndrome. A narrative review. J Crit Care, 2024;84:154867

Goodfellow, SM et al. A human pathogenic hantavirus circulates and sheds in taxonomically diverse rodent resevoirs. PLOS Pathogens, Published: January 21, 2025, https://doi.org/10.1371/journal.ppat.1012849