Hantavirus Infection – Causes, Symptoms, Treatment

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Hantavirus are a family of viruses spread mainly by rodents and can cause varied disease syndromes in people worldwide.  Infection with any hantavirus can produce hantavirus disease in people. Hantaviruses in the Americas are known as “New World” hantaviruses and may cause hantavirus pulmonary syndrome (HPS). Other hantaviruses, known as “Old World” hantaviruses, are found mostly in Europe and Asia and may cause hemorrhagic fever with renal syndrome (HFRS).

Each hantavirus serotype has a specific rodent host species and is spread to people via an aerosolized virus that is shed in urine, feces, and saliva, and less frequently by a bite from an infected host. The most important hantavirus in the United States that can cause HPS is the Sin Nombre virus, spread by the deer mouse.

Name and Nature of Infecting Organism of Hantavirus Infection

The term hantavirus refers to a genus covering several tens of species or genotypes globally; six so far in Europe, differing in their virulence to humans. Each hantavirus has a specific rodent host species or a group of closely related host species. Hantaviruses are expanding in Europe: they are found in new areas and the incidence has increased in several established endemic regions.

The most common European hantavirus disease is caused by Puumala hantavirus, carried by the bank vole (Myodes glareolus). The virus is widespread across most of the continent, except for the UK, the Mediterranean coastal regions and the northernmost areas.

Dobrava hantavirus, carried by the yellow-necked mouse (Apodemus flavicollis), is found only in south-east Europe, as far as the Czech Republic and southernmost Germany in the north, though the carrier species has a much wider distribution in Europe to the west and north.
Other hantaviruses in Europe, but with less public health importance, include Saaremaa hantavirus, carried by the striped field mouse (Apodemus agrarius) and found in eastern and central Europe and the Baltic states; Seoul hantavirus, carried by rats (Rattus norvegicusR. rattus); Tula hantavirus, carried by Microtus voles; and Seewis hantavirus, common in shrews (Sorex araneus), and only recently found in Europe.

Clinical illness results in hemorrhagic fever with renal syndrome (also called “nephropatia epidemic”) and causes less than 0.5% mortality.

Transmission of Hantavirus Infection

Where Hantavirus is Found

Cases of human hantavirus infection occur sporadically, usually in rural areas where forests, fields, and farms offer suitable habitat for the virus’s rodent hosts. Areas around the home or work where rodents may live (for example, houses, barns, outbuildings, and sheds) are potential sites where people may be exposed to the virus. In the US and Canada, the Sin Nombre hantavirus is responsible for the majority of cases of hantavirus infection. The host of the Sin Nombre virus is the deer mouse (Peromyscus maniculatus), present throughout the western and central US and Canada.

Several other hantaviruses are capable of causing hantavirus infection in the US. The New York hantavirus, carried by the white-footed mouse, is associated with HPS cases in the northeastern US. The Black Creek hantavirus, carried by the cotton rat, is found in the southeastern US. Cases of HPS have been confirmed elsewhere in the Americas, including Canada, Argentina, Bolivia, Brazil, Chile, Panama, Paraguay, and Uruguay.

Can pets transmit HPS to humans?

The hantaviruses that cause human illness in the United States are not known to be transmitted by any types of animals other than certain species of rodents. Dogs and cats are not known to carry hantavirus; however, they may bring infected rodents into contact with people if they catch such animals and carry them home.

How People Become Infected with Hantaviruses

In the United States, deer mice (along with cotton rats and rice rats in the southeastern states and the white-footed mouse in the Northeast) are reservoirs of the hantaviruses. The rodents shed the virus in their urine, droppings, and saliva. The virus is mainly transmitted to people when they breathe in air contaminated with the virus.

When fresh rodent urine, droppings, or nesting materials are stirred up, tiny droplets containing the virus get into the air. This process is known as “airborne transmission“.

There are several other ways rodents may spread hantavirus to people:

  • If a rodent with the virus bites someone, the virus may be spread to that person, but this type of transmission is rare.
  • Scientists believe that people may be able to get the virus if they touch something that has been contaminated with rodent urine, droppings, or saliva, and then touch their nose or mouth.
  • Scientists also suspect people can become sick if they eat food contaminated by urine, droppings, or saliva from an infected rodent.

The hantaviruses that cause human illness in the United States cannot be transmitted from one person to another. For example, you cannot get these viruses from touching or kissing a person who has HPS or from a health care worker who has treated someone with the disease.

In Chile and Argentina, rare cases of person-to-person transmission have occurred among close contacts of a person who was ill with a type of hantavirus called Andes virus.

Reservoir

Rodents like the bank voles and the yellow-necked mouse are the reservoir for hantaviruses. In the northern part of Europe, human epidemics occur during the cyclic population peaks of the host species. In temperate Europe, on the other hand, human epidemics are related to the (irregular) occurrence of mast years, i.e. years with heavy seed crops of oak and beech leading to an abundance of seed-eating rodents species including A. flavicollis. Carrier rodents often invade the human settlements in the autumn thus increasing risk. During rodent peak years, a high proportion of rodents can be seropositive. After being infected, bank voles start to shed the virus after 5–6 days, and the excretion continues for about two months.

Transmission mode

The rodents excrete hantaviruses in the urine, feces, and saliva, and human infection takes place mostly via inhalation of aerosolized virus-contaminated rodent excreta. Therefore rodent-infested dusty places are risk sites. No human-to-human transmission is known for European hantaviruses. No arthropod vectors are known for hantaviruses.

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People at Risk for Hantavirus Infection

Anyone who comes into contact with rodents that carry hantavirus is at risk of HPS. Rodent infestation in and around the home remains the primary risk for hantavirus exposure. Even healthy individuals are at risk for HPS infection if exposed to the virus.

Any activity that puts you in contact with rodent droppings, urine, saliva, or nesting materials can place you at risk for infection. Hantavirus is spread when virus-containing particles from rodent urine, droppings, or saliva are stirred into the air. It is important to avoid actions that raise dust, such as sweeping or vacuuming. Infection occurs when you breathe in virus particles.

According to the Centers for Disease Control and Prevention (CDC), hantaviruses are a family of viruses that are spread mainly by rodents and can cause varied diseases in people.

“Hantaviruses in the Americas are known as “New World” hantaviruses and may cause hantaviruses pulmonary syndrome (HPS). Other hantaviruses, known as “Old World” hantavirus, are found mostly in Europe and Asia and may cause hemorrhagic fever with renal syndrome (HFRS)”

What Occupations Are At Risk For Hantavirus Infection

Cases of Hantavirus infection contracted in Canada and the United States have been associated with these activities:

  • Sweeping out a barn and other ranch buildings.
  • Trapping and studying mice.
  • Using compressed air and dry sweeping to clean up wood waste in a sawmill.
  • Handling grain contaminated with mouse droppings and urine.
  • Entering a barn infested with mice.
  • Planting or harvesting field crops.
  • Occupying previously vacant dwellings.
  • Disturbing rodent-infested areas while hiking or camping.
  • Living in dwellings with a sizable indoor rodent population.

For workers that might be exposed to rodents as part of their normal job duties, employers are required to comply with relevant occupational health and safety regulations in their jurisdiction. Typically, employers are required to develop and implement an exposure control plan to eliminate or reduce the risk and hazard of Hantavirus in their workplace.

Causes of Hantavirus Infection

Each type of hantavirus has a preferred rodent carrier. The deer mouse is the primary carrier of the virus responsible for most cases of hantavirus pulmonary syndrome in North America. Other hantavirus carriers include the white-tailed mouse, cotton rat and rice rat.

Inhalation: Main route of transmission

Hantaviruses are transmitted to people primarily through the aerosolization of viruses shed in infected rodents’ droppings, urine or saliva. Aerosolization occurs when a virus is kicked up into the air, making it easy for you to inhale. For example, a broom used to clean up mouse droppings in an attic may nudge into the air tiny particles of feces containing hantaviruses, which you can then easily inhale.

After you inhale hantaviruses, they reach your lungs and begin to invade tiny blood vessels called capillaries, eventually causing them to leak. Your lungs then flood with fluid, which can trigger any of the respiratory problems associated with hantavirus pulmonary syndrome.

Person-to-person transmission

People who become infected with the North American strain of hantavirus pulmonary syndrome aren’t contagious to other people. However, certain outbreaks in South America have shown evidence of being transmitted from person to person, which illustrates variation across strains in different regions.

Symptoms of Hantavirus Infection

Early symptoms include fatigue, fever and muscle aches, especially in the large muscle groups—thighs, hips, back, and sometimes shoulders. These symptoms are universal.

  • There may also be headaches, dizziness, chills, and abdominal problems, such as nausea, vomiting, diarrhea, and abdominal pain.
  • Early symptoms of HPS include fever, fatigue, muscle aches, as well as headaches, dizziness, chills and abdominal problems. If left untreated, it can lead to coughing and shortness of breath which can be fatal. HPS has a mortality rate of 38 percent.

Overall, three syndromes are caused by hantaviruses

  • (1) Hemorrhagic fever with renal syndrome (HFRS), mainly in Europe and Asia;
  • (2) Nephropathy epidemic (NE), a mild form of HFRS, caused by Puumala hantavirus, and occurring in Europe;
  • (3) Hantavirus cardiopulmonary syndrome (HCPS), in the Americas.

The clinical features in patients with hantavirus disease are quite variable, from asymptomatic to severe. The incubation period is relatively long, mostly 2–3 weeks, but maybe up to six weeks. In endemic areas hantavirus infection should be suspected if acute fever is accompanied by thrombocytopenia, headache, often very severe, and abdominal and back pains without clear respiratory tract symptoms.

  • The case fatality rate due to Puumala virus infection ranges between less than 0.1 and 0.4%. Recovery usually begins during the second week of illness and is accompanied by improvement of urinary output resulting in polyuria. Full recovery may, however, take weeks. Longer-lasting complications are rare and include glomerulonephritis, Guillain-Barré syndrome, hypopituitarism, and hypertension.
  • The initial symptoms of HFRS are the same as HPS. HFRS causes low blood pressure, acute shock, vascular leakage, and acute kidney failure.
  • HPS cannot be transmitted from person to person, while HFRS transmission between people is extremely rare.

Late Symptoms

Four to 10 days after the initial phase of illness, the late symptoms of HPS appear. These include coughing and shortness of breath, with the sensation of, as one survivor put it, a “…tight band around my chest and a pillow over my face” as the lungs fill with fluid.

  • nausea and vomiting
  • muscle or body aches
  • tiredness and fatigue
  • appetite loss
  • sore throat, and
  • diarrhea.

Diagnosis of Hantavirus Infection

Hantavirus infection is diagnosed on the basis of a positive serological test and the confirmation of viral antigen in the tissue of the infected patients or the presence of viral RNA sequences in the patient’s blood or tissue, along with a compatible history of the disease.

Serologic assays

During the 1993 hantavirus outbreak, cross-reactive antibodies to the previously known hantaviruses, such as, Hantaan, Seoul, Puumala, and Prospect Hill virus were found in the acute- and convalescent-phase sera of some HPS patients. Since then, tests based on specific viral antigens from SNV have been developed and are widely used for the routine diagnosis of HPS. Enzyme-linked immunosorbent assay (ELISA) is the popular test for the detection of IgM antibodies in the patient’s blood that are raised against Hantaviruses during infection.

An IgG test in conjunction with the IgM-capture test is also used for the diagnosis of Hantavirus disease. Acute and convalescent-phase sera should reflect a fourfold rise in IgG antibody titer or the presence of IgM in acute-phase sera for positive hantavirus infection. It may be noted that acute-phase serum used as an initial diagnostic specimen may not yet have IgG. IgG is a long-lasting antibody, retained for many years after infection. Thus, SNV IgG ELISA has been used in serologic investigations of the epidemiology of the disease and appears to be appropriate for this purpose. Rapid immunoblot strip assay (RIBA) is an investigational prototype assay for the identification of serum antibodies to recombinant proteins and peptides specific for SNV and other hantaviruses. Also, neutralizing plaque assays have recently been performed for the serological confirmation of SNV infections. However, these specific assays are not commercially available. Isolation of hantaviruses from human sources is difficult and no isolates of SNV-like viruses have been recovered from humans. Thus, isolation of hantavirus is not considered for diagnostic purposes.

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Immunohistochemistry (IHC)

IHC testing of formalin-fixed tissues with specific monoclonal and polyclonal antibodies can be used to detect hantavirus antigens and has proven to be a sensitive method for laboratory confirmation of hantaviral infections. IHC has an important role in the diagnosis of HPS in patients from whom serum samples and frozen tissues are unavailable for diagnostic testing and in the retrospective assessment of disease prevalence in a defined geographic region.

Polymerase Chain Reaction (PCR)

Reverse transcriptase-polymerase chain reaction (RT-PCR) is a very sensitive assay and can be used for the detection of hantaviral RNA in infected samples, such as lung tissues and blood clots from infected patients. However, RT-PCR is very prone to cross-contamination and should be considered an experimental technique with limited use for diagnostic purposes of hantavirus infections.

Differential diagnosis

A variety of Infectious etiologies, such as pneumonia, sepsis with ARDS, and acute bacterial endocarditis can often be confused with HPS. Other conditions commonly found in the southwest United States have presentations similar to HPS, such as septicemic plague, tularemia, histoplasmosis, and coccidioidomycosis. In addition, noninfectious conditions, including myocardial infarction with pulmonary edema and Goodpasture’s syndrome should also be considered.

Treatment of Hantavirus Infection

There is no specific treatment, cure, or vaccine for hantavirus infection. However, we do know that if infected individuals are recognized early and receive medical care in an intensive care unit, they may do better. In intensive care, patients are intubated and given oxygen therapy to help them through a period of severe respiratory distress.

The earlier the patient is brought in to intensive care, the better. If a patient is experiencing full distress, it is less likely the treatment will be effective.

Initial supportive care includes the use of antipyretics and analgesics. Patients are immediately transferred to the intensive care unit (ICU) if preliminary symptoms indicate a higher probability of HPS. 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 administrated carefully due to higher chances of capillary leakage. Supplemental oxygen is necessary for hypoxic patients. Due to high risks of respiratory failure, ICU management should keep equipment and materials for intubation and mechanical ventilation readily available. Patients with severe HPS quickly progress to respiratory failure, and in the absence of ECMO (extracorporeal membrane oxygenation), almost all patients die within 24-48 hours of the onset of this severe phase.

Antiviral therapy including the use of ribavirin, a guanosine analog, has not been shown to be effective for the treatment of HPS. However, efficacy trials in HFRS patients in China have shown significant beneficial effects of ribavirin if started early in the disease course. Although ribavirin perturbs SNV replication in vitro, neither an open-label trial conducted during the 1993 outbreak nor an attempted placebo-controlled trial demonstrated clinical benefit for HPS. However, it has been suggested that ribavirin efficacy may depend on the phase of infection and the severity of the disease at the time of administration. Ribavirin is not recommended for the treatment of HPS and is not available for this use.

Supportive therapy

People with severe cases need immediate treatment in an intensive care unit. Intubation and mechanical ventilation may be needed to support breathing and to help manage fluid in the lungs (pulmonary edema). Intubation involves placing a breathing tube through your nose or mouth into the windpipe (trachea) to help keep your airways open and functioning.

Blood oxygenation

In extremely severe cases of pulmonary distress, you’ll need a method called extracorporeal membrane oxygenation (ECMO) to help ensure you retain a sufficient supply of oxygen. This involves continuously pumping your blood through a machine that removes carbon dioxide and adds oxygen. The oxygenated blood is then returned to your body.

Therefore, if you have been around rodents and have symptoms of fever, deep muscle aches, and severe shortness of breath, see your doctor immediately. Be sure to tell your doctor that you have been around rodents—this will alert your physician to look closely for any rodent-carried disease, such as HPS.

Prevention of Hantavirus Infection

Keeping rodents out of your home and workplace can help reduce your risk of hantavirus infection. Try these tips:

  • Block access – Mice can squeeze through holes as small as 1/4 inch (6 millimeters) wide. Seal holes with wire screening, metal flashing or cement.
  • Close the food buffet – Wash dishes promptly, clean counters and floors, and store your food — including pet food — in rodent-proof containers. Use tightfitting lids on garbage cans.
  • Reduce nesting material – Clear brush, grass, and junk away from the building’s foundation.
  • Set traps – Spring-loaded traps should be set along baseboards. Exercise caution while using poison-bait traps, as the poison also can harm people and pets.
  • Storing food (including pet food), water and garbage in heavy plastic or metal containers with tight-fitting lids.
  • Sealing any holes in structures where mice may enter.
  • Cutting back thick brush and keep the grass short. Keep woodpiles away from the building.
  • Using a rubber or plastic gloves when cleaning up signs of rodents, handling dead rodents, or other materials.  When finished, clean gloves with soapy water before taking them off. Wash hands with soapy water (again) after removing the gloves.
  • Setting traps when necessary.  Put rodents in a plastic bag, seal the bag, and dispose of.

or

  • Perform hand hygiene frequently, especially before touching the mouth, nose or eyes. Wash hands with liquid soap and water, and rub for at least 20 seconds. Then rinse with water and dry with a disposable paper towel or hand dryer. If hand washing facilities are not available, or when hands are not visibly soiled, hand hygiene with 70 to 80% alcohol-based hand rub is an effective alternative.
  • Eliminate sources of food and nesting places for rodents in our living environment:
    • Store food properly and handle pet food carefully so that it will not become food for rodents. Store all refuse and food remnants in dustbins with well-fitted cover. Dustbins must be emptied daily.
    • Keep premises, especially refuse rooms and stairways, clean. Avoid the accumulation of articles.
    • Inspect regularly all flowerbeds and pavements for rodent infestation.
  • Avoid the following high-risk activities to reduce contact with rodent
    • Handling live or dead rodents with bare hands; entering rodent-infested space; handling rodent excreta or nests; keeping wild rodents as pets; handling equipment or machinery kept in areas found with rodents, hand plowing or planting; lying on the ground, and living in residence frequented by rodents.
  • Travelers to places endemic for hantavirus infection should avoid visiting or living in places with poor environmental hygiene and avoid contacting rodents or their excreta.  Adventure travelers and campers should take precautions to exclude rodents from tents or other accommodation and to protect all food from contamination by rodents.
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How do I prevent Hantavirus pulmonary syndrome?

Keep rodents out of your home and workplace. Always take precautions when cleaning, sealing and trapping rodent-infested areas.

Seal up cracks and gaps in buildings that are larger than 1/4 inch including window and door sills, under sinks around the pipes, in foundations, attics and any potential rodent entry point.

  • Trap indoor rats and mice with snap traps.
  • Remove rodent food sources. Keep food (including pet food) in rodent-proof containers.

Clean up rodent-infested areas

  • Wear rubber, latex, vinyl or nitrile gloves. Note that dust mask may provide some protection against dust encountered during cleaning, but does not protect against viruses.
  • Do not stir up dust by vacuuming, sweeping, or any other means.
  • Thoroughly wet contaminated areas including trapped mice, droppings, and nests with a 10% hypochlorite (bleach) solution: Mix 1½ cups of household bleach in 1 gallon of water (or 1 part bleach to 9 parts water). Once everything is soaked for 10 minutes, remove all of the nest material, mice or droppings with a damp towel and then mop or sponge the area with bleach solution.
  • Steam clean or shampoo upholstered furniture and carpets with evidence of rodent exposure.
  • Spray dead rodents with disinfectant and then double-bag along with all cleaning materials. Bury, burn or throw out rodents in an appropriate waste disposal system.
  • Disinfect gloves with disinfectant or soap and water before taking them off.
  • After taking off the clean gloves, thoroughly wash hands with soap and water (or use a waterless alcohol-based hand rub when soap is not available).

What precautions should I use working, hiking, or camping outdoors?

  • Avoid coming into contact with rodents and rodent burrows or disturbing dens.
  • Air out cabins and shelters, then check for signs of rodent infestation. Do not sweep out infested cabins. Instead, use the guidelines above for disinfecting cabins or shelters before sleeping in them.
  • Do not pitch tents or place sleeping bags near rodent droppings or burrows.
  • If possible, do not sleep on the bare ground. Use tents with floors or ground cloth.
  • Keep food in rodent-proof containers!
  • Handle trash according to site restrictions and keep it in rodent-proof containers until disposed of.
  • Do not handle or feed wild rodents.

WHO Risk Assessment

HPS is a zoonotic, viral respiratory disease. The causative agent belongs to the genus Hantavirus, family Bunyaviridae. The infection is acquired primarily through inhalation of aerosols or contact with infected rodent excreta, droppings, or saliva of infected rodents. Cases of human hantavirus infection usually occur in rural areas (e.g. forests, fields, and farms) where sylvatic rodents hosting the virus might be found and where persons may be exposed to the virus. This disease is characterized by headache, dizziness, chills fever, myalgia, and gastrointestinal problems, such as nausea, vomiting, diarrhea, and abdominal pain, followed by sudden onset of respiratory distress and hypotension. Symptoms of HPS typically occur from two to four weeks after initial exposure to the virus. However, symptoms may appear as early as one week and as late as eight weeks following exposure. The case-fatality rate can reach 35-50%.

In the Americas, HPS cases have been reported in several countries. Environmental and ecological factors affecting rodent populations can have a seasonal impact on disease trends. Since the reservoir for hantavirus is sylvatic rodents, mainly Sigmodontinae species, transmission can occur when people come in contact with the rodent habitat. Limited human-to-human transmission of HPS due to the Andes virus in Argentina has been previously documented. There are no specific evidence-based procedures for HP’s patient isolation. Standard precautions1 should always be put in place, as well as rodent control measures.

WHO Advices

PAHO/WHO recommends that the Member States continue efforts of detection, investigation, reporting, and case management for the prevention and control of infections caused by hantavirus.

Particular attention should be paid towards travelers returning from the affected areas. Early identification and timely medical care greatly improve clinical outcomes. To raise awareness regarding potential HPS cases, clinicians should consult epidemiological data for the guidance of the possible exposure, and be vigilant of patients presenting with suspicious clinical signs and symptoms such as fever, myalgia, and thrombocytopenia.

Care during the initial stages of the disease should include antipyretics and analgesics as needed. In some situations, patients should receive broad-spectrum antibiotics while confirming the etiologic agent. Given the rapid progression of HPS, clinical management should focus on monitoring the patient’s hemodynamic status, fluid management, and ventilation support. Severe cases should be immediately transferred to intensive care units (ICU).

Ribavirin, an antiviral agent, is not approved for either treatment or prophylaxis of hantavirus pulmonary syndrome infection.

Health awareness campaigns must aim to increase the detection and timely treatment of the illness and prevent its occurrence by reducing people’s exposure. Preventive measures should cover occupational and eco-tourism related hazards. Most usual tourism activities pose little or no risk of exposure of travelers to rodents or their excreta. However, people who engage in outdoor activities such as camping or hiking should take precautions to reduce possible exposure to potentially infectious materials.

HP’s surveillance should be part of a comprehensive national surveillance system and must include clinical, laboratory and environmental components. The implementation of integrated environmental management, with the goal of reducing rodent populations, is recommended.

References

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