hantavirus

Generality

Hantavirus infections produce a heterogeneous group of acute-onset diseases, distributed worldwide. These viral agents are spread by various species of wild and domestic rodents; their transmission to humans occurs through inhalation or contact with urine, excrement or the saliva of an infected animal carrier.

• Hemorrhagic fever with renal syndrome (HFRS);
• Epidemic nephropathy, a mild form of HFRS, caused by the Puumala virus;
• Hantavirus pulmonary syndrome (HPS), which can be caused by the Andes virus, Sin Nombre virus (SNV) and many others.

There is no specific treatment or vaccination; eliminating or minimizing contact with rodents and their habitat is the best way to prevent hantavirus infection.

hantavirus

Hantaviruses belong to the Bunyaviridae family; these are negative-stranded RNA viruses , which replicate exclusively in the cytoplasm of the host cell. There are more than 20 known hantaviruses, some of which are associated with two serious, potentially deadly diseases in humans: haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Other hantavirus species have not been associated with known human diseases.

Vector

The natural hosts of hantavirus are wild and domestic rodents. Each type of hantavirus infects a specific animal carrier with preference; the presence of a particular rodent thus also influences the geographical distribution of the different clinical syndromes. In the United States, for example, the deer mouse (Peromyscus maniculatus) is the main vector of the virus responsible for most cases of hantavirus pulmonary syndrome in North America. Other vectors include the cotton rat (Sigmodon hispidus), the rice rat (Oryzomys palustris) and the white-legged mouse (Peromyscus leucopus) . Once infected, animal carriers eliminate the virus for the rest of their lives. Man represents an accidental guest.

Characteristics of some Hantaviruses associated with human disease

The Hantaan virus from Korea and the Dobrava virus from Slovenia (transmitted by the Apodemus flavicollis, a wild mouse with a yellow neck) are associated with a severe form of HFRS characterized by renal failure that may precede pulmonary edema and disseminated intravascular coagulation (CID ), with a mortality rate estimated at 5% to? 15%. A moderate form of HFRS caused by the Seoul virus - which, together with its carrier, is distributed worldwide - is responsible, every year, for thousands of Eurasian cases. The same virus also appears to be associated with chronic kidney disease.

Contagion

Hantavirus infection occurs:

• Through direct contact with urine, faeces and saliva disseminated by rodents infected in the environment;
• For inhalation of aerosol containing fresh or dried excretion particles dispersed in the environment.

Main route of transmission: inhalation

Hantaviruses are transmitted to the human host primarily through an "aerosol" consisting of the excrement particles, urine or saliva of infected rodents. For example, a broom used to clean an attic can disperse the tiny feces particles containing hantavirus into the air, which can then be easily inhaled. After the pathogens enter the airways, they reach the lungs and begin to invade the blood vessels triggering a series of events that cause the clinical manifestation of the infection.

Transmission from person to person

With some exceptions, hantaviruses are generally not transmitted from person to person. Patients suffering from the North American version of hantavirus pulmonary syndrome are not contagious to others; however, in a form of the South American disease caused by the milder Andes virus, transmission can be interpersonal, through contact with blood or bodily fluids of an infected person.

Incubation period

The incubation period is variable and can be a few days or a few months. In most cases it is 2-4 weeks.

Main clinical syndromes caused by hantavirus

The infections caused by hantavirus are acute viral diseases in which the vascular endothelium is damaged, leading to increased vascular permeability, hypotension, hemorrhagic manifestations and shock. Impaired renal function with oliguria is characteristic of haemorrhagic fever with renal syndrome (HFRS - Hantavirus hemorrhagic fever with renal syndrome ), while respiratory failure caused by acute non-cardiogenic pulmonary edema occurs in hantavirus pulmonary syndrome (HPS - Hantavirus pulmonary syndrome ). The outcome is fatal up to 15% of HFRS cases and 50% of HPS cases.

Pathogenesis

The pathogenesis of hantavirus-supported infections is unclear, as no suitable animal models are available to describe it (rats and mice do not seem to acquire a severe form of disease). The site of primary viral replication in the human body is not known, but in HFRS the ptaogenic effect is mainly localized in the blood vessels, while in HPS most of the symptoms occur in the lung.

• In hemorrhagic fever with renal syndrome - due to endothelial dysfunction - there is an increase in vascular permeability and a decrease in blood pressure, while at the level of the kidneys more dramatic damage is found.
• Lungs, spleen and gall bladder are involved in hantavirus pulmonary syndrome ; the first symptoms of HPS tend to present themselves in a similar way to the flu (muscle aches, fever and fatigue) generally starting 2-3 weeks after exposure to the virus. In the late phase of the disease, about 4-10 days after the onset of symptoms, breathing difficulties and other typical manifestations arise.

Hantavirus pulmonary syndrome

The hantavirus pulmonary syndrome is an infectious disease characterized by sudden-onset flu-like symptoms, which at the respiratory level can rapidly deteriorate to the point of being potentially fatal. The hantavirus pulmonary syndrome (HPS) is found mainly in the North, Central and South America, during the spring and summer months, especially in rural areas. Different types of hantaviruses can cause pulmonary syndrome. In the United States, the Sin Nombre virus (SNV, from Spanish, "virus without a name"), carried by the deer mouse ( Peromyscus maniculatus ), was recognized during the 1993 epidemic, in the "Four Corners" region. Since then, this etiological agent has been identified throughout the United States.

The probability of developing hantavirus pulmonary syndrome is greater in people who work or share spaces with animal carriers. Rodent control in and around homes, especially in rural areas, remains the best primary prevention strategy.

Symptoms

The symptoms of hantavirus pulmonary syndrome may develop 1-5 weeks after exposure to urine, excrement or saliva of infected rodents. The disease evolves through two distinct phases.

• In the first phase, flu-like symptoms and other generic manifestations may occur, which may include:
  • Fatigue and lethargy;
  • Fever and chills;
  • Headache and muscle pain;
  • Vomiting, nausea, diarrhea and abdominal pain.

About half of all patients with HPS experience these symptoms. In its early stages, it is therefore difficult to distinguish hantavirus infection from influenza, pneumonia or other viral diseases.

• 4-10 days after the onset of the disease, more serious signs and symptoms develop, which include:
  • Cough with secretions;
  • Shortness of breath;
  • Accumulation of fluids within the lungs;
  • Low blood pressure;
  • Reduced cardiac efficiency.

Late signs and symptoms may suddenly worsen. Rapid evolution to pulmonary edema is often fatal, despite mechanical ventilation and intervention with powerful diuretics. The mortality rate is 50%.

Diagnosis

The diagnosis is usually formulated based on the results of clinical and serological investigations. In the initial phase of the disease, the infection cannot be differentiated from other viral fevers. However, if the patient has increased body temperature, dyspnea, fatigue and has been in contact with rodents, the manifestations could be strongly suggestive of a hantavirus pulmonary syndrome. The doctor may indicate further analysis to rule out other conditions with similar presentation.

Diagnostic criteria for hantavirus pulmonary syndrome are considered:

• A positive result for serological tests (example: ELISA) for immunoglobulin M (IgM) or increasing titers of specific hantavirus IgG;
• The direct detection of the presence of viral antigen in the tissue by immunohistochemistry: it is a sensitive method, which plays an important role in the diagnosis of HPS and in the retrospective evaluation of the prevalence of the disease in a defined geographical region;
• The presence of amplified viral RNA sequences by polymerase chain reaction (RT-PCR) in clinical blood or tissue samples.

The isolation of the virus from human sources is difficult, therefore it is not considered for diagnostic purposes (from urine it is successful at the beginning of the disease, from the blood it is less consistent).

Treatments and drugs

Treatment options specific to hantavirus pulmonary syndrome are limited, but the prognosis improves with early recognition, immediate admission to an intensive care unit and adequate support for breathing.

Early stage therapy may include the administration of antipyretics and analgesics. Assisted breathing, through intubation or mechanical ventilation, can help keep airways open and functioning and prevent pulmonary edema. In extremely severe cases of pulmonary insufficiency, the patient may need extracorporeal membrane oxygenation (ECMO) to maintain a sufficient supply of oxygen.

Hemorrhagic fever with renal syndrome (HFRS)

Hemorrhagic fever with renal syndrome (HFRS) includes a group of clinically similar diseases caused by various hantaviruses , such as Korean hemorrhagic fever and epidemic nephropathy. The species that cause HFRS are found mainly in Europe, Asia and Africa. People may develop haemorrhagic fever with renal syndrome after inhalation of viral agents or after direct contact of rodent excretions infected with mucous membranes of the eyes, nose or mouth. Also, people who work with live rodents can be exposed to hantavirus through bites from infected animals. Transmission from one human being to another can occur, but it is an extremely rare occurrence.

Symptoms

The symptoms of HFRS develop within 7-15 days of exposure to contaminated material, but in rare cases it can take up to 8 weeks to arise. Initial symptoms occur suddenly and include headache, abdominal pain, fever, chills, nausea and blurred vision. Individuals may notice facial flushing, inflammation and redness of the eyes or a rash. Later, symptoms may include hypotension, acute shock, vascular leakage and acute renal failure, which can cause severe fluid overload. The severity of the disease depends on the viral load and varies depending on the virus that causes the infection. Hantaan and Dobrava virus infections tend to cause severe symptoms, while the forms caused by the Seoul, Saaremaa and Puumala viruses are usually moderate. Full recovery can take weeks or months.

Diagnosis

Numerous laboratory tests are used to confirm the diagnosis of HFRS in patients with a clinical history compatible with the disease. Diagnosis is confirmed in the presence of positive serological test results for hantavirus infection (IgM or IgG), detection of viral antigen in tissues by immunohistochemistry or evidence of the presence of specific viral RNA sequences in the blood or tissues.

Therapy

Supportive care is the mainstay of care for patients with hantavirus infections and includes:

• Quick transfer to intensive care;
• Careful monitoring and management of the electrolyte balance (for example, sodium, potassium, chloride) and of the patient's water balance
• Maintaining correct blood pressure and oxygen levels
• Appropriate treatment of any secondary infections

Dialysis may be necessary to correct a severe fluid overload. Ribavirin, an antiviral drug, has been shown to reduce HFRS-associated illness and death if used early.

Prophylaxis

Several classical and molecular vaccine approaches are in the pre-clinical phase of development; the biggest obstacle is the lack of adequate hantavirus-associated animal disease models, which allow to evaluate their complete efficacy and safety. Furthermore, no specific antiviral therapy is still available.

Risk for travelers

For most travelers, the risk of contracting a hantavirus infection is very low. However, there is a potential risk in any environment where large numbers of rodents are present, aggravated by all those conditions that facilitate contact. Travelers, hikers and campers - who may be exposed to carriers in countries or areas at risk for hantavirus infections - must take precautions to keep rodents away from tents or other accommodation, as well as protecting all food from contamination.