Hemorrhagic Fever Renal Syndrome - Beware of Rodents

Introduction:

Hemorrhagic fever renal syndrome is a viral infection caused by various species of viruses that comes under the Hantavirus genera. The Hantaviruses use rodents as hosts. It is an acute zoonotic disease that is transmitted through aerosolized urine, saliva, and droppings of infected rodents like mice, rats, shrews, and voles. The severity of the diseases and the outcome is based on the viral strain.

What Is Hemorrhagic Fever?

Hemorrhagic fever is a condition in which the organ systems of the body and the cardiovascular system are affected, and the body’s ability to function normally is reduced. Various strains of viruses usually cause hemorrhagic fever. Viruses damage the walls of the blood vessels and cause leakage. It also disrupts the ability to form clots. It causes severe internal bleeding as a life-threatening symptom.

What Is Hemorrhagic Fever Renal Syndrome?

Hemorrhagic fever renal syndrome is a viral disease caused by the serotypes within the Hantavirus genera. It is also referred to as Korean hemorrhagic fever and epidemic hemorrhagic fever. It is an acute zoonotic disease that spreads from the excrement of rodents and causes hemorrhagic fever and renal injury. The main characteristic feature of this disease is capillary leakage which is caused by viral factors and the host’s immune factors.

What Are the Causes of Hemorrhagic Fever Renal Syndrome?

• Hemorrhagic fever renal syndrome is caused by the serotypes within the Hantavirus genera in the Bunyaviridae family. This species is endemic to Asia and Europe, and the common serotypes causing this disease are Dobrava-Belgrade orthohantavirus, Seoul orthohantavirus, Puumala orthohantavirus, Saaremaa virus, Hantaan orthohantavirus, and other hantaviruses. Hantaan River virus and Dobrava-Belgrade viruses are responsible for the severe form of this syndrome and have high mortality rates.

• The disease caused by the Puumala virus is also known as nephropathia epidemica. The most common serotype in North America is SNV-Sin Nombre Virus, and the most common serotype in South America is the Andes Virus. However, these strains of this disease cause a different outcome called Hantavirus pulmonary syndrome.

• It is transmitted through the inhalation of aerosolized rodent excreta and contact infection. The transmission from person to person is not established. It is common in rural areas with high rodent densities. Forest workers, military personnel, shepherds, and woodcutters are at high risk for this infection.

How Does Hemorrhagic Fever Renal Syndrome Occur?

Hantavirus affects various rodents without causing any disease. Human transmission occurs through aerosolized rodent excreta. The incubation period for Hantavirus infection varies from two to four weeks. The endothelial cells are susceptible to Hantavirus infection. The major pathological change associated with hemorrhagic fever renal syndrome is vascular endothelial dysfunction, characterized by an increase in vascular permeability (ability of the blood vessels to allow small molecules and cells to pass through). It causes plasma exosmosis, hypotension, and hemoconcentration resulting in coagulation abnormalities. Hemorrhagic fever renal syndrome occurs through indirect mechanisms, which include the virus factors, immune factors, and host genetic factors.

• Virus Factors: The virus attacks the endothelial cells of the host and gains access through the receptors. After entering the cell, it causes cytoskeletal reorganization and decreases the endothelial cell barrier’s integrity. This leads to glomerular filtration dysfunction and capillary leakage.

• Immune Factors: Innate and adaptive immunity activates to vade off this infection. However, the overproduction of inflammatory cytokines plays a role in disease pathogenesis. It increases the disease severity.

• Host Factors: Men are commonly affected by this disease, and it is associated with men doing outdoor activities. Hemorrhagic fever renal syndrome is common in older people. Genetics also play a role in this disease; the HLA-B8-DR3 haplotype gene is associated with high mortality.

What Are the Effects of Hemorrhagic Fever Renal Syndrome?

Hemorrhagic fever renal syndrome causes high-grade fever, hemorrhage, circulatory collapse with hypotension, and acute kidney injury. The progression of the disease occurs through five stages: febrile, hypotensive shock, oliguric, polyuric, and convalescent. One or two phases may not be present in mild disease forms, and some phases may overlap in severe cases.

The main characteristics of this disease are capillary leakage, acute kidney injury, and thrombocytopenia. Tubulointerstitial nephritis causes acute kidney injury, and cytokines and thrombocytopenia result in capillary leakage and coagulation abnormalities. Tubulointerstitial nephritis is caused by the infiltration of inflammatory cells. Elderly patients with severe kidney injury develop shock, thrombocytopenia (low platelet level), hematuria (presence of blood in the urine), and leukocytosis (increased WBC count).

Thrombocytopenia increases blood vessel permeability and causes severe acute kidney injury in patients with Hantavirus infection. Thrombocytopenia is a common symptom and is present throughout the infection.

The cardiac, pulmonary, endocrinological, central nervous system and ocular findings are also present in this syndrome. Acute progressive noncardiogenic pulmonary edema presents as acute respiratory distress syndrome in this disease. The presence of conjunctival hemorrhage, agitation, and coma negatively impacts the outcome of this disease.

What Are the Complications of Hemorrhagic Fever Renal Syndrome?

This syndrome causes complications, including:

• Pulmonary edema (swelling caused by excess fluid in the lungs).

• Acute encephalomyelitis (swelling in the brain and spinal cord).

• Disseminated intravascular coagulation (abnormal clotting of blood).

• Acute respiratory distress syndrome (collection of fluid in the air sacs of the lungs).

• Multiorgan failure.

• End-stage renal disease.

How Is Hemorrhagic Fever Renal Syndrome Diagnosed?

Hemorrhagic fever renal syndrome diagnosis is based on exposure history, clinical manifestations, and other laboratory tests. It includes the following tests:

• Enzyme-Linked Immunosorbent Assay (ELISA) Test: The presence of antibodies such as IgM (immunoglobulin M) and IgG in the serum confirms the Hantavirus infection. IgM antibody is present on the fourth day, and IgG is present on the sixth day of infection.

• Western Blot Test: It helps in identifying the presence of viral antigens.

How Is Hemorrhagic Fever Renal Syndrome Treated?

Early diagnosis and supportive treatment help in reducing mortality rates. The treatment includes the following:

• Medications - Antiviral drugs like Ribavirin and Favipiravir are used against Hantavirus infection. Steroids and Cyclophosphamide have also been used. Clinical studies have shown that Icatibant, a bradykinin inhibitor is effective in Puumala infection.

• Supportive Therapy- Supportive measures such as transfusion of red blood cells and platelets are performed for patients with hemorrhage and severe thrombocytopenia. Hemodialysis is performed if fluid overload causing pulmonary edema, hyperkalemia, or uremic signs are present.

Conclusion:

Hemorrhagic fever renal syndrome is a zoonotic disease that affects the organ systems of the body. It causes severe bleeding as a life-threatening complication. Early diagnosis and proper treatment are essential to prevent fatal complications like severe bleeding and multiorgan failure.