Hantavirus

Hantaviruses are negative single-stranded RNA viruses, belonging to the Bunyaviridae family, that infect endothelial cells and damage capillaries, causing vascular leakage disease in the target organ: the kidney for hantaviruses causing HFRS and the lung for hantaviruses causing HPS.
Currently, more than 28 Hantaviruses causing disease in humans have been identified worldwide, ranging from acute renal failure to pulmonary edema and severe hemorrhagic diseases. However, Hantavirus infections go undetected in many countries, so there may be more as yet unknown. Although about 1,000 reports of HPS cases come in each year, it is estimated that more than 100,000 cases of HFRS occur worldwide during the same period.

The natural hosts of Hantaviruses are several species of rodents, with each type of virus typically infecting a specific type of animal and resulting, depending on the geographic distribution of the rodent, in the spread of the associated disease variant.
Infection of humans is generally accidental, occurring as a result of aerosol inhalation of rodent excretions (such as urine, feces, and saliva) or following a bite. The situations in which it occurs most readily are those in which there is a risk of exposure to the vector, such as harvesting hay and crops, cutting wood inside dusty woodsheds, cleaning basements, barns, sheds, or summer cottages in the fall, especially when these spaces are poorly ventilated.
Direct transmission between humans has only been demonstrated in one type of handavirus called Andes.

The spread is wide, with cases ranging from the Far East, to Europe, to the Americas, with different virus varieties depending on the distribution of the rodent reservoir.
They are predominantly found in Europe and Asia, where HFRS are most common with mortality rates ranging from <1 to 15% depending on the infecting virus. On the American continent, Hantaviruses include Andes virus (ANDV) and Sin Nombre virus (SNV); Choclo virus (CHOV) is found in Central America, which causes a pulmonary syndrome with a mortality rate of up to 40%.

Hantavirus infection in humans can cause two clinical syndromes: hemorrhagic fever with kidney syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS). The differences between the two depend on where the capillaries affected by the virus are located, in the kidneys or the lungs.

The incubation period can range from a few days to several months, but is typically around 2-4 weeks. The initial symptoms of all Hantavirus infections are similar, including a sudden onset of high fever, malaise, muscle aches and other flu-like symptoms. Other common factors are also increased vascular permeability leading to hypotension, thrombocytopenia, and leukocytosis. Hemorrhagic fever with renal syndrome (HFRS).
The severity of the disease can vary greatly depending on the type of virus responsible. All variants have a course that can be divided into two main phases, which are more precisely distinguished in the severe forms:

• Febrile, which begins suddenly after incubation with high fever, chills, headache, backache, abdominal pain, nausea, and vomiting. Drowsiness and visual disturbances (blurred vision) are frequently reported. This febrile phase usually lasts 3 to 7 days at the end of which conjunctival bleeding of the palate occurs.
• Hypertensive, it can last from a few hours to 2 days. In severe cases, hypotension results in irreversible fulminant shock, vascular leakage, and acute renal failure.

Hantavirus cardiopulmonary syndrome (HCPS).
Compared with HFRS, HCPS is a decidedly more severe one, with mortality rates as high as 50%. Again, the course typically occurs in two stages. The first has the same flu-like symptoms as HFRS, while the second is more severe, with symptoms including coughing with discharge, shortness of breath, fluid accumulation in the lungs, low blood pressure and reduced cardiac efficiency Patients who survive the acute phase of the disease enter the polyuric stage, accompanied by resolution of pulmonary edema. Although convalescence is slow and patients often complain of weakness, fatigue, and reduced exercise tolerance, recovery is generally complete, without consequences.

The diagnosis of HFRS and HCPS is based on clinical, epidemiological data and laboratory tests. Symptoms that should alert the physician to a possible Hantavirus infection are high fever, headache, abdominal and back pain combined with increased white blood cells, platelet deficiency, and elevated rates of protein and red blood cells in the urine. However, it is almost impossible to diagnose Hantavirus infections solely on clinical grounds, especially in cases with mild and moderate clinical symptoms, precisely because the early signs of the disease are not specific.
Laboratory diagnosis of acute Hantavirus infections is based on serology: indeed, all patients, at the onset of symptoms, have IgM antibodies and usually also IgG antibodies in serum. The most commonly used serological tests are indirect ELISAs for IgM and IgG and IgM capture ELISAs, which have higher specificity than indirect ELISAs.
Indirect immunofluorescence tests are also routinely used for diagnostics but have lower specificity.

No specific therapy is currently available for HFRS or HCPS. Treatment is mainly supportive. Patients with HCPS and severe HFRS should be transferred to an intensive care unit for close monitoring and care. Maintenance of water and electrolyte balance, along with circulatory volume, is very important and should be carefully monitored based on the patient's fluid status, amount of diuresis and renal function to avoid dangerous overhydration. Patients with severe renal failure, which is associated with severe fluid retention and pulmonary edema, may require dialysis treatmentRibavirin has demonstrated anti-hantaviral characteristics in vitro and in vivo and has been effective in the treatment of infected infant mice. It has been used in the treatment of HFRS in China, and clinical studies of Chinese patients with HFRS suggest that the therapy can significantly reduce the mortality rate if administered in the first 5 days after the onset of symptoms. However, in some limited studies, ribavirin treatment had no clinical benefit for patients.

Preventive measures are primarily based on controlling rodents by reducing their sheltering opportunities and food sources near human housing, and generally avoiding contact with potentially contaminated areas. Pest and rodent control and the implementation of measures to remove rodents from domestic environments are useful. Water and all food, including food for pets, should be protected from contact with rodents by metal netting. During all operations involving the handling of infected rodents or the decontamination of rodent-infested homes, protective clothing, rubber boots and gloves, masks and goggles should be used. In addition to the use of standard precautionary measures, the only way to minimize the risk of Hantavirus disease may be the use of effective vaccines. So far, Europe or the United States has not approved any for widespread use.Different discussion applies to the Republic of Korea, where the Hantavax vaccine has been in use for years. Derived from the brain of HTNV-infected infant mice inactivated in formalin, it would appear to be effective, although protective immunity requires frequent booster doses. Vaccination is not recommended for children under 2 years of age and should not be given during antibiotic or antimalarial treatment.