hantavirus

Hantavirus infections comprise a diverse group of diseases. Some of the more than 28 known Hantaviruses (of which two in particular severely affect humans severely), can cause haemorrhagic fever with kidney syndrome (HFRS), Hantavirus pulmonary syndrome (HPS) and Hantavirus cardiopulmonary syndrome (HCPS).

CAUSES

Hantaviruses are negative single-stranded RNA viruses belonging to the Bunyaviridae family. They can infect endothelium cells and damage capillaries, causing vascular leakage in the affected organ: the kidneys for hantaviruses that cause HFRS and the lungs for hantaviruses that cause HPS.

Currently, over 28 Hantaviruses that cause disease in humans have been identified worldwide. These diseases range from acute renal failure and pulmonary edema to severe haemorrhagic diseases. However, in many countries, Hantavirus infections go undetected, so there may still be other unknown diseases. Although roughly 1,000 HPS case reports come in each year, it is estimated that more than 100,000 HFRS cases occur worldwide during the same period.

TRANSMISSION

The natural hosts of Hantaviruses are several species of rodents, with each virus in the genus being associated with a specific rodent species which, depending on the geographic distribution of the rodent, results in the spread of the associated disease variant.

Infection of humans is usually accidental, occurring as a result of aerosol inhalation of rodent excretions (such as urine, faeces, and saliva), or following a bite from an infected rodent. This can occur more easily when there is an increased 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 observed in one form of hantavirus, called Andes.

GEOGRAPHICAL DISTRIBUTION

The diffusion is widespread, with cases reported from the Far East and Europe, to the Americas, with different variants of the virus depending on the distribution of the rodent reservoir.

They are predominantly found in Europe and Asia, where HFRS is most common, with a mortality rate 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%.

SYMPTOMS

Hantavirus infection in humans can cause two clinical syndromes: haemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS). The differences between the two depend on the location of the affected capillaries, i.e. 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 include increased vascular permeability, which can lead to hypotension, thrombocytopenia, and leukocytosis.

Haemorrhagic fever with renal syndrome (HFRS)

The severity of the disease can vary greatly, depending on the type of virus responsible. All of the variants have a course that can be divided into two key stages, which are more precisely distinguished in the more severe forms of the disease:

• Febrile, which starts 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 stage usually lasts 3 to 7 days, at the end of which conjunctival bleeding of the palate occurs.
• Hypertensive, may last from several hours to 2 days. In severe cases, hypotension can result in irreversible fulminant shock, vascular leakage, and acute renal failure.

Hantavirus cardiopulmonary syndrome (HCPS)

Compared to HFRS, HCPS has a significantly higher severity, with mortality rates as high as 50%.

Again, the course of the disease typically occurs in two stages. The first presents with the same flu-like symptoms as HFRS, while the second is more severe, with symptoms including coughing with secretions, shortness of breath, accumulation of fluid 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 generally concludes without further sequelae.

DIAGNOSIS

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 levels of protein and red blood cells in the urine. However, because the early signs of the disease are non-specific, it is almost impossible to diagnose Hantavirus infections solely on clinical grounds, particularly in cases with mild or moderate clinical symptoms.

Laboratory diagnosis of acute Hantavirus infection is conducted via serology: in fact, at the onset of symptoms, all patients have IgM antibodies and normally also IgG antibodies in their serum. The most commonly used serological tests are indirect IgM and IgG ELISAs, and IgM capture ELISAs, which have a higher specificity than indirect ELISAs.

Indirect immunofluorescence tests are also routinely used as a diagnostic tool but have a lower specificity.

TREATMENT

No specific therapy is currently available for HFRS or HCPS. Treatment is primarily supportive.

Patients with HCPS and severe HFRS should be transferred to an intensive care unit for close monitoring and care. Maintenance of fluids and electrolyte balance, along with circulatory volume, is very important and must be carefully monitored based on the patient's fluid levels, diuresis levels and renal function, to avoid the dangers of overhydration.

Patients with chronic renal failure, which is associated with severe fluid retention and pulmonary edema, may require dialysis.

Ribavirin has demonstrated anti-hantaviral characteristics in vitro and in vivo and has been effective in treating infected suckling 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 mortality rates, when administered in the first 5 days after the onset of symptoms. However, in some limited studies ribavirin treatment showed no clinical benefit for patients.

PREVENTION

Preventive measures are based primarily on controlling the rodent population, blocking their access to shelter and food sources near human habitations, and generally avoiding contact with potentially contaminated areas.

Pest and rodent control and the implementation of measures to remove rodents from domestic environments are helpful. Water and all food, including pet food, should be protected from rodents with metal netting.

Protective clothing, rubber boots, gloves, masks and goggles must be worn when handling infected rodents or decontaminating rodent-infested dwelling.

In addition to the use of standard precautionary measures, the only way to minimise the risk of Hantavirus disease may be the use of effective vaccines. However, so far, neither Europe nor the United States have approved them for largescale use.

The situation differs in the Republic of Korea, where the Hantavax vaccine has been in use for many 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 shots. Vaccination is not recommended for children under 2 years of age and should not be given during antibiotic or antimalarial treatment.

Bibliografy

1. T. Avsic-Zupanc, Institute of Microbiology and Immunology, Faculty of Medicine, Zaloska 4, 1000 Ljubljana, Slovenia;
2. Piet Maes,Jan Clement, Irina Gavrilovskaya,Marc Van Ranst. Hantaviruses: Immunology, Treatment, and Prevention. VIRAL IMMUNOLOGY Volume 17, Number 4, 2004 © Mary Ann Liebert, Inc. Pp. 481–497;
3. Rebecca L. Brocato and Jay W. Hooper. Progress on the Prevention and Treatment of Hantavirus Disease. Viruses 2019, 11, 610; doi:10.3390/v11070610