nephropathia endemica, NE.
Hantaviruses (genus Hantavirus, family Bunyaviridae) are a group of at least 25 antigenically distinct viruses carried in rodents. Some of these viruses can cause hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome in humans.
Hemorrhagic fever with renal syndrome (HFRS) is a group of clinically similar diseases that occur throughout Eurasia. HFRS includes several diseases that formerly had other names, including Korean hemorrhagic fever, epidemic hemorrhagic fever and nephropathia epidemica. Hantaviruses that can cause HFRS include Hantaan virus, Puumala virus, Dobrava virus and Seoul virus.
Hantavirus pulmonary syndrome (HPS) is a clinical syndrome caused by a number of hantaviruses in North and South America. In the United States, the Sin Nombre virus causes most cases. HPS can also result from infection by the New York, Black Creek, Bayou, Andes, Oran, Lechiguanas, Bermejo, Laguna Negra, Choclo, Araraquara and Castelo dos Sonhos viruses, as well as other unnamed hantaviruses.
Hantaviruses that have not been linked to human disease include the Isla Vista, Bloodland Lake, Muleshoe, Prospect Hill and El Moro Canyon viruses in North America, the Rio Segundo virus in Costa Rica and the Rio Mamore virus in Bolivia. European and Asian hantaviruses that have not been implicated in any human disease include Thailand virus in Thailand, Khabarovsk virus in Russia, Thottapalayam virus in India, Tula virus in Europe and Topografov virus in Siberia.
Hantaviruses are found worldwide in rodents. The viruses that cause hantavirus pulmonary syndrome seem to occur only in North, Central and South America. Confirmed human cases have been seen in the United States, Argentina, Bolivia, Brazil, Chile, Paraguay, Panama and Uruguay. Viruses associated with HPS in the United States include the Sin Nombre, New York, Black Creek and Bayou viruses. The Sin Nombre virus has also been found in Canada. In South America, HPS is caused by the Andes virus in Argentina and Chile, the Bermejo virus in Bolivia and Argentina, the Oran and Lechiguanas viruses in Argentina, the Laguna Negra virus in Paraguay and Bolivia, the Choclo virus in Panama, and the Araraquara and Castelo dos Sonhos viruses in Brazil.
HFRS is mainly seen in Europe and Asia; however, one causative agent, the Seoul virus, can be found worldwide and has been associated with cases of HFRS in the United States. HFRS is also caused by the Hantaan virus in China, Russia and Korea, the Puumala virus in Europe, Russia and Scandinavia, and the Dobrava virus in the Balkans.
Rodents are the reservoir host for hantaviruses; infections can be spread among the natural hosts by aerosols and bites. Virus is found in rodent saliva, feces and urine. Humans can become incidental hosts when they come into contact with infected rodents or their excretions. Often, rodent urine, droppings or nests are disturbed in enclosed areas; the viruses are then inhaled in aerosolized dust. Hantaviruses can also be transmitted through broken skin, the conjunctiva and other mucous membranes, by rodent bites and possibly by ingestion. Arthropod vectors do not seem to exist. Vertical transmission also appears to be negligible or nonexistent. Person to person spread has not been seen in HPS cases in North America or HFRS in Eurasia but may occur with the Andes virus in Argentina.
Hantaviruses are sensitive to drying but have been found in neutral solutions for several hours at 37° C and for several days in colder temperatures. Infectious viruses have also been detected in dried cell cultures for up to 2 days.
Hantaviruses are susceptible to 1% sodium hypochlorite, 2% glutaraldehyde and 70% ethanol. A 10% sodium hypochlorite solution has been recommended for heavily soiled areas. Hantaviruses are also susceptible to acid (pH 5) conditions and can be inactivated by heating to 60° C for 1 hour.
The incubation period varies from 3 to 60 days; most often, the symptoms appear after 14 to 30 days.
Hemorrhagic Fever with Renal Syndrome
The onset of HFRS is usually abrupt; the initial clinical signs may include fever, chills, prostration, headache and backache. Patients may also develop injected mucous membranes, a flushed face and conjunctivae, or a petechial rash, usually on the palate and axillae. The fever typically lasts for 3 to 8 days and is followed by a proteinuric stage. Hypotension may develop during this phase of the disease and can last for hours or days. Nausea and vomiting often occur and death may result from acute shock. This stage is typically followed by an oliguric phase then a diuretic phase as kidney function improves. Death can occur at any point, but is particularly common during the hypotensive or oliguric phases. In severe cases, kidney failure, pulmonary edema or disseminated intravascular coagulation may be seen. Convalescence can take weeks or months.
The severity of disease varies with the causative agent. Hantaan virus and Dobrava virus infections usually cause severe symptoms. Seoul virus generally results in more moderate disease and Puumala infections are typically mild.
Hantavirus Pulmonary Syndrome
Hantavirus pulmonary syndrome is usually characterized by pulmonary rather than kidney disease. The initial phase usually lasts for 3 to 5 days; the clinical signs during this period may include fever, myalgia, headache, chills, dizziness, malaise, lightheadedness, nausea, vomiting and sometimes diarrhea. Arthralgia, back pain and abdominal pain are occasionally seen. Respiratory distress and hypotension usually appear abruptly, with cough and tachypnea followed by pulmonary edema and evidence of hypoxia. Cardiac abnormalities may be seen, including bradycardia, ventricular tachycardia or fibrillation. After the onset of the cardiopulmonary phase, the disease usually progresses rapidly; patients may be hospitalized and require mechanical ventilation within 24 hours. Kidney disease develops occasionally, but is most often mild; kidney damage occurs more often with the Andes, Bayou and Black Creek viruses. Although recovery is rapid, convalescence may last for weeks or months. Asymptomatic or mild infections appear to be rare.
Although viruses can be found in the blood and urine of HFRS patients, no person-to-person transmission has been seen in cases of HPS in North America or HFRS in Eurasia. Person-to-person transmission has been reported during an outbreak of Andes virus in South America: a physician apparently contracted an infection after exposure to a patient’s blood and an adolescent seems to have contracted the disease from her parents. These cases remain to be confirmed by laboratory investigation.
Hantavirus infections are often diagnosed by serology. IgM in acute phase sera or a rise in IgG titer is diagnostic. Enzyme-linked immunosorbent assay (ELISA) assays are available for the Sin Nombre virus as well as other hantaviruses. Immunoblotting (Western blotting) and neutralizing plaque assays may also be used. A rapid immunoblot strip assay (RIBA) that detects antibodies to Sin Nombre and other hantaviruses is being developed.
Infections can also be diagnosed by finding antigens in tissues with immunohistochemistry or RNA with reverse transcriptase- polymerase chain reaction assays (RT-PCR). Virus isolation is rarely used, as hantaviruses are difficult to isolate from humans.
Treatment and Vaccination
Supportive care is the mainstay of treatment. Intensive care may be required. Ribavirin may be helpful in early cases of HFRS, but has not been effective for HPS to date. Vaccines are not available.
Morbidity and Mortality
Hantavirus outbreaks are often associated with increased rodent populations or environmental factors that lead to increased human exposure to rodents. Worldwide, approximately 150,000 to 200,000 people are hospitalized with HFRS each year. Different hantaviruses tend to cause mild, moderate or severe cases of HFRS; the mortality rate can vary from 0.1 to 3% for Puumala virus infections, to approximately 5% to 15% for Hantaan and Dobrava virus infections. Seoul virus tends to cause moderate disease with mortality rates of approximately 1%. Sin Nombre and New York virus infections are often fatal; the mortality rate is estimated to be 40 to 50%. The renal variant form of HPS caused by the Andes, Bayou and Black Creek viruses also has a high mortality rate. Convalescence from either HFRS or HPS can take weeks or months, but patients usually recover full lung function.
Hantaviruses are found naturally in various species of rodents. Infections do not appear to be pathogenic to their rodent hosts and may be carried lifelong.
Hantavirus-associated diseases have not been reported in domestic animals. Antibodies have been found in cats and dogs in the United States and western Canada and cats in Europe. In one study, 9.6% of healthy cats in the United Kingdom and 23% of cats with chronic diseases were seropositive. Horses, cattle and coyotes were seronegative in one U.S. survey.
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