Hantavirus

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Hantavirus

Introduction

Disease History, Characteristics, and Transmission

Scope and Distribution

Treatment and Prevention

Impacts and Issues

BIBLIOGRAPHY

Introduction

During the 1950s, more than 6,000 United Nations military personnel serving in Korea were stricken by a mysterious illness characterized by high fever, kidney failure, and spontaneous bleeding. Few realize that this disease continues to claim victims in the region, with 418 cases reported in 2006 alone. Eventually a group of viruses was identified as the cause of this “Korean hemorrhagic fever” and [the group] was named Hantaan virus, after the Hantaan River, which flows through Gangwon and Gyeonggi Provinces.

Subsequently, similar illnesses of varying severity in Asia and Europe were found to be caused by a number of distinct viruses, and the group came to be known as the Hantaviruses. In 1993, a new illness was reported in the southwestern United States. Unlike the Korean disease, prominent features included rapidly progressive lung infection with high mortality (death rates). Despite the unique nature of the disease, a viral agent was discovered which had all of the common biological features of the older Hantavirus group. The new illness was therefore referred to as Hantavirus pulmonary syndrome (HPS). 396 cases were reported by 32 American states as of July 6, 2005, including 142 fatal cases. As in the Asian variety, a large number of additional Hantavirus species have since been identified in the United States, as well as Central and South America.

Disease History, Characteristics, and Transmission

Regardless of differences in clinical presentation and geographic occurrence, all of the Hantaviruses are found in rodents. Man acquires the disease through inhalation of dried rodent excreta, or occasionally through ingestion of milk and other foods that had been contaminated by these animals. In fact, the ability of the virus to survive in dust and the contagious nature of infected material have suggested Hantaviruses as potential agents of biorerrorism.

Scope and Distribution

The following is a summary of the clinical features, distribution, and epidemiology (patterns, characteristics, and causes) of Hantaviruses that infect humans. Specific viruses (strains, or types) are arranged alphabetically.

Old World Hantaviruses

Clinical features Infection by the European and Asian Hantaviruses is characterized by sudden onset, with intense headache, backache, fever, and chills. Hemorrhage is manifested during the febrile phase as a flushing of the face or injection of the conjunctiva (membranes lining the eye) and mucous membranes. A petechial rash (tiny, red dots) may appear on the palate and axillary (underarm) skin folds. Extreme albuminuria (protein in the urine), typically appearing on the fourth day, is characteristic of severe hemorrhagic fever renal syndrome (HFRS).

As the febrile (with fever) stage ends, hypotension (low blood pressure) may develop and last for hours to days, accompanied by nausea and vomiting. One-third of deaths occur during this phase, related to vascular leakage (bleeding) and shock. Approximately 50% of deaths occur during the subsequent oliguric phase (when the kidneys produce very little urine). Patients who survive and progress to the diuretic phase show improved renal function, but may still die of shock or pulmonary (lung) complications. The final (convalescent) phase can last weeks to months.

Case-fatality rates (rates calculated to show the severity of disease; the number of deaths divided by number of cases expressed as a percentage) range from less than 0.1% for hemorrhagic fever renal syndrome (HFRS) caused by Puumala [PUU] virus to approximately 5% to 10% for HFRS caused by Hantaan (HTN) virus.

Epidemiology Dobrava/Belgrade virus causes severe hemorrhagic fever with renal (kidney) syndrome. The reservoirs (organisms that maintain the infective agent), Apodemus flavicolis (the yellow-necked mouse) and Apodemus agrarius, are found from England and Wales, through northwest Spain, France, southern Scandinavia, European Russia to the Urals, southern Italy, the Balkans, Syria, Lebanon, and Israel.

Hantaan virus causes epidemic hemorrhagic fever (Korean hemorrhagic fever and hemorrhagic fever with renal syndrome). The reservoir, the striped field mouse (Apodemus agrarius), is found in Central Europe south to Thrace, the Caucasus and Tien Shan Mountains, the Amur River to East Xijiang and East Hunnan, West Sichuan, Fujian, and Taiwan.

Puumala virus causes nephropathia epidemica (a usually less severe form of hemorrhagic fever). The reservoir, the bank vole (Clethrionomys glariolus) is found in the West Palearctic from France and Scandinavia to Lake Baikal, south to northern Spain, northern Italy, the Balkans, western Turkey, northern Kazakhstan, the Altai and Sayan Mountains, Great Britain, and southwestern Ireland. The house mouse (Mus musculus) is implicated in Serbia, and Clethrionomys rutilis in western Russia. The muskrat (Ondatra zibethicus) has been implicated as a disease reservoir in Germany. Note that Puumala virus may remain infective in the environment for as long as 12 to 15 days.

Saaremaa virus has been associated with human disease in Estonia, and is closely related to Dobrava virus.

Seoul virus causes less severe hemorrhagic fever with renal syndrome. The reservoir rat (Rattus norvegicus) is found worldwide. Wounds inflicted by other rats appear to be a major source for transmission among rats.

Thailand virus has been identified in humans and bandicoot rats (Bandicota indica, B. savilei) in Thailand.

Note: There are no proven cases of Hantaan or Seoul virus infections either from Europe or from western Russia (west of the Urals)—as of 2000, all claimed cases have turned out to be caused by Dobrava virus. Dobrava virus has been confirmed in the former Yugoslavia, Albania, Greece, Germany, Estonia and Russia. This is in contrast to the Balkan region, where Dobrova virus seems to be carried mainly by Apodemus flavicollis. In Estonia and Russia, the virus has only been found in Apodemus agrarius.

WORDS TO KNOW

CASE FATALITY RATE: The rate of patients suffering disease or injury that die as a result of that disease or injury during a specific period of time.

HEMORRHAGIC FEVER: A hemorrhagic fever is caused by viral infection and features a high fever and a high volume of (copious) bleeding. The bleeding is caused by the formation of tiny blood clots throughout the bloodstream. These blood clots—also called microthrombi—deplete platelets and fibrinogen in the bloodstream. When bleeding begins, the factors needed for the clotting of the blood are scarce. Thus, uncontrolled bleeding (hemorrhage) ensues.

RESERVOIR: The animal or organism in which the virus or parasite normally resides.

STRAIN: A subclass or a specific genetic variation of an organism.

Hantavirus pulmonary syndrome

Clinical features The typical illness is characterized by fever, chills, headache, and occasionally gastrointestinal symptoms. Five days after onset, patients develop dyspnea (difficult breathing), with rapid progression to pulmonary edema/ARDS (adult respiratory distress syndrome) within as little as 24 hours. Recently, cases of prodromic infection (having symptoms of oncoming disease) without severe pulmonary disease have been reported.

Epidemiology Andes virus is transmitted by the long-tailed pygmy rice rat (Oligoryzomys longicaudatus), found in the north central to southern Andes, approximately 50 degrees S latitude, in Chile, and Argentina (and possibly Uruguay).

Bermejo virus (reservoir Oligoryzomys species) has been associated with human infections in Bolivia.

Bayou virus is transmitted by the rice rat (Oryzomys palustris) in Louisiana and eastern Texas.

Black Creek Canal virus is transmitted by the cotton rat (Sigmodon hispidus), found in the eastern and southern United States from southern Nebraska to central Virginia, south to Southeastern Arizona and peninsular Florida; and from central to eastern Mexico through Central America and central Panama to northern Colombia and northern Venezuela.

Cano Delgadito virus (clinical significance unknown) is found in rodents in central Venezuela.

Central plata virus is associated with human infections in Uruguay, and is transmitted by the yellow pygmy rice rat (Oligoryzomys flavescens).

Choclo virus (reservoir Oligoryzomys fulvescens)is implicated in human infections in Panama. Calabazo virus (clinical significance unknown) has been identified in Zygodontomys brevicauda in Panama.

Convict Creek virus (similar, possibly identical to Sin Nombre virus) has been identified in California, and was implicated in a fatal case in Ontario, Canada.

Juquitiba virus, Ararquare virus and Castelos dos Sonhos virus have been implicated in human infections in Brazil; HU39694 (yet unnamed) in Argentina—reservoirs unknown.

Laguna negra virus has caused human disease in Argentina, Chile and Paraguay, and is transmitted by the vesper mouse (Calomys laucha). This rodent is found in northern Argentina and Uruguay, southeastern Bolivia, Chile, western Paraguay, and west-central Brazil.

Maporal virus (clinical significance unknown) has been identified in the fulvous pygmy rice rat (Oligoryzomys fulvescens) in western Venezuela.

Monongahela virus (similar, possibly identical to Sin Nombre virus) is found in the eastern United States and Canada, and carried by the white-footed mouse (Peromyscus leucopus) and possibly P. maniculatus nubiterrae.

New York-1 virus is transmitted by the white-footed mouse (Peromyscus leucopus), found in the Central and Eastern United States to Southern Ontario, Southern Alberta, Quebec and Nova Scotia; and Northern Durango and along the Caribbean coast of Mexico to the Isthmus of Tehuantepec and Yucatan Peninsula.

Oran virus (reservoir Ol. Longicaudatus), Lechiguanas virus (reservoir Or. Flavescens) and Andes virus (reservoir Ol. Longicaudatus) are found in Argentina.

Rio Mamore virus (reservoir Neacomys spinosus) has been associated with human infections in Peru.

Sin Nombre virus is transmitted by the deer mouse (Peromyscus maniculatus) in the southwestern United States. The reservoir is found from the Alaska panhandle across Northern Mexico, Canada, most of the continental United States, to southernmost Baja California and north central Oaxaca, Mexico. The mouse itself shows evidence of pneumonia. The virus has also been found in Pe. boylii, Pe. truei, Reithrodontomys spp., Mus musculus and Tamias spp.

Treatment and Prevention

Although the viruses in this group can be cultivated using standard techniques, viral culture is limited to a small number of institutions which meet strict standards of bio-safety. Diagnosis can also be established through testing for serum antibodies in specialized laboratories. Treatment is directed at support of renal, pulmonary and other systems affected by the viruses. The value of specific antiviral agents is not proven, but some authorities have suggested Ribavirin in the treatment of the Old Word Hantaviruses. A vaccine (Hantavax) has also been developed for the Old World variety.

Impacts and Issues

The Hantavirus pulmonary syndrome (HPS) was first identified as such in May 1993, in the so-called “Four Corners” region of the United States, where the states of New Mexico, Utah, Arizona, and Colorado meet. Initially, it was unclear what was able to quickly kill healthy adults in this region. Virologists from the U.S. Center of Disease Control (CDC) used techniques that allow an analysis of a virus at the molecular level, to link the pulmonary illness to a previously unknown type of hantavirus, which was later named Sin Nombre (Spanish for without name).

In addition to molecular and clinical studies, scientists are studying HPS through the study of rodent populations (which often requires the trapping and collection of various mice species), weather patterns, and climate change, Research in the southwestern United States has linked the years having higher levels of precipitation with a larger population of rodents, as the moisture leads to a greater supply of food for rodents, as well as higher vegetation growth, which provides ample habitat and protection for the rodents. Associated with the weather phenomenon El Niño in 1991 and 1993, rainfall levels increased in the southwestern United States. The population density of deer mice in New Mexico then increased from one deer mouse per hectare (2.47 acres) to twenty to thirty per hectare during that time period. It is thought that this large population of mice led to the first identified outbreak of HPS in May 1993.

Although rare, HPS has since been found throughout the United States. As of May 2007, rodent control remains the primary defense against the hantavirus.