The hantavirus belongs to the bunyaviridae family of viruses and is the worldwide etiological agent for a hemorrhagic fever type illness known as Hemorrhagic Pulmonary Syndrome (HPS). The bunyaviridae family consists of five genera: bunyavirus, phlebovirus, nairovirus, tospovirus, and hantavirus. All five genera are negative-sense single stranded RNA viruses with an arthropodal vector except for hantavirus, which is rodent borne. The American hantavirus is the only bunyavirus with pulmonary implications. The other bunyaviridae are generally implicated with renal hemorrhaging. The most prevalent American hantavirus is now known as the Sin Nombre Virus (previously the Four Corners Virus) and is the primary focus of this report.
Sin Nombre Virus is an enveloped viruses consisting of three single stranded RNA sequences designated Large (L) 6,652 nucleotides, medium (M) 3,696 nucleotides, and small (S) 2,059-2,060 nucleotides. The L sequence codes for the L protein, which is the viral transriptase/ replicase mechanism. The M sequence codes for the two glycoproteins, G1 and G2, which constitute the envelope, and The S sequence codes for the nucleocapsid (N) protein.1
The National Center For Biotechnology Information provides detailed descriptions of the genetic compositions of the three ssRNA strands as well as the genetic codes for thousands of other organisms. This site is particularly useful as it contains an electronic PCR function that allows an unknown sequence of DNA or RNA to be compared to a vast bank of known sequences, such as the gene data base at the National Center for Biotechnology Center.2
The hantavirus was first identified in Hantaan, N. Korea during the Korean war, when a number of U.N. soldiers contracted a disease with symptoms that resembled a flu virus at first, but rapidly progressed to a hemorrhagic fever type disease of the renal system with a ten percent mortality rate. The disease was thus dubbed Hemorrhagic Fever Renal Syndrome (HFRS) and the virus was named Hantavirus. The disease itself is actually considered to be an ancient sickness that has only recently been rediscovered. The renal hemorrhagic symptoms of hantavirus were technically described first in Russia in 1913.
Fast-forward to May 17th, 1993. Dr. Bruce Tempest of the Indian Health Service in Gallup, New Mexico noticed and reported a cluster of five related deaths clustered in the four corners region of the United States. Three days prior to Dr. Tempests findings the New Mexico Office of the Medical Investigator had notified the New Mexico Department of Health of 3 unexplained pulmonary deaths within the same region. Clearly an investigation was warranted.
An assembly of local physicians and state and federal health officials initiated that investigation, even as additional cases began to pour in. The common prodromal symptoms of the inflicted included flu like fever, chills, and myalgia. Proceeding the prodrome were much more severe symptoms of dyspnea (difficulty breathing), coughing, thrombocytopenia, and severe hemodynamic instability. Mortality rate in the initial group was approximately 80 %. The chest X-ray examinations revealed an interstitial infiltrate similar to that observed in patients with adult respiratory distress syndrome (ARDS), which is a common symptom in individuals suffering from any of a variety of diseases (e.g., bacterial sepsis or trauma). The new disease was subsequently called unexplained ARDS (UARDS; Duchin, 1994; Nolte, 1995), but was later renamed Hemorrhagic Pulmonary Syndrome (HPS).3
The most common reservoir for Sin Nombre Virus and Hemorrhagic Pulmonary Syndrome in the United States is Peromyscus maniculates, the deer mouse. The deer mouse is a deceptively cute rodent gray to reddish-brown in color (depending on age). The underbelly is characteristically white as are two sharply defined white stripes that run along the length of the tail on opposite sides. P. maniculatus is known to inhabit the majority of the United States except for the south-east region, which is home to Sigmodon hispidis, the cotton rat; the primary reservoir for Black Creek Canal Virus, another less common HPS type hantavirus. Another hantavirus, Prospect Hill, has been identified within the United States, but has not been implicated as a cause of human disease. Prospect Hill virus was isolated from Microtus pennsylvanicus (meadow vole) in Frederick, MD.
In general, it appears that hantavirus has coevolved with sigmondontine (rat), arvicolinine (vole), and murinine (mouse) genera to produce two distinct viral subtypes: pulmonary type and renal type. The exact mechanism and significance of this variation is currently unknown, but is being evaluated.1
The disease is transmitted through the aerosolized excreta (urine, feces, and saliva) of the particular rodent host. Once a rodent is infected with hantavirus it will continue to carry and transmit the virus throughout its lifetime. This could account for the rapid worldwide proliferation of hantavirus. Since the original American outbreak of 1993, 350-400 cases have been reported across the continent, primarily in the United States, but also in Canada, Central America and South America. Mortality presently averages about 45%.4 By contrast, Ebola is fatal 50% -90% of the time.5 At this time there is no description of specific virulence factors associated with hantavirus other than encapsulation.
Salk-type hantavirus vaccines have been used successfully for a number of years in China and Korea. Sophisticated recombinant and DNA vaccines are being developed in Europe and North America, but have not been made available to the public as of yet. This work is, however, producing highly useful results, such as recombinant human antibodies with good therapeutic. potential (J. Koch, Heidelberg, Germany). 6
Currently, the most useful means of controlling hantavirus in the United States is controlling the animal reservoir, the deer mouse. Identification of rodent populations in close proximity to human inhabitations, and subsequent counter measures will prevent transmission to a large degree. The original outbreak of 1993 was attributed to an unnaturally large pinion nut crop in the four corners region. This excess of food caused a deer mouse population explosion and the subsequent hantavirus outbreak.
Hantavirus is transmitted especially well in a dusty or dirty environment, such as a home or cabin with a dirt floor. This type of domicile is fairly common in and around Indian reservations of the Southwest (four corners region). Stirring up dust by walking on or sweeping such a floor results in the aerosolization of rodent excreta and hantavirus and consequently, infection.
According to the CDC, individuals in close proximity to rodent infested buildings with a confirmed hantavirus presence should take the most extreme measures to prevent transmission including: powered air purifying respirators with HEPA filters (N-100 series) or half mask negative pressure type respirators with HEPA filters, rubber boots and gloves, disposable coveralls, and on site decontamination facilities. HEPA filters should be able to filter 3-5 micron particles to be effective. Additionally, individuals working in a hantavirus-contaminated environment should have a base line serum sample drawn and available for analysis and comparison should any disease symptoms occur later on. This base line sample should be drawn prior to exposure and should be stored at -20 degrees Centigrade.7
Concerned individuals looking to reduce potential risk factors for hantavirus should adhere to the following guidelines:
The Hantavirus is particularly disturbing to North Americans, as it is a hemorrhagic fever virus in our own backyard. Ebola and Marburg virus are diseases that break out in Africa and South America. We read about them in the newspaper and feel somewhat secure in our environment; however Hantavirus disturbs that security. Currently, our only defenses against it are wide scale vaccinations, rodent population surveillance / control, and an informed public. Hantavirus is here and spreading. HPS is fatal 50% of the time regardless of your constitution and there is no cure for it.
Cited References:
1 National Center for Infectious Disease: Special Pathogens Branch; All About Hantavirus. NCID web site. 2000 Sept 21. Available from: http://www.cdc.gov/ncidod/diseases/hanta/hps/noframes/phys/virology.htm Accessed 2002 May 06
2 National Center for Biological Information (online Database) 2001 Oct 24. Available from: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=nucleotide&cmd=search&term=Hantavirus Accessed 2002 May 06
3 Hjelle, B. M.D. Department of Pathology University of New Mexico School of Medicine web site. 1995 Mar 15. Available from http://www.bocklabs.wisc.edu/ed/hanta.html Accessed 2002 May 06
4 World Health Organization (WHO): Communicable Disease Surveillance and Response; Hantavirus Pulmonary Syndrome in the Americas. WHO web site. 1997 Oct 02. Available from http://www.who.int/disease-outbreak-news/n1997/oct/n2oct1997b.html Accessed 2002 May 06
5 World Health Organization (WHO): Fact Sheet N0 103; Ebola Hemorrhagic Fever. WHO web site 2000 Dec. Available from http://www.who.int/inf-fs/en/fact103.html Accessed 2002 May 06
6The Fifth International Conference on Hemorrhagic Fever With Renal syndrome, Hantavirus Pulmonary Syndrome, and Hantaviruses. (Abstract) Emerging Infectious Diseases. 2002, (8)4 Taken from Medscape from Web M.D. Available from: http://www.medscape.com/viewarticle/423565 Accessed 2002 May 06
7 National Center for Infectious Disease: Special Pathogens Branch; All About Hantavirus. NCID; Special Precautions for Homes of Persons with Confirmed Hantavirus Infection or Buildings with Heavy Rodent Infestations. NCID web site. 2000, Sept 21. Available from: http://www.cdc.gov/ncidod/diseases/hanta/hps/noframes/prevent4.htm Accessed 2002 May 06