HANTAVIRUS SPP.

PATHOGEN SAFETY DATA SHEET - INFECTIOUS SUBSTANCES

SECTION I - INFECTIOUS AGENT

NAME: Hantavirus spp.

SYNONYM OR CROSS REFERENCE: Old world Hantavirus, New world Hanta virus, Hemorrhagic fever with renal syndrome (HFRS), hantavirus pulmonary syndrome (HPS), Korean hemorrhagic fever (KHF), epidemic hemorrhagic fever, hemorrhagic nephrosonephritis ^{(1, 2)}.

CHARACTERISTICS: Hantaviruses belong to the family Buynaviridae. They are enveloped viruses about 100 nm in diameter with a tripartite single-stranded negative sense RNA genome, enclosed within a spherical capsid ^{(2, 3)}. Hantaviruses can be divided into three groups, according to the taxonomic assignment of their principle hosts: 1) Muridae (old world rats and mice); 2) Arvicolinae (voles and lemmings); 3) Sigmodontinae (New world rats and mice) ⁽³⁾. There are several species of Hantavirus which are pathogenic to humans, including Puumala, Dobrava-Belgrade, Hantaan, Seoul, Andes, Bayou, Black Creek Canal, Laguna Negra, New York, and Sin Nombre virus ⁽³⁾.

SECTION II - HAZARD IDENTIFICATION

PATHOGENICITY/TOXICITY:

Hemorrhagic fever with renal syndrome (HFRS): HFRS can manifest as mild, moderate or severe disease, depending upon the causative virus ⁽⁴⁾. The clinical course can be divided into five phases: prodrome (or febrile), hypotensive, oliguric, diuretic, and convalescent ^{(3, 4)}. The prodrome begins with high fever, chills, headache, blurred vision, malaise, and anorexia, followed by abdominal or lumbar pain, gastrointestinal symptoms, facial flushing, petechiae, and an erythematous rash. This phase typically lasts 3 to 7 days ⁽³⁾. The hypotensive phase lasts several hours to many days. It is characterized by the sudden onset of hypotension which may progress to shock and hemorrhagic manifestations. The oliguric phase typically lasts 3 to 7 days, and, in this time, the blood pressure may return to normal or become high, urinary output falls dramatically, and severe haemorrhage may occur ⁽³⁾. Spontaneous diuresis indicates the beginning of recovery. The case fatality rate is 5 to 15% ⁽⁵⁾.

Hantavirus pulmonary syndrome (HPS): There are four clinical phases: prodrome, cardiopulmonary, diuresis, and convalescence. The prodrome phase is characterized by fever, myalgia and malaise, and other symptoms, including headache, dizziness, abdominal pain, and gastrointestinal symptoms, typically lasting 3-6 days. This is followed by the rapidly progressive cardiopulmonary phase, characterized by non-cardiogenic pulmonary edema, hypoxemia, cough, pleural effusion, gastrointestinal symptoms, tachypnea, tachycardia, myocardial depression, and cardiogenic shock. Hypotension and oligouria may occur. The diuresis phase involves rapid clearance of pulmonary edema and resolution of fever and shock ^(2-4). The case fatality is around 40% ⁽⁴⁾.

EPIDEMIOLOGY: Hantaviruses occur worldwide, with the distribution of specific viruses limited to the habitat of their rodent hosts ^{(3, 5)}. For example, Hantaan virus, which causes a severe form of HFRS, is endemic in Russia and China, and Andes virus is responsible for HPS in the New World ^(1-3). Approximately 150,000 to 200,000 cases of HFRS occur each year world wide, most of which occur in China ^{(3, 4)}. Depending upon the virus, the case fatality can range from <1% to12% ⁽⁴⁾. HPS is more common in the New World, with approximately 200 cases per year, and the average case fatality rate 40% ⁽⁴⁾. Incidence rates in different countries, however, fluctuate with the population of rodent hosts. Infections occur predominantly in rural areas, although some viruses (e.g., Seoul virus) occur in urban areas. The majority of Hantavirus infections occur in males and in individuals between the ages of 20-40 ⁽⁴⁾. Trappers, hunters, forestry workers, farmers, and military personnel have a higher risk of contracting the disease ^{(2, 4)}.

HOST RANGE: Humans, and several species of rodents (voles, mice, rats) ^{(3, 6)}.

INFECTIOUS DOSE: Unknown.

MODE OF TRANSMISSION: Transmission occurs mainly by inhalation of aerosolized droplets of urine, saliva, or respiratory secretions from infected rodents or of aerosolized particles of feces, dust, or other organic matter carrying the infectious virus ^{(1, 3)}. They may also be transmitted by rodent bites (however, few patients contracting hantaviruses report rodent bites prior to symptom development), ingestion of contaminated food or water, and direct contact of cutaneous injuries or mucous membranes with the infectious virus ^(1-3).

INCUBATION PERIOD: 2 to 4 weeks (range from few days to 2 months) for HFRS; and 14-17 days for HPS ^{(3, 4)}.

COMMUNICABILITY: Person-to-person transmission is very rare, but has been observed for Andes virus during an outbreak in Southern Argentina ^{(1, 7)}.

SECTION III - DISSEMINATION

RESERVOIR: Small rodents (mice, rats and voles) serve as the reservoirs of Hantaviruses ^(1-3).

ZOONOSIS: Yes, transmitted from rodents to humans ^{(1, 3)}. Puumala virus – bank vole (Myodes glareolus, formerly Clethrionomys glareolus) in northern and central Europe; Hantaan virus – striped field mouse (Apodemus agrarius) in east Asia; Dobrava virus – yellow-necked mouse (A. flavicollis) and striped field mouse (A. agrarius) in southern Europe; Seoul virus - Norway rat (Rattus norvegicus) worldwide; Sin nombre virus – deer mouse (Peromyscus maniculatus) in North America; Laguna Negra virus – small vesper mouse (Calomys laucha) in Argentina; Andes virus – long-tailed pygmy rice rat (Oligoryzomys longicaudatus) in South America; Bayou virus – marsh rice rat (Oryzomys palustris) Louisiana; and Black Creek Canal virus – hispid cotton rat (Sigmodon hispidus) in Florida ⁽¹⁾.

VECTORS: None known.

SECTION IV – STABILITY AND VIABILITY

DRUG SUSCEPTIBILITY: Susceptible to latoferrin (in vitro) and ribavirin (in vitro and in vivo) in cases of HFRS; however, the efficacy of these drugs on cases of HPS have not been shown ^{(1, 3, 6, 8)}.

SUSCEPTIBILITY TO DISINFECTANTS: Susceptible to 1% solution of sodium hypochlorite, 1-5% Clidox® (chlorine dioxide), 1-5% Dettol® (parachlorometaxylenol), 1-5% Halamid-d® (sodium-p-toluene-sulfonchloramide), 1-5% peracetic acid, or Virkon® with a 10 minute contact time. Also susceptible to absolute methanol with a 10 minute contact time and 70% ethanol with a 30 minute contact time ⁽⁹⁾.

PHYSICAL INACTIVATION: Inactivated by heat (15 min at 56ºC for viruses in cell culture medium, and 2 hours at 56^oC for dried viruses) ⁽¹⁰⁾.

SURVIVAL OUTSIDE HOST: Can survive for long periods in the environment: 12-15 days in contaminated beddings, 5-11 days at room temperature in cell culture supernatants, and 18 – 96 days at 4ºC in cell culture supernatants ^{(10, 11)}.

SECTION V – FIRST AID / MEDICAL

SURVEILLANCE: Monitor for symptoms. Diagnosis is based mainly on serological tests to detect Hantavirus specific IgM, IgG, and neutralizing antibodies against the N protein or glycoproteins. Many different serological methods can be used, including immunofluorescence assay, haemagglutination-inhibition assay, and complement fixation tests ^{(1-3, 6)}. RT-PCR assays (for the S and M genomic regions of Hanta virus) can also be used to detect Hanataviral RNA in clinical samples such as blood, serum, or tissues from both HPS and HFRS patients ⁽³⁾.

FIRST AID/TREATMENT: Treatment with antiviral ribavirin improves the outcome of HFRS, but has not been investigated for HPS ^{(1, 3)}. Treatment is supportive. Furthermore, extracorporeal CO₂ elimination system should be considered for HPS patients to prevent life threatening pulmonary edema and cardiogenic shock ^{(1, 3)}.

IMMUNIZATION: None.

PROPHYLAXIS: None.

SECTION VI - LABORATORY HAZARDS

LABORATORY-ACQUIRED INFECTIONS: Yes, 226 cases (no deaths) have been reported for Hantaan virus ⁽⁷⁾.

SOURCES/SPECIMENS: Blood, urine, cerebrospinal fluid, and respiratory secretions, as well as rodent urine ^{(3, 12)}.

PRIMARY HAZARDS: Ingestion, contact of mucous membranes or broken skin with infectious materials, inhalation, animal bites, and accidental parenteral inoculation ^{(1, 3, 13)}.

SPECIAL HAZARDS: Working with laboratory animals (exposure to animal excreta, fresh necroscropy material, and animal bedding) ^{(1, 12)}.

SECTION VII – EXPOSURE CONTROLS / PERSONAL PROTECTION

RISK GROUP CLASSIFICATION: Risk Group 3 ⁽¹⁴⁾. The risk group associated with Hantavirus reflects the genus as a whole, but does not necessarily reflect the risk group classification of every species within the genus.

CONTAINMENT REQUIREMENTS: Containment level 3 facilities, equipment and operational practices for all work involving infectious or potentially infectious materials, animals, or cultures. These containment requirements apply to the genus as a whole, and may not apply to each species within the genus.

PROTECTIVE CLOTHING: Personnel entering the laboratory should remove street clothing and jewellery, and change into dedicated laboratory clothing and shoes, or don full coverage protective clothing (i.e., completely covering all street clothing). Additional protection may be worn over laboratory clothing when infectious materials are directly handled, such as solid-front gowns with tight fitting wrists, gloves, and respiratory protection. Eye protection must be used where there is a known or potential risk of exposure to splashes ⁽¹⁵⁾.

OTHER PRECAUTIONS: All activities with infectious material should be conducted in a biological safety cabinet (BSC) or other appropriate primary containment device in combination with personal protective equipment. Centrifugation of infected materials must be carried out in closed containers placed in sealed safety cups, or in rotors that are loaded or unloaded in a biological safety cabinet. The use of needles, syringes, and other sharp objects should be strictly limited. Open wounds, cuts, scratches, and grazes should be covered with waterproof dressings. Additional precautions should be considered with work involving animals or large scale activities ⁽¹⁵⁾.

SECTION VIII – HANDLING AND STORAGE

SPILLS: Allow aerosols to settle, and wearing protective clothing, gently cover the spill with absorbent paper towel and apply appropriate disinfectant starting at the perimeter and working towards the center. Allow sufficient contact time before starting the clean up ⁽¹⁵⁾.

DISPOSAL: All wastes should be decontaminated before disposal either by steam sterilization, incineration or chemical disinfection ⁽¹⁵⁾.

STORAGE: The infectious agent should be stored in leak-proof containers that are appropriately labelled ⁽¹⁵⁾.

SECTION IX – REGULATORY AND OTHER INFORMATION

REGULATORY INFORMATION: The import, transport, and use of pathogens in Canada is regulated under many regulatory bodies, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment Canada, and Transport Canada. Users are responsible for ensuring they are compliant with all relevant acts, regulations, guidelines, and standards.

UPDATED: October 2010

PREPARED BY: Pathogen Regulation Directorate, Public Health Agency of Canada.

Although the information, opinions and recommendations contained in this Pathogen Safety Data Sheet are compiled from sources believed to be reliable, we accept no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information. Newly discovered hazards are frequent and this information may not be completely up to date.

Copyright ©
Public Health Agency of Canada, 2010
Canada

REFERENCES:

1. Krauss, H., Schiefer, H. G., Weber, A., Slenczka, W., Appel, M., von Graevenitz, A., Enders, B., Zahner, H., & Isenberg, H. D. (2003). Viral Zoonoses. Zoonoses: Infectious Disease Transmissible from Animals to Humans (3rd ed., pp. 77-81). Washington D.C.: ASM Press.
2. Simpson, S. Q., Spikes, L., Patel, S., & Faruqi, I. (2010). Hantavirus Pulmonary Syndrome. Infectious Disease Clinics of North America, 24(1), 159-173.
3. Fulhorst, C. F., & Bowen, M. D. (2007). Hantaviruses. In P. R. Murray (Ed.), Manual of Clinical Microbiology (9th ed., pp. 1501-1509). Washington D.C.: ASM Press.
4. Bi, Z., Formenty, P. B., & Roth, C. E. (2008). Hantavirus infection: a review and global update. Journal of Infection in Developing Countries, 2(1), 3-23.
5. Schmaljohn, C. S., & Nichol, S. T. (2007). Bunyaviridae. In D. M. Knipe, P. M. Howley, D. E. Griffin, M. A. Martin, R. A. Lamb, B. Roizman & S. E. Straus (Eds.), Fields Virology (5th ed., pp. 1739-1789). Philadelphia PA: Lippincott Williams & Wilkins.
6. Krüger, D. H., Ulrich, R., & Lundkvist, A. (2001). Hantavirus infections and their prevention. Microbes and Infection, 3(13), 1129-1144.
7. Paragas, J., & Endy, T. P. (2006). Viral Agents of Human Disease: Biosafety Concerns. In D. O. Fleming, & D. L. Hunt (Eds.), Biological Safety: Principles and Practices (pp. 179-207). Washington, D.C.: ASM Press.
8. Murphy, M. E., Kariwa, H., Mizutani, T., Yoshimatsu, K., Arikawa, J., & Takashima, I. (2000). In vitro antiviral activity of lactoferrin and ribavirin upon hantavirus. Archives of Virology, 145(8), 1571-1582.
9. Maes, P., Li, S., Verbeeck, J., Keyaerts, E., Clement, J., & Van Ranst, M. (2007). Evaluation of the efficacy of disinfectants against Puumala hantavirus by real-time RT-PCR. Journal of Virological Methods, 141(1), 111-115.
10. Kallio, E. R., Klingström, J., Gustafsson, E., Manni, T., Vaheri, A., Henttonen, H., Vapalahti, O., & Lundkvist, Å. (2006). Prolonged survival of Puumala hantavirus outside the host: Evidence for indirect transmission via the environment. Journal of General Virology, 87(8), 2127-2134.
11. Hardestam, J., Simon, M., Hedlund, K. O., Vaheri, A., Klingström, J., & Lundkvist, Å. (2007). Ex vivo stability of the rodent-borne Hantaan virus in comparison to that of arthropod-borne members of the Bunyaviridae family. Applied and Environmental Microbiology, 73(8), 2547-2551.
12. Viral agents (other than arboviruses): Hantavirus. (1999). In J. Y. Richmond, & R. W. and Mckinney (Eds.), Biosafety in microbiological and biomedical laboratories (4th ed., pp. 153-154). Washington, D.C.: CDC & NIH.
13. Collins, C. H., & Kennedy, D. A. (1999). Laboratory acquired infections. Laboratory acquired infections: History, incidence, causes and prevention (4th ed., pp. 1-37). Woburn, MA: BH.
14. Human pathogens and toxins act. S.C. 2009, c. 24, Second Session, Fortieth Parliament, 57-58 Elizabeth II, 2009. (2009).
15. Public Health Agency of Canada. (2004). In Best M., Graham M. L., Leitner R., Ouellette M. and Ugwu K. (Eds.), Laboratory Biosafety Guidelines (3rd ed.). Canada: Public Health Agency of Canada.