KYASANUR FOREST DISEASE VIRUS

PATHOGEN SAFETY DATA SHEET - INFECTIOUS SUBSTANCES

SECTION I - INFECTIOUS AGENT

NAME: Kyasanur forest disease virus.

SYNONYM OR CROSS REFERENCE: Kyasanur forest disease (KFD), KFDV, and monkey fever/disease^(1,2,3).

CHARACTERISTICS: As member of the Flaviviridae family, KFDV belongs to the Russian spring summer encephalitis virus group^(2,4,5). KFDV is a spherical, enveloped virus of 45 nm in diameter and has a single-stranded, positive-sense RNA genome⁽⁴⁾.

SECTION II – HAZARD IDENTIFICATION

PATHOGENICITY/TOXICITY: Clinical or post-mortem biopsies of organs have found that KFD infection occurs in four stages, each lasting around a week in length. The initial prodromal stage is brought on by a sudden onset of fever and severe headache, hypotension and hepatomegaly, sore throat, diarrhoea and vomiting, anorexia, insomnia, severe pain in the lower and upper extremities, and prostration^(2,4,5,6,7). Bradycardia and inflammation of the conjuctiva are also commonly observed, along with acute lymphopenia and eosinopenia which can occur within the first or second week of infection⁽⁴⁾. The next stage is characterized by haemorrhagic complications such as intermittent epistaxis, hematemesis, melena, and frank blood in stool⁽³⁾; neurological manifestations such as mental confusion, tremors, and abnormal reflexes; and bronchopneumonia or development of coma which may occur in some cases prior to death^(4,5,7). A stage of recovery may be observed next, followed by a last stage of fever in certain cases⁽⁴⁾. Other pathologic manifestations of KFD in human patients include parenchymal degeneration of the liver and kidney, haemorrhagic pneumonitis, and a moderate to marked prominence of the reticuloendothelial elements in the liver and spleen with marked erythrophagocytosis^(2,4,8,9).

EPIDEMIOLOGY: KFDV was first recognized in 1957 when it was isolated from sick and dying monkeys in the Kyasanur Forest of the Shimoga district, Karnataka State in India^(1,4,10). Veterinary scientists investigating the sick monkeys, as well as local people utilizing the forest, were bitten by KFDV infected ticks and developed a haemorrhagic disease. During the initial outbreak, there were 466 human cases and 181 more the following year⁽⁵⁾. KFDV is common in young adults exposed during the dry season in the forest and has caused epidemic outbreaks of haemorrhagic fever affecting 100 to 500 people per year since then, with a case fatality rate that is estimated between 2 and 10%^(2,5,6,10).

HOST RANGE: Humans, a variety of tick species, rodents (shrews, forest rats), monkeys (grey langur, black-faced langur, bonnet macaque), bats, squirrels, Indian crested porcupines, and, to a lesser extent, domestic animals (goats, cows, sheep)^(2,5,9,11).

INFECTIOUS DOSE: Unknown.

MODE OF TRANSMISSION: Tick ( Haemaphysalis spinigera ) bites, especially nymphal ticks that remain infectious throughout their lives^(4,5,12). The KFDV transmission cycle is postulated to involve ticks (at least 10 species are involved), wild vertebrates (small rodents, shrews, and monkeys), and insectivores (ground-dwelling birds and bats)^(2,4,5,9). Large domestic animals (cows, goats, sheep) that become infected are thought be important only for sustaining tick populations⁽⁹⁾. Also, lactating monkeys are believed to shed minute quantities of the virus in their milk⁽⁹⁾.

INCUBATION PERIOD: Usually 3 to 8 days^(2,4,5,6,7).

COMMUNICABILITY: No evidence for human-to-human transmission^(4,6,13).

SECTION III - DISSEMINATION

RESERVOIR: Ticks, small forest mammals (house musk shrews, white-tailed wood rats, squirrels) and Indian crested porcupines^{(2,5,9,11,12)}. Monkeys play an important role in amplification of the virus^(5,11).

ZOONOSIS: Direct transmission from rodents to humans is possible⁽⁴⁾.

VECTORS: Nymphal ticks, especially Haemaphysalis spinigera^{(2,4,5,6,9,11,12)}. Secondary vectors include the soft tick ( Ornithodoros tholozani )⁽²⁾. The density of tick vectors in a given year correlates with the incidence of human disease⁽⁹⁾.

SECTION IV – STABILITY AND VIABILITY

DRUG SUSCEPTIBILITY: None available to date.

SUSCEPTIBILITY TO DISINFECTANTS: Inactivated by 3 to 8% formaldehyde, 2% glutaraldehyde, 2 to 3% hydrogen peroxide, 500 to 5,000 ppm available chlorine, alcohol, 1% iodine, and phenol iodophors⁽⁹⁾.

PHYSICAL INACTIVATION: Inactivated by heat (50 to 60°C for at least 30 minutes), ultraviolet light, and gamma irradiation⁽⁹⁾.

SURVIVAL OUTSIDE HOST: Low temperatures preserve infectivity, with stability being greatest below -60°C⁽⁹⁾.

SECTION V – FIRST AID / MEDICAL

SURVEILLANCE: Monitor for symptoms, confirm by RT-PCR, viral isolation, serological analysis such as ELISA, immunofluorescence, haemagglutination inhibition test and/or a neutralization test^{(4,5,6,7,9,14)}.

Note: All diagnostic methods are not necessarily available in all countries.

FIRST AID/TREATMENT: Supportive therapy, including analgesics and antipyretics, intravenous fluids for those with hypotension, blood transfusion or fresh-frozen plasma and platelets for those with haemorrhagic symptoms, antibiotics for bronchopneumonia, and corticosteroids and anticonvulsants for neurological symptoms^(7,13,15).

IMMUNIZATION: A formalin inactivated KFDV vaccine produced in chick embryo fibroblasts has been licensed and is currently in use in the endemic areas in Karnataka state of India and shows effective protection^(4,16,17,18).

PROPHYLAXIS: Apart from immunization, minimize exposure to tick vectors using insect repellents and protective clothing in areas where ticks are endemic⁽⁵⁾.

SECTION VI - LABORATORY HAZARDS

LABORATORY-ACQUIRED INFECTIONS: Infection of laboratory personnel via inhalation of aerosols during cultivation of KFDV is the most common route^(13,14,19). Other modes of infection have been documented, including from performing autopsies, breakage of ampoules and glassware containing specimens, accidental ingestion, and accidental needlestick injury⁽¹⁴⁾. The total number of laboratory acquired cases of KFD is not well established, but includes 87 cases up to 1979 in the Virus Diagnostic Laboratory in Shimoga, India⁽¹⁴⁾.

SOURCES/SPECIMENS: Aerosols generated when processing tissue samples^(9,14,15,19).

PRIMARY HAZARDS: Accidental parenteral inoculation, ingestion, and inhalation of aerosols^(9,14,15,19).

SPECIAL HAZARDS: None.

SECTION VII – EXPOSURE CONTROLS / PERSONAL PROTECTION

RISK GROUP CLASSIFICATION: Risk Group 4⁽²⁰⁾.

CONTAINMENT REQUIREMENTS: Containment Level 4 facilities, equipment, and operational practices for work involving infectious or potentially infectious materials, animals, and cultures.

PROTECTIVE CLOTHING: Personnel entering the laboratory must remove street clothing, including undergarments, 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⁽²¹⁾.

OTHER PRECAUTIONS: All activities with infectious material should be conducted in a biological safety cabinet (BSC) in combination with a positive pressure suit, or within a class III BSC line. 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 integrity of positive pressure suits must be routinely checked for leaks. 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 animal activities⁽²¹⁾.

SECTION VIII - HANDLING AND STORAGE

SPILLS: Allow aerosols to settle and, wearing protective clothing, gently cover spill with paper towels and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (30 min)⁽²¹⁾.

DISPOSAL: Decontaminate all wastes before disposal by steam sterilization, incineration, or chemical disinfection. Contaminated materials include both liquid and solid waste⁽²¹⁾.

STORAGE: In sealed leak-proof containers that are appropriately labelled and contained within a Containment Level 4 facility⁽²¹⁾.

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: September 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:

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2. Brown, R. N., Lane, R. S., & Dennis, D. T. (2005). Geographic Distributions of Tick-Borne Diseases and Their Vectors. In J. L. Goodman, D. T. Dennis & D. E. sonenshine (Eds.), Tick-Borne Diseases of Humans (1st ed., pp. 363-391). Washington, DC: ASM press.
    
3. Pavri, K. (1989). Clinical, clinicopathologic, and hematologic features of Kyasanur Forest disease. Rev.Infect.Dis., 11 , 854.
    
4. Pattnaik, P. (2006). Kyasanur forest disease: An epidemiological view in India. Reviews in Medical Virology, 16 (3), 151-165.
    
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7. Adhikari Prabha, M. R., Prabhu, M. G., Raghuveer, C. V., Bai, M., & Mala, M. A. (1993). Clinical study of 100 cases of Kyasanur Forest disease with clinicopathological correlation. Indian Journal of Medical Sciences, 47 (5), 124-130.
    
8. IYER, C. G., LAXMANA RAO, R., WORK, T. H., & NARASIMHA MURTHY, D. P. (1959). Kyasanur Forest Disease VI. Pathological findings in three fatal human cases of Kyasanur Forest Disease. Indian Journal of Medical Sciences, 13 , 1011-1022.
    
9. Burke, D.S., and Monath, T.P. (2001). Flaviviruses . In D. M. Knipe, & P. M. Howley (Eds.), Fields Virology (4th ed., pp. 1046-1109). Philadelphia, PA.: Lippencott-Raven.
    
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11. Boshell, J. (1969). Kyasanur Forest disease: ecologic considerations. American Journal of Tropical Medicine and Hygiene, 18 (1), 67-80.
     
12. Bhat, H. R., Naik, S. V., Ilkal, M. A., & Banerjee, K. (1978). Transmission of Kyasanur forest disease virus by Rhipicephalus haemaphysaloides ticks. Acta Virologica, 22 (3), 241- 244.
     
13. Borio, L., Inglesby, T., Peters, C. J., Schmaljohn, A. L., Hughes, J. M., Jahrling, P. B., Ksiazek, T., Johnson, K. M., Meyerhoff, A., O'Toole, T., Ascher, M. S., Bartlett, J., Breman, J. G., Eitzen Jr., E. M., Hamburg, M., Hauer, J., Henderson, D. A., Johnson, R. T., Kwik, G., Layton, M., Lillibridge, S., Nabel, G. J., Osterholm, M. T., Perl, T. M., Russell, P., & Tonat, K. (2002). Hemorrhagic fever viruses as biological weapons: Medical and public health management. Journal of the American Medical Association, 287 (18), 2391- 2405.
     
14. Banerjee, K., Gupta, N. P., & Goverdhan, M. K. (1979). Viral infections in laboratory personnel. Indian Journal of Medical Research, 69 (3), 363-373.
     
15. Bronze, M.S., and Greenfield, R.A. (2005). Biodefense Principles and Pathogens. Horizon (pp. 377-389). Oklahoma City, OK.: Bioscience.
     
16. Mansharamani, H. J., Dandawate, C. N., & Krishnamurthy, B. G. (1967). Experimental vaccine against Kyasanur Forest disease (KFD) virus from tissue culture source. I. Some data on the preparation and antigenicity tests of vaccines. Indian Journal of Pathology & Bacteriology, 10 (1), 9-24.
     
17. Mansharamani, H. J., & Dandawate, C. N. (1967). Experimental vaccine against Kyasanur Forest disease (KFD) virus from tissue culture source. II. Safety testing of the vaccine in cortisone sensitized Swiss albino mice. Indian Journal of Pathology & Bacteriology, 10 (1), 25-32.
     
18. Dandawate, C. N., Desai, G. B., Achar, T. R., & Banerjee, K. (1994). Field evaluation of formalin inactivated Kyasanur forest disease virus tissue culture vaccine in three districts of Karnataka state. Indian Journal of Medical Research, 99 (APR.), 152-158.
     
19. MORSE, L. J., RUSS, S. B., NEEDY, C. F., & BUESCHER, E. L. (1962). Studies of viruses of the tick-borne encephalitis complex. II. Disease and immune responses in man following accidental infection with Kyasanur Forest disease virus. Journal of Immunology (Baltimore, Md.: 1950), 88 , 240-248.
     
20. Human pathogens and toxins act. S.C. 2009, c. 24, Second Session, Fortieth Parliament, 57- 58 Elizabeth II, 2009. (2009).
     
21. 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.