1887

Abstract

In 2002, a Scottish bat conservationist developed a rabies-like disease and subsequently died. This was caused by infection with (EBLV-2), a virus closely related to (RABV). The source of this infection and the means of transmission have not yet been confirmed. In this study, the hypothesis that lyssaviruses, particularly RABV and the bat variant EBLV-2, might be transmitted via the airborne route was tested. Mice were challenged via direct introduction of lyssavirus into the nasal passages. Two hours after intranasal challenge with a mouse-adapted strain of RABV (Challenge Virus Standard), viral RNA was detectable in the tongue, lungs and stomach. All of the mice challenged by direct intranasal inoculation developed disease signs by 7 days post-infection. Two out of five mice challenged by direct intranasal inoculation of EBLV-2 developed disease between 16 and 19 days post-infection. In addition, a simple apparatus was evaluated in which mice could be exposed experimentally to infectious doses of lyssavirus from an aerosol. Using this approach, mice challenged with RABV, but not those challenged with EBLV-2, were highly susceptible to infection by inhalation. These data support the hypothesis that lyssaviruses, and RABV in particular, can be spread by airborne transmission in a dose-dependent manner. This could present a particular hazard to personnel exposed to aerosols of infectious RABV following accidental release in a laboratory environment.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.46370-0
2006-06-01
2019-10-21
Loading full text...

Full text loading...

/deliver/fulltext/jmm/55/6/785.html?itemId=/content/journal/jmm/10.1099/jmm.0.46370-0&mimeType=html&fmt=ahah

References

  1. Arai, Y. T., Kuzmin, I. V., Kameoka, Y. & Botvinkin, A. D. ( 2003; ). New lyssavirus genotype from the lesser mouse-eared bat (Myotis blythi), Kyrghyzstan. Emerg Infect Dis 9, 333–337.[CrossRef]
    [Google Scholar]
  2. Atanasiu, P. ( 1965; ). Transmission of rabies by respiratory route to laboratory animals. C R Acad Sci Hebd Seances Acad Sci D 261, 277–279 (in French).
    [Google Scholar]
  3. Badrane, H., Bahloul, C., Perrin, P. & Tordo, N. ( 2001; ). Evidence of two Lyssavirus phylogroups with distinct pathogenicity and immunogenicity. J Virol 75, 3268–3276.[CrossRef]
    [Google Scholar]
  4. Baer, G. H. & Bales, G. L. ( 1967; ). Experimental rabies infection in the Mexican freetail bat. J Infect Dis 117, 82–90.[CrossRef]
    [Google Scholar]
  5. Baer, G. M., Cleary, W. F., Diaz, A. M. & Perl, D. F. ( 1977; ). Characteristics of 11 rabies virus isolates in mice: titers and relative invasiveness of virus, incubation period of infection, and survival of mice with sequelae. J Infect Dis 136, 336–345.[CrossRef]
    [Google Scholar]
  6. Botvinkin, A. D., Kuzmin, I. V. & Rybin, S. N. ( 1996; ). The unusual bat lyssavirus Aravan from Central Asia. Myotis 34, 101–104.
    [Google Scholar]
  7. Botvinkin, A. D., Poleschuk, E. M., Kuzmin, I. V., Borisova, T. I., Gazaryan, S. V., Yager, P. & Rupprecht, C. E. ( 2003; ). Novel lyssaviruses isolated from bats in Russia. Emerg Infect Dis 9, 1623–1625.[CrossRef]
    [Google Scholar]
  8. Bourhy, H., Kissi, B., Lafon, M., Sacramento, D. & Tordo, N. ( 1992; ). Antigenic and molecular characterization of bat rabies virus in Europe. J Clin Microbiol 30, 2419–2426.
    [Google Scholar]
  9. Bourhy, H., Kissi, B. & Tordo, N. ( 1993; ). Molecular diversity of the Lyssavirus genus. Virology 194, 70–81.[CrossRef]
    [Google Scholar]
  10. Charlton, K. M. & Casey, G. A. ( 1979; ). Experimental oral and nasal transmission of rabies virus in mice. Can J Comp Med 43, 10–15.
    [Google Scholar]
  11. Cliquet, F., Aubert, M. & Sagné, L. ( 1998; ). Development of a fluorescent antibody virus neutralisation test (FAVN test) for the quantitation of rabies-neutralising antibody. J Immunol Methods 212, 79–87.[CrossRef]
    [Google Scholar]
  12. Constantine, D. G. ( 1962; ). Rabies transmission by nonbite route. Public Health Rep 77, 287–289.[CrossRef]
    [Google Scholar]
  13. Constantine, D. G. ( 1966; ). Transmission experiments with bat rabies isolates: responses of certain Carnivora to rabies virus isolated from animals infected by nonbite route. Am J Vet Res 27, 13–15.
    [Google Scholar]
  14. Constantine, D. G. ( 1967; ). Rabies transmission by air in bat caves. In Public Health Service Publication No. 1617, pp. 1–51. Atlanta, GA: National Communicable Disease Center.
  15. Constantine, D. G., Emmons, R. W. & Woodie, J. D. ( 1972; ). Rabies virus in nasal mucosa of naturally infected bats. Science 175, 1255–1256.[CrossRef]
    [Google Scholar]
  16. Dean, D. J. & Abelseth, M. K. ( 1973; ). The fluorescent antibody test. In Laboratory Techniques in Rabies, 3rd edn, pp. 73–84. Edited by M. M. Kaplan & H. Koprowski. Geneva: World Health Organization.
  17. Elvin, S. J., Bennett, A. M. & Phillpotts, R. J. ( 2002; ). Role for mucosal immune responses and cell-mediated immune functions in protection from airborne challenge with Venezuelan equine encephalitis virus. J Med Virol 67, 384–393.[CrossRef]
    [Google Scholar]
  18. Fooks, A. R. ( 2004; ). The challenge of new and emerging lyssaviruses. Expert Rev Vaccines 3, 333–336.[CrossRef]
    [Google Scholar]
  19. Fooks, A. R., Brookes, S. M., Johnson, N., McElhinney, L. M. & Hutson, A. M. ( 2003a; ). European bat lyssaviruses: an emerging zoonosis. Epidemiol Infect 131, 1029–1039.[CrossRef]
    [Google Scholar]
  20. Fooks, A. R., McElhinney, L. M., Pounder, D. J. & 8 other authors ( 2003b; ). Case report: isolation of a European bat lyssavirus type 2a from a fatal human case of rabies encephalitis. J Med Virol 71, 281–289.[CrossRef]
    [Google Scholar]
  21. Heaton, P. R., Johnstone, P., McElhinney, L. M., Cowley, R., O'Sullivan, E. & Whitby, J. E. ( 1997; ). Heminested PCR assay for detection of six genotypes of rabies and rabies-related viruses. J Clin Microbiol 35, 2762–2766.
    [Google Scholar]
  22. Hronovsky, V. & Benda, R. ( 1969a; ). Experimental inhalation infection of laboratory rodents with rabies virus. Acta Virol 13, 193–197.
    [Google Scholar]
  23. Hronovsky, V. & Benda, R. ( 1969b; ). Development of inhalation rabies infection in suckling guinea pigs. Acta Virol 13, 198–202.
    [Google Scholar]
  24. Irons, J. V., Eads, R. B., Grimes, J. E. & Conklin, A. ( 1957; ). The public health importance of bats. Tex Rep Biol Med 15, 292–298.
    [Google Scholar]
  25. Jenson, A. B., Rabin, E. R., Bentinck, D. C. & Melnick, J. L. ( 1969; ). Rabiesvirus neuronotis. J Virol 3, 265–269.
    [Google Scholar]
  26. Johnson, N. & Fooks, A. R. ( 2005; ). Archival study of a Finnish isolate from the 1988/89 rabies outbreak. Arch Virol 150, 1407–1414.[CrossRef]
    [Google Scholar]
  27. Johnson, N., Selden, D., Parsons, G., Healy, D., Brookes, S. M., McElhinney, L. M., Hutson, A. M. & Fooks, A. R. ( 2003; ). Isolation of a European bat lyssavirus type 2 from a Daubenton's bat in the United Kingdom. Vet Rec 152, 383–387.[CrossRef]
    [Google Scholar]
  28. Kent, J. R. & Finegold, M. F. ( 1960; ). Human rabies transmitted by the bite of a bat: with comments on the duck-embryo vaccine. N Engl J Med 263, 1058–1065.[CrossRef]
    [Google Scholar]
  29. King, A. A. ( 1996; ). Cell culture of rabies virus. In Laboratory Techniques in Rabies, 4th edn, pp. 114–130. Edited by F.-X. Meslin, M. M. Kaplan & H. Koprowski. Geneva: World Health Organization.
  30. Lafay, F., Coulon, P., Astic, L., Saucier, D., Riche, D., Holley, A. & Flamand, A. ( 1991; ). Spread of the CVS strain of rabies virus and of the avirulent mutant AvO1 along the olfactory pathways of the mouse after intranasal inoculation. Virology 183, 320–330.[CrossRef]
    [Google Scholar]
  31. Messenger, S. L., Smith, J. S. & Rupprecht, C. E. ( 2002; ). Emerging epidemiology of bat-associated cryptic cases of rabies in humans in the United States. Clin Infect Dis 35, 738–747.[CrossRef]
    [Google Scholar]
  32. Messenger, S. L., Smith, J. S., Orciari, L. A., Yager, P. A. & Rupprecht, C. E. ( 2003; ). Emerging pattern of rabies deaths and increased viral infectivity. Emerg Infect Dis 9, 151–154.[CrossRef]
    [Google Scholar]
  33. Phillpotts, R. J., Brooks, T. J. G. & Cox, C. S. ( 1997; ). A simple device for the exposure of animals to infectious microorganisms by the airborne route. Epidemiol Infect 118, 71–75.[CrossRef]
    [Google Scholar]
  34. Selimov, M. A., Marinina, V. P., Nikitina, L. F. & Ilyasova, R. S. ( 1969; ). Experimental respiratory infection induced by rabies virus variants adapted to tissue culture. Acta Virol 13, 135–138.
    [Google Scholar]
  35. Tillotson, J. R., Axelrod, D. & Lyman, D. O. ( 1977; ). Rabies in a laboratory worker – New York. Morb Mortal Wkly Rep 26, 183–184.
    [Google Scholar]
  36. Tordo, N. ( 1996; ). Characteristics and molecular biology of the rabies virus. In Laboratory Techniques in Rabies, 4th edn, pp. 28–51. Edited by F.-X. Meslin, M. M. Kaplan & H. Koprowski. Geneva: World Health Organization.
  37. Warrell, M. J. & Warrell, D. A. ( 2004; ). Rabies and other lyssavirus diseases. Lancet 363, 959–969.[CrossRef]
    [Google Scholar]
  38. Winkler, W. G. ( 1968; ). Airborne rabies virus isolation. Wildl Dis 4, 37–40.[CrossRef]
    [Google Scholar]
  39. Winkler, W. G. ( 1975; ). Airborne rabies. In The Natural History of Rabies, vol. II, pp. 115–121. Edited by G. M. Baer. New York: Academic Press.
  40. Winkler, W. G., Baker, E. F., Jr & Hopkins, C. C. ( 1972; ). An outbreak of non-bite transmitted rabies in a laboratory animal colony. Am J Epidemiol 95, 267–277.
    [Google Scholar]
  41. Winkler, W. G., Fashinell, T. R., Leffingwell, L., Howard, P. & Conomy, P. ( 1973; ). Airborne rabies transmission in a laboratory worker. JAMA (J Am Med Assoc) 226, 1219–1221.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.46370-0
Loading
/content/journal/jmm/10.1099/jmm.0.46370-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error