Rabies — New Challenges by an Ancient Foe

  • Richard W. Emmons


It has only been four years since Dr. Jean Smith presented to the 5th session of this series of symposia an excellent talk entitled “The Changing World of Rabies” (Baer and Smith, 1986). That very timely report discussed new techniques in laboratory diagnosis, new knowledge of the pathogenesis of rabies and the host’s immune response, the exciting developments in monoclonal antibody analysis for strain differentiation, and hopeful trends in prevention and treatment of rabies. But it is worthwhile to check in again on the progress that is being made — and the challenges that still remain. I’ll need to repeat some of the topics covered in 1985, but will highlight some other new information as well; and anyway, this audience has changed; and the fascination and challenge of rabies are as great as ever.


Rabies Virus Rabies Vaccine Public Health Laboratory Human Rabies Immune Gamma Globulin 
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  1. Anderson LJ, Nicholson KG, Tauxe RV, Winkler WG (1984) Human rabies in the United States, 1960 to 1979: epidemiology, diagnosis and prevention. Ann Int Med 100:728–735.PubMedCrossRefGoogle Scholar
  2. Aoki FY, Rubin ME, Friesen AD, Bowman JM, Saunders JR (1989) Intravenous human rabies immunoglobulin for post-exposure prophylaxis: serum rabies neutralizing antibody concentrations and side effects. J Biol Standard 17:91–104.CrossRefGoogle Scholar
  3. Baer GM (Ed) (1975) The Natural History of Rabies, Volumes I and II; Academic Press, New York, San Francisco, London.Google Scholar
  4. Baer GM (1988) Research towards rabies prevention: overview. Rev Infect Dis 10(Suppl 4):S576–S577.CrossRefGoogle Scholar
  5. Baer GM, Smith JS (1985) Rabies virus, pp 790–795. In Lennette EH, Balows A, Hausier WJ, Jr., Shadomy HJ (Eds) Manual of Clinical Microbiology 4th Ed. American Society for Microbiology, Washington, D.C.Google Scholar
  6. Baer GM, Smith JS (1986) The changing world of rabies, pp 347–400. In de la Maza LM, Peterson EM (Eds) Medical Virology V. Lawrence Erlbaum Associates, Inc. Hillsdale, NJ.Google Scholar
  7. Baer GM, Bridbord K, Hui FW, Shope RE, Wunner WH, (Guest Editors) (1988) Research towards rabies prevention. A symposium. Washington, D.C, 3–5 November, 1986. Rev Infect Dis 10(Suppl 4):S573–S815.Google Scholar
  8. Berlin BS, Mitchell Jr, Burgoyne GH, Oleson D, Brown WE, Goswick C, McCullough NB (1982) Rhesus diploid rabies vaccine (adsorbed), a new rabies vaccine. Results of initial clinical studies of preexposure vaccination. JAMA 247(12):1726–1728.PubMedCrossRefGoogle Scholar
  9. Bourhy H, Rollin PE, Vincent J, Sureau P (1989) Comparative field evaluation of the fluorescent-antibody test, virus isolation from tissue culture, and enzyme immunodiagnosis for rapid laboratory diagnosis of rabies. J Clin Microbiol 27(3):519–523.PubMedGoogle Scholar
  10. Bryceson ADM, Greenwood BM, Warrell DA, Davidson N McD, Pope HM, Lawrie JH, Barnes HJ, Bailie WE, Wilcox GE (1975) Demonstration during life of rabies antigen in humans. J Infect Dis 131:71–74.PubMedCrossRefGoogle Scholar
  11. Burgoyne GH, Kajiya KD, Brown DW, Mitchell JR (1985) Rhesus diploid rabies vaccine (adsorbed): a new rabies vaccine using FRhL-2 cells. J Infect Dis 152:204–210.PubMedCrossRefGoogle Scholar
  12. Bussereau F, Vincent J, Coudrier D, Sureau P (1988) Monoclonal antibodies to Mokola virus for identification of rabies and rabies-related viruses (1988) J Clin Microbiol 26:2489–2494.PubMedGoogle Scholar
  13. Centers for Disease Control (1988) Rabies vaccine, absorbed: a new rabies vaccine for use in humans. MMWR 37:217–218, 223. Centers for Disease Control, Public Health Service, US Dept Health and Human Services, Atlanta, GA.Google Scholar
  14. Centers for Disease Control (1989) Human Rabies — Oregon, 1989. MMWR 38:335–337. Centers for Disease Control, Public Health Service, US Dept Health and Human Services. Atlanta, GA.Google Scholar
  15. Dietzschold B, Rupprecht CE, Tollis M, Lafon M, Mattei J, Wiktor TJ, Koprowski (1988) Antigenic diversity of the glycoprotein and nucleocapsid proteins of rabies and rabies-related viruses: implications for epidemiology and control of rabies. Rev Infect Dis 10(Suppl 4):S785–S798.PubMedCrossRefGoogle Scholar
  16. Dietzschold B, Tollis M, Rupprecht CE, Celis E, Koprowski H (1987) Antigenic variation in rabies and rabies-related viruses: cross-protection independent of glycoprotein-mediated virus-neutralizing antibody. J Infect Dis 156:815–822.PubMedCrossRefGoogle Scholar
  17. Ermine A, Tordo N, Tsiang H, (1988) Rapid diagnosis of rabies infection by means of a dot hybridization assay. Molec Cell Probes 2:75–82.PubMedCrossRefGoogle Scholar
  18. Esposito JJ, Knight JC, Shaddock JH, Novembre FJ, Baer GM (1988) Successful oral rabies vaccination of raccoons with raccoon poxvirus recombinants expressing rabies virus glycoprotein. Virology 165:313–316.PubMedCrossRefGoogle Scholar
  19. Fekadu M (1988) Pathogenesis of rabies virus infection in dogs. Rev Infect Dis 10(Suppl 4):S678–S683.PubMedCrossRefGoogle Scholar
  20. Fekadu M, Greer PW, Chandler FW, Sanderlin DW (1988) Use of the avidinbiotin peroxidase system to detect rabies antigen in formalin-fixed paraffin-embedded tissue. J Virol Methods 19:91–96.PubMedCrossRefGoogle Scholar
  21. Fishbein DB, Baer GM (1988) Animal rabies: implications for diagnosis and human treatment. Ann Intern Med 109:935–937.PubMedCrossRefGoogle Scholar
  22. Fishbein DB, Dobbins JG, Bryson JH, Pinsky PF, Smith JS (1988) Rabies surveillance, United States 1987. Centers for Disease Control, Public Health Service, US Department of Health and Human Services, Atlanta, GA. CDC Surveillance Summaries, Sept 1988; MMWR 37 (No SS-4):1-1Google Scholar
  23. Flamand A, Wiktor TJ, Koprowski H (1980a) Use of hybridoma monoclonal antibodies in the detection of antigenic differences between rabies and rabies-related virus proteins. I. The nucleocapsid protein. J Gen Virol 48:97–104.PubMedCrossRefGoogle Scholar
  24. Flamand A, Wiktor TJ, Koprowski H (1980b) Use of hybridoma monoclonal antibodies in the detection of antigenic differences between rabies and rabies-related virus proteins. II. The glycoprotein J Gen Virol 48:105–109.PubMedCrossRefGoogle Scholar
  25. Gode GR, Bhide NK (1988) Two rabies deaths after corneal grafts from one donor. Lancet ii:791.CrossRefGoogle Scholar
  26. Gode GR, Saksena R, Batra RK, Kalia PK, Bhide NK (1988) Treatment of 54 clinically diagnosed rabies patients with two survivals. Indian J Med Res 88:564–566.PubMedGoogle Scholar
  27. Grandien M, Fridell E Kindmark C-O (1985) Intradermal immunization with reduced doses of human diploid cell strain rabies vaccine: evaluation of antibody response by ELISA and mixed hemadsorption test. Scand J Infect Dis 17:173–178.PubMedGoogle Scholar
  28. Hattwick MW (1974) Human rabies. Publ Health Rev Vol III(3):229–273.Google Scholar
  29. Heberling RL, Kalter SS, Smith JS, Hildebrand DG (1987) Serodiagnosis of rabies by dot immunobinding assay. J Clin Microbiol 25:1262–1264.PubMedGoogle Scholar
  30. Heimick CG (1983) The epidemiology of human rabies postexposure prophylaxis, 1980–1981. JAMA 250:1990–1996.CrossRefGoogle Scholar
  31. Houff SA, Burton RC, Wilson RW, Henson TE, London WT, Baer GM, Anderson LJ, Winkler WG, Madden DL, Sever JL (1979) Human-to-human transmission of rabies virus by corneal transplant. N Eng J Med 300:603–604.CrossRefGoogle Scholar
  32. Immunization Practices Advisory Committee (1984) Rabies prevention United States, 1984. MMWR 33:393–402. Centers for Disease Control, Public Health Service, US Dept Health and Human Services, Atlanta, GA.Google Scholar
  33. Jenkins SR, Perry BD, Winkler WG (1988) Ecology and epidemiology of raccoon rabies. Rev Infect Dis 10(Suppl 4):S620–S625.PubMedCrossRefGoogle Scholar
  34. Johnson HN (1989) Rabies virus. Ch 26, pp 893–923. In Schmidt NJ, Emmons RW (Eds). Diagnostic Procedures for Viral, Rickettsial and Chlamydial Infections, 6th Ed, American Public Health Association, Washington, DC.Google Scholar
  35. Johnson KP, Swoveland PT, Emmons RW (1980) Diagnosis of rabies by immunofluorescence in trypsin-treated histologic sections. JAMA 244:41–43.PubMedCrossRefGoogle Scholar
  36. Kaplan C (1983) Recent studies on rabies. Ch 12, pp 255–262. In Waterson AP (Ed) Recent Advances in Clinical Virology. Number Three. Churchill Livingston, Edinburgh, London, Melbourne, New York.Google Scholar
  37. Kühler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497.CrossRefGoogle Scholar
  38. Koprowski H (1988) Glimpses into the future of rabies research. Rev Infect Dis 10(Suppl 4):S810–S813.PubMedCrossRefGoogle Scholar
  39. Kuwert E, Merieux C, Koprowski H, Bögel K (Eds) (1985) Rabies in the Tropics. Springer-Verlag, Berlin, Heidelberg, New York, Tokyo.CrossRefGoogle Scholar
  40. Lery L, Rotivel Y, Trabaud MA, Parvaz P, Mouterde S, Relyveld EH (1986) Combined tetanus-rabies vaccination. Dev Biol Stand 65:209–220.PubMedGoogle Scholar
  41. Mannen K, Mifune K, Reid-Sanden FL, Smith JS, Yager PA, Sumner JW, Fishbein DB, Tong TC, Baer GM (1987) Microneutralization test for rabies virus based on an enzyme immunoassay. J Clin Microbiol 25:2440–2442.PubMedGoogle Scholar
  42. Merigan TC, Baer GM, Winkler WC, Bernard KW, Gibert CG, Chany C, Veronesi R (1984) Human leucocyte interferon administration to patients with symptomatic and suspected rabies. Ann Neurol 16:82–87.PubMedCrossRefGoogle Scholar
  43. National Association of State Public Health Veterinarians, Inc. (1989) Compendium of Animal Rabies Control, 1989 MMWR 37:789–796. Centers for Disease Control, Public Health Service; US Dept Health and Human Services, Atlanta, GAGoogle Scholar
  44. Nicholson KG, Warrell MJ, Xueref C, Lee S (1985) pp 334–339. In Kuwert E, Merieux C, Koprowski H, Bögel K (Eds) Rabies in the Tropics. Springer-Verlag, Berlin, Heidelberg, New York, Tokyo.CrossRefGoogle Scholar
  45. Perrin P, Rollin PE, Sureau P (1986) A rapid rabies enzyme immuno-diagnosis (RREID): a useful and simple technique for the routine diagnosis of rabies. J Biol Stand 14:217–222.PubMedCrossRefGoogle Scholar
  46. Perrin P, Sureau P (1987) A collaborative study of an experimental kit for rapid rabies enzyme immunodiagnosis (RREID). Bull.WHO 65:489–493.PubMedGoogle Scholar
  47. Remington PL, Shope T, Andrew J (1985) A recommended approach to the evaluation of human rabies exposure in an acute-care hospital. JAMA 254:67–69.PubMedCrossRefGoogle Scholar
  48. Robinson PA (1984) Rabies virus. Ch 18, pp 485–511. In Belshe RB (Ed) Textbook of Human Virology. PSG Publishing Co, Inc. Littleton, MA.Google Scholar
  49. Rudd RJ, Trimarchi CV, Abelseth MK (1980) Tissue culture technique for routine isolation of street strain rabies virus. J Clin Microbiol 12:590–593.PubMedGoogle Scholar
  50. Rupprecht CE, Glickman LT, Spencer PA, Wiktor TJ (1987) Epidemiology of rabies virus variants. Differentiation using monoclonal antibodies and discriminant analysis. Amer J Epidemiol 126:298–309.CrossRefGoogle Scholar
  51. Smith AL, Tignor GH, Emmons RW, Woodie JD (1978) Isolation of field rabies virus strains in CER and murine neuroblastoma cell cultures. Intervirology 9:359–361.PubMedCrossRefGoogle Scholar
  52. Smith JS (1988) Monoclonal antibody studies of rabies in insectivorous bats of the United States. Rev Infect Dis 10(Suppl 4):S637–S643.PubMedCrossRefGoogle Scholar
  53. Smith JS, Reid-Sanden FL, Roumillat LF, Trimarchi C, Clark K, Baer GM, Winkler WG (1986) Demonstration of antigenic variation among rabies virus isolates by using monoclonal antibodies to nucleocapsid proteins. J Clin Microbiol 24:573–580.PubMedGoogle Scholar
  54. Smith JS, Sumner JW, Roumillat LF, Baer GM, Winkler WG (1984) Antigenic characteristics of isolates associated with a new epizootic of raccoon rabies in the United States. J Infect Dis 149:769–774.PubMedCrossRefGoogle Scholar
  55. Smith JS, Sumner J, Roumillat F, Baer GM, Winkler WG (1985) Epidemiological analysis of street rabies viruses from enzootic areas of the United States, pp 604–610. In Kuwert E, Merieux C, Koprowski H, Bögel K, (Eds) Rabies in the Tropics. Springer-Verlag, Berlin, Heidelberg, New York, Tokyo.CrossRefGoogle Scholar
  56. Sureau P (1988) History of rabies: advances in research towards prevention during the last 30 years. Rev Infect Dis 10(Suppl 4):S581–S584.PubMedCrossRefGoogle Scholar
  57. Sureau P, Lafon M, Baer GM (1988) Rhabdoviridae: Rabies and Vesicular Stomatitis Viruses. Ch 29, pp 571–594. In Lennette EH, Halonen P, Murphy FA (Eds) Laboratory Diagnosis of Infectious Diseases. Principles and Practice. Springer-Verlag. New York, Berlin, Heidelberg, London, Paris, Tokyo.CrossRefGoogle Scholar
  58. Sureau P, Portnoi D, Rollin P, Lapresle C, Lapresle C, Chaouni-Berbich A (1981) Prevention de la transmission interhumaine de la rage apres greffe de cornee. C R Acad Sci Paris III 293:689–692.Google Scholar
  59. Umoh JU, Blenden DC (1981) Immunofluorescent staining of rabies virus antigen in formalin-fixed tissue after treatment with trypsin. Bull.WHO 59:737–744.PubMedGoogle Scholar
  60. Umoh JU, Blenden DC (1983) Comparison of primary skunk brain and kidney and raccoon kidney cells with established cell lines for isolation and propagation of street rabies virus. Infect Immun 41:1370–1372.PubMedGoogle Scholar
  61. Umoh JU, Ezeokoli CD, Okoh AEJ (1985) Immunofluorescent staining of trypsinized formalin-fixed brain smears for rabies antigen: results compared with those obtained by standard methods for 221 suspect animal cases in Nigeria. J Hyg Camb 94:129–134.PubMedCrossRefGoogle Scholar
  62. Veterinary Public Health Unit (1988) Compendium of US Licensed Animal Rabies Vaccines and their application in dogs under the California Rabies Control Program. (September 1988) California State Department of Health Services, Berkeley, CA.Google Scholar
  63. Vishawapoka U, Hemachudha T, Tepsumethanon W, Polsuwan C, Tirawatnpong S, Phanuphak P (1988) Detection of rabies antigen in canine parotid glands by dot-blot technique. Lancet 1:881.PubMedCrossRefGoogle Scholar
  64. Vodopija I (1988) Current issues in human rabies immunization. Rev Infect Dis 10(Suppl 4):S758–S763.PubMedCrossRefGoogle Scholar
  65. Vodopija I, Sureau P, Smerdel S, Lafon M, Baklaic Z, Ljubicić M, Svjetlicić M (1988) Interaction of rabies vaccine with human rabies immunoglobulin and reliability of a 2-1-1 schedule application for postexposure treatment. Vaccine 6:283–286PubMedCrossRefGoogle Scholar
  66. Warrell DA, Warrell MJ (1988) Human rabies and its prevention: an overview. Rev Infect Dis 10(Suppl 4):S726–S731.PubMedCrossRefGoogle Scholar
  67. Warrell J, Looareesuwan S, Manatsathit S, White NJ, Phuapradit P, Vejjajiva A, Hoke CH, Burke DS, Warrell DA (1988) Rapid diagnosis of rabies and post-vaccinal encephalitides. Clin Exp Immunol 71:229–234.PubMedGoogle Scholar
  68. Webster WA (1987) A tissue culture infection test in routine rabies diagnosis. Can J Vet Res 51:367–369.PubMedGoogle Scholar
  69. Whetstone CA, Bunn TO, Emmons RW (1984) Use of monoclonal antibodies to confirm vaccine-induced rabies in ten dogs, two cats, and one fox. JAVMA 185:285–288.PubMedGoogle Scholar
  70. Wiktor TJ, Fernandes MV, Koprowski H (1964) Cultivation of rabies virus in human diploid cell strain WI-38. J Immunol 93:353–366.PubMedGoogle Scholar
  71. Wiktor TJ, Flamand A, Koprowski H (1980) Use of monoclonal antibodies in diagnosis of rabies virus infection and differentiation of rabies and rabies-related viruses. J Virol Methods 1:33–46.CrossRefGoogle Scholar
  72. Wiktor TJ, Koprowski H (1978) Monoclonal antibodies against rabies virus produced by somatic cell hybridization: detection of antigenic variants. Proc Natl Acad Sci USA 75:3938–3942.PubMedCrossRefGoogle Scholar
  73. Wiktor T, Plotkin SA, Koprowski H (1988) Rabies vaccine. Ch 22, pp 474–491. In Plotkin SA, Mortimer EA Jr (Eds) Vaccines. WB Saunders Co., Harcourt Brace Jovanovich, Inc. Philadelphia, London, Toronto, Montreal, Sydney, Tokyo.Google Scholar
  74. Wilde H, Chomchey P, Prakonongari S, Punyaratabandhu P (1987) Safety of equine rabies immune globulin (Letter). Lancet 2:1275.PubMedCrossRefGoogle Scholar
  75. Wilde H, Chomchey P, Prakongsri S, Puyaratabandhu P, Chutivongse S (1989) Adverse effects of equine rabies immune globulin. Vaccine 7:10–11.PubMedCrossRefGoogle Scholar
  76. Wunner WH, Larson JK, Dietzschold B, Smith CL (1988) The molecular biology of rabies viruses. Rev Infect Dis 10(Suppl 4):S771–S784.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Richard W. Emmons
    • 1
  1. 1.Viral and Rickettsial Disease Laboratory, Division of LaboratoriesCalifornia State Department of Health ServicesBerkeleyUSA

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