Laboratory diagnostics in dog-mediated rabies: An overview of performance and a proposed strategy for various settings

International Journal of Infectious Diseases

Volumn 46, Issue , 2016, Pages 107-114

  Duong, Veasna ^a   Tarantola, Arnaud ^a   Ong, Sivuth ^a   Mey, Channa ^a   Choeung, Rithy ^a   Ly, Sowath ^a   Bourhy, Hervé ^b   Dussart, Philippe ^a   Buchy, Philippe ^c  

^a INSTITUT PASTEUR DU CAMBODGE   (Cambodia)

^b INSTITUT PASTEUR   (France)

^c R and D Asia Pacific   (Singapore)

Author keywords

Animal; Diagnosis; Endemic; Human; Rabies; Virus

Indexed keywords

ANIMAL; DOG; DOG DISEASES; GENETICS; HOSPITAL LABORATORY; HUMAN; ISOLATION AND PURIFICATION; RABIES; RABIES VIRUS; STANDARDS; TRANSMISSION; VIROLOGY;

ANIMALS; DOG DISEASES; DOGS; HUMANS; LABORATORIES, HOSPITAL; RABIES; RABIES VIRUS;

EID: 84973096912     PISSN: 12019712     EISSN: 18783511     Source Type: Journal    
DOI: 10.1016/j.ijid.2016.03.016     Document Type: Review

References (79)

1. Roux EPP. Des nouvelles acquisitions sur la rage. Paris: A. Parent, Imprimeur de la Faculté de Médecine; 1883, Available at: (accessed January 20, 2016). http://www2.biusante.parisdescartes.fr/livanc/?cote=TPAR1883x398%26do=pdf.
2. Hanlon C.A., Nadin-Davis S.A. Laboratory diagnosis of rabies. Rabies. 2013, 409-459. Academic Press, Boston. Third ed. A.C. Jackson (Ed.).
3. Babes V. Traité de la rage 1912, Ballière, Paris, Available at: http://gallica.bnf.fr/ark:/12148/bpt6k5462676f (accessed January 20, 2016).
4. World Health Organization WHO hosts milestone international conference to target global elimination of dog-mediated human rabies 2016, WHO, Geneva, Switzerland, Available at: http://www.webcitation.org/6efTbkujx (accessed January 20, 2016).
5. Fardy J.M., Barrett B.J. Evaluation of diagnostic tests. Methods Mol Biol 2015, 1281:289-300.
6. Rupprecht C., Nagarajan T. Current laboratory techniques in rabies diagnosis, research and prevention 2015, Academic Press, Cambridge, Mass. (USA), Available at: http://www.sciencedirect.com/science/book/9780128000144 (accessed February 3, 2016).
7. Barrat J., Picard-Meyer E., Cliquet F. Rabies diagnosis. Dev Biol 2006, 125:71-77.
8. Meslin F.X., Kaplan M.M., Koprowski H. Laboratory techniques in rabies 1996, World Health Organization, Geneva, Switzerland. 4th ed.
9. Madhusudana S.N., Subha S., Thankappan U., Ashwin Y.B. Evaluation of a direct rapid immunohistochemical test (dRIT) for rapid diagnosis of rabies in animals and humans. Virol Sin 2012, 27:299-302.
10. Lembo T., Niezgoda M., Velasco-Villa A., Cleaveland S., Ernest E., Rupprecht C.E. Evaluation of a direct, rapid immunohistochemical test for rabies diagnosis. Emerg Infect Dis 2006, 12:310-313.
11. Voehl K.M., Saturday G.A. Evaluation of a rapid immunodiagnostic rabies field surveillance test on samples collected from military operations in Africa, Europe, and the Middle East. US Army Med Dep J 2014, 27-32.
12. Mani R.S., Madhusudana S.N. Laboratory diagnosis of human rabies: recent advances. Sci World J 2013, 2013:e569712.
13. Dacheux L., Bourhy H. Virus isolation in cell culture: the rabies tissue culture infection test. Current laboratory techniques in rabies diagnosis, research and prevention 2015, 25-31. Academic Press. C. Rupprecht, T. Nagarajan (Eds.).
14. Bourhy H., Rollin P.E., Vincent J., Sureau P. 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 1989, 27:519-523.
15. Barrat J., Barrat M.J., Picard M., Aubert M.F. Diagnosis of rabies by cell culture. Comp Immunol Microbiol Infect Dis 1988, 11:207-214.
16. World Health Organization WHO expert consultation on rabies (second report) 2013, WHO, Geneva, Switzerland.
17. OIE - World Organisation for Animal Health Manual of diagnostic tests and vaccines for terrestrial animals 2012, OIE, Paris. 7th ed.
18. Picard-Meyer E., Bruyère V., Barrat J., Tissot E., Barrat M.J., Cliquet F. Development of a hemi-nested RT-PCR method for the specific determination of European bat lyssavirus 1. Comparison with other rabies diagnostic methods. Vaccine 2004, 22:1921-1929.
19. Dacheux L., Reynes J.M., Buchy P., Sivuth O., Diop B.M., Rousset D., Rathat C., et al. A reliable diagnosis of human rabies based on analysis of skin biopsy specimens. Clin Infect Dis 2008, 47:1410-1417.
20. Rojas Anaya E., Loza-Rubio E., Banda Ruiz V.M., Hernández Baumgarten E. Use of reverse transcription-polymerase chain reaction to determine the stability of rabies virus genome in brains kept at room temperature. J Vet Diagn Invest 2006, 18:98-101.
21. Beltran F.J., Dohmen F.G., Del Pietro H., Cisterna D.M. Diagnosis and molecular typing of rabies virus in samples stored in inadequate conditions. J Infect Dev Ctries 2014, 8:1016-1021.
22. Araújo D.B., Langoni H., Almeida M.F., Megid J. Heminested reverse-transcriptase polymerase chain reaction (hnRT-PCR) as a tool for rabies virus detection in stored and decomposed samples. BMC Res Notes 2008, 1:17.
23. Albas A., Ferrari C.I., da Silva L.H., Bernardi F., Ito F.H. Influence of canine brain decomposition on laboratory diagnosis of rabies. Rev Soc Bras Med Trop 1999, 32:19-22.
24. David D., Yakobson B., Rotenberg D., Dveres N., Davidson I., Stram Y. Rabies virus detection by RT-PCR in decomposed naturally infected brains. Vet Microbiol 2002, 87:111-118.
25. Muleya W., Namangala B., Mweene A., Zulu L., Fandamu P., Banda D., Kimura T., et al. Molecular epidemiology and a loop-mediated isothermal amplification method for diagnosis of infection with rabies virus in Zambia. Virus Res 2012, 163:160-168.
26. Boldbaatar B., Inoue S., Sugiura N., Noguchi A., Orbina J.R., Demetria C., Miranda M.E., et al. Rapid detection of rabies virus by reverse transcription loop-mediated isothermal amplification. Jpn J Infect Dis 2009, 62:187-191.
27. Sugiyama M., Ito N., Minamoto N. Isothermal amplification of rabies virus gene. J Vet Med Sci 2003, 65:1063-1068.
28. Wacharapluesadee S., Phumesin P., Supavonwong P., Khawplod P., Intarut N., Hemachudha T. Comparative detection of rabies RNA by NASBA, real-time PCR and conventional PCR. J Virol Methods 2011, 175:278-282.
29. Fooks A.R., Johnson N., Freuling C.M., Wakeley P.R., Banyard A.C., McElhinney L.M., Marston D.A., et al. Emerging technologies for the detection of rabies virus: challenges and hopes in the 21st century. PLoS Negl Trop Dis 2009, 3:e530.
30. Hayman D.T., Banyard A.C., Wakeley P.R., Harkess G., Marston D., Wood J.L., Cunningham A.A., et al. A universal real-time assay for the detection of Lyssaviruses. J Virol Methods 2011, 177:87-93.
31. Mey C., Metlin A., Duong V., Ong S., In S., Horwood P.F., Reynes J.M., et al. Evidence of two distinct phylogenetic lineages of dog rabies virus circulating in Cambodia. Infect Genet Evol 2016, 38:55-61.
32. Bourhy H., Sureau P. Méthodes de laboratoire pour le diagnostic de la rage 1991, Institut Pasteur, Paris.
33. US Centers for Disease Control and Prevention CDC - Diagnosis Direct fluorescent antibody test-rabies 2011, CDC, Atlanta, GA, Available at: http://www.webcitation.org/6YLMcxOSW.
34. Robardet E., Andrieu S., Rasmussen T.B., Dobrostana M., Horton D.L., Hostnik P., Jaceviciene I., et al. Comparative assay of fluorescent antibody test results among twelve European national reference laboratories using various anti-rabies conjugates. J Virol Methods 2013, 191:88-94.
35. Perrin P., Sureau P. A collaborative study of an experimental kit for rapid rabies enzyme immunodiagnosis (RREID). Bull World Health Organ 1987, 65:489-493.
36. Perrin P., Gontier C., Lecocq E., Bourhy H. A modified rapid enzyme immunoassay for the detection of rabies and rabies-related viruses: RREID-lyssa. Biologicals 1992, 20:51-58.
37. Perrin P., Rollin P.E., Sureau P. A rapid rabies enzyme immuno-diagnosis (RREID): a useful and simple technique for the routine diagnosis of rabies. J Biol Stand 1986, 14:217-222.
38. Xu G., Weber P., Hu Q., Xue H., Audry L., Li C., Wu J., et al. A simple sandwich ELISA (WELYSSA) for the detection of lyssavirus nucleocapsid in rabies suspected specimens using mouse monoclonal antibodies. Biol J Int Assoc Biol Stand 2007, 35:297-302.
39. Xu G., Weber P., Hu Q., Xue H., Audry L., Li C., Wu J., et al. WELYSSA: a simple tool using mouse monoclonal antibodies for the detection of lyssavirus nucleocapsid in rabies suspected specimens. Dev Biol 2008, 131:555-561.
40. Oelofsen M.J., Smith M.S. Rabies and bats in a rabies-endemic area of southern Africa: application of two commercial test kits for antigen and antibody detection. Onderstepoort J Vet Res 1993, 60:257-260.
41. Miranda N.L., Robles C.G. A comparative evaluation of a new immunoenzymatic test (RREID) with currently used diagnostic tests (DME and FAT) for dog rabies. Southeast Asian J Trop Med Public Health 1991, 22:46-50.
42. Saxena S.N., Madhusudana S.N., Tripathi K.K., Gupta P., Ahuja S. Evaluation of the new rapid rabies immunodiagnosis technique. Indian J Med Res 1989, 89:445-448.
43. Kang B., Oh J., Lee C., Park B.K., Park Y., Hong K., Lee K., et al. Evaluation of a rapid immunodiagnostic test kit for rabies virus. J Virol Methods 2007, 145:30-36.
44. Yang D.K., Shin E.K., Oh Y.I., Lee K.W., Lee C.S., Kim S.Y., Lee J.A., et al. Comparison of four diagnostic methods for detecting rabies viruses circulating in Korea. J Vet Sci 2012, 13:43-48.
45. Dürr S., Naïssengar S., Mindekem R., Diguimbye C., Niezgoda M., Kuzmin I., Rupprecht C.E., et al. Rabies diagnosis for developing countries. PLoS Negl Trop Dis 2008, 2:e206.
46. Dyer J.L., Niezgoda M., Orciari L.A., Yager P.A., Ellison J.A., Rupprecht C.E. Evaluation of an indirect rapid immunohistochemistry test for the differentiation of rabies virus variants. J Virol Methods 2013, 190:29-33.
47. Wasniewski M., Labbe A., Tribout L., Rieder J., Labadie A., Schereffer J.L., Cliquet F. Evaluation of a rabies ELISA as an alternative method to seroneutralisation tests in the context of international trade of domestic carnivores. J Virol Methods 2014, 195:211-220.
48. Johnson N., Cunningham A.F., Fooks A.R. The immune response to rabies virus infection and vaccination. Vaccine 2010, 28:3896-3901.
49. World Health Organization WHO recommended surveillance standards. Rabies 1999, WHO, Geneva, Switzerland. 2nd ed.
50. Noah D.L., Drenzek C.L., Smith J.S., Krebs J.W., Orciari L., Shaddock J., Sanderlin D., et al. Epidemiology of human rabies in the United States, 1980 to 1996. Ann Intern Med 1998, 128:922-930.
51. Kasempimolporn S., Hemachudha T., Khawplod P., Manatsathit S. Human immune response to rabies nucleocapsid and glycoprotein antigens. Clin Exp Immunol 1991, 84:195-199.
52. Mallewa M., Fooks A.R., Banda D., Chikungwa P., Mankhambo L., Molyneux E., Molyneux M.E., et al. Rabies encephalitis in malaria-endemic area, Malawi, Africa. Emerg Infect Dis 2007, 13:136-139.
53. Tarantola A., Goutard F., Newton P., de Lamballerie X., Lortholary O., Cappelle J., Buchy P. Estimating the burden of Japanese encephalitis virus and other encephalitides in countries of the Mekong region. PLoS Negl Trop Dis 2014, 8:e2533.
54. World Health Organization. Criteria for application withholding of post-exposure treatment. Geneva, Switzerland: WHO. Available at: (accessed February 5, 2016). http://www.who.int/rabies/human/generalconsid/en/.
55. Velasco-Villa A., Messenger S.L., Orciari L.A., Niezgoda M., Blanton J.D., Fukagawa C., Rupprecht C.E. Identification of new rabies virus variant in Mexican immigrant. Emerg Infect Dis 2008, 14:1906-1908.
56. Hampson K., Coudeville L., Lembo T., Sambo M., Kieffer A., Attlan M., Barrat J., et al. Estimating the global burden of endemic canine rabies. PLoS Negl Trop Dis 2015, 9:e0003709.
57. Dacheux L., Wacharapluesadee S., Hemachudha T., Meslin F.X., Buchy P., Reynes J.M., Bourhy H. More accurate insight into the incidence of human rabies in developing countries through validated laboratory techniques. PLoS Negl Trop Dis 2010, 4:e765. 10.1371/journal.pntd.0000765.
58. Lherm C. Classement des agents biologiques 1999, INRS, France.
59. Advisory Committee on Dangerous Pathogens The approved list of biological agents 2013, Health and Safety Executive, Bootle, United Kingdom, Available at: http://www.hse.gov.uk/pubns/misc208.pdf (accessed).
60. Chosewood L.C., Wilson D.E. US Centers for Disease Control, National Institutes of Health. Biosafety in microbiological and biomedical laboratories 2010, US GPO, Washington.
61. Barrat J. Simple technique for the collection and shipment of brain specimens for rabies diagnosis. Laboratory techniques in rabies 1996, 425-432. WHO, Geneva, Switzerland. 4th ed. F.X. Meslin, M.M. Kaplan, H. Koprowski (Eds.).
62. OIE - World Organisation for Animal Health Terrestrial manual 2012, OIE, Available at: http://www.oie.int/en/international-standard-setting/terrestrial-manual/ (accessed February 4, 2016).
63. US Centers for Disease Control and Prevention Diagnosis in animals and humans-rabies 2011, CDC, Atlanta, GA, Available at: Available at: http://www.cdc.gov/rabies/diagnosis/animals-humans.html (accessed February 5, 2016).
64. Interstate Council for Standardization, Metrology and Certification Moscow, Russian Federation Methods of laboratory diagnostic of rabies 2013, CDC, Atlanta, GA, Available at: http://files.stroyinf.ru/Data2/1/4293777/4293777838.pdf (accessed January 20, 2016).
65. Aguèmon C., Tarantola A., Zoumènou E., Goyet S., Assouto P., Ly S., Mewanou S., et al. Rabies transmission risks during peripartum-two cases and a review of the literature. Vaccine 2016, 34(15):1752-1757. Epub 2016 Mar 3. 10.1016/j.vaccine.2016.02.065.
66. Tillotson J.R., Axelrod D., Lyman D.O. Epidemiologic notes and reports: rabies in laboratory worker-New York. MMWR Morb Mortal Wkly Rep 1977, 26:183-184.
67. Burnett L.C., Lunn G., Coico R. Biosafety: guidelines for working with pathogenic and infectious microorganisms. Current protocols in microbiology 2009, John Wiley and Sons, Inc, Hoboken, NJ, p. 1A.1.1-1A.1.14. R. Coico, A. McBride, J.M. Quarles, B. Stevenson, R.K. Taylor (Eds.).
68. Tarantola A., Crabol Y., Mahendra B.J., In S., Barennes H., Bourhy H., Peng Y., et al. Caring for rabies patients in developing countries-the neglected importance of palliative care. Trop Med Int Health 2016, 10.1111/tmi.12670.
69. Bryceson A.D., Greenwood B.M., Warrell D.A., Davidson N.M., Pope H.M., Lawrie J.H., Barnes H.J., et al. Demonstration during life of rabies antigen in humans. J Infect Dis 1975, 131:71-74.
70. Crepin P., Audry L., Rotivel Y., Gacoin A., Caroff C., Bourhy H. Intravitam diagnosis of human rabies by PCR using saliva and cerebrospinal fluid. J Clin Microbiol 1998, 36:1117-1121.
71. Tong T.R., Leung K.M., Lee K.C., Lam A.W. Trucut needle biopsy through superior orbital fissure for the diagnosis of rabies. Lancet 1999, 354:2137-2138.
72. Sudarsanam T.D., Chacko G., David R.D. Post-mortem trucut transnasal brain biopsy in the diagnosis of encephalitis. Trop Doct 2008, 38:163-165.
73. Andrulonis J.A., Debbie J.G. Effect of acetone fixation on rabies immunofluorescence in glycerine-preserved tissues. Health Lab Sci 1976, 13:207-208.
74. International Air Transport Association. UN 3373-biological substance, category B. IATA; 2015. Available at: (accessed January 20, 2016). https://www.iata.org/whatwedo/cargo/dgr/Documents/packing-instruction-650-DGR56-en.pdf.
75. World Health Organization Guidance on regulations for the transport of infectious substances 2009-2010 2008, WHO, Geneva, Switzerland, Available at: http://www.who.int/csr/resources/publications/biosafety/WHO_HSE_EPR_2008_10/en/ (accessed February 4, 2016).
76. Sakai T., Ishii A., Segawa T., Takagi Y., Kobayashi Y., Itou T. Establishing conditions for the storage and elution of rabies virus RNA using FTA(®) cards. J Vet Med Sci 2015, 77:461-465.
77. Picard-Meyer E., Barrat J., Cliquet F. Use of filter paper (FTA) technology for sampling, recovery and molecular characterisation of rabies viruses. J Virol Methods 2007, 140:174-182.
78. Chandramohan D., Maude G.H., Rodrigues L.C., Hayes R.J. Verbal autopsies for adult deaths: their development and validation in a multicentre study. Trop Med Int Health 1998, 3:436-446.
79. Hampson K., Dobson A., Kaare M., Dushoff J., Magoto M., Sindoya E., Cleaveland S. Rabies exposures, post-exposure prophylaxis and deaths in a region of endemic canine rabies. PLoS Negl Trop Dis 2008, 2:e339.