Low level of the immune response against rabies virus in dogs and cats - a cross-sectional study in sheltered animals, Santander, Colombia.

Rabies is an incurable and fatal progressive viral encephalomyelitis that causes approximately 61,000 deaths a year globally mainly by dog bites, which show the importance of anti-rabies vaccination in dogs to achieve elimination of the disease. In Colombia, multiple cases of human rabies transmitte...

Full description

Autores:
Ruiz Sáenz, Julián
Martínez Gutiérrez, Marlen
Trujillo Rojas, Lina María
Tipo de recurso:
Article of journal
Fecha de publicación:
2018
Institución:
Universidad Cooperativa de Colombia
Repositorio:
Repositorio UCC
Idioma:
OAI Identifier:
oai:repository.ucc.edu.co:20.500.12494/15167
Acceso en línea:
http://dx.doi.org/10.1590/1678-5150-pvb-5997
https://hdl.handle.net/20.500.12494/15167
Palabra clave:
Colombia
Santander
rabies virus
dogs
cats
sheltered animals
vaccination
Immune response
Rights
openAccess
License
Atribución – No comercial
id COOPER2_b1cc5528adaee2249087c3b500375aea
oai_identifier_str oai:repository.ucc.edu.co:20.500.12494/15167
network_acronym_str COOPER2
network_name_str Repositorio UCC
repository_id_str
dc.title.spa.fl_str_mv Low level of the immune response against rabies virus in dogs and cats - a cross-sectional study in sheltered animals, Santander, Colombia.
title Low level of the immune response against rabies virus in dogs and cats - a cross-sectional study in sheltered animals, Santander, Colombia.
spellingShingle Low level of the immune response against rabies virus in dogs and cats - a cross-sectional study in sheltered animals, Santander, Colombia.
Colombia
Santander
rabies virus
dogs
cats
sheltered animals
vaccination
Immune response
title_short Low level of the immune response against rabies virus in dogs and cats - a cross-sectional study in sheltered animals, Santander, Colombia.
title_full Low level of the immune response against rabies virus in dogs and cats - a cross-sectional study in sheltered animals, Santander, Colombia.
title_fullStr Low level of the immune response against rabies virus in dogs and cats - a cross-sectional study in sheltered animals, Santander, Colombia.
title_full_unstemmed Low level of the immune response against rabies virus in dogs and cats - a cross-sectional study in sheltered animals, Santander, Colombia.
title_sort Low level of the immune response against rabies virus in dogs and cats - a cross-sectional study in sheltered animals, Santander, Colombia.
dc.creator.fl_str_mv Ruiz Sáenz, Julián
Martínez Gutiérrez, Marlen
Trujillo Rojas, Lina María
dc.contributor.author.none.fl_str_mv Ruiz Sáenz, Julián
Martínez Gutiérrez, Marlen
Trujillo Rojas, Lina María
dc.subject.spa.fl_str_mv Colombia
Santander
topic Colombia
Santander
rabies virus
dogs
cats
sheltered animals
vaccination
Immune response
dc.subject.other.spa.fl_str_mv rabies virus
dogs
cats
sheltered animals
vaccination
Immune response
description Rabies is an incurable and fatal progressive viral encephalomyelitis that causes approximately 61,000 deaths a year globally mainly by dog bites, which show the importance of anti-rabies vaccination in dogs to achieve elimination of the disease. In Colombia, multiple cases of human rabies transmitted by dogs and cats have been reported since 1999, showing an increased significance of cats in the transmission of rabies, mainly in rabies of wild origin. Therefore, the aim of the present study was to evaluate the development of neutralizing antibodies in dogs and cats during the mass vaccination campaign of the second half of 2015 in the city of Bucaramanga. For this purpose, a descriptive cross-sectional study with convenience sampling was conducted in 382 dogs and cats (295 dogs, 87 cats), and an evaluation of the humoral immune response of the animals was performed by quantitative ELISA. The prevalence of optimal neutralizing antibodies (>0.5 IU/ml) was only 32.76% (95% CI=28.05-37.46%) in the entire population studied and most of the animals did not have an adequate response to the vaccination, or seroconversion was not detected on them (65.45-95% confidence interval, CI=60.68-70.21%). Significant difference was found between the neutralizing antibody titers in cats and dogs, with a higher neutralizing response in cats. In conclusion, although mass vaccination campaigns for dogs and cats are the most important measure to interrupt virus circulation among the animals, achievement of a good neutralizing immune response in the animals is useful to demonstrate that vaccination has been successful, allowing the maintenance of the required minimum levels of population immunity. These results will allow the implementation of corrective measures in Bucaramanga to achieve better seroconversion rates. Other cities are expected to implement similar seroconversion assessments to verify the quality of effective anti-rabies vaccination in animal populations.
publishDate 2018
dc.date.issued.none.fl_str_mv 2018-11
dc.date.accessioned.none.fl_str_mv 2019-11-20T20:46:22Z
dc.date.available.none.fl_str_mv 2019-11-20T20:46:22Z
dc.type.none.fl_str_mv Artículo
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.coar.none.fl_str_mv http://purl.org/coar/resource_type/c_6501
dc.type.coarversion.none.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.driver.none.fl_str_mv info:eu-repo/semantics/article
dc.type.version.none.fl_str_mv info:eu-repo/semantics/publishedVersion
format http://purl.org/coar/resource_type/c_6501
status_str publishedVersion
dc.identifier.issn.spa.fl_str_mv 0100-736X
dc.identifier.uri.spa.fl_str_mv http://dx.doi.org/10.1590/1678-5150-pvb-5997
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12494/15167
dc.identifier.bibliographicCitation.spa.fl_str_mv Trujillo Rojas, L. M., Martinez Gutierrez, M. y Ruiz-Saenz, J. (2019) Low level of the immune response against rabies virus in dogs and cats, a cross-sectional study in sheltered animals, Santander, Colombia. Pesq. Vet. Bras. 2018.38:11;2109-2116.
identifier_str_mv 0100-736X
Trujillo Rojas, L. M., Martinez Gutierrez, M. y Ruiz-Saenz, J. (2019) Low level of the immune response against rabies virus in dogs and cats, a cross-sectional study in sheltered animals, Santander, Colombia. Pesq. Vet. Bras. 2018.38:11;2109-2116.
url http://dx.doi.org/10.1590/1678-5150-pvb-5997
https://hdl.handle.net/20.500.12494/15167
dc.relation.isversionof.spa.fl_str_mv http://ref.scielo.org/4nn4cd
dc.relation.ispartofjournal.spa.fl_str_mv Pesquisa Veterinária Brasileira
dc.relation.references.spa.fl_str_mv Abela-Ridder B. 2015. Rabies: 100 per cent fatal, 100 per cent preventable. Vet. Rec. 177(6):148-149. <http://dx.doi.org/10.1136/vr.h4196> <PMid:26251539>
Afonso C.L., Amarasinghe G.K., Bányai K., Bào Y., Basler C.F., Bavari S., Bejerman N., Blasdell K.R., Briand F.-X., Briese T., Bukreyev A., Calisher C.H., Chandran K., Chéng J., Clawson A.N., Collins P.L., Dietzgen R.G., Dolnik O., Domier L.L., Dürrwald R., Dye J.M., Easton A.J., Ebihara H., Farkas S.L., Freitas-Astúa J., Formenty P., Fouchier R.A., Fù Y., Ghedin E., Goodin M.M., Hewson R., Horie M., Hyndman T.H., Jiāng D., Kitajima E.W., Kobinger G.P., Kondo H., Kurath G., Lamb R.A., Lenardon S., Leroy E.M., Li C.X., Lin X.D., Liú L., Longdon B., Marton S., Maisner A., Mühlberger E., Netesov S.V., Nowotny N., Patterson J.L., Payne S.L., Paweska J.T., Randall R.E., Rima B.K., Rota P., Rubbenstroth D., Schwemmle M., Shi M., Smither S.J., Stenglein M.D., Stone D.M., Takada A., Terregino C., Tesh R.B., Tian J.H., Tomonaga K., Tordo N., Towner J.S., Vasilakis N., Verbeek M., Volchkov V.E., Wahl-Jensen V., Walsh J.A., Walker P.J., Wang D., Wang L.F., Wetzel T., Whitfield A.E., Xiè J.T., Yuen K.Y., Zhang Y.Z. & Kuhn J.H. 2016. Taxonomy of the order Mononegavirales: update 2016. Arch. Virol. 161(8):2351-2360. <http://dx.doi.org/10.1007/s00705- 016-2880-1> <PMid:27216929>
Albas A., Picolo M.R., Soares C.N., Bachega H.V.U. & Tarumoto M.H. 2013. Humoral immune response in dogs and cats vaccinated against rabies in southeastern Brazil. J. Venom. Anim. Toxins incl. Trop. Dis. 19(1):17. <http://dx.doi.org/10.1186/1678-9199-19-17> <PMid:23899101>
Almeida M.F., Aguiar E.A., Martorelli L.A., Presotto D., Brandão M.M. & Pereira O.A. 1997. Resposta imune humoral de cães à vacina inativada, de cérebro de camundongos lactentes, utilizada nas campanhas anti-rábicas no Brasil. Revta Saúde Públ. 31(5):502-507. <http://dx.doi.org/10.1590/ S0034-89101997000600009>
Arismendy A., García A., Gonzales C., Pinzón C., Delgado E. & Flóres F. 2010. Primer censo canino, felino del área urbana del municipio de Bucaramanga. Universidad Cooperativa de Colombia, Facultad de Medicina Veterinaria y Zootecnia. 130p
dc.rights.license.none.fl_str_mv Atribución – No comercial
dc.rights.accessrights.none.fl_str_mv info:eu-repo/semantics/openAccess
dc.rights.coar.none.fl_str_mv http://purl.org/coar/access_right/c_abf2
rights_invalid_str_mv Atribución – No comercial
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.extent.spa.fl_str_mv 2109-2116
dc.coverage.temporal.spa.fl_str_mv 38 (11)
dc.publisher.spa.fl_str_mv Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Medicina Veterinaría y Zootecnia, Bucaramanga
dc.publisher.program.spa.fl_str_mv Medicina veterinaria y zootecnia
dc.publisher.place.spa.fl_str_mv Bucaramanga
institution Universidad Cooperativa de Colombia
bitstream.url.fl_str_mv https://repository.ucc.edu.co/bitstreams/f321f7ac-e1f7-497c-9552-0465ba584817/download
https://repository.ucc.edu.co/bitstreams/20916399-79bf-40ae-b75d-5d9557831a28/download
https://repository.ucc.edu.co/bitstreams/f960cce4-cce1-4c0c-a8e1-58fc4a97e0be/download
https://repository.ucc.edu.co/bitstreams/16073bc0-a775-49da-894b-c93a248e4b23/download
https://repository.ucc.edu.co/bitstreams/4c009d8b-80e0-4faf-800c-70d972566514/download
https://repository.ucc.edu.co/bitstreams/0fa06300-c5cc-410f-ba3d-97428fcbddaa/download
https://repository.ucc.edu.co/bitstreams/51aff92d-77e7-48de-a226-2888344da886/download
bitstream.checksum.fl_str_mv 00a16f439d1a1b1c80e7df9dbf4e8c5f
bef995fe9fe8bd223ce6ccc4ebe157a8
3bce4f7ab09dfc588f126e1e36e98a45
eb56627ad8e72d7d8286d22899c9c5f9
73bb857df3fcabaf0f412f0d69939576
ff05f22add49e3a604bd414478e0d6ab
9224a1cd079ca6626412129432e50415
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositorio Institucional Universidad Cooperativa de Colombia
repository.mail.fl_str_mv bdigital@metabiblioteca.com
_version_ 1814247256961843200
spelling Ruiz Sáenz, JuliánMartínez Gutiérrez, MarlenTrujillo Rojas, Lina María38 (11)2019-11-20T20:46:22Z2019-11-20T20:46:22Z2018-110100-736Xhttp://dx.doi.org/10.1590/1678-5150-pvb-5997https://hdl.handle.net/20.500.12494/15167Trujillo Rojas, L. M., Martinez Gutierrez, M. y Ruiz-Saenz, J. (2019) Low level of the immune response against rabies virus in dogs and cats, a cross-sectional study in sheltered animals, Santander, Colombia. Pesq. Vet. Bras. 2018.38:11;2109-2116.Rabies is an incurable and fatal progressive viral encephalomyelitis that causes approximately 61,000 deaths a year globally mainly by dog bites, which show the importance of anti-rabies vaccination in dogs to achieve elimination of the disease. In Colombia, multiple cases of human rabies transmitted by dogs and cats have been reported since 1999, showing an increased significance of cats in the transmission of rabies, mainly in rabies of wild origin. Therefore, the aim of the present study was to evaluate the development of neutralizing antibodies in dogs and cats during the mass vaccination campaign of the second half of 2015 in the city of Bucaramanga. For this purpose, a descriptive cross-sectional study with convenience sampling was conducted in 382 dogs and cats (295 dogs, 87 cats), and an evaluation of the humoral immune response of the animals was performed by quantitative ELISA. The prevalence of optimal neutralizing antibodies (>0.5 IU/ml) was only 32.76% (95% CI=28.05-37.46%) in the entire population studied and most of the animals did not have an adequate response to the vaccination, or seroconversion was not detected on them (65.45-95% confidence interval, CI=60.68-70.21%). Significant difference was found between the neutralizing antibody titers in cats and dogs, with a higher neutralizing response in cats. In conclusion, although mass vaccination campaigns for dogs and cats are the most important measure to interrupt virus circulation among the animals, achievement of a good neutralizing immune response in the animals is useful to demonstrate that vaccination has been successful, allowing the maintenance of the required minimum levels of population immunity. These results will allow the implementation of corrective measures in Bucaramanga to achieve better seroconversion rates. Other cities are expected to implement similar seroconversion assessments to verify the quality of effective anti-rabies vaccination in animal populations.http://scienti.colciencias.gov.co:8081/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0000153095https://orcid.org/0000-0002-1447-1458julian.ruizs@campusucc.edu.coMarlen.martinezg@campucucc.edu.colinatrujillor@gmail.comhttps://scholar.google.com/citations?user=o3Y7mZwAAAAJ&hl=es2109-2116Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Medicina Veterinaría y Zootecnia, BucaramangaMedicina veterinaria y zootecniaBucaramangahttp://ref.scielo.org/4nn4cdPesquisa Veterinária BrasileiraAbela-Ridder B. 2015. Rabies: 100 per cent fatal, 100 per cent preventable. Vet. Rec. 177(6):148-149. <http://dx.doi.org/10.1136/vr.h4196> <PMid:26251539>Afonso C.L., Amarasinghe G.K., Bányai K., Bào Y., Basler C.F., Bavari S., Bejerman N., Blasdell K.R., Briand F.-X., Briese T., Bukreyev A., Calisher C.H., Chandran K., Chéng J., Clawson A.N., Collins P.L., Dietzgen R.G., Dolnik O., Domier L.L., Dürrwald R., Dye J.M., Easton A.J., Ebihara H., Farkas S.L., Freitas-Astúa J., Formenty P., Fouchier R.A., Fù Y., Ghedin E., Goodin M.M., Hewson R., Horie M., Hyndman T.H., Jiāng D., Kitajima E.W., Kobinger G.P., Kondo H., Kurath G., Lamb R.A., Lenardon S., Leroy E.M., Li C.X., Lin X.D., Liú L., Longdon B., Marton S., Maisner A., Mühlberger E., Netesov S.V., Nowotny N., Patterson J.L., Payne S.L., Paweska J.T., Randall R.E., Rima B.K., Rota P., Rubbenstroth D., Schwemmle M., Shi M., Smither S.J., Stenglein M.D., Stone D.M., Takada A., Terregino C., Tesh R.B., Tian J.H., Tomonaga K., Tordo N., Towner J.S., Vasilakis N., Verbeek M., Volchkov V.E., Wahl-Jensen V., Walsh J.A., Walker P.J., Wang D., Wang L.F., Wetzel T., Whitfield A.E., Xiè J.T., Yuen K.Y., Zhang Y.Z. & Kuhn J.H. 2016. Taxonomy of the order Mononegavirales: update 2016. Arch. Virol. 161(8):2351-2360. <http://dx.doi.org/10.1007/s00705- 016-2880-1> <PMid:27216929>Albas A., Picolo M.R., Soares C.N., Bachega H.V.U. & Tarumoto M.H. 2013. Humoral immune response in dogs and cats vaccinated against rabies in southeastern Brazil. J. Venom. Anim. Toxins incl. Trop. Dis. 19(1):17. <http://dx.doi.org/10.1186/1678-9199-19-17> <PMid:23899101>Almeida M.F., Aguiar E.A., Martorelli L.A., Presotto D., Brandão M.M. & Pereira O.A. 1997. Resposta imune humoral de cães à vacina inativada, de cérebro de camundongos lactentes, utilizada nas campanhas anti-rábicas no Brasil. Revta Saúde Públ. 31(5):502-507. <http://dx.doi.org/10.1590/ S0034-89101997000600009>Arismendy A., García A., Gonzales C., Pinzón C., Delgado E. & Flóres F. 2010. Primer censo canino, felino del área urbana del municipio de Bucaramanga. Universidad Cooperativa de Colombia, Facultad de Medicina Veterinaria y Zootecnia. 130pColombiaSantanderrabies virusdogscatssheltered animalsvaccinationImmune responseLow level of the immune response against rabies virus in dogs and cats - a cross-sectional study in sheltered animals, Santander, Colombia.Artículohttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1http://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionAtribución – No comercialinfo:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2PublicationORIGINALTrujillo Rojas, et al Rabies.pdfTrujillo Rojas, et al Rabies.pdfapplication/pdf1754163https://repository.ucc.edu.co/bitstreams/f321f7ac-e1f7-497c-9552-0465ba584817/download00a16f439d1a1b1c80e7df9dbf4e8c5fMD51Licencia Paper Rabia.pdfLicencia Paper Rabia.pdfapplication/pdf171539https://repository.ucc.edu.co/bitstreams/20916399-79bf-40ae-b75d-5d9557831a28/downloadbef995fe9fe8bd223ce6ccc4ebe157a8MD53LICENSElicense.txtlicense.txttext/plain; charset=utf-84334https://repository.ucc.edu.co/bitstreams/f960cce4-cce1-4c0c-a8e1-58fc4a97e0be/download3bce4f7ab09dfc588f126e1e36e98a45MD54THUMBNAILTrujillo Rojas, et al Rabies.pdf.jpgTrujillo Rojas, et al Rabies.pdf.jpgGenerated Thumbnailimage/jpeg5591https://repository.ucc.edu.co/bitstreams/16073bc0-a775-49da-894b-c93a248e4b23/downloadeb56627ad8e72d7d8286d22899c9c5f9MD55Licencia Paper Rabia.pdf.jpgLicencia Paper Rabia.pdf.jpgGenerated Thumbnailimage/jpeg5157https://repository.ucc.edu.co/bitstreams/4c009d8b-80e0-4faf-800c-70d972566514/download73bb857df3fcabaf0f412f0d69939576MD56TEXTTrujillo Rojas, et al Rabies.pdf.txtTrujillo Rojas, et al Rabies.pdf.txtExtracted texttext/plain51079https://repository.ucc.edu.co/bitstreams/0fa06300-c5cc-410f-ba3d-97428fcbddaa/downloadff05f22add49e3a604bd414478e0d6abMD57Licencia Paper Rabia.pdf.txtLicencia Paper Rabia.pdf.txtExtracted texttext/plain5600https://repository.ucc.edu.co/bitstreams/51aff92d-77e7-48de-a226-2888344da886/download9224a1cd079ca6626412129432e50415MD5820.500.12494/15167oai:repository.ucc.edu.co:20.500.12494/151672024-08-09 12:04:44.9open.accesshttps://repository.ucc.edu.coRepositorio Institucional Universidad Cooperativa de Colombiabdigital@metabiblioteca.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