Professional Documents
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1154 Minsa1263-1
1154 Minsa1263-1
1154 Minsa1263-1
XI INTERNATIONAL MEETING ON RESEARCH ADVANCES AND RABIES CONTROL IN THE AMERICAS OCTOBER, 18-21,
2000
Molecular Epidemiology
19:00 hrs.
Ceremonia de Clausura
Closing Ceremony
Reception Cocktail Reception sponsored by Visit to the Laboratories Exhibit of the peruvian
Rosa Alarco Chorus Chiron/Behring Corp. at of the Instituto Nacional dog by the Kennel Club
Folkloric Group of the ~ the Sonesta EI Olivar de Salud (previous of Peru
Universidad Nacional Hotel registration is required)
Mayor de San .Marcos
XI REUNION INTERNACIONAL SOBRE INTERNATIONAl MEETING ON RESEARCH
AVANCES EN LA INVESTIGACION Y CONTROL ADVANCES AND RABIES CONTROL
DE LA RABIA EN LAS AMERICAS IN THE AMERICAS
INDICE - INDEX
Pag.
Presentaci6n - Presentation II
Programa Cientlfico 1
Scierltific Program 9
Resumenes - Abstracts 17
SESION DE CARTELES 1 65
SESION DE CARTELES 2 70
SESION DE CARTELES 3 77
PRESENT ACION
Para el Peru es motivo de satisfaccion recibir a los participantes a la "DECIMO PRIMERA REUNION
INTERNACIONAL SOBRE AVANCES EN LA INVESTIGACION Y CONTROL DE LA RABIA EN LAS
AMERICAS"
Este esfuerzo que realizan los Estados Unidos. Canada y Mexico desde 1990, tiene la especial
connotacion de haberse extendido a los demas pafses de America Latina, en el afan de aunar
iniciativas y experiencias con el fin de controlar esta zoonosis.
Esta Decimo Primera Reunion, es una valiosa oportunidad para intercambiar las experiencias que se
acumulan en el exterior como dentro del pais. Las conclusiones que se obtengan del trabajo en las
diferentes jornadas, deberan ser un importante referente para la toma de decisiones de aquellos que
tienen la responsabilidad de crear condiciones saludables para la poblacion en sus diferentes parses de
origen.
Como Ministro de Salud del Peru, qlJiero expresarles una vez mas nuestra cordial invitacion y
bienvenida. Estoy seguro que las jornadas de trabajo seran fructfferas y espero que sea una ocasion
para que puedan apreciar la hospitalidad y la cultura de nuestra patria.
PRESENTATION
April 2000
For Peru is reason of satisfaction to receive the participants to the ELEVENTH INTERNATIONAL
MEETING ON PROGRESS IN RESEARCH AND CONTROL OF RABIES IN THE AMERICAS
This effort that the United States, Canada, and Mexico carry out since 1990, has the special connotation
to have spread to the other countries of Latin America, in the eagerness to join together initiatives and
experiences for the purpose of controlling this zoonosis.
Rabies is an old problem in the history of Medicine. And the bold work that the 'investigators',
authorities, and all the personnel do in the different areas in which serve, tries to monitor, prevent, and
control this disease, and thus prevent that collects levels of reemergence.
This Eleventh Meeting is a valuable opportunity to share the experiences that are gained abroad as
within the couQtry. The conclusions that are obtained from the work in the different days should be an
important referent for the decision-making of the ones that have the responsibility of creating healthy
conditions for the population in your different countries of origin.
As Minister of Health of Peru, I want to express you once more our cordial invitation and welcome. I am
certain that the working days will be fruitful and I hope that it is an occasion so that they can appreCiate
the hospitality and the culture of our native country.
II
XI REUNION INTERNACIONAL SOBRE INTERNATIONAL MEETING ON RESEARCH
AVANCES EN LA INVESTIGACION Y CONTROL ADVANCES AND RABIES CONTROL
DE LA RABIA EN LAS AMERICAS IN THE AMERICAS
DR. CHRISTOPHER NUNAN, RABIES RESEARCH UNIT, ONTARIO MINISTRY OF NATURAL RESOURCES, CANADA
DR. CHARLES RUPPRECHT, CENTERS FOR DISEASE CONTROL AND PREVENTION, USA
III
XI REUNI6N INTERNACIONAL SOBRE INTERNATIONAL MEETING ON RESEARCH
AVANCES EN LA INVESTIGACI6N Y CONTROL ADVANCES AND RABIES CONTROl
DE LA RASIA EN LAS AMERICAS IN THE AMERICAS
COORDINACION GENERAL
ORA. ANA MARfA NAVARRO VELA, MINISTERIO DE SALUD, PERU
DR. CHRISTOPHER NUNAN, RABIES RESEARCH UNIT. ONTARIO MINISTRY OF NATURAL RESOURCES, CANADA
ORA. CECILIA DE MATTOS, CENTERS FOR DISEASE CONTROL AND PREVENTION, USA
DR. CARLOS DE MATTOS, CENTERS FOR DISEASE CONTROL AND PREVENTION, USA
COMITE TECNICO
DR. VICTOR ALTAMIRANO FERNANDEZ, PROGRAMA DE ZOONOSIS, MINISTERIO DE SALUD, PERU
DR. JOSE LUIS BUSTAMENTE NAVARRO, PROGRAMA DE ZOONOSIS, MINISTERIO DE SALUD, PERU
DR. ENRIQUE CARDENAS BROU, DIRECCION DE SALUD LIMA CIUDAD, MINISTERIO DE SALUD, PERU
DR. JUAN MONTEVERDE MORZAN, DIRECCION DE SALUD LIMA NORTE, MINISTERIO DE SALUD, PERU
ORA. BETTY TABOADA ESPINO, DIRECCION DE SALUD CALLAO, MINISTERIO DE SALUD, PERU
DR. JUSTINO ALADINO SOpAN, DIRECCION DE SALUD LIMA SUR, MINISTERIO DE SALUD, PERU
L1C. JUAN CASAS EGOAVIL, DIRECCION DE SALUD LIMA ESTE, MINISTERIO DE SALUD, PERU
SR. IVAN VARGAS MENESES, DIRECCION DE SALUD LIMA NORTE, MINISTERIO DE SALUD, PERU
GRUPO DE APOYO
SRTA. DULCINEA ZUNIGA, PROGRAMA DE ZOONOSIS, MINISTERIO DE SALUD, PERU
SRTA. BERTHA CIRIACO, DIRECCION DE SALUD LIMA NORTE, MINISTERIO DE SALUD. PERU
SR. IvAN CULQUI JULCA, DIRECCION DE SALUD LIMA CIUDAD, MINISTERIO DE SALUD, PERU
Nota: La recopilacien de estos resumenes se realize a partir de los escritos enviados par los autores, transmitidos par correa
electrenico y disco flexible, los cuales fueron incorporados de manera directa; as! como los recibidos par correa regular y fax, los
cuales fueron transcritos en su totalidad. Es por ella que ofrecemos una disculpa a tad as los autores y a quienes interese leer
este documento, por los errores que se hubieran cometido al momenta de su transcripcion.
IV
INTERNATIONAl MEETING ON RESEARCH
ADVANCES AND RI\BIES CONTROL
IN THE AMERICAS
PROGRAMA CIENTIFICO
Miercoles, 18 de Octubre
08:45 - 17:00 Inscripcion y Registro de Participantes
18:00 - 19:00 Inauguracion
Cocktail
Jueves 19 de Octubre
08:00 - 18:00 Presentacion de Poster
08:00 - 08:15 BIENVENIDA
08:'15 - 13:00 Sesi6n 1: Programas de Prevenci6n y Control de Rabia
Coordinadores: Dr. Michell Aubert AFSSA, France/Dr Albino Belotto OPS/OMS USA
08:15 - 08:30 Retos y oportunidades de la eliminacion de la rabia en el mundo
Dr. Michell Aubert - Lab. Rage France
09:00 - 09: 15 Rabies Surveillance in the United States During 1999 and 2000 (2)
John W. Krebs, Charles E. Rupprecht, James E. Childs
11 :00 - 11: 15 Rabies serology and animal transport to rabies free areas (7)
Kristen Schweitzer*, Deborah Briggs, Dewey Sturges
14:30 - 14:45 Quality Control of fluorescent antibody tests for rabies virus (10)
15:00 - 15:15 A change in Sampling Methodology at the KSU Rabies Diagnostic Lab (12)
Klancee Willis*, Tanya Tims, Kristen Schweitzer, Rolan Davis, Deborah Briggs
15:30 - 15:45 Molecular diagnoses of isolated rabies virus in the state of Sao Paulo between
1989 and 1999 (14)
15:45 - 16:00 Use of in situ hybridization technology for rabies virus strain typing in formalin
fixed tissues S.A. (15)
16:00 - 16:15 Development of a polyclonal reagent for the diagnosis of rabies (99)
2
XI REUNION INTERNACIONAL SOBRE INTERNATIONAL MEETING ON RESEARCH
AVANCES EN LA INVESTIGACION Y CONTROL ADVANCES AND RABIES CONTROL
DE l.A RABIA EN LAS AMERICAS IN THE AMERICAS
08:45 - 09:00 Vigilancia centinela escolar del riesgo a rabia silvestre en la Provincia de Alta
Amazonas - Loreto - Peru (22)
Melvy Ormaeche*
09:00 - 09: 15 Rabies knowledge and vaccine use among cavers (23)
Gibbons R.V.*, Holman R.C., Rupprecht C.
10:30 - 10:45 Post-exposure prophylacis of health care personnels and another contacts of a
rabid human case (28)
Mirjana Stantic-Pavlinic
10:45 - 11 :00 Accidentes con perros con relaci6n al lugar donde paso la agresi6n en el
Municipio de Sao Paulo, Brasil en 1998 (29)
11 :30 - 11 :45 Primer caso de rabia humana en Chile debido a variante viral de murcielago
insectivoro (32)
Myriam Favi C.*. Veronica Yung, Cecilia C. De Mattos, Carlos De Mattos, Luis Lopez, Eveling Chala
11 :45 - 13:00 Mesa Redonda: Aspectos clfnicos, tratamiento y profilaxis de la infecci6n por el
virus de la rabia. Tratamiento post-exposici6n en pacientes inmunodeprimidos.
Participantes:
Dr. Charles Rupprecht - CDC Atlanta EUA
Dr. Jean Lang Aventis Pasteur Francia
Dr. Wolgang Haupt Chi ron-Behring Alemania (33)
Dr. Raul Nalvarte MINSA . Peru
3
XI REUNION INTERNACIONAl SOBRE INTERNATIONAL MEETING ON RESEARCH
AVANCES EN LA INVESTIGACION Y CONTROl ADVANCES AND RABIES CONTROl
DE LA RABIA EN LAS AMERICAS IN THE AMERICAS
15:15 - 15:30 DNA-Based immunization protects dogs against a rabies virus challenge: from
anti-rabies to anti Lysavirus and multivalent vaccines (35)
N. Tordo. Y. Jacob, E. Desmezieres, C. Jallet, A. Aguilar-Setien, E. Loza-Rubio, M. Aubert, F.
Cliquet, P. Perrin
15:45 - 16:00 Maintenance medium research producing antirrabic vaccine in BHK cells (37)
Carlos Perez Suazo, Nelin Fernandez, Nalsy I.Reyes, Ramona Guerrero, Ana Digna Uribe
Sabado 21 de Octubre
08:00 - 17:00 Presentaci6n de Poster
08:00 - 10:45 Sesi6n 6: Vacunaci6n Animal- trabajos de investigaci6n
Coordinadores Dr. Alberto Sato OPS - Peru! Dr. Carlos A. De Mattos CDC-EUA
08:00 - Q8: 15 Vacunaci6n oral en animales terrestres silvestres yen perros
Dr. Michell Aubert Lab. Rage Francia
08:15 - 08:30 Oral vaccination with SAG2 baits and international rabies control (44)
Oliver Segal*
08:30 - 08:45 Use and efficacy of the SAG2 rabies vaccine bait in France (45)
Cliquet F:, Bruyere V., Rosenthal F., Aubert M.F.A.
4
XI REUNION INTERNACIONAL SOBRE
AVANCES EN LA INVESTIGACION Y CONTROL
DE LA RABIA EN LAS AMERICAS
09:00 - 09:15 Kinetics of rabies immune response of young foxes (Vulpes vulpes) orally
Blasco E.*, Cliquet F., Barrat J., Brochier B., Pastoret P.P., Aubert M.F.A.
09:15 - 09:30 Dynamics of SAD B19 derived maternal immunity against rabies in fox cubes
Thomas Muller*, Ad Vos, Peter Schuster, Thomas Selhorst, Uwe Wenzel, Andreas Neubert
11 :00 - 11 :15 Proposal for action in areas presenting canine and feline Desmodus rotundus
11 :15 - 11 :30 Estudio sobre facto res de riesgo de mordeduras por murcielagos hematofagos
12:00 - 12: 15 Capture and management of vampire bats in captivity, as a model to study
Ora. Jean Smith* CDC Atlanta - EUA, Sharon Messenger, Jennifer McQuiston, Lillian Orciari,
Pamela Yager
5
INTERNACIONAL SOBRE
LA INVESTIGACION Y CONTROL
EN LAS AMERICAS
15:00 - 15: 15 Densidad poblacional y predaci6n del vampiro comun (Desmodus rotundus) en
ecosistemas naturales y ganaderos
Dr. Horacio Delpietro - SENASA-Argentina
15:15 - 15:30 Impacto de los cambios del medio ambiente en las poblaciones de murcielagos
Dr. Gary Mc Craken, Univ. de Tennesse, USA
15:30 - 15:45 Rabies in frugivorous bats (Artibeus lituratus) in Sao Paulo, Brazil (59)
Miriam Silva*, Luciana Gomes* Luzia Martorelli*
15:45 - 16:00 Brote de Rabia Silvestre Bovina en Betania y Aguas Calientes, Loreto Peru(60)
Percy Cardenas*, Martin Casapla, Jose Bustamante, Juana Valera
16:00 - 16:15 Use of vampiricide on poultry for haemathophagous bat population control
feeding on human beings(61)
Romijn, P.C:, Silva,R.C.F., Medeiros, M.1.
17:00 - 17:15 Rabies in Tadarida brasiliensis mexicana: evidence of the ocurrency both V4
and V9 rabies virus variants in Mexico (63)
Victor Juarez-Islas*, Irma Padilla*, Gustavo Hernandez-Rodriguez*, Alejandra Melendes*,Ticul
Alvarez*, Jorge Villalpando* y Andres Velasco-Villa*
17:45 - 18:50 Mesa Redonda: Experiencias en el Control de Rabia Silvestre en America Latina
Miembros del panel: Dr, Carlos de Mattos CDC Atlanta - EUA (66)
Dr. Carlos Pavletic Director Programa de Rabia Chile
Dr. Director Programa de Control de Rabia Mexico (67)
Dr. Director Programa de Control de Rabia Brasil
18:50 - 19:00 Presentaci6n Sede XII Reunion Internacional sobre Avances en la Investigaci6n
y Control de la Rabia en las Americas
Comite Cientffico del RIA
19:00 - 20:00 Clausura
PROGRAMA DE PRESENTACION DE CARTELES
Jueves, 19 de octubre de 2000
Hora: 08:00 - 18:00
SESION DE CARTELES 1 - COORDINADOR: LlC. JUAN CASAS
Respuesta inmune obtenida en personas expuestas al virus rabico, despues de recibir
tratamiento post exposicion: Sueroheterologo Vacuna CRL (69)
Ora. Clemencia Garcia*, Ora. Sonia Cortes, Ora. Cecilia Saad, Dr. Jorge Boshell
6
XI REUNION INTERNACIONAL SOBRE RESEARCH
AVANCES EN LA INVESTIGACION Y CONTROl CONTROL
DE LA RABIA EN LAS AMERICAS AMERICAS
Dr. V. Le Mener*, Dr. Y. Rotivel*, Dr. J.C. Cetre*, Dr. J. Lang* and study investigators*
Molecular and antigenic characterization of rabies viruses isolated in Israel, Jordan and Egypt (74)
Dr. David Dan*, Dr. Boris Yakobson*, Dr. Aldomy Fuad*, Dr. Mazen Abdel Magid*, Dr. Shoukry Shafic Guirguis*, Dr.
Carlos De Mattos*, Ora. Cecilia C. De Mattos* y Dr. Jean Smith*
Dr. Humberto Carol*, Ora. Esther Ma. Fajardo*, Dr. Daniel Cazallas, Ora. Arlene Rebull, Ora. Briseida Rodriguez, Ora.
Mirian Diaz
Dr. Andres Paz*, Ora. Ximena Duarte, Ora. Silvia Pulido, Ora. Clemencia Garcia, Dr. Jorge Boshell
Control de brote de rabia silvestre bovina en Yurirnaguas, estrategia de prevencion Peru (82)
Lie. Melvy Ormaeche*
Dr. Rodolfo Gonzales*, Dr. Marco Antonio Arrieta, Dr. Carlos Holguin, Dr. Victor Alva, Dr. Jaime Nombera
Evolution of bovine and equine rabies in the region of Braganca Paulista, Sao Paulo, from 1997
to 2000 (85)
Dr. Carrien. M.L.*, Dr. Carnieli Jr., P., Dr. Favoretto S.A.L:, Dr. Diniz 0., Dr. Braga A.C., Dr. Takaoka N.Y., Dr.
Dr. Gomez M.J .. Aguilar B.W.*, Dr. Burgos M.J'*, Dr. Ronderos G.A.A.*, Dr. Caliao P.M.'
.. ~.,'t;
7
XI REUNION INTERNACIONAL SaBRE
AVANCES EN LA INVESTIGACI6N Y CONTROL
DE LA RABIA EN LAS AMERICAS
Elimination of rabies virus variant-3 by saliva from a naturally infected feline (87)
Ora. Silvana Favoretto*, Ora. Marlon V. Silva, M.V. Gouvea, Ora. Ailyn Y.K. Endo
Ora. Ana Marfa Burga*, Lie. Jorge A Miranda, Dr. Manuel Agreda
The Sao Paulo Pasteur Technique for measuring canine population (92)
Ora. Marina Ruiz de Matos", Ora. Ma. Cecilia Goi Porto Alves, Ora. Marfa de Lourdes AB. Reichmann, Ora. Margaret
H.S. Dominguez
Brasil (93)
Ora. Silvana Favoretto*, Ora. Cecilia C. De Mattos, Ora. Luiza Carrieri, Dr. Carlos A De Mattos
Descripcion epidemiologica de brotes de rabia silvestre en el Provincia La Mar Ayacucho, PenJ (96)
M.V. Nelly Huamanf*
Lie. Melvy Ormaeche*, Dr. Jorge Gomez*, M.V. Betty Taboada, Lie. Carolina Cardenas, et all.
Use of vampiricide on poultry for haemathophagous bat population control feeding on human
beings (61)
8
INTERNATIONAL MEETING ON RESEARCH
ADVANCES AND R~BIES CONTROL
IN THE AMERICAS
SCIENTIFIC PROGRAM
Wednesday, October 18th
08:45 - 17:00 Registration
18:00 - 19:00 Inauguration
Cocktail
Thursday, October 19th
08:00 - 18:00 Poster session
08:00 - 08:15 WELCOME
08: 15 - 13:00 Session I: Rabies prevention and control programs
Moderators: Michel Aubert AFSSA, France/ Albino Belotto PAHOIWHO Washington D.C. USA
08:15 - 08:30 Challenges and opportunities in rabies elimination in the world.
Dr. Michell Aubert - Lab. Rage, France
09:00 - 09: 15 Rabies Surveillance in the United States During 1999 and 2000 (2)
John W. Krebs, Charles E. Rupprecht, James E. Childs
09:15 - 09:30 Actividad para el control de la rabia paralftica bovina en el estado de Veracruz (98)
Mario Gutierrez*, Efrafn Acosta*
10:45 - 11 :00 Stable expression of rabies nucleoprotein in a mammalian cell line (6)
Rolan Davis* , Zhen Fu
11 :00 - 11: 15 Rabies serology and animal transport to rabies free areas (7)
Kristen Schweitzer"', Deborah Briggs, Dewey Sturges
9
XI REUNION INTERNACIONAL SOBRE INTERNAIIONAL MEETING ON RESEARCH
AVANCES EN LA INVESTIGACION Y CONTROL ADVANCES AND RABIES CONTROL
DE LA RABIA EN LAS AMERICAS IN THE AMERICAS
~.~ --_._-----------------------------
14:45 - 15:00 Application of molecular biology techniques in rabies surveillance in Latin America
15:00 - 15:15 A change in Sampling Methodology at the KSU Rabies Diagnostic Lab (12)
Klances Willis*, Tanya Tims, Kristen Schweitzer, Rolan Davis, Deborah Briggs
15:15 - 15:30 Molecular characterization of rabies virus in domestic and wild mexican animals(13)
Javier Reyna*, Jose Aguilar, Elizabeth Loza-Rubio, Octavio De Paz, Miguel Camara, Jose Carmen Gudino,
Baltazar Cortez, Raul Vargas y Juan Antonio Montano
15:30 - 15:45 Molecular diagnoses of isolated rabies virus in the state of Sao Paulo between 199989
an 1999 (14)
15:45 - 16:00 Use of in situ hybridization technology for rabies virus strain typing in formalin-fixed
tissues (15)
S.A. Nadin Davies', M. Sheen, G. Turner, E. Loza-Rubio, A.1. Wandeler
17:00 - 19:00 Round table: Advances in the molecular characterization of rabies virus in Latin America
Panel: Cisterna Daniel, ANUS, Argentina
Elberger Diana, SENASA, Argentina
Favi Miriam, instituto de Salud Publica ,Chile
Favoretto Silvana, Instituto Pasteur Sao Paulo, Brasil
Lopez Ricardo, INS, Peru
Papo-Vulkelic Sara, Instituto de Investigaciones, Maracay, Venezuela
Velasco Andres, INDRE, Mexico
Guaqueta Alexandra, ICA, Colombia
08:45 - 09:00 Vigilancia centinela escolar del riesgo a rabia silvestre en la Provincia de Alto
Amazonas Loreto, Peru (22)
Melvy Ormaeche*
09:00 - 09: 15 Rabies knowledge and vaccine use among cavers (23)
Gibbons R.V.*, Holman R.C., Rupprecht C.
10
INTERNATIONAL MEETING
ADVANCES AND
09:30 - 09:45 Conocimiento y comportamiento humano relacionada con la rabia canina en Colombia (25)
Melanie Morrow·, Ricardo Leon*, Peter J. Winch
10:30 - 10:45 Post-exposure prophylacis of health care personnels and another contacts of a rabid
human case (28)
Mirjana Stantic-Pavlinic*
10:45 - 11 :00 Accidentes con perros con relacion allugar donde paso la agresion en el Municipio de
Sao Paulo, Brasil en 1998 (29)
Pedro Melguizo·, Pedro Silva
11 :00 - 11 :15 Estudio de las implicaciones de la rabia canina y el tratamiento antirrabico post
exposicion en Santa Cruz, Bolivia (30)
Fidel Villegas*, Erick Eulert
11 :30 11 :45 Primer caso de rabia humana en Chile debido a variante viral de murcielago insectivoro
(32)
Miriam Favi*, Veronica Yung, Cecilia C. De Mattos, Carlos De Mattos, Luis Lopez, Eveling Chala
11 :45 - 13:00 Round table: Clinical and pathologic aspects of rabies infection-prophylaxis. Post
exposure treatment in immunodeficient patients
Panel: Haupt Wolgang, Chiron-Behring, Germany
Lang Jean, Aventis Pasteur, France
Nalvarte Raul, MINSA, Peru
Rupprecht Charles, CDC, Atlanta, USA
13:00 - 14:30 Lunch
14:30 - 15:00 Presentation of the Latin American Investigator Award by a Representative of the RIA
Scientific Committee
Rabies virus antigenic characterization in support of rabies surveillance in Mexico: One
of the first approaches for rabies control and prevention (16)
Andres Velazco Villa*, Mauricio Gomez-Sierra, Irma Padilla, Gustavo Hernandez-Rodriguez, Victor
Juarez-Islas, Ticul Alvarez, Jorge Villapando, Alejandra Melendez
15:15 - 15:30 DNA-based immunization protects dogs against a rabies virus challenge: from anti
rabies to anti Lyssavirus and multivalent vaccines (35)
N. Tordo, Y. Jacob, E. Desmezieres, C. Jallet, A. Aguilar-Setien, E. Loza-Rubio, M. Aubert, F. Cliquet, P.
Perrin
11
...
15:30 - 15:45 An E1-deleted recombinant human adenovirus vaccine against rabies. Immunogenicity
studies(36)
Ad Vos*, Andreas Neubert, Elke Pommerening, Leopold Dohner, Ken Hughes, Larissa Neubert, Thomas
Muller
15:45 - 16:00 Maintenance medium research producing antirrabic vaccine in BHK cells (37)
Carlos Perez Suazo, Nelin Fernandez, Nalsy Reyes, Ramona Guerrero, Ana Digna Uribe
16:45 - 17:00 Desarrollo de una vacuna antirrabica expresada en malz transgenico y su evaluaci6n
en bovinos (39)
Saturday, October 21 th
08:00 - 17:00 Poster session
08:00 - 10:45 Session 6: Animal rabies vaccination
Moderators: Alberto Sato PAHOIWHO, Peru/ Carlos A. de Mattos, CDC, USA
08:00 - 08: 15 Oral vaccination in dogs and terrestrial wildlife
Michel Aubert AFSSA, France
08: 15 - 08:30 Oral vaccination with SAG2 baits and international rabies control (44)
Oliver Segal*
08:30 - 08:45 Use and efficacy of the SAG2 rabies vaccine bait in France (45)
C!iquet F.*, Bruyere V., Rosenthal F., Aubert M.F.A.
09:00 - 09:15 Kinetics of rabies immune response of young foxes (Vulpes vulpes) orally Vaccinated
with VRG vaccines (48)
Blasco E.*, Cliquet F., Barrat J., Brochier b., Pastoret P.P., Aubert M.F.A.
09:15 - 09:30 Dynamics of SAD B19 derived maternal immunity against rabies in fox cubes (Vulpes
vulpes) (49)
Thomas Muller*, Ad Vos, Peter Schuster, Thomas Selhorst, Uwe Wenzel, Andreas Neubert
12
XI REUNI6N INTERNACIONAL SOBRE
AVANCES EN LA INVESTIGACI6N Y CONTROL
DE LA RABIA EN LAS AMERICAS
10:30 - 10:45 Determinaci6n de niveles de anticuerpos contra virus de la rabia en caninos y evaluaci6n
de algunos facto res de riesgo en Ciudad Bolivar - Santa Fe, Bogota 1997-1998 (51-A)
Ricardo Leon*, Jesus Moreno, Juan Manuel Rodriguez
11 :00 - 11: 15 Proposal for action in areas presenting canine and feline Desmodus rotundus
transmitted rabies cases (52)
Carrieri, M.L.*, Harmani, N.M.S., Perez, N.F., Kotalt, I.
11 :15 - 11 :30 Estudio sobre facto res de riesgo de mordeduras por murcielagos hemat6fagos en
localidades de los distritos de Ayna y Santa Rosa en la Provincia de La Mar Dpto. de
Ayacucho, Peru 1999 (53)
Jorge Gomez*, Melvy Ormaeche*
11 :30 - 11 :45 Determinaci6n de facto res de riesgo de rabia silvestre en comunidades nativas
Aguarunas de la Provincia de San Ignacio - Departamento de Cajamarca, Peru (54)
Manuel Arana*, Ana Marfa Navarro
11 :45 - 12:00 Estudio retrospectivo y caracterizaci6n de la rabia bovina en los Llanos Oreintales de
Colombia 1982-1999 (55)
Edilberto Brito Sierra*
12:00 - 12: 15 Capture and management of vampire bats in captivity, as a model to study several
aspects if rabies virus (56)
Elizabeth Loza-Rubio*, Octavio De Paz, Labrandero I.E.
12:15-13:00 Visit
13:00 - 14:30 Lunch
14:30 - 14:45 Phylogenetic evidence for involvement of Lasionycteris noctivagans an Pipestrellus
subflavus in recent human rabies infections (58-A)
Jean Smith*, CDC, Atlanta, USA, Sharon Messenger, Jennifer Mc QUiston, Lillian Orciari, Pamela Yager
14:45 - 15:00 Rabies in hematophagous bats and its economic impact in agriculture
Rexford Lord, Venezuela
15:00 - 15: 15 Population density and predation of the common vampire bat (Desmodus rotundus) in
15: 15 - 15:30 Impacto de los cam bios del medio ambiente en las poblacines de murcielagos
15:30 - 15:45 Rabies infrugivorous bats (Artibeus lituratus) in Sao Paulo city, Brazil (59)
15:45 16:00 Brote de Rabia Silvestre Bovina en Betania y Aguas Calientes Loreto, Peru )60
16:00 - 16:15 Use of vampiricide on poultry for haemathophagous bat population control feeding on
13
IlL
XI REUNION INTERNACIONAL SOBRE INTERNATIONAL MEETING ON RESEARCH
AVANCES EN LA INVESTIGACION Y CONTROL ADVANCES AND RABIES CONTROL
DE LA RASIA EN LAS AMERICAS ,\),. .. IN THE AMERICAS
16:45 - 17:00 Metodologfa para la identificaci6n de zona de riesgo a rabia silvestre en la Provincia de
Alto Amazonas - Loreto, Peru (62)
Melvy Ormaeche*
17:00 - 17:15 Rabies in Tadarida brasiliensis mexicana: evidence of the occurrency both V4 and V9
rabies virus variants in Mexico (63)
Victor Juarez-Islas*, Mauricio Gomez-Sierra, Irma Padilla, Gustavo Hernandez-Rodriguez, Alejandra
Melendez, Ticual Alvarez, Jorge Villalpando, Andres Velasco-Villa
17:30 - 17:45 Rabia en murcialagos no hemat6fagos en la provincia de Oxapampa, Peru 1996 julio 2000 (58)
Norka Verde*, Jorge G6mez*
18:50 - 19:00 Presentation of the XII International Meeting on Research Advances and Rabies
Control in the Americas
RIA Scientific Committee
19:00 - 20:00 Closing remarks
POSTERS SESSIONS
Thursday, October 19 th
Time: 08:00 - 18:00
POSTER SESION 1 - CHAIRMAN: LlC. JUAN CASAS
Respuesta inmune obtenida en personas expuestas al virus rabico, despues de recibir
tratamiento post exposici6n: Sueroheter610go - Vacuna CRL (69)
Ora. Clemencia Garcia*, Ora. Sonia Cortes, Ora. Cecilia Saad, Dr. Jorge Boshell
Dr. V. Le Mener*, Dr. Y. Rotivel*, Dr. J.C. Cetre*, Dr. J. Lang* and study investigators*
Molecular and antigenic characterization of rabies viruses isolated in Israel, Jordan and Egypt (74)
Dr. David Dan*, Dr. Boris Yakobson*, Dr. Aldomy Fuad*, Dr. Mazen Abdel Magid*, Dr. Shoukry Shafic Guirguis*,
14
XI REUNI6N INTERNACIONAL INTERNATIONAL MEETING
AVANCES EN LA ADVANCES AND
DE LA RABIA EN
Dr. Humberto Carol*, Ora. Esther Ma. Fajardo*, Dr. Daniel Cazallas, Ora. Arlene Rebull, Ora. Briseida Rodriguez, Ora.
Mirian Oiaz
Friday, October 20 th
Time: 08:D0 18:00
POSTER SESSION 2 - CHAIRMAN: DR. IVAN VARGAS
Macrophage activity stimulation and natural killer activity induced by antirabies vaccine and P.
Dr. Andres Paz', Ora. Ximena Duarte, Ora. Silvia Pulido, Ora. Clemencia Garcia, Dr. Jorge Boshell
Dr. Rodolfo Gonzales*, Dr. Marco Antonio Arrieta, Dr. Carlos Holguin, Dr. Victor Alva, Dr. Jaime Nombera
Evolution of bovine and equine rabies in the region of Braganca Paulista, Sao Paulo, from 1997
to 2000 (85)
Dr. Carrieri, M.L.*, Dr. Carnieli Jr., P., Dr. Favoretto S.A.L:, Dr. Oiniz 0., Dr. Braga A.Co,
Dr. Takaoka N.Y., Dr. Panachao M.A.I., Dr. Taddei V.A., Dr. Kotait I.
Evaluacion del Programa de Control de Rabia can ina en Colombia y recomendaciones para
Dr. Gomez M.J:, Aguilar B.W:, Dr. Burgos M.J:, Dr. Ronderos G.A.A:, Dr. Cajiao P.M.*
Elimination of rabies virus variant-3 by saliva from a naturally infected feline (87)
Ora. Silvana Favoretto·, Ora. Marlon V. Silva, M.V. Gouvea, Ora. Ailyn Y.K. Endo
Saturday, October 21 th
Time: 08:00 17:00
POSTER SESSION 3 - CHAIRWOMAN: ORA. BETTY TABOADA
N protein of rabies virus work as immunomodulator in an avian influenza vaccine, in poultry (89)
Ora. Elizabeth Loza*, Dr. Banda RVM, Dr. Molina GJA, Montano HJA, Verdugo RA
15
.....
Estimacion y anal isis de la poblacion can ina en la costa Libertena, Peru (91)
Ora. Ana Marfa Burga*, Lie. Jorge A. Miranda, Dr. Manuel Agreda
The Sao Paulo Pasteur Technique for measuring canine population (92)
Ora. Marina Ruiz de Matos*, Ora. Ma. Cecilia Goi Porto Alves, Ora. Marfa de Lourdes A.B. Reichmann, Ora. Margaret
H.S. Dominguez
Paulo,Brasil (93)
Ora. Silvana Favoretto*, Ora. Cecilia C. De Mattos, Ora. Luiza Carrieri, Dr. Carlos A. De Mattos
Descripcion epidemiologica de brotes de rabia silvestre en el Provincia La Mar Ayacucho, Peru (96)
M.V. Nelly Huamani*
Lie. Melvy Ormaeche*, Dr. Jorge Gomez*, M.V. Betty Taboada, Lie. Carolina Cardenas, et all.
16
.L....
XI REUNI6N INTERNACIONAL SOBRE INTERNATIONAL MEETING ON RESEARCH
AVANCES EN LA INVESTIGACI6N Y CONTROL ADVANCES AND RABIES CONTFIOL
DE LA RABIA EN LAS AMERICAS IN THE AMERICAS
RESUMENES - ABSTRACTS
EI perro en America ha acompanado al hombre desde hace 10-12 mil anos, convirtiendose en el animal
domestico mas popular e integrandose como un miembro mas de la familia.
EI hombre tam bien ha permitido que el perro se reproduzca en forma indiscriminada, que busque su
alimento :en las calles y que se convierta en un serio problema de salud publica. La presencia de
perros erl' la vfa publica, mercados, parques, basureros, puestos de comida, playas, carreteras y en
cualquier sitio en donde pueden encontrar desperdicios para alimentarse, es una imagen comun,
especialmente en Latinoamerica.
Existe la conviccion de que el perro en las calles se ha convertido en un grave problema en areas
urbanas y suburbanas. Las acciones aisladas no han dado resultado para controlarlo en forma integral.
Medidas como captura, esterilizacion y sacrificio de animales no parecen ser eficientes a mediano y
largo plazo ya que existe una continua reincorporacion de perros sin control hacia la via publica.
La mayorfa de los perros que deambulan temporal 0 permanentemente en las calles tienen uno 0
varios duenos, quienes no se responsabilizan de cuidar adecuadamente a sus animales ni de los danos
que estos puedan ocasionar a terceras personas 0 al medio ambiente. Los autores proponen la
denominacion de Perros de Dueno Irreflexivo (PDI) para este grupo de animales.
Los principales problemas generados por este tipo de perros son: agresiones -principalmente a ninos-,
transmision de rabia y otras enfermedades zoonoticas, fecalismo, dispersion de basuras, accidentes
viales, regresion al estado semi-salvaje e imagen de atraso social en las comunidades y ciudades que
tienen canes callejeros.
Existen censos sobre la cantidad de perros existentes y la relacion habitantes/perros, efectuados en
diversos paises, que proporcionan cifras muy variadas que en general fluctuan entre 10:1 y 6:1. Sin
embargo, otro tipo de datos publicados, particularmente en Latinoamerica, dan informacion que puede
resumirse en 10 siguiente: a menor nivel socioeconomico mayor cantidad de perros sin control (PDI), la
mayorfa de los perros son jovenes -menores de 3 anos-, hay mas machos que hembras, 30-35 % de la
poblacion de perros se renueva cada ano, predominan los perros mestizos, un numero elevado no
tiene confinamiento, la mayorla se alimenta de sobras y desperdicios, si reciben alguna vacuna es la
antirrabica, el porcentaje que recibe atencion especializada de Medicos Veterinarios es muy bajo 0
inexistente y son mantenidos principalmente para vigilancia y proteccion.
La problematica deriva no del numero de perros existentes, sino de la gran cantidad de animales que
pertenecen a personas que no se responsabilizan de ellos.
Las tres causas principales que generan la presencia de perros sin control en la calle son: a) falta de
EDUCACION de la poblacion sobre la responsabilidad que implica tener perros problema. b) no existe
REGLAMENTACION adecuada para la tenencia de perros, especial mente en areas urbanas y
semiurbanas y c) no se asignan RECURSOS ECONOMICOS suficientes para enfrentar el problema.
La solucion INTEGRAL para disminuir este creciente problema socioeconomico tan complejo, implica
la necesaria y obligada participacion conjunta de la COMUNIDAD AFECTADA, LAS AUTORIDADES
LOCALES Y LOS GOBIERNOS CENTRALES.
A nivel comunitario general el principal esfuerzo debe dirigirse a educar a la poblacion y muy
particularmente a los ninos, sobre la importancia que tiene cuidar adecuadamente a los perros y crear
conciencia del grave deterioro ambiental y la problematica que generan los animales que permanecen
en las calles. Se propone un decalogo de puntos basicos sobre los que pueden basarse las campanas
educativas en radio, television, prensa y dHusion en escuelas.
1) La familia tiene carino y respeto por su perro. 2) Solamente posee los perros que puede cuidar y
mantener adecuadamente. 3) No permite que su perro deambule Iibremente en la calle. 4) No 10 suelta
para que busque su alimento. 5) No 10 saca a defecar en la via publica. 6) Si saca su perro a la calle, 10
hace con collar y correa y si defeca recoge el excremento para depositarlo en la basura. 7) EI dueno se
preocupa de que su perro este actualizado en su calendario de vacunacion. 8) Lleva a su perro con el
Medico Veterinario. 9) No los reproduce indiscriminadamente para venderfgs 0 regalarlos a quien no
17
INTERNATIONAL MEETING ON RESEARCH
ADVANCES AND RABIES CONTROL
IN THE AMERICAS
puede cuidarlos. Es preferible esterilizarlos. 10) Hace co-partfcipes a todos los integrantes de la familia
especialmente a los ninos, de la responsabilidad que implica tener un perro.
DE LA PARTICIPACION DEL GOBIERNO LOCAL Y DE LA COMUNIDAD: Los elementos que se
requieren a nivel comunitario para iniciar un programa integral de control canino son: 1) Campanas de
educacion previa a las acciones a tomar durante el programa. 2) Establecer los reglamentos que se
pretende implementar y los objetivos que se quieren alcanzar, fundamentados en legislaciones si las
hay. 3) Contar con centros de control canino que puedan prestar, entre otros, servicios de esterilizacion
de perros, recoleccion de perros en la calle, sacrificio de animales no reclamados y disposicion
sanitaria de cadaveres. 4) Eficientizar la recoleccion y disposicion de basura. 5) Establecer una meta a
cumplir, en conjunto con autoridades y ciudadanos que permita dirigir esfuerzos y evaluar resultados.
Los gobiernos federales deberan implementar acciones de caracter general pero tendientes a apoyar a
los gobiernos locales a cumplir con sus programas. EI soporte debe ser dirigido a: 1) Educacion
permanente de la poblacion, utilizando los medios masivos de comunicacion. 2) Incluir en los libros de
texto y programas de educacion basica y media temas sobre la posesion responsable de perros. 3)
Legislar a nivel nacional sobre la tenencia de perros, danos a terceros provocados por los mismos,
comercializacion indiscriminada, transporte, proteccion a los animales, esterilizacion, sacrificio
humanitario y disposicion de cadaveres. 4) Incluir en las campanas nacionales de vacunacion
antirrabica mensajes sobre la responsabilidad de tener perros. 5) Apoyar economicamente a las
comunidades y gobiernos locales que establezcan programas de control canino y estimular a aquellos
que obtengan buenos resultados. 6) Efectuar censos que permitan conocer la dinamica de la poblacion
can ina para tomar medidas viables y evaluar su impacto.
La suma de acciones de los tres niveles mencionados; comunidad, gobiernos locales y gobierno central
dirigidas hacia la educacion, reglamentacion y apoyo economico para implementar programas
integrales de control canino en areas urbanas y suburbanas, son indispensables para lograr objetivos a
mediano y largo plazo. La inversion en educacion a la poblacion y particularmente a los ninos, parece
ser la medida mas viable para reducir la presencia de perros en las calles.
RABIES SURVEILLANCE IN THE UNITED STATES DURING 1999 AND 2000 (2)
John W. Krebs, Charles E. Rupprecht, James E. Childs
During 1999, 49 states, the District of Columbia, and Puerto Rico reported 7,067 cases of rabies in
nonhuman animals to the Centers for Disease Control and Prevention, a decrease of 11.2% from 7,961
cases in nonhuman animals and 1 case in a human being reported in 1998. Ninety-one and one-half
percent (6,466 cases) were in wild animals, whereas 8.5% (601 cases) were in domestic species
(compared with 92.4% in wild animals and 7.6% in domestic species in 1998). Decreases were evident
in all of the major contributing species groups, with the exception of cattle, sheep/goats, and swine. The
relative contributions of the major groups to the total reported for 1999 were as follows: raccoons
(41.0%; 2,872 cases), skunks (29.4%; 2,076), bats (14.0%; 989), foxes (5.4%; 384), cats (3.9%; 278),
cattle (1.9%; 135), and dogs (1.6%; 111). Reported cases (6) of rabies associated with the epizootic of
rabies in raccoons in Ohio declined from those (26) reported in 1998. Fifteen of the 19 states where the
raccoon variant of the rabies virus is enzootic reported fewer cases of rabies during 1999, compared
with 12 states and the District of COlumbia that reported decreases during 1998. Massachusetts and
Rhode Island, states with enzootic raccoon rabies, each reported more rabid skun~s than rabid
raccoons for the third consecutive year. In Texas, the numbers of rabies cases associated with the dog
coyote variant of the rabies virus remained low, whereas cases associated with the gray fox variant of
the virus increased. The numbers of rabies cases in skunks decreased by 8.6% from those reported in
1998. Equal numbers of states where skunks are the predominant terrestrial reservoir reported
increases and decreases in their respective overall totals of animals that tested positive for rabies virus.
At the national level, the number of reported cases of rabies among horses and mules declined 21 %
from 82 cases in 1998 to 65 cases in 1999. The number of cases of rabies reported in bats (989) was
approximately the same as the number reported during 1998 (992) and represented almost 14.0% of
the total number of rabid animals reported during 1999. Reported cases of rabies in cats (278) and dogs
(111) decreased by 1.4% and 1.8%, respectively, whereas cases in cattle (135) increased by 16.4%
over those reported in 1998. No cases of rabies were reported in human beings in 1999.
During the "first 6 months of 2000, totals of reported cases of rabies in the United States have been only
slightly lower than those re.ported in 1999. Past and current rabies control efforts have been credited
18
XI REUNION INTERINA(~IONAI INTERNATIONAL RESEARCH
AVANCES EN LA Y CONTROl ADVANCES CONTROL
DE LA RASIA EN LAS AMFRICAS AMERICAS
with contributing to the decline of cases of rabies reported from areas and regions where such control
programs have been or are in place. No cases of rabies in raccoons, or any other terrestrial species,
have been reported in Ohio. Along borders with neighboring countries, no cases of rabies associated
with the dog-coyote variant of the rabies virus have been reported in south Texas and only 46 cases of
rabies associated with the gray fox variant were reported in west-central Texas. Reports of raccoon
associated rabies continue to decline in New York State. Although intensive rabies control measures
have been employed in Ontario, Canada, since the initial reports of raccoon rabies in that province (7
cases) during the latter half of 1999, the numbers of cases of raccoon rabies reported have continued to
increase during 2000 (27 cases). Most recently, a skunk infected with the raccoon variant of the rabies
virus has been reported in New Brunswick. This incident probably represents a second route of
extension of the raccoon rabies epizootic into Canada via movement from the state of Maine.
One case 'Of indigenously acquired rabies in a man from Amador County, California, reported during
September 2000, was determined to be the result of infection with a bat variant of the rabies virus.
Reportamos una enfermedad zoonotica en la sierra central del Peru (Huancayo), que por sus
caracterlsticas geograficas (3250 msnm) y condiciones favorables presentan gran incidencia en la
zona.- Desde 1996 al 2000 (Agosto) se reporto 98 casos de Rabia canina, siendo el ano de 1997 que
se disemina la enfermedad con 51 casos de rabia animal, entre ellos (1 vacuno, cerdo) y 04 casos de
Rabia Humana, el ultimo caso de Rabia Canina se presento en Abril del ano 1999.
La rabia canina aparecio en zonas urbanas de Huancayo, Chilca, Tambo, Chupaca, Concepcion y
areas rurales, centrandose en la Provincia de Huancayo.
Como consecuencia de un deficiente control de foco esta Zoonosis fue extendiendose, de igual
manera las medidas preventivas no fueron efectivas.
A partir del ano 1998, se logra controlar esta enfermedad, ejecutando acciones preventivas a todo
nivel ,reactivando el Laboratorio de Diagnostico de Rabia, comprometiendo el trabajo del personal de
salud , coordinacion Intra e Interinstitucional, y participacion activa de la comunidad.
La Provincia de Huancayo presenta condiciones epidemiologicas favorables (incremento de la
poblacion can ina y aumento de canes vagos).- Para ello se esta ejecutando medidas y acciones, con
los organismos responsables, para un mejor control de esta enfermedad, razon por la cual se esta
disminuyendo considerablemente la presentacion de los casos des de hace mas de un ano.
Una de las enfermedades que ha causado gran temor a traves de los siglos en la sociedad ha sido la
rabia, la cual ha constituido un enigma para los cienWicos a 10 largo de la historia y actualmente
continua siendo un problema para la salud publica y una amenaza permanente para las poblaciones
humanas en muchas partes del mundo.
En el presente trabajo se recogen las secuencias de hechos historicos sobre la Rabia en Cuba. Se
incluyen aspectos fundamentales del virus, destacandose brevemente las principales caracterfsticas
como agente causal de la enfermedad. Tambien se menciona el comportamiento epidemiologico y
epizootiologico, aspectos de vital importancia para el diagnostico posterior de la enfermedad. Por ultimo
se destacan los trabajos de investigacion y desarrollo en los que nos encontramos enfrascados en
estos momentos. aSI como los logros obtenidos en nuestro pais.
Consideramos que este trabajo nos brinda una base teorico-historico del quehacer constante el cual a
tenido que enfrentar nuestro pars durante aproximadamente 280 anos. Ademas los aspectos tratados
desde el punto de vista epidemiologico serviran de referencia u orientacion a todos aquellos
interesados en el estudio de la enfermedad, aSI como en el campo de la investigacion y desarrollo,
pretendemos que nuestra experiencia sirva de premisa para sentar las pautas de futuros trabajos con
otros grupos afines al tema
""'-~}'
19
...
While the etiologic agent of rabies encephalitis was believed to be unique for a long time, the use of
news tools for analysis has revealed an important diversity between Iyssaviruses, at phylogenetic,
antigenic, pathogenic levels and concerning biological properties.
1. Phylogenetic analysis distinguished 7 genotypes (GT) which in turn segregated into two major
phylogroups. Phylogroup 1 comprises the world-wide GT 1 (rabies), the European GT5 (EBL 1) and GT6
(EBL2), the African GT 4 (Duvenhage) and the Australian GT7 (ABL). Phylogroup 2 comprises the
African GT2 (Lagos bat) and GT3 (Mokola).
2. Immunogenic properties are in agreement with the phylogenetic grouping. Within each phylogroup,
the G protein ectodomains share >74% amino acid identity and anti-G virus neutralizing antibodies
display cross-neutralisation. Between the phylogroups, the identity is <62% and cross-neutralisation is
absent, explaining the current inefficiency of classical rabies vaccines (phylogroup 1) to protect against
Iyssaviruses from phylogroup 2.
3. Pathogenic properties are also in agreement with the phylogenetic grouping. Viruses from phylogroup
1 are pathogenic by both intracerebral and intramuscular routes, while viruses from phylogroup 2 are
only pathogenic by intracerebral route. In the latters, R333 (a G protein residue essential for virulence) is
naturally replaced by a 0 333 , potentially resulting in their attenuated pathogenicity.
4. The recognition of specific receptor is less tighly respective of the phylogrouping. Using a specific
binding assay on the low-affinity nerve-growth factor receptor (P75NTR), one potential receptor for
rabies virus (GT1) recently characterized, we showed that P75NTR interacts with G proteins of
GT1 (CVS, PV, fox rabies virus) and GT6 (EBL2). But no interaction was evidenced with G proteins from
the other GTs (2, 3, 4 and 5).
In summary, Iyssavirus are showing a world of diversity that not only helps to understand the molecular
basis of their immunogenicity or pathogenesis, but also provides us with a panel of viruses with different
neurotropic properties.
Rolan Davis
Dr. Zhen Fu
POSTER PRESENTATION:Two interesting rabies variants have been shown to exist in the mid-western
United States. The first variant is from Oklahoma where the expected rabies variant is south-central
skunk, which is carried primarily by the striped skunk (Mephitis mephitis). This variant has lost reactivity
to one of the monoclonal antibodies in the panel commonly used in the United States for variant typing
(marketed by Chemicon, Inc Tecemula, CA). This variant is not recognized by the Mab, often referred
to as CR54, which binds to an epitope that is unique to south-central skunk and raccoon variants. The
second new variant comes from South Dakota, which typically has cases caused by north-central skunk
variant. It has only been documented in two cases from McCook county. Both cases, although positive
by routine diagnostic methods, do not stain with the antibody C4, which distinguishes '~rabies viruses
from other non-rabies Iyssaviruses. In attempt to verify both of these findings, our lab6'ratory used an
expression vector system to express the nucleoprotein of rabies virus in BHK cells. Briefly, the genome
of both variants and a CVS control was amplified by RT -PCR and inserted into a bacterial plasmid.
These plasm ids were used to drive expression of rabies N protein in viable cell culture. These cells
were then used to do monoclonal antibody experiments. Findings show that the expression vector
system is an efficient method of introducing a single rabies protein into cell culture. The absence of
specific epitopes in both mutant variants was con"firmed when these cells were subjected to Mab
analysis. The specifics of the methodology described previously will be presented.
20
,
Kansas State University, 800 Denison Ave. Mosier Hall Manhattan, KS, USA
Rabies antibody testing has become increasingly popular as a method of verifying rabies vaccination
and immune response in dogs and cats that are being imported to rabies free areas. This is in part due
to increasing public pressure for a reduction in lengthy quarantines. The two types of serology testing,
FAVN and RFFIT, will by compared and contrasted. Kansas State University has become
internationally recognized as a leader in the performance of both tests. Specific testing and vaccination
requirements of common rabies free areas such as Australia, Hawaii, and various Caribbean islands will
be overviewed,
INTRODUCCION: La rabia en los humanos yen los perros en Mexico ha representado un problema de
salud publica; los registros del SIVERAlOPS de los ultimos 30 arios, destacan la permanente
notificaci6n de los casos acumulandose 1,738 en el humano, siendo ei perro el principal transmisor con
el 80.8%, seguldos del murcielago con el 8.6% del total; los casos de rabia canina confirm ada por
laboratorio suman 89,820. Por decenios esa casuistica observa reducciones, en el humane de 58.1 % Y
en perros de 41 A% entre las decadas de los 70' y 90'; en ambos las tendencias son descendentes con
valores maximos de 87 y 4,100 (1970) y mlnimos de 30 y 1,900 (1999) respectivamente; con una cafda
por debajo de la tendencia a partir de 1992 en humanos y en 1991 en perros. En los casos de rabia
humana hasta 1997 predomino el perro como especie agresora, posteriormente se pierde esa relacion.
Desarrollo. EI cambio en la casufstica ocurrio a partir de la segunda mitad de la decada de los 80's y
durante los 90's, en el marco del programa de eliminacion de la rabia urbana en la' America Latina; el
compromiso de la Secretarfa de Salud es controlar la rabia transmitida por el perro, con las siguientes
estrategias: Mejorar la atenci6n antirrabica de las personas agredidas. Privilegiar la vacunacion
antirrabica can ina en acciones intensivas, masivas, gratuitas. Mejorar la vigilancia epidemiologica de la
rabia.
RESULTADOS: Mejorar la atencion antim:lbica de las personas agredidas. En la decada de los 90's el
promedio que atendio la Secretarfa de Salud corresponde a 95 mil, iniciando la vacunaci6n el 35%; al
aplicar los biologicos a estas personas(1994} se cambia la historia del tratamiento antirrabico en
Mexico; la vacuna utilizada tradicionalmente en tejido nervioso (CRL), se sustituye por vacunas en
cultivos celulares (VERO y PCEC) observandose mejor aceptaci6n del tratamiento (medico-paciente).
Es elevado el porcentaje de personas que se indica vacunar; para resolverlo se capac ita al personal
medico y paramedico responsable.
Vacunaci6n Antirrabica Canina en Acciones Intensivas, considero las siguientes Ifneas de accion:
• Disponer de un biologico de calidad, en cantidad y oportunidad requerida (tipo inactivada, en
cultivos celulares potencia minima 2 U.I.) se han adquirido 102 millones de dosis (223 lotes).
• Orientar las acciones de vacunaci6n en areas de alto riesgo
• Convocar la participacion de instituciones oficiales y de la comunidad
• Difusion para la poblaci6n en general, mediante un plan de medios de comunicaci6n que consta de
un cartel oficial y promocionales para radio y television.
• Ejecucion de la Semana Nacional de Vacunaci6n Antirrabica Canina a partir de 1990 evaluandose:
'" Impacto epidemiologico: Reduccion gradual de los casos de rabia en el humano transmitido por
perro, 60 11990) a 3 (1999) 95%; Y de rabia canina confirmada par laboratorio 3949 (1990) a 317
(1999) - 89.6%.
Resultados: incrementar el numero de perros vacunados en corto tiempo, con relacion al total
alcanzado en el arlO, 42.2% (1990) a 68A% (1999). ~
~~::;<t
21
...
DE LA RASIA IN THE
* Participacion Social: incremento del numero de personas que participan en esta actividad
(brigadas) promedio por dfa, 10 mil (1990) a 54 mil (1999).
Mejorar la vigilancia epidemiologica de la rabia, mediante dos Ifneas de accion:
• Establecer y operar el informe semanal de casos de rabia; los positivos confirmados por
laboratorio, el lIenado del formato inforrne de foco rabico (1997-1999); en 864 perros estudiados se
destaca que 71 % ten Ian propietario, 58% su edad es menor a un ana y 92% no estaban
vacunados.
• Caracterizacion de las vanantes antigenicas del virus rabico en muestras de animales y personas
que murieron de rabia; a la fecha el Laboratorio de Rabia del Instituto Nacional de Diagnostico y
Referencias Epidemiologicas ha practicado 116 estudios (1998-2000), identificandose las variantes
V1, V3, V5, V7, V8, V9, V10 Y V11 ; predominando la variante V1 con el 53% de los estudios.
Conclusiones. Los avances en el control de la rabia en Mexico, demuestran que las estrategias
implementadas han reducido el problema; sin embargo, es necesario adecuarlas y re-orientarlas, para
lograr el abatimiento total de la rabia can ina y enfrentar el creciente registro de rabia en fauna silvestre,
para eliminar el riesgo de transmision al ser humano y optimizar el consumo de los biologicos
antirrabicos en el humano.
(1) Director del Programa Nacional de Control de Zoonosis del Ministerio de Salud
(2) Medico Veterinario del Programa Nacional de Control de Zoonosis del Ministerio de Salud.
Introduccion: La aparicion de la rabia en el Peru, no puede ser precisada con exactitud, investigaciones
demuestran que en el Antiguo Peru no existio esta enfermedad por hecho de que los Incas no dejaron
huellas en sus obras. Asf mismo en el lenguaje quechua y aymara no existe palabra que signifique
rabia como enfermedad. Los primeros datos que se tiene sobre esta zoonosis es a traves de las Obras
Cientrficas y Literarias de Don Hipolito Unanue (1,914) quien refiere" no hay memoria de que los perros
hayan padecido el mal de rabia en los anteriores en toda esta America, mas en principios de este siglo,
hacia el ano 1,803, se observo en los valles de la Costa Norte, durante los calores del es1l0 y siguio
recorriendo la costa sur, habiendo IIegado a la ciudad de Arequipa en la primavera de 1807 y
notandose en Lima en el propio ana entre el es1l0 y el otono". Desde entonces la rabia se constituyo
en un mal endemico en el Peru, de gran importancia en Salud Publica. En los ultimos 20 anos se han
presentado en el Peru 02 brotes epizooendemicos de gran magnitud, en 1,982 donde se presentaron
1,893 casos en perros con una tasa de 104 x 100,000 canes causando la muerte de 39 personas con
una tasa de 0.16 por 100,000 habitantes y en 1,990 don de se registraron 832 casos en canes y 33
personas fallecidas por esta causa. En los cas os de rabia humana en la decada del 80, el 76% de los
casos era debido a la mordedura de perros con rabia y el 40% por murcielagos hematofagos, sin
embargo en los ultimos cinco anos (1,995-1,999) el 45% de los casos humanos registrados es debido a
la mordedura de perros. En esta ultima dec ada se ha evidenciado una disminucion ostensible de los
casos de rabia humana urbana de 33 casos en 1990 (0.16 x 100.000 hab.) a 2 casos en 1,999 (0.01 x
100,000 hab), Asf tambien los casos de rabia canina de 832 casos en 1990 (37.2 x 100,000 canes) a
76 casos caninos en 1999 (3.10 x 100,000 canes).
Estrategias empleadas: Considerando el Plan de Eliminacion de la Rabia Urbana en Am'erica Latina, a
fines de los 80 y principalmente durante la decada del 90 con el compromiso del Gobierno a traves del
Ministerio de Salud se obtiene importantes avances en la eliminacion de la rabia urbana del territorio
nacional, con las siguientes estrategias: el mejoramiento de la calidad de atencion a las personas
expuestas al virus rabico, el fortalecimiento de la educacion sanitaria orientando a la notificacion
oportuna de personas mordidas, la promocion de la colaboracion interinstitucional e intersectorial,
priorizando la vacunacion antirrabica del 80% de la poblacion canina a traves de campanas masivas,
tenencia responsable de mascotas, observacion clfnica de los animales mordedores y la vigilancia
epidemiologica activa, con envfo de muestras para diagnostico, teniendo como meta referencial el 0.2
% de la poblacion can ina estimada.
Resultados: Incremento de la notificacion de personas mordidas En la decada de los 80 y hasta 1,992
el promedio de personas mordidas que se notificaban era de 43,771 anuales, consecuencia de la
subnotificacion existente e~ el pafs, actualmente con la continua difusion sobre que hacer frente a un
22
,
accidente de mordedura se esta logrando la participacion de la comunidad para denunciar este hecho,
habiendose en 1,999 reportado 86,684 accidentes. ASI mismo, el inicio del tratamiento antirrabico ha
disminuido de 33.44% a 21.27%, dado que se esta priorizando la observaci6n clfnica del animal
mordedor, antes de decidir un tratamiento antirrabico por la parte medica, para 10 cual se realiza
continua capacitaci6n al personal de salud sobre los esquemas de tratamiento antirrabico; la vacuna
que se viene aplicando es CRL siendo el Pais autosuficiente en su producci6n; en los ultimos 16 anos
no se ha registrado casos de reacciones postvacunales neurol6gicas por el uso de este tipo de
vacunas en nuestro medio. La actividad nuclear que ha permitido la exitos en el camino de la
eliminaci6n de la rabia es la vacunaci6n antirrabica canina anual a traves de jornadas masivas y en
forma descentralizada, aSl desde 1,990 en que se vacun6 271 ,078 canes con una cobertura de 12.1
%, se ha incrementado esta, correspondiendo a 1,999 un total de 2'464,897 canes vacunados que
°
representa'tJn acumulado de 97.68 % de cobertura. No existe dificultades en el abastecimiento normal
y oportuno~' de los biol6gicos necesarios. La vigilancia de esta zoonosis a traves de la remisi6n de
muestras encefalicas, habiendose procesado 3,894 en 1,998 y 4,052 en 1,999, 10 que nos esta
permitiendo determinar la circulaci6n del virus rabico en el Pais, para 10 cual se dispone de 10
laboratorios regionales y 01 referencial, que es el Instituto Nacional de Salud, distribuidos
estrategicamente.
CONCLUSIONES: Las acciones de prevenci6n y control de rabia que se vienen realizando en nuestro
PaiS, esta determinando la disminuci6n de la incidencia de esta zoonosis, con 10 que se esta
contribuyendo a lograr la meta de eliminar la rabia urbana en el Peru.
QUALITY CONTROL FOR FLUORESCENT ANTIBODY TESTS FOR RABIES VIRUS (10)
Jean S. Smith
MS G33, Rabies Laboratory, CDC, 1600 Clifton Rd., Atlanta, GA ,USA 30333
Although most fluorescent antibody (FA) reagents for rabies are of high quality, no immunologic test is
free of undesired reactions. Immune serum (IS) reagents contain extraneous, potentially cross-reactive
antibodies. Monoclonal antibody (Mab) reagents risk over-specificity and failure to recognize viral
variants. Both reagents are subject to non-specific binding to Fc receptors. To monitor the quality of
diagnostic reagents used for testing of animals in the United States, we retest samples submitted to the
CDC using FA specificity controls and both IS and Mab based anti-rabies conjugates. Findings are
confirmed by virus isolation and/or reverse transcription-polymerase chain reaction (RT-PCR). We
retested 70 samples submitted to us from state public health laboratories to confirm antigen
accumulations which stained with diminished intensity or were of an atypical morphology as compared
to control rabies virus preparations. For all 70 samples, repeat FA tests either failed to duplicate the
observations of the state laboratory and resulted in an unequivocal negative diagnosis or produced
evidence of non-specific staining by one or more of the rabies reagents. RT-PCR was used to interpret
the FA test results of 17170 samples. RT-PCR was negative for 14/17 samples, including 9 samples
which were negative on the repeat FA test and 5 samples for which non-specific or undesired staining
obscured a clear diagnostic test for rabies. RT-PCR was positive for 3/17 samples, but only in tests for
short amplicons. All 3 samples rlad been negative on repeat FA tests at CDC. Isolation attempts were
negative for 2/3 samples. (Isolation was not attempted on the third sample.) Rabies positive samples
submitted for virus typing (> 300 samples) were retested with IS and Mab reagents. No recognition
failures were found in tests representing all of the variants of rabies virus known to infect animals in the
United States. For all variants, a 1450 bp N gene product could be amplified by RT-PCR with a single
pair of oligonucleotide primers. For any variant, successful amplification of virus from decomposed
samples or from infections localized to discrete brain areas required additional primers and was limited
to small amplicons of <400 bp. Because an animal's shedding of virus in saliva occurs after virus
replication in the brain, all infections of public health importance should be detectable by an FA test that
examines multiple brain areas. FA and isolation negative: RT-PCR positive results occur with sampling
errors when an animal's infection is limited to one area of the brain or when a negative sample is
contaminated with small amounts of material from a positive sample. It was not possible to fully
investigate the cases reported here, because no case included a complete brain. Good quality control
of FA tests for rabies requires unused brain material be held in reserve until a tWst report is completed.
23
Positive tests of animals which are unexpected hosts for rabies and samples in which antigen
distribution is sparse or unusual should be retested by making slides from reserved brain tissue taken at
necropsy. Reserved material should be sectioned so that touch impressions can be made from internal
areas unlikely to have been contaminated with virus from another sample.
DE LA RABIA (11)
Cecilia de Mattos
POSTER PRESENTION: In 1998, Kansas State University began diagnostic testing for rabies suspect
animal samples from Nebraska, along witl1 samples from Kansas. Due to this increase in the number of
speCimens, our laboratory has adopted a new methodology for acquiring samples of medulla,
cerebellum and hippocampus. This method has helped to decrease cross contamination, and also to
minimize the amount of time and labor required for each specimen. The poster will demonstrate the
method of sampling including photographs of tissues, and the verification of the methodology prior to
implementation.
24
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Jose Alvaro Aguiiar Setien, Elizabeth Loza Rubio, Octavio de Paz Villafan, Miguel Camara, Jose Carmen Gudino, Baltazar cortez
Departamento de Medicina Veterinaria y Zootecnia dellnstitutO Tecnologico de Sonora y Facultad de Medicina Veterinaria y
Con la finalidad de conocer la variabilidad en el genom a del virus de la rabia en Mexico, se tomaron 32
muestras positivas arabia por la tecnica de inmunofluorescencia (IF) y una vez realizada una
amplificacion por la tecnica de la reaccion en cadena de la polimerasa (RT ·PCR, por sus siglas en
ingles), se analizaron por medio de la prueba del polimorfismo del largo de los fragmentos de
restriccion (RFLP, por sus siglas en ingles). Dichas muestras proceden de varios estados del pafs y
entre elias ~se encuentran muestras de fauna domestica como bovinos, perros, caballos, cabras y
cerdos, al igual que muestras de fauna silvestre como murcielagos, zorrillo, tejon y gato montes. En
este estudio en lugar de utilizar cuatro enzimas de restriccion 0 endonucleasas, como se ha establecido
en trabajos previos, se utilizaron unicamente dos: BamHI y BsrGI. Los cortes se lIevaron a cabo en un
segmento del genoma conocido como pseudogen ('¥) porcion que une a la proterna G y L del virus
rabico. Se observaron los "sitios de restriccion" establecidos para el cicio conocido como "terrestre"
(perros, gato montes, etc) y el cicio "aereo" (murcielagos hematofagos), mientras tanto las muestras de
un zorrillo y un bovino no presentaron ningun "sitio de restriccion" para las endonucleasas utilizadas
(BamHI y BsrGI). AI igual que en trabajos precedentes, en este estudio, el virus rabico circulante en
zorrillo puede clasificarse en un cicio aparte denominado "hipervariable", exclusivo de esta especie.
Respecto a la muestra bovina procedente de Chiapas que tam poco presento cortes con las enzimas de
restriccion (unico caso) podemos sospechar de una agresion por zorrillo con virus rabico 10 que nos da
evidencias de otra posible fuente de infeccion de rabia en bovinos (enfermedad del derriengue) sin
embargo es necesario comprobar esto mediante un anal isis de la muestra por secuenciacion.
Palabras claves: caracterizacion molecular, fauna domestica, fauna silvestre, PCR, RFLP, ciclos aereo,
silvestre e hipervariable, zorrillo, sitio de restriccion, Mexico.
**Laboratorio de Virologia Cllnica e Molecular ICB - Universidade de Sao Paulo SP, Brasil
The techniques of molecular biology allow the acknowledgement of endemic strains, the identification of
the differences among strain of rabies virus, the discovery of the source of infection in free rabies areas
and the strategic plan related to the studied species. The purpose of this experiment is to compare the
RT-PCR with the Fluorescent antibody test (FA) and the Mouse Inoculation test (MIT). Sixty-two
samples of isolated rabies virus from different species of animals from several cities in Sao Paulo State
were used, between 1989 and 1999, granted by the Rabies Diagnosis Laboratory of the Zoonosis
Control Center, diagnosed by FA and MIT. The fragment of the nerve tissue were submitted to the FA
and MIT techniques again, and after the viral RNA was extracted in order to make the comparison of the
techniques. For the RT-PCR it was used the primers for the N gene was designed from the nucleotides
sequences of the sample Pasteur Virus - PV. Among all the samples 57 had positive responses to FA,
48 to MIT and 56 to PCR. Submitting the results reached from the sensibility and specification test
related to FA, the PCR technique showed 96% of sensibility and 100% of specification. However,
compared to the MIT, the PCR showed 100% of sensibility, and it was observed that the specificity was
to 43%. The low specification can be related to the condition of the former samples (autolysins),
damaging the MIT because it is a biological test. We get to the conclusion that the PCR technique has
good sensibility and specificity. In addition it is faster when compared with the MIT and the virus does
not to be intact. Furthermore, the sensibility and speed of RT-PCR techniques concerning the
conventional methods for the detecting the /yssavirus can be important mainly when detecting the virus
in samples, which are in decay. The amplification of the genome allows the formation of a cDNA file that
when stored allows the preservation of the sequences for future observations.
....-....:~:
25
....
Nadin-Davis*
M. Sheen G. Turner E. Loza-Rubio- and A. 1. Wandeler' Affiliations: 1 Rabies Center of Expertise, Animal Diseases Research
Insfitute, CFIA, Nepean, Ontario, Canada. K2H 8pg: 2 Centro Nacional de Microbiologia Veterinaria-INIFAP, Carretera Federal
In Canada rabies circulates in several wildlife reservoirs inciuding arcbc and red foxes, skunks, many
speCies of insectivorous bats and, more recently, the raccoon. Whilst the range of the disease in each
terrestrial host is geographically restricted, the viraj strains associated with bats are widely dispersad.
Furthermore the ranges of many of these reservoirs overlap so that methods for accurate strain
dfscrimination are required. Whlist standard antigenic and genetic methods are sufficient for this
purpose in most cases. where fresh or frozen brain material is available, occasionally formalin-'fixed
embedded tissues are the oniy material available and typing is then far more challenging. To address
this problem a series of strain-specific probes, which target the highly variable central region of the
rabies virus P gene, has been developed. After carefui optimization of in situ hybridization conditons
these probes ali discrImination bet-en many of the rabies virus strains currently circulating in Ontario
and neighboring regions. The utilization of these probes will be demonstrated Wth particular reference
to a rabies posifive equine specimen which was not amenable to viral typing by other methods. In
additfon, recent genetic characterization of rabies virus isolates from Mexico suggests the possibiiity of
developing P probes for discriminating the strains responsable for rabies in this country; such probes
wouid allow typing of strains in formalin "fixed brains. Progress in these studies will be describes.
In Canada rabies circulates in several Widlife reservoirs including arcbc and red foxes, skunks, many
species of insectivorous bats and, more recendy, the raccoon, Whilst the range of the disease in each
terrestrial host is geographically restricted, the virai strains associated with bats are widely dispersad.
Furthermore the ranges of many of these reservoirs overlap so that methods for accurate strain
discrimination are required. Whilst standard antigenic and genefic methods are sufficient for this
purpose in most cases. where fresh or frozen brain material is available, occasionally formalin-fixed
embedded tissues are the oniy material available and typing is then far more challenging. To address
this problem a series of strain-specific probes, which target the highly variable central region of the
rabies virus P gene, has been developed. After careful optimization of in situ hybridization conditons
these probes allow discrimination between many of the rabies virus strains currently circulating in
Ontario and neighboring regions. The utilization of these probes will be demonstrated with particular
reference to a rabies posifive equine specimen which was not amenable to viraj typing by other
methods. In addition, recent genetic characterization of rabies virus isolates from Mexico suggests the
possibility of developing P probes for discriminating the strains responsable for rabies in this country;
such probes wouid allow typing of strains in formalin "fixed brains. Progress in these studies will be
describeb.
2 Chemicon International Inc., 28835 Single Oak Drive, Temecula, CA, USA, 92590
There is a growing need for reagents to use in contemporary rapid diagnostic techn,~ques for the
detection of rabies virus in animal tissues. A collaboration between the Canadian Food Inspection
Agency and Chemicon International, Inc. was initiated to develop a high-quality, inexpensive reagent for
the detection of rabies virus and other Iyssaviruses in infected tissue. Two goats were immunized with
purified rabies (ERA strain) ribonucleoprotein (RNP) and bled approximately every two weeks. When
goats displayed signi'ficant rabies-specific serum antibody (Ab) titers, measured by indirect
immunofluorescence, serum immunoglobulin was purified and labeled with fluorescein (FITC). The
labeled product was analyzed for specificity by direct immunostaining of acetone-'fixed brain
impressions. Brilliant apple-green fluorescence, with little to no background, was observed upon
binding of the conjugate (20 ug/mL) to ribonucleoprotein inclusions. The conjugate reacts with all
representatives tested 'from each Iyssavirus genotype, including Australian Bat Iyssaviruses. Diluent
optimization, additional cross-reactivity studies, and further quality control are in progress to ensure the
timely scale-up production of conjugate for commercial use.
26
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EI Instituto de Zoonosis "Luis Pasteur" es la denominacion actual del viejo Laboratorio Pasteur fundado
por el Dr. Davel en 1886. Es la primera institucion en America en la que se vacuno contra la rabia. A
traves de su accionar ininterrumpido durante mas de 110 arios, logro controlar la rabia humana y en
animales domesticos de la ciudad de Buenos Aires. Actualmente realiza la vigilancia epidemiologica de
la enfermedad mediante la tipificacion antigenica de capas de virus rabico por medio de anticuerpos
monoclonales que se utilizan desde 1992. En total se han realizado 120 tipificaciones en cepas
procedentes de la Argentina, Paraguay y Brasil y sus primeros resultados ya fueron publicados.
Hasta la feCha, hemos encontrado 5 variantes, la Variante 1 en un total de 9 casos; un humano, un
bufalo, un bovino, una llama, 5 perros, en 2 de los cuales el A.M.N°18 reacciono en forma positiva yen
uno el A.M. N°9 reacciono en forma debil, en nuestro primer trabajo publicado los denominamos
Subvariantes 1a y 1b respectivamente. La Variante 2 se encontro en 127 perros procedentes de las
zonas rurales de Argentina y Paraguay, en 5 de ellos, el A.M. N° 9 reacciono en forma variable y en 4
en forma debil, a estos casos, en nuestro primer trabajo los denominamos Subvariantes 2a y 2b
respectivamente.
Ademas la Variante 2 fue encontrada en un zorro procedente del Chaco yen 2 bovinos de Misiones. En
2 bovinos de Formosa el A.M. N°9 reacciono en forma variable y debil respectivamente (Subvariantes
2a y 2b).
De la Variante 3 encontramos un total de 44 casos: uno perteneciente a un zorro de la provincia del
Chaco, 37 a bovinos, 1 equino de Brasil, 4 cepas se encontraron en Desmodus rotundus y una en
murcielago frugfvoro (Artibeus lituratus) de Brasil. EI A.M. N°15 reacciono en forma positiva en un
grupo de 10 bovinos procedentes de Argentina, Brasil y Paraguay, en un equino de Formosa y en un
Artibeus lituratus de Candelaria, Misiones, por 10 tanto en nuestro primer trabajo, a estas 12 muestras
las denominamos Subvariante 3a. La Variante 4 fue encontrada en murcielagos insectfvoros: 20
Tadarida brasiliensis, 4 Lasiurus cinereus y 3 Molussus molussus En otros 2 Tadarida
brasiliensis encontramos algunas diferencias en los patrones de reaccion de los A.M. N°1, 15 Y 19
por 10 que 10 denominamos Subvariantes 4g y 4b. La Variante 6 fue encontrada en 3 Lasiurus
cinereus procedentes de la Provincia de Buenos Aires, en otro Lasiurus cinereus de la Provincia de
Buenos Aires, el A.M. N° 1 reacciono en forma positiva.
Centers for Disease Control and Prevention, Rabies Section - Atlanta Georgia USA
A rapid immunohistochemical technique (RIT) has been developed for confirmation of rabies diagnosis
on formalin fixed brain impressions, using anti-rabies monoclonal antibodies and an avidin-biotin
colorimetric detection system and is currently under evaluation in the United States (Niezgoda M.,
th
Rupprecht CE.. Towards the development of another rabies diagnostic test. 10 Annual Rabies in the
Americas Meeting, San Diego, California, USA, November 14-19, 1999). Ideally, this test requires only
ordinary light microscopy for rabies diagnosis in laboratories without immunofluorescence equipment
and also in the field. Moreover, formalin fixation compared to acetone more completely inactivates
rabies virus in tissues enhancing biosafety conditions. Preliminary tests using brain material from
naturally and experimentally infected animals with a diversity of Iyssaviruses have demonstrated that
RIT sensitivity and specificity are comparable to those of the standard direct immunofluorescence
antibody test (DFA). These advantages will make RIT an invaluable tool as a confirmatory test or as an
alternative method to DFA.
Due to the important advances in rabies surveillance and viral molecular typing achieved during the last
5 years in Latin America, a high degree of antigenic and genetic diversity has been demonstrated
among rabies virus isolates in this region. This diversity could potentially hinder the successful
application of this proposed economic and easy to perform diagnostic method. To evaluate the ability of
this test to recognize different variants circulating in Latin America, 240 rabies isolates obtained from
known reservoirs and still unidentified reservoirs in 7 di'fferent countries xvere analyzed with this
technique. A positive colorimetric reaction was obtained with all rabies variah'Ys tested. These results
27
~
XI REUNION INTEFmACIONAL "I rERN/I.110r'AI MEETING ON RESEARCH
AVANCES EN A[)VA~,CES AND CONTROL
DE LA RASIA THE AMERICAS
strongly support the feasibility of the use of RIT as a potential confirmatory test or as a possible
alternative to DFA for rabies diagnosis in Latin America. Further evaluation of this technique under
actual field conditions in each country is essential to determine its specificity and sensitivity with local
isolates before its application as a rabies diagnosis method could be considered in Latin America.
Souza. M. C. A. M; Kotait, L
While the incidence of rabies transmitted by domestic animals, mainly dogs, decreases in Brazil and
other countries from the Americas, the number of rabies cases transmitted by bats is Increasing, as well
as the number of cases transmitted by other wild animals.
Records from the Ministry of Health show that in the last ten years nearly 15% of the cases of rabies in
humans was transmitted by bats. Rabies epidemiologic surveillance has shown that the disease occurs
in two different cycles. The urban cycle, with the dog as the main reservoir, and the sylvatic cycle, with
different species acting as reservoirs or transmitters, which vary from region to region.
The molecular characterization of rabies isolates in conjuction with surveillance data IS essential for the
better understanding of rabies epidemiology.
To know more about the intra and inter species transmission pathways of rabies virus ,we have
antigenically and genetically characterized isolates obtained from humans, domestic animals, bats and
other wildlife species in Brazil, Paraguay and Bolivia, from 1989 to July 2000.
Two hundred and ninety six samples were studied. From those, 101 were obtained from dogs, 12 from
cats, 32 from bovines, 21 from equines, 88 from bats, 30 from humans, 6 from sheep, 1 from a goat, 1
from a pig, 1 from a fox, 1 from a quati, 1 from a monkey and 1 from a sagOi. PV virus, propagated in
BHK-21 cells, and CVS-32, mantained by intracerebral passages in mice were also characterized. All
viruses were antigenically characterized at the "Pasteur" Institute of Sao Paulo, Brazil, using a indirect
immunoHuorescence test, with a panel of 8 monoclonal antibodies, directed to the viral nucleoprotein,
kindly provided by Centers for Disease Control and Prevention (C.D.C)., Atlanta, Georgia, U.S.A. and
pre-established by The Panamerican Health Organization (P.A.H.O.), for studies on molecular
epidemiology of rabies virus in Latin America. From these group, 84 isolates from Brazil and Paraguay
were also genetically characterized at C.D.C. by the sequencing of a portion of their viral nucleoprotein
gene, and their philogenetic comparison with rabies variants previously described in the region.
Antigenic variants (AgV) 1,2,3,4,6 and a Lab variant previously described with this panel were identified.
Five new patterns of reaction were also detected.
Antigenic variant 3, which reservoir is Desmodus rotundus, was found in isolates from Brazil as follows:
10% (8) of dogs; 27,2% (3) of cats; in 11 % (3) of humans; in 100%(1) of goats; in 80% (5) of the
sheep; in 100% (21) of the equines; in 100% (27) of the bovines. This variant was also found in 100%
(34) of the hematophagous bats and in 55,5% (55) of the non-hematophagous bats (22) frugivorous, 32
insectivorous and 1 non identl"fied to species) We also found an antigenic variant, similar to AgV 5 in
several species of insectivorous bats and in a cat from Sao Paulo State.
In the samples from Paraguay, AgV2 was identified in isolates from dogs and cats, and AgV 3, in an
isolate from a bovine. In the samples from Bolivia, AgV 1 was found in isolates from dgQs, cats, one
human, one bovine, one equine and one non-human primate. This results are different from those
obtained in Brazil and Paraguay,where AgV 2 was the antigenic variant present in samples from the
urban cycle.
A high degree of genetic diversity was found in samples obtained from insectivorous bats. The genetic
variant mantained by Desmodus rotundus was also identified in isolates from insectivorous and
frugivorous bats. Despite the antigeniC homogeneity found in rabies isolates from the urban cycle, all
characterized as AgV2, they showed marked genetic diversity.
The high degree of antigenic and genetic diversity obsrved in this study strongly indicates the need for
the elaboration of improved surveillance programs together with viral molecular characterization for the
better understanding or rabies epidemiology in Latin America.
28
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EI Instituto Colombiano Agropecuario (ICA), entidad adscrita al Ministerio de Agricultura, tiene como
una de sus funciones la proteccion de la sanidad pecuaria del pars, a traves de actividades de
vigilancia epidemiologica para las patologfas animales, entre elias la encefalitis rabica. Oficinas de
Sanidad Animal distribuidas en todo el territorio nacional y 27 Centros de Diagnostico (dos de ellos con
capacidad para el diagnostico regular por inmunofluorescencia directa e inoculacion en raton) ubicados
en las principales ciudades, ejecutan las labores de vigilancia mediante la deteccion y atencion de
focos, toma y envfo de muestras al laboratorio, analisis de resultados y adopcion de medidas
sanitarias para ia prevencion y el control. Como Centro de referencia actua el Laboratorio Nacional de
Diagnosticc{Veterinario, ubicado en la ciudad de Bogota, en donde, ademas del diagnostico regular, se
realiza la investigacion de los virus rabicos aislados.
Las tecnicas disponibles en el Laboratorio Nacional de Referencia, para el diagnostico e investigacion
de la rabia son:
• Inmunofluorescencia directa y prueba biologica por inoculacion en raton.
• Tipificacion antigenica.
EI Ministerio de Salud posee cuatro (4) laboratorios para el diagnostico de la rabia urbana y un
laboratoric de referencia.
EI Laboratorio Nacional de Diagnostico Veterinario del ICA ha realizado la tipificacion antigenica de 125
aislados virales de todo el pars (77 de bovin~s, 37 de canin~s, 5 de equin~s, 2 de felinos, 2 de zorros, 1
panel de ocho (8) anticuerpos monoclonales suministrado por el CDC (Atlanta - Georgia, USA).
Este estudio ha permitido demostrar que las variantes antigenicas actuantes en el pafs son la I
29
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If Hi flNATIOc{!\L ON
AL1VMK'f'" RABIES
IN THE
nacional.
a) Realiza diagnostico de referencia directo y serologico, para los laboratorios provinclales del Sector.
b) Produce reactivos estandares para diagnostico serologico: lotes de antfgeno y suero indicador para
Centro Nacional de Laboratorios en Salud Publica del Instituto Nacional de Salud, Lima-Peru
Se presento un brote de rabia human a en el Departamento de Madre de Dios durante el presente ano.
EI estudio epidemiologico del caso no permitio deslindar el origen urbano 0 silvestre debido a que el
caso estuvo en contacto en zonas de rabia urbana y rabia silvestre. Para poder determinar el origen
del caso de rabia humana se empleo un set de ocho anticuerpos monoclonales del CDC y para la
caracterizacion genetica se amplifico un producto de la region que codifica la protefna N de 1468 pares
de bases con los prim eros 10g. Y 304. Este producto obtenido fue cion ado para luego ser secuenciado
geneticam ente.
Se presentan los resultados del analisis antigenetico y genetico.
30
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UNR, Facultad de Ciencias Veterinarias, Area Salud Publica: */**Profesor Titular y Adjunto: ****
En poblaciones de nivel socioeconomico bajo, las relaciones entre el hombre y los animales pueden
constituir un factor de riesgo sanitario que agrava la situacion de salud de esos grupos vulnerables. La
activacion ~ocial de conductas poblacionales orientadas a la atencion sanitaria animal, puede
transformarse en una estrategia de comunicacion que trascienda ese campo y se convierta en un
instrumento de movilizacion que promocione la salud del hombre. La accion interdiscfpifnada e
intersectorial de la Facultad de Cs. Veterinarias de la UNR, la Secretaria de Promocion Social de la
Municipalidad de Rosario, Asociaciones Vecinales, el sector educacion y organizaciones no
gubernamentales (ONG), religiosas, sociales, y deportivas, implemento un "Programa de tenencia
responsable de perros y gatos dirigido a poblaciones con necesidades basicas insatisfechas (NBI)",
basado en actividades de: - promocion de la participacion comunitaria - educacion para la salud - censo
canino y feline - esterilizacion animal; desarrollado de mayo a noviembre de 1999, a fin de dar
respuesta a problemas como la alta demanda de asistencia hospitalaria por agresiones animales y la
existencia de elevado numero de animales vagabundos con y sin dueno. Otros programas estatales se
ejecutaban simultaneamente orientados: - al empleo temporada por contrato (sus beneficiarios
participaron en la realizacion del censo de poblacion animal), - y a la asistencia alimentada. EI objetivo
era prevenir la transmision de zoonosis y las lesiones por agresion animal. Las acciones se
desarrollaron en treinta y cuatro barrios situados al oeste, sur y norte del ejido municipal. Las personas
residentes se nucleaban socialmente en siete comisiones vecinales, que en sus dependencias
instalaron los centr~s de esterilizacion, con asistencia economica del municipio y fueron ambito para las
reuniones comunitarias; sus asociados colaboraron en tareas organizativas, administrativas y de
limpieza. Las esterilizaciones quirurgicas las hacfan equipos de docentes de la Catedra de Cirugfa
asistidos por alum nos. A estas, se integraban agrupaciones de proteccion animal y grupos religiosos.
EI sector educacion, fue responsable con docentes y alumnos de la Catedra de Salud Publica de la
divulgacion y promocion del Programa en escuelas, con entrega de material didactico.} Se realizaron
visitas domiciliadas y 125 reuniones comunitarias, a las que asistieron 1661 personas, se esterilizaron
533 animales, el 67,5% (360) eran perros, 95.3% (343) hembras, 4.7% (1 7) machos. EI 32.2% (172)
eran gatos: 70.3%, (121) hembras y 29.6% (51) machos. Se censaron 4371 perros: hembras 1809
(41.4%), machos 2562 (58.6%) Y 1092 gatos: hembras 473 (43.3%), machos 619 (56.7%). La relacion
hombre/ perro fue de 3/1, la relacion hombre/gato fue de 13/1. Se efectuaron 697 tratamientos
antiparasitados extern os y 672 tratamientos antiparasitarios internos. Se identificaron barreras en la
comunicaci6n: la existencia de otros problemas prioritados en un marco de creciente pobreza y
marginalidad social; valores culturales, creencias y mitos antagonicos al contenido de los rnensajes;
procesos electorales y prejuicios con respecto de intenciones encubiertas de los actores intervinientes.
Facilitaron al mismo el fuerte vinculo existente entre personas y animales; la presencia de la
Universidad en la ejecucion del programa y la influencia de las organizaciones de base.
Frente a la cdsis del Estado y la disgregacion social, un aporte de la Universidad es constituir un
espacio despojado de connotaciones interesadas para el encuentro y concertaci6n entre los distintos
actores sociales.
31
XI REUNI6N INTERNACIONAL SOBRE Ir,nERNATIONAL Mt:ETING ON RESEARCH
AVANCES EN LA INVESTIGACI6N Y CONTROL ADVANCES AND RABIES CONTROL
DE LA RABIA EN LAS AMERICAS IN THE AMERICAS
Direccion de Salud III Lima Norte - Direcci6n Ejecutiva de Salud Ambiemtal - Lima-Peru
A pesar de los esfuerzosrealizados en los ultimos decenios, la rabia constituye un grave problema para
la salud v economfa, sobre todo en el Peru donde predomina la rabia urbana y rabiasilvestre con un
alto numero de casos en animales domesticos. En el perfodo de 1990 a 1999 del ue rabia humana en
el departamento de Lima v Callao fue de 27 casos. correspondiendo a Lima Norte 8, de estos al distrito
de San Juan de Lurigancho Ie correspondieron 5 casos de rabia humana, en relaci6n a la rabia canina
en el departamento de Lima v Callao fue de 626 casos, correspondiendo a Lima Norte 331, de estos a
San Juan de Lurigancho Ie correspondieron 141 canes con rabia. por esto el distrito de San Juan de
Lurigancho fue el de mayor problema con relaci6n a rabia urbana, siendo su ultimo caso de rabia
humana en 1993 v su ultimo caso de rabia canina 1996. En 1999 se notificar6n en los establecimientos
de San Juan de Lurigancho 2533 personas mordidas por perros y.. en el Centro Antirrabico de Lima 241
fueron atendidos pertenecientes a este distrito. siendo la morrdedura de perro la causa de la gran
mayoria de los accidentes en San Juan de Lurigancho y ademas de la gran cantidad de herida que
requieren tratamiento antirrabico preventivo como tambien atenci6n medica y/o quirurgica. Por otra
parte el gran crecimiento demografico de Peru sobre todo en los centros urbanos, permite suponer que
esta situaci6n podria agravarse aun mas. Por estas razones se decidio efectuar una investigaci6n
epiciemiol6gica del problema de la rabia urbana y accidentes por mordeduras en una zona altamente
poblada e industrializada del Peru, en San Juan de Lurigancho, Distrito de Lima, provincia Lima.
Nuestro objetivo fue determinar la importancia que tiene en la salud y economfa de la poblaci6n las
mordeduras, de perro como causa de lesiones y riesgo de rabia en una zona como hemos indicado
donde la enfermedad por sus caracterfsticas podrfa rebrotar, caracterizar los aspectos epidemiologicos
y sugerir medidas para la prevenci6n y control. Nuestra metodologia fue determinar una zona de
estudio que fue el distrito de San Juan de Lurigancho, que es uno de los 43 distritos de la provincia de
Lima, uno de los diez correspondiente a la Direcci6n de Salud III Lima Norte (como provincia de Lima)
la tecnica que empleamos fue el de Encuesta. se selecciono en forma aleatoria 401 personas de 2533
personas mordidas por perro, se realizaron entrevistas domiciliarias con fichas de encuestas yestudio
de las historias clfnicas, obtuviendose datos de la persona mordida, informaci6n del perro mordedor,
informaci6n sobre el accidente, caracteristicas de las mordeduras, tratamiento de las heridas, medidas
de profilaxis antirrabica post-exposici6n, secuelas de la mordeduras, repercusiones econ6micas de las
mordeduras. Los resultados del presente trabajo demuestran que las mordecduras de perro constituyen
un importante problema de salud publica, tal como se observa en los siguientes casos: Entre algunas
caracterfsticas epidemiol6gicas, se consideran las del grupo humano mas expuesto al riesgo de sufrir
mordeduras de perros. el alto porcentaje de. mordidos recae en los ninos menores de 14 anos (54%)
por 10 que se incidiran en trabajos de educaci6n para la salud en ninos de esa edad. Se determin6 las
circunstancias en que, ocurren los accidentes en relaci6n a esta enfermedad; gran porcentaje 66,84%
fueron en el interior y inmediaciones de la vivienda del dueno. EI numero y naturaleza de las lesiones
provocadas por mordeduras; alto porcentaje de complicaciones; secuelas esteticas 361, y tratamiento
medico 0 quirurgico - 0 ambos - requerido como consecuencia de dichas lesiones. Por otro lado, el
riesgo de contraer la rabia provoc6 que un gran numero de personas debiera someterse a tratamiento
antirrabico preventivo 55,86% preescrito por el profesional correspondiente a pesar de, qAJe la mayorfa
de las mordeduras fueron en zonas del cuerpo consideradas no graves y la mayoria fue tipificada
como rasguno 64% en el miembro inferior y miembro superior excepto mana (74% de las mordeduras),
un alto porcentaje de los animales agresores fueron observados 79% de las circunstancias en que
ocurren los accidentes. por 10 que la mayor parte de los vacunados se ponen en riesgo a los efectos
post-vacunales y inutiles gastos econ6mico, del programa, por 10 que se debe incidir en curso de
refrescamiento a personal medico, a los serumistas que asumen muchas veces los Establecimientos
de Salud periurbano. Los 94 trabajadores que integraban la muestra perdieron en conjunto 483 dfas de
trabajo como consecuencia de mordeduras, 10 representa una perdida de casi cinco dfas laborables por
persona. Por ultimo, se sugieren medidas para la prevenci6n y control del problema.
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INTRODUCCION: La Rabia transmitida por murcialagos constituye un grave problema de salud publica
en el pafs especialmente en las zonas de selva donde se han producido el 90% de los brotes de Rabia
silvestre. Las poblaciones rurales mestizas e indfgenas de la amazonia estan expuestas en forma
permanente a la mordedura de murcialagos encontrandose en alto riesgo de enfermar y morir por
rabia, siendo el grupo etareo mas afectado el menor de 15 arios. En los brotes registrados en la
Provincia de Alto Amazonas (1991 - 1995) el 80% de los casos correspondfa al grupo etareo de 5 a 14
arios. En el ari01996 el 85% de los expuestos a mordeduras de murcialago registrados correspondfa al
grupo etareQ~de 5 a 14 arios.
OBJETIVO: Implementacion de un sistema de vigilancia centinela en la poblacion escolar para vigilar
el RIESGO de exposicion a mordeduras de murcialagos en la poblacion de las ZONAS DE RIESGO
(ZR) de transmision de Rabia transmitida por murcialagos.
JUSTIFICACION:
1. La poblacion de 5 a 14 arios de edad es el grupo donde se registran el mayor numero de
mordeduras de murcialagos.
2. La vigilancia Centinela en este grupo permite tener inforrnacion de alrededor del 80% de la
poblacion expuesta teniendo una elevada representatividad.
3. La Poblacion escolar es accesible al sistema de Vigilancia Epidemiologica, a travas de la
participacion de los profesores
4. Todas las comunidades cuentan con un Centro educativ~ de nivel primario.
5. Los profesores de los Centro educativos de las ZR es el personal con rnayor nivel educativo dentro
de la comunidad, son bilingOes y cuentan con la aceptacion de la poblacion.
METODOLOGfA:
1. La vigilancia Centinela Escolar (VCE) se implemento en las ZR de transmision de Rabia transmitida
por murcialagos.
2. Se capacito y sensibilizo a los profesores de las ZR de transmision de Rabia transmitida por
murcialagos.
3. Se diserio de formulario para el registro de la frecuencia de mordeduras en la poblacion escolar y
otros miembros de la comunidad.
4. La informacion es recogida por el profesor una vez a las semana, en el momenta de la formacion al
inicio de las clases.
5. EI profesor registra en el formulario la informacion, en la celda de la semana correspondiente, hasta
completar el meso
6. Este registro semanal, permitira al profesor evaluar la conducta de las mordeduras, en caso de
observar un incremento debera informar al personal de salud.
7. EI personal de salud registra esta informacion en un grafico de frecuencias, 10 que Ie permite
realizar el monitoreo de la exposicion en forma mensual.
RESULTADOS:
1. Se capac ito en Rabia Silvestre y vigilancia Centinela a 104 profesores bilingDes de las ZR.
2. Se implemento la VCE en 77 comunidades de Alto Riesgo (AR).
3. La informacion obtenida por los profesores permitio detectar un incremento inusual de las
mordeduras de murcialagos, interviniendo oportunamente en comunidades de AR.
4. Se protegieron con vacunacion antirrabica a 567 personas que habfan sido mordidas por
murcialagos.
5. Se identificaron las comunidades con mayor actividad de murcialagos hematofagos 10 que permitio
su captura en momentos de mayor actividad, obtencion de muestras y el control de la poblacion de
murcialagos.
6. Perrnite un mayor conocimiento del comportarniento de los murcialagos hematofagos
7. Permite evaluar las medidas de proteccion adoptadas por la poblacion.
33
XI REUNION INTERNACIONAL SOBRE INTERNATIONAL MEETING ON RESEARCH
AVANCES EN LA INVESTIGACION Y CONTROL ADVANCES AND RABIES CONTROL
DE LA RABIA EN LAS AMERICAS IN THE AMERICAS
Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
INTRODUCTION: Historically, spelunkers (or cavers) have been recommended to receive preexposure
prophylaxis against rabies because of the potential contact with bats, known reservoirs for the disease.
Nevertheless, one survey conducted in the past 30 years found that only 14% of spelunkers actually
received preexposure vaccination. Knowledge and attitudes are poorly documented about rabies and its
prevention among such risk groups.
METHODS: We administered a questionnaire to 1508 cavers attending the National Speological Society
Convention held in Elkins, West Virginia, USA, in June, 2000.
RESULTS: Questionnaires were returned from 392 persons (response rate = 26%). The mean age of
respondents was 47 (range 12-84), and 68% were male, while 76% had a college degree. Persons had
been caving an average of 23 years (range 1-58) and an average of 16 times in the past year. Only
20% of cavers had received rabies preexposure prophylaxis. Of the 22% that had been advised to
consider vaccine, for 77% the rationale for reception was caving and 69% had received it. College
graduates were more likely to be advised to receive pre-exposure vaccine (24% vs. 17%) and to obtain
it (21 % vs. 14%). Approximately 70% reported that they see bats on half or more of their caving trips. Of
respondents, 85% felt a bat bite, 60% felt a bat scratch, 13% felt a bat contacting skin, 3% felt a bat
contacting clothing, and 11 % felt that being around bats without contact was a risk for rabies. College
graduates were more likely to think rabies was a risk from any of these scenarios, respectively, (89% vs.
74%; 66% vs. 46%; 14% vs. 10%; 3% vs. 1%; 13% vs. 9%). Although 24 (1.6%) respondents felt they
had been exposed to rabies, only 1 indicated the exposure was associated with caving: 12 were bite
exposures, 6 were not true exposures, 6 were unable to be classified, and 5 respondents had
exposures to bats.
DISCUSSION: The study is limited by a low response rate, but suggests that despite longstanding
guidelines for cavers to receive preexposure immunization for rabies only 20% have done so.
Increasing awareness of the recommendation likely would increase compliance as more than two-U'lirds
of those advised to receive vaccination had done so. At least 15% of respondents did not consider a bat
bite a risk for rabies, rising to 26% if those without college degrees were considered. Given the
familiarity of cavers with bats, this latter percentage may be higher in the general public. Most recent
cases of human rabies associated with bat rabies virus variants are unexplained. Patients may not know
to seek health care for a bat bite and the rlistory of the bite may be unattainable.
Instituto: PESAGRO-RIO - Alameda Sao Boaventura, 770, Fonseca, Niteroi, Rio de Janeiro, BRASIL
A multidisciplinary action was set up to prevent the occurrence of rabies among individuals of human
communities with a history of vampire bat attacks, in a delimited ecosystem less then five kilometres
'from an hydrographic basin of endemic bovine rabies. Research carried out by Agricultur~1 officials in
Rio de Janeiro/Brazil during the last decade proved that the only efficient method of reducing rabies
risks in endemic areas is by carrying out population control of vampire bats close to human dwellings.
During the month of January/99, more than 10 human individuals from a closed community of island IIha
Grande/Angra dos Reis/RJ/Brazil were bitten by vampire bats. The main communities of the island were
interviewed by Public Health Nurses university group with semi-structured questionnaires applied to the
local Health authorities, social and religious community leaders, and school heads, as well as members
of families bitten by the bats. General orientation was given, specially about the relation man
environment. This group was followed by a second group of researchers in animal Health (veterinarians
and biologists with experience in rabies epidemiology), Wllich collected bat samples in the areas
identified by the first group, with known vampire bat attacks to animals and humans, together with
technical advice about how to deal with the subject. All collected samples were analysed by a third
group of biologists, experienced in bat biology, that carried out ecological and biological studies, as well
as laboratory studies on the I2resence of rabies virus and other agents capable of causing zoonoses. A
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group of students and a local team of Public Health agents participated in all activities and the later was
trained to follow-up the action and give continuity to the program. Knowledge, attitudes and practices to
deal with a possible rabies outbreak among a distinct community were identified. It was concluded that
once the expression of a community's demands is induced, its immediate attenda.nce develops the trust
and integration that will not only lead to the solving of the actual problem, but also of a large part of all
Health needs of the human community in question, possibly extrapolating to a very large social
economical impact.
Fundaci0'1 Fulbright, Ministerio de Salud de Colombia, y Johns Hopkins University School of Hygiene and Public Health.
EI presente""estudio examina los facto res sociales que influyen en la Rabia Canina, con el fin de guiar el
diseno de programas educativos sobre Rabia Canina en Colombia, Sudamerica. Especfficamente,
evalua en forma metodol6gica los conocimientos populares acerca de la Rabia Canina, observaci6n de
los cuidados que reciben los animales domesticos, y evaluaci6n de actitudes y comportamientos de la
comunidad frente al accidente nlbico y otras acciones de prevenci6n de la rabia. Se estructur6 una
encuesta teniendo en cuenta la cadena epidemiol6gica de la rabia canina, y la metodologfa de
investigacion social, se hizo adem as observacion sobre el comportamiento de las personas mordidas
por caninos y frente a las actividades de prevencion. Se realizaron 1600 encuestas en 1.996 en
comunidades urbanas y a nivel rural en los departamentos andinos de Cundinamarca y Boyaca, la
muestra urbana se hizo teniendo en cuenta los estratos sociales (del 1 al 6), a pesar de que el 96% de
los encuestados sablan que la rabia era una enfermedad del perro basicamente, que estos la podfan
transferir al humano (96% 10 sabia), sin embargo se confundfa la enfermedad con otros estados
morbosos del perro y no estaba claro que era un agente biologico (virus) el que la producfa, sin que un
47% de los encuestados contestaron que la enfermedad era un producto de diferentes causas. Esta
confusion sobre definicion y etiologfa de la rabia, interfiere en las medidas de prevencion de la
enfermedad, especial mente en la vacunacion animal. Solo un 15% de las personas del area urbana y
un 27% en el area rural, respondieron que lavarfan la herida con agua y jab6n, en el evento de ser
agredido por un perro. Menos de la mitad de los encuestados , un 49%, respondieron que restringen la
salida de los perros sueltos a la calle. Esta situacion era peor en el area rural, en la cual el 89% de los
propietarios de perros encuestados, dejan salir a la calle a los animales durante las horas del dfa y un
95% durante la noche. La mayorfa (67%) dijo haber vacunado a su perro, pero solo el 55% se constato
tenlan certificado de vacunacion vigente. Diferentes razones se adujeron para la no vacunaci6n: la
vacuna Ie haria dano al perro, dificultad para el manejo del perro hasta el puesto de vacunaci6n, no se
enteraron de la vacunaci6n 0 no ubicaron puestos de vacunacion cerca de la casa.
Se concluye:
1. Que si los programas de Prevencion de Rabia, no consideran tan importante corno la vacunaci6n
rnasiva la ejecuci6n de actividades educativas, no se genera impacto.
2. Estas actividades deben estar basadas en una metodologfa pedagogica especial, analftica y con
participaci6n comunitaria en todo el proceso, y previo diagnostico de conocimientos, actitudes y
comportamiento de la comunidad.
3. Las ayudas audiovisuales deben someterse a un proceso de validacion con la comunidad y
considerarse no como la estrategia educativa, sino corno un soporte para esta.
Mientras no se logren cambios de comportamiento en los duenos 0 tenedores de mascotas, como 10
relacionado con los cuidados higienicos, el someterlos a un esquema de vacunacion y la permanencia
de los animales dentro de su domicilio, sera bien dificil eliminar algunos facto res de riesgo de la Rabia
en animales domesticos.
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INTERNACIONAL SOBRE INTFRNATIONAI ON
LA INVESTIGACION Y CONTROL ADVANCES RABiES
EN LAS AMERICAS IN THE
Chromatographically Purified Rabies Vaccine, CPRV, is produced on Vero cells using the Wistar Rabies
Pittmann Moore Strain WI38-1503-3M, and propagated on microcarriers. Purification of the viral
suspension is performed by 3 chromatography steps to remove DNA and protein residues. The virus is
inactivated by beta-propiolactone. Previous studies have shown that CPRV is as immunogenic and safe
as PVRV. An efficacy study has shown that a PET schedule of CPRV protected patients bitten by
proven rabid animals. This randomized double-blind study, carried out in 5 veterinary schools in France
and Belgium aimed to evaluate the immunogenicity, safety and consistency of 3 commercial batches of
CPRV uS,ing a PET schedula.in young healthy adults.
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INTERNATIONAL MEETING ON
ADVANCES AND RABIES
IN Tl-lE
Three intramuscular doses were given to 460 students on days 0, 7 and 28. One year later, 416 of them
received a booster dose with the same batch as received for primary immunization. Antibody titers were
measured on days 0, 28, 42, and 379 by the Rapid Fluorescent Focus Inhibition Test. Tolerance was
evaluated after each vaccination by investigators. Students reported adverse events in safety diaries.
Seroconversion rates and GMTs were compared on days 42 and 379. On day 42, all students had
seroconverted (serum titer;:::: 0.5 IU/ml). GMTs were similar in the three groups (27.7 IU/ml to 28.9
IU/ml). Two weeks after the booster dose (0379), all students had antibody titers above 0.5 IU/ml and
the GMTs were respectively 28.6 IU/ml, 27.5 IU/ml and 32.4 IU/ml. No immediate reaction was reported
during the trial. Most reactions were of mild or moderate intensity and occurred with the same incidence
in the 3 groups. Local reactions, mainly mild pain at the injection site, concerned a maximum of 60% of
the students. Systemic reactions, mainly headache, asthenia, fever, nausea, and myalgia, were
reported by a maximum of 20% of the students after primary immunization and by less than 7% after the
booster. NO' hypersensitivity reactions were reported. The use of CPRV for complete pre-exposure
prophylaxis, including priming and booster in young adults demonstrated good immunogenicity and
safety profiles.
Mirjana Stantic-PavilincMD,MSc
Rabies is present almost allover the world and is classified into re-emerging infectious diseases. How
to protect health care personnel from the possibility of contracting some of the infectious disease,
including rabies, is a matter of continuous discussion. These discussions focus on health care
personnel, their managers an expert workers, responsible for prevention of hospital infections. For some
vaccines, which are used for exposed health care personnel, we can learn abaout from elementary
medical books; for some other vaccines, we can rarely find reports in medical journals. It is often
supposed that a rabid human case could be a potential source of infection for health care personnel, in
charge of serving the patient. Rabies virus was laboratory confirmed in many tissues and fluids of
infected patients: tracheal laboratory confirmed in many tissues and fluids of infected patients: tracheal
scretion, sputum, lachrymal galnd, saliva, salivary glands, nasal swabs, pharyngeal swabs, eye sawabs,
cerebrospinal fluid, urine, blood, serum, peripheral nerve, skeletal muscle, skin, heart, lever, adrenal,
kidney, lung, spleen, pancreas, brain. But transmission of rabies virus from human to human is rarely, if
ever seen. In Eurupe, where the human cases of rabies are rarely seen, and are usually imported, pre
exposure treatment of health care personnel is not indicated. In a case of care for the patient with
laboratory confirmed rabies, the post-exposure treatment of all contacts including the heslth care
personnel are usually practiced. The same practice is olso used in the United States. In
underdeveloped countries, the situation is somewhat different. It is based on health education with
emphasis on precautionary measures. These meaures are to be taken to prevent potential transmission
within family members, when a rabid patient is cared for al home. Data of post-exposure treatment of
contacts are missing. Some infectious diseases are transmitted from human to human very rarely; or
this way of transmissions is difficult to prove. Safe and efficient cell culture rabies vaccines are
available-therefore, if PET is indicated for health care personnel, they must be done with them and by
no means with substandard nerve tissue derived rabies vaccines.
Aunque sub-notificados los accidentess con humanos, involucran, animales. porque ni todas las
vfctimas buscan asistencia medica, ellos alcanzan al numeros mucho preocupantes. En el Municipio de
Sao Paulo, en el periodo de 1995 a 1999. 106,904 personas fuer<Jn atendidas de accidentes con
animales, de este total 83.552 fueron atendidas por la Secretaria Municipal de Salud de Sao Paulo
at raves del Programa de Prevenci6n de la Rabia en Humanos y los tratamientos antirrabicos indicados
para 8.874 des as personas uno que equivalente a 10,5% de indicaci6n del tratamiento. Debe
senalarse que ese promedio de indicacion de tatamiento de 10,5% se manti~e desde 1986 y pasa
37
XI REUNION INTERNACIONAL SOBRE '''Tr-'~~'AT'',''A, MEETING ON
AVANCES EN LA INVESTIGACION Y CONTROL AND RABIES
DE LA RASIA EN LAS AMERICAS IN THE
debido a todas las acciones del Programa de Control de la Rabia sea implantado y la rabia encontrarse
en condiciones de control epidemico: el ultimo caso de rabia en humanos ocurrio en 1981 yen perros y
gatos en 1983, EI Municipio de Sao Paulo tiene 10 Administraciones Regionales de Salud (ARS), Ella
area en estudio fue ARS-6: Sao Miguel - Emelino Matarazo que tiene area de 64 Km2 y 938,600
habitantes 10 que representa la proporcion mas grande densidad de poblqcion del municipio: 14.666
habitantes para el quilometro cuadrado. En esta area de 1995 a 1999 fueron atendidas 17.574
personas vlctimas de accidentes con animales 10 que represento 21 % del total de asistencias y es el
area con el numero mas grande de este tipo de accidentes. Se analizaron 2.090 fichas de
investigacion de accidentes con animales ocurridos en esta area en estudio, en el ana de 1998,
primero sea separado por especies animales involucradas en el accidente. En las fichas de accidentes
con perros sea separado por el lugar del accidente residencia 0 lugar publico (calles, parques,
escuelas, el etc) y la informacion de la identincacion del perro agresor fue analizada. Con relacion las
especies animales involucradas en el accidente se registraron: 1.967 accidentes con perros (94,11 %),
70 con gatos (3.35%), 48 con ratones (2,30%) y 5 accidentes con otras especies (3 conejos, 1
morcielago y 1 mono) - (0,24%). De los accidentes, com perros en 256 fichas analizadas no era
asinalado ellugar del accidente 10 que equivale a 13% de los accidentes con esa especie . En los 1.711
casos restantes con relacion al lugar del accidente se verifico que en 1,330 Casos (66%) ellos pasaron
en la casa del propietario del animal y en 581 casos (34%) en lugares publicos (calles, escuelas, etc.).
De los accidentes ocurridos en lugares pl.Jblicos en 321 casos (18,8% del total) la vlctima puede
identificar al animal agresor 10 que permite la observacion cllnica. Estos accidentes en su gran mayorfa
se pasaron en la calle don de mora la vlctima y el perro era de la propiedad de vecinos. En los otras
260 cas os (15,2% del total) la vlctima no, identifico al perro agresor y el tratamiento antirrabico fue
indicado. En estos casos en la mayorla eran ninos y tambien son alto el porcentaje de los alcoholicos
involucradros en esos accidentes. La mayorfa de los accidentes se paso en la cas a del propietario del
perro que hace pensar en campanas educativas para la prevencion de esos accidentes, Estas
campanas deben lograrse preferencialmente en escuelas porque los ninos son las principales vfctimas,
Si nosotros agregamos los accidentes que pasaron en residencias (66%) con el de lugares publicas en
que el perro agresor se identifico (18,8%) se tiene en 84,8% de los casos era posible la observacion
clfnica del animal en perreras de aislamiento 0 en la residencia del propfetario. Debe senalar que de
acuerdo con las "Normas Tecnicas de Profilactica de la Rabia en Humanos" en los casos de accidentes
con perros cuando estos sf presentan saludable paso 10 dias despues del accidente, ellos permiten
con seguridad la liberacion del tratamiento antirrabico la vlctima del accidentes con esa especie del
animal. Otro factor a ser asinalado es que en 18,8% del total de los casos analizados era posible
identificar el perro responsable por el accidente que se paso en lugar publico 10 que indica la promocion
de una campana del educacion sobre la propiedad responsable de animales y la aplicacion de la
legislacion con multas al propietario que deja su animal suelto en lugares publicos.
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informacion completa por cada variable cuando se hicieron las comparaciones. Para el analisis
estadfstico fue utilizado EPI-INFO version 6.04b enero 1997. La prueba de Chi cuadrado fue aplicada
en la mayorfa de las variables excepto en aquellas donde los valores fueron menores a 5, para estos
fue utilizado la prueba de Fishers.
RESULTADOS: Los resultados fueron tambien divididos en dos partes:
1ra. variables de los pacientes. Se observo que el 53% (322) de los pacientes fueron mordidos en una
cas a y el 47% (284) fueron mordidas en la calle. En cuanto a las edades los ninos fueron mas mordidos
que las ninas, tres cuartos (3/4)de los casos involucra a ninos menores de 5 anos,- La mitad de las
vfctimas son ninos menores a 10 anos. Los ninos fueron los que recibieron mas mordeduras en la cara
que los adultos. Tambien se registro que 707 pacientes recibieron mas mordidas punzantes que
desgarrantes y superficiales. En cuanto al numero de mordidas 196 vfctimas recibieron multiples
mordeduras""y 108 solo recibieron una sola mordedura. En cuanto al tratamiento antirrabico se registro
que el 42%~' (332) de los pacientes recibieron tratamiento completo (10 dosis), 30% (240) recibieron
media tratamiento (5 dosis) y el 28% (220) no recibio ningun tratamiento. Se evidencio que el grupo de
o a 5 anos recibieron mas tratamiento completo y parcial que los otros grupos de edades.
2da. variables de los animales agresores. En esta parte se comprobo que 627 animales fueron
registrados en las fichas de las 807 pacientes. EI 91 % (568) de estos animales fueron canes, el 5%
gatos, 3% monos yel restante 1% fueron ratas y murcielagos. EI 81 % de estos canes fueron conocidos
CONCLUSION: Por los resultados obtenidos se concluye que la mayorfa de los ataques ocurridos en la
ciudad de Santa Cruz fueron causados por perros con duerlo. Tambien se evidencio que los esquernas
The number of confirmed human rabies deaths worldwide, estimated to be approximately 30,000, has
not changed in over two decades. This is due to the fact that relatively little information pertaining to
human rabies deaths is available. Experts agree that accurate mortality data are virtually impossible to
obtain due to the fact that in many countries, rabies deaths are not reported. However, most experts
agree that 80% of human rabies cases that occur globally are reported from India where canine rabies
is endemic. One of the many contributing factors that cause such a high mortality rate in India is that
only 10% of animal bite cases receive post-exposure treatment (PET). In spite of the appalling number
of human deaths attributed to rabies, and the fact that it is virtually 100% preventable through PET,
rabies is virtually an "overlooked" disease. It is unfortunate to report that a large number of human
rabies deaths in developing countries occur in children. The percent of human deaths in developing
countries attributed to rabies infection in children less than 15 years old ranges from 24% in China to
60% in Cambodia. The age group of children at highest risk for exposure to rabies is between 5 - 10
years of age. Children in this age group are less closely monitored by parents then are infants, and are
the correct height for an easy attack by a dog to the head and upper body. In a recent survey of dog bite
cases in India, 64% occurred in children less than 15 years of age. When children are taken to a
physician or anti-rabies clinic for treatment often times primary wound care has not been given. Other
factors attributing to the high incidence of rabies in children in developing countries include: delay of
suturing of the wound without prior treatment of RIG, inappropriate treatment with herbal medicine
or cauterization, and the use of low quality Semple nerve tissue vaccines. There are several factors that
could reduce the incidence of rabies in children including canine vaccination or elimination programs
and the replacement of Semple nerve tissue vaccine with modern cell culture vaccines. Due to cultural
limitations and because there are over 18 million stray dogs in India, governmental sponsored canine
vaccination programs that have proven to be successful in countries like Brazil are not economically
feasible. Therefore other innovative methods must be found to bring an increased awareness to the
problem of human rabies in countries where canine rabies is endemic.
...,....-~;'
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AVANCES EN LA INVESTIGACION Y CON1ROL
DE LA RABIA EN LAS AMERICAS 'P'",
INSECTfvORO ( 32)
Myriam Favi C. *
Veronica Yung P*, Cecilia deMattos**, Carlos deMattos**,Luis Lopez v **; Eveling Chala C**
*Instituto de Salud Publica de Chile, **Center for Disease Control and Prevention Santiago Chile
La importancia de los ani males silvestres en la transmisi6n de la rabia en Chile fue reconocida en 1985,
cuando se detect6 por primera vez rabia en murcielagos insectfvoros. A partir de entonces el patr6n
epidemiol6gico de la rabia se ha caracterizado por una endemia en quir6pteros. Esta nueva situaci6n
epidemiol6gica alcanza su mayor relevancia al reportarse un caso de rabia humana, despues de 24
anos silentes en un nino de 7 atlos que ingres6 al hospital con sfntomas inespecfficos y se sospecha
de poliradiculoneuritis, se inicia tratamiento con gama-globulina IV, a las 48 horas desde el ingreso
present6 signos y sfntomas especfficos de rabia para caer en un paro respiratorio, se conect6 a
ventilaci6n mecanica por 24 dfas. AI 7°dfa de hospitalizaci6n se envi6 al laboratorio una muestra de
suero y frotis de cornea. La determinaci6n de anticuerpos especfficos contra el virus rabico en el suero,
por la tecnica de IFI, arroj6 un resultado positivo con tftulos > a 1:625, el frotis de cornea fue negativo.
EI paciente no tenfa antecedentes de haber sido mordido ni de vacunaci6n antirrabica anterior. AI 20°
dfa de evoluci6n se envfa al laboratorio una segunda muestra de suero y LCR cuyos tftulos de
anticuerpos antirrabicos fueron 1:15625 y 1:125 respectivamente. AI 26° dfa el paciente se
desconecta de la ventilaci6n mecanica y muere. Las biopsias de cerebelo y pie I fueron positivas arabia
por la tecnica de IFD. EI virus fue aislado en rat6n lactante y caracterizado antigenicamente como
variante 4 Tadarida brasiliensis .La caracterizaci6n genetica fue hecha secuenciando 320 p.b. del gen
de la nucleoprotefna, y se compar6 con secuencias de animales domesticos y murcielagos insectfvoros
de centros urbanos en chile entre 1977 y 1998, el anal isis filogenetico demostr6 que el aislamiento
humano segrega en el grupo cuyo reservorio es claramente Tadarida brasiliensis. Estos resultados
indican que los murcielagos insecHvoros son un riesgo real de presentaci6n de casos de rabia en el
hombre en Chile.Con los importantes carnbios en la epidemiologfa de la rabia en America Latina esta
enfermedad deberfa ser incluida en el diagn6stico diferencial de las enfermedades neurol6gicas
caracterizadas por una encefalitis aguda y una paralisis progresiva aun cuando no exista historia
previa de mordida de animal.
A total of 82 clinical trials of PCEC vaccines have been conducted with about 5000 vaccinees since
1981, including 26 pre-exposure studies, 49 post-exposure studies, and 7 booster studies, with follow
up times of 1, 2, 3, and even 10 years. Studies conducted in the early to mid-1980s compared PCEC
vaccine with HDCV, which was the gold standard at that time. All studies showed PCEC vaccine to be
effective and safe, and no type III hypersensitivity reactions have been observed. Today,)here are six
WHO recommended rabies vaccination schedules for cell culture vaccines. The standard post-exposure
vaccination schedule is the 'Essen' 5-dose intramuscular regimen with one dose each on days 0, 3, 7,
14, 30. Adequate titres are achieved latest on day 14 in all vaccinees. Since 1997 the 2-1-1 (4-dose)
Lm. schedule is recommended by the WHO as alternative post-exposure schedule without any
restriction. On day 0 one dose each is given in both the right and left deltoid. In addition, a single dose is
given in the deltoid on day 7 and day 21. Using this immunization regimen and the PCEC rabies
vaccine, it could be demonstrated that on day 7 (after two injections) already 83% of the vaccinees had
adequate titers of ? 0.5 IU/ml. On day 14, all (100%) of the vaccinees had protective titers. This
schedule has become the standard PET schedule in various European countries and is used
alternatively in some Asian countries. Low dose (0.1 ml) intradermal (Ld.) administration of modern cell
culture rabies vaccines either for pre-exposure immunization or for post-exposure treatment is used in
some regions of the world. The latest clinical findings of intradermal studies are discussed. The Ld.
method is particularly appropriate where vaccine or money is in short supply and in rabies centers
dealing.with numbers of patients daily, where there is an established cold storage system and well
40
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INTERNATIONAL MEETING ON RESEARCH
ADVANCES AND RAI3IES CONTROL
IN THE AMERICAS
trained medical staff for proper intradermal administration of the vaccine. Recently, Dietzschold and
Hooper studied the effectiveness of rabies vaccines against silver-haired bat rabies virus (SHBRV) and
canine rabies virus (COSRV) strains, which have been shown to possess extensive differences in
antigenic makeup. National Institutes of Health in vivo mouse protection test results have shown that
both PCEC vaccine and HCDV protect against lethal infection with SHBRV and COSRV. In this study
however, both vaccines in mice were found to be significantly more potent against COSRV than against
SHBRV. These in vivo protection data were confirmed by in vitro rabies virus neutralizing antibody
(RVNA) tests, which demonstrated that mice immunized with PCEC vaccine or HDCV developed
significantly higher RVNA titers against COSRV than against SHBRV. In contrast, RVNA tests of sera
from individuals immunized with PCEC vaccine or HDCV showed that humans, as opposed to mice,
developed significantly higher RVNA titers against SHBRV than against COSRV. These results suggest
that both vaccines will protect humans against infection with SHBRV as well as COSRV strains. The
efficacy anti safety of PCECV was examined in persons infected with HIV. Thirty healthy, non-infected
persons served as control population. There was a significant difference in the serologic response to the
standard Lm. post-exposure schedule between the non-infected control group, the asymptomatic HIV
infected patients and the symptomatic HIV-infected patients, where only a weak serologic response was
observed. In addition, the serologic response was positively related to the remaining CD4+ count of the
patients. Not in Latin America, the US or Europe but in Asia treatment failures, although applying potent
modern cell culture vaccines, are still reported. When analysing the treatment failures reported in the
literature and in our internal files, the essential mistakes in rabies post-exposure treatment could be
identified. In all cases one or more deviations from the official treatment recommendations were made.
Besides not giving rabies immunoglobulin altll0ugh indicated, multiple wounds andlor head and neck
bites, insufficient wound treatment or delay in start of treatment were the major mistakes or risk factors.
To summarise these findings, one can say, non of the cases reported received complete post-exposure
treatment according to the current WHO guidelines. The problem is not failure of cell culture vaccines
but inadequate management of post-exposure treatment, particularly in regions where short incubation
periods are frequently observed and where vaccines and more often immunoglobulins are in short
supply. Based on these findings, ten golden rules for rabies prevention and treatment for patients and
physicians can be formulated. They will be discussed.
CONCLUSION: Effective cell culture vaccines and economic regimens are available. Current post
exposure vaccination schedules build up the protective antibody tit res within 7-14 days after the first
dose. The protection gap from day 0 to day 7, in case of severe bites (cat. III), requires the
simultaneous administration of rabies immunoglobulin. When WHO 1 national guidelines are strictly
followed, treatment failures should hardly occur.
MEXICO: ONE OF THE FIRST APPROACHES FOR RABIES CONTROL AND PREVENTION (16)
Mauricio Gomez Sierra, Irma Padilla Medina, Gustavo Hernandez Rodriguez, Victor Juarez-Islas, *
Rabies control and prevention remains being a priority in governments of developing nations. The
limited information in Ministries of Health about rabies virus reservoirs within a territory give rise to a
lack of data characterization of rabies virus with a reduced panel of eight monoclonal kindly provided by
the CDC is an easily approach to determine rabies virus reservoirs in the Americas. In the present study
we summarized data about the antigenic characterization of 191 rabies virus isolates, collected from
different species through out Mexico during the period 1996- August 2000. In human beings we found
the following antigenic variants; the 86% (31/36= V1 6% (3136) V10 3% (1/361 V3 and 3% (1/36) of V11.
These results suggest that rabid dogs were the main source of human infection in the last four years.
However the most common source of human infection last two years associated with skunk and
haemotophagous bat transmission. In livestock of different species we have find next kind of viruses;
V11 44% (28/63), V1 27% (17/63), V_ 10% (6163), V10 3% (2/63), V3 8% (5/63), V5 3% (2/63) and V4
5% (3/63). The latter results showed a great heterogeneity of rabies virus variants in livestock species
and therefore the extend of exposure of those species to both domestic and wild rabies reservoirs.
Additionally they reflect the low level of vaccination in those species, especially in those regions where
the cases were detected. Rabies surveififiiance by means of antigenic typing of rabies virus in livestock
may yield very important information to evaluate human risk in those areas where there are not any
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XI REUNION INTERNACIONAl SOBRE INTERNATIONAL MEETING ON RESEARCH
AVANCES EN LA INVESTIGACION Y CONTROL ADVANCES AND RABIES CONTROL
DE LA RABIA EN LAS AMERICAS IN THE AMERICAS
other sources of information for knowing rabies epizootiology, in rabid cats we have found V8 2/6 and
V14 4/6 rabies virus variants, which demonstrates that non vaccinated cats in Mexico have been victims
of rabid dogs and skunks. Our results in reservoir species were the following. In 89 dog samples out of
70 (99%) we found V1 and in the remnant 1% (1170) V5 was detected. These results suggest that
domestic dog is the main reservoir of V1 rabies virus through out Mexico as well as non vaccinated
dogs could sporadically be infected by other wild reservoirs. Regarding skunk rabies we have detected
two foci; one northern Mexico in the south of the peninsula of BAJA California, and other in the central
region of the country (Bajio) in the first one, Spilogale putorius lucasana is the reservoir of V10 rabies
virus and the main transmitter of rabies to humans and cattle in the region. In the latter foci. Spilogale
putorius leucoparia is the main reservoir of V8 rabies virus and the responsible for rabies transmission
to cats and calle. In Urocyon cineroargentous known as the gray fox, we have detected V7 rabies virus.
This rabies virus has been located in northern mexico, in the states of Sonora and Zacatecas in the
Sierra Madre Occidental. With respect rabies in insectivorous bats we have found V4 and V9 in tadarida
brasiliensis mexicana and v4 in livestock. On the other hand we have detected V3 and, V5 and V11
rabies viruses in livestock, however their reservoir or reservoirs are not clear so far. All this information
provided by the antigenic typing of rabies virus with the CDC's panel of MoAb have been a very
valuable tool to know rabies epizootiology in Mexico, besides it has been useful to evaluate the
effectiveness of massive vaccination campaigns in dogs.
Recombinant techniques to produce vaccines have become an important tool in the worldwide fight
against rabies. However, in our enthusiasm for these new and potentially powerful tools are we taking
into account all aspects of the problem. Parallels can be drawn between recombinant vaccines for
rabies and the ongoing controversy surrounding the use of genetically manipulated organisms (GMO's)
in North American agriculture. The use of GMO's in agriculture has caused problems because, (i) the
recombinant plants were sold to producers as time and money savers rather than to consumers, and
consumer backlash has severely inhibited access of GMO' s to the marketplace, and (ii) the public does
not trust "scientists". Such problems are likely to be encountered in licensure of new, recombinant
vaccines. Although the possibility of biological problems in the proper use of recombinant vaccines
appears remote - as it did with genetically modified organisms - the likelihood of public relations/concern
problems may be significant. In order to reduce this risk, when developing a new adenovirus
recombinant rabies vaccine the Ontario Ministry of Natural Resources plans to develop a
comprehensive communications plan to inform the general public of progress in adenovirus
development. Forethought now in the early stages of recombinant technological applications in Rabies
may help reduce similar problems in the future. This presentation was supported by toe generous
contributions of Chiron Vaccines and Therapeutics, USA, Merial Limited, USA and Artemis
Technologies Inc., Canada.
3 1
N. Tordo\ Y. Jacob\ E. Desmezieres\ C. Jallet\ A. Aguilar-Setien 2 , E. Loza-Rubi02 , , M. Aubert , F. Cliquee & P. Perrin •
There are 7 genotypes (GT) of Iyssaviruses: GT1 (rabies), GT2 (Mokola), GT3 (Lagos bat), GT4
(Duvenhage), GT5 (EBL 1), GT6 (EBL2) and GT7 (ABL). Currently available vaccines (strains from GT1)
are effective against rabies (GT1), more or less against GT 4-7, totally ineffective against GT2-3. On the
other hand, most of the 50.000 human deaths/year due to rabies are linked to dog exposure in
developing countries. Thus, !here are two priorities in Iyssavirus vaccinology: (1) promoting not expensive
42
XI REUNION INTERNACIONAL SOBRE
AVANCES EN LA INVESTIGACION Y CONTROL
DE LA RABIA EN LAS AMERICAS
and efficient vaccines, in particular to prevent and control dog rabies; (2) broadening the protection
spectrum of rabies vaccines toward Iyssavirus. The potential of DNA-based immunization in both
priorities was investigated using the Iyssavirus glycoprotein (G) which is involved in the induction of virus
neutralyzing antibodies and protection.
1. Beagles dogs immunized by intramuscular (Lm.) injection (100- g on day 0 and 175) of a plasmid
encoding the G protein gene of rabies virus (PV strain, GT1) survived a lethal challenge with a wild-type
dog rabies strain (Ariana, Tunisia, GT1) on day 231. However, significant levels of virus neutralizing
antibodies (VNAbs) were detected only 28 days after the first injection. These titers were stronger against
GT1, lower against GT5 (EBL 1).
2. Chimeric G proteins were constructed by fUSing the COOH-half of PV (GT1) with the NH2-half of other
genotypes (GT3 or GT5). Mice immunized by Lm. injection with plasm ids expressing the chimeric
proteins exhibited a complete immune response (both humoral and cellular) and were protected not only
against the "parental GTs but also against other GTs. This shows that the spectrum of anti-rabies
vaccines can be increased to aillyssaviruses.
4. different combinations of foreign epitopes (C3 « B » epitope of poliovirus VP1 protein; « CTL » H2d
MHC I restricted epitope of the LMCV nucleoprotein) have been inserted in the hinge region between the
NH2 and COOH halves. The resulting chimeric plasmid induces VNAbs against both Iyssaviruses and
poliovirus and protection against LCMV. This demonstrates that the G protein can be used as a carrier
for foreign epitopes or antigens and different combinations are currently under investigation. This is a
prototype of a DNA multivalent vaccines against various diseases including rabies and other zoonoses.
Ad Vos*, Andreas Neubert (1), Elke Pommerening (1), Leopold Dohner (2), Ken Hughes (3),
(4) Institute for Epidemiological Diagnostics, Federal Research Institute for Virus Diseases of Animals, GERMANY
The immunogenetic properties of an E1-deleted human adenovirus type 5 as a rabies vaccine virus was
investigated. The construct was given to mice, foxes and dogs using different routes of administration.
The replication defective construct contains in the site of the E1-region a nucleotide sequence
comprised of a HCMV-promoter directing the replication and expression of the nucleotide sequence
encoding the rabies glycoprotein derived from the ERA-strain followed by a SV40 poly-adenylation
signal. The construct is cultured by infecting E1-producing N293S host cells. NMRI-mice received
1()A5.8, 1()A5.3, 10"4.3, 101\3.3 and 1()A2.3 TCID50 p.o. and Lm. In constrast to similar constructs, mice
could be vaccinated by the oral route, although not as effectively as animals vaccinated Lm. After direct
oral administration of the construct (101\8.0 TCID50), 6 of 8 foxes developed rabies virus neutralizing
antibodies (VNA), although the immune response was lower than with the orally administered live
modified rabies virus vaccines, SAD B19 and SAD P5/88. Furthermore, all 4 foxes with pre-existing
immunity against canine-adenovirus developed rabies VNA after oral application of the construct.
Thirteen fox cubs (24-29 days old) born from rabies-immune vixens developed very high levels of rabies
VNA after the construct was applied Lm., indicating that the construct could surpass maternally
transfered immunity. In dogs (n=2), the construct also induced a very strong immune response after
Lm. administration. Unfortunately, no immune response was detectable in dogs after the construct was
administered by direct oral administration (n=10).
.,...\,~.
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XI REUNION INTEFlNACIONAL INTERNATIONAL MEETING ON RESEARCH
AVANCES EN ADVANCES AND RABIES CONTROL
DE LA RABIA IN THE AMERICAS
JUSTIFICATION:The object of this investigation is to find out the way to decrease biological production
costs maintaining high quaiity. In that order we can make the product competitive in all aspects.
METHODE:The method consist in susbtituting ali the differents mediums of maintenance with bovine
albumina as the principal component and controffing it's antigenical power by the NIH test.
PARTIALS RESULTS:The maintenance medium for Eagle 199 in spite of the fact that it produces a good
Actually, final test are not finished yet. Rigth now are in proyect: a) Eagle Salino A b) Sales de Earles B
c) Sales de Earles C.
NATIONAL CONTIBUTION:Dominican Republic will count with a sheaper biological medium with less
imported components.
Oral vaccination of wildlife is an important adjunct to traditional public health methods of rabies control.
Over the past decade, more than 15 million baits containing a vaccinia-rabies glycoprotein (V-RG)
recombinant virus vaccine have been distributed in the USA through programs designed to control
rabies among free-ranging raccoons, foxes and coyotes, without adverse effects to humans. For
example, since 1997, oral vaccination campaigns in Ohio each autumn and spring have led to a highly
significant reduction in raccoon rabies. Notably, during the most recent vaccine distribution in
September 2000, a 28 yr old pregnant woman from NE Ohio was bitten on the finger and left forearm,
when she tried to remove a V-RG recombinant virus-laden bait from her dog's mouth. She washed the
finger wound vigorously, but did not attend to the rather superficial arm bites. Within 10 days she
developed an intensive local inflammatory reaction around two necrotic lesions at the forearm bite sites,
and axillary adenitis. She went on to develop generalized erythroderma that subsided spontaneously
after exfoliation. The patient, with a history of epidermolytic hyperkeratosis, received antibiotics and
wound debridement. Material from the wound was incubated upon a monolayer culture of Vero cells.
Cytopathic effect was observed within 12 hrs. Thin section electron microscopy performed upon the
infected Vero cells revealed typical poxvirus morphology. Nucleic acid extracted from cell culture yielded
a positive PCR product using primers to both vaccinia and rabies viruses, and direct sequence analYSis
of the PCR product exhibited 100% homology with the ERA strain rabies viral glycoprotein. Laboratory
mice inoculated with infected cell culture passaged material remained clinically normal. Convalescent
patient serum obtained three weeks post-bite contained rabies virus-specific neutralizing antibodies.
This unusual incident underlies the heightened need for continued prevention activities and field
surveillance for accidental human exposure to the V-RG virus, particularly as future ~ildlife rabies
vaccination efforts intensify on a national level. "
The production of non isotopically labeled probes were developed for detection of rabies virus Nand G
genes. The hibridization of probes were made in the amplified of genes obtained through RT-PCR and
revealed by immunochemiluminescence, For controlling of reactions, it had been built a plasmid, called
pSH-G, containing the insert of clonade G gene of PV vaccinal sample. The detection of N gene have
diagnostical value by the differents rabies virus samples. The detection of G gene is used in
epidemiologicals studies, but without diagnostical value because it's in a variable genomic region of
rabies vkus.
44