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Topic:Infectious Disease

Infectious diseases in horses encompass a range of illnesses caused by bacteria, viruses, fungi, or parasites. These diseases can affect various systems within the equine body, leading to symptoms that range from mild discomfort to severe systemic illness. Common infectious diseases in horses include equine influenza, strangles, equine herpesvirus, and West Nile virus. These diseases can be transmitted through direct contact with infected animals, contaminated surfaces, or vectors such as insects. Understanding the mechanisms of transmission, pathogenesis, and immune response is essential for effective prevention and control. This page compiles peer-reviewed research studies and scholarly articles that explore the epidemiology, diagnosis, treatment, and management of infectious diseases in horses.
Indirect immunofluorescence test using polyclonal antibodies for the detection of Taylorella equigenitalis.
Research in veterinary science    December 3, 2009   Volume 88, Issue 3 369-371 doi: 10.1016/j.rvsc.2009.11.003
Breuil MF, Duquesne F, Sรฉvin C, Laugier C, Petry S.Contagious equine metritis is a horse disease that causes endometrial inflammation due to Taylorella equigenitalis. Since Taylorella asinigenitalis was characterized, genital swab culture has proved to be an insufficient method for distinguishing between the two Taylorella species. Here, we developed an indirect immunofluorescence (IIF) test using polyclonal antibodies. Specificity, sensitivity, and detection limit were assessed using isolated bacteria (55 T. equigenitalis strains, 46 T. asinigenitalis strains and 18 other bacterial species), experimental and genital swabs in comparison to bac...
Nucleotide sequence heterogeneity in the small subunit ribosomal RNA gene within Theileria equi from horses in Sudan.
Parasitology research    December 2, 2009   Volume 106, Issue 2 493-498 doi: 10.1007/s00436-009-1691-7
Salim B, Bakheit MA, Kamau J, Nakamura I, Sugimoto C.This is a molecular epidemiological investigation on Theileria equi, a causative agent of equine piroplasmosis. Blood samples were collected from 127 horses from different geographical locations in Sudan. The small subunit of rRNA gene (18S; ~1,600 bp) was amplified from 20 positive field samples and subsequently subjected to direct sequencing and analysis to reveal possible strain differences and the presence of a novel species or genotypes. Sequences were compared with published sequences mainly from South African and Spanish isolates. Eleven distinct T. equi sequences within 18S rRNA gene w...
The effect of age on the immune response of horses to vaccination.
Journal of comparative pathology    December 1, 2009   Volume 142 Suppl 1 S85-S90 doi: 10.1016/j.jcpa.2009.10.010
Muirhead TL, McClure JT, Wichtel JJ, Stryhn H, Markham RJ, McFarlane D, Lunn DP.Few studies have investigated immunosenescence in the horse, but it is accepted that the primary and secondary (anamnestic) immune responses may differ between aged and younger horses. The aim of the present study was to determine whether aged horses have a protective immune response post-vaccination. Thirty-four aged healthy horses (> or =20 years) and 29 younger adult horses (4-12 years) of various breeds were vaccinated with commercially produced killed rabies and influenza vaccines. Rabies serum neutralizing antibody titres and equine influenza virus specific antibody subclasses (immuno...
Use of a reverse line blot assay to survey small strongyle (Strongylida: Cyathostominae) populations in horses before and after treatment with ivermectin.
Veterinary parasitology    December 1, 2009   Volume 168, Issue 3-4 332-337 doi: 10.1016/j.vetpar.2009.11.021
Ionita M, Howe DK, Lyons ET, Tolliver SC, Kaplan RM, Mitrea IL, Yeargan M.A sensitive and specific PCR hybridization assay was applied for species-specific monitoring of the small strongyle (Strongylida: Cyathostominae) populations in horses in a herd before and after treatment with the anthelmintic drug ivermectin. Fecal samples were collected pre- and post-treatment weekly from eight individual horses (four foals and four yearlings) for 6 weeks to determine counts of strongyle eggs per gram of feces (EPGs). Additionally, one foal and one yearling were nontreated controls. Also, one horse, from another herd known to be infected with Strongylus spp., was a positive ...
Characterization of a thymidine kinase-deficient mutant of equine herpesvirus 4 and in vitro susceptibility of the virus to antiviral agents.
Antiviral research    November 30, 2009   Volume 85, Issue 2 389-395 doi: 10.1016/j.antiviral.2009.11.007
Azab W, Tsujimura K, Kato K, Arii J, Morimoto T, Kawaguchi Y, Tohya Y, Matsumura T, Akashi H.Equine herpesvirus 4 (EHV-4) is an important equine pathogen that causes respiratory tract disease among horses worldwide. A thymidine kinase (TK)-deletion mutant has been generated by using bacterial artificial chromosome (BAC) technology to investigate the role of TK in pathogenesis. Deletion of TK had virtually no effect on the growth characteristics of WA79DeltaTK in cell culture when compared to the parent virus. Also, virus titers and plaque formation were unaffected in the absence of the TK gene. The sensitivity of EHV-4 to inhibition by acyclovir (ACV) and ganciclovir (GCV) was studied...
EIAV S2 enhances pro-inflammatory cytokine and chemokine response in infected macrophages.
Virology    November 28, 2009   Volume 397, Issue 1 217-223 doi: 10.1016/j.virol.2009.11.005
Covaleda L, Fuller FJ, Payne SL.Equine infectious anemia virus (EIAV) infection is distinctive in that it causes a rapid onset of clinical disease relative to other retroviruses. In order to understand the interaction dynamics between EIAV and the host immune response, we explored the effects of EIAV and its S2 protein in the regulation of the cytokine and chemokine response in macrophages. EIAV infection markedly altered the expression pattern of a variety of pro-inflammatory cytokines and chemokines monitored in the study. Comparative studies in the cytokine response between EIAV(17) and EIAV(17DeltaS2) infection revealed ...
Environmental risk factors associated with West Nile virus clinical disease in Florida horses.
Medical and veterinary entomology    November 28, 2009   Volume 23, Issue 4 357-366 doi: 10.1111/j.1365-2915.2009.00821.x
Rios LM, Sheu JJ, Day JF, Maruniak JE, Seino K, Zaretsky H, Long MT.The objective of this study was to examine the extrinsic risk factors of West Nile virus (WNV) clinical disease in Florida horses as established from confirmed and negative horses tested within the state from 2001 to 2003. An Arboviral Case Information Form (ACF) was submitted by a referring veterinarian at the time of testing to the Florida Department of Agriculture and Consumer Services on every horse suspected of a viral encephalitis in Florida. A follow-up survey that focused on arbovirus prevention and farm ecology was created and mailed to the owner of each tested horse. Data from the fo...
Seroprevalence of Leptospira spp. in clinically healthy racing horses in Korea.
The Journal of veterinary medical science    November 27, 2009   Volume 72, Issue 2 197-201 doi: 10.1292/jvms.09-0273
Jung BY, Lee KW, Ha TY.Leptospirosis is a zoonotic disease of global importance, and has a worldwide distribution. The present study aimed to determine leptospiral seroprevalence in clinically healthy racing horses from all three racecourses in Korea. Serum samples from 1,226 racing horses were examined using a microscopic agglutination test to detect the presence of antibodies against 18 Leptospira serovars. Of the tested samples, 307 (25.0%) were found to be positive. The distribution of seroprevalence differed significantly by racecourse (P=0.004); the Jeju course had the highest incidence (31.1%), followed by th...
Age patterns of disease and death in insured Swedish dogs, cats and horses.
Journal of comparative pathology    November 25, 2009   Volume 142 Suppl 1 S33-S38 doi: 10.1016/j.jcpa.2009.10.008
Bonnett BN, Egenvall A.From 1995 to the present Agria Animal Insurance, Sweden (Agria Djurfรถrsรคkring, Stockholm, Sweden) has provided data on both health care and life insurance claims for descriptive and analytical research. From these data we have published extensively on insured dogs and horses and have recently submitted a study on cat mortality. Over the periods studied most extensively (1995-2002 for dogs, 1997-2004 for horses and 1999-2006 for cats), Agria has insured approximately 200,000 dogs, 100,000 horses and up to 200,000 cats per year. Estimates based on formal research or market surveys suggest that...
Vaccination of ponies with the IE gene of EHV-1 in a recombinant modified live vaccinia vector protects against clinical and virological disease.
Veterinary immunology and immunopathology    November 24, 2009   Volume 135, Issue 1-2 108-117 doi: 10.1016/j.vetimm.2009.11.009
Soboll G, Breathnach CC, Kydd JH, Hussey SB, Mealey RM, Lunn DP.The control of EHV-1 infection by cytotoxic T-cell responses (CTL) via a reduction in cell associated viremia remains an important goal in horses. Unfortunately, current vaccines are inefficient at inducing these responses. We have identified the immediate early (IE) gene of EHV-1 as a potent stimulator of virus-specific CTL responses in ponies expressing a specific MHC class I serological haplotype (A3/B2). This study was designed to determine if vaccination of A3/B2 MHC I positive ponies with the IE gene could induce protection and immune responses associated with cell mediated immunity. Pon...
Development and evaluation of real-time PCR assays for the quantitative detection of Babesia caballi and Theileria equi infections in horses from South Africa.
Veterinary parasitology    November 20, 2009   Volume 168, Issue 3-4 201-211 doi: 10.1016/j.vetpar.2009.11.011
Bhoora R, Quan M, Franssen L, Butler CM, van der Kolk JH, Guthrie AJ, Zweygarth E, Jongejan F, Collins NE.A quantitative real-time polymerase chain reaction (qPCR) assay using a TaqMan minor groove binder (MGB) probe was developed for the detection of Babesia caballi infection in equids from South Africa. Nine previously published sequences of the V4 hypervariable region of the B. caballi 18S rRNA gene were used to design primers and probes to target unique, conserved regions. The B. caballi TaqMan MGB qPCR assay was shown to be efficient and specific. The detection limit, defined as the concentration at which 95% of positive samples can be detected, was determined to be 0.000114% parasitized eryt...
Serological and parasitological survey of dourine in the Arsi-Bale highlands of Ethiopia.
Tropical animal health and production    November 20, 2009   Volume 42, Issue 4 769-776 doi: 10.1007/s11250-009-9485-6
Hagos A, Abebe G, Bรผscher P, Goddeeris BM, Claes F.This study was conducted from August 2005 to January 2007 to determine prevalence and distribution of dourine in horses and to investigate the occurrence of clinical and carrier cases in donkeys and mules in the Arsi-Bale highlands. Study methodology was based on questionnaire, serological, clinical and parasitological survey. The questionnaire indicated that dourine is a major health problem of equines in the Arsi-Bale highlands. Though dourine is commonly observed throughout the year, it has a seasonal character and occurs mostly during the breeding season from June to late September. Serolo...
Identification of Western equine encephalitis virus structural proteins that confer protection after DNA vaccination.
Clinical and vaccine immunology : CVI    November 18, 2009   Volume 17, Issue 1 176-179 doi: 10.1128/CVI.00377-09
Gauci PJ, Wu JQ, Rayner GA, Barabรฉ ND, Nagata LP, Proll DF.DNA vaccines encoding different portions of the structural proteins of western equine encephalitis virus were tested for the efficacy of their protection in a 100% lethal mouse model of the virus. The 6K-E1 structural protein encoded by the DNA vaccine conferred complete protection against challenge with the homologous strain and limited protection against challenge with a heterologous strain.
Investigation of equine influenza transmission in NSW: walk, wind or wing?
New South Wales public health bulletin    November 18, 2009   Volume 20, Issue 9-10 152-156 doi: 10.1071/nb08025
Spokes PJ, Marich AJ, Musto JA, Ward KA, Craig AT, McAnulty JM.An outbreak of equine influenza occurred in New South Wales in 2007. In addition to the local spread of the disease between bordering properties, windborne spread over several kilometres had been postulated as a possible method of transmission in this outbreak. This study aimed to describe potential modes of transmission for a property infected with equine influenza where no apparent epidemiological links to other infected properties were reported. Methods: A semi-structured questionnaire was administered to owners of affected properties. The questionnaire collected detailed transmission-risk ...
Antiviral effect of recombinant equine interferon-gamma on several equine viruses.
Veterinary immunology and immunopathology    November 18, 2009   Volume 135, Issue 1-2 93-99 doi: 10.1016/j.vetimm.2009.11.006
Sentsui H, Wu D, Murakami K, Kondo T, Matsumura T.Recombinant equine interferon-gamma (reIFN-gamma) was prepared using a baculovirus expression system and its antiviral activity was investigated using several equine viruses. The reIFN-gamma suppressed the replication of all equine viruses used in the present experiment in horse cell cultures, but did not affect the growth of host cells at concentrations of less than 1000 u/ml. A strong antiviral effect was observed, especially against RNA viruses. Equine picornavirus, equine rhinovirus and equine arteritis virus could not be propagated at all in 100 u/ml reIFN-gamma when 100 TCID(50) of infec...
Surgical repair of an oesophageal stricture and prestenotic dilatation in a horse.
Tijdschrift voor diergeneeskunde    November 17, 2009   Volume 134, Issue 18 740-743 
Voermans M, Skidell J, Winberg F.Prestenotic oesophageal dilatation and stricture were diagnosed in a horse with a history of trauma in the cervical area and recurrent oesophageal obstruction. The diagnosis was established on the basis of the clinical examination, endoscopy, and positive contrast oesophagography. Conservative treatment was unsuccessful and surgical intervention was necessary. Oesophageal myectomy combined with myoplasty was performed, simultaneously relieving the dilatation and the stricture. No abnormalities were detected 8 weeks after surgery. The horse was on a normal diet and oesophageal obstruction did r...
Enterococcus casseliflavus endophthalmitis associated with a horse tail injury.
Archives of ophthalmology (Chicago, Ill. : 1960)    November 11, 2009   Volume 127, Issue 11 1551-1552 doi: 10.1001/archophthalmol.2009.282
Khurana RN, Leder HA, Nguyen QD, Do DV.No abstract available
Comparison of four methods to quantify Equid herpesvirus 1 load by real-time polymerase chain reaction in nasal secretions of experimentally and naturally infected horses. Pusterla N, Hussey SB, Mapes S, Leutenegger CM, Madigan JE, Ferraro GL, Wilson WD, Lunn DP.The objective of the current study was to compare the performance of 4 methods to quantify Equid herpesvirus 1 (EHV-1) by real-time polymerase chain reaction (PCR) in nasal secretions from experimentally and naturally infected horses. Nasal secretions were collected on the challenge day and daily thereafter for 13 days from 4 experimentally infected horses. Additional nasal swabs were collected from 30 horses with clinical signs consistent with natural EHV-1 infection. Absolute quantitation of EHV-1 target molecules was performed using standard curves for EHV-1 and equine glyceraldehyde-3-phos...
A multisystem approach for development and evaluation of inactivated vaccines for Venezuelan equine encephalitis virus (VEEV).
Journal of virological methods    November 10, 2009   Volume 163, Issue 2 424-432 doi: 10.1016/j.jviromet.2009.11.006
Fine DL, Jenkins E, Martin SS, Glass P, Parker MD, Grimm B.A multisystem approach was used to assess the efficiency of several methods for inactivation of Venezuelan equine encephalitis virus (VEEV) vaccine candidates. A combination of diverse assays (plaque, in vitro cytopathology and mouse neurovirulence) was used to verify virus inactivation, along with the use of a specific ELISA to measure retention of VEEV envelope glycoprotein epitopes in the development of several inactivated VEEV candidate vaccines derived from an attenuated strain of VEEV (V3526). Incubation of V3526 aliquots at temperatures in excess of 64 degrees C for periods >30 min i...
[Two horses with neurological symptoms: could this be equine botulism?].
Tijdschrift voor diergeneeskunde    November 7, 2009   Volume 134, Issue 19 790-795 
Roest HI, de Bruijn CM, Picavet MT, Prins B, Parmentier D, de Zwart GM, Dijkstra YE, van Zijderveld FG.Symptoms, diagnosis and therapy of equine botulism are discussed by the presentation of two detailed reports of horses with neurological symptoms and the results of laboratory investigations over the period 2003-2008 in the Netherlands. In addition a brief summary of the available literature is presented. Prevailing symptoms of botulism in horses include paralysis of the tongue, salvation, dysphagia and paresis and paralysis of the skeletal muscles, as well as signs of colic. Symptoms and prognosis vary with the amount of botulinum neurotoxin (BoNT) involved. For early clinical diagnosis of bo...
Eumycetoma caused by Madurella mycetomatis in a mare.
Medical mycology    November 6, 2009   Volume 48, Issue 4 639-642 doi: 10.3109/13693780903393905
Elad D, Blum S, Kol A, Ederi N, David D.A case of equine eumycotic mycetoma caused by Madurella mycetomatis is described. This is the first report of M. mycetomatis as the etiologic agent of human or animal infections in Israel. The definitive identification of the isolate was established by molecular methods. In addition the mold was cultured on various media through which we found that its growth rate was significantly augmented on incubation on trypticase soy agar, more so if horse serum was added to this medium. Sixteen previously published cases defined by the authors as mycetoma in horses are briefly reviewed. Among these, onl...
A comparative study of serological tests and PCR for the diagnosis of equine piroplasmosis.
Parasitology research    November 6, 2009   Volume 106, Issue 3 709-713 doi: 10.1007/s00436-009-1669-5
Jaffer O, Abdishakur F, Hakimuddin F, Riya A, Wernery U, Schuster RK.A total of 105 serum samples from endurance horses from different stables in Dubai were examined for the presence of antibodies against Theileria equi and Babesia caballi using immunofluorescence antibody test (IFAT) and competitive enzyme-linked immunosorbent assay (cELISA). A TaqMan real-time polymerase chain reaction (PCR) was used to detect DNA of piroplasms in specimens of clotted blood or EDTA blood samples of the same animals. Out of the 105 serum samples, the IFAT detected antibodies against T. equi in 35 (33.3%) cases while the cELISA gave 34 (32.4%) positive results. Eleven (10.5%) o...
The effect of siRNA treatment on experimental equine herpesvirus type 1 (EHV-1) infection in horses.
Virus research    November 5, 2009   Volume 147, Issue 2 176-181 doi: 10.1016/j.virusres.2009.10.017
Brosnahan MM, Damiani A, van de Walle G, Erb H, Perkins GA, Osterrieder N.Available vaccines fail to induce lasting and protective immunity to equine herpesvirus 1 (EHV-1) associated diseases. RNA interference is a novel approach showing promise for therapeutic use in outbreak situations. This study examined the effect of small interfering RNA (siRNA) on clinical signs as well as the presence of live virus and viral DNA in nasal secretions and peripheral blood mononuclear cells (PBMCs) in horses experimentally infected with EHV-1. siRNA targeting two EHV-1 genes (glycoprotein B and the origin binding protein) was administered 12h before and 12h after intranasal infe...
Equine herpesvirus type 1 quantification in different types of samples by a real-time PCR.
Polish journal of veterinary sciences    November 5, 2009   Volume 12, Issue 3 311-315 
Dzieciatkowski T, Przybylski M, Cymerys J, Turowska A, Chmielewska A, Tucholska A, Banbura MW.Equine herpesvirus type 1 (EHV-1) is one of the major viral agents causing diseases in horses common worldwide. A variety of techniques, including PCR, have been used to diagnose EHV-1 infections. In this paper, an attempt of real-time PCR has been described, which uses specific fluorochrome-labeled TaqMan probes for detection of viral DNA. This method does not require post-amplification manipulations, thereby reducing the risk of cross-contamination. The assay was sensitive enough to detect EHV-1 sequences in different clinical samples, as well in mice neuronal cell cultures. The technique wa...
Proliferation of Streptococcus zooepidemicus and Pseudomonas aeruginosa within a simulated subpalpebral lavage flushed with equine serum.
Veterinary ophthalmology    November 4, 2009   Volume 12, Issue 6 343-349 doi: 10.1111/j.1463-5224.2009.00725.x
Jacobi S, Townsend WM, Bolin CA.To evaluate whether equine serum administered via a simulated subpalpebral lavage system (SPL) supports proliferation of Streptococcus zooepidemicus or Pseudomonas aeruginosa within the tubing. Methods: A sterile i.v. catheter with injection cap was inserted into sterilized silicone tubing (Mila). To mimic an SPL within the dorsal conjunctival fornix, the tubing was secured to an elevated platform. The tip of the tubing extended from the platform into a vial containing culture medium just inoculated with approximately 1.5 x 10(8) CFU/mL P. aeruginosa or S. zooepidemicus. To mimic administratio...
Evolutionary patterns of eastern equine encephalitis virus in North versus South America suggest ecological differences and taxonomic revision.
Journal of virology    November 4, 2009   Volume 84, Issue 2 1014-1025 doi: 10.1128/JVI.01586-09
Arrigo NC, Adams AP, Weaver SC.The eastern equine encephalitis (EEE) complex consists of four distinct genetic lineages: one that circulates in North America (NA EEEV) and the Caribbean and three that circulate in Central and South America (SA EEEV). Differences in their geographic, pathogenic, and epidemiologic profiles prompted evaluation of their genetic diversity and evolutionary histories. The structural polyprotein open reading frames of all available SA EEEV and recent NA EEEV isolates were sequenced and used in evolutionary and phylogenetic analyses. The nucleotide substitution rate per year for SA EEEV (1.2 x 10(-4...
Seroprevalence survey of equine Lyme borreliosis in France and in sub-Saharan Africa.
Vector borne and zoonotic diseases (Larchmont, N.Y.)    November 3, 2009   Volume 10, Issue 5 535-537 doi: 10.1089/vbz.2009.0083
Maurizi L, Mariรฉ JL, Aoun O, Courtin C, Gorsane S, Chal D, Davoust B.A precise assessment of the epidemiological extent of equine Lyme disease is not well established in metropolitan France, French Guiana, and Africa (Chad, Djibouti, Ivory Coast, Gabon, and Democratic Republic of Congo). Blood samples were obtained from 570 horses. The samples were tested for Borrelia burgdorferi infection by a commercial ELISA Dot-Blot method (SNAP 4 Dx; IDEXX S. Laboratory). Lyme disease antibodies were only detected in metropolitan France, specifically in the eastern and center-western regions (48% and 31%). The geographical distribution of the disease follows the distributi...
Equine protozoal myeloencephalitis caused by Neospora hughesi in an adult horse in Saskatchewan.
The Canadian veterinary journal = La revue veterinaire canadienne    November 3, 2009   Volume 50, Issue 8 851-853 
Wobeser BK, Godson DL, Rejmanek D, Dowling P.A protozoal parasite identified as Neospora hughesi was found in inflammatory lesions in the central nervous system of a Canadian-born adult horse presented with neurological signs. This is believed to be the first case of equine protozoal myeloencephalitis (EPM) caused by Neospora hughesi in a horse outside of the United States. Un parasite protozoaire identifiรฉ comme a รฉtรฉ trouvรฉ dans les lรฉsions inflammatoires du systรจme nerveux central dโ€™un cheval adulte nรฉ au Canada prรฉsentant des signes neurologiques. On croit quโ€™il sโ€™agit du premier cas dโ€™encรฉphalomyรฉlite protozoai...
Comparison of two modern vaccines and previous influenza infection against challenge with an equine influenza virus from the Australian 2007 outbreak.
Veterinary research    October 29, 2009   Volume 41, Issue 2 19 doi: 10.1051/vetres/2009067
Bryant NA, Paillot R, Rash AS, Medcalf E, Montesso F, Ross J, Watson J, Jeggo M, Lewis NS, Newton JR, Elton DM.During 2007, large outbreaks of equine influenza (EI) caused by Florida sublineage Clade 1 viruses affected horse populations in Japan and Australia. The likely protection that would be provided by two modern vaccines commercially available in the European Union (an ISCOM-based and a canarypox-based vaccine) at the time of the outbreaks was determined. Vaccinated ponies were challenged with a representative outbreak isolate (A/eq/Sydney/2888-8/07) and levels of protection were compared.A group of ponies infected 18 months previously with a phylogenetically-related isolate from 2003 (A/eq/South...
Differences in replication kinetics and cell tropism between neurovirulent and non-neurovirulent EHV1 strains during the acute phase of infection in horses.
Veterinary microbiology    October 28, 2009   Volume 142, Issue 3-4 242-253 doi: 10.1016/j.vetmic.2009.10.015
Gryspeerdt AC, Vandekerckhove AP, Garrรฉ B, Barbรฉ F, Van de Walle GR, Nauwynck HJ.Equine herpesvirus 1 (EHV1) replicates in the respiratory tract of horses, after which infected leukocytes transport virus throughout the body, resulting in abortion or nervous system disorders. Two EHV1 strains circulate in the field: neurovirulent and non-neurovirulent. To investigate differences in replication in the upper respiratory tract (URT), an experimental inoculation study in ponies was performed with both strains. Two groups of six ponies, were inoculated intranasally with 10(6.5) TCID(50) of either strain. Clinical signs, nasal shedding and viremia were evaluated. At early time po...