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This chapter discusses porcine respiratory disease complex (PRDC) in the broader sense of mixed respiratory infections that occur in swine of any age. It demonstrates a clear trend towards increasing case numbers of pneumonia due to porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza virus (SIV), porcine circovirus type 2 (PCV2), Mycoplasma hyopneumoniae, Pasteurella multocida, Streptococcus suis, Bordetella bronchiseptica, and Actinobacillus suis. The increased incidence of PRRSV, PCV2, and A. suis-induced pneumonia is most remarkable. The sixfold increase in SIV can in large part be explained by the introduction of subtype H3N2 into the United States in 1998. The number of cases of pneumonia due to pseudorabies virus (PRV), A. pleuropneumoniae, and Salmonella choleraesuis is steady or decreasing. The chapter discusses some of the successful models of mixed infection and theories as to the pathogenic mechanisms of interaction. Epidemiological evidence that secondary bacterial infections often follow viral respiratory diseases is well documented. Although some of these superinfections have been replicated experimentally, specific mechanisms of interactions are poorly understood and often inferred based on pathogenesis of the viral infections. PRV, possibly porcine respiratory coronavirus (PRCV), SIV, and PRRSV are all common viral respiratory pathogens of pigs, and all have been variously implicated in increasing the incidence of bacterial respiratory disease in herds which circulate the viruses. The chapter also talks about methods of treatment or prevention of respiratory disease in swine herds, which fall into the categories of management changes, vaccination, and antibiotic usage.
Interaction of viral, bacterial, and adverse management conditions which result in porcine respiratory disease complex (PRDC).
Areas and defense mechanisms which are affected by primary pathogens of the pig, allowing them and opportunistic pathogens to establish infection.
1. Albina, E.,, L. Piriou,, E. Hutet,, R. Cariolet,, and R. L’Hospitalier. 1998. Immune responses in pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV). Vet. Immunol. Immunopathol. 61: 49– 66.
2. Allan, G. M.,, S. Kennedy,, F. McNeilly,, J. C. Foster,, J. A. Ellis,, S. J. Krakowka,, B. M. Meehan,, and B. M. Adair. 1999. Experimental reproduction of severe wasting disease by coinfection of pigs with porcine circovirus and porcine parvovirus. J. Comp. Pathol. 121: 1– 11.
3. Allan, G. M.,, F. McNeilly,, J. P. Cassidy,, G. A. Reilly,, B. Adair,, W. A. Ellis,, and M. S. McNulty. 1995. Pathogenesis of porcine circovirus: experimental infections of colostrum deprived piglets and examination of pig foetal material. Vet. Microbiol. 44: 49– 64.
4. Allan, G. M.,, F. McNeilly,, S. Kennedy,, B. Meehan,, J. Ellis,, and S. Krakowka. 2000. Immunostimulation, PCV-2 and PMWS. Vet. Rec. 147: 170– 171.
5. Amass, S. F.,, L. K. Clark,, W. G. van Alstine,, T. L. Bowersock,, D. A. Murphy,, K. E. Knox,, and S. R. Albregts. 1994. Interaction of Mycoplasma hyopneumoniae and Pasteurella multocida infections in swine. J. Am. Vet. Med. Assoc. 204: 102– 107.
6. Asai, T.,, M. Okada,, M. Ono,, T. Irisawa,, Y. Mori,, Y. Yokomizo,, and S. Sato. 1993. Increased levels of tumor necrosis factor and interleukin 1 in bronchoalveolar lavage fluids from pigs infected with Mycoplasma hyopneumoniae. Vet. Immunol. Immunopathol. 38: 253– 260.
7. Asai, T.,, M. Okada,, M. Ono,, Y. Mori,, Y. Yokomizo,, and S. Sato. 1994. Detection of interleukin-6 and prostaglandin E2 in bronchoalveolar lavage fluids of pigs experimentally infected with Mycoplasma hyponeumoniae. Vet. Immunol. Immunopathol. 44: 97– 102.
8. Balasch, M.,, J. Segales,, C. Rosell,, M. Domingo,, A. Mankertz,, A. Urniza,, and J. Plana-Duran. 1999. Experimental inoculation of conventional pigs with tissue homogenates from pigs with post-weaning multisystemic wasting syndrome. J. Comp. Pathol. 121: 139– 148.
9. Benfield, D. A.,, J. Christopher-Hennings,, E. A. Nelson,, R. R. R. Rowland,, J. K. Nelson,, C. C. L. Chase,, K. D. Rossow,, and J. E. Collins. 1997. Persistent fetal infection of porcine reproductive and respiratory syndrome (PRRS) virus. Proc. Am. Assoc. Swine Pract., p. 455– 458.
10. Bertram, T. A. 1990. Actinobacillus pleuropneumoniae: molecular aspects of virulence and pulmonary injury. Can. J. Vet. Res. 54: S53– S56.
11. Brockmeier, S. L.,, M. V. Palmer,, and S. R. Bolin. 2000. Effects of intranasal inoculation of porcine reproductive and respiratory syndrome virus, Bordetella bronchiseptica, or a combination of both organisms in pigs. Am. J. Vet. Res. 61: 892– 899.
12. Brockmeier, S. L.,, M. V. Palmer,, S. R. Bolin,, and R. B. Rimler. 2001. Effects of intranasal inoculation with Bordetella bronchiseptica, porcine reproductive and respiratory syndrome virus, or a combination of both organisms on subsequent infection with Pasteurella multocida in pigs. Am. J. Vet. Res. 62: 521– 525.
13. Brockmeier, S. L.,, and K. B. Register. 2000. Effect of temperature modulation and bvg mutation of Bordetella bronchiseptica on adhesion, intracellular survival and cytotoxicity for swine alveolar macrophages. Vet. Microbiol. 73: 1– 12.
14. Brockmeier, S. L.,, K. B. Register,, T. Magyar,, A. J. Lax,, G. D. Pullinger,, and R. A. Kunkle. 2002. Role of the dermonecrotic toxin of Bordetella bronchiseptica in the pathogenesis of respiratory disease in swine. Infect. Immun. 70: 481– 490.
15. Brown, G. B. 1999. Streptococcus suis Intranasal Challenge Model and Identification of a Potential Antiphagocytic Virulence Factor in S. suis Supernatant. Ph.D. thesis. Iowa State University, Ames..
16. Brown, I. H.,, D. J. Alexander,, P. Chakraverty,, P. A. Harris,, and R. J. Manvell. 1994. Isolation of an influenza A virus of unusual subtype (H1N7) from pigs in England, and the subsequent experimental transmission from pig to pig. Vet. Microbiol. 39: 125– 134.
17. Brown, I. H.,, P. Chakraverty,, P. A. Harris,, and D. J. Alexander. 1995. Disease outbreaks in pigs in Great Britain due to an influenza A virus of H1N2 subtype. Vet. Rec. 136: 328– 329.
18. Brown, I. H.,, S. H. Done,, Y. I. Spencer,, W. A. Cooley,, P. A. Harris,, and D. J. Alexander. 1993. Pathogenicity of a swine influenza H1N1 virus antigenically distinguishable from classical and European strains. Vet. Rec. 132: 598– 602.
19. Brown, I. H.,, S. Ludwig,, C. W. Olsen,, C. Hannoun,, C. Scholtissek,, V. S. Hinshaw,, P. A. Harris,, J. W. McCauley,, I. Strong,, and D. J. Alexander. 1997. Antigenic and genetic analyses of H1N1 influenza A viruses from European pigs. J. Gen. Virol. 78: 553– 562.
20. Brown, I. H.,, R. J. Manvell,, D. J. Alexander,, P. Chakraverty,, V. S. Hinshaw,, and R. G. Webster. 1993. Swine influenza outbreaks in England due to a new H1N1 virus. Vet. Rec. 132: 461– 462.
21. Callan, R. J.,, F. A. Hartmann,, S. E. West,, and V. S. Hinshaw. 1997. Cleavage of influenza A virus H1 hemagglutinin by swine respiratory bacterial proteases. J. Virol. 71: 7579– 7585.
22. Caruso, J. P.,, and R. F. Ross. 1990. Effects of Mycoplasma hyopneumoniae and Actinobacillus (Haemophilus) pleuropneumoniae infections on alveolar macrophage functions in swine. Am. J. Vet. Res. 51: 227– 231.
23. Carvalho, L. F.,, J. Segales,, and C. Pijoan. 1997. Effect of porcine reproductive and respiratory syndrome virus on subsequent Pasteurella multocida challenge in pigs. Vet. Microbiol. 55: 241– 246.
24. Castrucci, M. R.,, I. Donatelli,, L. Sidoli,, G. Barigazzi,, Y. Kawaoka,, and R. G. Webster. 1993. Genetic reassortment between avian and human influenza A viruses in Italian pigs. Virology 193: 503– 506.
25. Cheung, A. K. 1995. Investigation of pseudorabies virus DNA and RNA in trigeminal ganglia and tonsil tissues of latently infected swine. Am. J. Vet. Res. 56: 45– 50.
26. Chung, W. B.,, L. R. Backstrom,, and M. T. Collins. 1994. Experimental model of swine pneumonic pasteurellosis using crude Actinobacillus pleuropneumoniae cytotoxin and Pasteurella multocida given endobronchially. Can. J. Vet. Res. 58: 25– 30.
27. Ciprian, A.,, C. Pijoan,, T. Cruz,, J. Camacho,, J. Tortora,, G. Colmenares,, R. Lopez- Revilla,, and M. de la Garza. 1988. Mycoplasma hyopneumoniae increases the susceptibility of pigs to experimental Pasteurella multocida pneumonia. Can. J. Vet. Res. 52: 434– 438.
28. Cooper, V. L.,, A. R. Doster,, R. A. Hesse,, and N. B. Harris. 1995. Porcine reproductive and respiratory syndrome: NEB-1 PRRSV infection did not potentiate bacterial pathogens. J. Vet. Diagn. Investig. 7: 313– 320.
29. Cowart, R. P.,, L. Backstrom,, and T. A. Brim. 1989. Pasteurella multocida and Bordetella bronchiseptica in atrophic rhinitis and pneumonia in swine. Can. J. Vet. Res. 53: 295– 300.
30. De Bruin, M. G.,, J. N. Samsom,, J. J. Voermans,, E. M. van Rooij,, Y. E. De Visser,, and A. T. Bianchi. 2000. Effects of a porcine reproductive and respiratory syndrome virus infection on the development of the immune response against pseudorabies virus. Vet. Immunol. Immunopathol. 76: 125– 135.
31. DeBey, M. C.,, and R. F. Ross. 1994. Ciliostasis and loss of cilia induced by Mycoplasma hyopneumoniae in porcine tracheal organ cultures. Infect. Immun. 62: 5312– 5318.
32. Duan, X.,, H. J. Nauwynck,, and M. B. Pensaert. 1997. Virus quantification and identification of cellular targets in the lungs and lymphoid tissues of pigs at different time intervals after inoculation with porcine reproductive and respiratory syndrome virus (PRRSV). Vet. Microbiol. 56: 9– 19.
33. Dugal, F.,, M. Belanger,, and M. Jacques. 1992. Enhanced adherence of Pasteurella multocida to porcine tracheal rings preinfected with Bordetella bronchiseptica. Can. J. Vet. Res. 56: 260– 264.
34. Duncan, J. R.,, F. K. Ramsey,, and W. P. Switzer. 1966. Pathology of experimental Bordetella bronchiseptica infection in swine: pneumonia. Am. J. Vet. Res. 27: 467– 472.
35. Duncan, J. R.,, R. F. Ross,, W. P. Switzer,, and F. K. Ramsey. 1966. Pathology of experimental Bordetella bronchiseptica infection in swine: atrophic rhinitis. Am. J. Vet. Res. 27: 457– 466.
36. Ellis, J.,, L. Hassard,, E. Clark,, J. Harding,, G. Allan,, P. Willson,, J. Strokappe,, K. Martin,, F. McNeilly,, B. Meehan,, D. Todd,, and D. Haines. 1998. Isolation of circovirus from lesions of pigs with postweaning multisystemic wasting syndrome. Can. Vet. J. 39: 44– 51.
37. Ellis, J.,, S. Krakowka,, M. Lairmore,, D. Haines,, A. Bratanich,, E. Clark,, G. Allan,, C. Konoby,, L. Hassard,, B. Meehan,, K. Martin,, J. Harding,, S. Kennedy,, and F. McNeilly. 1999. Reproduction of lesions of postweaning multisystemic wasting syndrome in gnotobiotic piglets. J. Vet. Diagn. Investing. 11: 3– 14.
38. Fenwick, B. W. 1990. Virulence attributes of the liposaccharides of the HAP group organisms. Can. J. Vet. Res. 54: S28– S32.
39. Frey, J.,, J. T. Bosse,, Y. F. Chang,, J. M. Cullen,, B. Fenwick,, G. F. Gerlach,, D. Gygi,, F. Haesebrouck,, T. J. Inzana,, R. Jansen,, E. M. Kamp,, J. Macdonald,, J. I. Macinnes,, K. R. Mittal,, J. Nicolet,, A. N. Rycroft,, R. P. A. M. Segers,, M. A. Smits,, E. Stenbaek,, D. K. Stuck,, J. F. Van Den Bosch,, P. J. Wilson,, and R. Young. 1993. Actinobacillus pleuropneumoniae RTX toxins: uniform designation of haemolysins, cytolysins, pleurotoxin and their genes. J. Gen. Microbiol. 139: 1723– 1728.
40. Fuentes, M.,, and C. Pijoan. 1986. Phagocytosis and intracellular killing of Pasteurella multocida by porcine alveolar macrophages after infection with pseudorabies virus. Vet. Immunol. Immunopathol. 13: 165– 172.
41. Fuentes, M. C.,, and C. Pijoan. 1987. Pneumonia in pigs induced by intranasal challenge exposure with pseudorabies virus and Pasteurella multocida. Am. J. Vet. Res. 48: 1446– 1448.
42. Galina, L.,, C. Pijoan,, M. Sitjar,, W. T. Christianson,, K. Rossow,, and J. E. Collins. 1994. Interaction between Streptococcus suis serotype 2 and porcine reproductive and respiratory syndrome virus in specific pathogen-free piglets. Vet. Rec. 134: 60– 64.
43. Griffiths, I. B.,, S. H. Done,, and B. W. Hunt. 1991. Pneumonia in a sow due to Streptococcus suis type II and Bordetella bronchiseptica. Vet. Rec. 128: 354– 355.
44. Guan, Y.,, K. F. Shortridge,, S. Krauss,, P. H. Li,, Y. Kawaoka,, and R. G. Webster. 1996. Emergence of avian H1N1 influenza viruses in pigs in China. J. Virol. 70: 8041– 8046.
45. Halbur, P. G.,, P. S. Paul,, M. L. Frey,, J. Landgraf,, K. Eernisse,, X. J. Meng,, J. J. Andrews,, M. A. Lum,, and J. A. Rathje. 1996. Comparison of the antigen distribution of two US porcine reproductive and respiratory syndrome virus isolates with that of the Lelystad virus. Vet. Pathol. 33: 159– 170.
46. Halbur, P. G.,, P. S. Paul,, M. L. Frey,, J. Landgraf,, K. Eernisse,, X. J. Meng,, M. A. Lum,, J. J. Andrews,, and J. A. Rathje. 1995. Comparison of the pathogenicity of two US porcine reproductive and respiratory syndrome virus isolates with that of the Lelystad virus. Vet. Pathol. 32: 648– 660.
47. Halbur, P.,, R. Thanawongnuwech,, G. Brown,, J. Kinyon,, J. Roth,, E. Thacker,, and B. Thacker. 2000. Efficacy of antimicrobial treatments and vaccination regimens for control of porcine reproductive and respiratory syndrome virus and Streptococcus suis coinfection of nursery pigs. J. Clin. Microbiol. 38: 1156– 1160.
48. Hamel, A. L.,, L. L. Lin,, and G. P. Nayar. 1998. Nucleotide sequence of porcine circovirus associated with postweaning multisystemic wasting syndrome in pigs. J. Virol. 72: 5262– 5267.
49. Harding, J. C. S.,, and E. G. Clark. 1997. Recognizing and diagnosing postweaning multisystemic wasting syndrome (PMWS). Swine Health Prod. 5: 201– 203.
50. Harms, P. A.,, S. D. Sorden,, P. G. Halbur,, S. Bolin,, K. Lager,, I. Morozov,, and P. S. Paul. 2001. Experimental reproduction of severe disease in CD/CD pigs concurrently infected with type 2 porcine circovirus and porcine reproductive and respiratory syndrome virus. Vet. Pathol. 38: 528– 539.
51. Heinen, P. P.,, A. P. van Nieuwstadt,, J. M. Pol,, E. A. De Boer-Luijtze,, J. T. Van Oirschot,, and A. T. Bianchi. 2000. Systemic and mucosal isotype-specific antibody responses to pigs to experimental influenza virus infection. Viral Immunol. 13: 237– 247.
52. Hines, R. K.,, and P. D. Lukert. 1994. Porcine circovirus as a cause of congenital tremors in newborn pigs. Proc. Am. Assoc. Swine Pract., p. 344– 345.
53. Iglesias, G.,, C. Pijoan,, and T. Molitor. 1989. Interactions of pseudorabies virus with swine alveolar macrophages: effects of virus infection on cell functions. J. Leukoc. Biol. 45: 410– 415.
54. Iglesias, G.,, C. Pijoan,, and T. Molitor. 1992. Effects of pseudorabies virus infection upon cytotoxicity and antiviral activities of porcine alveolar macrophages. Comp. Immunol. Microbiol. Infect. Dis. 15: 249– 259.
55. Iglesias, G. J.,, M. Trujano,, J. Lokensgard,, and T. Molitor. 1992. Study of the potential in- volvement of pseudorabies virus in swine respiratory disease. Can. J. Vet. Res. 56: 74– 77.
56. Iglesias, J. G.,, M. Trujano,, and J. Xu. 1992. Inoculation of pigs with Streptococcus suis type 2 alone or in combination with pseudorabies virus. Am. J. Vet. Res. 53: 364– 367.
57. Inzana, T. J. 1990. Capsules and virulence in the HAP group of bacteria. Can. J. Vet. Res. 54: S22– S27.
58. Jacques, M.,, M. Belanger,, M. S. Diarra,, M. Dargis,, and F. Malouin. 1994. Modulation of Pasteurella multocida capsular polysaccharide during growth under iron-restricted conditions and in vivo. Microbiology 140: 263– 270.
59. Karasin, A. I.,, C. W. Olsen,, and G. A. Anderson. 2000. Genetic characterization of an H1N2 influenza virus isolated from a pig in Indiana. J. Clin. Microbiol. 38: 2453– 2456.
60. Kennedy, S.,, D. Moffett,, F. McNeilly,, B. Meehan,, J. Ellis,, S. Krakowka,, and G. M. Allan. 2000. Reproduction of lesions of postweaning multisystemic wasting syndrome by infection of conventional pigs with porcine circovirus type 2 alone or in combination with porcine parvovirus. J. Comp. Pathol. 122: 9– 24.
61. Kielstein, P. 1986. On the occurrence of toxin-producing Pasteurella multocida strains in atrophic rhinitis and in pneumonias of swine and cattle. J. Vet. Med. Ser. B 33: 418– 424.
62. Kiupel, M.,, G. W. Stevenson,, S. K. Mittal,, E. G. Clark,, and D. M. Haines. 1998. Circovirus- like viral associated disease in weaned pigs in Indiana. Vet. Pathol. 35: 303– 307.
63. Kluge, J. P.,, G. W. Beran,, H. T. Hill,, and K. B. Platt,. 1992. Pseudorabies (Aujeszkey’s disease), p. 312– 323. In A. D. Leman,, B. E. Straw,, W. L. Mengeling,, S. D’Allaire,, and D. J. Taylor (ed.), Diseases of Swine, 7th ed. Iowa State University Press, Ames..
64. Krakowka, S.,, J. A. Ellis,, B. Meehan,, S. Kennedy,, F. McNeilly,, and G. Allan. 2000. Viral wasting syndrome of swine: experimental reproduction of postweaning multisystemic wasting syndrome in gnotobiotic swine by coinfection with porcine circovirus 2 and porcine parvovirus. Vet. Pathol. 37: 254– 263.
65. Lanza, I.,, I. H. Brown,, and D. J. Paton. 1992. Pathogenicity of concurrent infection of pigs with porcine respiratory coronavirus and swine influenza virus. Res. Vet. Sci. 53: 309– 314.
66. Larsen, D. L.,, A. Karasin,, F. Zuckermann,, and C. W. Olsen. 2000. Systemic and mucosal immune responses to H1N1 influenza virus infection in pigs. Vet. Microbiol. 74: 117– 131.
67. Lee, B. W.,, R. F. Bey,, M. J. Baarsch,, and M. E. Larson. 1995. Class specific antibody response to influenza A H1N1 infection in swine. Vet. Microbiol. 43: 241– 250.
68. Meehan, B. M.,, F. McNeilly,, D. Todd,, S. Kennedy,, V. A. Jewhurst,, J. A. Ellis,, L. E. Hassard,, E. G. Clark,, D. M. Haines,, and G. M. Allan. 1998. Characterization of novel circovirus DNAs associated with wasting syndromes in pigs. J. Gen. Virol. 79: 2171– 2179.
69. Messier, S.,, and R. F. Ross. 1991. Interactions of Mycoplasma hyopneumoniae membranes with porcine lymphocytes. Am. J. Vet. Res. 52: 1497– 1502.
70. Molitor, T. W.,, E. M. Bautista,, and C. S. Choi. 1997. Immunity to PRRSV: double-edged sword. Vet. Microbiol. 55: 265– 276.
71. Molitor, T. W.,, J. Xiao,, and C. S. Choi. 1996. PRRS virus infection of macrophages: regulation by maturation and activation state. Proc. Am. Assoc. Swine Pract., p. 563– 569.
72. Morin, M.,, C. Girard,, Y. ElAzhary,, R. Fajardo,, R. Drolet,, and A. Lagace. 1990. Severe proliferative and necrotising pneumonia in pigs: a newly recognized disease. Can. Vet. J. 31: 837– 839.
73. Morozov, I.,, T. Sirinarumitr,, S. D. Sorden,, P. G. Halbur,, M. K. Morgan,, K. J. Yoon,, and P. S. Paul. 1998. Detection of a novel strain of porcine circovirus in pigs with postweaning multisystemic wasting syndrome. J. Clin. Microbiol. 36: 2535– 2541.
74. Narita, M.,, K. Kawashima,, S. Matsuura,, A. Uchimura,, and Y. Miura. 1994. Pneumonia in pigs infected with pseudorabies virus and Haemophilus parasuis serovar 4. J. Comp. Pathol. 110: 329– 339.
75.. National Animal Health Monitoring System. 1996. Swine ‘95: Grower/Finisher. Part II. Reference of 1995 U.S. Grower/Finisher Health and Management Practices, p. 14– 16. U.S. Department of Agriculture, Fort Collins, Colo..
76. Nicolet, J. 1990. Overview of the virulence attributes of the HAP-group of bacteria. Can. J. Vet. Res. 54: S12– S15.
77. Olsen, C. W.,, M. W. McGregor,, A. J. Cooley,, B. Schantz,, B. Hotze,, and V. S. Hinshaw. 1993. Antigenic and genetic analysis of a recently isolated H1N1 swine influenza virus. Am. J. Vet. Res. 54: 1630– 1636.
78. Ottis, K.,, L. Sidoli,, P. A. Bachmann,, R. G. Webster,, and M. M. Kaplan. 1982. Human influenza A viruses in pigs: isolation of a H3N2 strain antigenically related to A/England/42/72 and evidence for continuous circulation of human viruses in the pig population. Arch. Virol. 73: 103– 108.
79. Paul, P. S.,, P. G. Halbur,, and E. M. Vaughn. 1994. Significance of porcine respira- tory coronavirus infection. Comp. Cont. Educ. Pract. Vet. 16: 1223– 1233.
80. Pijoan, C.,, R. B. Morrison,, and H. D. Hilley. 1983. Serotyping of Pasteurella multocida isolated from swine lungs collected at slaughter. J. Clin. Microbiol. 17: 1074– 1076.
81. Pol, J. M.,, L. A. van Leengoed,, N. Stockhofe,, G. Kok,, and G. Wensvoort. 1997. Dual infections of PRRSV/influenza or PRRSV/ Actinobacillus pleuropneumoniae in the respiratory tract. Vet. Microbiol. 55: 259– 264.
82. Rappouli, R., 1994. Pathogenicity mechanisms of Bordetella, p. 319– 336. In J. L. Dangl (ed.), Bacterial Pathogens of Plants and Animals. Springer- Verlag, Berlin, Germany.
83. Rasschaert, D.,, M. Duarte,, and H. Laude. 1990. Porcine respiratory coronavirus differs from transmissible gastroenteritis virus by a few genomic deletions. J. Gen. Virol. 71: 2599– 2607.
84. Rekik, M. R.,, D. J. Arora,, and S. Dea. 1994. Genetic variation in swine influenza virus A isolate associated with proliferative and necrotizing pneumonia in pigs. J. Clin. Microbiol. 32: 515– 518.
85. Rogers, D. G.,, A. A. Andersen,, and B. D. Hunsaker. 1996. Lung and nasal lesions caused by a swine chlamydial isolate in gnotobiotic pigs. J. Vet. Diagn. Investig. 8: 45– 55.
86. Rosell, C.,, J. Segales,, J. Plana-Duran,, M. Balasch,, G. M. Rodriguez-Arrioja,, S. Kennedy,, G. M. Allan,, F. McNeilly,, K. S. Latimer,, and M. Domingo. 1999. Pathological, immunohistochemical, and in-situ hybridization studies of natural cases of postweaning multisystemic wasting syndrome (PMWS) in pigs. J. Comp. Pathol. 120: 59– 78.
87. Rosell, C.,, J. Segales,, J. A. Ramos-Vara,, J. M. Folch,, G. M. Rodriguez-Arrioja,, C. O. Duran,, M. Balasch,, J. Plana-Duran,, and M. Domingo. 2000. Identification of porcine circovirus in tissues of pigs with porcine dermatitis and nephropathy syndrome. Vet. Rec. 146: 40– 43.
88. Rycroft, A. N.,, and J. M. Cullen. 1990. Complement resistance in Actinobacillus (Haemophilus) pleuropneumoniae infection of swine. Am. J. Vet. Res. 51: 1449– 1453.
89. Sakano, T.,, I. Shibata,, Y. Samegai,, A. Taneda,, M. Okada,, T. Irisawa,, and S. Sato. 1993. Experimental pneumonia of pigs infected with Aujeszky’s disease virus and Actinobacillus pleuropneumoniae. J. Vet. Med. Sci. 55: 575– 579.
90. Schneider, J. D.,, and K.-J. Yoon. 2001. Characterization of H3N2 swine influenza viruses in Iowa swine. Proc. Am. Assoc. Swine Vet., p. 23– 25.
91. Segales, J.,, M. Domingo,, M. Balasch,, G. I. Solano,, and C. Pijoan. 1998. Ultrastructural study of porcine alveolar macrophages infected in vitro with porcine reproductive and respiratory syndrome (PRRS) virus, with and without Haemophilus parasuis. J. Comp. Pathol. 118: 231– 243.
92. Segales, J.,, M. Domingo,, G. I. Solano,, and C. Pijoan. 1999. Porcine reproductive and respiratory syndrome virus and Haemophilus parasuis antigen distribution in dually infected pigs. Vet. Microbiol. 64: 287– 297.
93. Segales, J.,, M. Sitjar,, M. Domingo,, S. Dee,, M. Del Pozo,, R. Noval,, C. Sacristan,, A. De las Heras,, A. Ferro,, and K. S. Latimer. 1997. First report of post-weaning multisystemic wasting syndrome in pigs in Spain. Vet. Rec. 141: 600– 601.
94. Shibata, I.,, M. Okada,, K. Urono,, Y. Samegai,, M. Ono,, T. Sakano,, and S. Sato. 1998. Experimental dual infection of cesarean-derived, colostrum-deprived pigs with Mycoplasma hyopneumoniae and pseudorabies virus. J. Vet. Med. Sci. 60: 295– 300.
95. Sirinarumitr, T.,, Y. Zhang,, J. P. Kluge,, P. G. Halbur,, and P. S. Paul. 1998. A pneumovirulent United States isolate of porcine reproductive and respiratory syndrome virus induces apoptosis in bystander cells both in vitro and in vivo. J. Gen. Virol. 79: 2989– 2995.
96. Solano, G. I.,, E. Bautista,, T. W. Molitor,, J. Segales,, and C. Pijoan. 1998. Effect of porcine reproductive and respiratory syndrome virus infection on the clearance of Haemophilus parasuis by porcine alveolar macrophages. Can. J. Vet. Res. 62: 251– 256.
97. Solano, G. I.,, J. Segales,, J. E. Collins,, T. W. Molitor,, and C. Pijoan. 1997. Porcine reproductive and respiratory syndrome virus (PRRSv) interaction with Haemophilus parasuis. Vet. Microbiol. 55: 247– 257.
98. Stevenson, G. W.,, M. Kiupel,, S. K. Mittal,, J. Choi,, K. S. Latimer,, and C. L. Kanitz. 2001. Tissue distribution and genetic typing of porcine circoviruses in pigs with naturally occurring congenital tremors. J. Vet. Diagn. Investig. 13: 57– 62.
99. Thacker, E. L.,, P. G. Halbur,, R. F. Ross,, R. Thanawongnuwech,, and B. J. Thacker. 1999. Mycoplasma hyopneumoniae potentiation of porcine reproductive and respiratory syndrome virus-induced pneumonia. J. Clin. Microbiol. 37: 620– 627.
100. Thacker, E. L.,, B. J. Thacker,, and B. H. Janke. 2001. Interaction between Mycoplasma hyopneumoniae and swine influenza virus. J. Clin. Microbiol. 39: 2525– 2530.
101. Thacker, E. L.,, B. J. Thacker,, M. Kuhn,, P. A. Hawkins,, and W. R. Waters. 2000. Evaluation of local and systemic immune responses induced by intramuscular injection of a Mycoplasma hyopneumoniae bacterin to pigs. Am. J. Vet. Res. 61: 1384– 1389.
102. Thanawongnuwech, R.,, G. B. Brown,, P. G. Halbur,, J. A. Roth,, R. L. Royer,, and B. J. Thacker. 2000. Pathogenesis of porcine reproductive and respiratory syndrome virus-induced increase in susceptibility to Streptococcus suis infection. Vet. Pathol. 37: 143– 152.
103. Thanawongnuwech, R.,, P. G. Halbur,, M. R. Ackermann,, E. L. Thacker,, and R. L. Royer. 1998. Effects of low (modified-live virus vaccine) and high (VR-2385)-virulence strains of porcine reproductive and respiratory syndrome virus on pulmonary clearance of copper particles in pigs. Vet. Pathol. 35: 398– 406.
104. Thanawongnuwech, R.,, E. L. Thacker,, and P. G. Halbur. 1997. Effect of porcine reproductive and respiratory syndrome virus (PRRSV) (isolate ATCC VR-2385) infection on bactericidal activity of porcine pulmonary intravascular macrophages (PIMs): in vitro comparisons with pulmonary alveolar macrophages (PAMs). Vet. Immunol. Immunopathol. 59: 323– 335.
105. Thanawongnuwech, R.,, T. F. Young,, B. J. Thacker,, and E. L. Thacker. 2001. Differential production of proinflammatory cytokines: in vitro PRRSV and Mycoplasma hyopneumoniae coinfection model. Vet. Immunol. Immunopathol. 79: 115– 127.
106. Tischer, I.,, H. Gelderblom,, W. Vettermann,, and M. A. Koch. 1982. A very small porcine virus with circular single stranded DNA. Nature 295: 64– 66.
107. Tuomanen, E. 1986. Piracy of adhesins: attachment of superinfecting pathogens to respiratory cilia by secreted adhesins of Bordetella pertussis. Infect. Immun. 54: 905– 908.
108. Vahle, J. L.,, J. S. Haynes,, and J. J. Andrews. 1995. Experimental reproduction of Haemophilus parasuis infection in swine: clinical, bacteriological, and morphologic findings. J. Vet. Diagn. Investig. 7: 476– 80.
109. Vahle, J. L.,, J. S. Haynes,, and J. J. Andrews. 1997. Interaction of Haemophilus parasuis with nasal and tracheal mucosa following intranasal inoculation of cesarean derived colostrum deprived (CDCD) swine. Can. J. Vet. Res. 61: 200– 206.
110. Van Alstine, W. G.,, G. W. Stevenson,, and C. L. Kanitz. 1996. Porcine reproductive and respiratory syndrome virus does not exacerbate Mycoplasma hyopneumoniae infection in young pigs. Vet. Microbiol. 49: 297– 303.
111. van Diemen, P. M.,, M. F. de Jong,, G. de Vries Reilingh,, P. van der Hel,, and J. W. Schrama. 1994. Intranasal administration of Pasteurella multocida toxin in a challenge-exposure model used to induce subclinical signs of atrophic rhinitis in pigs. Am. J. Vet. Res. 55: 49– 54.
112. Van Reeth, K.,, G. Labarque,, H. Nauwynck,, and M. Pensaert. 1999. Differential production of proinflammatory cytokines in the pig lung during different respiratory virus infections: correlations with pathogenicity. Res. Vet. Sci. 67: 47– 52.
113. Van Reeth, K.,, and H. Nauwynck. 2000. Proinflammatory cytokines and viral respiratory disease in pigs. Vet. Res. 31: 187– 213.
114. Van Reeth, K.,, H. Nauwynck,, and M. Pensaert. 1996. Dual infections of feeder pigs with porcine reproductive and respiratory syndrome virus followed by porcine respiratory coronavirus or swine influenza virus: a clinical and virological study. Vet. Microbiol. 48: 325– 335.
115. Van Reeth, K.,, H. Nauwynck,, and M. Pensaert. 1998. Bronchoalveolar interferon-alpha, tumor necrosis factor-alpha, interleukin-1, and inflammation during acute influenza in pigs: a possible model for humans? J. Infect. Dis. 177: 1076– 1079.
116. Van Reeth, K.,, H. Nauwynck,, and M. Pensaert. 2000. A potential role for tumour necrosis factor-alpha in synergy between porcine respiratory coronavirus and bacterial lipopolysaccharide in the induction of respiratory disease in pigs. J. Med. Microbiol. 49: 613– 620.
117. Van Reeth, K.,, and M. Pensaert. 1994. Prevalence of infections with enzootic respiratory and enteric viruses in feeder pigs entering fattening herds. Vet. Rec. 135: 594– 597.
118. Van Reeth, K.,, and M. B. Pensaert. 1994. Porcine respiratory coronavirus-mediated interference against influenza virus replication in the respiratory tract of feeder pigs. Am. J. Vet. Res. 55: 1275– 1281.
119. Vecht, U.,, J. P. Arends,, E. J. van der Molen,, and L. A. van Leengoed. 1989. Differences in virulence between two strains of Streptococcus suis type II after experimentally induced infection of newborn germ-free pigs. Am. J. Vet. Res. 50: 1037– 1043.
120. Vecht, U.,, H. J. Wisselink,, J. E. van Dijk,, and H. E. Smith. 1992. Virulence of Streptococcus suis type 2 strains in newborn germfree pigs depends on phenotype. Infect. Immun. 60: 550– 556.
121. Wesley, R. D.,, W. L. Mengeling,, and K. M. Lager. 1998. Prior infection of nursery-age pigs with porcine reproductive and respiratory syndrome virus does not affect the outcome of transmissible gastroenteritis virus challenge. J. Vet. Diagn. Investig. 10: 221– 228.
122. Wills, R. W.,, J. T. Gray,, P. J. Fedorka- Cray,, K. J. Yoon,, S. Ladely,, and J. J. Zimmerman. 2000. Synergism between porcine reproductive and respiratory syndrome virus (PRRSV) and Salmonella choleraesuis in swine. Vet. Microbiol. 71: 177– 192.
123. Wills, R. W.,, J. J. Zimmerman,, K.-J. Yoon,, S. L. Swenson,, M. J. McGinley,, H. T. Hill,, K. B. Platt,, J. Christopher- Hennings,, and E. A. Nelson. 1997. Porcine reproductive and respiratory syndrome virus: a persistent infection. Vet. Microbiol. 55: 231– 240.
124. Yagihashi, T.,, T. Nunoya,, T. Mitui,, and M. Tajima. 1984. Effect of Mycoplasma hyopneumoniae infection on the development of Haemophilus pleuropneumoniae pneumonia in pigs. Nippon Juigaku Zasshi 46: 705– 713.

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