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Dose-dependent Responses of Sheep Inoculated Intranasally with a Type O Foot-and-mouth Disease Virus

https://doi.org/10.1053/jcpa.2002.0560Get rights and content

Abstract

Unlike foot-and-mouth disease (FMD) in cattle and pigs, which spreads rapidly, resulting in easily detectable foci of clinical infection, the disease in sheep is characterized by restricted transmission, low morbidity and sporadic clinical cases. The study described was designed to investigate whether the ability of sheep to transmit and maintain FMD virus was dose-related. The viral isolate used was known to be associated epidemiologically with rapid fade-out of transmission within sheep flocks. Five separate transmission experiments were performed, with different doses of FMD virus, each experiment containing five intranasally inoculated donor sheep and 10 in-contact recipient sheep. The lowest dose required to cause clinical infection by inoculation (104 50% tissue culture infectious doses; 104 TCID50) was also the optimum dose for producing in-contact transmission. Inoculation of donor sheep with higher doses (105 and 106 TCID50) resulted in reduced transmission, characterized by reduced duration and degree of viraemia and an early humoral and cell-mediated immune response. Principal component analysis was used to interpret the complex interactions of the dose-related responses to infection.

References (24)

  • R. Burrows

    The persistence of foot-and-mouth disease virus in sheep

    Journal of Hygiene, Cambridge

    (1968)
  • S.N. Chevskii et al.

    Clinical and anatomical manifestations of foot and mouth disease in new-born lambs

    Trudy Ulyanov Sel»khozmashiny Instituta Zootechologii Veterinaria

    (1964)
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    Correspondence to: G. J. Hughes, Division of Viral and Rickettsial Diseases, National Centers for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop G33, Atlanta, GA 30333, USA.

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