Abstract. Sheep scrapie is a prion disease that requires interaction of exogenous prions with host prion protein (PrP) supporting prion formation. Disease is associated with deposition of a host-generated conformational variant of PrP, PrP sc , in a variety of tissues, including brain, resulting in fatal spongiform encephalopathy. Efficiency of PrP sc formation is determined by polymorphisms in the PrP-coding sequence. This article adds to previous data of natural sheep scrapie, concentrating on the effect of host genotype and age on PrP sc accumulation patterns during preclinical and clinical disease. Two entire scrapie-infected, predominantly Suffolk-cross, sheep flocks euthanized for regulatory purposes were genotyped and analyzed for PrP sc deposition in various tissues using single-and dual-label immunohistochemistry. Scrapie, as defined by PrP sc deposition, occurred in 13/80 sheep. Preclinical disease was evident in nearly 70% of infected sheep, ranging in age from 14 months to 7 years. PrP sc accumulated systemically in the nervous tissue, various lymphoid tissues, both alimentary tract related and non-alimentary tract related, and the placenta. Clinical neurological illness was always associated with spongiform encephalopathy and PrP sc deposition in the brain. Only 6 of 9 sheep with preclinical scrapie had PrP sc deposition in the brain but widespread PrP sc deposition in peripheral lymphoid tissue, supporting previous data showing peripheral PrP sc accumulation preceding deposition in the brain. PrP sc colocalized with a marker for follicular dendritic cells throughout the lymphoid system. PrP sc also accumulated in the peripheral nervous system, particularly the nervous supply of the gastrointestinal tract. Abundant PrP sc was evident in trophoblast cells of placentomes but not in the endometrium, myometrium, or associated nervous plexus. PrP sc deposits were not observed in the mammary parenchyma or bone marrow. Scrapie susceptibility was defined genetically by PrP codon 171: PrP sc deposition was restricted to PrP genotype AA 136 RR 154 QQ 171 in 12/13 cases or AV 136 RR 154 QQ 171 in 1/13 cases. The earliest accumulation was observed in the single VRQ/ARQ heterozygous animal, consistent with the reported high scrapie susceptibility and brief incubation period observed in breeds with predominance of the V 136 R 154 Q 171 allele. Disease occurred within, as well as independent of, motherdaughter lines, suggesting both maternal and nonmaternal transmission in the flocks.
Abstract. False-positive results on serologic assays for Mycobacterium avium subsp. paratuberculosis (MAP) are believed to occur due to cross-reacting antibody produced by Corynebacterium pseudotuberculosis (C. pstb) infection in goats. This issue of compromised specificity was evaluated by testing 771 adult goats from 10 Midwestern goat herds in 2004. Assays for MAP infection included radiometric fecal culture and 2 enzyme-linked immunosorbent assays (ELISAs); ELISA-positive samples were tested by agar gel immunodiffusion (AGID). A synergistic hemolysin inhibition assay (SHI) was used to detect C. pstb antibody. Four infection status categories were evaluated. Category 1 goats (free of both MAP and C. pstb infection) tested negative on all MAP fecal cultures and SHI tests. Five of 181 goats were positive in both ELISAs, and 2 more were positive in ELISA-1 only. For Category 2 (MAP infected; no C. pstb infection), all animals were SHI negative. Six goats were fecal culture positive and strongly positive in both ELISAs; 2 more goats were positive only in ELISA-1. For Category 3 (C. pstb infected or vaccinated; no history of MAP infection), all fecal cultures were negative and 91% were SHI test-positive. In this population, only 2 goats were positive in both MAP ELISAs, while 84 additional goats were test-positive only on ELISA-1. In the absence of C. pstb infection, both ELISAs performed comparably, but when C. pstb infection was present the performance of ELISA-1 was significantly perturbed. Use of the ELISA-2 for goats is an effective and efficient method for Johne's disease surveillance in any goat herd.
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