Konold Timm, Moore S Jo, Bellworthy Susan J, Simmons Hugh A
Neuropathology, Veterinary Laboratories Agency Weybridge, New Haw, Addlestone, Surrey KT15 3NB, UK.
BMC Vet Res. 2008 Apr 8;4:14. doi: 10.1186/1746-6148-4-14.
The risk of scrapie infection increases with increased duration and proximity of contact between sheep at lambing. Scrapie infectivity has not been detected in milk but cellular prion protein, the precursor of disease-associated prion protein PrPd, has been found in milk from ruminants. To determine whether milk is able to transmit scrapie, 18 lambs with a prion protein genotype associated with high susceptibility to scrapie (VRQ/VRQ) were fed milk from twelve scrapie-affected ewes of the same genotype, and 15 VRQ/VRQ sheep reared on scrapie-free dams served as controls.
Three lambs fed milk from scrapie-affected ewes were culled due to intercurrent diseases at 43, 44 and 105 days of age respectively, and PrPd was detected in the distal ileum of the first two lambs, whilst PrPd was not found in lymphoreticular tissues in the third lamb. A control lamb, housed in a separate pen and culled at 38 days of age, was also negative for PrPd in a range of tissues. Samples of recto-anal mucosa associated lymphoid tissue collected from the remaining 15 live lambs at seven months of age (between five to seven months after mixing) were positive for PrPd in the scrapie milk recipients, whereas PrPd was not detected in the remaining 14 controls at that time. A subsequent sample collected from control lambs revealed PrPd accumulation in two of five lambs eight months after mixing with scrapie milk recipients suggestive of an early stage of infection via lateral transmission. By contrast, the control sheep housed in the same building but not mixed with the scrapie milk recipients were still negative for PrPd.
The presence of PrPd in distal ileum and rectal mucosa indicates transmission of scrapie from ewe to lamb via milk (or colostrum) although it is not yet clear if such cases would go on to develop clinical disease. The high level of infection in scrapie-milk recipients revealed by rectal mucosal testing at approximately seven months of age may be enhanced or supplemented by intra-recipient infection as these lambs were mixed together after feeding with milk from scrapie-affected ewes and we also observed lateral transmission from these animals to lambs weaned from scrapie-free ewes.
产羔时,绵羊之间接触的持续时间越长、距离越近,感染羊瘙痒病的风险就越高。在牛奶中未检测到羊瘙痒病感染性,但在反刍动物的牛奶中发现了细胞朊病毒蛋白,即与疾病相关的朊病毒蛋白PrPd的前体。为了确定牛奶是否能够传播羊瘙痒病,用来自12只相同基因型的感染羊瘙痒病母羊的牛奶喂养了18只具有与高羊瘙痒病易感性相关的朊病毒蛋白基因型(VRQ/VRQ)的羔羊,并将15只由未感染羊瘙痒病的母羊饲养的VRQ/VRQ绵羊作为对照。
分别在43、44和105日龄时,三只食用感染羊瘙痒病母羊牛奶的羔羊因并发疾病而被淘汰,在前两只羔羊的回肠末端检测到PrPd,而在第三只羔羊的淋巴网状组织中未发现PrPd。一只单独圈养并在38日龄时被淘汰的对照羔羊在一系列组织中PrPd检测也为阴性。在7个月大时(混合后5至7个月之间)从其余15只存活的羔羊收集的直肠-肛门黏膜相关淋巴组织样本中,接受羊瘙痒病牛奶的羔羊PrPd呈阳性,而此时其余14只对照羔羊中未检测到PrPd。随后从对照羔羊收集的样本显示,在与接受羊瘙痒病牛奶的羔羊混合8个月后,5只羔羊中有2只出现PrPd积累,提示通过横向传播处于感染早期。相比之下,饲养在同一栋楼但未与接受羊瘙痒病牛奶的羔羊混合的对照绵羊PrPd检测仍为阴性。
回肠末端和直肠黏膜中存在PrPd表明羊瘙痒病可通过牛奶(或初乳)从母羊传播给羔羊,尽管尚不清楚这些病例是否会发展为临床疾病。在大约7个月大时通过直肠黏膜检测发现接受羊瘙痒病牛奶的羔羊感染率很高,可能是由于接受者自身感染增强或补充了感染,因为这些羔羊在食用感染羊瘙痒病母羊的牛奶后被混合在一起,并且我们还观察到这些动物向从未感染羊瘙痒病母羊断奶的羔羊的横向传播。