Abstract：
BACKGROUND: Prions are renowned for their distinct resistance to chemical or physical inactivation, including steam sterilization. Impaired efficacy of inactivation poses a risk to patients for iatrogenic transmission of Creutzfeldt-Jakob disease (CJD) via contaminated surgical instruments.
OBJECTIVE: Most established prion inactivation methods were validated against scrapie agents, although those were found to be generally less thermostable than human prions. Thus, knowledge gaps regarding steam-sterilization kinetics of CJD prions should be filled and current guidelines reviewed accordingly.
METHODS: Prion inactivation through widely recommended steam sterilization at 134°C was assessed for several holding times by analysing the residual prion seeding activity using protein misfolding cyclic amplification (PMCA).
RESULTS: Scrapie 263K was found to be the least thermoresistant prion strain showing no seeding activity after 1.5 min at 134°C, while variant CJD was the most stable one demonstrating some seeding activity even after 18 min of steam sterilization. Sporadic CJD subtype VV2 exhibited residual seeding activity after 3 min, but no detectable activity after 5 min at 134°C.
CONCLUSIONS: Validated steam sterilization for 5 min at 134°C as previously recommended for the routine reprocessing of surgical instruments in contact with high-risk tissues is able to substantially reduce the seeding activity of CJD agents, provided that no fixating chemical disinfection has been performed prior to sterilization and that thorough cleaning has reduced the protein load on the surface to less than 100 μg per instrument.
OBJECTIVE: Most established prion inactivation methods were validated against scrapie agents, although those were found to be generally less thermostable than human prions. Thus, knowledge gaps regarding steam-sterilization kinetics of CJD prions should be filled and current guidelines reviewed accordingly.
METHODS: Prion inactivation through widely recommended steam sterilization at 134°C was assessed for several holding times by analysing the residual prion seeding activity using protein misfolding cyclic amplification (PMCA).
RESULTS: Scrapie 263K was found to be the least thermoresistant prion strain showing no seeding activity after 1.5 min at 134°C, while variant CJD was the most stable one demonstrating some seeding activity even after 18 min of steam sterilization. Sporadic CJD subtype VV2 exhibited residual seeding activity after 3 min, but no detectable activity after 5 min at 134°C.
CONCLUSIONS: Validated steam sterilization for 5 min at 134°C as previously recommended for the routine reprocessing of surgical instruments in contact with high-risk tissues is able to substantially reduce the seeding activity of CJD agents, provided that no fixating chemical disinfection has been performed prior to sterilization and that thorough cleaning has reduced the protein load on the surface to less than 100 μg per instrument.
摘要：
背景：朊病毒以其对化学或物理失活的独特抗性而闻名，包括蒸汽灭菌。失活的功效受损会给患者带来通过受污染的手术器械医源性传播克雅氏病（CJD）的风险。
目的：大多数已建立的朊病毒灭活方法已针对瘙痒病制剂进行了验证，尽管发现这些病毒的热稳定性通常低于人类病毒。因此，应填补有关CJD病毒蒸汽灭菌动力学的知识空白，并相应地审查当前指南。
方法：通过使用蛋白质错误折叠循环扩增（PMCA）分析残留的朊病毒接种活性，评估了在134°C下广泛推荐的蒸汽灭菌对朊病毒灭活的几次保持时间。
结果：Scrapie263K被发现是在134°C下1.5分钟后没有播种活性的耐热性最低的朊病毒菌株，而变体CJD是最稳定的一种，即使经过18分钟的蒸汽灭菌，也表现出一定的播种活性。散发性CJD亚型VV2在3分钟后表现出残留的播种活性，但在134℃5分钟后没有检测到的活性。
结论：先前推荐的与高风险组织接触的手术器械的常规再处理在134°C下进行5分钟的经过验证的蒸汽灭菌能够大大减少CJD试剂的接种活性，前提是在灭菌之前未进行固定化学消毒，并且彻底清洁已将表面上的蛋白质负载减少到每个仪器的100μg以下。
目的：大多数已建立的朊病毒灭活方法已针对瘙痒病制剂进行了验证，
方法：通过使用蛋白质错误折叠循环扩增（PMCA）分析残留的朊病毒接种活性，评估了在134°C下广泛推荐的蒸汽灭菌对朊病毒灭活的几次保持时间。
结果：Scrapie263K被发现是在134°C下1.5分钟后没有播种活性的耐热性最低的朊病毒菌株，
结论：先前推荐的与高风险组织接触的手术器械的常规再处理在134°C下进行5分钟的经过验证的蒸汽灭菌能够大大减少CJD试剂的接种活性，
