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Chronic wasting disease (CWD) is a prion disease affecting cervid species primarily in the United States of America and Canada; however, it is now emerging in Scandinavian countries. Although CWD cases have not been reported in Japan, in case of a CWD outbreak occuring, it is critical to prepare for testing a large number of specimens. The present study showed that a rapid post‐mortem test kit, which is used for bovine spongiform encephalopathy surveillance in Japan, is valid for the detection of CWD prion. [ABSTRACT FROM AUTHOR]

Prion gene (PRNP) mutations are associated with diverse disease phenotypes, including familiar Creutzfeldt-Jakob Disease (CJD), Gerstmann-Sträussler-Scheinker disease (GSS), and fatal familial insomnia (FFI). Interestingly, PRNP mutations have been reported in patients diagnosed with Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease, and frontotemporal dementia. In this review, we describe prion mutations in Asian countries, including Republic of Republic of Korea, China, and Japan. Clinical phenotypes and imaging data related to these mutations have also been introduced in detail. Several prion mutations are specific to Asians and have rarely been reported in countries outside Asia. For example, PRNP V180I and M232R, which are rare in other countries, are frequently detected in Republic of Korea and Japan. PRNP T188K is common in China, and E200K is significantly more common among Libyan Jews in Israel. The A117V mutation has not been detected in any Asian population, although it is commonly reported among European GSS patients. In addition, V210I or octapeptide insertion is common among European CJD patients, but relatively rare among Asian patients. The reason for these differences may be geographical or ethical isolation. In terms of clinical phenotypes, V180I, P102L, and E200K present diverse clinical symptoms with disease duration, which could be due to other genetic and environmental influences. For example, rs189305274 in the ACO1 gene may be associated with neuroprotective effects in cases of V180I mutation, leading to longer disease survival. Additional neuroprotective variants may be possible in cases featuring the E200K mutation, such as KLKB1, KARS, NRXN2, LAMA3, or CYP4X1. E219K has been suggested to modify the disease course in cases featuring the P102L mutation, as it may result in the absence of prion protein-positive plaques in tissue stained with Congo red. However, these studies analyzed only a few patients and may be too preliminary. The findings need to be verified in studies with larger sample sizes or in other populations. It would be interesting to probe additional genetic factors that cause disease progression or act as neuroprotective factors. Further studies are needed on genetic modifiers working with prions and alterations from mutations.

There have been more than 400 patients who contracted Creutzfeldt-Jakob disease (CJD) via a medical procedure, that is, through the use of neurosurgical instruments, intracerebral electroencephalographic electrodes (EEG), human pituitary hormone, dura mater grafts, corneal transplant, and blood transfusion. The number of new patients with iatrogenic CJD has decreased; however, cases of variant CJD that was transmitted via blood transfusion have been reported since 2004. Clearly, iatrogenic transmission of CJD remains a serious problem. Recently, we investigated medical procedures (any surgery, neurosurgery, ophthalmic surgery, and blood transfusion) performed on patients registered by the CJD Surveillance Committee in Japan during a recent 9-year period. In a case-control study comprising 753 sporadic CJD (sCJD) patients and 210 control subjects, we found no evidence that prion disease was transmitted via the investigated medical procedures before onset of sCJD. In a review of previously reported case-control studies, blood transfusion was never shown to be a significant risk factor for CJD; our study yielded the same result. Some case-control studies reported that surgery was a significant risk factor for sCJD. However, when surgical procedures were categorized by type of surgery, the results were conflicting, which suggests that there is little possibility of prion transmission via surgical procedures. In our study, 4.5% of sCJD patients underwent surgery after onset of sCJD, including neurosurgeries in 0.8% and ophthalmic surgeries in 1.9%. The fact that some patients underwent surgery, including neurosurgery, even after the onset of sCJD indicates that we cannot exclude the possibility of prion transmission via medical procedures. We must remain vigilant against prion diseases to reduce the risk of iatrogenesis. [ABSTRACT FROM AUTHOR]

We identified cDNAs coding for homologues to tetrapod prion proteins (PrPs) in Atlantic salmon (Salmo salar) and Japanese pufferfish (Fugu rubripes), which were termed ‘similar to PrPs’ (stPrPs). Besides significant sequence homologies the fish stPrPs display characteristic structural features in common with tetrapod PrPs. In addition, two stPrPs were shown to be highly expressed in brain tissue. None of the so far identified PrP-homologues of fish resembles doppel. Hence, the duplication of the PrP gene, which generated doppel, may have occurred not in fish but later in the tetrapod lineage. The identification of fish PrPs provides a basis to address concerns about a possible susceptibility of fish to prion infections. [Copyright &y& Elsevier]

There has been no report on Chronic wasting disease (CWD) cases in Japan to date; however, there is concern about the geographic spread of CWD. To clarify the CWD status in Japan, we conducted CWD monitoring using real-time quaking-induced conversion (RT-QuIC) assay which can detect the low level of CWD prions. A total of 690 obex samples collected from sika deer and Reeves's muntjac in Hokkaido and Honshu was tested for CWD prions. No CWD-positive cases were found, suggesting that CWD is nonexistent in Japan. Our results also indicate that RT-QuIC assay is useful for continuous monitoring of CWD. Furthermore, nucleotide sequence analysis of the PrP gene revealed sika deer in Japan harbor CWD susceptible allele.

A classical type of bovine spongiform encephalopathy (C-BSE), recognized in 1987, had a large impact on public health due to its zoonotic link to variant Creutzfeldt-Jakob disease by the human consumption of dietary products contaminated with the C-BSE prion. Thus, a number of countries implemented BSE surveillance using rapid post-mortem test kits that were approved for detection of the C-BSE prion in the cattle brain. However, as atypical BSE (L- and H-BSE) cases emerged in subsequent years, the efficacy of the kits for the detection of atypical BSE prions became a matter of concern. In response to this, laboratories in the European Union and Canada evaluated the kits used in their countries. Here, we carried out an evaluation study of NippiBL®, a kit currently used for BSE screening in Japan. By applying the kit to cattle brains of field cases of C-BSE and L-BSE, and an experimental case of H-BSE, we showed its comparable sensitivities to C, L-, and H-BSE prions, and satisfactory performance required by the European Food Safety Authority. In addition to NippiBL®, two kits (TeSeE® and FRELISA®) formerly used in Japan were effective for detection of the L-BSE prion, although the two kits were unable to be tested for the H-BSE prion due to the discontinuation of domestic sales during this study. These results indicate that BSE screening in Japan is as effective as those in other countries, and it is unlikely that cases of atypical BSE have been overlooked.