Risk Of Creutzfeldt-Jakob Disease Research Articles

Incidence of Creutzfeldt-Jakob disease in Taiwan: a prospective 10-year surveillance

This study was performed to estimate the incidence of Creutzfeldt-Jakob Disease (CJD) in Taiwan from 1998 to 2007. Suspected cases of CJD were reported to the Taiwan Creutzfeldt-Jakob Disease Surveillance Unit, a nationwide, hospital-based case report system initiated since 1996 to prospectively conduct a CJD epidemiological study. Consecutive patients who met the diagnostic criteria recommended by the World Health Organization were enrolled. The clinical information of each suspected case was collected and case ascertainment was performed by an expert committee. A total of 123 sporadic CJD were identified without any iatrogenic or new variant CJD cases. The overall annual incidence rate (95% CI) was 0.55 (0.46-0.65) cases per million person-year. There was no statistically significant difference between the calendar year of disease onset (P = 0.97). The incidence rates were not significantly different between women and men (P = 0.63). Age was the main factor for the risk of CJD (P < 0.0001). Age-specific incidence rate increased after the age of 40 years with the peak being in the 70-79 years age group. Our data showed low annual incidence rate and high frequency of methionine homozygous prion protein genotype of sCJD in Taiwan. This report provided important epidemiological data on ethnic Chinese.

Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease risk management in Switzerland

In 1990, Switzerland became the first country in mainland Europe to report a native case of bovine spongiform encephalopathy (BSE), despite a low level of live bovine and meat and bone meal (MBM) imports from the UK, the country generally recognised as the origin of the epidemic. Although an MBM to ruminant feed ban was immediately put into effect, the incidence of BSE continued to increase in cohorts born subsequently, possibly because of cross-contamination. The prompt decision to remove specified risk material (SRM) such as bovine brain and spinal cord from human food contributed to a low risk of variant Creutzfeldt-Jakob Disease (vCJD); despite having had one of the highest rates of BSE of any country, Switzerland has yet to report a case of vCJD.

Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease risk management in Spain

Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease risk management in Spain

Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease risk management in Belgium

Italy experienced two imported cases of bovine spongiform encephalopathy (BSE) in 1994 and viewed the disease as a 'foreign' problem. Early, precautionary actions including: a 1989 ban on UK meat and bone meal (MBM), 1990 ban on UK beef, 1994 domestic ban on mammalian MBM to ruminants, and 1996 ban on UK live cattle, protected Italy from a much larger outbreak. In 2001 Italy implemented an effective and active BSE surveillance system in compliance with European Union regulations. Probably little MBM feeding or amplification of BSE agent occurred within Italian herds after 1996. BSE cases have declined since 2001. In 2007, the European Commission recognised Italy as a controlled BSE risk country. To date only two cases of variant Creutzfeldt-Jakob disease (vCJD) have been reported. A limited blood donor exclusion policy is in place to prevent cases of blood transfusion mediated vCJD.

Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease risk management in the Netherlands

Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease risk management in the Netherlands

Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease risk management strategies in the People's Republic of China

During the late 1970s, the People's Republic of China (PRC) launched a series of far-reaching economic reforms in rural areas of the country in order to develop a market economy; after three decades, these nationwide reforms have achieved enormous success. The country witnessed phenomenal growth in its economic development and became the second largest exporter in the world by 2005. With the growing economy, food safety in the PRC has become both an important domestic and international issue. To date, China has witnessed no domestic cases of either bovine spongiform encephalopathy (BSE) or variant Creutzfeldt-Jakob disease (vCJD), the human version of BSE. However, recent outbreaks of food poisoning from contaminated pork and chicken have prompted the government to promulgate additional measures designed to enhance food safety, including various BSE preventive measures. China established a national CJD surveillance program in year 2002, and participates in an international CJD surveillance network.

Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease risk management in Nordic countries

The prevalence of bovine spongiform encephalopathy (BSE) in Nordic countries is low. To date, there have been 14 BSE cases in domestic cattle in Denmark, three cases in Danish cattle exported to other countries, one case in Finland, one in Sweden, and no cases in Norway. As of April 2008, no cases of variant Creutzfeldt-Jakob disease (vCJD) have been identified. All Nordic countries had stopped imports of live cattle from the UK by 1990, implemented ruminant MBM bans in 1990-1991, and introduced active surveillance in 2000-2001. Although the implementation of other risk management interventions varied, all Nordic countries were assessed as having stable systems for mitigating BSE by 2001.

Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease risk management in Italy

Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease risk management in Italy

Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease risk management in Central European Countries: Czech Republic, Slovakia, Slovenia and Poland

The Czech Republic, Slovakia, Slovenia and Poland are economically stable countries located in the Central and Eastern part of Europe that became European Union Member States on May 1, 2004. These countries reported their first domestic bovine spongiform encephalopathy (BSE) cases in 2001-2002. Several national and European Union legislative measures were adopted by veterinary officials to reduce external and internal risk factors which limited the spread of the BSE within national herds. To date, the national control programs against BSE in cattle have been successful. The herd incidence of BSE is either at a low level or in decline. All four countries meet the World Organisation for Animal Health (OIE) requirements for the status of BSE controlled risk countries. Risk management measures adopted by these Central European national authorities to reduce BSE risk factors and protect the general public from primary and secondary vCJD are reviewed.

Is Surgery a Risk Factor for Creutzfeldt-Jakob Disease? Outcome Variation by Control Choice and Exposure Assessments

To determine whether methodological differences explain divergent results in case-control studies examining surgery as a risk factor for Creutzfeldt-Jakob disease (CJD). After case-control studies were systematically identified using PubMed, we performed a homogeneity analysis and applied models to effect sizes (odds ratio [OR] with 95% confidence interval [CI]) using 2 parameters: type of control subject used and consistency of data ascertainment. The hospitals and communities were located in Europe, Japan, and Australia. Patients were CJD case subjects and age- and sex-matched control subjects in the hospital or community. Because of the natural history of the disease, CJD subjects are not considered reliable sources of information for these studies. Therefore, individuals who are considered close to the subjects and who have knowledge of their medical history, including spouses and relatives, are necessarily identified as proxy informants for the surgical record of the case subjects. Overall, the effect sizes lacked homogeneity (P<.0001). Three studies that used control subjects from the community revealed a significantly elevated risk of CJD for patients who underwent surgery (OR, 1.82; 95% CI, 1.41-2.35 [P<.0001]), whereas 3 investigations that used control subjects from the hospital revealed a significantly reduced risk (OR, 0.69; 95% CI, 0.52-0.90 [P=.0069]). Two studies that used proxy informants to acquire information about case subjects and control subjects (consistent ascertainment) found that the risk of CJD was significantly lower in those subjects who underwent surgery (OR, 0.65; 95% CI, 0.48-0.87 [P=.0043]). Conversely, 4 studies in which proxy informants acted only on behalf of case subjects (inconsistent data ascertainment) found a significant positive association between surgery and CJD (OR, 1.67; 95% CI, 1.32-2.12 [P<.0001]). Both models fit the data very well, leaving no remaining variance in effect sizes to explain. Variation in the type of control subjects used and in exposure assessment in case-control studies may partially explain conflicting data regarding the association between surgery and CJD. However, there was almost complete confounding of these 2 parameters, making interpretation more difficult. Planning of future investigations must carefully consider these design elements.

Manganese and copper imbalance in the food chain constituents in relation to Creutzfeldt-Jakob disease

The objective of the study was to investigate the possible role of manganese and copper (Mn/Cu) imbalance of the food chain in the focally increased occurrence of Creutzfeldt-Jakob disease (CJD). Mn and Cu concentrations in soil, drinking water and foodstuffs collected from households in the region of focal accumulation of CJD patients and the control region were measured by FAAS. Considerably higher Mn/Cu ratios in the studied region than those in the control region were found for soil (49.3 vs. 21.1), honey (8.05 vs. 4.86), and for the main local food items: potatoes (2.09 vs. 1.07) and bread (5.85 vs. 5.35), however, only soil and potatoes were of statistical significance. The results could indicate a rare coincidence of the verified endogenous CJD risk (genetic) with a very probable exogenous CJD risk factor (Mn/Cu dietary/environmental imbalance), but whether and how this coincidence may contribute to the unique, continual temporo-spatial clustering of genetic CJD should be investigated in further studies.

A Case of Creutzfeldt-Jakob Disease Associated With a Dura Mater Graft in the United States

We describe a case of Creutzfeldt-Jakob disease associated with a dura mater graft (Lyodura brand) in a 26-year-old man who underwent several neurosurgical procedures as a child. Clinicians and infection control personnel should be aware that recipients of Lyodura brand dura mater grafts processed before May 1987 may remain at increased risk for Creutzfeldt-Jakob disease throughout their lives.

Human Prion Disease and Relative Risk Associated with Chronic Wasting Disease

The transmission of the prion disease bovine spongiform encephalopathy (BSE) to humans raises concern about chronic wasting disease (CWD), a prion disease of deer and elk. In 7 Colorado counties with high CWD prevalence, 75% of state hunting licenses are issued locally, which suggests that residents consume most regionally harvested game. We used Colorado death certificate data from 1979 through 2001 to evaluate rates of death from the human prion disease Creutzfeldt-Jakob disease (CJD). The relative risk (RR) of CJD for CWD-endemic county residents was not significantly increased (RR 0.81, 95% confidence interval [CI] 0.40-1.63), and the rate of CJD did not increase over time (5-year RR 0.92, 95% CI 0.73-1.16). In Colorado, human prion disease resulting from CWD exposure is rare or nonexistent. However, given uncertainties about the incubation period, exposure, and clinical presentation, the possibility that the CWD agent might cause human disease cannot be eliminated.

Is there a real risk of transmitting variant Creutzfeldt-Jakob disease by donor sperm insemination?

Although >99% of cases of Creutzfeldt-Jakob disease (CJD) are caused by spontaneous or inherited mutations in the prion protein, ‘variant’ CJD (vCJD) arose from dietary exposure to meat products infected with the bovine spongiform encephalopathy prion. While European and Canadian sperm donor candidates are rejected for significant CJD risk factors, American sperm donors are managed like blood donors (excluding all men who spent ≥3 months in the UK during 1980–1996 or ≥5 years in Europe since 1980), even though no evidence exists for sexual transmission of prion disease. This study surveyed international experts on either prions/prion disease or donor sperm/cryobanking as to the risk of vCJD transmission via semen/donor spermatozoa (45/104 replied). Consensus expert opinion was that the risk of transmission was <1:10,000,000, even for UK men, hence ultra-conservative risk avoidance would have minimal impact on public safety. Defining ‘high vCJD risk’ should be based on knowledge rather than fear, and due caution founded upon quantifying real risks rather than avoiding theoretical risks. Women seeking treatment using donor spermatozoa should be allowed to judge the negligible risk of vCJD infection in comparison with acceptable everyday risks, and given the choice of accepting spermatozoa from donors screened according to European-style criteria.

Creutzfeldt–Jakob disease risk andPRNPcodon 129 polymorphism: necessity to revalue current data

The polymorphism at codon 129 (M129V) of the prion protein gene (PRNP) is a recognized genetic marker for susceptibility to Creutzfeldt-Jakob disease (CJD) in the Caucasians. The distribution of this polymorphism in healthy individuals provides an important starting point for the evaluation of CJD risk in the general population. Early studies of reference population cohorts demonstrated that methionine/valine heterozygosity was the most frequent genotype. These studies were performed in relatively small numbers of control subjects and do not correspond with the findings of more recent investigations. In this study, we present an analysis of the codon M129V distribution in 613 corneal donors, representing one of the largest control groups examined to date. Methionine homozygotes represented 48.1%, valine homozygotes 8.7% and methionine/valine heterozygotes 43.2%. While age-related difference was not significant, differentiation according to the gender showed significant difference. The observed highest proportion of methionine homozygotes and statistically significant difference between genders as well as comparison with results obtained in other countries underline the need to re-evaluate the generally used reference data on M129V, including consideration of the gender, age and geographical distribution.

Tissue classification for the epidemiological assessment of surgical transmission of sporadic Creutzfeldt-Jakob disease. A proposal on hypothetical risk levels

BackgroundEpidemiological studies on the potential role of surgery in Creutzfeldt-Jakob Disease transmission have disclosed associations with history of specific surgical interventions or reported negative results.MethodsWithin the context of a case-control study designed to address surgical risk of sporadic Creutzfeldt-Jakob Disease in Nordic European countries (EUROSURGYCJD Project), a strategy was adopted to categorise reported surgical procedures in terms of potential risk of Creutzfeldt-Jakob Disease acquisition. We took into account elements of biological plausibility, either clinically or experimentally demonstrated, such as tissue infectivity, PrP expression content or successful route of infection.ResultsWe propose a classification of exposed tissues and anatomic structures, drawn up on the basis of their specific putative role as entry site for prion transmission through contact with surgical instruments that are not fully decontaminated.ConclusionsThis classification can serve as a reference, both in our study and in further epidemiological research, for categorisation of surgical procedures in terms of risk level of Creutzfeldt-Jakob Disease acquisition.

The population distribution of the Met allele at the PRNP129 polymorphism (a high risk factor for Creutzfeldt-Jakob disease) in various regions of France and in West Europe

The present study has been conducted to ascertain the level of allelic variation at codon 129 of the prion protein gene in France. Six French populations have been studied (Paris, Lille, Rennes, Chambéry, Grasse and Perpignan), totalling 1374 normal subjects. Mean heterozygosity in France is 46.5%, and the mean Met 129 allele (a high risk susceptibility factor for Creutzfeldt-Jakob disease) is 0.674. There is a genetic heterogeneity ( χ 2 = 38.44, p < 0.001) between the six populations compared, and Met allele frequencies are inversely correlated with latitude ( r = −0.93, p < 0.01). Such an inverse correlation with latitude ( r = −0.78, p = 0.01) is also found when Met allele frequencies in France are compared to those already published in five other European countries and in Turkey. We hypothesise that high Met 129 frequencies populations may be at higher risk for Creutzfeldt-Jakob disease.

Long-term mortality in the United States cohort of pituitary-derived growth hormone recipients

Objective Patients who received pituitary-derived growth hormone (GH) are at excess risk of mortality from Creutzfeldt-Jakob disease. We investigated whether they were at increased risk of death from other conditions, particularly preventable conditions. Study design A cohort (N = 6107) from known US pituitary-derived GH recipients (treated 1963-1985) was studied. Deaths were identified by reports from physicians and parents and the National Death Index. Rates were compared with the expected rates for the US population standardized for race, age, and sex. Results There were 433 deaths versus 114 expected (relative risk [RR], 3.8; 95% confidence interval [CI], 3.4-4.2; P<.0001) from 1963 through 1996. Risk was increased in subjects with GH deficiency caused by any tumor (RR, 10.4; 95% CI, 9.1-12.0; P<.0001). Surprisingly, subjects with hypoglycemia treated within the first 6 months of life were at extremely high risk (RR, 18.3; 95% CI, 9.2-32.8; P<.0001), as were all subjects with adrenal insufficiency (RR, 7.1; 95% CI, 6.2-8.2; P<.0001). A quarter of all deaths were sudden and unexpected. Of the 26 cases of Creutzfeldt-Jakob disease, four cases have died since 2000. Conclusions The death rate in pituitary-derived GH recipients was almost four times the expected rate. Replacing pituitary-derived GH with recombinant GH has eliminated only the risk of Creutzfeldt-Jakob disease. Hypoglycemia and adrenal insufficiency accounted for far more mortality than Creutzfeldt-Jakob disease. The large number of potentially preventable deaths in patients with adrenal insufficiency and hypoglycemia underscores the importance of early intervention when infection occurs in patients with adrenal insufficiency, and aggressive treatment of panhypopituitarism.

Update: Creutzfeldt-Jakob Disease Associated With Cadaveric Dura Mater Grafts—Japan, 1979-2003

In 1997, a nongovernment surveillance group for Creutzfeldt-Jakob disease (CJD) in Japan supported financially by the Ministry of Health and Welfare (MHW) reported 43 cases of CJD associated with receipt of cadaveric dura mater grafts. In all but one case, the most probable vehicle of transmission was a single brand of dural graft (LYODURA [B. Braun Melsungen AG, Melsungen, Germany]) produced before May 1987. As of March 2003, ongoing surveillance in Japan had identified an additional 54 dura mater graft--associated cases. This report summarizes the investigation of the 97 cases, which indicated that during 1983-1987, the estimated minimum risk for CJD within 17 years of receipt of the implicated product in Japan was approximately one case per 1,250 grafts. No cases have been reported among patients who received their first dural graft after 1991; however, because of the long latency period between graft placement and symptom onset, additional cases of graft-associated CJD are likely to be reported.

Creutzfeldt-Jakob disease in United Kingdom patients treated with human pituitary growth hormone.

To investigate risk factors for Creutzfeldt-Jakob disease (CJD) in patients in the United Kingdom treated with human pituitary growth hormone (hGH). Incidence rates of CJD, based on person-year denominators, were assessed in a cohort of 1,848 patients treated with hGH in the United Kingdom from 1959 through 1985 and followed to the end of 2000. CJD developed in 38 patients. Risk of CJD was significantly increased by treatment with hGH prepared by the Wilhelmi method of extraction from human pituitaries. Risk was further raised if this treatment was administered at ages 8 to 10 years. The peak risk of CJD was estimated to occur 20 years after first exposure, and the estimated lifetime cumulative risk of CJD in Wilhelmi-treated patients was 4.5%. Size-exclusion chromatography, used in non-Wilhelmi preparation methods, may prevent CJD infection. Susceptibility to CJD may vary with age, and susceptibility may be present in only a few percent of the population.