Saturday, April 19, 2014

Estimation of the Exposure of the UK Population to the Bovine Spongiform Encephalopathy Agent through Dietary Intake During the Period 1980 to 1996

Estimation of the Exposure of the UK Population to the Bovine Spongiform Encephalopathy Agent through Dietary Intake During the Period 1980 to 1996


Chu-Chih Chen mail,


Yin-Han Wang


Published: April 15, 2014 •DOI: 10.1371/journal.pone.0094020




Although the incidence of variant Creutzfeldt-Jakob disease (vCJD) has declined to 1 since 2012 in the UK, uncertainty remains regarding possible future cases and the size of the subclinical population that may cause secondary transmission of the disease through blood transfusion. Estimating the number of individuals who were exposed to the bovine spongiform encephalopathy (BSE) infectious agent and may be susceptible to vCJD will help to clarify related public health concerns and plan strategies. In this paper, we explore this estimate by describing the probability of potential exposure due to dietary intake throughout the BSE epidemic period from 1980 to 1996 as a stochastic Poisson process. We estimate the age- and gender-specific exposure intensities in food categories of beef and beef-containing dishes, burgers and kebabs, pies, and sausages, separating the two periods of 1980–1989 and 1990–1996 due to the specified bovine offal legislation of 1989. The estimated total number of (living) exposed individuals during each period is 5,089,027 (95% confidence interval [CI] 4,514,963–6,410,317), which was obtained by multiplying the population size of different birth cohorts by the probability of exposure via dietary intake and the probability of survival until the end of 2013. The estimated number is approximately doubled, assuming a contamination rate of . Among those individuals estimated, 31,855 (95% CI 26,849–42,541) are susceptible to infection. We also examined the threshold hypothesis by fitting an extreme-value distribution to the estimated infectious dose of the exposed individuals and obtained a threshold estimate of 13.7 bID50 (95% CI 6.6–26.2 bID50) (Weibull). The results provide useful information on potential carriers of prion disease who may pose a threat of infection via blood transfusion and thus provide insight into the likelihood of new incidents of vCJD occurring in the future.






In this study, we estimated the number of exposed individuals in the UK during the BSE epidemic period 1980–1996 based on the estimated BSE-infected cattle in the last year of incubation and unreported or differentially slaughtered for consumption [15], [17], [42], the average age-specific bovine meat intake [28]–[32], and the national statistics [40]. We then estimated the numbers of subclinical carriers of abnormal prion for different genotypes at PRNP codon 129 after being exposed from the posterior susceptibility estimate with prior information obtained from the literature [13], [17]. We describe the probability of being exposed via dietary intake through the entire period by a stochastic Poisson process. This approach requires only an estimation of the mean exposure intensity of the infectious agent in bovine meat products. Thus, the assumption of the incubation period distribution and time of infection based on the observed vCJD cases, as in the back-calculation method [15]–[23] and other simulation-based approaches [24]–[27], is avoided, which significantly reduces estimation uncertainty. Furthermore, the possibility of repeated exposure [41] and the data concerning age-specific bovine meat consumption [28]–[32] are naturally taken into account in the estimation procedure. Therefore, the results provide important estimates of the prevalence of subclinical infection from mathematical modeling, in addition to the scale of exposure of the UK population to the BSE infectious agent, which cannot be derived simply from the observed vCJD cases.


Observed cases of vCJD occurring via the primary infection route of bovine meat consumption remain very small in recent years [1], as does prediction for future incidents [2]. However, uncertainty regarding the secondary infection route – blood transfusion from asymptomatic infected donors – has raised great concerns for public health and related administration strategies [3]–[7]. The estimate of approximately 32,000 exposed individuals who are potential subclinical carriers of abnormal prions provides a more concise estimate and is consistent with the results obtained from several large-scale biomarker studies on infection prevalence in the UK [5]–[13]. We obtained our estimates mainly based on the survey outcomes of Gill et al. [13], especially for the MV and VV genotypes, because previous surveys did not provide prevalence information on age and genotype [9]–[11]. Also, the infection function given by Valleron et al. [17] is for the MM genotype only. The approximately the same scale across different age groups essentially shows that both the susceptibility estimate of Valleron et al. [17] and the survey outcomes of Gill et al. [13] are reflected in the posterior estimate. A similar explanation applies to estimates for the MV and VV genotypes. These carriers are most likely subclinical to vCJD without developing into a case if they were exposed to a relatively low infectious dose. However, for the null prevalence of certain age categories and the 1990–1996 birth cohort (mainly from Valleron et al. [17]), the numbers may change substantially if positive sample(s) were detected for these categories in future surveys.


We have further justified the threshold hypothesis [4], [34]–[39] and provided an explicit threshold estimate of the infectious dose by fitting an extreme-value distribution model to the estimated number of exposed individuals and comparing that with the number of vCJD cases in each birth cohort. The existence of a threshold dose for infection has been conjectured and assessed in the literature [4], [36]–[39]. Based on the dose-response curve observed in mice, Fryer and McLean conclude that there is no evidence of the existence of such a threshold [38]. However, if this were the case in humans, the number of vCJD cases would have been far more than what has been observed to date, given our exposed individual estimate and the exponential growth rate of abnormal prions in the brain once infected [35]. The close model fitting to the observed vCJD cases justifies the threshold hypothesis. Furthermore, the threshold dose estimate of approximately 12 bID50 with an equivalent weight of 1.2 g of a BSE-infected bovine brain [39] also appears reasonable, which may alternatively be interpreted as the species barrier between bovine and human [39], [50].


The estimated number of exposed individuals is based on the estimation of the BSE-infected bovines in the last year of incubation and unreported or differentially slaughtered for consumption during the 1980–1996 period [16]. The figure could be much higher if all of the pre-clinical bovines and contaminated meat products made from beef that entered the food chain are considered when deriving the exposure intensity. Also, we exclude trigeminal ganglia, ileum, tonsil, spleen and eyes in our estimate of contaminated MRM because these parts are typically removed before meat consumption. However, bovine intestine was used for the manufacture of natural sausage casings prior to the SBO ban in 1989 [42]. Therefore, it is possible that individuals might be exposed through consumption of sausages with castings from contaminated intestine, which may substantially increase the number of exposed individuals. Because of the thinness, the infectivity in casings (if there is any) would be very low compared to that in contaminated MRM and head meat. Offals such as rectums and small intestines are also reported being exported to Germany for sausage manufacture and casings [45]. Based on these considerations, we choose to ignore the number of exposed individuals through this route. We rule out the possibility of being exposed by consumption of brain from preclinical BSE bovine directly, given that the major sources entering the food chain in the period were MRM and head meat [45] and none of the vCJD cases have reported eating bovine brain [42].


We adopt a Bayesian simulation approach to handle the great uncertainties in the proportions of MRM and head meat used in producing beef and beef-containing dishes, burgers and kebabs, pies, and sausages that might have contained BSE infectious agents during the 1980–1996 period. The results show that although the simulated 95% CIs cover a wide range, the estimated numbers are of approximately the same scale. Also, although the excess numbers of estimated individuals exposed due to ingestion of contaminated meat are very large, the amount of the exposure dose may be negligible for most people, except for the subclinical carriers who might be exposed to a certain amount of infectivity. As shown in Table 4, the numbers of possibly exposed individuals and subclinical carriers increase substantially with a CR of . However, the threshold dose estimate remains approximately the same when the mean exposure dose decreases to about a quarter of that given in the scenario of CR = 0. Therefore, the future vCJD prediction is not expected to change because of exposure uncertainty.


In summary, the estimated current numbers of exposed individuals and those who are susceptible or carry the vCJD infectious agent may provide necessary information regarding the extent of the potential public health threat in the tail of the vCJD epidemic in the UK. The number of susceptible exposed individuals is especially important for assessing the risk of secondary transmission via blood transfusion, plasma products, or contaminated surgical instruments; assessment of this risk has been inconclusive or inconsistent based on the results of several large-scale biomarker studies [5]–[14]. Furthermore, the almost exact match between the predicted and observed vCJD cases and the threshold infectious dose estimate has greatly reduced the uncertainty regarding future incidents via the primary transmission route, food intake. However, the results obtained cannot infer the likelihood of secondary transmission from the asymptotic carriers of prion disease.


see full text ;



CJD and Baby foods (the great debate 1999)


Subject: Re: Girl, 13, shows CJD symptoms.


From: "Terry S. Singeltary Sr."


Reply-To: Bovine Spongiform Encephalopathy


Date: Wed, 24 Nov 1999 11:35:44 -0600 Content-Type: text/plain Parts/Attachments: text/plain (67 lines)



Sunday, May 18, 2008





 Sunday, May 18, 2008





 Monday, May 19, 2008





“Cases of vCJD peaked in 2000, leading some scientists to speculate that the disease has an incubation period of about a decade. Yet studies of different forms of CJD suggest that the incubation time of vCJD could be much longer, indicating that many people in Britain could be carrying the infection without symptoms.”



Monday, October 14, 2013


Researchers estimate one in 2,000 people in the UK carry variant CJD proteins



However, I think that the specific confusion there is that people talk about sporadic CJD occurring at 1 per million. That is not your individual risk. Your risk is 1 per million every year. Actually, it is nearer 2 per million per year of the population will develop sporadic CJD, but your lifetime risk of developing sporadic CJD is about 1 in 30,000. So that has not really changed. When people talk about 1 per million, often they interpret that as thinking it is incredibly rare. They think they have a 1-in-a-million chance of developing this disease. You haven’t. You’ve got about a 1-in-30,000 chance of developing it.



Cases of vCJD peaked in 2000, leading some scientists to speculate that the disease has an incubation period of about a decade. Yet studies of different forms of CJD suggest that the incubation time of vCJD could be much longer, indicating that many people in Britain could be carrying the infection without symptoms.



Friday, February 14, 2014


Creutzfeldt-Jakob disease (CJD) biannual update (February 2014), with briefing on novel human prion disease National CJD Research and Surveillance Unit NCJDRSU



Wednesday, December 11, 2013


*** Detection of Infectivity in Blood of Persons with Variant and Sporadic Creutzfeldt-Jakob Disease ***



To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. ***In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.



Thursday, August 12, 2010


Seven main threats for the future linked to prions


First threat


The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.


***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.


Second threat





BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein


Variant Creutzfeldt–Jakob disease (vCJD) has been recognized to date only in individuals homozygous for methionine at PRNP codon 129. Here we show that transgenic mice expressing human PrP methionine 129, inoculated with either bovine spongiform encephalopathy (BSE) or variant CJD prions, may develop the neuropathological and molecular phenotype of vCJD, consistent with these diseases being caused by the same prion strain. Surprisingly, however, BSE transmission to these transgenic mice, in addition to producing a vCJD-like phenotype, can also result in a distinct molecular phenotype that is indistinguishable from that of sporadic CJD with PrPSc type 2. These data suggest that more than one BSE-derived prion strain might infect humans; it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure.



-------- Original Message --------


Subject: re-BSE prions propagate as either variant CJD-like or sporadic CJD


Date: Thu, 28 Nov 2002 10:23:43 -0000


From: "Asante, Emmanuel A"


To: "''"


Dear Terry,


I have been asked by Professor Collinge to respond to your request. I am a Senior Scientist in the MRC Prion Unit and the lead author on the paper. I have attached a pdf copy of the paper for your attention.


Thank you for your interest in the paper.


In respect of your first question, the simple answer is, yes. As you will find in the paper, we have managed to associate the alternate phenotype to type 2 PrPSc, the commonest sporadic CJD. It is too early to be able to claim any further sub-classification in respect of Heidenhain variant CJD or Vicky Rimmer's version. It will take further studies, which are on-going, to establish if there are sub-types to our initial finding which we are now reporting. The main point of the paper is that, as well as leading to the expected new variant CJD phenotype, BSE transmission to the 129-methionine genotype can lead to an alternate phenotype which is indistinguishable from type 2 PrPSc.


I hope reading the paper will enlighten you more on the subject. If I can be of any further assistance please to not hesitate to ask. Best wishes.


Emmanuel Asante






Dr. Emmanuel A Asante MRC Prion Unit & Neurogenetics Dept. Imperial College School of Medicine (St. Mary's) Norfolk Place, LONDON W2 1PG Tel: +44 (0)20 7594 3794 Fax: +44 (0)20 7706 3272 email: (until 9/12/02) New e-mail: (active from now)





Wednesday, October 09, 2013








Saturday, April 19, 2014


Exploring the zoonotic potential of animal prion diseases: In vivo and in vitro approaches




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