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
Abstract
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.
snip...
Discussion
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
MAD COW DISEASE BSE CJD CHILDREN VACCINES
Sunday, May 18, 2008
BSE Inquiry DRAFT FACTUAL ACCOUNTS DFAs
Monday, May 19, 2008
*** SPORADIC CJD IN FARMERS, FARMERS WIVES, FROM FARMS WITH BSE HERD AND
ABATTOIRS ***
“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
snip...
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" e.asante@ic.ac.uk
To: "'flounder@wt.net'" flounder@wt.net
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: e.asante@ic.ac.uk (until
9/12/02) New e-mail: e.asante@prion.ucl.ac.uk (active from now)
____________________________________
Wednesday, October 09, 2013
WHY THE UKBSEnvCJD ONLY THEORY IS SO POPULAR IN IT'S FALLACY, £41,078,281
in compensation REVISED
U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001
Saturday, April 19, 2014
Exploring the zoonotic potential of animal prion diseases: In vivo and in
vitro approaches
TSS
