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From: TSS (216-119-139-159.ipset19.wt.net)
Subject: Re: Natural Rubber, Latex Gloves, Condoms and TSEs aka MAD COW DISEASE
Date: November 7, 2003 at 2:25 pm PST
In Reply to: Natural Rubber, Latex Gloves, Condoms and TSEs aka MAD COW DISEASE posted by Terry S. Singeltary Sr. on November 6, 2003 at 11:12 am:
Clusters of cases
Something which is difficult to reconcile with the hypothesis that the
initial event in spCJD is a spontaneous conformational change in PrP, in
the absence of exogenous factors, is the existence of apparent clusters
of cases. There have been at least eight of these reported19,
25,
36–
39
and one for
vCJD.Libyan Jews
A countrywide search for CJD in Israel uncovered 29 cases with onset
between 1963–72.25
The
incidence in various ethnic groups varied from 0.4 to 1.9 per million,
except among Jewish immigrants from Libya, among whom the incidence was
31.3 per million. The eating of lightly cooked sheep brain, a delicacy
amongst Mediterranean Jews, was at first postulated to be responsible,
but the incidence of CJD amongst other ethnic groups with the same
dietary habits was only 1–2 cases per million of the population.
Subsequently a genetic mutation at codon 200 of the prion protein gene
(PRNP) has been discovered in this ethnic group40
and would
explain this increased rate of disease seen. The accepted view is that
this mutation predisposes an individual to spontaneous transformation of
the normal soluble prion protein into the abnormal insoluble isoform.
This hypothesis is supported by the experimental observation that
transgenic mice carrying one of the mutations associated with
Gerstmann-Straussler-Scheinker disease (GSS), a rare hereditable human
prion disease, also spontaneously develop a spongiform encephalopathy.41
However,
could this mutation have its effect by predisposing to susceptibility to
an environmental cofactor? A more recent study by Zilber42
attempted
to answer this question. They argue that a direct answer could be
obtained by studying, either the incidence of CJD among the non-Jewish
population in Libya (same environment as the Libyan immigrants to Israel
but different ethnic group) or the incidence of CJD among Israeli born
Jewish population of Libyan ancestry (different environment but same
ethnic origin). Unfortunately little epidemiological data exist about
the incidence of CJD in Libya, and most of the cases, who emigrated to
Israel in 1949 and their children, born in Israel, are still too young
for epidemiological study. Instead, they tested their environmental
hypothesis indirectly. They made the assumption that the probability of
becoming infected would increase with length of stay in Libya if there
were an environmental risk factor. They found no indication of any
difference in probability of CJD by age at immigration.The codon 200 mutation is not confined to Libyan Jews. It has been found
in families affected by familial CJD in Slovakia,43
Chile,44
America and
Japan,45
countries with very different cultures. This suggests that an
environmental cofactor would have to be ubiquitous. Also the codon 200
mutation does not automatically predict development of clinical disease.
Low degrees of disease penetrance (as low as 56% carrying the mutation44
) also
suggest that other genes or environmental factors may contribute to the
expression of disease in these mutation positive families.The English clusters
Matthews described three geographical clusters in England. The first
concerned a small rural community in the Midlands and involved three
cases. Case 1, a woman of 46, died in 1964 and 4 years later, case 2, a
woman of 34, died of CJD. Case 2 had regularly spent time at her
sister's residence 2 km from the first case. Case 1 probably met case 2,
but this remains unconfirmed. In 1971, case 3, a 54-year-old man died of
CJD. He had lived in the same village as the sister of case 2 during the
1960s. The second cluster involved five cases with onsets between 1969 and 1973
in four towns/villages in eastern England (separated by no more than 20
km), of whom at least three had lived locally since 1960. No definite
contact between cases could be established. The third cluster described a patient who died of confirmed CJD in 1965.
In 1968, a patient who lived within 250 m also died of the disease.
Although they shared the same General Practitioner, their medical
records had been destroyed, and no further information was available. In
1980, a patient who lived midway between the two previous patients and
within sight of both houses died of pathologically-proven CJD. This last
patient had been a dentist from 1950–77, and used his house as a
surgery. Although the dental records have been examined, they were
incomplete and did not include records of either of the previous two
patients.39 An Italian cluster
Eleven cases of CJD occurred in and around Parma, Italy, between 1975
and 1979. Of the 11 cases, five were farmers. Case 1 was a man aged 50
who had been born into a farming family. From 1936–9, he had lived in
Ethiopia, and from 1940 to 1946 in Libya. Since then he had been a lorry
driver. He had been otherwise fit, except for contracting malaria at age
30, and having surgery in Libya for a strangulated hernia. Case 2 was a
miller who lived in the country 10 km from Parma. Cases 3, 4 and 5 were
described as small landowners and farmers. Case 4 had a gastrectomy in
1960. Case 6 was a blacksmith, and had previous surgery for carcinoma of
the lip. No details are given for case 7. Case 8 lived permanently in
Parma but had spent two short holidays in the same village where case 3
had lived. Case 9 had been a farmer, and cases 10 and 11 had both been
housewives, although the latter had at one time been a cook.38
No
spatio-temporal analysis was attempted and no conclusions can be drawn.The Chilean cluster
A cluster in Chile, involving four cases of histologically-proven CJD in
three farmers and one housewife, occurred in 1982–3. The four lived in
small rural communities situated within a 20-km radius of the town of
Chillian. They were unrelated and did not know each other. Their life
long dietary habits are of interest, but uncertain relevance. They all
consumed uncooked sheep blood and poorly-cooked sheep blood and brain. Although the existence of clusters might be said to constitute
persuasive evidence for an exogenous environmental factor in the
aetiology of CJD, it must be remembered that some clustering may occur
by chance and that ascertainment of a first case may predispose to
ascertainment of further cases.46
Case-to-case transmission in humans: case reports and series in which
spread through everyday human contact is suggested
There are six reports in which this possible mode of transmission is
considered. The most recent is that of a couple from the USA who had
been married for 30 years.47
The husband
died at age 53. He had no relevant family history, but had had a rotator
cuff repair one year before disease onset. His wife developed symptoms
four and half years after her husband's death. She was morbidly obese
and had had a previous hysterectomy, hernia repair and cholecystectomy.
Both occasionally ate brains in the form of ‘kizka’, a type of sausage.Immunocytochemistry confirmed pathogenic prion protein deposition in
brain tissue from both husband and wife. Full sequencing of the open
reading frame of the PRNP failed to demonstrate any pathogenic
mutations. Another suspected conjugal case has recently been shown not
to be CJD. The histopathological specimens did not stain for prion
protein despite the microscopic appearance of spongiform change.48
Sporadic CJD has been described in two co-workers who shared a school
wing for 9 months.49
The first
was a 48-year-old Californian-born man of Hispanic American descent who
had had a traumatic leg amputation at age 23, but was otherwise well.
The second was a 48-year-old Chilean-born male who had a blood
transfusion 6 months before onset of symptoms, and was known to eat
lambs' brains. The first patient developed symptoms 5 months after the
last contact with his colleague and was confirmed to have spCJD 2 months
after this. The second patient developed symptoms months later and died
9 months after the last contact with his colleague.An English woman, who died of CJD, histologically confirmed at post
mortem, was known to have contact with several affected members of a
family with familial CJD and was related to them by marriage.39
She had
known one of the family, who later died of CJD and had afternoon tea
with her at family gatherings, twice a year, for 20 years, as well as
visiting in her final illness. The woman herself died 12 years later.
There is another similar case of probable CJD, reported in a Chilean
woman who died 13 years after contact with a family with familial CJD.
No details of contact are given. A third case of death from CJD in
someone related in marriage to a family with familial CJD has been
reported in France, in a Tunisian family. No details are given with
regards to family history or contact.21
What is
notable about these last three incidents of supposed infection by social
contact is that all have occurred in association with familial CJD.
Although these patients were not known to have been genetically related
to their spouses, the possibility that they came from the same gene pool
cannot be dismissed.Iatrogenic case-to-case transmission in humans: case reports and series
in which iatrogenic transmission has been proposed
It is clear that CJD can be transmitted from person to person by
injecting or implanting CJD infected instruments, tissue extracts and
organs.50–
52
Several
points relevant to a wider understanding of the epidemiology arise. (i)
The time from inoculation to disease onset is dependent on the route of
entry, the shortest incubation being approximately 16 months, in the
case of implantation of cerebral electrodes and recipients of corneal
grafts. By contrast, the longest incubation time is 30 years following
subcutaneous and intramuscular injection of growth hormone extract and
of gonadotrophins. These incubation times call into question some of the
proposed case-to-case transmission scenarios (above). (ii) The route of
transmission predicts the clinical appearance. Those infected directly
into the central nervous system develop a global dementia, whereas those
infected peripherally develop a progressive cerebellar syndrome. The
genotype of the prion gene does not explain this difference. That the
peripheral route of infection presents as a cerebellar syndrome would
support the view that vCJD is acquired peripherally by, for example,
diet, as cerebellar signs are an early prominent feature of vCJD but not
of spCJD.snip... Occupational exposure: observations from case reports and series
Case reports and series focus on two main occupational groups; health
professionals and those who are exposed to farm animals, in particular
sheep and cattle. There are at least 26 reports of sporadic CJD in health-care workers
world-wide.69–
71
These
include seven physicians, including a neurologist and head of an
intensive care unit, two neurosurgeons, an orthopaedic surgeon and a
pathologist, three dentists, a dental surgeon, nine nurses, three
nursing assistants and two histopathology technicians. Clinical details
are available for six of the cases.Berger70
describes a 58-year-old physician who died of definite CJD and who, 20
years previously, had frequently performed autopsies. Weber71
described a
case in a 55-year-old orthopaedic surgeon who died of definite CJD. The
clinical picture was suggestive of a peripheral route of infection.
Twenty years previously, he had handled both sheep and human dura mater.
The specimens of dura mater were later sent to a company that sold dura
mater preparations that subsequently transmitted CJD on six occasions.
His wife did not remember any definite injury during the time he was
working with dura mater. Schoene72
reported a
case with an atypical clinical presentation including necrotizing
cutaneous lesions with vasculitis in a 54-year-old neurosurgeon, which
was later confirmed, as CJD, by experimental transmission. There was no
definite history of exposure to any case of CJD. In a case in a
pathologist,73
he is known
to have performed over 14 000 autopsies, but it is not known if any of
them were cases of CJD. There is no information on the dentists or
nurses. One of the two histopathology technicians had been a
neuropathology technician for 22 years74
and had
come into contact with two cases of CJD, 16 and 11 years before the
onset of her disease. The other technician75
had been
exposed to animal and human brain.A wide range of occupations have been reported among cases of sporadic
CJD.6, 21
Several
case series quote an excess number of farmers and farmers' wives.24,
30
In an
Italian study,24
the
incidence was three times the expected. An analysis of epidemiological
surveillance data in the UK from 1970–9616
revealed a
statistically significant excess of cases among dairy farm workers and
their spouses and among people with greater degrees of contact with live
cattle infected with BSE. No such excess was found in abattoir workers
butchers or meat cutters.snip... Conclusions The hypothesis that spCJD is caused solely by genetic abnormalities
leading to a spontaneous mutation of prion protein, favoured in the
1980s, looks increasingly incomplete. As predicted by Matthews in 1979,
reservoirs of infection, notably zoonotic, may well exist and a perhaps
a smaller number of cases are caused through iatrogenic and
person-to-person contact. It is possible at least some cases of what has
been labelled spCJD are caused by a complex zoonotic cycle of the type
familiar to us, for example, from Hydatid Disease, Lyme Disease or
toxoplasmosis. Delineating this will unravel further the complex
epidemiology of these diseases, and may assist critically in their
prevention. http://qjmed.oupjournals.org/cgi/content/full/93/9/617
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