Cattle are susceptible to experimental infection with the Stetsonville
isolate of the transmissible mink encephalopathy (TME) agent.
Susceptibility to other TME isolates was investigated in 2 groups of calves
inoculated intracerebrally with the homogenate of mink brain containing
the Hayward or the Blackfoot isolates. A third group was inoculated with
a brain homogenate from a steer infected with the Stetsonville isolate in
its primary cattle passage and a fourth group was inoculated with a pool
of brain homogenate from the 3 cattle experimentally infected with a
sheep and goat scrapie agent in its primary cattle passage.
Clinical signs
of neurological disease appeared in each steer of every group between 15
and 25 months after inoculation. An encephalopathy characterized by
severe spongiform change and pronounced astrocytosis occurred in the
3 groups inoculated with the TME agent. The neurohistological changes
in the steers inoculated with the cattle-passaged scrapie agent were
slight and subtle. Analysis of the octapeptide repeat region of the bovine
protease-resistant protein (PrP) gene showed that variations in
incubation period, clinical signs, and neurohistological changes were
unrelated to the homozygous or heterozygous condition of 6 or 6/5
octapeptide repeats.
What Marsh found, however,
was a TSE that caused different symptoms: infected animals simply fall over,
like downer cows. "Downer Cow Disease" is a syndrome involving a far larger
number of animals than rabies, and no procedure for routine diagnosis.
Accordingly, Marsh concludes that:
But maybe the limits are off in multiparous, old age animals, especially
when receiving hormones and turning over massive amounts of calcium.
"In the months since Gajdusek's arrest and weeks since Saitoh's murder, as
no other explanations have come forward, I have wondered what could have
been the motivation, what the intimidation could be about. Certainly the
murder of Saitoh and his daughter could have been a mistake. Gajdusek could
simply have gone too far in his cultural relativism.
But there are some big money issues in the mix, such as transgenic mice,
growth hormone, drug development, and chemical toxin liability. I have
become intrigued by Saitoh's interest in the shift in the glutamate -
calcium intracellular flux and the resulting shift to amyloid accumulation
intracellularly as opposed to an intercellular messenger path.
The University of Kentucky Brown-Sanders Center for Aging has an
Alzheimer's Ezine with a summary by Saitoh and a Eulogy in the same issue."
If it is this excitotoxic process which accelerates the neurodegeneration
in Alzheimer's Disease, and also in other neurodegenerative diseases, then
I could see a link to BSE. That's the long way around to what Saitoh would
have to do with intimidation about BSE. Not the cause, but the mechanisms
by which a neurodegenerative process picks up speed, is what I think could
be the link. Gajdusek seemed to hope he had the key, from the Papua New
Guinea population, for resisting the neurodegeneration of HTLV-1.
Field advisories paint a picture for Downer Cow Syndrome of mostly
neurological symptoms for mostly Milk Fever, in mostly aged cows, around
parturition, with a largely confused and extreme set of suggestions for
more, or less calcium, and additional hormones. With plenty of glutamate in
the diet as well, a neural excitotoxic episode at parturition could put a
cow's brain down as quickly as indicated in the reports.
The similarity in pattern I was referring to is the increased calcium
turnover, increased endocrine disruption, and perhaps increased pesticide
use, which, in comparison to earlier decades, could accelerate an age
related, stress related, genetically predisposed disorder to an epidemic,
even without the addition of an infectious vehicle in feed supplements.
That is the pattern that I see as similar on U.S. and European dairy farms.
Milk fever, or parturient paresis, is a metabolic disease of dairy cows
which usually afflicts animals just preceding or immediately following
freshening. While the exact cause of this disease is not completely
understood, it is associated with the onset of lactation and failure of the
animal to maintain an adequate supply of calcium from both feed intake and
mobilization from the bone. In milk fever animals, the blood serum calcium
levels will drop from a normal g to 12 milligrams (mg)/100 milliliter (ml)
to 3 to 7 mg/100 ml, and blood phosphorus levels will drop from a normal of
6 to 8 mg/100 ml to below 5 mg/100 ml.
Several factors are known to affect the incidence of milk fever in dairy
cattle. Older animals are more susceptible than are young cows. Milk fever
occurs more frequently in Jerseys than in the other dairy breeds. High
producing animals are more prone to milk fever than are low producers. Cows
with a previous history tend to have repeat cases of milk fever.
SYMPTOMS OF MILK FEVER
FEEDING TO PREVENT MILK FEVER
Providing a ration with adequate levels of calcium and phosphorus during
the dry period is the most practical method of reducing the incidence of
milk fever. The feeding program should be adjusted so the calcium:
phosphorus ratio of the total ration is between 1.5:1 and 2.5:1. Ratios not
in this range increase the risk of milk fever.
The actual amounts of calcium and phosphorus in the diet are also
important. Minimum percentages needed in the total diet for dry cows are
0.40 percent calcium and 0.26 percent phosphorus (dry basis). Intakes of
more than 0.2 pounds of calcium per dry cow per day should be avoided.
The dairy cow's parathyroid gland secretes a hormone which draws calcium
from the cow's bones to help meet the increased demand for calcium when
milk flow begins at freshening. High levels of calcium in the dry cow diet
cause the parathyroid gland to become less active. When this mechanism of
bone calcium mobilization is not activated, the cow is forced to rely
mainly on calcium absorption from the gut which is often inadequate for
high levels of milk production. Feeding rations low in calcium for two
weeks prior to calving has been helpful in stimulating parathyroid activity
and reducing the incidence of milk fever. This practice should be used only
in problem herds. It is important that adequate levels of calcium be fed
both before and after the two week treatment period.
2. Refractory or atypical milk fever - Acute form with little or no
response to treatment. Cow may remain alert, eat and milk but cannot regain
its feet, may become a "creeping" downer cow with flexed pasterns and
posterior paralysis. Rupture of the large muscle or group of muscles in one
or both hind legs may complicate the picture. Similar fracture or
dislocation of a high joint may have occurred when the cow went down
initially or in struggling to rise. In addition to usual treatment,
administer intramuscularly 50 mg of selenium and 680 units vitamin E. As a
last resort, do not milk for 24-48 hours or inflate udder with air, and
administer 2 lbs of Epsom salts in one gallon of water to remove possible
toxins and provide ample magnesium.
3. Tremors or sub-acute - Cows easily excited, twitching, tremors. Usually
a number of cows involved, many of which are in late lactation, dry or
recently fresh. Often there is magnesium involvement.
Observations by the author indicate that cattle with broken limbs are a
small percentage of downers, and many downed cattle are weak and emaciated.
McNaughton, M.T.(1993). Not for sale, mobile slaughterers: the meat
industry's grey trade. Meat and Poultry, September,28-44
[This is correct and in line with Marsh's conclusions. Marsh speculates that
if a strain of BSE is responsible for TMEs, it may be occurring through
spontaneous mutations similar to the mutations which have been theorized as
the cause for incidence of "spontaneous CJD" in the human population at a
rate of one case per million people per year. This is, of course, theory and
conjecture.]Robinson, M. M.\ Hadlow, W. J.\ Knowles, D. P.\ Huff, T. P.\ Lacy, P.
A.\ Marsh, R. F.\ Gorham, J. R.
Journal of Comparative Pathology 1995 113 3 241-251
USDA-ARS Animal Disease Research Uni
In "Bovine Spongiform Encephalopathy: A New Disease of Cattle?" Marsh writes:
"Most believe that [BSE] is of recent origin initiated by feeding rendered
animal protein from scrapie-infected sheep to cattle. . . . This paper
explores an alternative hypothesis that BSE existed in cattle populations in
an unrecognized form for a much longer time until amplified by changes in the
rendering process that allowed cattle to cattle transmission to occur. This
viewpoint is supported by observations that transmissible mink
encephalopathy, a disease that first occurred 45 years ago, is likely caused
by feeding downer cows to mink."
In "Transmissible mink encephalopathy"
co-authored with W.J. Hadlow, Marsh
writes, "There are two incidents of [transmissible mink encephalopathy] which
occurred in Ontario in 1963 and Stetsonville (Wisconsin) in 1985, where the
mink rancher stated with a high degree of certainty that sheep had not been
fed. The Stetsonville incident is especially interesting because this rancher
was a 'dead stock' feeder who used mostly dairy cows which he collected daily
within a 50-mile radius of his mink ranch. ... If TME results from feeding
infected cattle tissues to mink, there must be an unrecognized BSE-like
infection in American cattle and in other countries where TME has been
reported. This hypothetical agent need not have biological properties
identical to those of the BSE agent because it is likely that cattle could be
infected with several 'strains' as are sheep."
In his interview in AgriView, Marsh states: "I went
to the meeting of the U.S. Livestock Association (in late 1985) and reported
that there is strong circumstantial evidence that mink encephalopathy is
caused by feeding infected dairy cows to the mink. I tried to put them on the
alert to look for such a disease in dairy cows. To try to experimentally back
this up, we inoculated two Holstein steers with the mink brain in the summer
of '85. Within 18 months, both of these cows came down with the brain lesions
seen with spongiform encephalopathy. ... The reason I feel so strongly is
that we have a unique perspective here in this laboratory because we work on
mink encephalopathy. I believe mink encephalopathy is caused by feeding
downer cows to mink. I think our evidence is very sound, and I think our
experimental studies on inoculation of cattle are sound."
Marsh considers USDA surveillance measures inadequate.
The "high risk samples" being tested for BSE in the U.S. are rabies-negative
cows, on the assumption that the staggering and drooling symptoms shown by
British Mad Cows could be misdiagnosed as rabies. "The only way to absolutely prevent
cattle-to-cattle transmission ... is to ban the feeding of ruminant animal
protein to other ruminants. ... It is unlikely that surveillance programs
will provide adequate warning since it will be almost impossible to detect
the disease in the first few animals affected, and an incubation period of
3-8 years may allow a decade of exposure before the disease is recognized."
(Source: "BSE: A New Disease in Cattle?")
Marsh sees mink outbreaks, like zoo or wildlife
outbreaks, as naturally limiting in terms of contagion, but massive
outbreaks of contained animals, where there is ample opportunity for
contagion, as limited by genetic variation, age, gender and normative
compensatory processes.
Listserve correspondence ... 22.7.96
Listserve correspondent ... 21 July 96
HERD AND ANIMAL HEALTH 1979Symptoms commonly observed in animals with milk fever include:
1. Dull eyes and action
2. Subnormal body temperature
3. Cold and drooping ears
4. Staggering gait and incoordination
5. Weakness and partial paralysis of rear legs
6. Muscle spasms
7. Inability to rise
8. Lying on the sternum with head tucked into flank
In advanced cases, the cow may lie completely outstretched on her side. If
left untreated complete paralysis and coma, followed by death, will result.
Death can occur within a few hours from the onset of milk fever. Therefore,
immediate attention is necessary. Usually, animals will respond quickly to
a slow intravenous infusion of a calcium gluconate solution. This solution
must be administered slowly; it can stop the heart if given too quickly.
Cows which do not respond to the intravenous injection may be suffering
from a complication of the condition called the "downer cow" syndrome.
Therefore, it is advisable to contact your veterinarian for diagnosis
before starting treatment.
ADAMS, R.S., & L.J. HUTCHINSON HERD AND ANIMAL HEALTH, 1987Probable Causes:
1. Decreased mass of the calcium pool prior to parturition and failure of
calcium absorption to increase fast enough after the onset of lactation.
2. Excessive bone formation due to elevated levels of gonadal hormones.
Probable Factors Involved:
1. Low calcium intake especially for dry cows
2. Low phosphorus intake
3. Excessive calcium intake (High legume intake by dry cows; Over
supplementation with calcium.)
. . .
10. Toxemia
11. Nerve or muscle damage (Injury at calving, damage from going down, or
lying on limbs for a prolonged period.)
Problem Situations:
1. When over 10-15% of the cows are afflicted on an annual basis, the
higher value applies to a herd with a lot of previous cases which may make
the cows more susceptible.
2. When a high proportion of cows in a sizeable group of freshenings is
afflicted. (ex. 5 out of 8 cows).
Forms:
1. Typical milk fever - Acute form affecting cows usually within a few days
after parturition, but sometimes in late lactation or dry period. Responds
well to treatment.Control Suggestions:
1. Make certain that standard plus mineral tests on forages are available.
2. Submit feed program request with notation of high incidence in proper
place on form.
3. Submit blood samples for metabolic profiling at the Large Animal
Diagnostic Lab, Penn State or other laboratories.
. . .
5. Use plain calcium borogluconate for the initial treatment to
keep refractory cases at a minimum.
6. Last resort - use one of the following:
a. Feed mixed with the grain or other quickly eaten feed, 100 grams (3.5
oz) of ammonium chloride per head daily beginning not less than 2 days
before and continuing at least 2 days after freshening..\
. . .
d. Administer high calcium boluses (about 75 grams of calcium
carbonate as soon as possible after calving and within 8 hours of
freshening.
Excerpts from Temple Grandin
Journal of the American Veterninary Medical Association, vol. 204, Feb. 1, 1994Nonambulatory (downer) cattle are . . . Less than 1% of the cattle handled
and transported are downers, . . . Dairy cattle are 75% of the downers
(McNaughton,1993). . . . In New Zealand, downed cattle that arrive at the
slaughter plant at night are often euthanized and sent to rendering.l. . .
. The emphasis needs to be on preventing downer animals. I estimate that
75% of all downed cattle are preventable by good management. It is likely
that 10% of the bad dairies areresponsible for 90% of the downers.
1) Last case in U.S. of TME in mink was in 1985, over ten years ago.
2) Non-ambulatory cattle still fed (raw) to U.S. mink.
3) Since 1985 outbreak, the U.S. Mink industry has realized
that sheep materials should be avoided due to scrapie.
[Actually, scrapie was considered the likely cause of TME for quite some time
PRIOR to the 1985 outbreak, which is significant primarily because it
contraindicates sheep as the source of infection.]
4) Setsonville Mink Rancher does not support the comment that
only 'downed' cows were fed prior to 1985 outbreak. States
that other "uncharacterized" animal materials were fed.
[If by "uncharacterized" you mean "not exclusively downer cows," this is
correct. However, the rancher was emphatic that sheep were NOT fed.]
5) USDA concluded 1993 report with "Given the potentially
large number of nonambulatory cows fed to mink and the
historically sporatic occurrence of spongiform
encepalopathy in mink, it was concluded that if a TSE
exists in U.S. cattle, then it is very rare or the
conditions for its transmission to mink must be highly
specific." (BSE: Implications for the U.S., 12/93,
USDA:APHIS:VS).
Marsh, R.F., 1993: Bovine spongiform encephalopathy: a new disease
of cattle? Arch. Virol. Suppl.7, 255-259.
R.F. Marsh and W.J. Hadlow, "Transmissible encephalopathy," Rev. sci. tech.
Off. int. Epiz., 1992, 11 (2), 539-550.
Joel McNair, "BSE: A Ticking Time Bomb in Downer Cows?" in Agri-View (a
weekly farm newspaper), Iola, WI, June 17, 1993.
R.F. Marsh, "Transmissible Mink Encephalopathy, Scrapie and Downer Cow
Disease: Potential Links," Proceedings of the Third International Workshop on
Bovine Spongiform Encephalopathy, Bethesda, MD, December 9-10, 1992.
R.F. Marsh, Richard A. Bessen, Scott Lehmann and G.R. Hartsough,
"Epidemiological and experimental studies on a new incident of transmissible
mink encephalopathy," Journal of General Virology (1991), 72, 589-794.
Jeremy Cherfas, "Mad Cow Disease: Uncertainty Rules," Science, Sept. 28,
1990, pp. 1492-1493.
Marsh, Richard and Wustenberg, William, "Is it safe to feed meat and bone
meal?" Hoard's Dairyman. (Sorry, I don't have the date of publication.)
R.F. Marsh and R.A. Bessen, "Epidemiological and Experimental Studies on
Transmissible Mink Encephalopathy," in Transmissible Spongiform
Encephalopathies: Impact on Animal and Human Health, Karger-Verlag,
Developments in Biological Standardization (Fred Brown, ed.), Heidelberg,
June 23-24, 1992.
Marsh, R.F., "Transmissible Mink Encephalopathy," in Prion Disease of Humans
and Animals (S.B. Prusiner, ed.), Ellis Horwood, Chichester, England, pp.
299-306.