Creutzfeldt Jakob Disease and Veterans and how they are treated at death
Hospital released vet who refused study
Widow sees priority as research, not care
Audrey Hudson (Contact)
Friday, August 22, 2008
An Army veteran seeking treatment for his sudden loss of motor skills was turned away from a veterans hospital in the Bronx, N.Y., in May 2007 after he refused to participate in a human subject experiment on Alzheimer's disease.
Joe Fitzgerald, 74, died of Creutzfeldt-Jakob disease - the human form of mad cow disease - less than a month after being dismissed without diagnosis from James J. Peters VA Medical Center.
His widow is demanding answers from the Department of Veterans Affairs (VA) as to whether human research testing is taking a priority over the health care of veterans at its hospitals.
"I want them to be held accountable for this, to prevent this from happening to someone else," Aimee Fitzgerald said. "Nothing could have saved Joe, but the care there was hateful and incompetent."
Mrs. Fitzgerald said the research study doctor, Christine Bergmann, told the family that her husband's participation in the study would enable researchers to make a quicker diagnosis of his condition.
But VA officials said Dr. Bergmann did not have the authority to offer a diagnosis.
"[The study] has very little to do with their diagnosis, and it is not consistent with what occurred," said MaryAnn Musumeci, director of the Bronx hospital.
"That's mind-boggling. That's not true," Mrs. Fitzgerald said. "Dr. Bergmann made it very clear to us that the benefit of signing up for the study would be that she would develop an individual profile of Joe that would help them to arrive at a diagnosis faster."
The VA made several officials available for comment, but not Dr. Bergmann.
VA officials and the Fitzgerald family also differ over the circumstances of Mr. Fitzgerald's discharge and whether the hospital provided care.
Miss Musumeci said Mr. Fitzgerald was admitted only for testing and clinical evaluation and that he was referred back to his physician at Castle Point VA Hospital for further care and testing.
"He was released because his work-up was complete. We did all the tests we could have done," Miss Musumeci said.
In an interview with The Washington Times, VA officials said they knew Mr. Fitzgerald was suffering from a rapidly debilitating disease.
Asked why the hospital released instead of treating the veteran, Miss Musumeci said, "He was in need of hospice care, and that is what Castle Point provides."
Castle Point VA Hospital, a part of the VA Hudson Valley Healthcare System in Dutchess County, N.Y., does not identify itself as a hospice facility and does not advertise its hospice care among its patient services.
Mrs. Fitzgerald said she was advised to keep future testing appointments with Castle Point and that the Bronx hospital never recommended hospice care or said they knew her husband's health was deteriorating.
Mr. Fitzgerald's discharge papers stated that he was in stable condition.
The Bronx VA hospital incident is the latest to raise questions about the ethics of human subject research experiments conducted at VA facilities nationwide.
A recent investigation of experiments conducted at an Arkansas veterans hospital uncovered rampant violations, including missing consent forms, secret HIV testing and failure to report more than 100 deaths of subjects participating in studies.
PHOTOGRAPH PROVIDED BY FITZGERALD FAMILY UNDIAGNOSED: Joe Fitzgerald, 74, died in June 2007, less than a month after being turned away.
Moreover, Iraq war veteran James Elliott told a congressional committee in July that he sought treatment from the VA for post-traumatic stress disorder (PTSD) and instead was persuaded to join a smoking-cessation study. While taking a smoking-cessation drug, he suffered a psychotic episode.
Mr. Elliott said the first doctor he visited at the Central Arkansas Veterans Healthcare System in Little Rock to seek treatment for PTSD "wasn't concerned about my day-to-day life. ... He wasn't concerned with my wartime experiences. He wasn't concerned about if I was going to make it home safely after the appointment."
Arthur Caplan, one of the nation's premier medical ethicists and director of the Center for Bioethics at the University of Pennsylvania, said the first obligation of any caregiver is to treat the patient.
"It is only when there is no therapy, or the therapy that is available is of doubtful utility, that someone can be recruited to research," Mr. Caplan said.
"Every researcher and every institution that does research must be sure to make an accurate diagnosis of a patient, to then offer them whatever therapy is available at the institution, to give them all their options in terms of treatment anywhere else and then and only then to pursue the possibility of trying something new in a research study," Mr. Caplan said.
"No one should ever be penalized for failing to volunteer for a study, ever," Mr. Caplan said.
"The goal of any medical encounter must be first and foremost to provide the latest and best care when care is available," Mr. Caplan said. "The chance to participate as a subject in research has to take a secondary role to receiving care as a patient."
Miss Musumeci, director of the Bronx hospital and a registered nurse, said participation in the studies is routinely offered to patients seeking care at the VA facility, including healthy patients who may be admitted to studies as control subjects.
Mary Sano, the Bronx hospital's director of research, said that "the opportunity to participate in research is widespread" and does not interfere with clinical treatment.
PHOTOGRAPH PROVIDED BY FITZGERALD FAMILY Veteran Joe Fitzgerald refused to participate in a human subject experiment on Alzheimer's disease at the James J. Peters VA Medical Center in the Bronx, N.Y.
"The research team is completely independent of the clinical team, and the clinical team has priority and determines if a person is approachable," Miss Sano said. "If they say no, the research team goes away."
Miss Musumeci said that many hospital patients welcome the opportunity to participate in studies because "they appreciate the opportunity to stay busy."
Mrs. Fitzgerald said the VA researchers wanted her husband to enroll in the Alzheimer's experiment to observe the natural and ravaging course of the disease and his eventual death.
Vera Sharav, president and founder of the Alliance for Human Research Protection, a patient-advocacy group, said the circumstances faced by the Fitzgerald family are "not unique."
"You come to a hospital in critical need and you want care, even if you are not cured, and instead they say they are going to observe the degeneration and death?"
http://washingtontimes.com/news/2008/aug/22/hospital-released-vet-who-refused-study/http://washingtontimes.com/news/2008/aug/22/hospital-released-vet-who-refused-study/?page=2http://washingtontimes.com/news/2008/aug/22/hospital-released-vet-who-refused-study/?page=3CJD STAFF SGT. JAMES ALFORD 25
http://www.blackfive.net/main/2004/10/a_dying_hero_ss.htmlhttp://www.blackfive.net/main/2004/03/ssg_james_alfor.htmlhttp://brain.hastypastry.net/forums/archive/index.php/t-3238.htmlPosted by: Sgt. B. January 25, 2005 at 10:34 AM
Friday, 11/03/06
Soldier's battle with disease continues to surprise family
Brain-wasting rarity ended career in 2003
By LEON ALLIGOOD
Staff Writer
James Alford turned 28 on Thursday under the watchful gaze of his parents, John and Gail.
No one expected that day would come, most certainly not the cadre of doctors who have examined him in the past three and a half years.
The physicians, every one of them, said he would die — and sooner rather than later.
In summer 2003, when Alford was 24 and a Green Beret based at Fort Campbell, he was diagnosed with the human variant of mad-cow disease, Creutzfeldt-Jakob disease.
The rare brain disorder produces severe behavior changes, failing memory, a loss of mobility and eventually leads to a coma and death.
But the decorated soldier, a veteran of fighting in Afghanistan and Iraq who was initially stripped of his Green Beret because of his illness, is still among the living, defying all expectations.
"I honestly don't know why he's still with us," Gail Alford said via phone from her family's home in Karnack, Texas. Jamie, as the parents call their son, has lived with them since he was diagnosed.
"In June of 2003 they told us he wouldn't see his 25th birthday; then in August they were absolutely certain he wouldn't be here at Christmas.
"Here we are at his fourth birthday since he was diagnosed. I'm not ready to say anything about having a fourth Christmas with him, but we're headed in that direction."
Alford was assigned to the U.S. Army's 5th Special Forces Group. His illness was chronicled in a front-page story in The Tennessean in November 2003.
According to the Creutzfeldt-Jakob Foundation, the incidence of CJD in the United States is one case per 9,000 adults age 55 and older; it occurs much less frequently in people 30 and younger.
The disease can be contracted by contamination during surgery or inherited at birth, but 85 percent of cases are of the "sporadic" variety, meaning the cause for the disease is unknown, the CJD Foundation reported. That's the case in Alford's situation.
Because he was so well traveled as a Special Forces soldier, his family said he may have eaten contaminated beef in England, where more than 125 persons have contracted the disease after eating beef from cows that were fed products rendered from scrapie-infected sheep. Scrapie is a form of a brain disorder found in sheep.
The soldier also told his family that in 2001 he ate a sheep's brain while stationed in Oman. However, while the disease is linked to cattle that have eaten sheep-byproducts, there has been no evidence of direct transfer from sheep to humans, according to the CJD Foundation.
Alford was a stellar soldier until 2003 when his unit went to Iraq. Less than a year after earning a Bronze Star in Afghanistan, the staff sergeant became a foul-up of his unit.
His inability to stay on task prompted his commander to order him to keep a pad and pen handy on which to write down orders. He was demoted in rank and in April 2003 was sent home from Iraq to be drummed out of the Special Forces.
After Alford was diagnosed with the fatal disease the Army made amends, restoring the soldier's rank and making it retroactive to the day of his demotion. But his soldiering days were over.
Today, Alford sleeps on a hospital bed at his parents' home. A nurse helps his mother and father care for their son.
"He's still conscious. He will still look at his dad and I and the nurse. He'll track us with his eyes. That's the most response we get from him," Gail Alford said.
Music or movies are playing almost all the time in his room. The doctors tell the family "it's good stimulation." He receives nourishment through a feeding tube and is given supplemental oxygen to help him breathe.
"He's got everybody fooled, and we're certainly glad," said John Alford.
"You just don't really know why he's hung on as long as he has. If I had to sum it up, I would guess it would be he's hanging on for mine and Gail's sake. I don't know. There's no medical reason at all for this."
The father, a retired Army man himself, said the staff sergeant's military buddies call and visit often.
"They come by when they can, if they get leave, or if they're in the area. Sometimes they have dinner. Sometimes they just sit and visit with Jamie. They haven't deserted him," John Alford said.
"We just take it day by day, doing the best we can with what we've got," added Gail Alford. •
http://www.fairviewobserver.com/apps/pbcs.dll/article?AID=/20061103/COUNTY05/611030402/1321/MTCN06http://www.blackfive.net/main/2004/10/a_dying_hero_ss.htmlSubject: O'Reilly FACTOR HELPING SPECIAL FORCES WAR HERO DYING HIDEOS DEATH AFTER BEING DEMOTED CJD (AKA MAD COW DISEASE)
Date: December 6, 2003 at 6:31 pm PST
-------- Original Message --------
Subject: [Fwd: [CJDVoice] Re: SPECIAL FORCES WAR HERO DYING HIDEOS DEATH AFTER BEING DEMOTED (AKA MAD COW DISEASE)]
Date: Sat, 06 Dec 2003 16:05:48 -0600
From: "Terry S. Singeltary Sr."
Friday, December 05, 2003
This is a partial transcript from The O'Reilly Factor, December 4, 2003.
Watch The O'Reilly Factor weeknights at 8 p.m. and 11 p.m. ET and listen
to the Radio Factor!
BILL O'REILLY, HOST: In the Personal Story segment tonight, the tragic saga of 25-year-old Green Beret James Alford.
In 2001, the staff sergeant was assigned duty in the country of Oman, and, while there, he ate a traditional dinner of goat brains. About a year later, Alford's behavior began to get bizarre, and he was demoted in rank. Despite that, the Army deployed him to Iraq in January 2003, but his health continued to decline, as did his behavior. Finally, in April 2003, he was sent to Fort Campbell in Kentucky to be court-martialed and kicked out of the Special Forces. But, while there, doctors made a startling discovery. James Alford had mad cow disease, which causes progressive dementia. His brain was literally being eaten away.
The Army then declared Alford medically incompetent and began processing his retirement. They also reinstated his rank.
But his family says there are still problems. What a mess. Joining us now from Dallas are the parents of Staff Sergeant Alford, retired Sergeant Major John Alford and his wife, Gail. Also, from Boston, Fox News Military Analyst Colonel David Hunt. Sergeant Alford, first, we want to ask you about James. How's he doing right now?
SGT. MAJ. JOHN ALFORD, FATHER OF GREEN BERET: He's about the same that he has been lately. He's not doing any better. He's sleeping quite a bit more. Sometimes he sleeps by day and stays awake all night, but we've just adjusted to that.
O'REILLY: All right. Can you carry on a conversation with him? Is he lucid?
JOHN ALFORD: No, sir. We talk to him. We talk to him just as if he was coherent, and I think he hears us, but he cannot answer us. He cannot communicate in any way.
O'REILLY: All right. So he's in like a vegetative state here, that you have to care for him, feed him, and all of that?
JOHN ALFORD: Yes, sir. He's fed through a tube, but he does take some foods orally, baby foods, and some foods that we process ourselves.
O'REILLY: All right. So he's in bed all the time.
JOHN ALFORD: Yes, sir.
O'REILLY: You have to take care of him, make sure he's alive. Now this is not going to change, right? You can't turn this around, correct?
JOHN ALFORD: No, sir. As far as we know, we cannot.
O'REILLY: All right. Now, Mrs. Alford, what do you want to see happen here?
GAIL ALFORD, MOTHER OF GREEN BERET: I want my son to remain on active duty until his death, and I want his durable power of attorney that he initiated for me prior to being deployed to be honored by the Army.
O'REILLY: What does that mean, though, in concrete terms for you?
GAIL ALFORD: In concrete terms, I want them to fully reinstate his pay and to honor it completely.
O'REILLY: All right, but his rank has been reinstated. I assume he's gotten the back pay that he...
JOHN ALFORD: No.
O'REILLY: No? He hasn't gotten the back pay yet?
GAIL ALFORD: No.
JOHN ALFORD: No. They took him back to his E-6 -- his staff sergeant pay grade, but they're still processing and working on his back pay, and we assume it will be forthcoming.
O'REILLY: Yes, the Army tells us it will be.
JOHN ALFORD: Yes.
O'REILLY: So I wouldn't worry about the financial end of it.
JOHN ALFORD: Yes, but what we're concerned with now -- his pay has been frozen, and it was released temporarily pending my wife being appointed guardian, and then they're only going to pay 80 percent of his pay.
O'REILLY: All right.
JOHN ALFORD: He's an American soldier and he's entitled to it.
O'REILLY: You're right. Got it. You think that he was wounded in the line of duty because, you know, you eat this stuff over in a country where you're posted, so he should get full pay until he's deceased?
JOHN ALFORD: Yes, sir.
O'REILLY: All right.
JOHN ALFORD: And medical benefits.
O'REILLY: And medical benefits. Well, we assume that the V.A. is taking care of him, are they not?
JOHN ALFORD: Well, sir, they would. We want our son to be provided the best medical care available, and we would like to see that either in a military medical facility, not a V.A. hospital, but a military medical facility or a commercial hospital. If he is retired as they're trying to do, he can be treated in a civilian facility, but they will only pay 80 percent of it.
O'REILLY: Eighty percent of it, all right.
JOHN ALFORD: Yes, sir.
O'REILLY: Now, Colonel Hunt, you're heard this terrible story. I mean everybody watching it now -- this poor guy goes over there, and, through no fault of his own, I mean, what is he, 27, 28 years old.
COL. DAVID HUNT (RET.), U.S. ARMY: Twenty-five.
O'REILLY: Well, I think that was when he was -- OK.
JOHN ALFORD: No, sir. He celebrated his 25th birthday three Sundays ago.
O'REILLY: All right. So he's 25 -- geez, just 25 years old. Amazing. So, anyway, he's going to die. And, you know, what do you do? What should the Army do here?
HUNT: This the worst case of abuse of a soldier I've seen in 30 years.
O'REILLY: Really?
HUNT: I have never seen, heard, read, dreamed that the United States Army, that this Special Forces group that I'm a proud member of, a historic unit, would treat another human being, a soldier, a Special Forces soldier like this. The last thing this great kid remembers is the Army called him a liar.
What they've got to do is get the chief of staff of the Army -- this has got to happen fast. He doesn't have a lot of time. His parents -- his mother -- his father is a 34-year veteran of the military, his mother is a nine-year veteran in the military, and his wife is a three-year veteran.
The power of attorney is so stupid, they deployed over in Iraq together, so they had to have a power of attorney with somebody else.
The Army has made a mistake every step of the way. This guy made staff sergeant in five years. It takes normally seven to 10 years.
He got sick, by the way, not at Fort Campbell, but trying out for Delta Force. Besides SEAL Team 6, the Army's Delta Force, the premier counter-terrorism unit in the world. That's the kind of guy he is, four-time volunteer, Bronze Star medal-winner in Afghanistan, goes to Iraq, and they treat him like dirt.
And they're still doing it to his family. This is the biggest outrage I have ever heard of in 30 years.
O'REILLY: So we need to contact the head of the Army right now, right?
HUNT: They ought to get this fixed. There's a great guy who's a deputy commander at 5th Special Forces group, who heard about this in the paper.
This wouldn't have been done without Fox News and The O'Reilly Factor doing this and some local papers writing about it. And they need rank to push this fast.
It's got to be fixed immediately, it will take about a four-star general, pick up the phone, talk to this man's family, 34-year veteran father, a sergeant major, and a nine-year veteran mother and fix it now.
O'REILLY: All right. Well, we can make that happen. I think we can make that happen. So he should get full back pay right away, and he should get into the best medical facility the government can provide and they should pay 100 percent of it, right?
HUNT: Absolutely. Absolutely. And they can do that, exceptions, it doesn't matter, take care of this guy now.
O'REILLY: All right. And that would be OK with you folks if we get your full pay coming in and then the best medical facility the government can provide a hundred-percent paid?
JOHN ALFORD: Sir, that's what we're asking for, that and respect and honor the power of attorney, not just for my son, but if he's having this problem, we're having this problem -- we're losing people every day in Iraq, and there's got to be a lot of other families having the same trouble and don't know what to do about it.
O'REILLY: All right. Well, let's work on this first, and then we'll get to the other problem.
All right. Well, we're going to work with Colonel Hunt, and we're going to try to get a definitive word by Monday. You know, we'll give the Army a little time to cut through the bureaucracy, but I think we'll work it out. I really do, and if we don't...
HUNT: I do, too.
O'REILLY: Yes. If we don't it ain't going to be good. All right. Mr. and Mrs. Alford, we want you to have a very merry Christmas, and we're very sad that this happened to your son.
HUNT: God bless the family.
O'REILLY: And we will try to do everything we can for you. And, Colonel, as always, we appreciate it.
And we'll have an update on Monday about this situation
http://www.foxnews.com/story/0,2933,105003,00.html-------- Original Message --------
Subject: [CJDVoice] Re: SPECIAL FORCES WAR HERO DYING HIDEOS DEATH AFTER BEING DEMOTED (AKA MAD COW DISEASE)
Date: Fri, 05 Dec 2003 14:21:34 -0600
From: "Terry S. Singeltary Sr."
Reply-To: cjdvoice@YAHOOGROUPS.COM
To: OREILLY@FOXNEWS.COM
CC: CJDVOICE
References: <3fc22f84.6040305@wt.net>
Hello again Bill,
I heard you ran a story last night on our war hero and CJD and what the Gov. did to him. I want to thank you, We all want to thank you. I am sorry to say I missed the show. Is there any transcript of the show we can locate on the www (url)? if so I would very much like to read it. again, many many thanks. BUT, there are many more out there that the Gov. is refusing to acknowledge. I only hope that you continue to pursuit and keep a close eye on this issue of human/animal TSEs aka mad cow disease in the USA, _especially_ the sporadic CJDs and the continued denial and flat refusal to rapid test USA cattle for TSEs and to refuse to make CJD reportable Nationally ASAP...
again, many thanks,
I am sincerely,
Terry S. Singeltary Sr.
Terry S. Singeltary Sr. wrote:
------ Original Message --------
Subject: SPECIAL FORCES WAR HERO DYING HIDEOS DEATH AFTER BEING DEMOTED (AKA MAD COW DISEASE)
Date: Mon, 24 Nov 2003 10:19:16 -0600
From: "Terry S. Singeltary Sr."
To: OREILLY@FOXNEWS.COM
Hey Bill, maybe you can help this family out. After this soldier being a special forces war hero, and then left to die a most hideous death, this is not right. Another thing, this is a 25 year old dying from sporadic CJD. please do not let the Government confuse you with the myth that sporadic CJD just falls from the sky with no route and source. This is total crap......please help this family;
Family of dying GI battles bureaucracy
Associated Press
KARNACK - By the time he shipped out for the war in Iraq in January, Special Forces Sgt. James Alford was a wreck of a soldier.
For five months, he had been doing odd things. He disappeared from Fort Campbell, Ky., for several days. He lost equipment and lied to superiors. In December, he was demoted from staff sergeant to sergeant.
In the Kuwaiti desert, he came apart. The hotshot Green Beret, who a year earlier ran circles around his team members and earned a Bronze Star in Afghanistan, was ordered to carry a notepad to remember orders. By March, he was being cited for dereliction of duty, larceny and lying to superiors. He couldn't even keep up with his gas mask.
Finally, in April, his commanders had had enough. They ordered him to return to Fort Campbell to be court-martialed and kicked out of the Special Forces.
"Your conduct is inconsistent with the integrity and professionalism required by a Special Forces soldier," Lt. Col. Christopher Conner of the 2nd Battalion, 5th Special Forces Group Headquarters in Kuwait wrote April 10.
Confused and disgraced, the soldier moved back into his off-base home, where he ate canned meat and anchovies, unaware of the day, the month or the year.
Sensing something was wrong, a neighbor called Alford's parents. They drove 600 miles from East Texas to find a son who had lost 30 pounds and could no longer drink from a glass, use a telephone, button his shirt or say "Amber," the name of his soldier wife, who was still stationed in the Middle East.
They rushed him to an emergency room. A month and several hospitals later, Alford's family learned that he was dying of a disease eating away his brain. He had Creutzfeldt-Jakob disease, an extremely rare and fatal degenerative brain disorder akin to mad cow disease that causes rapid, progressive dementia.
Now, as the 25-year-old soldier wastes away in his boyhood home, his parents and his wife are struggling to understand how the military could have misdiagnosed Alford's erratic, forgetful behavior as nothing more than the symptoms of a sloppy, incompetent soldier.
"He had to hold his hands to keep them from shaking, but they saw nothing wrong with my child," his mother, Gail Alford, a nine-year Army veteran, said recently from her home in Karnack, a rural community near Marshall.
Alford's parents say Special Forces staff members told them that a doctor in Kuwait had found nothing wrong with him and that a psychiatrist there had said Alford was "faking it."
Army officials have acknowledged that the 5th Special Forces Group erred and, more than eight months after Alford's demotion, they reinstated his staff sergeant rank.
But the dying soldier's family members want more. They want a public apology for the ridicule and disgrace that they say filled Alford's final days of service.
"They called him stupid, told him he was lazy, he was a liar, that he wasn't any good, that he was a faker," his mother said, recalling what little her son could tell her about his time in Kuwait. "I want them shamed the way they shamed my son."
And they want his pay restored and his medical benefits maintained. The Army declared Alford medically incompetent, placed him on retirement status and froze his pay this month until his parents can prove in court that they are his legal guardians. His mother said she was given power of attorney long ago.
Special Forces blamed
Alford's father, retired Army Command Sgt. Maj. John Alford, who served 34 years, said that Army doctors have been caring and professional and that commanders stationed his son's wife, Spc. Amber Alford, in Texas near her husband.
He mainly faults the Special Forces.
"I think they did everything they could to break him, mentally and physically," he said.
A Special Forces spokesman did not respond to phone messages and an e-mail request for an interview with The Associated Press.
In a July 30 letter responding to an inquiry by U.S. Rep. Max Sandlin, D-Marshall, Army Lt. Col. Johan Haraldsen wrote that the Special Forces group to which Alford belonged expressed "its deepest concerns" to the soldier and his family.
"All actions taken ... involving Sergeant Alford were appropriate based on the best information available at that time," Haraldsen wrote.
Alford himself may have tried to conceal his symptoms, said Dr. Steve Williams, a clinical fellow in the division of infectious diseases at Vanderbilt University Medical Center in Nashville, Tenn.
"He was capable of masking the symptoms because he was resourceful and he was a smart guy," said Williams, who diagnosed Alford with Creutzfeldt-Jakob. "I'd ask him what floor he was on, and I could catch him looking outside and counting the number of windows."
Doctors believe that Alford has the classic form of the disease, which develops spontaneously. It affects one in 100 million people under 30, according to the Centers for Disease Control and Prevention.
Col. David Dooley, an infectious-disease doctor at Brooke Army Medical Center in San Antonio, said Special Forces staff members shouldn't take the blame for missing Alford's illness. A delayed diagnosis is "typical and classic"; the average lag time for the disease is five to seven months, he said.
"If I'm going to hold anything against them, they might have come around a little faster when a medical problem was recognized," Dooley said. "The Special Forces group was fairly inert to the face of data that we medics were showing them."
Alford's parents believe that he has the variant form of the disease, caused by eating brains or nervous-system tissue from an infected cow. They worry that he may have gotten it from eating sheep brains locals served to soldiers as an honor in Oman two years ago.
But there is no evidence that people can get the disease from sheep.
Doctors also note that Alford didn't have the outbursts of anger and depression usually associated with the variant form and that the fast progression of his illness is more consistent with the classic form.
Losing everything
Alford was the youngest man in the 5th Special Forces Group, and his wife says some of his team members resented his promotion. At least one said Alford seemed a bit immature and made a few bad decisions when he first joined, but military records show that he earned decorations.
He was awarded the Bronze Star in May 2002 for "gallant conduct" in leading reconnaissance patrols in the southern Afghan city of Kandahar and helping capture Iranian terrorism suspects.
Staff Sgt. Miguel Fabbiani, a friend of Alford's and a member of the same team based at Fort Campbell, said Alford's symptoms escalated during wartime when he was working with a new group that didn't know him as well.
Alford's parents said they didn't see him enough to detect a problem. His wife was stationed near him for a while in Kuwait, but she chalked up his odd behavior to stress.
Alford's father said the actions of his son's superiors broke the spirit of a young man who had wanted to become a soldier since he was 4.
He now lies in pastel sheets next to a wall painting of John Wayne. Wearing a Houston Texans T-shirt that hangs like a hospital gown, he stares absently into a television that glows 24 hours, his hands gripping stuffed animals to keep them from clenching shut.
"He knows his name, sometimes," says his wife, a tiny woman in sneakers who helps tend to her husband as she ponders a life alone. "Sometimes I'll go up to him, wink at him and make kissy faces, and he laughs."
Her eyes well up as she remembers the handsome, arrogant boy she met as a teen-ager at a barrel-racing contest in Texas.
As his brain deteriorates, his organs will fail.
"He will go blind, he will go deaf, he will lose everything," his father said.
He stopped walking more than a month ago, mumbles when he tries to speak, is fed intravenously and takes medicine for insomnia, pain and tremors. Doctors have told the family that he probably won't live to see Christmas.
The Army has said that the issues over Alford's pay could be resolved within weeks, but the family members are skeptical. They aren't sure how they will pay his bills and maintain his 24-hour care without his salary.
"It's very sad when the people who are putting their life on the line for this country should be treated like this," Alford's father said. "This has been a bureaucratic nightmare. We've got enough to deal with on a daily basis, caring after our son and dealing with our pain and weariness and our suffering to have to fight the U.S. Army."
They fought for four months before his rank was reinstated in September.
John Alford knew his son might not live long enough to get the good news, so he had already told him a "white lie" that he had been vindicated.
"It was very important to him because he kept saying, 'I didn't do anything wrong, Daddy.' "
http://sierratimes.com/03/11/23/ap_gi_battle.htm12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY
snip...
A The Present Position with respect to Scrapie A] The Problem
Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries.
The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep.
It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible.
Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"
Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.
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76/10.12/4.6
http://www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine
Spongiform Encephalopathy (BSE)
http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf[Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirement for the Disposition of Non-Ambulatory Disabled Cattle
03-025IFA
03-025IFA-2
http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdfTHE SEVEN SCIENTIST REPORT ***
http://www.fda.gov/ohrms/dockets/dockets/02n0273/02n-0273-EC244-Attach-1.pdfTerry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
http://www.blackfive.net/main/2004/10/a_dying_hero_ss.htmlhttp://www.blackfive.net/main/2004/03/ssg_james_alfor.htmlhttp://brain.hastypastry.net/forums/archive/index.php/t-3238.htmlHis commander wrote on April 10 that he would initiate action to revoke Staff Sgt. Alford's Special Forces designation.
Critical comments
"Your conduct is inconsistent with the integrity and professionalism required by a Special Forces soldier," wrote Lt. Col. Christopher E. Conner of the 2nd Battalion, 5th Special Forces Group Headquarters in Kuwait. "I do not believe you are suitable for further Special Forces duty." The Alfords were later told that Staff Sgt. Alford had been seen by a doctor in Kuwait, who reportedly said nothing was wrong with him. A psychiatrist in Kuwait reportedly said that he was "faking it."
"Jamie was a good soldier," said his mother, who has left her job to care for her son. "When all this started happening, anyone should have known he was sick."
The cause of Staff Sgt. Alford's disease, diagnosed as "sporadic" CJD, is unknown.
http://www.valdezlink.com/pages/alford.htmBovine Spongiform Encephalopathy and variant Creutzfeldt-Jakob Disease Questions and Answers 9 March 2001
5. Of the reported vCJD fatalities, were any of them U.S. Service Members? No. There are no reported cases of vCJD in the US, including service members and their families wherever they are stationed.
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3. What was the source of beef consumed by military personnel stationed in Europe? For service members stationed in Europe prior to 1996, beef sources were: a) Dining Facilities: U.S. beef has been served in all military dining facilities since before 1980. b) Operational rations: In MRE’s, T rations, UGRs, field feeding and all other operational rations only US beef was used. c) Commissaries: Prior to 1990, commissaries in Europe procured approximately 35% of the beef from the UK and 65% from other European countries. Since 1990, commissaries in Germany, Netherlands, Belgium and the UK (excluding Edsal commissary in Scotland) received only US beef. Commissaries in Italy, Spain, Greece, and Turkey (and the Edsal commissary in Scotland) continued getting the majority of their beef from the UK until 1996 when all procurement of beef from the UK ended. d) Army and Air Force Exchange Service (AAFES): European beef was used up until 2000. Approximately 20% of this was from the UK until March 1996. In March 1996, DoD stopped procurement and sale of beef from the UK and other countries with confirmed cases of BSE. Since March 2000, DoD stopped procurement and sale of ruminant (e.g., cattle, sheep, and goat) meat and meat products of European origin. The procurement of these meat items is now required to be from US and non-European approved sources. 4. What was the source of beef consumed by military personnel stationed overseas in areas other than Europe? The possibility exists for UK or other European beef to have been consumed in areas outside of Europe. For example, it may have been purchased by naval ships resupplying in the Mediterranean, or provided to service members in SW Asia following Operations Desert Shield/Desert Storm. From 1990 to March 1996, military dining facilities in Southwest Asia utilized beef originating from several countries, including the UK. DoD policy excluded UK beef after March 1996 and European beef after March 2000.
http://chppm-www.apgea.army.mil/MadCowDisease/QA.pdfTHE QUESTION SHOULD HAVE BEEN, Of the reported CJD fatalities, were any of them U.S. Service Members? FOR THE FOLLOWING REASONS ; "the biochemical signature of PrPres in the BASE-inoculated animal was found to have a higher proteinase K sensitivity of the octa-repeat region. We found the same biochemical signature in three of four human patients with sporadic CJD and an MM type 2 PrP genotype who lived in the same country as the infected bovine."
http://bse-atypical.blogspot.com/2008/08/atypical-bse-base-transmitted-from.htmlGuidance for Industry Questions and Answers on FDA Guidance Entitled "Revised Preventive Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob (CJD) Disease and Variant Creutzfeldt-Jakob Disease (vCJD) by Blood and Blood Products"
Updated January 22, 2004
http://www.fda.gov/Cber/gdlns/cjdvcjdq&a.htmEmerging and Re-emerging Infectious Diseases CME
Disclosures
John G. Bartlett, MD
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Variant Creutzfeldt-Jakob disease
Variant Creutzfeldt-Jakob disease (vCJD) was included in the literature review by John Bartlett, citing evidence of transmission by blood transfusion of the prion protein (PrP) in England.[4,5] This case strongly supports the hypothesis that blood and blood components, presumably leukocytes, can transmit this universally fatal disease. The initial report was followed by a second case, which was quite different in several ways.[6] This patient was discovered because a look-back suggested a possible acquisition of PrP from a blood donation of a patient who subsequently died of vCJD. However, the recipient was heterozygote at codon 129 of the PrP gene and died of a ruptured aneurysm with no clinical evidence of vCJD. The PrP was detected in a lymph node and the spleen, indicating that the pool of infected patients may not be restricted to those who are homozygote at codon 129. (All cases of vCJD to date have been homozygote with M/M at codon 129 of the prion gene).
US Food and Drug Administration looks at transfusion practices. To bring this issue up-to-date, the relevance of these data for transfusion practices was reviewed in US Food and Drug Administration (FDA) hearings in October 2004. The network of look-backs (ie, patients warned of possible transfusion-associated vCJD) has now been expanded to about 6000 persons in England. Also, there is concern about a possible resurgence of long-incubation cases in patients who are heterozygote at codon 129. Against this background, Gary Roselle reported the results of an intensive look-back of potential transmission of CJD in the Veterans Affairs (VA system).[7] The cases involved a donor who had donated over 10 gal prior to developing CJD (not vCJD). These donations were divided into over 200 lots and given to thousands of recipients. A decision was made to not conduct a look-back because there was no evidence that CJD could be transmitted by blood or blood products, but the VA made a different decision. There were 1615 recipients of blood and blood products from this single donor who were patients at 68 VA sites. Look-backs in 429 persons who are still living failed to show any evidence of transmitted CJD. Discussion with the presenter indicated minimal difficulties encountered with the notification of patients of this possible complication of their prior transfusions.
http://www.medscape.com/viewarticle/499461From: Terry S. Singeltary Sr.
To: FREAS@CBER.FDA.GOV
Cc: william.freas@fda.hhs.gov ; rosanna.harvey@fda.hhs.gov
Sent: Friday, December 01, 2006 2:59 PM
Subject: Re: TSE advisory committee for the meeting December 15, 2006 [TSS SUBMISSION
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ONE FINAL COMMENT PLEASE, (i know this is long Dr. Freas but please bear with me)
THE USA is in a most unique situation, one of unknown circumstances with human and animal TSE. THE USA has the most documented TSE in different species to date, with substrains growing in those species (BSE/BASE in cattle and CWD in deer and elk, there is evidence here with different strains), and we know that sheep scrapie has over 20 strains of the typical scrapie with atypical scrapie documented and also BSE is very likely to have passed to sheep. all of which have been rendered and fed back to animals for human and animal consumption, a frightening scenario. WE do not know the outcome, and to play with human life around the globe with the very likely TSE tainted blood from the USA, in my opinion is like playing Russian roulette, of long duration, with potential long and enduring consequences, of which once done, cannot be undone.
These are the facts as i have come to know through daily and extensive research of TSE over 9 years, since 12/14/97. I do not pretend to have all the answers, but i do know to continue to believe in the ukbsenvcjd only theory of transmission to humans of only this one strain from only this one TSE from only this one part of the globe, will only lead to further failures, and needless exposure to humans from all strains of TSE, and possibly many more needless deaths from TSE via a multitude of proven routes and sources via many studies with primates and rodents and other species. ...
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
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http://www.regulations.gov/fdmspublic/ContentViewer?objectId=09000064801f3413&disposition=attachment&contentType=msw84th case of variant CJD infection associated with blood transfusion 18 January 2007
A new case of variant-Creutzfeldt-Jakob disease (vCJD ) associated with a blood transfusion has recently been diagnosed.
This latest patient has been diagnosed with vCJD about nine years after receiving a blood transfusion from a donor who later went on to develop vCJD. A transfusion from the same blood donor was also associated with one of the previously identified cases. The patient is still alive and is under specialist care.
This fourth case of vCJD infection associated with blood transfusion increases the concern about the risk of vCJD transmission between humans via blood transfusion. All four cases relate to the transfusion of blood components: no cases have been reported relating to treatment with plasma products.
The patient is one of a small number (less than 30) of living individuals who are known to have received a blood transfusion in the UK from a donor who later developed vCJD. All these individuals have previously been informed of their potential exposure to vCJD and asked to take certain precautions to reduce the chance of passing on vCJD to other people via healthcare procedures, such as surgery.
The Health Protection Agency has been in contact with doctors caring for the other patients who have been exposed to blood transfusions from donors who later developed vCJD. This is to ensure that they are informed of this new development and provide access to the latest information and specialist advice about their risk due to blood transfusion.
Professor Peter Borriello, Director of the HPA's Centre for Infections said, "This new case of vCJD infection increases our concern about the risk to the small group of people who had blood transfusions from donors who unknowingly at the time of donation must have had vCJD infection. However, this new case does not change our understanding of the risk for other people in any specific way. It does however reinforce the importance of the precautions that have already been taken to reduce the risk of transmission of vCJD infection by blood."
Dr Angela Robinson, Medical Director of NHS Blood and Transplant said, "Blood transfusions are often given to save or prolong the life of patients who are very ill and the benefit of receiving a transfusion when needed must always be balanced against any possible risk. Nonetheless, our primary concern is the safety of our patients through maintaining the quality of blood used for medical treatment. Since 1997, the NBS has introduced a range of precautionary measures against the risk of vCJD."
vCJD is a rare disease, and less than 2% of the vCJD cases reported to date in the UK have been associated with blood transfusion.
Notes to Editors:
To date, there have been 66 people identified in the UK who have received vCJD implicated blood transfusions. The transfusions received by these 66 individuals were donated by eighteen different donors who were diagnosed with vCJD after their blood donation. Of these 66 people, 40 have died of illnesses other than vCJD, including one patient who was found to have evidence of vCJD in parts of their body after their death. Including the new (4th) case, 3 of these people who have received vCJD implicated blood transfusions have developed symptoms of vCJD. There are 23 people who have received vCJD implicated blood transfusions who are alive and have not been diagnosed with vCJD.
The identification of cases of variant-CJD associated with blood transfusion has depended on the Transfusion Medicine Epidemiology Review, a collaborative study between the National Blood Services, the National CJD Surveillance Unit and the Office of National Statistics. For further information about this study see Hewitt et al Creutzfeldt-Jakob disease and blood transfusion: results of the UK Transfusion Epidemiology Review study. Vox Sanguinis 2006 91:221-230.
'Blood Transfusion' means transfusion with labile blood components (e.g. red cells, platelets, fresh frozen plasma). This latest case (and the previous three referred to) relate to transfusion of blood components and not treatment with plasma products (i.e. products that are manufactured from plasma). To date, no case of vCJD has been associated with treatment with plasma-products (e.g. clotting factors used to treat individuals with bleeding disorders such as haemophilia).
This fourth case has been classified by the National CJD Surveillance Unit ( www.cjd.ed.ac.uk ) as a 'probable' case of vCJD. Of the 158 vCJD cases that have died (data to 5 Jan 2007), all 112 that have undergone post-mortem (46 have not) have been 'confirmed' by neuropathological examination (examination of brain tissue).
The first clinical case of vCJD associated with transfusion was identified in December 2003. A case of vCJD 'infection' associated with transfusion was identified a few months later. The patient had no symptoms but evidence of infection (abnormal prion proteins) was identified in a post mortem investigation. The individual died from causes unrelated to vCJD.
Following the first case of vCJD associated with a blood transfusion in 2003, the Department of Health asked all recipients of blood transfusions not to donate blood as a precautionary measure to protect the blood supply from vCJD.
Patients who are informed that they are considered to be 'at risk' of vCJD for public health purposes are asked to take the following precautions to reduce the chance of passing on vCJD to other people: Not to donate blood, tissues or organs and To inform their healthcare providers of their 'at-risk' status so that special procedures may be arranged for certain instruments used in their healthcare (NB. Their GPs are also asked to do this.)
A range of measures have been put in place by the Department of Health to minimise the possible risk of vCJD being passed through blood:
Since 1997 all cases of vCJD that are reported to the National CJD Surveillance Unit and diagnosed as having 'probable' vCJD, result in a search of the UK Blood Services blood donor records. If the patient has donated blood, any unused parts of that blood are immediately removed from stock. The fate of all used components of blood from the donor is traced, and surviving recipients informed of their risk. In July 1998, the Department of Health announced that plasma for the manufacture of blood products, such as clotting factors, would be obtained from non-UK sources. Since October 1999, white blood cells (which may carry the greatest risk of transmitting vCJD) have been removed from all blood used for transfusion. In August 2002 the Department of Health announced that fresh frozen plasma for treating babies and young children born after 1 January 1996 would be obtained from the USA, extended to all children under 16 years of age (Summer 2005). In December 2002, the Department of Health completed its purchase of the largest remaining independent US plasma collector, Life Resources Incorporated. This secures long-term supplies of non-UK blood plasma for the benefit of NHS patients. Since April 2004, blood donations have not been accepted from people who have themselves received a blood transfusion in the UK since 1980. This has been extended to include apheresis donors and donors who are unsure if they had previously had a blood transfusion (August 2004). Since late 2005, blood donations have not been accepted from donors whose blood was transfused to patients who later developed vCJD. The UK Blood Services continue to promote the appropriate use of blood and tissues and alternatives throughout the NHS.
The likelihood of a person who may be infected with vCJD going onto develop symptoms of the disease is uncertain, and may depend on individual susceptibility. It is possible that infected individuals may never develop symptoms.
For further information contact the HPA press office on 0208 327 7098/7097/6055
Specialist care for vCJD is available from The NHS National Prion Clinic, based at The Hospital for Neurology and Neurosurgery, Queen Square, London http://www.nationalprionclinic.org/
The National CJD Surveillance Unit is based at the Western General Hospital Edinburgh: www.cjd.ed.ac.uk
For further information about vCJD go to:
http://www.hpa.org.uk/infections/topics_az/cjd/menu.htmhttp://www.dh.gov.uk/PolicyAndGuidance/HealthAndSocialCareTopics/CJD/fs/enhttp://www.blood.co.uk/ http://www.cjd.ed.ac.uk
http://www.nationalprionclinic.org/Last reviewed: 13 December 2007
http://www.hpa.org.uk/webw/HPAweb&HPAwebStandard/HPAweb_C/1195733711457?p=1171991026241TRANSFUSION MEDICINE
EPIDEMIOLOGY REVIEW (TMER)
The Transfusion Medicine Epidemiology Review (TMER) is a collaborative project between the UK NCJDSU and the UK Blood Services. The main purpose is to investigate whether there is any evidence that Creutzfeldt-Jakob disease (CJD) or variant Creutzfeldt-Jakob disease (vCJD) may have been transmitted via the blood supply.
This website contains data on vCJD donors and cases of vCJD who have received transfusions in the past but does not contain data on the ongoing study of sporadic CJD.
This site was last updated on 11 March 2008
Methods
Results
vCJD donor summary
Use of blood donations from vCJD cases
Fate of recipients
vCJD cases who received blood tranfusion(s) in the past
Relevant Publications
Back to NCJDSU Home Page
http://www.cjd.ed.ac.uk/TMER/TMER.htmThursday, July 24, 2008
Prion diseases are efficiently transmitted by blood transfusion in sheep
http://vcjdblood.blogspot.com/2008/07/prion-diseases-are-efficiently.html4th CASE VCJD VIA BLOOD TRANSFUSION, BSE, BASE, AND SPORADIC CJD
By Terry S Singeltary
Bacliff, Texas USA Jan 24, 07
http://www.bloodindex.com/view_news_zone.php?id=206Subject: Re: Docket No. 2005N-0373 RIN number 0910-AF54 Use of Materials Derived From Cattle in Medical Products REOPENING COMMENT PERIOD Date: March 30, 2007 at 11:37 am PST
Subject: Re: Docket No. 2005N-0373 RIN number 0910-AF54 TSS SUBMISSION Date: March 30, 2007 at 10:57 am PST
http://madcowfeed.blogspot.com/2008/07/docket-no-2005n-0373-and-rin-number.html18 January 2007 - Draft minutes of the SEAC 95 meeting (426 KB) held on 7 December 2006 are now available.
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4. Members had received information about the notification by the Health Protection Agency (HPA) of recipients of four batches of plasma products that had been produced from blood donated by individuals that had later developed variant Creutzfeldt Jakob Disease (vCJD). THESE batches HAD NOT been included in a similar notification exercise in 2004, as the fate of these products COULD NOT BE TRACED at that time. The fourteenth annual report of the National CJD Surveillance Unit had been published. The European Food Safety Authority (EFSA) had issued a consultation on a revised methodology for geographical bovine spongiform encephalopathy (BSE) risk assessment. Members could submit individual responses. Submission of a SEAC response was under consideration.
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ITEM 9 - ANY OTHER BUSINESS
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***$$$***
64. A member noted that at the recent Neuroprion meeting, a study was presented showing that in transgenic mice BSE passaged in sheep may be more virulent and infectious to a wider range of species than bovine derived BSE. Other work presented suggested that BSE and bovine amyloidotic spongiform encephalopathy (BASE) MAY BE RELATED. A mutation had been identified in the prion protein gene in an AMERICAN BASE CASE THAT WAS SIMILAR IN NATURE TO A MUTATION FOUND IN CASES OF SPORADIC CJD. A study also demonstrated that in a mouse model it was possible to alleviate the pathological changes of prion disease by suppressing expression of the prion protein gene after infection.
http://www.seac.gov.uk/minutes/95.pdfMolecular Mechanisms of Prion Pathogenesis
Adriano Aguzzi, Christina Sigurdson, and Mathias Heikenwaelder Institute of Neuropathology, University Hospital of Z¨ urich, CH-8091 Z¨ urich, Switzerland; email: adriano.aguzzi@usz.ch, mathias.heikenwaelder@usz.ch, christina.sigurdson@usz.ch Annu. Rev. Pathol. Mech. Dis. 2008. 3:11–40 First published online as a Review in Advance on August 8, 2007 The Annual Review of Pathology: Mechanisms of Disease is online at pathmechdis.annualreviews.org This article’s doi: 10.1146/annurev.pathmechdis.3.121806.154326 Copyright c 2008 by Annual Reviews. All rights
Annu. Rev. Pathol. Mech. Dis. 2008. 3:11–40 First published online as a Review in Advance on August 8, 2007 The Annual Review of Pathology: Mechanisms of Disease is online at pathmechdis.annualreviews.org This article’s doi: 10.1146/annurev.pathmechdis.3.121806.154326 Copyright c 2008 by Annual Reviews. All rights reserved 1553-4006/08/0228-0011$20.00
Abstract
Prion diseases are infectious neurodegenerative diseases occurring in humans and animals with an invariably lethal outcome. One fundamental mechanistic event in prion diseases is the aggregation of aberrantly folded prion protein into large amyloid plaques and fibrous structures associated with neurodegeneration. The cellular prion protein (PrPC) is absolutely required for disease development, and prion knockout mice are not susceptible to prion disease. Prions accumulate not only in the central nervous system but also in lymphoid organs, as shown for new variant and sporadic Creutzfeldt- Jakob patients and for some animals. To date it is largely accepted that prions consist primarily of PrPSc, a misfolded and aggregated â-sheet-rich isoform of PrPC. However, PrPSc may or may not be completely congruent with the infectious moiety. Here, we discuss the molecular mechanisms leading to neurodegeneration, the role of the immune system in prion pathogenesis, and the existence of prion strains that appear to have different tropisms and biochemical characteristics.
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As an example in the field of human medicine, four cases of vCJD have been reported to be caused by blood transfusion (9– 11). This indicates that BSE prions can be recycled among humans, which has caused considerable alarm that the supply of bloodderived pharmaceuticals may be threatened (12). In particular, the report of a subclinical blood-derived vCJD infection in an individual carrying a heterozygote methionine/ valine polymorphism at codon 129 of the human PRNP gene (10) suggests that transmission of BSE prions to humans enhances their virulence and broadens the spectrum of susceptible recipients. In this respect, it has been demonstrated that polymorphisms at codon 129 of the human PRNP gene control susceptibility and incubation time in human patients (e.g., 129MM versus 129MV or 129VV drastically increases the susceptibility of humans to BSE prions). It was reported only recently that most individuals who suffered from kuru and were polymorphic at codon 129 showed incubation times longer than 50 years (13). Moreover, recent reports indicate that there is still a lot to be learned about the mechanisms of prion transmission (e.g., human to human or within scrapie-affected animal flocks) and prion tropism underlining the complex alternating distribution patterns of PrPSc (e.g., PrPSc deposition in lymphoid tissue, the CNS) and prion infectivity under varying conditions (e.g., chronic inflammation) and hosts (e.g., sheep, elk and deer, human): Chronic inflammation can alter the tropism of prion infectivity or PrPSc to organs hitherto believed prion free (e.g., liver, pancreas, kidney of mice, mammary gland of sheep, muscle of humans) (14–16). Moreover, PrPSc was reported in spleen and muscle tissue of sporadic Creutzfeldt-Jakob disease (sCJD) patients (17), and prion infectivity was demonstrated in muscle, blood, and saliva of deer suffering from CWD (18, 189). Also, prion infectivity was shown to be excreted via urine of prion-infected nephritic mice, a process defined as prionuria (19). These results emphasize the need for further assessment of possible public health risks from TSE-affected extraneural organs. It is very well possible that preexisting pathophysiological conditions of the infected host additionally contributed to unexpected distribution patterns of prion infectivity. For example, the presence of prion infectivity in the blood of sheep or deer may influence the deposition of prion infectivity in various organs previously deemed prion free. Therefore, it should be carefully reconsidered whether only organs of the CNS and the lymphoreticular system should be included in the current risk classifications of biologicals in the future. It will be important to test altered prion tropism profiles in nonlymphoid organs and body fluids (e.g., blood, urine, milk, saliva) of ruminants (e.g., sheep, goat, cattle, elk, and deer) and human patients suffering from sCJD and vCJD.
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Recent in vivo evidence indicated that a similar phenomenon of conformational variants may occur in Alzheimer’s disease (151). Here the existence of Aâ strains that can seed and accelerate aggregation and Aâ pathology was posited. These intriguing observations support the hypothesis that the pathogenetic mechanisms operating in Alzheimer’s disease and in prion diseases have more in common than we often appreciate (152). Perhaps future studies will address whether different Aâ strains with distinct biochemical or neuropathological characteristics occur in humans. Can multiple prion strains coexist and effect prion replication? Two subtypes of sporadic CJD have recently been demonstrated to coexist in humans (62). Experimental studies have shown that when two strains infect the same host, one strain can impede the ability of the second strain to cause disease (153). Bartz and colleagues (154) recently suggested that this might be caused by the suppression of prion replication of the second strain. Strain features are useful for tracing prion infections between species. When transmitted to primates, BSE causes lesions strikingly similar to that of vCJD (155, 156). BSE is most likely transmissible to humans too, and strong circumstantial evidence (157–159) suggests that BSE is the cause of vCJD, which has claimed more than 200 lives in the United Kingdom (3, 160), as well as a much smaller number in some other countries (161).
NATURAL TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES: WHAT IS NEW? Cattle Prions More than a few surprises have come from further investigations of prion strains in field cases of TSEs. Until recently, BSE was believed to be associated with one single prion strain, classified by an exclusive and remarkably stable biochemical profile of PrPSc. However, distinct molecular signatures have recently been discovered through the large-scale screening of cattle mandated by European authorities in the context of BSE surveillance. These atypical profiles fall into either of two groups: H-type cases of protease-resistant fragments with a molecular weight higher than BSE, and bovine amyloidotic spongiform encephalopathy, or L type (lower) (162). To test whether these different biochemical and histopathological properties correspond to distinct strains, the Laude laboratory transmitted H-type-PrPSc isolates from French cattle into transgenic mice expressing bovine or ovine PrP (163). The recipient mice developed neurological signs exhibiting strain-specific features clearly distinct from that of the classical BSE agent, providing pivotal evidence that the underlying strains are distinct.
Atypical Sheep Scrapie In 1998, aberrant cases of sheep scrapie were described in Norway and the strain was newly classified as Nor98 (164). Active European Union surveillance later revealed additional cases of atypical scrapie in several other countries (165, 166). Sheep infected with Nor98, or atypical scrapie, accumulated PrPSc primarily in the cerebellum and cerebral cortex rather than in the brainstem target in the classical strain (167). Additionally, on western blot analysis of atypical scrapie cases, an additional small-molecular-weight (10–12 kDa) PrP fragment appeared afterPKdigestion and was shown by epitope mapping to lack both N and C termini of PrP (167, 168). Furthermore, atypical scrapie cases occurred not only in the classical scrapie-susceptible genotypes (A136 R154 Q171), but also in genotypes associated with high resistance to classical scrapie (A136 R154 R171) (165, 166). Were these atypical scrapie cases also infectious? In 2001, atypical scrapie cases were shown to be transmissible prion diseases after inoculated ovine PrP-expressing transgenic mice developed disease and prion aggregates (169). In the meantime, several countries appear to be reporting extremely high incidences of atypical scrapie, and in fact atypical scrapie appears to be the rule rather than the exception in some geographical areas.
Chronic Wasting Disease Among all animal prion diseases, CWD of cervids is likely the most efficiently transmitted. CWD infections occur in mule deer (Odocoileus hemionus), white-tailed deer (O. virginianus), Rocky Mountain elk (Cervus elaphus nelsoni) (170), and moose (Alces alces shirasi) (171). Prevalence can reach as high as 30% in dense, free-ranging deer populations and nearly 100% in captive animals (171). Hypotheses for CWD transmission range from spread via direct contact to exposure through grazing in areas contaminated by prion-infected secretions, excretions (saliva, urine, feces), tissues (placenta), or decomposed carcasses. Insightful experimental studies have recently revealed two key findings: (a) Saliva from CWD-infected deer can transmit disease (18), and (b) CWD-infected carcasses allowed to decay naturally in confined pastures can lead to CWD infections in captive deer (172). Additionally, the abundant CWD-prion accumulation within lymphoid tissues may also lead to CWD prion buildup in nonlymphoid organs with lymphoid follicles, as was recently shown in kidney, potentially shifting shedding routes (173). It is unknown whether other types of inflammation, such as the granulomatous inflammation in the intestine seen in Johne’s disease (Mycobacterium avium subsp. paratuberculosis; affects ruminants, including deer and elk) or parasitic inflammation, could lead to or perhaps increase prion excretion by fecal routes. The environmental prion contamination in CWD underscores the difficulties of CWD disease management.Within North America,CWDinfected deer and elk have been detected in 14 states and two Canadian provinces (170, 174, 175). CWD surveillance in Europe has been more limited. However, in Germany, a total of 7300 captive and free-ranging cervids were tested forCWDwith no sign of infection (176). Reindeer or caribou (Rangifer tarandus), from North America or Northern Europe respectively, have a highly homologous prion sequence compared with mule deer and thus are likely susceptible to CWD. Other European cervids such as moose and red deer (C. elaphus) are also expected to be CWD susceptible. The deer and elk primary protein structures are highly conserved, as seen in other mammals. Interestingly, a polymorphism at codon 225S/F may influence CWD susceptibility in mule deer. When comparing the frequency of genotypes among CWDnegative and -positive deer (n = 1482), the odds that a CWD-infected animal was 225SS was 30 times greater when compared with 225SF, whereas the frequency of 225SF/FF genotypes in CWD-negative deer was 9.3%, but only 0.3% in CWD-positive deer (177).
Additionally, elk have a polymorphism at codon 132 (M/L) of Prnp, corresponding to polymorphic codon 129 (M/V) in humans. Elk expressing 132ML and 132LL Prnp were reported to be overrepresented among elk with CWD when compared with uninfected controls (178), and 132LL elk experimentally infected with CWD have resisted infection for at least four years, whereas 132MM or 132ML elk (n = 2 each) developed terminal clinical prion disease by 23 or 40 months post inoculation, respectively, confirmed by immunohistochemistry and western blotting for PrPSc (179). White-tailed deer also have Prnp polymorphisms that may affect their CWD susceptibility. A reduced susceptibility to CWD was linked to a G96S and a Q95H polymorphism in a study comparing allelic frequencies from CWD-positive and CWDnegative free-rangingWisconsin white-tailed deer (180).
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http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.pathmechdis.3.121806.154326USA PRION UNIT BLOG
http://prionunitusaupdate2008.blogspot.com/Sunday, April 20, 2008 Progress Report from the National Prion Disease Pathology Surveillance Center April 3, 2008
Atypical forms of BSE have emerged which, although rare, appear to be more virulent than the classical BSE that causes vCJD.
see full text ;
http://prionunitusaupdate2008.blogspot.com/2008/04/progress-report-from-national-prion.htmlCJD TEXAS (cjd clusters)
http://cjdtexas.blogspot.com/USA WRITTEN CJD QUESTIONNAIRE ???
http://cjdquestionnaire.blogspot.com/The statistical incidence of CJD cases in the United States has been revised to reflect that there is one case per 9000 in adults age 55 and older. Eighty-five percent of the cases are sporadic, meaning there is no known cause at present.
http://www.cjdfoundation.org/fact.html>>>"the biochemical signature of PrPres in the BASE-inoculated animal was found to have a higher proteinase K sensitivity of the octa-repeat region. We found the same biochemical signature in three of four human patients with sporadic CJD and an MM type 2 PrP genotype who lived in the same country as the infected bovine." <<< href="http://www.vetres.org/index.php?option=article&access=standard&Itemid=129&url=/articles/vetres/pdf/2008/04/v07232.pdf">http://www.vetres.org/index.php?option=article&access=standard&Itemid=129&url=/articles/vetres/pdf/2008/04/v07232.pdf< /a>
please see full text ;
http://bse-atypical.blogspot.com/2008/06/review-on-epidemiology-and-dynamics-of.html***Atypical forms of BSE have emerged which, although rare, appear to be more virulent than the classical BSE that causes vCJD.***
Progress Report from the National Prion Disease Pathology Surveillance Center
An Update from Stephen M. Sergay, MB, BCh & Pierluigi Gambetti, MD
April 3, 2008
http://www.aan.com/news/?event=read&article_id=4397&page=72.45.45Sunday, March 16, 2008
MAD COW DISEASE terminology UK c-BSE (typical), atypical BSE H or L, and or Italian L-BASE
http://bse-atypical.blogspot.com/2008/03/mad-cow-disease-terminology-uk-c-bse.htmlHUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory JUNE 2008
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Tissue infectivity and strain typing of the many variants Manuscript of the human and animal TSEs are paramount in all variants of all TSE. There must be a proper classification that will differentiate between all these human TSE in order to do this. With the CDI and other more sensitive testing coming about, I only hope that my proposal will some day be taken seriously. ...
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http://cjdmadcowbaseoct2007.blogspot.com/2008/06/human-and-animal-tse-classifications-ie.htmlAtypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate
http://organicconsumers.org/forum/index.php?showtopic=1951http://bse-atypical.blogspot.com/2008/08/atypical-bse-base-transmitted-from.htmlThursday, July 10, 2008
A New Prionopathy
http://cjdmadcowbaseoct2007.blogspot.com/2008/07/new-prionopathy-update-july-10-2008.htmlSunday, August 10, 2008
A New Prionopathy OR more of the same old BSe and sporadic CJD
http://creutzfeldt-jakob-disease.blogspot.com/2008/08/new-prionopathy-or-more-of-same-old-bse.htmlWednesday, August 20, 2008
Bovine Spongiform Encephalopathy Mad Cow Disease typical and atypical strains, was there a cover-up ?
http://bse-atypical.blogspot.com/2008/08/bovine-spongiform-encephalopathy-mad.htmlUPDATE AUGUST 28, 2008
LETTER TO EDTOR: Care over research
Tuesday, August 26, 2008 Comment Print Listen Font Size Share Ask a Question You Report I, and every reader, can feel the pain and anguish of the family chronicled in The Times article "Hospital released vet who refused study" (Page 1, Friday). The disease mentioned, Creutzfeldt-Jakob disease, is devastating, unremitting and, as yet, without cure.
It is also difficult to sort out from other diseases with similar symptoms. Medicine does not know why it progresses more quickly in some people than in others. It is for these reasons that medical research is done - to understand better how to improve the chances of the next veteran who has such a problem.
In this case, a National Institutes of Health (NIH) study in which the Department of Veterans Affairs partnered with Mount Sinai Hospital, a world renowned academic medical center, was offered to the patient. The study was designed, as noted, to observe and to learn more about "conditions affecting memory or thinking, including Alzheimer's disease and related disorders." The research was to study the progression of disease, not to offer an experimental treatment. The study's consent form even states that "this study is not designed to benefit participants."
I can only apologize that Aimee Fitzgerald perceived a sense of callousness or a sense that there were some additional diagnostic or other measures to be offered as she sought answers to unanswerable questions about her ailing husband, Joe. It will renew our emphasis to VA staff about sensitivity in communicating. I and the VA completely share the view of bioethicist Arthur Caplan that the goal of the medical encounter must be first and foremost to provide the latest and best care when care is available, that research must take a secondary role to receiving patient care and that no one should be penalized for failing to volunteer for a study, ever.
It is the VA's policy - clearly stated in our regulations, directives, patient literature and the protocol consent form - that a patient has a right to say no to participating in a research study and that decision will not affect the VA health care or benefits the patient receives.
In serving our veterans, we have an absolute obligation to provide not only the highest quality care and to provide that care with attention and compassion, but to find better ways to care for our patients through research with the highest scientific and ethical standards. It is what we strive for every single day across our system. I can only apologize for the family's perception in this tragic case and to let them know that it will serve as a systemwide reminder about the importance of clear and compassionate communication.
DR. JAMES B. PEAKE
Secretary of veterans affairs
Washington
http://washingtontimes.com/news/2008/aug/26/care-over-research/VA chief offers family apology Vet died after refusing research Audrey Hudson (Contact) Tuesday, August 26, 2008
The secretary of the Department of Veterans Affairs has apologized to the family of an Army veteran who died last year after being turned away from a Bronx VA hospital after he refused to participate in an Alzheimer's disease study.
Joe Fitzgerald, 74, died of Creutzfeldt-Jakob disease - the human form of mad cow disease - less than a month after being dismissed without diagnosis or treatment at James J. Peters VA Medical Center, The Washington Times reported Friday.
His widow, Aimee Fitzgerald, has demanded answers from the VA as to whether human research testing is taking a priority over the health care of veterans after the agency responded that the Alzheimer's study was a "mandate."
"I can only apologize that Mrs. Fitzgerald perceived a sense of callousness, or a sense that there was some additional diagnostic or other measures to be offered," Veterans Affairs Secretary James B. Peake said in a letter to the editor at The Times. "It will renew our emphasis to VA staff about sensitivity in communicating."
The VA has come under scrutiny and criticism over its human-subject experiments since a Washington Times/ABC News investigation revealed in July that the agency had failed to quickly notify participants in a smoking-cessation study about the potentially dangerous side effects of a drug some participants were taking.
A recent investigation of experiments conducted at an Arkansas veterans hospital uncovered rampant violations, including missing consent forms, secret HIV testing and failure to report more than 100 deaths of subjects participating in studies.
Mr. Fitzgerald sought treatment for his sudden loss of motor skills at the Bronx VA hospital when his attending physician, Dr. Ruth Walker, said that enrolling in the Alzheimer's study would enable a quicker diagnosis of his disease, Mrs. Fitzgerald said.
Dr. Walker introduced the family to Dr. Christine Bergmann, who headed the Alzheimer's study. VA officials said Dr. Bergmann did not have the authority to offer a diagnosis.
"I can only apologize for the family's perception in this tragic case and to let them know that it will serve as a system-wide reminder about the importance of clear and compassionate communication," Mr. Peake said in his letter to the editor.
The Times also reported that Arthur Caplan, one of the nation's premier medical ethicists and director of the Center for Bioethics at the University of Pennsylvania, said the first obligation of any caregiver is to treat the patient.
In his letter, Mr. Peake - a physician himself - said he and his agency "completely share Mr. Caplan's view."
http://washingtontimes.com/news/2008/aug/26/va-chief-offers-family-apology/Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
Labels: atypical bse, SPORADIC CJD, USA, veterans
