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By DAN OLMSTED, UPI Senior Editor   |   July 6, 2006 at 4:40 PM

WASHINGTON, July 6 (UPI) — On April 26 a Scottish child named Anna Duncan attended a party where two children had chickenpox. Nine days later she got her routine measles-mumps-rubella vaccination. Four days after that she developed classic chickenpox symptoms — spots and fever.

One week later, on May 14, Anna was dead from an apparent seizure. She was 17 months old.

Now her father, John, is struggling with the sudden loss of a bright, lively child — and increasingly suspicious that the MMR shot during an apparent chickenpox infection triggered her death.

Those suspicions deepened after he came across Age of Autism’s recent investigative series, Pox, which found that giving MMR and chickenpox vaccines at the same time might raise the risk of autism in a susceptible subset of children. By happenstance, the series began the week before Anna’s exposure to chickenpox and ended the week after her death.

In Anna’s case, Duncan believes the chickenpox she caught at the party suppressed her immune system to the point that the measles virus from the MMR triggered a fatal seizure.

“I feel now that I have an answer to our daughter’s death,” said Duncan, of Cardrona, Scotland. “What I’m going to try to do with this is force a fatal accident inquiry, because there is a potential scenario here where it could happen again, and if (they) realize that this is a developing story, it can only get bigger.”

The Pox series centered on several autistic children in Olympia, Wash., whose families had problematic histories with chickenpox and related herpesviruses. All of the children got the MMR and chickenpox vaccines, in most cases at their 12-month checkups; two of the children were in Merck & Co. clinical trials of investigational chickenpox vaccines in combination with the MMR.

John Duncan said that like the Olympia families, he also had unusual reactions to viral infections and experienced a monthlong outbreak of pox-like spots just after Anna was born. He took photographs at the time to document the spots, which spread diffusely from his abdomen.

“I believe her response to the MMR while infected with chickenpox was due to her genetic makeup from myself,” Duncan wrote in a posting on the British Web site jabs.org.uk.

“Anna’s normal response to a benign childhood illness, for which recovery was a formality, was interrupted by the MMR vaccine, which due to her understandable immunosuppression resulted in the replication of the measles virus — ‘virus replication,’ an accepted and understood medical event in relation to vaccines.”

It will be weeks before laboratory tests confirm whether Anna had chickenpox and health authorities rule on cause of death. But authorities in both Britain and the United States assert there is no association between the vaccines and serious health problems. They say the real risk is foregoing vaccinations based on unfounded fears.

The Daily Mail reported in June that “Britain is now in the grip of the biggest measles outbreak since the vaccine’s introduction in 1988. Doctors have reported hundreds of cases of measles since January in just three areas of the country, including the death of a 13-year-old boy.”

Last week “a group of Britain’s leading pediatricians and childhood vaccination experts … warned that more children will die unless a line is drawn under the autism and MMR vaccine controversy,” according to Britain’s Guardian newspaper.

“In an open letter, 30 scientists, including some of the country’s most eminent child health experts, say that an overwhelming body of evidence shows the vaccine is safe. They add that urgent immunizations are necessary to prevent potentially devastating outbreaks among schoolchildren.”

The MMR vaccine Anna received was Priorix, manufactured by GlaxoSmithKline. Chickenpox vaccine is not routinely administered in Britain; in the United States it is recommended by health authorities for all children beginning at age 12 months.

John Duncan provided this sequence of events leading up to Anna’s death.

Wednesday, April 26 — Anna attended the party with her mother, Veronica, where one child was getting over chickenpox and that child’s younger sister had all the symptoms of chickenpox.

Friday, May 5 — Anna got her MMR shot at Haylodge Health Centre, Peebles, Scottish Borders; her mother questioned whether Anna’s runny nose and exposure to chickenpox was a cause for concern. The healthcare worker said it was not.

Tuesday, May 9 — Anna developed signs of chickenpox with spots appearing and a slight fever. This developed into what appeared to be classic chickenpox.

Sunday, May 14 — Anna died around 9 a.m. with what appeared to be a seizure, with evidence of blood on her lips and on sheets in close proximity to her mouth.

“When Anna had chickenpox we gave her (a fever reducer) to bring her temperature down when it spiked,” John Duncan said. “Her temperature according to her mother, who is a nurse, seemed to stabilize on the Saturday night through to Sunday morning, but Anna became restless early on Sunday morning and had two very smelly nappy (diaper) changes. A tired mother put Anna in her cot at around 6 p.m. as she seemed to be more contented on her own.

“Anna’s death came as a major shock to us all because at no time did we think that she was going to die. The seizure would have been undetectable in the circumstances. I was with (son) Cameron that morning downstairs because I thought Anna had turned the corner.”

Duncan said a doctor who came to the house to confirm the death told his wife it appeared “Anna had chickenpox.” She may also have started developing new spots characteristic of measles, he said.

“I would say at time of death there were more measles-like spots appearing around her neck. But I cannot be too sure.”

Duncan asked on the Jabs site: “Could this scenario cause autism? Is there a genetic susceptibility in some children to deal with the herpesvirus in a different way to the normal response, making these children more at risk to a bad reaction from MMR at the time of herpes infection? …

“Had Anna survived her bout of seizure 10 days after her MMR, her brain very possibly could have been damaged and a diagnosis of autism eventually given.”

—

Next: Chickenpox and measles — a troubling combination.

By DAN OLMSTED, UPI Senior Editor   |   June 13, 2006 at 11:43 AM

WASHINGTON, June 12 (UPI) — Dr. Andrew Wakefield, the British gastroenterologist who first raised the prospect of a link between the measles-mumps-rubella vaccine and autism, is being pursued by British medical authorities.

According to the BBC: “The Independent newspaper reports that the General Medical Council will accuse Mr. Andrew Wakefield of carrying out ‘inadequately founded’ research. Vaccination rates fell sharply after Dr Wakefield questioned the safety of MMR, raising fears of a measles epidemic. His initial Lancet paper has since been disowned by the journal.”

Let’s put aside the issues surrounding the Lancet paper and concerns about a measles epidemic and go straight to the heart of the matter: Does the MMR cause autism? In other words, is Wakefield right?

After looking into the topic for more than a year, I’m very concerned that he may be — that, especially in children whose immune systems have been rendered susceptible by any number of possible exposures, the combined live-virus vaccine has its fingerprints all over numerous cases of regressive autism.

Until researching the seven-part Age of Autism series in Olympia, Wash., that concluded last month, I would not have said that. But when you encounter case after case of perfectly normal children regressing after live-virus vaccinations — in this case, the MMR in close proximity to the chickenpox shot — you have to keep your options open.

The families in Olympia noticed a common thread: They had unusual histories of chickenpox and other herpesviruses in their families; their child got the chickenpox and MMR shots in close temporal proximity, often at the same 12-month office visit when both are first recommended; and the child subsequently was diagnosed with regressive autism.

Despite the sweeping assurances that there’s no link between the MMR and autism, no one seems to have looked at whether such a family history of susceptibility to viruses used in vaccines might raise a risk factor. Call me hypervigilant, but I would have expected that to be rigorously reviewed a long time ago.

Two of the Olympia children, in fact, were in small trials at age 12 months of chickenpox and MMR vaccines. One of the vaccines, called ProQuad, combines the MMR and chickenpox, kicking in 10 times the standard amount of chickenpox vaccine to overcome the “immune interference” that can occur when live viruses interact.

Such interference is at the heart of Wakefield’s concern about the combined MMR vaccine — that the viruses suppress the immune system in such a way that weakened-but-live measles viruses can set up house and trigger a delayed neurological infection: autism.

And measles is not benign — that’s why there’s such a push to vaccinate against it. In a small percentage of cases, the wild, or naturally occurring, infection can lead to delayed brain damage and death.

It’s a neurotoxic virus, in short. Wakefield’s question and concern is whether in some cases the live-virus vaccine is neurotoxic, too.

Not such a wild idea, really, and listening to him talk makes you hope to God the vaccine manufacturers and regulators are a lot smarter than he makes them sound:

“What alarms me about the cavalier approach of the industry and everybody else, the regulators, to these viruses is they presume the wild infection to be nasty and the vaccines to be innocuous — that they can manipulate something that is biologically highly intelligent and exploit it to their advantage.

“And they can’t. The viruses don’t behave like that and they never will. They merely come back to haunt you as something different.”

Multiple epidemiological studies have allegedly ruled out this chilling scenario as a factor in autism — the Institute of Medicine calls it “theoretical only.” But epidemiology is only as good as its data and its practitioners, and well-known for its potential pitfalls and flaws. What concerns me is, if the epidemiology is wrong, preventable cases of autism are going to keep happening till the cows come home.

Recall, also, that Wakefield never suggested banning the measles, mumps or rubella immunizations. He suggested separating them and giving them a year apart.

Especially concerning are the stories that parent after parent tells about physical illness after the shots, followed by autistic regression. It’s kind of freaky, really, the way they keep popping up.

After finishing the Pox series, I attended the Autism One convention in Chicago and happened to be interviewed by a Web-based documentary filmmaker. During a break, I asked how he got involved. He told me his daughter got the MMR, came down immediately with a 103-degree fever and regressed forthwith into autism.

“It’s like someone took out her good brain and replaced it with a bad brain,” he said. It was that immediate.

I had another conversation with the mother of fraternal twins who told me this story: Both sons were scheduled to get two shots — the MMR and another vaccination — on the same day at the same office visit.

But — oops — the healthcare worker gave the first child two MMR shots, not the MMR and the second vaccine. That child soon developed autism; the second one didn’t.

And I spoke recently with a Texas man whose son got the MMR in 1993; the injection site swelled up to the size of his father’s fist; he had seizures at the dinner table that night, and within days was spinning, flapping, chewing wood and not talking ever again.

You get the picture. “Anecdotal evidence.” But you have to wonder how many of these stories — one is tempted to say, bodies — must pile up before the medical authorities go back and take a fresh look at the issue.

This blithe disregard for case histories — for what parents, the supposed bedrock of our “family-friendly” society, say — is one of the most appalling features of the current climate surrounding autism research. In fact, Sen. Joseph Lieberman, D-Conn., has talked publicly of forcing the Centers for Disease Control and Prevention, which sets the childhood immunization schedule and stoutly rejects a link with autism, to actually go out and interview some of these parents.

One person who is making things awkward for the authorities is Dr. Peter Fletcher, another British ne’er-do-well — or, to use his official title, the former chief scientific officer at Britain’s Department of Health.

As I noted in a column earlier this year, the Daily Mail reported: “A former British government medical officer responsible for deciding whether medicines are safe has accused the government of ‘utterly inexplicable complacency’ over the MMR triple vaccine for children.”

The official, Dr. Peter Fletcher, became an expert witness for parents’ lawyers, which of course creates a competing interest that needs to be factored in. But Fletcher said his new role gave him access to documents that deeply concerned him.

“There are very powerful people in positions of great authority in Britain and elsewhere who have staked their reputations and careers on the safety of MMR and they are willing to do almost anything to protect themselves,” he said.

Gosh, this is starting to get interesting, and not just for Andrew Wakefield.

By DAN OLMSTED, UPI Senior Editor   |   June 9, 2006 at 4:23

WASHINGTON, June 9 (UPI) — This week the Food and Drug Administration approved a vaccine to prevent cervical cancer in women. In an odd way, the announcement highlights what may be wrong with government policy on another vaccination, the very first one children receive.

The FDA’s approval of Gardasil is intended to block human papillomavirus, or HPV, the most common sexually transmitted disease and one that causes almost all cases of cervical cancer. The agency approved the vaccine for girls beginning at age 9 to protect them before they become sexually active.

Some cultural conservatives oppose making the shots mandatory for public-school attendance because of what they fear is an implicit endorsement of pre-marital sex. That’s an issue an advisory committee of the Centers for Disease Control and Prevention — and ultimately, each of the 50 states — will have to grapple with.

Regardless, the decision to wait till the cusp of adolescence to give the shot seems sensible — and drives home the contrary approach that the CDC has taken with the hepatitis B vaccination mandated for every newborn child.

To listen to some public-health officials, you’d think the nation was in the grip of an incipient Hep B epidemic lurking in the nation’s hygienically challenged daycare centers — an epidemic contained solely by vaccination on the day of birth.

In fact, hepatitis B is overwhelmingly a disease of sexual contact and intravenous, illegal drug use. Except in cases where the mother tests positive for Hep B, the risk to children vs. the risk of such an early vaccination seems questionable in the eyes of many critics of CDC immunization policy.

Over the course of the past year, as I’ve reported on concerns that vaccines may be linked to a huge increase in autism diagnoses beginning in the 1990s, the hepatitis B vaccination at birth stood out; the vaccination was first recommended in 1991.

At least two doctors tell me their faith in the government’s entire childhood immunization schedule was shattered by the CDC’s insistence that every newborn needs a Hep B shot as an urgent matter of public health.

“It is universally accepted that such mandate was forced upon our children only because they were ‘available,’ while efforts to vaccinate high-risk adults had repeatedly failed,” Dr. F. Edward Yazbak testified in 2001 before the Massachusetts House of Representatives.

“The continued mandate of this vaccine with all its problems may result in parents losing faith in vaccine programs in general, and opposing all vaccinations, many of which we know are necessary and effective,” he said.

The National Vaccine Information Center, which supports parental choice and awareness of immunization hazards, raises similar issues. “Unlike other infectious diseases for which vaccines have been developed and mandated in the U.S., hepatitis B is not common in childhood and is not highly contagious,” the NVIC says.

“Hepatitis B is primarily an adult disease transmitted through infected body fluids, most frequently infected blood, and is prevalent in high risk populations such as needle using drug addicts; sexually promiscuous heterosexual and homosexual adults; residents and staff of custodial institutions such as prisons; health care workers exposed to blood; persons who require repeated blood transfusions and babies born to infected mothers.”

Dr. Mayer Eisenstein, medical director of the family-practice Homefirst Medical Services in Chicago, told the Illinois Legislature in 1997 that mandating Hep B for newborns was absurd.

“The idea of giving this vaccine to a one-day old baby, a newborn, is preposterous. There is no scientific evidence for this. In fact, I called up the manufacturer and I had (a representative) come to St. Mary of Nazareth Hospital, where I am Chairman of the Department of Medicine, and I asked him: ‘Show me your evidence on one-day old infants as to side effects (from the hepatitis B vaccine)’ — we have none. Our studies were done on 5 and 10 year olds.

“As a father, grandfather, a physician, as a lawyer, I want the option of not giving it to my children unless I believe the scientific evidence is there.”

Yet waiting until genuine risk looms — via sexual activity, intravenous drug use or a healthcare job — has been rejected out of hand. That view was confirmed earlier this year by both the CDC and the American Academy of Pediatrics, whose members administer the vaccines.

“The Academy has endorsed CDC recommendation for hepatitis B vaccine, ‘A Comprehensive Immunization Strategy to Eliminate Transmission of Hepatitis B Virus Infection in the United States,’” the AAP said in a news release.

“The CDC recommends that all newborns receive a birth dose of hepatitis B vaccine before leaving the hospital unless a physician provides a written order to defer the birth dose.”

Compare that to waiting till age 9 for the new Gardasil vaccine. While the reasonable concerns of some parents are yet to be resolved, this already stands in stark contrast to the public health establishment’s hepatitis B hammerlock on the nation’s newborns.

True, the mercury-based preservative thimerosal that some believe is behind the rise in autism has been removed from Hep B and other routine childhood vaccines. But the issue of whether children are getting an unnecessarily early and heavy load of vaccines — and whether that could explain the rise in autism or chronic illnesses like asthma — remains squarely on the table, at least to this observer.

In years to come, I suspect, the Hep B shot at birth may be regarded as a case study in doctors gone wild.

By DAN OLMSTED, UPI Senior Editor   |   May 23, 2006 at 6:03 PM

WASHINGTON, May 23 (UPI) — When a mother in Washington state and a researcher in Washington, D.C., offer an identical observation about autistic kids, you can’t help but notice.

That observation is simple but potentially significant: Children later diagnosed with regressive autism often got physically sick around the time of their live-virus vaccinations.

Here’s how Denise Rohrbeck, the mom in Olympia, Wash., put it after collecting vaccine records and medical histories from fellow parents of local preschoolers diagnosed with full-syndrome autism.

“Most of the parents recall their child had a viral illness — roseola, rotavirus or an unnamed flu — less than four months before or after those live-virus shots.”

Denise’s three-year-old son, Grant, is a case in point. A couple of months before he got the live-virus chickenpox and measles-mumps-rubella shots at the same office visit at age 1, Grant had a stubborn and severe case of roseola, which like chickenpox is a herpesvirus.

Four days after the MMR and chickenpox injections he became ill with a fever and lay limp in his mother’s arms for the first time in his life.

“He began having chronic diarrhea, and by his 15-month checkup he had regressed so drastically that his pediatrician suggested he could be autistic,” Rohrbeck recalled in Part 1 of this series. The doctor agreed to the parents’ request for an immediate neurodevelopmental evaluation, which eventually confirmed their fears. By age 2 Grant was diagnosed with full-syndrome autism.

An even more immediate example is Ryan Boe, an Olympia child profiled in the last installment. He got his MMR at 16 months and his chickenpox and three other vaccines two months later. During that visit, Ryan broke out in hives while still at the doctor’s office, had a 105-degree fever by the end of the day that lasted a week, and displayed classic signs of regressive autism within the month.

The second source for the same observation about vaccines, illness and autism is British researcher Paul Shattock. In an interview in April while attending an autism conference in Washington, Shattock said he suspects that children who contract viral infections too close to their MMR shot may have an increased risk for autism.

He noticed that parents who believed the MMR vaccine triggered their child’s autism tended to cite an “undisclosed viral illness” around the time of the shot.

Shattock decided to test that observation. Britain doesn’t give kids chickenpox shots, meaning they still get chickenpox, so he looked for a diagnosis of that unmistakable childhood disease around the time of the MMR vaccination.

He studied the records of 100 children whose parents blame the MMR for the onset of autism, compared to 100 children whose parents do not, to see if there was more chickenpox in the three months on either side of the MMR immunization.

“Now, there was,” Shattock said. “It wasn’t statistically significant at the 95 percent level — but enough to make you think that if it was a huge study, it might be.”

The implication: Too many viruses too close together from whatever sources might overload the immune system, lead to persistent infection and, ultimately, cause brain damage resulting in autism. To Shattock, old-fashioned chickenpox interacting with measles, mumps and rubella vaccines looked like a red flag.

What resonates in Olympia is not just the pattern of illness but the families’ problematic histories with chickenpox and other herpesviruses. The specter: Live-virus chickenpox vaccine and viral infections like roseola playing the same “overload” role in vulnerable children as real-live chickenpox in Shattock’s suspected British cases.

Consider, for example, Jimmy Flinton. As outlined in Part 3, his father, Paul, had an unusual case of shingles, the reactivated form of the virus, at 15; his paternal grandmother, Mary Southon, had a case at 20 and a lifelong problem with cold sores — a kind of herpesvirus — that eventually infected her eyes and may require cornea transplants.

Jimmy is one of two Olympia children with autism who were in clinical trials of investigational, apparently high-dose chickenpox vaccines in conjunction with the MMR shot.

In 2002, Jimmy was given ProQuad, a four-in-one chickenpox-MMR vaccine that has about 10 times the typical dose of chickenpox virus. That is necessary to overcome a phenomenon known as immune interference when live viruses are combined, according to a spokesman for Merck & Co., which developed the vaccine.

During the 42-day “study window” following his vaccination, Jimmy may have had a slight, brief fever, his mother, Jennifer, recalls. But she said it was nothing notable, and she didn’t record it on the adverse-event log she was asked to keep.

But less than four months later Jimmy had an acute illness with a fever around 102. After that, in retrospect, his development stalled, and he eventually was diagnosed with full-syndrome autism.

The other child, Timothy Baltzley, was in a clinical trial two years earlier. As described in Part 4, he got a Merck “process upgrade” chickenpox shot that his mother, Kimberly, was told had a much higher amount of live-virus vaccine.

Again, chickenpox history seems potentially relevant: After two mild cases as a child, Kimberly had an unusually severe and late case of chickenpox at 16, just three years before Timothy was born.

In his clinical trial, Timothy got the experimental chickenpox shot at the same office visit as the standard MMR. Kimberly says the pediatrician told her it was part of the development of the combined chickenpox-MMR vaccine; Merck, to the contrary, said the two trials were completely unrelated.

Midway through the 42-day “study window,” Timothy had an acute illness — a fever of 102, vomiting and listlessness. Again the pattern: Four live-but-weakened viruses including a big dose of chickenpox; family susceptibility; physical illness, and autism.

Both Kimberly Baltzley and Jennifer Flinton are emphatic that the pediatrician who performed the trials in Olympia, Dr. Carl Lindgren, is not the source of their concern. (Lindgren referred our questions to Merck.)

“Dr. Lindgren has been incredibly conscientious and proactive in his dealings with us regarding Jimmy’s autism — much more so than most pediatricians would be,” Jennifer said.

“So, not only do we not think he did anything wrong with the clinical trial, but we actually think he went above and beyond the call of duty after the trial.”

Other Olympia parents say similar things, concerned that broader issues of vaccine safety and a possible link to autism will get translated into criticism of individual doctors.

“I worry about pediatricians being vilified,” said Denise Rohrbeck, the mom who collected the vaccination records. “We vaccinated our son because we shared their faith that vaccines were safe.

“If it turns out that some vaccines are not safe for all children and that these hazards could have been found with more rigorous testing — or worse, that the dangers were already known — that’s the fault of the CDC, the FDA and the manufacturers,” she said.

“I’ll defend doctors to the end on this point. They are a convenient front line for those agencies to hide behind — it’s just shameful.”

That puts the issue squarely in the lap of the drug companies and the public-health authorities. They say vaccines simply don’t cause autism, period — so the idea of susceptibility to a viral overload from live-virus vaccines, coincident viral infections or any other source is a non-starter.

“We don’t see an association,” Merck spokeswoman Christine Fanelle said, citing as confirmation a 2004 report by the widely respected Institute of Medicine, part of the National Academies. That report rejected a link between autism and either the MMR vaccine or the mercury-based preservative thimerosal. The report also urged that research dollars be spent on “more promising” autism research.

“There will always be some people who say vaccines cause autism despite the lack of scientific evidence,” Fanelle said. She noted ProQuad subsequently was approved by the FDA and its safety profile is the same as the individual chickenpox and MMR shots. Merck acknowledged, however, that it did not report the two Olympia autism cases to the FDA until this March — six months after ProQuad’s approval — which is when it says it became aware of them.

The FDA did not respond to requests for comment.

That is where the matter now rests. But several researchers who remain concerned about a link between vaccines and autism — in particular from combined live-virus shots — say the Olympia cases, grounded in the parents’ concerned but careful observations, may prove hard to ignore indefinitely.

“It’s actually heartbreaking, listening to these parents, for more than just the immediate reasons their child has met this fate,” said British researcher Dr. Andrew Wakefield, whose controversial theories on the MMR vaccine and autism essentially drove him out of England. He is now doing research in the United States and met with several of the Olympia parents during an autism conference in Portland, Ore.

“It’s that you’re staring into an abyss,” Wakefield said. “You’re listening to stories which reflect the fundamental misconception of vaccine manufacturers of what viruses are and what they do.”

And what now?

“The way forward is clearly to alert the regulatory authorities to the fact that these children exist,” Wakefield said, “that their stories are consistent with a delayed adverse reaction to the vaccine and that this would not have been picked up in the (clinical) trials.”

Meanwhile, in Washington state, a law takes effect July 1 requiring proof of chickenpox immunization before a child can enroll in school or daycare. The Centers for Disease Control and Prevention says ProQuad now is the preferred way to administer chickenpox and MMR vaccines, ideally on a child’s first birthday or as soon thereafter as possible.

By DAN OLMSTED, UPI Senior Science Writer   |   May 17, 2006 at 1:33 PM

WASHINGTON, May 17 (UPI) — In 1942 a 12-month-old child named Richard M. got a live-virus smallpox vaccination that triggered a fever and diarrhea from which he recovered “in somewhat less than a week.”

We know about Richard because he is Case 3 in psychiatrist Leo Kanner’s landmark study, “Autistic Disturbances of Affective Contact,” which alerted the world to a condition that differed “markedly and uniquely from anything reported so far.”

Autism.

Kanner’s paper appeared in 1943 in the quaintly named journal The Nervous Child. Kanner believed autism was “inborn,” present from birth. But if any of his detailed case histories suggest otherwise, it is Richard M.

There is no mention of “going backward” by the parents of the other 10 children, making Richard the first plausibly regressive case of autism ever described in medical literature.

Thirty-eight years later, in 1976, an article appeared in a German medical journal under the title “Autistiches Syndrom (Kanner) und Pockenschutzimpfung.” Translation: Autistic Syndrome (Kanner) and Vaccination against Smallpox.

The English abstract reads:

“3-4 weeks following an otherwise uncomplicated first vaccination against smallpox a boy, then aged 15 months … gradually developed a complete Kanner syndrome. The question whether vaccination and early infantile autism might be connected is being discussed. A causal relationship is considered extremely unlikely. But vaccination is recognized as having a starter function for the onset of autism.”

U.S. health authorities emphatically reject the idea of any such “starter function” — they cite multiple studies that have found no cause-and-effect relationship whatsoever between immunizations and autism.

But as outlined in earlier articles in this series, several parents of children 6 and under in the Washington state capital of Olympia are concerned about just such a connection. They point to an association between unusual chickenpox histories in families clustered in one Olympia neighborhood; close timing of their child’s live-virus chickenpox and measles-mumps-rubella shots, and the onset of regressive autism.

Two of the children were in clinical trials of Merck & Co. vaccines that involved investigational chickenpox formulations. One of those vaccines, ProQuad, was approved by the Food and Drug Administration last September. A combined chickenpox-MMR immunization, it contains about 10 times more chickenpox vaccine than the standalone Merck chickenpox shot, Varivax.

Several of the autistic Olympia children, coincidentally or not, got physically sick soon after those vaccinations, pointing to possible problems with their immune system’s handling of the attenuated (weakened) live viruses.

A striking case in point is Ryan Boe, who at age 18 months got four shots at one office visit including Varivax. (Ryan got his MMR shot two months earlier.)

Ryan’s mother, Lisa Boe, had an unusual case of chickenpox as a child, with only one “pock” appearing rather than the typical chickenpox pattern. But she definitely has had it, because she now tests immune.

Ryan’s father, Eric, has a sister who was diagnosed with shingles when she was 19. Shingles, the reactivated form of the chickenpox virus, painfully inflames nerve endings under the skin. It typically affects older people and those with weakened immune systems.

Like Richard M. 63 years earlier, Ryan got sick right after his shots. Like the “pockenschutzimpfung” child in Germany 30 years ago, Ryan’s behavior began changing within the month.

“Before we could leave the office he had an allergic reaction where he broke out in hives on his legs where they’d given him the shots,” Ryan’s mother recalls about that day — Nov. 3, 2003. “And then I think it was about two or three hours later after leaving the doctor’s office that he started running a fever.

“It went up to 105 and it lasted for five days. We were giving him Tylenol and Motrin, and as soon as those two things would run out he would spike right back up. He was very lethargic.

“Within a month after that is when you could look at pictures and start seeing him have no expression,” Lisa said. “We got pictures of going to look at Christmas trees and we had them developed right at Christmastime and my mom said, ‘There’s no expression.’

“I remember we went down for Christmas and I started saying to my mom, ‘Wow, he’s just different.’”

On Christmas morning, the only toy that interested Ryan was a Thomas the Train windmill. “He picked it up and just spun it. That was all he wanted to do. We have all these pictures and he’s just staring at the windmill.”

“At the end of that vacation, Christmas break, my mom said, ‘You need to go back to the doctor, something’s really wrong here.’ And people who hadn’t seen him since that summer said, ‘Whoa, he was just the happiest baby, and so much expression.

“‘And look at him — he looks so, just, lost.’”

Because autism is usually first noticed in the second year of life, it’s easy to mistakenly connect it to childhood immunizations given at that age, health authorities say.

The American Academy of Pediatrics refers those with such concerns to the National Network for Immunization Information, which it helps fund. Under “Vaccine Safety: Cause or Coincidence,” the NNII Web site (immunizationinfo.org) states:

“Many vaccines are given to children at the ages when developmental and other problems are being recognized for the first time. Because something happened at about the same time that a vaccine was given does not mean that the vaccine caused the problem. …

“Although vaccines have saved millions of lives around the world, some have blamed them for causing conditions that are not completely understood despite the fact that there is no scientific evidence that the vaccines caused the condition — for example, asthma, autism, diabetes type 1, multiple sclerosis, and sudden infant death syndrome (SIDS) among others.”

Parents are also told that signs usually were present from birth but that they missed them.

Lisa Boe said the idea that something was even subtly wrong with Ryan in his first year of life is nonsense, as confirmed by the observations of other family members and friends. After Ryan’s diagnosis, experts began telling her that subtle clues probably had been there all along, “and you get used to how your child is now, and so you think OK, well maybe he has been like this.

“But then I start putting away toys and I think no, he used to play with this, appropriately,” Lisa said. “He was riding his horsy around.

“And so I started finding out more about autism and the shots, and looking back at when we started seeing the problems, and I was like, well, those are the shots that he had, and that’s when we started seeing the problem.

“After the shots, he was gone.”

By DAN OLMSTED, UPI Senior Editor   |   May 15, 2006 at 11:21 PM

WASHINGTON, May 15 (UPI) — In a clinical trial of an investigational drug, two questions are front-and-center: “Does it work?” and “Is it safe?”

In two clinical trials of Merck vaccines in Olympia, Wash., the study protocols called for drawing the child’s blood; giving the shots; waiting 42 days, and then drawing blood again to see if antibodies developed.

That would show whether the drugs — in this case, attenuated or weakened live-virus vaccines against chickenpox, measles, mumps and rubella — were effective.

To answer the safety question, parents were asked to keep a log of any unusual events that occurred during the 42 days.

About halfway through that six-week “study window” a 1-year-old child in Olympia named Timothy Baltzley became quite ill. As outlined earlier in this series, Timothy got an investigational “process upgrade” chickenpox shot in January of 2001, along with the routine MMR immunization.

Timothy developed a fever that spiked to 102, and he was listless and sick to his stomach, his mother, Kimberly, recalled.

“He was just laying in one place,” she said. “We had to carry him down the stairs and things like that. He wound up after a couple of days being a little better,” and he appeared to completely recover.

But over the next few months, Timothy’s behavior became increasingly odd and his development stalled; eventually, he was diagnosed with full-syndrome autism. The clinical trial and the illness lingered in Kimberly’s mind.

Kimberly said Timothy’s trial was explained to her as a step in the development of a four-in-one chickenpox-measles-mumps-rubella vaccine — that’s why the chickenpox and MMR shots were given at the same. For the same reason, the chickenpox shot Timothy got had a much higher dose of virus than the standard shot, she recalls being told, although the consent form did not mention any increase.

A higher dose was necessary because when viruses are combined, they can interfere in ways that undercut the effectiveness of individual vaccines, she was told. Merck studies already had shown more chickenpox would be needed to overcome such interference in a four-in-one immunization.

Kimberly’s concerns were not assuaged when she met Jennifer Flinton, whose son, Jimmy, was diagnosed with autism after being in a subsequent trial nearly two years later at the same pediatrician’s office.

The shot Jimmy got was the four-in-one vaccine Kimberly had been told was under development in Timothy’s trial. Called ProQuad, it was approved by the Food and Drug Administration last September. ProQuad has about 10 times as much chickenpox virus as the standalone chickenpox shot. The consent form Jennifer Flinton signed for the ProQuad trial made no mention of that.

Merck said the trials Timothy and Jimmy participated in were unrelated; a spokesman did not respond to a question from UPI about how much chickenpox virus was in any of the shots.

Jennifer Flinton said she has a “very vague” recollection that Jimmy, like Timothy, had a temperature during his 42-day study window. “Because I was recording it every day, I did notice that it got close to 100 or at 100.”

The temperature was short-lived and not alarming because a slight fever was listed as a possible side effect of the shot. But four months later, Jimmy got acutely ill.

“He was laying there with his head drooped over,” she recalls, running a 102-103 temperature. The illness started on a Friday and was fading by Sunday — physically, that is.

“He came out of it and stopped pointing, clapping, speaking, eye contact, joint attention, the whole bit — everything that you’d write as a typical kid all went away.” The abruptness of the change did not immediately register with the Flintons; they thought he might simply be slow in recovering from the physical illness.

But two months later at his 18-month checkup, she told pediatrician Dr. Carl Lindgren, who had conducted both trials, about Jimmy’s loss of skills and the words he had been saying excitedly just a few months before.

“He seems to have stagnated,” she told Lindgren, broaching her concern that Jimmy had developed autism. “He had emerging skills and they were gone all of a sudden.”

Lindgren referred Jimmy to specialists at the Olympia School District, and by age 2 he had been diagnosed with full-syndrome autism. Jennifer said Lindgren told her after the diagnosis, “‘You’re probably going to hear something about vaccines being related to it.’ I think he just said, ‘Don’t be alarmed if you hear that.’”

Lindgren referred UPI’s questions about the trials to Merck. Although Jimmy’s physical illness occurred well outside the 42-day study window for the ProQuad vaccine, a company spokesman told UPI it reported both Jimmy’s and Timothy’s autism diagnoses to the FDA in March. That was when UPI first raised the issue with Merck and the federal agency.

Merck said it alerted the FDA after the parents reported the cases; Kimberly Baltzley and Jennifer Flinton said they never contacted the company. Kimberly said Lindgren told her in September 2001 he would report Timothy’s diagnosis to the study even though he did not believe there was a connection; Jennifer called the federal government’s Vaccine Adverse Event Reporting System last summer and attributed Jimmy’s autism to the cumulative effect of his vaccinations.

Jimmy and Timothy each have family histories of problematic reactions to chickenpox and other herpesviruses, raising concern they might have been unusually vulnerable to the high-dose chickenpox vaccines. Parents of other autistic children the same age who lived in the same Olympia neighborhood say they saw a similar pattern: problems with those viruses in their families; separate but in most cases simultaneous MMR and chickenpox shots by 15 months; and the onset of regressive autism in their children prior to 18 months of age.

Both Kimberly Baltzley and Jennifer Flinton said they do not know if the trial, the physical illnesses and the subsequent autism diagnoses are related in any way. They are concerned, though, that both cases fit with a controversial theory: because of immune interference, combination live-virus vaccines might warp the body’s normal immune response, trigger persistent infection by one or more of the viruses and cause delayed but devastating damage to the child’s developing brain — namely, regressive autism.

Federal health authorities and Merck said there is no evidence of such a biological mechanism — calling it “theoretical only” — or any link between vaccinations and the disorder. There is no dispute, however, that vaccines can trigger physical and neurological problems.

Merck is conducting an ongoing study of fever-related seizures following ProQuad immunization, a study the FDA cited when it approved ProQuad last September.

“Merck will conduct a large-scale observational post-licensure safety study to evaluate the rate of febrile seizures in recipients of ProQuad in 25,000 subjects,” the FDA’s Norman W. Baylor, director of the Office of Vaccines Research and Review, wrote Merck in the approval letter.

The study was to begin in January and be completed by June 2008, the approval letter said.

“A seizure is an abnormal electrical discharge from the brain,” according to the pediatric neurology Web site childbrain.com.

As Jennifer Flinton thought back over Jimmy’s ProQuad clinical trial, she realized something. There had been no second blood draw to test for immunity, despite the protocol detailed on the consent form:

“At the second visit the study doctor or staff will draw a blood sample … to determine if your child has responded to the vaccination. … If the study vaccine works for your child, it may protect your child against developing meales, mumps, rubella, and chickenpox. On the other hand, it may not work for your child and there may be no benefit.”

Jennifer recently asked the doctor about that and says she was told the study already had enough data when it came time to draw Jimmy’s blood; the information was no longer needed for the clinical trial.

So along with concern the vaccine might not have been safe for Jimmy, no one knows if it worked, either.

—

Next: Ryan’s reaction

By DAN OLMSTED, UPI Senior Editor   |   May 13, 2006 at 9:09 AM

WASHINGTON, May 13 (UPI) — When Timothy Baltzley of Olympia, Wash., went for his 1-year-old well-baby checkup in December 2000, his mother was invited to enroll him in a clinical trial of experimental chickenpox vaccine.

The eight-page consent form said two versions of a “process upgrade” vaccine manufactured by Merck & Co. were being compared. Children ages 12 to 23 months would get one of the shots at random at the same time as their standard measles-mumps-rubella inoculation.

Known as P31 and P32, the chickenpox shots were “investigational vaccines, which means they have not been licensed for marketing by the U.S. Food and Drug Administration,” according to the consent form.

Timothy’s mother, Kimberly Baltzley, signed the form and Timothy got the chickenpox and MMR shots on Jan. 3, 2001, a couple of weeks after his first birthday.

Everyone agrees on all that. But exactly why Merck was testing those chickenpox vaccines is in dispute, and just how much attenuated live chickenpox virus was in each shot is uncertain — potentially significant facts given that Timothy later was diagnosed with autism.

Timothy was the first of two children in less than two years to develop autism in the same Olympia pediatric practice after participating in Merck trials involving chickenpox and MMR vaccines. The second child, Jimmy Flinton, got a four-in-one chickenpox-MMR shot called ProQuad in October of 2002.

Timothy’s trial had 68 children; Jimmy’s had 33. Along with participating in the trials, Timothy and Jimmy have in common unusual family backgrounds of problems with chickenpox virus.

Kimberly had mild cases twice as a child and then a severe case at 16, three years before Timothy was born; her 15-year-old sister, Amanda, had an even worse case at the same time, leading to scars and ongoing balance problems from pox in her inner ear.

Jimmy’s paternal grandmother had shingles — the reactivated form of the virus — at 20 and recurrent cold sores that led to herpesvirus in her corneas; Jimmy’s father had shingles at 16. Shingles usually afflicts older people or those with weakened immune systems.

Parents of other autistic children the same age who lived in the same Olympia neighborhood say they saw a similar pattern: an unusual history with chickenpox and other herpesviruses in their families; separate, but in most cases simultaneous, MMR and chickenpox shots by 15 months; and the onset of regressive autism in their children prior to 18 months of age.

While Merck and federal health authorities say there is no evidence of a link between vaccines and autism, a minority of researchers are concerned that inherited susceptibility to viruses in vaccines might constitute an unrecognized risk factor. They say the Olympia children may be troubling cases in point, underscored by Jimmy’s and Timothy’s diagnoses after similar clinical trials.

The consent form Kimberly Baltzley signed for Timothy made no mention of the amount of vaccine in the “process upgrade” chickenpox shots. But she said her pediatrician told her it was significantly higher than the standard shot because the trial was part of the development of a combined chickenpox-MMR vaccine — the shot Jimmy received two years later.

Combination vaccines can require higher doses to overcome a phenomenon known as interference, in which viruses undercut each other’s ability to trigger an immune response.

“My understanding at the time was they were trying to combine the MMR and the chickenpox,” she said one recent evening while straightening up after a meeting of a local support group she heads up for parents of autistic children.

“The way it was explained to me was they knew that when they combined them, they had to increase the amount of chickenpox that was in there,” she said. “(The doctor) said the worst thing, barring some kind of an allergy or other reaction we don’t know about, is that there is so much chickenpox virus in there that kids will catch the chickenpox. That’s what they were trying to figure out.

“They (the shots) were given separately because, I was told at that time, they had not been given the OK to combine them,” she said.

“What they were trying to do was get the OK.”

A neighbor of the Baltzleys whose daughter was in the same clinical trial was given the same explanation, she said.

Merck, however, offered an entirely different explanation of the trial, saying it had nothing to do with developing the four-in-one ProQuad shot.

“Please note (the study) was NOT a trial of ProQuad nor was it conducted for any reason related to ProQuad,” Merck spokeswoman Christine Fanelle said in an e-mail response to questions from United Press International.

“It was a trial we conducted in preparation for a process upgrade done for manufacturing purposes only,” she said.

When UPI sent Kimberly Baltzley’s description of the trial to Fanelle, she responded: “All I can do is confirm once again that our records indicate that (the pediatrician) participated in the two trials I noted.”

Fanelle did not directly respond to a question about how much chickenpox virus was in the process-upgrade shots, saying that “P31 and P32 work the same way — both stimulate antibodies against the varicella (chickenpox) virus. The manufacturing process is what would differ in subtle ways.

“Further details around our manufacturing process upgrade varicella vaccine are proprietary for competitive reasons,” Fanelle said. The FDA did not respond to requests for comment about the trials. The Olympia pediatrician, Dr. Carl A. Lindgren, referred questions to Fanelle.

Also at issue is when and why Merck alerted the FDA to the two autism cases. Fanelle told UPI that Merck “just received these reports in March 2006 and they were sent to the FDA after we received them.” That was the same month UPI first raised the issue with Merck and the FDA.

Fanelle said Merck received the reports from parents.

Kimberly Baltzley and Jennifer Flinton said they didn’t make any such reports. “If they want me to call them I will,” Kimberly Baltzley said when told of Merck’s account, “but I don’t have their number.”

What did happen, she said, is that nearly five years ago, she returned with Timothy to her pediatrician, concerned about developmental delays and strange behavior in the months since his participation in the study. The doctor said Timothy should be evaluated by experts, and he subsequently received an autism diagnosis. They also discussed the chickenpox-MMR trial and the controversy over whether vaccines can trigger the disorder.

“He told me, ‘I don’t think they had anything to do with each other, but I have to report any kind of problem to the trial.’ He told me that back in September of ’01. Dr. Lindgren is a very conscientious person so I know he probably reported it that week.”

In Jimmy’s case, Jennifer Flinton said she called the federal government’s Vaccine Adverse Event Reporting System last summer. She attributed Jimmy’s autism to the cumulative effects of vaccination, although she did not specifically mention the 2002 ProQuad trial.

The employee who spoke with her said she would follow up by obtaining Jimmy’s vaccination records for an official adverse event report.

ProQuad was approved by the FDA last September. Because of immune interference among the components, Merck’s Fanelle said, “we had to increase the varicella component,” but she did not specify the amount. Other officials have said that amount was “about a log,” or ten times, higher than the standalone Varivax chickenpox shot.

“However, our studies showed the same safety and immunogenicity profile was seen with ProQuad compared to the profile seen with the two vaccines administered as separate shots,” Fanelle said.

—

Next: Getting sick

By DAN OLMSTED, UPI Senior Editor   |   April 29, 2006 at 8:16 PM

When 12-month-old Jimmy Flinton joined a clinical trial of a new immunization for chickenpox, measles, mumps and rubella, no one told his family it contained about 10 times the usual dose of live-virus chickenpox vaccine.

And no one considered whether his family’s unusual chickenpox history — including adolescent shingles and herpesvirus in the eyes — might raise the risk of adverse reactions to the vaccine.

Now that Jimmy has been diagnosed with regressive autism, they wish someone had done so.

In 2002 Jimmy’s mom, Jennifer Flinton, signed a seven-page “Research Subject Consent Form — Vaccine Study (Children)” at the office of her pediatrician in Olympia, Wash.

“Your child is invited to be in a research study,” reads the form, which lists Merck & Co. of Whitehouse Station, N.J., as the sponsor. “You need to decide whether or not you want your child to be in this study. Please take your time to make your decision.”

The purpose was “to test the safety of the study vaccine, ProQuad refrigerated and to show that this vaccine provides a similar level of protection as compared to another study vaccine, ProQuad frozen.” Both versions contained attenuated — substantially weakened — live viruses designed to trick the body into developing immunity to real-live measles, mumps, rubella (German measles) and chickenpox.

Previously, those first three vaccines were combined into one shot called the MMR, made by Merck; the chickenpox vaccine came in a separate shot called Varivax, also by Merck.

ProQuad was Merck’s investigational vaccine designed to put all four in one shot.

Tests already had determined ProQuad required more chickenpox virus than Varivax to produce the same level of immunity. A phenomenon called immune interference, in which viruses interact and interfere with each other in the human body, rendered the dose from the standalone vaccine insufficient.

The consent form Jennifer Flinton signed did not say anything about more chickenpox virus. It simply said ProQuad was “a combination of two licensed vaccines,” the MMR and Varivax.

Merck wouldn’t confirm exactly how much more chickenpox virus is in ProQuad, characterizing it only as “higher.” But in 2004, a Merck scientist said the amount in ProQuad was “about a log” — 10 times — higher, according to minutes of a meeting at the Centers for Disease Control and Prevention.

As already reported in this series, Jimmy Flinton’s family is one of several in the same Olympia neighborhood who spotted a common thread: They had unusual histories of chickenpox and other herpesviruses in their families; their child got the chickenpox and MMR shots in close temporal proximity, often at the same 12-month office visit when both are first recommended; and the child subsequently was diagnosed with regressive autism.

Jimmy is one of two children who were in small trials at age 12 months of chickenpox and MMR vaccines. Jimmy’s group had 33 participants, according to the Western Institutional Review Board in Olympia, which approved the protocol.

The second child was among 68 trialing Merck “process upgrade” chickenpox shots given with the standard MMR.

The local trials were part of Merck studies of the vaccines in the United States and abroad. Spokeswoman Christine Fanelle would not address whether any other cases of autism had been reported in the broader trials, but she emphasized that neither Merck not independent experts have found a relation between vaccines and autism.

“We don’t see an association,” she said, citing as confirmation a 2004 report by the widely respected Institute of Medicine, part of the National Academies. That report rejected a link between autism and either the MMR vaccine or the mercury-based vaccine preservative thimerosal, and it urged that research dollars be spent on “more promising” autism research.

“There will always be some people who say vaccines cause autism despite the lack of scientific evidence,” Fanelle said.

Based on their admittedly anecdotal observations, however, the Olympia parents are concerned that inherited problems handling vaccine viruses may be an overlooked risk factor for autism in some children.

Jimmy Flinton’s paternal grandmother, Mary Southon, had a routine case of chickenpox in kindergarten. Fifteen years later, in 1970, she developed shingles on her right leg — painful, blister-like pustules at nerve endings caused by reactivated chickenpox virus.

That is decidedly not routine. Shingles usually occur in older people or those with immune suppression, such as cancer patients undergoing chemotherapy.

“I was a healthy 20-year-old woman,” Southon said, recalling her surprise at the outbreak. The infection lasted several weeks and left her with permanent mild circulatory weakness in her leg and edema just above the ankle.

“I remember how painful it was and how it seemed to go on for the longest time,” said Southon, who lives in Olympia. She was going through a divorce at the time and suspects stress might have triggered the outbreak. She also suffered from lifelong recurrent cold sores, another herpesvirus.

Twenty years later, in 1990, Southon made a painful mistake that reminded her of that vulnerability.

“What happened was, I stuck a hard contact (lens) in my mouth, not knowing I was getting a cold sore. I put it into my eye and did it with the other contact, too.

“I developed cold sores on both corneas. That was very painful and went on for several weeks before the doctors finally figured out what it was,” she said. The doctor put her on medication for shingles and the problem cleared up, though not before doing damage she says will one day require cornea transplants.

Coincidentally or not, Southon said she has not had any cold sores since she took the shingles medicine.

Her son, Paul Flinton, also had chickenpox as a child. At age 15, Paul got shingles, too — also remarkable, doubly so given his mother’s similar history. The shingles spread along his neck, primarily on the right side, up to his jaw line; he even had a spot on his forehead.

“The doctor did diagnose it as shingles and was just amazed someone that young had developed it,” Southon recalled. It was also a stressful period in Paul life’s, she said, but the ongoing family pattern suggests unusual, inherited susceptibility to the virus.

“It just seems there is a genetic weakness towards it, a tendency to pick up the herpesvirus and run with it,” Mary Southon said. Given that, they might not have enrolled Paul son’s Jimmy in the ProQuad trial if they knew it had 10 times the standard dose of chickenpox virus.

She questioned why Merck would allow a child with Jimmy’s family background to test any chickenpox vaccine.

“It’s heartbreaking to think this could have been prevented if they (Merck) had done a little more research or had been a little more imaginative in (considering) what could have happened,” she said.

“I just think the rush to develop the vaccine is criminal. Why would they want to give babies 10 times the amount of the virus? Where is the thinking on that?”

Several vaccine researchers who remain concerned abut a possible autism link told this column they find the Olympia cluster, and Jimmy’s case in particular, deeply disturbing. The children’s histories fit one of the major vaccine-autism hypotheses like a surgical glove: the idea that interference among live viruses in vaccines could warp the body’s natural immune response, leading to persistent infection and delayed neurological problems.

After Age of Autism outlined the cases to him last month, British gastroenterologist Dr. Andrew Wakefield — the chief proponent of that controversial theory — met with several of the Olympia parents. He called their stories heartbreaking and likened the experience to “staring into an abyss” of unintended vaccination consequences that he fears are not confined to Olympia.

“The key to many of the problems you see with viral vaccines is interference,” he said afterward.

“The host control of a viral infection is fundamentally mediated through an adequate immune response, and that immune response has been conditioned by tens of thousands of years of evolution,” said Wakefield. “And the outcome of an infection is dependent on the pattern of exposure.

“So measles is innocuous when encountered under normal circumstances of dose and age of exposure. But when it’s encountered under atypical circumstances early in life, particularly at high dose, then the outcome is very different. And the problem for these viruses is persistence and delayed disease,” he said.

“So if they can establish persistent infection, elude the host immune response, then they can all come back and cause delayed disease later in life.”

“And herpesviruses do exactly the same thing,” he added.

“What alarms me about the cavalier approach of the industry and everybody else, the regulators, to these viruses is they presume the wild infection to be nasty and the vaccines to be innocuous — that they can manipulate something that is biologically highly intelligent and exploit it to their advantage.

“And they can’t. The viruses don’t behave like that and they never will. They merely come back to haunt you as something different.”

Wakefield, who left Britain in the wake of the controversy generated by his theories and now is conducting research in the United States, said it is well-established that problems coping with viruses can be inherited. His theories are based on research into the MMR vaccine; Britain does not give routine chickenpox immunizations.

The Institute of Medicine’s 2004 report dismissed Wakefield’s concerns as speculation untethered to any scientific foundation. It said “the body of epidemiological evidence favors rejection of a causal relationship between the MMR vaccine and autism. … The committee further finds that potential biological mechanisms for vaccine-induced autism that have been generated to date are theoretical only.”

“The overwhelming evidence from several well-designed studies indicates that childhood vaccines are not associated with autism,” said Dr. Marie McCormick of the Harvard School of Public Health, who chaired the IOM’s immunization review committee.

“We strongly support ongoing research to discover the cause or causes of this devastating disorder. Resources would be used most effectively if they were directed toward those avenues of inquiry that offer the greatest promise for answers. Without supporting evidence, the vaccine hypothesis does not hold such promise.”

The CDC, whose Advisory Committee on Immunization Practices recommends the childhood vaccination schedule that states adopt, funded the Institute of Medicine study along with the National Institutes of Health.

“Groups of experts, including the American Academy of Pediatrics, agree that MMR vaccine is not responsible for recent increases in the number of children with autism,” the CDC noted.

“The existing studies that suggest a causal relationship between MMR vaccine and autism have generated media attention,” the CDC said. “However, these studies have significant weaknesses and are far outweighed by the epidemiologic studies that have consistently failed to show a causal relationship between MMR vaccine and autism.”

On Oct. 30, 2002, James George Flinton had his blood drawn as a baseline for the clinical trial in Olympia. At the same office visit, he got the ProQuad shot — the refrigerated version, as it turned out.

For his participation, Jimmy’s family got a $50 gift certificate, with another to come at the end of a 42-day safety follow-up period when his blood would be drawn again to see if ProQuad worked.

Last September, the Food and Drug Administration approved frozen ProQuad for children 12 months to 12 years old. Merck said it is still working on the refrigerated version.

—

Next: Downward spiral

By DAN OLMSTED, UPI Senior Editor   |   April 20, 2006 at 10:27 PM

This week, The Age of Autism began a series of articles entitled “Pox,” laying out the compelling observations of a group of parents in Olympia, Wash., who are concerned live-virus vaccines are triggering autism.

These parents spotted a possibly troublesome trio of factors in their children’s cases: Chickenpox and measles-mumps-rubella (MMR) vaccinations clustered together at the earliest recommended ages; a family history of problematic reactions to naturally occurring chickenpox and other herpesviruses; and the onset of autism in their children, often following a brief but notable physical illness.

Two of the children had been in clinical trials in Olympia of vaccines not yet approved by the U.S. Food and Drug Administration, vaccines with investigational chickenpox formulas. The FDA subsequently approved one of those drugs, called ProQuad, last September.

What does the FDA say to these concerns, and in particular to a case of regressive full-syndrome autism after a clinical trial of a drug it just approved?

Nothing.

In Part 1, we reported: “The Food and Drug Administration, which approves drugs after determining they are safe and effective and monitors reports of side effects after they come on the market, did not respond to repeated inquiries from UPI about the Olympia cases or parents’ concerns about family chickenpox histories.”

On Monday, March 20 — a month ago — I sent an e-mail to FDA spokesman Stephen King asking about the autistic Olympia children from the clinical trials. King had already told me that there were no minutes available for an FDA advisory committee hearing prior to ProQuad’s approval, because no meeting had been held.

Such meetings sometimes are called if there are concerns about safety or other issues surrounding proposed or already-approved medicines.

ProQuad combines the existing MMR and the standalone chickenpox vaccine, Varivax, but with a major difference: It contains about 10 times more chickenpox vaccine, apparently in order to overcome immune interference from the other weakened live viruses in the shot.

My e-mail:

“Hi Stephen,

I left you a voice mail last week and wanted to follow up with this written query. …

Questions:

— Was the FDA aware of these or any other reports of autism following (clinical trials)? If not, would they have been of concern and are they of concern now?

— Why was it necessary to put significantly more varicella (chickenpox) virus in ProQuad than in the standalone Varivax shot? …

— Has the FDA ever considered immune status of parents re live virus vaccines as a possible factor in the child’s ability to handle them? The mother of one of the children had a severe case of chickenpox just three years before her child was born; the father of the other had shingles as a teenager, which is unusual.

Thanks for considering these questions. I would appreciate hearing from you this week.

Sincerely,

Dan Olmsted

United Press International”

There was no response.

I also learned that one of the Olympia parents, Jennifer Flinton, last summer called the federal government’s Vaccine Adverse Events Reporting System, jointly monitored by the FDA and the Centers for Disease Control and Prevention, to report her son Jimmy’s autism. She attributed his regression to cumulative exposure to vaccinations; the worker who took the report said she would follow up by collecting all the information about the vaccines he was given.

Jimmy Flinton had been in the ProQuad clinical trial in 2002 and developed autism four months afterwards. He was one of 33 children in the Olympia arm of the trial.

Merck & Co., which funded the trials and manufactures the vaccines involved including ProQuad, said it reported the two autism cases from Olympia to the FDA this March, which is when Age of Autism first asked about them. Merck said that is also when the parents made the reports, but the parents said they don’t know what Merck is talking about.

Maybe federal health officials have just plain had it with these concerns, which they clearly consider preposterous. Study after study, they say, has shown no evidence that vaccines are linked to autism, and in 2004 the widely respected Institute of Medicine said the case was closed and it was time to look elsewhere for the cause or causes of autism. Dr. Marie McCormick, the distinguished Harvard professor who headed that review, famously derided as “really terrifying, the scientific illiteracy that supports these suspicions.”

A single case several months after a child receives an investigational chickenpox vaccine in a trial with 33 other children certainly wouldn’t threaten that view.

Nor would another case at the same pediatrician’s office in the same city using the same live viruses in another small clinical trial, this one with 68 kids.

Nor would problematic chickenpox histories in those families, nor would the same pattern among other families with autistic children in the same neighborhood. …

Still, at some point, wouldn’t you expect someone somewhere in the nation’s public health hierarchy to raise an eyebrow? Yet getting anyone’s attention is just about impossible — in Washington state no less than Washington, D.C.

Dr. Diana Yu of the Thurston County Health Department in Olympia insisted to me over a period of several weeks that no clinical trials whatsoever had been conducted by any pediatricians there. This, despite my faxing her consent forms signed by the parents.

One seven-page documents begins: “Research Subject Consent Form: Vaccine Study — Children. Your child is invited to be in a research study … The study is being done for Merck & Co. … (B)oth investigational drugs … have not been licensed by the U.S. Food and Drug Administration.”

Yu told me: “None of the practices were in any ‘clinical trials’ as part of any vaccine study. Some practices may have been ‘trying things out’ but have not made it a policy for their clinic yet. With all due respect, these doctors are not on trial and should not be painted with such a broad stroke.”

Nobody’s indicting pediatricians. It’s public health officials and drug companies they’re wondering about.

“I worry about pediatricians being vilified,” said Denise Rohrbeck, one of the Olympia parents quoted in Pox — Part 1. “We vaccinated our son because we shared their faith that vaccines were safe.

“If it turns out that some vaccines are not safe for all children and that these hazards could have been found with more rigorous testing — or worse, that the dangers were already known — that’s the fault of the CDC, the FDA and the manufacturers,” she said.

Meanwhile, another potentially significant issue in Olympia remains unanswered weeks after I raised it with the health department there. The first thing that caught the parents’ attention was a seeming absence of autism cases at one of the two big medical practices in town, Pediatric Associates.

The parents, who know each other through a countywide support group, haven’t been able to find a single case of full-syndrome autism among preschoolers who were vaccinated from birth at PA, as the parents call it.

Anecdotal, yes — but intriguing: Autism cases are not hard to find at the other pediatric practices in town, no surprise given a rate of autistic disorders of 1 in 166 American children.

So what’s up at PA?

Parents say they learned at least half the doctors there delay the chickenpox and MMR shots until 18 months, and the other half tend to break them up — giving one at 12 or 15 months and the other about six months later. Records parents gathered suggest this trend at PA started sometime after 2000 — records collected from 1999 show the two shots given together as early as 12 months.

Interestingly, parents found full-syndrome kids from PA born before 2000.

The CDC recommends that the MMR and chickenpox shots be given as soon as possible beginning at 12 months and no later than 15 months for the MMR and 18 months for chickenpox. That’s when the autistic kids the parents in Olympia are talking about got them — sooner rather than later and usually at the same time, not widely spaced or starting at 18 months as appears to be the case at Pediatric Associates.

Thus the PA kids and their shot patterns might be an informal “control group” right in the middle of this state capital of just over 50,000 on the South Puget Sound.

Pediatric Associates did not respond to questions about its immunization policies. Neither did the county health department, although Yu acknowledged it would be “simple” for the department to check its records and determine whether there really is a difference in immunization schedules.

As this series on the Olympia kids unfolds over the next several weeks, the parents are hopeful that more information — maybe even some sort of response from the nation’s drug regulators — will be forthcoming.

Stay tuned. Don’t hold breath.

By DAN OLMSTED, UPI Senior Editor   |   April 19, 2006 at 5:46 PM

Children in families with problematic reactions to chickenpox virus may be at risk for developing autism if they get that live-virus immunization too close to other live-virus vaccines, a three-month United Press International investigation of cases in one northwest U.S. city suggests.

Several such families in the Washington state capital of Olympia watched their children regress into full-syndrome autism — losing language and social skills and adopting repetitive behaviors — in the months following the shots. Two children had participated in small clinical trials in Olympia of investigational Merck & Co. chickenpox vaccines in combination with the live-virus mumps-measles-rubella vaccine — the MMR.

Federal health authorities consistently have rejected concerns about a link between immunizations and autism. But a family background of problems coping with viruses used in live-virus vaccines has not been considered a possible risk factor, experts said.

One of the children in the clinical trials, Jimmy Flinton, now 4, got about 10 times the standard dose of chickenpox vaccine in a shot that also contained the MMR.

Called ProQuad, that combined immunization was approved by the U.S. Food and Drug Administration last September — the first time four “attenuated” or weakened live viruses have been mixed together in a single shot.

The second child, Timothy Baltzley, now 6, got an investigational “process upgrade” chickenpox shot and a separate MMR shot at the same office visit.

Both children have a parent who had unusual reactions to chickenpox virus.

Timothy’s Baltzley’s mother, Kimberly, had chickenpox three times, the last at age 16, just three years before he was born. Jimmy Flinton’s father, Paul, had shingles as a teenager. Shingles is reactivated chickenpox virus that painfully inflames nerves and mostly affects older people or those with weakened immune systems.

Both children got the vaccines at 12 months, the age at which chickenpox and MMR immunizations are first recommended by the Centers for Disease Control and Prevention. They were among a total of 101 subjects in the two trials in Olympia, according to the Western Institutional Review Board, which approved the trial protocols.

Half-a-dozen other parents of preschool-age autistic children from the same neighborhood in Olympia recognized a common thread: unusual chickenpox histories in their families and simultaneous or closely timed chickenpox and MMR shots in their children.

“It’s the proximity of the chickenpox and MMR vaccinations” and the family histories that stand out, said Denise Rohrbeck, mother of 3-year-old Grant.

Rohrbeck has not been able to develop immunity to chickenpox despite being twice vaccinated as an adult, the last time just two years before her son was born. A couple of months before he got the standard chickenpox and MMR shots at the same office visit at age 1, Grant had a stubborn and severe case of roseola, which like chickenpox is a herpesvirus.

Four days after the MMR and chickenpox injections he became ill with a fever and lay limp in his mother’s arms for the first time in his life.

“He began having chronic diarrhea, and by his 15-month checkup he had regressed so drastically that his pediatrician suggested he could be autistic,” Rohrbeck recalled. The doctor agreed to the parents’ request for an immediate neurodevelopmental evaluation, which resulted in a diagnosis of full-syndrome autism.

Rohrbeck said she began looking for a possible connection between vaccines and autism among neighborhood children after the Thurston County Health Department did not follow up on parents’ concerns raised at a meeting last October. With the parents’ continued involvement, she has now compiled vaccination records of 14 Olympia children diagnosed with autism, as well as 16 who are not.

The admittedly unscientific chickenpox-MMR association continues to be striking, and the two cases following the clinical trials seemed to underscore it, she said.

A Merck spokeswoman said the company reported those two cases to the FDA this March — the same month UPI asked Merck about them.

“We just received these reports in March 2006, six months after ProQuad was approved in the U.S., and they were sent to the FDA after we received them,” Merck’s Christine Fanelle said in a statement. She said Merck received “the two reports of autism AEs from Olympia — one from the parent of a child in the ProQuad trial and one from the parent of a child in (the ‘process upgrade’ chickenpox) study.”

Parents Jennifer Flinton and Kimberly Baltzley say they never called Merck and wouldn’t know who to contact there; last summer, Jennifer Flinton reported Jimmy’s autism to the federal government’s Vaccine Adverse Events Reporting System, attributing it to the cumulative effects of vaccination. The federal health employee she spoke to on the phone said she would follow up by gathering lot numbers and other information on the vaccines.

The parents said their pediatrician, who conducted both of the Merck-funded trials in Olympia, knew about their children’s autism diagnoses within months of their participation in January 2001 and October 2002.

The Olympia trials were part of wider Merck studies conducted at several sites in the United States and abroad. Fanelle said Merck would not disclose information about any other reports of autism.

“We have confirmed your original inquiry on whether we received the two reports out of Olympia,” she said. “We are not going to comment on reports beyond this.

“There were more than 7,000 children in our ProQuad trials, 5,800 of whom received ProQuad vaccine,” she added.

Diana Sparby of the Western Institutional Review Board in Olympia said it had not received reports of autism from the local ProQuad study, but she noted the protocol “was not designed to assess long-term safety, as it called for follow-up for only 42 days following vaccine administration.”

The FDA, which approves drugs after determining they are safe and effective and monitors reports of side effects after they come on the market, did not respond to repeated inquiries from UPI about the Olympia cases or parents’ concerns about family chickenpox histories.

Other unusual histories in neighborhood families with autistic children 6 and under:

— Another child had roseola 12 weeks before getting his chickenpox and MMR shots;

— Another father had shingles as a teenager;

— Another mother had chickenpox as an adult two years before her pregnancy;

— A mother had chronic cold sores, also a herpesvirus, as a child that were so severe they had to be treated medically;

In addition, another mother had a case of measles as an adult.

Merck, which manufactures the standard MMR shot and the standalone Varivax chickenpox shot as well as the experimental vaccines used in the clinical trials, said repeated studies show no relation between vaccines and autism.

“We don’t see an association,” spokeswoman Fanelle said, citing as confirmation a 2004 report by the widely respected Institute of Medicine, part of the National Academies. That report rejected a link between autism and either the MMR vaccine or the mercury-based preservative thimerosal. The report also urged that research dollars be spent on “more promising” autism research.

“There will always be some people who say vaccines cause autism despite the lack of scientific evidence,” Fanelle said.

In the United States, controversy over a possible link has centered on thimerosal. Beginning in the late 1980s children were exposed to increasing amounts of thimerosal, which is half ethyl mercury, as more vaccines were mandated.

Thimerosal was phased out of routine childhood immunizations — but not all flu shots given to children and pregnant women — beginning in 1999. Although the Olympia children with autism were born after the phase-out was recommended, their vaccine records show more than half of them got at least one shot containing thimerosal during the first year of life. It is possible all of them did, but incomplete information from manufacturers makes that uncertain.

Chickenpox and MMR immunizations don’t contain thimerosal because the mercury would inactivate the viruses, but some proponents of a vaccine-autism link suspect thimerosal exposure from other immunizations could have a potentiating effect, damaging a child’s defenses and paving the way for live viruses to wreck havoc.

All live-virus vaccines are attenuated — significantly weakened based on the theory that this creates immunity without causing the actual disease or other adverse health consequences. Other vaccines on the U.S. childhood immunization schedule, including hepatitis B and the polio shot, contain killed or so-called inactivated viruses. Live polio virus was dropped in 2000 after health authorities determined it was actually causing polio in a small number of cases.

Despite the Olympia parents’ concern, none points an accusing finger at doctors.

“I worry about pediatricians being vilified,” said Rohrbeck. “We vaccinated our son because we shared their faith that vaccines were safe.

“If it turns out that some vaccines are not safe for all children and that these hazards could have been found with more rigorous testing — or worse, that the dangers were already known — that’s the fault of the CDC, the FDA and the manufacturers,” she said.

“I’ll defend doctors to the end on this point. They are a convenient front line for those agencies to hide behind — it’s just shameful.”

The theory that live virus immunizations could trigger autism first arose in 1998 in Britain, when gastroenterologist Dr. Andrew Wakefield published a paper suggesting a possible association between childhood MMR immunization, bowel disease and regressive autism.

The premise: Interaction between viruses — scientifically known as immune interference — could depress a susceptible child’s immune system, lead to persistent infection by the measles virus in the GI tract and possibly the nervous system itself, and trigger autism-inducing brain damage. While the case has not been proven, it gains plausibility from the fact that naturally occurring measles infection is known to cause delayed brain damage in a small percentage of children, proponents of the theory say.

Wakefield’s study, and his plea in Britain to separate the component measles, mumps and rubella (German measles) vaccines and administer them a year apart to reduce possible risk, caused an uproar. Co-authors subsequently repudiated part of the paper, conflict-of-interest allegations emerged, and the prestigious Lancet, which originally published the study, issued a statement calling it “fatally flawed.”

Wakefield was asked to leave his medical job in Britain and is now doing research in Austin, Texas.

After the Olympia cases were described to him by UPI in March, Wakefield met with several of those parents at an autism conference in Portland, Ore. He also read studies Merck cites as central to the FDA approval of ProQuad.

“It’s actually heartbreaking, listening to these parents, because you’re staring into an abyss,” Wakefield said afterwards. “You’re listening to stories which reflect the fundamental misconception of vaccine manufacturers of what viruses are and what they do. The whole perception of these people is dangerously naïve.”

In contrast to the United States, British health authorities have not recommended chickenpox immunization. But an MMR-chickenpox shot was under discussion there at one point, and Wakefield said he warned its developers that putting four live viruses in one shot was a bad idea.

He says the Olympia cases show why.

“As far as I’m concerned, you are further increasing the likelihood of persistent infection and delayed disease, which they are never looking for and therefore they will never find if it does occur, as it did clearly in a relatively short space of time with some of these children, and it’s never ascribed to an adverse reaction to the vaccine.”

On its Web site, the CDC says such concerns — and Wakefield’s studies in particular — are not based on good science.

“Current scientific evidence does not support the hypothesis that MMR vaccine, or any combination of vaccines, causes the development of autism, including regressive forms of autism,” the CDC says.

“The existing studies that suggest a causal relationship between MMR vaccine and autism have generated media attention. However, these studies have significant weaknesses and are far outweighed by epidemiological studies … that have consistently failed to show a causal relationship between MMR vaccine and autism.”

(http://www.cdc.gov/nip/vacsafe/concerns/autism/autism-mmr.htm)

Dr. Jeff Bradstreet, a family practitioner in Florida who treats 3,000 autistic children and has worked with Wakefield, said he believes the risk of autism rises the earlier and closer together that live-virus vaccines are administered. He warned the Institute of Medicine in 2004 that it was ignoring the possibility that younger children are more vulnerable because their immune and neurological systems are immature.

“There’s definitely been an association of kids getting MMR at 12 months and crashing (becoming autistic),” Bradstreet said.

He said adding 10 times the standard dose of chickenpox virus, called varicella-zoster, to the MMR shot and administering it to 1-year-olds is playing with fire.

“We think putting varicella with MMR is just nuts.”

British researcher Paul Shattock sees another reason to be concerned with combining the four viruses: He suspects that children who get wild — or naturally occurring — chickenpox too close in time to the MMR shot face a higher risk for autism. That scenario parallels the one Olympia parents noticed with the chickenpox vaccination.

Shattock, director of the Autism Research Unit in the School of Sciences at the University of Sunderland, said he noticed that autistic British children whose parents blame the MMR for triggering the disorder had a pattern of “undisclosed viral illness” around the time of the shot.

He studied the records of 100 of those children, compared to 100 children whose parents did not cite the MMR as the trigger, to see if there was a higher incidence of chickenpox cases three months before or after the MMR immunization.

“Now, there was,” Shattock said in an interview while attending an autism conference this month in Washington, D.C. “It wasn’t statistically significant at the 95 percent level — but enough to make you think that if it was a huge study, it might be.”

His concern about adding chickenpox to the MMR shot: “I’m worried about it because of the interference of the vaccines, mainly because it depresses the immune system by yet another mechanism.”

A Merck scientist discussed that issue at a CDC meeting in 2004, the year before ProQuad was approved, according to agency minutes. Dr. Florian Schodel “confirmed the possibility” that the chickenpox virus component of ProQuad was “causing a local immune suppression and an increase in measles virus replication. …

“The current hypothesis is that the varicella and measles virus are co-infecting the same or proximate areas of the body and engaging in a specific interaction, but how that works is as yet unknown.”

He said the interference appeared to involve only the chickenpox and measles viruses — “there is no such effect for the mumps or rubella vaccines administered locally at the same time.”

At the same meeting, Merck’s Dr. Barbara Keller said the amount of chickenpox virus in ProQuad is “about a log” — or 10 times — higher than Merck’s standalone chickenpox vaccine, Varivax, in order to overcome immune interference.

Both Wakefield and Shattock said the Olympia families’ unusual histories with chickenpox are worrisome because their children might have inherited problems coping with the vaccine.

“There’s no doubt the immune response to viruses is determined by our genetic constitution,” Wakefield said. “It may well be there is a genetically determined predisposition to abnormal handling of chickenpox virus, at least in children.

“This kind of phenomenon has been shown to (play a role in) measles. The immune response to measles is determined by your genetic profile. It’s certainly consistent with what is known about the immune response to viruses.”

ProQuad is likely to be widely adopted by healthcare professionals who previously administered separate MMR and Varivax shots.

“Use of licensed combination vaccines, such as (ProQuad), is preferred to separate injection of their equivalent component vaccines,” says the new edition of the CDC’s authoritative “Pink Book” on vaccine-preventable diseases.

“When used, (the immunization) should be administered on or after the first birthday, preferably as soon as the child becomes eligible for vaccination.”

This series of articles, based on reporting in Olympia in February and March, tells the families’ stories, looks at the scientific controversy and examines implications for the autism-vaccine debate.