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Published: April 19, 2006 at 5:46 PM
By DAN OLMSTED
UPI Senior Editor
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.
Next: "He has gone backward mentally ... "
E-mail: dolmsted@upi.com
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