ProQuad

proquad-knockdownSo Ben is injected with ProQuad on April 18, 2007 and immediately after he begins to change. Now I don’t mean to suggest that it was as dramatic as lights on, lights off, but over the next few months he flickered off and on,  and then dimmed.

ProQuad is manufactured  by Merck in West Point, PA at a plant that was found by the FDA to have failed to thoroughly investigate when vaccine batches did not meet specifications, even if those batches had been distributed. Some drug components were tainted, and the plant lacked proper procedures and safeguards to ensure purity. FDA conducted the inspections between November 26, 2007, and January 17, 2008.

ProQuad was taken off the market in April 2007, a week or so after Ben’s shots. Merck claims that the shortage of the vaccine — a combination of the company’s measles, mumps, rubella (MMR II) vaccine and its varicella-zoster (chickenpox shot ) licensed by the Food and Drug Administration (FDA) on September 6, 2005– is designed for children from 12 months to 12 years of age.

In terms of potential side effects, Dr. Henry Shinefield, a clinical professor of pediatrics and dermatology at the University of California, San Francisco School of Medicine and a consultant to Merck, doesn’t see any more danger than there is with the current two vaccines. “It is important that children and parents be made aware of every side effect,” he said. “The side effects with this vaccine are inline with what we see with other vaccines.”

At the time of FDA approval, there was evidence of a slightly increased risk of fever-related seizures among children who got the vaccine, but the vaccine was approved with a commitment from Merck to do a large post-marketing study to further understand this risk. Now, these studies are showing that children who get this vaccine are twice as likely to have seizures caused by high fevers.

The federal Advisory Committee on Immunization Practices (ACIP) made new recommendations on key vaccines at its February 2008 meeting in Atlanta, ACIP voted to withdraw the preferential recommendation for the measles, mumps, rubella, and varicella vaccine (MMRV, marketed by Merck & Co., Inc. as ProQuad) as the vaccine of choice for initial vaccination of infants. Researchers in the study looked at 43,000 children between the ages of 12 and 23 months who had been vaccinated with ProQuad and 315,000 who had received two separate MMR and chicken pox vaccines. They found that within seven to 10 days after vaccination, those given ProQuad suffered twice as many cases of fever followed by seizures as those given the separate shots. This amounted to one extra seizure per 2,000 children receiving ProQuad.

In absolute terms, nine of every 10,000 children receiving ProQuad suffered fever-related seizures, compared with four in 10,000 children in the dual vaccine group.

On February 27, 2008 the FDA accepted the new language to be used in ProQuad’s adverse reaction labeling. The Adverse Reactions section of the label has been revised to include two adverse events, encephalitis (Encephalitis is an acute inflammation of the brain. It can be caused by a bacterial infection such as bacterial meningitis spreading directly to the brain, or may be a complication of a current infectious disease such as measles. Certain parasitic or protozoal infestations can also cause encephalitis in people with compromised immune systems. Lyme disease may also cause encephalitis. Brain damage occurs as the inflamed brain pushes against the skull, and can lead to death) and epididymitis, (Epididymitis is a medical condition in which there is inflammation of the epididymis -a curved structure at the back of the testicle in which sperm matures and is stored) to reflect updated data from post-marketing surveillance reports. Information regarding the potential risk of febrile seizures following ProQuad® administration has also been added to this section.

ProQuad has about 10 times as much chickenpox virus as the standalone chickenpox shot. Roseola, which like chickenpox is a herpesvirus. Ben had Roseola prior to receiving ProQuad.

ProQuad cost about $124, sales of the vaccine amounted to over 2 billion dollars in revenue for Merck, during the 2 years it was on the market.  That’s more than 200 million does sold. The National Vaccine Injury Compensation Program (VICP) was established in 1988 to compensate individuals and families of individuals injured by covered childhood vaccines.  The compensation money  has been funded by an excise tax of 75 cents on every purchased dose of covered vaccine. 200 million doses @ .75 each is $150,000,000.

In 1990, Merck & Co., manufacturer of the mumps-measles-rubella vaccine known as the MMR, made a significant but little-noticed change: It quadrupled the amount of mumps virus in the combination shot, from 5,000 to 20,000 units. Then in 2007 it reversed course, reducing the amount to 12,500 units. Neither the measles nor the rubella (German measles) component of the MMR was changed at all — each remained at 1,000 units throughout.

Merck also makes the single-component mumps shot, and in 1990 it also increased the potency of that shot by the same amount, from 5,000 to 20,000 units. But unlike the MMR shot, the standalone mumps shot’s potency was not scaled back in 2007. It remains at 20,000 units.

In 1990, Merck & Co., manufacturer of the mumps-measles-rubella vaccine known as the MMR, made a significant but little-noticed change: It quadrupled the amount of mumps virus in the combination shot, from 5,000 to 20,000 units. Then in 2007 it reversed course, reducing the amount to 12,500 units. Neither the measles nor the rubella (German measles) component of the MMR was changed at all — each remained at 1,000 units throughout.

Merck also makes the single-component mumps shot, and in 1990 it also increased the potency of that shot by the same amount, from 5,000 to 20,000 units. But unlike the MMR shot, the standalone mumps shot’s potency was not scaled back in 2007. It remains at 20,000 units.

The huge rise in autism cases began about the time the mumps component in the MMR was raised in 1990. One theory, dismissed by Merck and federal public health officials, is that viral interference between the components in the MMR could create a persistent sub-clinical measles infection in a subset of vulnerable children; and because the measles virus can cause brain damage, that could lead to autism.

A study released last week by the M.I.N.D. Institute at UC Davis reported that most of the fivefold increase in full-syndrome autism — from 9 in 10,000 children in 1990 to 44 in 10,000 children in 2000– is real and cannot be accounted for by broader categories or diagnostic substitution. And from 1990 to 2007, the mumps portion of the MMR was higher by roughly the same amount — quadruple.

Merck’s decision to cut back on the increase in the mumps vaccine also is surrounded by interesting timing.  The cutback, in 2007, came at the same time Merck announced it was suspending its recently introduced, much-hyped four-in-one shot, ProQuad — the MMR with the chickenpox vaccine added to it. In suspending ProQuad, Merck cited a shortage of chickenpox vaccine; subsequently, a study showed ProQuad caused twice as many fever-induced seizures as separate MMR and chickenpox shots given at the same time, and a CDC advisory committee withdrew its preferential recommendation of the vaccine. Merck won’t say when ProQuad will return to the market.

Could ProQuad’s higher rate of measles rash and fever-induced seizures be a warning sign that something is amiss with the MMR itself, especially beginning in 1990 when Merck tinkered with the proportions of the components?

A related finding comes from a study funded by Merck.  In 2005, the study reported that the four-in-one ProQuad shot — the MMR and chickenpox — was “generally well tolerated” and had a safety profile similar to the MMR and the chickenpox shot (also made by Merck and called Varivax) when given separately.

But there were a couple of interesting differences. First, “Measles-like rash and fever during days 5-12 were more common after the first dose of MMRV [ProQuad]” than after the MMR and Varivax given separately. The difference was substantial — 5.9 percent who got the MMRV had the rash and 27.7 percent had fever, compared to 1.9 percent with rash and 18.7 fever after getting separate shots. While that did not alarm the researchers, it could be a foreshadowing of the doubled rate of fever-induced seizures that was spotted after ProQuad was approved.

Second, even though the new element in ProQuad was the chickenpox portion, something new and unexpected was also going on with the mumps and measles components. “Geometric mean titers to measles and mumps were significantly higher after 1 dose of MMRV than after administration” of MMR and Varivax separately, according to the study’s summary. Later, the authors state: “This suggests that the measles and mumps virus replication is greater after MMRV than it is” after the MMR and Varivax given separately.

In non-scientific language, it looks like the addition of another live virus — chickenpox — potentiated the measles and mumps components: It kicked both viruses into higher gear and they replicated at rates higher than in the MMR.

At the same time, the researchers observed a greater incidence of measles-like rash, and fever, in those who got ProQuad. Were the increased measles and mumps viruses interacting in some unexpected and potentially dangerous way?

Then, for whatever reason, sometime between February and December of last year Merck reduced the mumps component of the MMR from 20,000 units to 12,500 while leaving the standalone mumps shot as it was. During that same period, it decided to suspend production of ProQuad. In April 2007, it announced the suspension, and said no more would be available after July. Then in early 2008, Merck’s study showing the doubled risk of seizures in ProQuad was unveiled and the CDC withdrew its recommendation.

And just last year, Merck said it would stop making the individual MMR component shots including, of course, the mumps shot. That leaves the MMR as the only vaccine in town, and it means there will no longer be a mumps vaccine formulation on the market with the dose the MMR contained from 1990 to 2007.

Merck acknowledges the three viruses can indeed interact to affect a child’s immune system, although in ways it says are not harmful.

A Merck scientist publicly discussed the interference 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.’”

Yet based on Merck’s own 2005 study cited above, ProQuad triggers an increase in mumps virus replication, too. Live viruses in ProQuad seem to be behaving in ways “as yet unknown” that cause immune suppression, co-infection, interaction and increased replication. Even without ProQuad on the market, interaction between the MMR components and the chickenpox virus remains a possibility. The CDC started recommending the chickenpox shot in the mid-1990s at the same 12-month well-baby visit as the MMR.

That suggests the pattern highlighted by ProQuad could be at work through the increased mumps component of the MMR and the addition of chickenpox to the childhood immunization schedule in the mid-1990s. The lesson could be that combining live viruses, and then increasing them or adding new ones, is inherently dangerous, especially when invasion of the brain by one of them “is not an uncommon event.”

Two additional points worth noting: After the increase in 1990 and decrease in 2007, there is still more than twice as much mumps virus in the MMR as there was in 1990.

The changes in the mumps virus component of the MMR serves as a potent reminder of something else: MMR is not one thing but three different exposures. And over the period 1980-2009 the MMR has changed significantly at least twice, making epidemiological studies even more difficult to interpret.

Gathered from Dan Olmsted is Editor of Age of Autism.

ProQuad has been taken off the market, coincidentally within a week or two after Ben’s shot. The manufacturer of ProQuad, Merck, has yet to reintroduce the vaccine back to the marketplace, but if they do the FDA has made a requirement in 2008 that ProQuad list as an adverse reaction, siezures and encephalitis (swelling of the brain), both of which my son developed after his vaccine.

Ben’s neurologist feels Ben’s encephalitis is caused by a viral infection, most likley the measles. But who knows?

What I do know is that ProQuad generated nearly 2 billion dollars for Merck the two years it was on the market. It was their second biggest bread winner, just behind Gardasil.

Just prior to Merck pulling ProQuad the FDA inspected their plant in West Point, PA and issued Merck a warning that Merck officials didn’t thoroughly investigate when vaccine batches failed to meet specifications, even if those batches had been distributed. Some drug components were tainted, and the plant lacked proper procedures and safeguards to ensure purity.

The federal Advisory Committee on Immunization Practices (ACIP) made new recommendations on key vaccines at its February 2008 meeting in Atlanta, ACIP voted to withdraw the preferential recommendation for the measles, mumps, rubella, and varicella vaccine (MMRV, marketed by Merck & Co., Inc. as ProQuad) as the vaccine of choice for initial vaccination of infants.

On October 1, 1988, the National Childhood Vaccine Injury Act of 1986 (Public Law 99-660) created the National Vaccine Injury Compensation Program (VICP). The VICP was established to ensure an adequate supply of vaccines, stabilize vaccine costs, and establish and maintain an accessible and efficient forum for individuals found to be injured by certain vaccines. The VICP is a no-fault alternative to the traditional tort system for resolving vaccine injury claims that provides compensation to people found to be injured by certain vaccines. The U. S. Court of Federal Claims decides who will be paid.

As of January, 2009, 12,850 cases have been filed with the National Vaccine Injury Compensation Program (VICP) , 5,535 representing autism cases. Of the total, 6,979 have been adjudicated, with 2,260 being compensated. Claims arising from vaccinations given prior to October 1, 1988, were paid from general appropriations. Petitioners filed 4,259 pre-1988 claims, with 1,187 being compensated. Over 900 million dollars of general revenue was paid for pre-October 1988 cases, including attorneys’ fees at a statutorily capped level. Payments for post- October 1988 cases come from a trust fund supported by an excise tax on each dose of vaccine that is covered by the Program. Thus far, 8,591 post-1988 claims have been filed, with 1,071 being compensated. Over 939 million dollars has been paid in compensation from the trust fund for the post- 1988 cases, including attorneys’ fees and costs. There is currently nearly 3 billion dollars in the trust fund. There is a wide range of awards depending on the severity of injury, with the highest award currently being $9.1 million in present dollars.

2008 there were 144 awards totaling $83,743,524.93 (avg. over a half million dollars per award) 5 million dollars in attorney fees were paid, in the 70 dismissed cases, the court paid out over 2 million in attorney fees (about $30,000 per case.

See http://www.hrsa.gov/vaccinecompensation for more detailed statistical information regarding the VICP.

Lastly, just the other day I discovered on the the Vaccine Adverse Event Reporting System (VAERS) Web site that ProQuad has had two deaths attributed to the vaccine. Both were submitted on November 3rd and entered in on November 4th. (VAERS ID 331196 & 331194 .

ProQuad was removed from the market back in May of 2007. A year and a half later two deaths show up on the VAERS website. This reminds me of the April 18, 2006 article in AoA about ProQuad’s study that determined that there were twice the number of children with seizures than those receiving the MMR and the chicken pox vaccine separately. Apparently in the Washington state capital of Olympia, a couple of injuries resulting from the administration of the vaccine back in January 2001 and October 2002. The injuries were not reported to the FDA until 2006, 3 months after the FDA approved ProQuad and after a reporter asked if the FDA had them. See the comments section for more about this AoA report. (to find all the Pox articles by AoA editor Dan Olmsted click here and scroll down to April 2006)

If anyone knows how to get information on the two deaths listed in VAERS please email me at bensmyson@gmail.com, obviously both did not die in November of 2008.

Also look for the post on this blog regarding the link between Varicella-Zoster virus also known as Herpes Zoster and Acquired Childhood Aphasia (ACA) which is a language impairment resulting from an unspecified brain damage. This brain damage can have different causes, such as head trauma, tumors, cerebrovascular accidents, encephalitis, or seizure disorders. Most, but not all authors state that ACA is preceded by a period of normal language development.


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2 responses to “ProQuad

  1. ►May 24, 2006 – The Age of Autism: Pox — Part 7 – United Press International via redOrbit – “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.”

    ►May 17, 2006 – The Age of Autism: Pox — Part 6 – United Press International via RichardGWhite.com – “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.'”

    ►May 15, 2006 – The Age of Autism: Pox — Part 5 – United Press International via RichardGWhite.com – “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.”

    ►May 13, 2006 – The Age of Autism: Pox — Part 4 – United Press International via RichardGWhite.com – “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.”

    ►April 30, 2006 – The Age of Autism: Pox — Part 3 – United Press International via redOrbit – “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.”

    ►April 20, 2006 – The Age of Autism: Pox — Part 2 – United Press International via redOrbit – “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.”

    ►April 18, 2006 – The Age of Autism: Pox — Part 1 – United Press International via redOrbit – “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.”

  2. The Age of Autism: Pox — Part 1

    Posted on: Tuesday, 18 April 2006, 00:00 CDT

    By DAN OLMSTED

    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, Rohrback recalled. The doctor agreed to the parents’ request for an immediate neurodevelopmental evaluation, which resulted in a diagnosis of full-syndrome autism.

    Rohbeck 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 na&175;ve.

    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.

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