Chickenpox Vaccine Cuts Deaths - Raises Shingles Questions

[flonharry65]

Chickenpox Vaccine Cuts Deaths but Raises Questions on Shingles
By ANDREW POLLACK

he vaccine against chickenpox has sharply cut the death rate from the
childhood disease, according to a study released yesterday.

But even as the vaccine protects children, questions are arising about
whether its use will increase the incidence of a related disease, shingles,
in adults.

The concern arises from a hypothesis, backed by some evidence, that exposure
to children with chickenpox helps increase adults' immunity to shingles,
which is caused by the same virus. With far fewer children contracting
chickenpox because of the vaccine, that effect would vanish, and adults, who
have by and large, not been vaccinated, would be at greater risk of
shingles.

"We already know the impact the varicella vaccine has had on chickenpox,"
Dr. Marietta Vásquez, an assistant professor of pediatrics at Yale
University School of Medicine, said as she used the medical term for the
vaccine. "Now it's time to see what impact the varicella vaccine has had on
shingles."

Dr. Vásquez, along with a Yale colleague, Dr. Eugene D. Shapiro, wrote a
commentary in the current edition of The New England Journal of Medicine
that hailed the effectiveness of the vaccine for chickenpox but urged more
study of its effects on shingles.

The same journal includes the study that shows that deaths from chickenpox
in the United States dropped to 66 a year from 1999 to 2001, from 145 a year
in 1990 to 1994.

The vaccine was introduced in 1995. While not usually fatal, chickenpox can
be deadly, particularly to infants or adults or to people sick with another
illness.

The paper, written by researchers at the Centers for Disease Control and
Prevention, was based on nationwide statistics culled from death
certificates.

The new information could spur greater use of the vaccine, researchers said.

The vaccine has been somewhat controversial and is not routinely used
overseas. In the United States the vaccination rate for children, although
having risen to 85 percent, is still below that for some other vaccines,
said Dr. Jane F. Seward, the chief of the viral vaccine preventable disease
branch at the C.D.C. and a senior author of the paper on the mortality from
chickenpox.

One concern in other countries is whether using the vaccine would increase
the rate of shingles in adults. Shingles, evidenced by a rash, blisters and
pain, can lead to nerve damage called post-herpetic neuralgia that can last
for weeks or months and cause excruciating pain, even from the touch of a
shirt against the skin.

Infectious disease modelers at the Health Protection Agency in Britain
estimated that shingles might increase 30 percent to 50 percent from
vaccination. The harm from that increase would outweigh the benefits of
reducing chickenpox rates in children, the modelers said. They conceded that
their conclusions rested on assumptions about how much the rate of shingles
would increase, which is not known.

Dr. Ann M. Arvin, a professor of pediatric infectious disease at Stanford,
who has been a consultant to Merck, maker of the chickenpox vaccine, said,
"We definitely need to pay attention to this question, but at this point
it's a hypothetical question, I think."

Shingles, also called herpes zoster, is caused by reactivation in the body
of the varicella-zoster virus, the cause of chickenpox. After people have
chickenpox, the virus remains dormant, held in check by the body's immune
system. But sometimes it becomes active again, particularly in elderly
people or those with compromised immune systems.

There is already evidence that exposure to children with chickenpox helps
act like a booster shot to the immune system, keeping shingles from
occurring.

Mothers caring for children with chickenpox experience an increase in
immunity against the virus, as shown by measurements of their blood. And a
study by researchers at the London School of Hygiene and Tropical Medicine
that compared 244 people with shingles with controls without the disease
found that people who had the most contact with children had one-fifth the
risk of shingles of those with the least exposure.

Whether shingles is increasing in the United States is not clear. Dr. Seward
said the disease control center was conducting studies. One study, using
records from the Group Health Cooperative, a health system in Seattle, has
not shown an increase, she said, adding that she could not discuss the study
in detail because it is awaiting publication.

"We would say based on the best available data we have that we don't see any
increase in herpes zoster," Dr. Seward said.

Kaiser Permanente, a big health maintenance organization, has experienced an
increase in hospitalizations for shingles. It appears to be the result of an
aging of the population, said Dr. Steven B. Black, director of the vaccine
studies center at the organization.

One researcher said the incidence of shingles among unvaccinated children in
the Antelope Valley outside Los Angeles was much higher than expected. The
valley is one of two locations where the disease control center is closely
monitoring the effects of the chickenpox vaccine. The researcher, Dr. Gary
S. Goldman, whose degree is in computer science, was a data analyst on the
project but said he quit in 2002 because his superiors were trying to
suppress the findings on shingles. He managed to have his papers published
in the journal Vaccine in 2003.

Scientists from the disease control centers sharply criticized Dr. Goldman's
statistical methods and assumptions in a commentary also published in that
journal. The center said it did not believe that shingles had increased.

People who receive the chickenpox vaccine are widely considered less likely
to contract shingles. In several decades, when today's vaccinated children
become elderly adults, the shingles rate is generally expected to decline,
even if it increases between now and then.

But if using the vaccine does raise the risk of shingles, the manufacturer
also has a solution. Merck has said it will apply in the first half of the
year to the Food and Drug Administration for approval of a shingles vaccine
for older adults.

The vaccine is a stronger version of the chickenpox vaccine. Merck and
investigators expect results soon from trials in more than 38,000 people
older than 60.

"We'll probably be able to handle an increase in zoster," said Dr. Michael
N. Oxman of the University of California, San Diego, and the Veterans
Affairs medical center there, who was lead investigator in the trial.

[Gary S. Goldman, PH.D.]

Additional information regarding New York Times article…

It is estimated that shingles disease results in nearly five times as many hospitalizations and three times as many deaths as that caused by chickenpox. After a person has had chickenpox, the virus goes dormant or hibernates in the body usually for several decades and then can reactivate as a painful rash called shingles. Both chickenpox (or varicella) and shingles (or herpes-zoster) are related in that they derive from the same varicella-zoster virus. However, it should be noted that roughly 75% of all medical costs related to varicella-zoster virus are due to shingles. While it is true that morbidity and mortality due to chickenpox is lower as a result of the universal varicella vaccination program, public health has largely ignored the affect such program will have on the closely related shingles disease.

It was previously thought that as an individual ages, he or she experiences a decline in immunity resulting in increased risk of shingles. Recent studies however, indicate that this explanation for the increasing trend of shingles with advancing age is not entirely correct.

It is interesting to note that as adults age, they generally tend to have fewer and fewer contacts with children who have chickenpox. In the era prior to the chickenpox vaccine, children who had previous histories of chickenpox, also experienced the most contact with other children having chickenpox during the annual epidemics that occurred in schools. Children also demonstrated the lowest risk of shingles relative to older age groups. The explanation for the rare occurrence of shingles in children was that with every contact they had to a child infected with chickenpox, they received an immunologic boost that yielded a protective effect that helped suppress the reactivation of shingles. Next, parents with children experienced lower incidence of shingles relative to those without children since parents with children had more opportunity for re-exposures to children with chickenpox. Finally, grandparents and elderly adults had the highest risk of shingles since they had relatively few exposures to children with chickenpox.

In reality, the increasing trend of shingles with advancing age was due to the fact that with advancing age, an individual received less and less opportunity for periodic re-exposures to children with chickenpox and therefore received less immunologic boosting—causing increased risk of shingles.

Dr. Hope-Simpson, in 1965, was the first to propose, “The peculiar age distribution of [shingles] may in part reflect the frequency with which the different age groups encounter cases of varicella and because of the ensuing boost to their antibody protection have their attacks of [shingles] postponed.”

The universal varicella (or chickenpox) vaccination of all healthy children has dramatically reduced the occurrence of natural chickenpox in communities throughout the United States and therefore the opportunities for immunologic boosting are now rare. Dr. Gary S. Goldman has reported that the incidence of shingles among children with a previous history of chickenpox is approaching that of older adults, likely due to the reduced opportuntities for boosting due to decreasing exposures to children with chickenpox. It is logical that as immunity gradually wanes over time, all adults, 95% of which have had chickenpox, will be at increased risk for reactivating with shingles at the same high rate as adults currently aged 50 or 60 years. Other British researchers, Brisson and Edmunds, estimate that a shingles epidemic will result in the U.S. lasting a duration of 30 to 50 years—until such time as the adult population is largely replaced by vaccinated persons.

Interestingly, Merck & Co. who markets the Varivax vaccine, also markets the antiviral (Zovirax or Acyclovir) prescription drug which is used to treat shingles. Often quoted is the statistic, “From the societal perspective, the program would save more than $5 for every $1 invested in vaccination” based on a cost of $35 per dose. As of the last update on April 15, 2003, the Vaccines for Children (VFC) Program CDC Vaccine Price List indicates varicella vaccine cost to the private sector is 66% higher than that modeled, or $58.11 per dose. Based on a cost-benefit model by Lieu and other researchers, the mean vaccine and administration costs approach $146 million and thus create an annual net medical cost deficit of $66 million for varicella, resulting in a benefit-cost ratio of 0.55:1, costing the health payer $16.50 per case of chickenpox prevented (instead of a cost of $2 per case as initially derived assuming $35 per dose).

These above costs assumed that one dose of vaccine was sufficient to provide life-long immunity and there would be no adverse effects on shingles.

CDC and Michael Oxman, a Merck researcher, are quick to reply that any increase in adult shingles can be accommodated by vaccinating adults. Adult vaccination programs have historically been unsuccessful. What CDC and Oxman are suggesting is in effect a chickenpox vaccine that serves as a booster in place of the natural immunity that derived when epidemics of chickenpox occurred naturally in the community. The cost-benefit analysis has never taken into account a cost of $10 billion (200 million adults at $50.00 per dose) required to vaccinate the entire adult population. Nor has the cost-benefit analysis considered that two doses (instead of one) will be required in children now that boosting from contact with other children with chickenpox is rare.

Studies conducted by the Massachusetts Department of Public Health Behavioral Risk Factor Surveillance System (BRFSS) and Group Health Cooperative (GHC) (a) have lower vaccination coverage than the communities under active surveillance and (b) use a small sample size. Due to insufficient statistical power, it is invalid for Jane Seward of the CDC to draw the conclusion that these studies “show no change in shingles incidence to date.” The BRFSS telephone survey, for example, was based on a sample size of 4,916 and 3,123 respondents aged 1 to 19 years in 1999 and 2000, respectively.

Yet, since 2000, Antelope Valley VASP had been reporting preliminary results by age and vaccination status from a population-based study of shingles among the 318,000 residents of the Antelope Valley, 118,685 of which were aged <20 years. Shingles cases among adults aged 20 years and older reported principally by healthcare providers increased 18% from 237 shingles cases in 2000 to 279 in 2001 with increases in nearly every 10-year age group from 20–29 through 60–69. Young adults that previously received the most outside boosting in the prelicensure era generally experienced the greatest percentage increase in case reports relative to the older adults. A total of 370 shingles cases reported among adults in 2002 represented an increase of 32.6% and 56.1% over those cases reported in 2001 and 2000, respectively. This increase in the Antelope Valley was not due to simply an aging population.

In Japan, immunity following vaccination lasted 20 years. However, in Japan only 1 out of 5 children received the vaccine so that those vaccinated were frequently boosted by exposure to other children with natural chickenpox. The U.S. is the first to implement a universal varicella vaccination program where, in time, naturally occurring varicella and its booster effect will be nearly eradicated. It may be difficult to design booster interventions that are cost-effective and meet or exceed the level of protection provided by immunologic boosting that existed naturally in the community in the pre-licensure era.

While the CDC has published manuscripts using virtually all analyses and data provided by Dr. Goldman that highlight benefits of varicella vaccination; they have attempted to suppress the publication of deleterious or adverse trends that he has objectively detailed in manuscripts submitted to medical journals. Feeling that only selective data were being reported and published, Dr. Goldman resigned after serving nearly 8 years as Research/Analyst on the Antelope Valley Varicella Surveillance and Epidemiological Studies Project (in joint cooperation with the Centers for Disease Control and Prevention) stating, “When research data concerning a vaccine used in human populations is being suppressed and/or misrepresented, this is very disturbing and goes against all scientific norms and compromises professional ethics.” Conflicts of interest between the pharmaceutical industry and public health agencies have severely compromised public health, introducing constant disease and treatment cycles. Monetary enrichment appears to be the current priority rather than public health and this will continue to be the case until research is conducted independent of the agencies that sponsor both the testing and distribution of vaccines. Statements by the CDC, along with their recent analyses that fail to correct for the under-reporting of shingles cases, create the impression that CDC is trying to manipulate the scientific data and prevent publication of analyses that could adversely influence immunization rates, regardless of the potential public health consequences. Public policies that are based on invalid assumptions and conclusions may ultimately be damaging to public health.

Dr. Goldman currently serves a founder and President of the Public Benefit Corporation--Medical Veritas International (MVI) Inc.--and serves as the Editor-in-Chief of Medical Veritas: The Journal of Medical Truth. Additional information on vaccines and healthcare issues can be found at www.MedicalVeritas.com. He may be contacted by phone (661) 944-5661, fax: (661) 944-4483, or e-mail: pearblossominc@aol.com.