From the Polycarp Research Institute and deepest appreciation to Dr. Chris Kahlenborn for the printing of this important article on the Varicella (chickenpox) vaccine.
Medical Critique of the
On March 17, 1995 the FDA approved the use of Varivax-the varicella
vaccine (i.e., chicken pox vaccine) made by Merck-for use in healthy young
children. A review of the
literature shows that a number of concerns have already been raised, and yet
before the use of this vaccine becomes widespread, a number of other concerns
still need to be addressed.
First, there is the question of efficacy-will the vaccine work or will it
offer "attenuated immunity?" Specifically,
will adults who have been vaccinated be at increased risk as the immunity fades?
In adults the chickenpox virus carries 35 times the morbidity and twenty
times the mortality as compared to youngsters.
Although Merck's literature and that of various other researchers note
that antibody to the varicella zoster virus (VZV) remains high even twenty years
after vaccination, almost all openly admit that this is due to a booster effect
from subclinical re-infection from naturally occurring chickenpox occurring
(years) after vaccination-that is, one gets the vaccine, and then is later
exposed to a child who has a real case of the chicken pox, which serves to
"booster" the child who originally received the vaccine.
Unfortunately, in the future, if the incidence of chickenpox decreases,
subclinical re-infection (i.e., the "booster phenomenon) will become rarer
and one will have to rely solely on the vaccination's immunity.
The literature, however, clearly notes that both vaccine-induced immunity
fades with time, specifically: humoral immunity (Asano, Pediatrics
12/1977; Bogger, J. of Inf. Dis. 8/1982) and cell mediated immunity (CMI)
[Gershon JID April, 1990) either drops dramatically or gives far lower
levels of protection than natural varicella infection when measured months after
vaccination instead of years (when the booster effect has already occurred).
For example, Bogger notes that
the antibody level following natural infection is more than twenty-five times as
high as that found in vaccinated individuals when measured fourteen months after
exposure; he also notes that antibody levels fell more than eight-fold within a
fourteen-month period whether one had acquired natural varicella or had been
vaccinated, thus giving a strong indication of what can be expected once the
booster effect diminishes. Gershon
notes that the stimulation index (SI)-the measure of CMI-is over fourfold
greater in adults after natural infection than adults who received the
vaccination. What happens
if vaccinated adults are found to be susceptible?
Researchers for Merck claim that they could be revaccinated, but this may
not be so simple. As internists
know, most adults never get their 10-year tetanus updates-compliance may be a
problem and travelers will have to make sure they are "up to date"
when flying to any country in which they might be exposed to the virus.
Another potentially serious
problem concerns the newborn child of the vaccinated mother.
Normally about 95% of U.S. born mothers have been exposed to the
varicella virus and pass the antibodies on to their newly born babies which give
them protection for the first five and one-half months of life.
Newborns who get the varicella virus without having maternal antibody
protection are known to be at high risk for mortality (31%) (Preblud, Pediatrics,
Suppl. 1986, p.731.) Will
the newborn baby who is born to the mother who was vaccinated as a child still
receive enough (any?) antibody, and will he or she now be vulnerable to the
virus at this critical stage when the baby's immune system may not be able to
fight the virus? One way to
examine this might be to vaccinate a group of young teenage women who never had
chickenpox before-assuming they gave their permission and the ethical concerns
regarding the vaccine were resolved [see below]-who lived in a country with a
low incidence of varicella, thus avoiding the booster effect .
Then one could measure the level of antibodies in their newborns.
If these levels were undetectable then one would be forewarned of the
danger of a mass vaccination program. [Interestingly
a similar strategy-that is vaccinating children in a country which has a very
low rate of natural chickenpox and then measuring their antibody and stimulation
index levels several years later-would give one a good idea of the efficacy of
the vaccine's long term immunity profile by, in effect, subtracting out the
booster effect since the booster phenomenon would be unlikely in such a
The second point is the presence of a seemingly
overt bias which appears evident in a number of papers concerning the
costs/benefits of the vaccine. It
is true that 60 - 90 people die each year from the virus-about 40% of these are
adults and 25% are immunocompromised children.
As noted, we really do not know if the long-term mortality will decrease
with mass vaccination although it would appear that some reduction is likely.
Merck is estimated to receive $150 million annually from sales (Severyn,
1995) which American families will fund either through higher taxes or via
higher insurance premiums. Of note,
each year 2000 youngsters drown and 600 die in bicycle accidents.
Is it not likely that if we were to spend $150 million annually in safety
programs and radio and television awareness ads that fewer youngsters would die
from these causes as well? Perhaps in anticipation to arguments like these or
others, some researchers have noted the "savings to society" that
Varivax would bring since mothers would have to take less time off to care for
their sick children. In one study funded
by Merck and published in the Journal of Pediatrics, (6/94) Daniel M.
Huse notes how he estimates the value of a typical day of lost wages for the
woman who takes care of her sick child: "Finally our estimate that the
value of a day lost from work would be $103 was based on one-fifth of the 1991
average weekly earnings for U.S. women."
There is, however, one major problem with this "economic
analysis." Mr. Huse has missed
the obvious and has failed to attach any economic value to the time which
mothers spend with their sick children.
Of note, these mothers must deem the time they spend with their sick
children to be worth more than a day's wages or they would not be taking off in
the first place. By failing to take
account of the economic worth of the mother's time with her sick child the
authors seem to imply a rather shallow assumption-namely, that this time
Third, no one has a definite sense of what will happen to the incidence
of herpes zoster in the future. It
is true that the rate of zoster in vaccinated children does not appear to exceed
the zoster rate in children after natural exposure, but as Merck freely admits,
no one knows what will happen in the future: "The long-term effect of
Varivax on the incidence of herpes zoster, particularly in those vaccinees
exposed to natural varicella is unknown at present." (Merck, 1995 Varivax
Fourth, it is a bit
disconcerting to note that 11 out of 26 papers that I reviewed concerning the
varicella vaccine had been funded by Merck.
Some of this is probably unavoidable since Merck is the sole manufacturer
of the vaccine. Unfortunately, it
does not look good, when a cost/benefit study is funded by the same drug
organization which manufactures the drug (Huse, 1994).
Neither can one take comfort when one notes in the paper entitled
"Recommendations for the Use of Live Attenuated Varicella
Vaccine,"(Hall Carolyn et. al., Pediatrics, May 5, 1995) that the recommendation
committee members of the American Academy of Pediatrics members are listed
at the end of the paper: two of the authors might catch one's attention-one is a
member of the Food and Drug Administration and another has previously
published a paper that was funded by Merck!
This hardly makes for an independent process.
Members of the FDA, Merck and the American Academy of Pediatrics should
not be issuing collaborative
opinions in a process that is supposedly being evaluated independently!
Finally, an ethical controversy has started regarding the source of the
cell line in which the vaccine is currently grown (MRC-5).
Pro-life groups have taken note that this cell line (MRC-5) was derived
from an aborted child: "Fetal lung tissue taken from a 14 week-old male
fetus removed for psychiatric reasons from a 27 year-old woman..." (Jacobs,
Nature 7/11/70.) Merck
freely admits that vaccinees will receive DNA from this very same cell line: the
vaccine contains "residual components of the MRC-5 cell line including DNA
and protein." Which patients
are ever told that the vaccine their children are about to receive contains DNA
from surgically aborted babies?
In summary at a time in which we involved in a massive program of
childhood vaccination, it would appear that there are a number of concerns that
have not been resolved. The vaccine
may well prove beneficial in terms of decreasing morbidity and mortality but
before embarking on a venture of this magnitude the ethical problems (e.g.,
especially the MRC-5 cell line and another named WI 38) must be resolved
[e.g., use/develop an alternate cell line(s)-[see below, Hoskins,*1967] and
major efficacy concerns (i.e., the neonatal immunity question) must be properly
Asano Yoshizo, MD et al. "Clinical
and Serologic Testing of a Live Varicella Vaccine and Two-Year Follow-up for
Immunity of the Vaccinated Children," Pediatrics Vol. 60 #6 Dec.
Bogger-Goren S. "Antibody Response to Varicella-Zoster Virus after Natural
or Vaccine-Induced Infection," The Journal of Infectious Diseases
Vol. 146 8/82 p. 260.
Gershon, Anne, A. "Live Attenuated Varicella Vaccine: Protection in Healthy
Adults Compared with Leukemic Children," Journal of Inf. Dis. Vol.
161, 1990, p. 661-6.
Preblud Stephen "Varicella: Complications and Costs," Pediatrics
Supplement 1986, V.78 p.728.
Severyn, Kristine R.Ph, Ph. D., Director,
"Children to be used as 'Guinea Pigs' for Drug Company
Profits," Ohio Parents for Vaccine Safety: May 10, 1995. [251 West
Ridgeway Drive Dayton, Ohio 45459].
Huse Daniel, "Childhood Vaccination against Chickenpox
An Analysis of Benefits and Costs," Journal of Pediatrics V. 124
June, 1994, p. 869-73.
Merck: Description of product VARIVAX by Merck (PDR format) 1995:
Hall Caroline B. "Recommendations for the Use of Live Attenuated Varicella
Vaccine," Pediatrics V. 95 May, 1995. p.791.
Jacobs J. Patrick, Jones C.M.: Baille J.P., "Characteristics of Human
Diploid Cell Designated MRC-5,"
Nature Volume 227. July 11, 1970: p.168-170.
*Hoskins J.M., Plotkin S.A., "Behaviour of Rubella Virus in Human Diploid
Strains," Wistar Institute of Anatomy and Biology, Philadelphia, PA. Jan
16, 1967. - The authors describe
two cell lines, one developed from spontaneously
abortions and one from induced abortions.
Both were capable of sustaining
growth of the rubella virus.
thanks to Mrs. Susan L. McKinney, M.L.S. and Mrs. Nancy Zachocki, L.T.
from St. Margaret Memorial Hospital Library
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