A Medical Critique of the Varicella Vaccine

Transcription

1 A Medical Critique of the Varicella Vaccine 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

2 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 country]. 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 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

3 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 "is valueless"! 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 insert). 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

4 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 addressed. 1) 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 /82 p ) Gershon, Anne, A. "Live Attenuated Varicella Vaccine: Protection in Healthy Adults Compared with Leukemic Children," Journal of Inf. Dis. Vol. 161, 1990, p ) Preblud Stephen "Varicella: Complications and Costs," Pediatrics Supplement 1986, V.78 p ) 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, [251 West Ridgeway Drive Dayton, Ohio 45459]. 6) Huse Daniel, "Childhood Vaccination against Chickenpox x: An Analysis of Benefits and Costs," Journal of Pediatrics V. 124 June, 1994, p ) Merck: Description of product VARIVAX by Merck (PDR format) 1995: 8) Hall Caroline B. "Recommendations for the Use of Live Attenuated Varicella Vaccine," Pediatrics V. 95 May, p ) Jacobs J. Patrick, Jones C.M.: Baille J.P., "Characteristics of Human Diploid Cell Designated MRC-5," Nature Volume 227. July 11, 1970: p ) *Hoskins J.M., Plotkin S.A., "Behaviour of Rubella Virus in Human Diploid Strains," Wistar Institute of Anatomy and Biology, Philadelphia, PA. Jan 16, 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.

5 Special thanks to Mrs. Susan L. McKinney, M.L.S. and Mrs. Nancy Zachocki, L.T. from St. Margaret Memorial Hospital Library Author: Chris Kahlenborn, MD