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Will the same vaccine be used for children with leukemia as for normal children?
Dr Brunell: There will be two different doses. A
lower dose will be used for leukemic children than for normal children.
A question that seems to come up frequently is the relationship of the vaccine to zoster. Someone wants to know whether the vaccine will prevent zoster, and perhaps we ought to
ask whether giving repeated doses might pos-sibly increase the risk of zoster or even make zoster more painful.
Dr Gershon: We have had only one case of zoster
that was definitely shown to be caused by the vaccine virus in patients with leukemia. Interest-ingly, the zoster rash appeared at the site of
injec-tion of the vaccine. This child had only one injec-tion of the vaccine and was not one of the vaccines who received two injections; we have no evidence that giving more than one injection would increase the incidence on severity of zosten.
If an infant gets chickenpox at 3 months of age, will he or she be at increased risk for zoster during childhood or infancy?
Dr Guess: Based on the results of our study, it would appear that chickenpox that occurs in the first few months of life increases the risk of getting zoster early in life. There is an insufficient number of cases of chickenpox, however, to be able to make that statement on a firm, statistical basis. We can say only that the risk of early zoster is increased if
chickenpox occurs during the first year of life.
Why are adults different from children in their response to vaccine?
Dr Gershon: I think that children, in general,
must respond to vaccines better than adults, but we do not have a large experience in use of live viral vaccines in adults.
Dr. Plotkin: It is a generalization that has been demonstrated for several vaccines, notably hepati-tis B but also, as I recollect, for polio vaccine as well. The immunologic response is lower in the adult than it is in the child. Put it another way, I suppose that immunologic debility or senility sets in earlier than we would like to think.
Dr Brunell: Speak for yourself.
There is some concern about how long im-munity will last in normal children. Would someone discuss the possibility that repeated doses of vaccine may be needed in normal children, or are you comfortable that a single dose will produce permanent immunity?
Dr Plotkin: I think the only honest answer is that we do not know at this stage for sure. There is an important point that I do not think has been men-tioned so far this evening. Dr Gershon and we and others have evidence that, on exposure to natural vanicella, even individuals who previously had nat-unal vanicella can be reinfected. Vaccinees appear to be, if anything, more likely to be reinfected. What I am saying is that booster responses are going to occur in vaccinees exposed to natural vanicella. Therefore, I think it is likely that their effective immunity is going to last for a very long time and,
perhaps, permanently.
Dr Gershon: I think it would be a mistake to
extrapolate from the experience in leukemic chil-dren to normal children in terms of loss of immu-nity. The leukemic children that we immunized had
had months and years of chemotherapy that I am sure leave lasting effects on the immune system. I would not want to extrapolate from either healthy adults or leukemic children to normal children.
Dr Preblud: Anytime a live vaccine is licensed one has to make a decision based on a certain amount of information and then one has to do very careful post-marketing surveillance. In this country, the best example I think was with rubella vaccine. We decided to vaccinate young children to protect them from infection in adulthood. That was a big decision which was based on a limited amount of informa-tion, and obviously, very careful surveillance over the years has been necessary. So, too, with measles vaccine, and I think with vanicella there will be no
exception. Very careful watch will have to be made.
Dr Arbeiter: We must differentiate between loss of antibody and loss of protection. We have expe-nienced in adult vaccinees that when they received a very low titer of vaccine they seroconvented
mi-tially and then lost antibody. When exposed, they developed vanicella that was extremely mild. It was so mild, in fact, that it went unnoticed as vanicella until a day or two went by. At this time the vaccinee called on the telephone and said I have a few spots; do you think it could be chickenpox? I think we areat Viet Nam:AAP Sponsored on September 7, 2020
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764 EPILOGUE
dealing with a phenomenon that, although we even lose the ability to detect antibody in the laboratory, there is a level of protection that we cannot mea-sure. This has been the case with leukemic children, and it appears to be the case from our experience even with healthy children.
uated and attenuation was not a result of injecting it by a different route. If you give it by the nespi-ratory or natural route, it is also attenuated. We
have given vanicella vaccine by inhalation to 50 on 60 normal children. The same immunologic re-sponse was obtained as with parenteral inoculation without reactions.
There are some questions about the need for screening in order to give vaccine to seroneg-ative adults and adolescents. Women, for ex-ample, during pregnancy would be tested for varicella as well as rubella titer to identify seronegatives so they could be protected. There is some concern about the expense of serologic testing.
Dr Plotkin: I will not speak to the issue of cost effectiveness. Let me just say in general terms that
a positive history of vanicella is a pretty good mdi-cation that the individual has really had chickenpox before. A negative history, that is the claim that
the individual has not had chickenpox, is not very specific. Only a quarter of those with negative his-tories, on serologic testing, do not have antibodies. If we vaccinate without testing, we are going to be vaccinating a lot of senopositive people, which may not matter. If anything, it gives them a boost in their vanicella antibody. One could either screen
first and vaccinate seronegatives or just vaccinate all with a negative history without doing specific antibody testing. We are talking about a very large number of individuals; when we screened our hos-pital populations, we found 3% to 5% of individuals without protection against vanicella. That is a very
dangerous pool of people. If you extrapolate that percentage to the female population who are going to be bearing children and who will then be exposed to vanicella from their children, we will have a lot of adults who deserve vaccination.
How does one differentiate Reye syndrome from varicella encephalitis?
Dr Preblud: I think the safest way to try to differentiate Reye syndrome and the postinfectious encephalitis would be serum ammonia determina-tion. I think that is the easiest test to distinguish
between the two today.
One of the questions that was asked is quite interesting and I think we ought to ask Dr Takahashi about what happens if you take this vaccine and spray it at people instead of injecting it?
Dr Takahashi: This is a very important question because it tells us that the vaccine is really
atten-Is acyclovir effective for treatment of van-cella and zoster?
Dr Preblud: Acyclovir and vidarabine are proba-bly equivalent, but I think most people are tending toward acyclovin for a number of reasons. A large fluid volume is needed to give vidanabine. In addi-tion, many people feel more comfortable in terms
of the potential but small risk of central nervous system, bone marrow, and liver complications. The only problem with acyclovin, thusfar, is renal ob-struction in oligunic patients.
One of the questions concerns patients with AIDS. What happens to them when they get chickenpox?
Dr Genshon: Unfortunately, being a resident of New York City, I have seen a number of children
with AIDS acquired congenitally or by blood trans-fusions; one child at Bellevue who had AIDS died of chickenpox. The reason that he died was that no one at the institution where he was being cared for really took it seriously. I think the situation is similar to what happens with leukemic children. A number of years ago, some people reported a
num-ben of fatalities in leukemic children due to chick-enpox; others observed only six or seven leukemic children who had chickenpox, and it was unevent-ful. Some of the children with AIDS will develop
chickenpox and will recover from it and not have a severe infection, while others will become quite sick. If you know a child has AIDS on even AIDS-related complex, and an exposure has taken place, I would use passive immunization. If such a child has not been passively immunized and develops
chickenpox, I would treat the child immediately with acyclovin.
The last question that has been asked is prob-ably a good point for us to summarize the meeting. It concerns licensure. The very sorts of question that many of you in the audience have asked this evening are the sort of ques-tions that the experts who make this decision will have to address in terms of the licensure of the vaccine. It is a vaccine with which there
is a great deal of experience. We have heard
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doubt whether waiting another 10 years is going to answer the questions that we have raised. The question now is should we con-tinue to withhold the benefits of this vaccine.
SUPPLEMENT 765
Dr Takahashi’s experience that predated the experience in the United States by many years. As we mentioned earlier, the vaccine now is in its second decade. There is a lot of
experience in normal children, and I really (Applause)
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