986
SMALLPOX
VACCINATION:
BEFORE
OR
AFTER
ONE
YEAR
OF
AGE?
John M. Neff, M.D., and J. Michael Lane, M.D.
From the Department of Pediatrics, The Johns Hopkins Hospital, Baltimore, and the Smallpox Eradication Program, National Communicable Disease Center, Atlanta, Georgia
EDITOR’S appearance
Nom:
in the ‘
The article by Doctors Neff and Lane seems highly st4itable for
‘Diagnosis and Treatment” section this month.
D
ATA have been reported recentlymdi-eating that complications following
smallpox vaccination occur more frequently in children less than 1 year old than in any
other age group. A review of illnesses
at-tributed to smallpox vaccination in England and Wales from 1951 to 1960 demonstrated that dermal complications, particularly
gen-eralized vaccinia, occurred two to three
times as frequently in children vaccinated
before the first birthday as in any other
childhood age group.#{176}’2 A review of
small-pox vaccination
complications
in
the United States in 1963 yielded similar results.3’ Asa result, the American Academy of
Pediat-rics Committee on the Control of Infectious
Diseases and the Public Health Service
Ad-visor)’ Committee on Immunization
Prac-tices have recommended that primary
small-pox vaccination
be deferred until after the first birthday.5’#{176} Despite this, manyphysi-cians have expressed reluctance to adopt
this recommendation as was most evident
by the general comments made at the recent
panel on immunization at the meetings of
the American Academy of Pediatrics in
Oc-tober 1967 and by letter to members of the
Smallpox Eradication Program at the
Na-tional Communicable Disease Center. The
purpose of this paper is to review briefly the arguments for and against routine smallpox vaccination in children under 1 year of age.
The principal objections to deferring vac-cination until after the first birthday are as follows:
1. If vaccination is not routinely
prac-ticed during the first several well-baby clinic
visits, many children, particularly those
from clinics in the large cities, might not return for subsequent clinic visits and there-fore might not have the benefit of a small-pox vaccination.
2. Children vaccinated within the first 3
months of life may have milder reactions
to primary vaccination as a result of
ma-ternal antibodies.
3. Vaccination after the first birthday
might result in a greater frequency of auto-inoculation and contact vaccinia.
In response to these objections one can
make the following points:
Number one-There is no reason why
smallpox vaccination cannot he deferred
logistically until after the first birthday. In
this day of multiple well-baby visits, many immunizations are given to a child after the
age of 1 year. If for some reason a child has
still missed primary vaccination between
the first and the second birthday, he can be vaccinated at the time of entry into school.
Number two-The incidence of
complica-tions to smallpox vaccination by monthly
age group has not been defined.
Unfortu-nately, it has not been possible to ascertain
from the data from the United Kingdom and
the United States the possible difference in the frequency of vaccination complications in children less than 6 months of age as
com-pared to those over 6 months of age.14 The
Smallpox Eradication Program at the
Na-tional Communicable Disease Center is
presently undertaking a survey which will
ADDRESS: (J.M.N. ) Department of Pediatrics, Johns Hopkins Hospital, Baltimore 21205.
ARTICLES 987
gather such data, but a definite conclusion will not be reached for at least another year.
It is known that young infants may be
sue-cessfully vaccinated with minimal side
ef-fects. Kempe7 has shown that maternal
an-tibodies can attenuate primary vaccination
responses; Espmark and Rabo8 vaccinated
26 infants at the age of 25 to 35 days and
demonstrated that the resulting
neutraliza-tion antibody response was equivalent to
vaccination of a similar group at the age of
9 to 12 months. In a population composed of
individuals recently vaccinated or
fre-quently revaccinated, maternal antibodies may be significant in attenuating primary
infant vaccination. However, in general,
particularly in populations served by large
city clinics, frequent maternal vaccinations
are not common so that little or no residual
antibody may be available for maternal
transfer. For example, in a recent
vaccina-tion program involving 6,000 hospital and
university employees at the Johns Hopkins Hospital, only 35% reported a vaccination within the preceding 15 years.9 Such a
pop-ulation, according to the present recommen-dations, should have been more frequently
exposed
to
vaccination
than the generalpopulation. Therefore, although maternal
antibodies may offer some protection to
in-fant primary vaccination in some individ-uals, it is unlikely that maternal antibodies detectably affect the incidence of smallpox vaccination complications in large popula-tions.
Number three-At the present there are no data that clearly define the incidence of
autoinoculation on contact vaccinia in
in-fants as compared to older age groups. As
a generalization, there is a distinct
possibil-ity that older children are more likely to
autoinoculate by purposeful scratching, and
chances of contact vaccinia probably
in-crease as mobility and social activities
de-velop. In part, however, these
complica-tions are preventable. Many severe facial
autoinoculations can be avoided by taking
cane to wipe excess vaccine off the arm
im-mediately following vaccination. The
inci-dence of contact vaccinia can be reduced by
careful questioning for exudative skin
le-sions in family members and withholding vaccination in such instances. In families
free of skin disorders, vaccination can be
given
simultaneously
to
all householdnon-immunes over the age of 1 year. On the
basis of existing data, however, it is difficult
to say
whether or not autoinoculation orcontact vaccinia will increase in frequency
if vaccination is deferred until after the first birthday.
On the other hand, what are the reasons
for deferring
vaccination
until after the firstbirthday? In the surveys from England and
Wales, generalized vaccinia and vaccinia
necrosum were found to occur more
fre-quently in infants than in any other child-hood age group.1’2 In the United States there were similar findings both for generalized
vaccinia and eczema vaccinatum.2’4 Of
per-haps greaten importance, 30 deaths resulting
from smallpox vaccination were reported
from England and Wales from 1951 to 1960.
All 4 with eczema vaccinatum, all 7 with
vaccinia necrosum, and 16 of the 19 with
central nervous system disease were
chil-dren less than 1 year of age. From the
re-view from the United States, only seven
deaths were reported; five were a result of
central nervous system complications and
two were a result of contact eczema
vac-cinatum. The deaths were scattered through all age groups. Although none were reported in infants, the numbers of vaccinees are two
few for adequate statistical analysis.
Re-cently, the National Death Certificates
from the United States for deaths that could have been attributed to smallpox
vaccina-tion from 1959 through 1964 have been
re-viewed.10 Twelve deaths were found. Three
of these occurred from contact eczema
vac-cinatum and can be excluded. Four of the
nine deaths from vaccination occurred in
children vaccinated before the first
birth-day. These four deaths included three
chil-dren with vaccinia necrosum at 10 weeks,
8 months, and 10 months of age, and one
vac-cination. The five deaths over the age of 1
year were all cases of post-vaccinial
en-cephalitis-a 4 year old, two 5 year olds, a
6
year old and a 12 year old. Although there-ports of deaths through the National Death
Certificates are probably incomplete, the
findings of four out of nine deaths in
chil-dren less than 1 year are suggestive that
this group is at higher risk than any other
age group. According to the National
Tm-munization Surveys in 1963, only 10% of all pnimary vaccinations were in the infant age group.1’
There is another consideration which
sup-ports the recommendation not to vaccinate
children less than 1 year of age. Conybearel2
and Apostolov and associates13 have
de-scribed a syndrome following vaccination in
the very young which is similar to the
sud-den death syndrome of infancy and
sugges-tive of an overwhelming vinemia. Four cases
have been described with a very similar
clinical picture. The age of vaccination in
these apparently normal children was
be-tween 2 and 7 months. Hyperpyrexia
oc-curred suddenly as the major presenting
symptom on the eighth or ninth day
follow-ing vaccination. Death occurred within 24
hours after onset of symptoms in all cases.
In one case, vaccinia was isolated from mul-tiple organ sites. It is impossible to deter-mine the actual frequency of this
complica-tion or the number of times that this may
have occurred without being recognized or
reported. However, the fact that this can
occur in infants, is another reason why
vac-cination should be deferred until the child has attained an age of greater maturity.
In conclusion, it would seem that
vac-cination should be deferred until after the first birthday. Although the actual incidence
of autoinoculation or contact vaccinia might
increase, these are relatively benign
com-plications in contrast to the systematically
more severe and often fatal complications
which seem to occur more frequently in
in-fants than in any other age group. To defer vaccination until after the first birthday will
also offer the physician an opportunity to
recognize absolute contraindications to
vaccination such as lymphopenic
agama-globulinemia, which might easily be
undi-agnosed at an earlier age and would cer-tainly result in a fatality if vaccination were done.
REFERENCES
1. Conybeare, E. T. : Illness attributed to small-pox vaccination during 1951-1960, Part I: Illness reported as “generalized vaccinia.” Monthly Bull., Minist. Health, 23: 126, 1964. 2. Conybeare, E. T. : Illness attributed to small-pox vaccination during 1951-1960. Part II: Illness reported as affecting the central ner-vous system. Monthly Bull., \Iinist. Health,
23:150, 1964.
3. Neff, J. M., Lane, J. M., Pert, J. H., Morre, R., Millar, J. D., and Henderson, D. A.: Com-plications of smallpox vaccination. I. Na-tional Survey in the United States, 1963. New Eng. J. Med., 276:125, 1967.
4. Neff, J. M., Levine, R. H., Lane, J. NI., Ager, E. A., Morre, R., Rosenstein, B. J., Millar,
J. D., and Henderson, D. A.: Complications
of smallpox vaccination in the United States. II. Four statewide surveys. PsmAmIC5, 39:
916, 1967.
5. Report of the Committee on the Control of Infectious Diseases, ed 15. Evanston, liii-nois: American Academy of Pediatrics, 1966. 6. \‘Iorbidity and Mortality Report 15. Atlanta,
Georgia : Communicable Disease Center, pp. 404-407, 1966.
7. Kempe, C. H. : Studies on smallpox and
com-plications of smallpox vaccination. PEDIAT-RICS, 26: 176, 1960.
8. Espmark, J. A., and Rabo, E. : The formation of neutralizing antibody following smallpox vaccination in young infants with maternal immunity. Acta Paediat. Scand., 54:341, 1965.
9. Smith, J. W., Seidl, L. C., and Johnson, J. E.: Smallpox vaccination in hospital personnel.
J. A. M. A. 197:309, 1966.
10. Abrutvn, E., and Lane, J. NI. : Unpublished data.
11. Poliomyelitis Surveillance Report, No. 284. At-lanta, Georgia : Communicable Disease Cen-ter, April 1964.
12. Conybeare, E. T. : Illnesses attributed to small-pox vaccination during 1951-1960. Part III: Fatal illnesses reported as associated with vaccination but not as generalized or as post-vaccinal encephalomyelitis. Monthly Bull. Minist. Health, 23:182, 1964.
13. Apostolov, K., Flevett, T. NI., and Thompson, K. S.: Death of an infant in hyperthermia
ARTICLES 989
APPENDIX
Consultants for Distribution of Vaccinia Immune Globulin
The Committee of American Red Cross Volunteer Consultants
(
and alternates-shownby asterisk
)
for the distribution of vaccinia immune globulin(
V.I.G.)
clears requests forvaccinia immune globulin, consults in the management and therapy of complications of
smallpox vaccination, and reports such cases to the National Communicable Disease
Cen-ten, Atlanta, Georgia. Their names, addresses, and telephone numbers are listed below:
NI. Grossman, M.D., San Francisco General Hospital, San Francisco, California 941 10, 415/MI
8-8200, Ext. 441, 415,/OV 1-0475
Paul F. Wehrle, M.D., Los Angeles County General Hospital, Los Angeles, California 90033,
213,225-3115, Ext. 28Z5, 213/287-9858
*John M. Leedom, M.D., Los Angeles County General Hospital, Los Angeles, California 90033,
213/225-3115, Ext. 2825, 213/289-7994
*Allen W. Mathies, M.D., Los Angeles County General Hospital, Los Angeles, California 90033, 213/225-3115, Ext. 3283, 213/799-7006
C. Henry Kempe, M.D., 4200 East 9th Avenue, Denver, Colorado 80220, 303/399-1211, 303/
322-4457
*N S. Yeager, M.D., 4200 East 9th Avenue, Denver, Colorado 80220, 303/399-1211, Ext. 7558 Edward L. Buescher, Col., M.C., Walter Reed Army Medical Center, Washington, D.C. 20012,
202/576-3757, 202/RA 3-1000, Ext. 3757, 301/JU 8-8835
*Malcolm S. Artenstein, M.D., Walter Reed Army Medical Center, Washington, D.C. 20012, 202/576-3758, 301/299-6211
Allen S. Chnisman, M.D., American National Red Cross, 17th and D Streets, N.W., Washington,
D.C. 20006, 202 737-8300, Ext. 472, 301/654-8418
*Robert H. Parrott, M.D., The Children’s Hospital of the District of Columbia, 2125 13th Street, N.W., \Vashington, D.C. 20009, 202/DU 7-4220, Ext. 280, 301/EM 5-0810
Andre
J.
Nahmias, M.D., 69 Butler Street, S.E., Atlanta, Georgia 30303, 404/523-4711, Ext. 226, 404/634-9955*J.
Michael Lane, M.D., National Communicable Disease Center, Atlanta, Georgia 30333, 404/ 633-3311, Ext. 3441, 404/377-4834Sharon Bintliff, M.D., 226 North Kaukini Street, P.O. 3799, Honolulu, Hawaii 96817 #{176}Harry Shirkey, M.D., 226 North Kaukini Street, P.O. 3799, Honolulu, Hawaii 96817
Irving Schulman, M.D., 840 South Wood Street, Chicago, Illinois 60612, 312/633-6711, 312 VE
5-0160
Margaret H. D. Smith, M.D., Tulane University School of Medicine, New Orleans, Louisiana
701 12, 505/523-3381, 504/861-4304
#{176}MarkA. Belsey, M.D., Tulane University School of Medicine, New Orleims, Louisiana 70112, 504 /523-3381
John NI. Neff, M.D., 601 North Broadway, Baltimore, Maryland 21205, 301/955-3271, 301/ 338-1173
Horace Hodes, M.D., Mt. Sinai Hospital, 100 Street and Fifth Avenue, New York, New York
10029, 212/TR 6-1158, 212/TR 6-1000, 516/MA 7-3691
#{176}Eugene Ainbender, M.D., Mt. Sinai Hospital, 100 Street and Fifth Avenue, New York, New York
10029, 212/TR 6-1158, 212/TR 6-1000, 914/RO 2-1148
#{176}Julian B. Schorr, M.D., American Red Cross, Community Blood Council, 50 Amsterdam Avenue, New York, New York 10023, 212/787-1000, 212/UN 1-7705, 914/592-5721
