Ped iui rics
VOLUME 49 APRIL 1972 NUMBER 4
COMMENTARIES
THE
END
OF
ROUTINE
SMALLPOX
VACCINATION
IN
THE
UNITED
STATES
1971 was the year in which the Sur-geon General of the United States Public
Health Service, the Redbook Committee of
the American Academy of Pediatrics, and
the Territorial Health Officers agreed that the time had come to discontinue routine primary smallpox vaccination for American children. As a result of this it may also be expected that school vaccination laws pres-ently in effect in some 28 states will soon be repealed or will not be enforced with vigor.
The American pediatrician views these
developments with mixed feelings, since there have been extensive and often spir-ited debates regarding the timing for
dis-continuation of routine smallpox
vaccina-tion. When, at the annual meeting of the
American Pediatric Society in Philadelphia
in 1964, we described the results of a 1-year
survey of the complications of smallpox
vaccination and proposed that routine pri-mary vaccination of American children could be discontinued because the danger of the procedure far outweighed the risk of exposure to disease, a lively discussion en-sued. To the best of my memory, of all the
people who commented following our
pre-sentation, only Dr. Margaret Smith sup-ported our stand. Subsequently, the United
States Public Health Service undertook sev-eral careful and more sophisticated studies to determine the niortality rates following smallpox vaccination and the chance of im-portation of smallpox to this country. They
also reviewed what should be done in the
event importation did occur. In 1971, on the basis of their studies, the United States
Public Health Service was able to
recom-mend that smallpox vaccination in the
United States should be used selectively rather than as a routine procedure.
Imple-mentation of their recommendation should
result in a marked decrease in the number
of vaccinations that are performed at any
age and a subsequent prompt drop in
mor-tality and morbidity.
It has been shown repeatedly that an
ap-preciable number of cases of smallpox must
exist within a country (or area) in order for
it to be the source of exported cases. The mere presence of a few cases is not likely to lead to exportations over long distances.
The World Health Organization has had an
intensive international eradication program.
Since 1964, under the leadership of Dr.
D. A. Henderson, this campaign has made
enormous strides. In 1966, 43 nations had
substantial numbers of cases of smallpox;
by 1970 that number had dropped to 13;
and in 1971 only five nations (Ethiopia,
Su-dan, India, Pakistan, and Indonesia) had a
significant number of cases. During the last
year, smallpox has been essentially
elim-inated as a major problem in the
West-ern Hemisphere through the energetic and
successful eradication program in Brazil,
the last stronghold in the New World.
It is now recommended that the only
490 END OF VACCINATION
dividuals
( adults
or children) who should receive smallpox vaccination are those whorequire it because they will travel to a
country where smallpox is endemic, or be-cause they serve in a health profession and might be early contacts of an imported case
before it has been diagnosed. Health
pro-fessionals should maintain adequate immu-nity because of the experience in Europe
where, over the past 20 years, one half of
all secondary cases were found among doc-tors and nurses.
The often expressed fear that delay in
primary vaccination until adult life would yield a higher rate of complications seems to be unfounded. Although it was formerly believed that the complication rate was two
or three times higher in adults than in
chil-dren, recent careful studies in the United States, where more than a quarter million
primary vaccinations are performed on
adults each year, has disclosed no evidence that the rate of complications is higher in
adults than in infants or children. From a
review of death certificates, only one death was reported in a 9-year period following
adult primary vaccination. Those who are
unduly concerned that primary adult vacci-nation might result in an increased
inci-dence of vaccinia encephalitis should be
aware that the simultaneous use of
vac-cinia-immune gamma globulin at the time
primary vaccination is carried out will sig-nificantly further decrease the incidence of
this rare complication.
Further experience with attenuated vac-cinia (CVI-78) is required to assess its use
prior to standard smallpox vaccination. In
time, vaccination for those select
individu-als who need to be immunized might be a
two-step procedure with attenuated vaccinia
being given first followed by the administra-tion of the standard strain. It is to be
ex-pected that the number of individuals who will need to be vaccinated will decrease
tremendously, probably to less than 250,000
per year. Indeed, if successful eradication
campaigns further reduce the volume of
smallpox abroad, the disease may for all
practical purposes no longer be considered
a problem.
But what if, after 10 or 20 years of the control of smallpox, it should suddenly ap-pear in a virgin population totally
suscepti-ble and with no “herd” immunity?
Forth-nately smallpox does not spread as does
chickenpox or measles. Modern techniques
of surveillance, prompt vaccination of
con-tacts, the use of vaccine immune gamma
globulin, and prophylactic use of methisa-zone (Marboran) would make it possible to control smallpox importation adequately. This has already been shown to be an
effec-tive way on a number of occasions. Great
Britain discontinued compulsory vaccina-tion in the 50’s and by 1960 had a
popula-tion in which 90% of the people had not
been immunized or had last been
vacci-nated 10 or more years previously. Despite
this, Great Britain had had no more secon-dary cases than had occurred on the conti-nent where compulsory vaccination has
been continued to the present. In the last 5
years the average importation outbreak in
Europe has resulted in 10 cases. The
num-bers would only have been half as large if
hospital personnel (doctors, nurses, and so
forth) had been adequately protected. In
Great Britain, 13 cases of smallpox were
im-ported from other countries between 1951
and 1970. This gave rise to 103 secondary cases of smallpox with 37 deaths. But dur-ing the same period there were 100 deaths
from smallpox vaccination given in Great
Britain.
The worldwide number of reported cases
has declined in the past 4 years from 131
thousand to 27 thousand. Vaccination
re-quirements for travel have also changed in
some countries. At the present time, in the
United States, evidence of vaccination is
only required of those returning to this
country if the traveler had been in a country reporting to have smallpox in the previous
14 days.
The concept that “herd” immunity in
COMMENTARIES 491
a modified disease which is quite
infec-tious but much more difficult to diagnose, and that our well-vaccinated infants are not
a numerically important barrier to importa-tions. To have a thoroughly immunized
pop-ulation it would be necessary to vaccinate
and revaccinate more people and at more
frequent intervals than we do now. We can
be said to be well vaccinated but not well immunized.
The fear has been expressed that discon-tinuation of routine primary vaccination of
all children in favor of a policy of
vaccina-tion limited to travelers returning from
areas where smallpox is endemic, and to
doctors and nurses, might result in less
ef-fort by those countries still having the
dis-ease to continue vigorous campaigns of
eradication. On the contrary, I feel that it has been the very success of smallpox
vacci-nation over the years that has made it possi-ble to modify our attitude toward smallpox control in this country, and to concentrate
our financial efforts, and technical and
pro-fessional support, in helping the World
Health Organization and its member
gov-ernments accomplish total eradication
within the next 5 years. This goal is now
within sight. The conquest of this dread
disease would be a wonderful tribute to the
memory of Edward Jenner and to the
inter-national collaboration exemplified by the
WHO eradication campaign. But even if
to-tal eradication is not attainable at this time, the importation of smallpox and the
devel-opment of secondary cases will not result in any more deaths than we suffer from
small-pox vaccination itself. As in all other phases of preventive, diagnostic, and therapeutic
medicine, we must weigh the risk of our
actions against the need to proceed, in
terms of the patients’ welfare.
C. HENRY KEMPE, M.D. Department of Pediatrics
University of Colorado
Medical
Center4200 East Ninth Avenue
Denver, Colorado 80220
SELECTED BIBLIOGRAPHY
Bauer, 0. J., St. Vincent, L., Kempe, C. H., Young, P. A., and Downie, A. W. : Prophylaxis of small-pox with methisazone. Amer. j. Epidemiol., 90: 130, 1969.
Benenson, A. S.: Possible alternatives to routine smallpox vaccination in the United States. Amer.
J.
Epidemiol., 93 :248, 1971.Dick, C. : Routine smallpox vaccination. Brit. Med.
J,, 3:163, 1971.
Foege, W. H., Foster, S. 0., and Goldstein,
J.
A.: Current status of global smallpox eradication.Amer. J. Epidemiol., 93:223, 1971.
Katz, S. L., and Krugman, S.: Smallpox vaccina-tion. New Eng.
J.
Med., 281 :22, 1969.Katz, S. L.: The case for continuing “routine” childhood smallpox vaccination in the United States. Amer. J. Epidemiol., 93:241, 1971. Kempe, C. H.: Studies on smallpox and
complica-tions of smallpox vaccination. PEDIATRICS, 26:
176, 1960.
Kempe, C. H.: An evaluation of the risks of small-pox vaccination in the United States. Part 2.
J.
Pediat., 67:1017, 1965.
Kempe, C. H., and Benenson, A. S.: Smallpox im-munization in the United States. J.A.M.A., 194: 161, 1965.
Kempe, C. H.: To vaccinate or not. Hospital
Prac-tice, 2:28, 1968.
Kempe, C. H.: Smallpox vaccination of eczema pa-tients with attenuated live virus. Yale J. Biol.
Med., 41:1, 1968.
Kempe, C. H., Fulginiti, V., Minimitani, M., and
Shinefield, H.: Smallpox vaccination of eczema
patients with a strain of attenuated live vaccinia (CVI-78). Pimwriucs, 42:980, 1968.
Lane, J. M., Ruben, F. L., Neff, J. M., Millar, J. D.: Complications of Smallpox
Vaccina-tion, 1968. National Surveillance in the United
States. New Eng. J. Med., 281:12-1-1208, 1969.
Lane, J. M., Ruben, F. L., Abrutyn, E., and Millar,
J. D.: Deaths attributable to smallpox
vaccina-tion. 1959-1966, 1968. J.A.M.A., 212:441, 1970. Lane, J. M., Ruben, F. L., Neff, J. M., et al: Com-plications of smallpox vaccination, 1968. II. Re-suits of ten statewide surveys J. Inf. Dis., 122:
303, 1970.
Lane, J. M., and Millar, J. D.: Risks of smallpox vaccination in the United States. Amer. J. Epi-demiol., 93:238, 1971.
492 HEXACHLOROPHENE
Neff, J. M., Lane, J. M., Pert, J. H., et al.: Compli-cations of smallpox vaccination. I. National sur-vey in the United States, 1963. New Eng. J. Med., 276:125, 1967.
Neff, J. M., Levine, R. H., Lane, J. M., Ager, E. A., Moore, H., Rosenstein, B. J., Millar, J. D.,
and Henderson, B. A.: Complications of small-pox vaccination, United States, 1963. II. Results
obtained by four statewide surveys. PEDIATRICS,
39:916, 1967.
Neff, J. M.: The case for abolishing routine child-hood smallpox vaccination in the United States. Amer. J. Epidemiol., 93:245, 1971.
Public Health Service Recommendation on Small-pox Vaccination. Morbidity and Mortality: 20:
339, 1971.
HEXACHLOROPH
ENE
Y
ET another chemical widely used by thepopulation has been discovered to be
potentially dangerous. Hexachlorophene was first synthesized in 1939 and found to have both bactericidal and fungicidal prop-erties, but its toxicity has only been appre-ciated in the last few years. Probably the
most alarming aspects are that the chemical is not only neurotoxic but is also readily
ab-sorbed from the skin.
Although muscle twitching and coma
were observed 3 years ago in burn patients treated with hexachlorophene, these
obser-vations were not actually responsible for
the recent toxicity studies which have
fo-cused attention on this subject and raised many important questions. These studies, begun in 1970 at the FDA Division of Pesti-cide Chemistry and Toxicology in Atlanta, were related to the use of hexachlorophene as a fungicide on citrus fruits and a number
of vegetables, including cucumbers, toma-toes, and potatoes. Rats fed
hexachioro-phene daily developed cerebral edema and
cystic spaces in the white matter of the
brain and spinal cord. The findings were
presented at the Society of Toxicology
meeting in March of 1971 and the implica-tions immediately became apparent, partic-ularly for the newborn. Blood levels were
determined in infants given daily baths
with hexachlorophene in a 3% emulsion
and reported in the Lancet in August 1971.
In some cases these levels were nearly 50%
of those associated with neurotoxicity in the
rats which had been fed the chemical.
The FDA immediately notified the
Academy Committee on the Fetus and
Newborn of these developments and
pro-posed a warning statement. The initial reac-tion of the Committee at its meeting in Oc-tober of 1971 was that more information
was needed and the experiments in rats
might not be relevant to the human. Conse-quently the Committee did not agree to
en-dorse the statement at that time.
Shortly thereafter, results of testing the effect of skin washing with
hexachloro-phene in newborn monkeys became
avail-able. The animals were washed daily with
one teaspoonful of a detergent containing 3% hexachlorophene which was subsequent-ly washed off. After 90 days all of six ani-mals showed extensive lesions in the brain and spinal cord, and two had papilledema.
No lesions were detected in five control
animals. The experiments left a number of
questions unanswered. The amount of
hexachiorophene used in the small animals,
which weighed only approximately 400 gm
at birth, was proportionally greater per unit of body surface than is customarily used in
the human infant. There might be
differ-ences in absorption due to the number of
sweat glands in the skin of the monkey,
some of the chemical might have been
licked from the skin, and there also might
have been difficulties in washing the
ma-terial off because of hair. There was no
indication as to how rapidly these lesions
developed nor whether they might be