Morbidity and mortality

MISSING IMAGE

Material Information

Title:
Morbidity and mortality
Uniform Title:
Morbidity and mortality (Washington, D.C. : 1952)
Running title:
Weekly mortality report
Weekly morbidity report
Morbidity and mortality weekly report
Abbreviated Title:
Morb. mortal.
Physical Description:
25 v. : ; 27 cm.
Language:
English
Creator:
United States -- National Office of Vital Statistics
Communicable Disease Center (U.S.)
National Communicable Disease Center (U.S.)
Center for Disease Control
Publisher:
The Office
Place of Publication:
Washington, D.C
Publication Date:
Frequency:
weekly
regular

Subjects

Subjects / Keywords:
Communicable diseases -- Statistics -- Periodicals -- United States   ( lcsh )
Mortality -- Periodicals -- United States   ( lcsh )
Morbidity -- Periodicals -- United States   ( mesh )
Mortality -- Periodicals -- United States   ( mesh )
Statistics, Medical -- Periodicals -- United States   ( lcsh )
Statistics, Vital -- Periodicals -- United States   ( lcsh )
Genre:
federal government publication   ( marcgt )
statistics   ( marcgt )
periodical   ( marcgt )

Notes

Additional Physical Form:
Also issued online.
Statement of Responsibility:
Federal Security Agency, Public Health Service, National Office of Vital Statistics.
Dates or Sequential Designation:
Vol. 1, no. 1 (Jan. 11, 1952)-v. 25, no. 9 (Mar. 6, 1976).
Issuing Body:
Issued by: U.S. National Office of Vital Statistics, 1952-Jan. 6, 1961; Communicable Disease Center, 1961- ; National Communicable Disease Center, ; Center for Disease Control, -Mar. 6, 1976.
General Note:
Title from caption.

Record Information

Source Institution:
University of Florida
Rights Management:
All applicable rights reserved by the source institution and holding location.
Resource Identifier:
oclc - 02246644
lccn - 74648956
issn - 0091-0031
ocm02246644
Classification:
lcc - RA407.3 .A37
ddc - 312/.3/0973
nlm - W2 A N25M
System ID:
AA00010654:00029

Related Items

Preceded by:
Weekly mortality index
Preceded by:
Weekly morbidity report
Succeeded by:
Morbidity and mortality weekly report

Full Text









RECOMMENDATIONS


SUPPLEMENT
Collected Recommendations of the
Public Health Service Advisory Committee on Immunization Pr;


The Public Health Service Advisory Committee on
Immunization Practices has in the last 5 years made
recommendations concerning the use of vaccines and
other biologics in the prevention of 16 diseases. Each
statement by the ACIP is regularly published in the
Morbidity and Mortality Weekly Report upon com-
pletion or revision.
The full series of recommendations has never been
printed as a single document. However, it was felt that a
supplement to the MMWR incorporating all of the exis-
ting ACIP recommendations would be a useful reference.


Page
3
4 -
6 -
9 -
10 -
12 -
14 -
15 -
17 -
21 -
23 -
26 -
27 -
28 .


The Committee has reviewed all of its statements
within the past several months. Only minor revisions and
editorial changes were made. No substantive modifica-
tions resulted from this annual review. Each of the state-
ments carries the dates of original publication and past
revisions.
For the first time, a brief list of selected references is
appended to each statement. These bibliographies are
not meant to be definitive, but are a starting point for
more extensive review of the pertinent literature on the
disease, the vaccine, and its appropriate uses.


CONTENTS


Cholera Vaccine
Diphtheria and Tetanus Toxoids and Pertussis Vaccine
Immune Serum Globulin for Prevention of Viral Hepatitis
Influenza Vaccine-1969-70
Measles Vaccines
Mumps Vaccine
Plague Vaccine
Poliomyelitis Vaccines
Rabies Prophylaxis
Rubella Virus Vaccine Prelicensing Statement
Smallpox Vaccine
Typhoid Vaccine
Typhus Vaccine
Yellow Fever Vaccine





PUBLIC HEALTH SERVICE
ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES


Since its establishment in 1964, the Public Health
Service Advisory Committee on Immunization Practices
has prepared recommendations on the principal biologics
used in the United States. Some of its earlier statements
have been modified as the incidence of disease has
changed and as additional information about the bio-
logics has been accumulated. The ACIP reviews all state-
ments annually and revises or confirms the recommenda-
tions according to current findings.
As statements are developed or revised, they appear
first in the Morbidity and Mortality Weekly Report and
are often reprinted elsewhere. Although intended pri-
marily for use in public health, their broader applicabili-
ty is acknowledged. Therefore, special attention is paid
to the established practices in medical specialties where
immunizing agents are commonly used. Minor differ-


ences in emphasis have not been felt to compromise the
goal of achieving immunity in vaccinees.
The Advisory Committee on Immunization Practices
was established by the Surgeon General of the Public
Health Service to advise him on the status of immunizing
agents and their use for optimal benefit. The Committee
is sponsored by the National Communicable Disease
Center, and its membership is drawn from the fields of
public health, medicine, and research. Ex officio mem-
bership is from government agencies with particular
responsibility and involvement in licensing biologics and
in civilian immunization programs. Special consultants
regularly join the ACIP in its deliberations. Surveillance
reviews, laboratory and field investigations, and other
support are provided by NCDC.


Members of the ACIP at the time of the 1969 review were:


Chairman
David J. Sencer, M.D.
Director
National Communicable Disease Center
Atlanta, Georgia
Executive Secretary
H. Bruce Dull, M.D.
Assistant Director
National Communicable Disease Center
Atlanta, Georgia

Members
Geoffrey Edsall, M.D.
Superintendent
Institute of Laboratories
Massachusetts Department of Public Health
Boston, Massachusetts
Johannes Ipsen, Jr., M.D.
Professor of Epidemiology and Medical
Statistics
Department of Community Medicine
University of Pennsylvania
Philadelphia, Pennsylvania

David T. Karzon, M.D.
Professor of Pediatrics
Medical College
Vanderbilt University
Nashville, Tennessee
Ira L. Myers, M.D.
State Health Officer
Alabama Department of Public Health
Montgomery, Alabama


Donald R. Peterson, M.D.
Director, Epidemiology and Communicable
Disease Control
King County Department of Public Health
Seattle, Washington

Jay P. Sanford, M.D.
Professor of Internal Medicine
Texas Southwestern Medical School
Dallas, Texas
Gene H. Stollerman, M.D.
Professor and Chairman
Department of Medicine
The University of Tennessee
Memphis, Tennessee
Ex officio
Alice D. Chenoweth, M.D.
Chief, Program Services Branch
Children's Bureau
Department of Health, Education, and
Welfare
Washington, D.C.
Roderick Murray, M.D.
Director
Division of Biologics Standards
National Institutes of Health
Bethesda, Maryland
Liaison-American Academy of Pediatrics
Margaret H.D. Smith, M.D.
Professor of Pediatrics
Tulane University
New Orleans, Louisiana





CHOLERA VACCINE


INTRODUCTION
Cholera generally occurs in endemic and epidemic
form only in South and Southeast Asia. In recent years,
however, it has also been epidemic in certain areas of the
Middle East.
Infection is acquired from contaminated water or
food. It is believed to result from personal contact only
in rare instances.

CHOLERA VACCINE
Various cholera vaccines have been widely used, but
until recently their efficacy was unproved. Carefully
controlled field studies have now clearly demonstrated
the effectiveness of current vaccines against both the
classical and El Tor strains of cholera vibrios. However,
severe cases of cholera have occurred in vaccinated per-
sons.
The duration of immunity induced by vaccine is rela-
tively brief. Antibody titers reach a peak within 4 weeks
of vaccination and are maintained for about 3 months.
Protection against disease seems to last no more than 6
months after the primary series or a booster dose.
Vaccine available in the United States is prepared
from a combination of inactivated suspensions of classi-
cal Inaba and Ogawa strains of cholera vibrios grown on
agar or in broth and preserved with phenol.

VACCINE USAGE
Vaccination for International Travel
A primary vaccination or a booster dose within the
previous 6 months is generally required for persons
traveling to or from countries with cholera.* Vaccina-
tion requirements are published annually by the World
Health Organization and summarized by the Public
Health Service in its booklet Immunization Information
for International Travel (PHS Publication No. 384).
Because cholera sometimes reappears in countries free of
the disease for several years, travelers should seek up-to-
date information to determine the need for a valid Inter-
national Certificate of Vaccination.
Physicians administering vaccine to travelers should
emphasize that an International Certificate of Vaccina-
tion must be validated for it to be acceptable to quaran-
tine authorities. Validation can be obtained at most city,
county, and State health departments. Failure to secure
validation can cause travelers to be revaccinated or
quarantined during the course of travel. The Certificate
remains valid for 6 months.
The traveler's best protection against cholera, as well
as against many other enteric diseases, is to avoid poten-
tially contaminated food and water. Persons following

*For a current listing, consult the most recent issue of the World
Health Organization's Weekly Epidemiological Record.


the usual tourist itinerary through countries reporting
cholera and using standard accommodations run virtual-
ly no risk of acquiring cholera.

Primary Immunization
Injections may be given subcutaneously or intra-
muscularly.
For travelers vaccinated in the United States, a single
0.5 ml dose of cholera vaccine is considered adequate to
satisfy the International Sanitary Regulations. The single
dose for children is proportionately smaller (see table
below).
Two doses of cholera vaccine, 0.5 ml and 1.0 ml,
preferably given a month or more apart, are recom-
mended for adults traveling or working in areas where
cholera is epidemic or known to be endemic and living
under conditions in which sanitation is less than ade-
quate. The doses for children are suggested in the sum-
mary table. A two-dose schedule of vaccination is also
advisable for persons working with cholera vibrios in the
laboratory.

Booster Doses
Booster injections should be given every 6 months as
long as the likelihood of exposure exists. In areas where
cholera only occurs in a 2 to 3 month "season," protec-
tion is optimal when the booster dose is given at the
beginning of the season. The primary series need never
be repeated for booster doses to be effective.

Summary
The following table summarizes the recommended
doses for primary and booster vaccination:


Dose
Number

2 & Boosters


Age (Years)
Under 5 5 10


Over 10


0.1 ml 0.3 ml 0.5 ml
0.3 ml 0.5 ml 1.0 ml


Reactions
Vaccination often results in discomfort at the site of
injection for one or more days. The local reaction may
be accompanied by fever, malaise, and headache.

Contraindication
Rarely, severe reactions of various kinds follow ad-
ministration of cholera vaccine. If one experiences such
a reaction, revaccination is not advisable. Most govern-
ments will permit such an individual to proceed provided
he carries a physician's statement of the medical contra-
indication. However, any inadequately vaccinated
traveler coming from an infected area may be quaran-
tined or placed under surveillance for 5 days.

Published MMWR: Vol. 17, No. 20, 1968.





SELECTED BIBLIOGRAPHY
Benenson, A.S., Mosley, W.H., Fahimuddin, M., and
Oseasohn, R.O.: Cholera Vaccine Field Trials in East Pakistan. 2.
Effectiveness in the Field. Bull. WHO, 38:359-372, 1968.
Gangarosa, E.J., and Mosley, W.H.: Asiatic Cholera. In: Tice's
Practice of Medicine, 1969.
Mosley, W.H., Ahmad, S., Benenson, A.S., Ahmed, A.: The
Relationship of Vibriocidal Antibody Titer to Susceptibility to
Cholera in Family Contacts of Cholera Patients. Bull. WHO,
38:777-785, 1968.


Mosley, W.H., Benenson, A.S., and Barui, R.A.: Serological
Survey for Cholera Antibodies in Rural East Pakistan. Bull
WHO, 38:327-346, 1968.
Philippines Cholera Committee: A Controlled Field Trial of
the Effectiveness of Cholera and Cholera El Tor Vaccines in the
Philippines: Preliminary Report Bull. WHO, 32:603-625, 1965.
Phillips, R.A.: Asiatic Cholera (With Emphasis on Patho-
physiological Effects of the Disease). Annual Rev. Med,
19:69-80, 1968. *


DIPHTHERIA AND TETANUS TOXOIDS AND PERTUSSIS VACCINE


INTRODUCTION
Routine immunization against diphtheria, tetanus,
and pertussis during infancy and childhood has been
widely advocated and generally practiced in the United
States in the past 25 years. Its effectiveness is reflected
in decreasing incidence of and mortality from these
three diseases.
Diphtheria
There has been continuing decline in the annual inci-
dence of diphtheria since World War II, and diphtheria is
now a rare disease in many parts of the United States.
However, localized outbreaks continue to appear with
some severe cases and a case-fatality ratio often greater
than 10 percent. In 1968, 260 cases were reported.
Although most diphtheria cases occur in children,
cases and deaths are reported in all age groups. Nearly all
cases occur in inadequately immunized individuals.
Diphtheria toxoid, when administered according to
recommended schedules, prevents diphtheria mortality
and greatly reduces clinical illness and complications.
Following adequate immunization, protective levels of
antitoxin appear to persist for 10 years or more.

Tetanus
Although its incidence in the United States has de-
clined in recent years, tetanus remains a public health
problem which can only be prevented by universal active
immunization. In 1968, 163 cases of tetanus were re-
ported, the majority in unimmunized adults; the median
age was 48, excluding neonates. The national death-to-
case ratio was more than 65 percent. Thus, primary
immunization and periodic boosters must be emphasized
not only for children but also for all adults. Adequate
immunization with tetanus toxoid provides effective and
durable protection against disease and eliminates the
need for passive immunization at the time of injury.
Universal active immunization will ensure protection
against the significant proportion of tetanus infections
which follow trivial injury or through uniecogni/ed por-
tals of entry.
Tetanus toxoid is an almost ideal immunizing agent.
It is highly effective, has almost no side effects, and
provides lhnglating protection. Because there is no


natural immunity to the ubiquitous tetanus organism
and no general contraindications to tetanus toxoid, the
importance of immunization is universal.
Pertussis
The high mortality from pertussis in infancy is the
major rationale for immunization early in life. The dis-
ease is highly communicable, and attack rates up to 90
percent are reported among unimmunized household
contacts. Most cases occur in infants and young children.
In 1967, nearly three-fourths of pertussis deaths oc-
curred in infants less than a year old some 40 percent
of the total occurred in infants 3 months of age or less.
Pertussis immunization is effective in reducing both
cases and deaths. Mortality from pertussis has declined
dramatically with increasingly widespread use of stan-
dardized pertussis vaccines beginning in the mid 1940's.
Because the incidence of and mortality from pertussis
decrease with age, pertussis immunization is not gener-
ally required past age 6 years or after entry to elemen-
tary school.
Severe central nervous system reactions, occasionally
with permanent sequelae or death, occur very rarely
after administration of pertussis vaccine. Their inci-
dence, however, is much lower than the incidence of
similar serious reactions following the disease itself.

PREPARATIONS USED FOR IMMUNIZATION
Diphtheria and tetanus toxoids are prepared by for-
maldehyde treatment of the respective toxins. Pertussis
vaccine is made from a killed suspension of bacteria or a
bacterial fraction.
The toxoids and pertussis vaccine are available in
both fluid and adsorbed forms. Comparative tests have
shown that the adsorbed toxoids are clearly superior in
stimulating high antibody titers and achieving durable
protection. The promptness of antibody responses to
booster doses of either fluid or adsorbed toxoids is not
sufficiently different to be of clinical importance. There-
fore, adsorbed toxoids are the agents of choice for both
primary and booster immunization.
These three antigens are available in various combina-
tions and concentrations for specific purposes. Three
preparations are important for public health use.





1. Diphtheria and Tetanus Toxoids and Pertussis Vac-
cine (DTP)
2. Tetanus and Diphtheria Toxoids, Adult Type (Td)
3. Tetanus Toxoid (T)

All preparations contain comparable amounts of tetanus
toxoid, but the diphtheria component in the adult type
of tetanus and diphtheria toxois (Td) is only about 15
to 20 percent of that contained in the standard DTP
preparation used in infants and young children.

VACCINE USAGE
Schedule and Dose
Recommendations are based upon immunologic and
epidemiologic considerations, taking into account the
possibly increased risks of exposure at school entrance.
Since the concentration of antigens varies in different
manufacturers' products, the labeling provides specific
information on the proper volume of a single dose.
Primary Immunization
Children 2 months through 6 years: The recom-
mended dose of DTP given intramuscularly on three oc-
casions at 4 to 6 week intervals with a reinforcing dose
approximately 1 year after the third injection. Ideally,
immunization is begun at age 2 to 3 months or at the
time of a 6-week "check-up" if such timing is an estab-
lished routine.
Schoolchildren and adults: The recommended dose of
Td* given intramuscularly or subcutaneously on two oc-
casions at 4 to 6 week intervals with a reinforcing dose
approximately 1 year after the second.

Booster Doses
Children 3 through 6 years (Preferably at time of
school entrance kindergarten or elementary school):
The recommended dose of DTP intramuscularly.
Thereafter and for all other persons: The recom-
mended dose of Td intramuscularly or subcutaneously
every 10 years. (If a dose is administered sooner as part
of wound management see specific recommendations
- the next booster is not needed for another 10 years.)
More frequent booster doses are not indicated and may
be associated with increased frequency and severity of
reactions.

TETANUS PROPHYLAXIS
IN WOUND MANAGEMENT
An important part of the management of wounds is
prevention of tetanus. The physician is then often faced


*Td is considered the agent of choice for immunization of
school-age children on the basis of data regarding its adequacy
in primary immunization of older children and adults and be-
cause of increasing reactions to full doses of diphtheria toxoid
with age. Such reactions are not uncommon from about age 6
in the southern United States, to 10 or 12 in the northern
portions of the country. The use of Td obviates the need for
Schick or Moloney testing prior to immunization.


with questions of using tetanus toxoid for active protec-
tion and Tetanus Immune Globulin (Human) (TIG) or
tetanus antitoxin of animal origin for passive protection.
Available evidence demonstrates that complete primary
immunization with tetanus toxoid (initial doses plus re-
inforcing dose) provides a very long-lasting basis for
active protection against tetanus. Therefore, passive pro-
tection need be considered only when the patient has no
valid history of any previous tetanus toxoid. This liberal
interpretation is justifiable in view of evidence that per-
sons who have previously received even one dose of
tetanus toxoid will respond adequately to a single boost-
er, even after an interval of many years.
The following outline is a conservative guide to active
and passive tetanus immunization in wound manage-
ment. It presumes a reliable knowledge of the patient's
immunization history. (Considerable evidence indicates
that immunity often persists very much longer than the
specified 1 year interval; but until this observation is
established conclusively, the 1 year interval is reasonable
for general purposes.)
1. Primary immunization or last booster dose less
than 1 year before injury: No tetanus prophylaxis re-
quired.
2. Primary immunization or last booster dose more
than 1 year before injury: The recommended single dose
of Tdt intramuscularly or subcutaneously.
3. Incompletely immunized: Complete primary im-
munization.
4. Unimmunized or immunization history uncertain:
Initiate primary immunization.

The decision to administer concomitant passive
prophylaxis in this case will depend upon medical judg-
ment after evaluating such factors as location of wound,
its type and severity, the degree and kind of contamina-
tion, and the time elapsed since injury. If passive therapy
is to be used, TIG is preferable. It offers the advantages
of a longer period of protection and freedom from un-
desirable reactions. The currently recommended pro-
phylactic dose of TIG is 250 units for wounds of average
severity. When used concurrently, tetanus toxoid and
globulin should be given in separate syringes at separate
sites.
Should TIG be unavailable, equine or bovine anti-
toxin may be used, bearing in mind the risk that serious
reactions may follow injections of animal serum. The
usual dose is 3,000 to 5,000 units. Its administration
should always be preceded by careful screening for sensi-
tivity in accordance with instructions furnished with the
antitoxin by the manufacturer.
t If there is any reason to suspect hypersensitivity to the diphthe-
ria component, tetanus toxoid (T) should be substituted for Td
(adult type).



Published MMWR: Vol. 15, No. 48, 1966.





SELECTED BIBLIOGRAPHY
Diphtheria
Ipsen, J.: Circulating Antitoxin at the Onset of Diphtheria in
425 Patients. J. Immun., 54:325-347, 1946.
Naiditch, M.J. and Bower, A.G.: Diphtheria A Study of
1,433 Cases Observed During a Ten-Year Period at the Los
Angeles County Hospital. Amer. J. Med., 17:229-245, 1954.
National Communicable Disease Center: Diphtheria Surveil-
lance Report No. 9, March 24, 1969.
Scheibel, I., et aL: Duration of Immunity to Diphtheria and
Tetanus After Active Immunization. Acta Path. Microbiol. Scan.,
67:380-392, 1966.
Tasman, A. and Lansberg, H.P.: Problems Concerning the
Prophylaxis, Pathogenesis, and Therapy of Diphtheria. Bull.
WHO. 16:939-973, 1957.
WHO Technical Report Series No. 61, Diphtheria and Per-
tussis Vaccination, Report of Conference of Heads of Labora-
tories Producing Diphtheria and Pertussis Vaccines, Part 1 -Diph-
theria, 1953.
Tetanus
Eckmann, L. (ed): Principles on Tetanus: Proceedings of the
International Conference on Tetanus, Bern, July 15-19, 1966.
Bern: Huber, 1967.
Gottlieb, S., et al.: Long-Term Immunity to Diphtheria and
Tetanus: Mathematical Model. Amer. J. Epidem., 85:207-219,
1967.
LaForce, F.M., Young, L.S., and Bennett, J.V.: Tetanus in
the United States (1965-1966): Epidemiologic and Clinical Fea-
tures. New Eng. J. Med., 280:569-574, 1969.


Peebles, T.C., et al.: Tetanus-Toxoid Emergency Boosters: A
Reappraisal. New Eng. J. Med., 280:575-581, 1969.
Rubbo, S.D.: New Approaches to Tetanus Prophylaxis. Lan-
cet, 2:449-453, 1966.
Scheibel, I., et al.: Duration of Immunity to Diphtheria and
Tetanus After Active Immunization. Acta Path. Microbiol. Scan.,
67:380-392, 1966.
Volk, V.K., et al.: Antigenic Response to Booster Dose of
Diphtheria and Tetanus Toxoids: Seven to Thirteen Years
After Primary Inoculation of Noninstitutionalized Children. Pub.
Health Rep., 77:185-195, 1962.
White, W.G., et al.: Duration of Immunity After Active Im-
munization Against Tetanus. Lancet, 2:95-96, 1969.

Pertussis
Berg, J.M.: Neurologic Complications of Pertussis Immuniza-
tion. Brit. Med. J., 2:24-27, 1958.
Bradford, W.L.: The Bortella Group, In: Dubos and Hisch,
Bacterial and Mycotic Infections of Man. 4th Edition, Philadel-
phia, J.B. Lippincott, 1965, 742-751.
Eldering, G.: Some Laboratory Aspects of a Pertussis Surveil-
lance Program. Proceedings of the Fifth Annual Immunization
Conference, San Diego, California. U.S. Department of Health,
Education, and Welfare, PHS, HSMHA, National Communicable
Disease Center, 1968, 91-95.
Gordon, J. and Hood, R.I.: Whooping Cough and Its
Epidemiological Anomalies. Amer. J. Med. Sci., 222:333-361,
1951.
Lambert, H.J.: Epidemiology of a Small Pertussis Outbreak
in Kent County, Michigan. Pub. Health Rep., 80:365-369, 1965.


IMMUNE SERUM GLOBULIN
FOR PREVENTION OF VIRAL HEPATITIS
(Infectious Hepatitis and Transfusion-Associated Hepatitis)


INFECTIOUS HEPATITIS
The agent that causes human infectious hepatitis has
not yet been identified but is presumed to be a virus. No
vaccine is available. Administration of Immune Serum
Globulin (ISG)* to exposed persons can, however,
afford a high degree of protection against infectious
hepatitis. ISG substantially reduces the frequency of
overt clinical disease, although inapparent infection may
occur. Following such infection, lifelong active im-
munity is thought to develop.
Patients with infectious hepatitis have been shown to
excrete virus in stool as much as 2 to 3 weeks before and
2 weeks after onset of jaundice. Viremia has been
demonstrated approximately 2 weeks before and less
than I week after onset of jaundice.
Transmission of the disease is principally by the fecal-
oral route and is most likely to occur under conditions
of inadequate sanitation or close contact with infected
individuals. Direct person-to-person spread of infection



*Official name: Immune Serum Globulin (Human). Poliomyelitis
Immune Globulin (Human) is an equivalent product and may
also be used; other immune globulin products are not suitable.


otherwise is unusual. Transmission is also possible by the
parenteral route. The incubation period of infectious
hepatitis is relatively long, in most cases between 15 and
50 days (average 25 to 30 days).

IMMUNE SERUM GLOBULIN
ISG is prepared for intramuscular injection from large
pools of plasma (1,000 or more donors) obtained from
venous and/or placental blood. The product is a 16.5
percent solution of globulin prepared by cold alcohol
fractionation. Serum hepatitis has not been transmitted
by ISG of this type.

ISG FOR PREVENTING INFECTIOUS
HEPATITIS
The decision to administer ISG should be based on
assessment of the epidemiologic circumstances -
specifically, whether the exposure could result in infec-
tion. The administration of ISG is relevant when there
is: 1) definite exposure to a known case or source of
infection, or 2) anticipated continuous or intermittent
exposure.
ISG given after known exposure should be given as
soon as possible. Its prophylactic value decreases as time





increases after exposure. The use of ISG more than 5 to
6 weeks after exposure is not indicated.

Dosage
The dosage patterns of ISG in common use have been
derived primarily from field and clinical observations.
Da a from these observations provide operational guide-
lines on which to base recommendations.
Under most conditions of exposure, protection has
been afforded by giving 0.01 ml of ISG per pound of
body weight (0.01 ml/lb or approximately 0.02 ml kg)
This dosage may be conveniently simplified (Table 1):



Table 1
Guidelines for ISG Prophylaxis of Infectious Hepatitis
for General Use


Person's Weight (lb)


ISG Dose (ml)*


up to 50 0.5
50-100 1.0
over 100 2.0
*Within limits, larger doses of ISG provide longerlasting but not
necessarily more protection. Higher doses are, therefore, used
under certain circumstances (See Institutional Contacts and
Travelers to Foreign Countries).



Individual Recommendations
Household contacts: There is good evidence that
close personal contact, such as occurs among permanent
or even temporary household residents, is important in
spreading infectious hepatitis. Secondary attack rates are
high for household contacts, panricularly children and
teenagers. Although secondary attack rates are some-
what lower for adults, their illnesses tend to be more
severe. For these reasons, ISG is recommended for all
household contacts who have not already had infectious
hepatitis.
School contacts: Although the highest incidence of
hepatitis is among school-age children, contact at school
is usually not an important means of transmitting this
disease. Therefore, routine administration of ISG is not
indicated for pupil or teacher contacts of a case. How-
ever, when epidemiologic study has clearly shown that
school or classroom contact is responsible for continued
transmission of disease, it is reasonable to administer
ISG to individuals at risk.
Institutional contacts: In contrast to schools, con-
ditions favoring transmission of infectious hepatitis exist
in. institutions such as prisons and facilities for the
mentally retarded. Sporadic cases as well as epidemics
have frequently been reported in such institutions. ISG
administered to patient and staff contacts of cases in the
doses shown in Table 1 effectively limited the spread of
disease in these circumstances.


Where infectious hepatitis exists endemically, particu-
larly in very large institutions with high rates of ad-
mission and discharge. residents and staff personnel may
be subject to frequent and continuing exposure. Under
these conditions, use of ISG has not resulted in eradica-
tion of hepatitis However, it has been shown to provide
temporary protection when administered in doses of
0.02 to 0.05 ml/lb at the time of admission or employ-
ment. It may be necessary to readminister ISG in the
same dose after 6 months if the risk is felt to persist.
Hospital contacts: Routine prophylactic administra-
tion of ISG to hospital personnel is not indicated.
Emphasis should be placed on sound hygienic practices.
Intensive, continued education programs pointing out
the risks of exposure to infectious hepatitis and the
recommended precautions should be directed toward
hospital personnel who have close contact with patients
or infectious materials.
For those accidentally inoculated with blood or
serum of patients with hepatitis, the appropriate
prophylactic dose of ISG is that recommended in Table
1. There is no reason to give a larger dose because ISG
appears to be effective in preventing only infectious
hepatitis, not transfusion-associated (serum) hepatitis
(See Transfusion-Associated Hepatitis).
Office and factory contacts: Routine administration
of ISG is not indicated for persons in the usual office or
factory situation exposed to a fellow worker with hepa-
titis.
Common source exposures: When a vehicle, such as
food or water, is identified as a common source of infec-
tion of multiple hepatitis cases, administration of ISG
should be considered for all those exposed to the source.
Pregnancy: Current information does not indicate
that pregnancy in itself should alter the recommenda-
tions for ISG prophylaxis.
Travelers to foreign countries: The risk of infectious
hepatitis for US. residents traveling abroad varies with
living conditions and the prevalence of hepatitis in the
areas to be visited. Travelers may be at no greater risk
than in the United States when their travel involves
ordinary tourist activities and little exposure to un-
cooked foods or water of uncertain quality. For these
travelers, ISG is not recommended.
For travelers visiting areas where hepatitis is a major
health problem who may be exposed to infected persons
and to contaminated food and water, there is increased
risk of acquiring hepatitis. A single dose of ISG is recom-
mended for them as shown in Table 2, which gives guide-
lines for U.S. residents traveling in foreign countries.
(Large geographic areas have been defined for ease of
interpretation and because information is inadequate to
permit developing more precise boundaries.)
For individuals who reside abroad in areas where
hepatitis is common, the risk of hepatitis is greatly in-
creased and appears to continue'so for years. Experience
has shown that regular administration of ISG offers at





least partial protection against hepatitis. It is recom-
mended that prophylactic ISG be repeated every 6
months at doses indicated in Table 2.*


Table 2
Guidelines for ISG Prophylaxis of Infectious Hepatitis
for U.S. Residents Traveling or Living in
Foreign Countries*
(See text for additional details)


Area


Africa
Asia
North America
Central America
Mexico (Rural)
Pacific Region
Philippine Islands
South Pacific
Islands
South America
Europe
North America
Canada
Caribbean Islands
Mexico (Urban)
Pacific Region
Australia
Japan
New Zealand


Person's Short-Term
Weight Travel
Weit (1-2 months)
(lb) ISG Dose (ml)




up to 50 0.5
50-100 1.0

over 100 2.0


Extended Travel
or Residence
(3-6 months)**
ISG Dose (ml)


Routine ISG prophylaxis is not indicated


*In all travel, care should be exercised in consuming uncooked
foods and water of uncertain quality.
**Repeat every 6 months of travel or residence.



Reactions
Intramuscular administration of ISG rarely is fol-
lowed by adverse reactions. Discomfort may occur at the
site of injection, especially when larger volumes are used.
A few instances of hypersensitivity have been reported,
but in view of the very large number of persons who
have received ISG, the risk is exceedingly small.
ISG should not be administered intravenously be-
cause of the danger of severe reactions.
Antibody against gamma globulin may appear fol-
lowing administration of ISG although its clinical signifi-



*Some agencies have used up to 0.05 ml/lb each 5 to 6 months
rather than the 5 ml for adults recommended here.


chance is unknown. When ISG is indicated for pro-
phylaxis of infectious hepatitis, this theoretical con-
sideration should not preclude its administration.



TRANSFUSION-ASSOCIATED HEPATITIS
The risk of transmitting viral hepatitis by blood trans-
fusion is a serious and continuing problem. Several re-
ports indicate that the incidence of clinical hepatitis is
greater among recipients of blood obtained from certain
categories of donors. The risk also becomes greater as
the number of transfusions increases. Furthermore, the
case-fatality rate of transfusion-associated hepatitis in-
creases with advancing age.
Evidence has been advanced both for and against the
effectiveness of ISG as prophylaxis of transfusion-
associated hepatitis. Although some investigators have
reported that 10 ml of ISG at the time of transfusion
and again 1 month later reduced the number of cases,
other equally careful studies have not substantiated this
claim. Existing evidence provides no adequate basis for
recommending that ISG be given routinely to recipients
of blood transfusions.
Among the means of effectively lowering the inci-
dence of transfusion-associated hepatitis are: careful
selection of donors, development of central registries of
known or suspect carriers, and use of blood and poten-
tially icterogenic blood products only when necessary.

Published MMWR: Vol. 17, No. 31, 1968.


SELECTED BIBLIOGRAPHY

Cline, A., Mosley, J.W., and Scovel, F.G.: Viral Hepatitis
Among American Missionaries Abroad. JAMA,
199:551-553,1967.
Drahe, M.E. and Ming, C.: Gamma Globulin in Epidemic
Hepatitis: Comparative Value of Two Dosage Levels, Apparently
Near the Minimal Effective Level. JAMA. 155:1302-1305, 1954.
Holland, P.V., et al.: Gamma Globulin in the Prophylaxis of
Post-Transfusion Hepatitis. JAMA. 196:471-474, 1966.
Kluge, T.: Gamma-globulin in the Prevention of Viral Hepati-
tis A Study of the Effect of Medium-size Doses. Acta Med.
Scan., 174:469-477, 1963.
Krugman, S., Ward, R., and Giles, J.P.: The Natural History
of Infectious Hepatitis. Amer. J. Med., 32:717-728, 1962.
Mirick, G., Ward R., and McCollum, R.W.: Modification of
Post-Transfusion Hepatitis by Gamma Globulin. New Eng. J.
Med., 273:59-65, 1965.
Mosley, J.W., et al.: Comparison of Two Lots of Immune
Serum Globulin for Prophylaxis of Infectious Hepatitis. Am. J.
Epidem., 89:539-550, 1968.
Mosley, J.W. and Galambos, J.T.: Viral Hepatitis. In: Schiff,
Diseases of the Liver. 3rd Edition, Philadelphia, J.B. Lippincott,
1969, 410-497, in press.
Stokes, J., Jr., and Neefe, J.R.: The Prevention and Attenua-
tion of Infectious Hepatitis by Gamma Globulin. JAMA,
127:144-145, 1945.





INFLUENZA VACCINE-1969-70


INTRODUCTION
The nationwide epidemic of A2 influenza in the
United States in the fall and winter of 1968-69 showed
the impact of a major antigenic change in the prevalent
influenza viruses. The Hong Kong strain responsible for
the epidemic was the most distinctive variant among A2
influenza viruses identified since initial appearance of
the A2 sub-type in 1957. The 1968-69 epidemic high-
lighted again the problems that are encountered in
rapidly developing and producing sufficient quantities of
vaccine incorporating a new antigen.
Forty-four States reported widespread outbreaks of
Hong Kong strain influenza; in six, involvement was less
extensive. In all nine geographic divisions of the country,
excess pneumonia and influenza mortality peaked
sharply in early January 1969.
In December 1968, Washington State reported an
outbreak of type B influenza concurrent with Hong
Kong strain A2. In January and February 1969, 18 addi-
tional States reported type B influenza; it was wide-
spread only in States in the central part of the country.
Unlike Hong Kong strain A2 influenza, which affected
all age groups, type B influenza illness occurred pri-
marily in school-age children.

INFLUENZA VIRUS VACCINES
The Division of Biologics Standards, National lAsti-
tutes of Health, regularly reviews influenza vaccine
formulation, and, when indicated, recommends revision
to include contemporary antigens. After characterization
of the A2 Hong Kong virus in September 1968, a
monovalent vaccine incorporating the new strain was
recommended.
While some influenza vaccines have achieved 60 per-
cent or greater effectiveness in protection against the
same or closely related virus strains, vaccines in general
civilian use often have not been this effective. Final data
on vaccine field trials conducted in the 1968-69 in-
fluenza season are being compiled. Preliminary data indi-
cate the monovalent Hong Kong strain vaccine was con-
siderably less effective than would have been desirable.
For 1969-70, both standard and highly purified
bivalent influenza vaccines will be available. The recom-
mended adult dose will contain 400 chick cell aggluti-
nating (CCA) units of Hong Kong strain antigen
(A2/Aichi/2/68) and 300 CCA units of type B antigen
(B/Mass/3/66). The highly purified vaccine is equivalent
in potency to the standard vaccine but contains less non-
viral protein.
VACCINE USAGE
General Recommendations
It is unlikely that there will be more than sporadic
cases of influenza due to A2 strains in the 1969-70


season. Type B influenza may appear in areas where it
did not occur in 1968-69.
Until good protection is provided consistently by
influenza vaccine, it is not recommended for healthy
adults and children.
Acknowledging its limited effectiveness, vaccine
should be considered only for persons of any age with
certain chronic debilitating conditions: 1) rheumatic
heart disease, especially mitral stenosis; 2) such cardio-
vascular disorders as arteriosclerotic heart disease and
hypertension, particularly with evidence of cardiac insuf-
ficiency; 3) chronic bronchopulmonary diseases, such as
asthma, chronic bronchitis, cystic fibrosis, bron-
chiectasis, pulmonary fibrosis, pulmonary emphysema,
and advanced pulmonary tuberculosis; or 4) diabetes.
mellitus or Addison's disease.
Although the indications of vaccination are less clear,
older persons, who may have incipient or potential
chronic disease, particularly cardiovascular and broncho-
pulmonary, should also be considered candidates for vac-
cination.
Schedule
The primary series consists of two dose; administered
subcutaneously, preferably 6 to 8 weeks apart. (Dose
volume for adults and children is specified in the manu-
facturers' labeling.) Persons at high risk who regularly
receive influenza vaccines and had one or more doses of
the monovalent vaccine containing Hong Kong strain
antigen in the 1968-69 season require only a single full
dose booster of bivalent vaccine. Immunization should
be scheduled for completion by early December.
Local or mild systemic reactions to standard in-
fluenza vaccines are common. They occur in up to 50
percent of adults and appear to be related primarily to
the non-viral components of the vaccine.
Individuals who should receive influenza vaccine but
have had severe local or systemic reactions to the stan-
dard vaccine might be given a highly purified vaccine
subcutaneously.
Precautions
Influenza vaccine should not be administered to any-
one who is clearly hypersensitive to eggs because the
vaccine viruses are grown in embryonated chicken eggs.
Published MMWR: Vol. 18, No. 25, 1969.


SELECTED BIBLIOGRAPHY

Davenport, F. M.: Present Status of Inactivated Influenza
Virus Vaccines. In: First International Conference on Vaccines
Against Viral and Rickettsial Diseases of Man. Pan American
Health Organization Scientific Publication No. 147, 1967, 3-8.
Dull, H. B.: Influenza 1967-1968: A Backdrop for Appraisal.
Arch. Environ. Health, 16:611-613, 1968.





Eickhoff, T. C., Sherman, 1. L., and Serfling, R. E.: Observa-
tions on Excess Mortality Associated with Epidemic Influenza.
JAMA. 176:776-782, 1961.
Francis, T., Jr.: Epidemic Influenza: Immunization and Con-
trol. Med. Clin. N. Amer., 51:781-790, 1967.
International Conference on Asian Influenza. Am. Rev. Resp.
Dis. 83 (No. 2): Part 2, 1961.
Langmuir, A. D., Henderson, D. A., and Serfling, R. E.: The
Epidemiological Basis for the Control of Influenza. Am. J. Public
Health, 54:563-571. 1964.
Morris, J. A., et al.: Immunity to Influenza as Related to
Antibody Levels. New Eng. J. Med., 274:527-535, 1966.


National Communicable Disease Center: Influenza-Respira-
tory Disease Surveillance Report No. 84, September 15, 1968.
Robinson, R.Q.: Natural History of Influenza Since the
Introduction of the A2 Strain. Prog. Med. ViroL, 6:82-110,
1964.
Stuart, W.H., et al.: Evaluation of Monovalent Influenza Vac-
cine in a Retirement Community During the Epidemic of
1965-66. JAMA, 209:232-238, 1969.
Stuart-Harris, C. H.: Influenza and Other Virus Infections of
the Respiratory Tract. 2nd Edition, Baltimore. Williams & Wl-
kins, 1965.


MEASLES VACCINES


INTRODUCTION
Highly effective, safe vaccines are available for elimi-
nating measles in the United States. Collaborative efforts
of professional and voluntary medical and public health
organizations in vaccination programs have brought
a 95 percent reduction in the incidence of measles, but a
continuing effort to immunize all susceptibles in the
childhood population is necessary if the goal of measles
eradication is to be realized.
Measles is often a severe disease, frequently accom-
panied by complications such as bronchopneumonia,
middle ear infection, and encephalitis. Encephalitis,
which follows measles in approximately one of every
1,000 cases, often causes permanent brain damage and
mental retardation. One in every 10,000 measles cases is
fatal.

MEASLES VIRUS VACCINES
Live, attenuated measles virus vaccines*, the original
Edmonston B and the further attenuated strains
(Schwarz and Moraten), are widely used in the United
States. Edmonston B strains are prepared in either chick
embryo or canine renal cell culture; the further atten-
uated strains are prepared only in chick embryo cell cul-
ture.
These measles virus vaccines produce a mild or in-
apparent, non-communicable infection. Fifteen percent
ot children receiving either the Edmonston B strain with
Measles Immune Globulin (MIG) or the further atten-
uated strains experience fever, with temperatures of
1030F. (rectal) or higher, beginning about the sixth day
after vaccination and lasting up to 5 days. About twice
as many (30 percent) of those receiving Edmonston B
without MIG have similar febrile responses. The great
majority of reports indicate that even children with high
fevers experience relatively little discomfort and minimal
toxicity. As a result, febrile reactions often go unnoticed
by the parents.



*The official name of the product in use is Measles Virus Vac-
cine, Live, Attenuated.


An antibody response develops in virtually all suscep-
tible children given live measles virus vaccine. Edmon-
ston B vaccine administered without MIG induces anti-
body at about the level of natural measles infection.
Antibody titers in response to Edmonston B with MIG
or to further attenuated vaccine are slightly lower. How-
ever, all of these vaccines appear to confer durable pro-
tection in most individuals.
Experience with more than 35 million vaccinations in
the United States by mid-1969 indicates that live
measles virus vaccines are among the safest immunizing
agents available. Reports of reactions to measles vaccina-
tion have been rare, and in no case has it been shown
that the reaction was actually vaccine induced and not
merely temporally associated.

VACCINE USAGE
General Recommendations
All susceptible children those who have not had
natural measles or measles vaccine should be vac-
cinated. It is particularly important to vaccinate suscep-
tibles entering nursery school, kindergarten, or elemen-
tary school. They are often responsible for transmitting
measles to other children in the community. In order to
achieve adequate measles protection, communities
should encourage ongoing programs to vaccinate all
children at about 1 year of age.
The risk of acquiring measles in the United States has
been greatly reduced by extensive vaccination, and sus-
ceptible children are therefore unlikely to be infected.
The risk in other countries may be considerably greater;
therefore, it would be wise to immunize susceptible chil-
dren before they travel abroad.
Dose: The single dose of live measles vaccine should
be given subcutaneously. No booster dose is needed.
Administration of the Edmonston B strain should
ordinarily be accompanied by MIG 0.01 ml/lb, given
with a different syringe at a different site. MIG should
not be given with further attenuated measles vaccine.
Age: For maximum efficacy, measles virus vaccine
should be administered when children are at least 12





months old. It may be given to infants at 9 to 12 months
of age recognizing that the proportion of serocon-
versions may be slightly reduced. The proportion is fur-
ther decreased if MIG is administered with vaccine.
Vaccination of adults at the present time is rarely
necessary, because nearly all Americans over 15 years
old now are immune. Limited data indicate that
reactions to vaccine are no more common in adults than
in children.
High risk groups: Immunization against measles is
particularly important for children with chronic ill-
nesses, such as heart disease, cystic fibrosis, and chronic
pulmonary diseases, for malnourished children, and for
those in institutions.

Use of Vaccine Following Exposure
Live, attenuated measles virus vaccine can usually pre-
vent disease if administered before or on the day of
exposure to natural measles; study findings indicate that
protection is not conferred when vaccine is administered
after the day of exposure. No untoward effects have
been observed when vaccination followed exposure to
natural measles.
Precautions
Severe febrile illnesses: Vaccination should be post-
poned until the patient has recovered.
Tuberculosis: Exacerbations of tuberculosis known to
follow natural measles infection might, by analogy, be
associated with the live, attenuated measles virus. There-
fore, an individual with known active tuberculosis
should be under treatment when given measles vaccine.
Although tuberculin skin testing is desirable as part of
ideal health care, it need not be a routine prerequisite in
community measles immunization programs. The value
of protection against natural measles outweighs the
theoretical hazard of possible exacerbation of an un-
suspected tuberculosis infection by vaccination.
Recent Immune Serum Globulin administration:
After administration of Immune Serum Globulin, vac-
cination should be deferred for 3 months. Persistence of
measles antibody from the globulin might interfere with
suitable response to the vaccine.
Marked hypersensitivity to vaccine components:
Measles vaccine produced in chick embryo cell culture
should theoretically not be given to children clearly
hypersensitive to chicken eggs. Similarly, vaccine pro-
duced in canine renal cell culture should not be admin-
istered to children highly sensitive to dog hair or dander.
To date, however, there have been no documented re-
ports of serious or anaphylactic hypersensitivity re-
actions to measles vaccine in the United States.
Contraindications
Altered immune states: Administration of measles
virus vaccine to children with leukemia has occasionally
been followed by such serious complications as fatal
giant cell pneumonia. Theoretically, attenuated measles
virus infection might be potentiated by severe under-
lying diseases, such as lymphomas and generalized malig-


nancies, or by lowered resistance, such as from therapy
with steroids, alkylating drugs, antimetabolites, or radia-
tion; therefore, vaccination of such patients should be
avoided.
Pregnancy: On theoretical grounds, it would be
reasonable to avoid vaccinating pregnant women with
live, attenuated measles virus vaccine.
Management of Patients with Contraindications
If immediate protection against measles is required
for persons for whom live, attenuated measles virus vac-
cine is contraindicated, passive immunization with MIG
(dose approximately 0.1 ml/lb or 0.25 ml/kg) should be
given as soon as possible after a known exposure. It is
important to note, however, that this dose of MIG which
is effective in preventing measles in normal children may
not be equally effective in children with acute leukemia.
To decrease the risk of measles infection for such chil-
dren, all their close contacts who are susceptible to
measles should be immunized.
Prior Immunization with Inactivated
Measles Virus Vaccine
Atypical measles, sometimes severe, has occasionally
followed exposure to natural measles in children pre-
viously inoculated with inactivated measles virus vac-
cines.
Untoward local reactions such as induration and
edema have at times been observed when live measles
virus vaccine was administered to persons who had pre-
viously received inactivated vaccine. Despite the risk of
local reaction, children who have previously been given
inactivated vaccine should also be given the live vaccine
for full and lasting protection against natural infection.

SIMULTANEOUS ADMINISTRATION
OF LIVE VIRUS VACCINES
There are obvious practical advantages to adminis-
tering two or more live virus vaccines simultaneously.
Data from specific investigations are not yet sufficient to
develop comprehensive recommendations on simul-
taneous use, but a summary of current experience, atti-
tudes, and practices provides useful guidance.
It has been generally recommended that live virus vac-
cines be given at least a month apart whenever possible
- the rationale for this being that more frequent and
severe adverse reactions as well as lower antibody
responses otherwise might result. Field observations indi-
cate, however, that with simultaneous administration of
certain live virus vaccines, results of this kind have been
minimal or absent. (For example, the third dose of triva-
lent oral polio-virus vaccine, which is recommended
during the second year of life, is commonly given at the
same time as smallpox vaccination without evident dis-
advantage.)
If the theoretically desirable 1-month interval is not
feasible, as with the threat of concurrent exposures or
disruption of immunization programs, the vaccines
should preferably be given on the same day at dif-
ferent sites for parenteral products. An interval of about





2 days to 2 weeks should be avoided because inter-
ference between the vaccine viruses is most likely then.

COMMUNITY IMMUNIZATION PROGRAMS
Ongoing Programs
Universal immunization as part of good health care
should be accomplished through routine and intensive
programs carried out in physicians' offices and public
health clinics. Programs aimed at immunizing children at
about 1 year of age against measles should be established
by all communities. In addition, all susceptible children
entering nursery school, kindergarten, and elementary
school should receive vaccine because of their role in
community spread of natural measles.
Special Intensive Programs
Community-wide immunization programs have been
useful in the rapid distribution of live measles virus vac-
cine. Attention should now be directed toward sys-
tematic programs for groups of susceptible children re-
maining in both urban and rural areas.
Control of Measles Epidemics
Studies have shown that community-wide measles
epidemics can be controlled by prompt administration
of measles vaccine to selected groups of children, par-
ticularly the susceptibles in nursery schools, kinder-
gartens, and the first two or three grades of elementary
school. However, once measles is widely disseminated in
a community, it may be necessary to immunize suscep-
tible children of all ages to alter the course of the epi-
demic.

CONTINUED SURVEILLANCE
Continued careful surveillance of measles and its com-
plications is necessary to appraise nationally and locally
the effectiveness of measles immunization programs, par-
ticularly efforts at measles eradication. Surveillance can


delineate failures to achieve adequate levels of pro-
tection and define groups in need of control programs.
Although more than 35 million doses of measles virus
vaccine have now been administered in the United
States, continuous and careful review of any adverse re-
action remains important. All serious reactions or
suspected measles illnesses in vaccinated children should
be carefully evaluated and reported in detail to local and
State health officials.

Published MMWR: Vol. 14, No. 7, 1965; addition, Vol. 14,
No. 36, 1965; revised, Vol. 15, No. 16, 1966; revised, Vol. 16,
No. 32, 1967.


SELECTED BIBLIOGRAPHY
Burnet, Sir MacFarlane: Measles as an Index of Immuno-
logical Function. Lancet, 2:610-613, 1968.
Enders, J.F. and Katz, S.L.: Present Status of Live Rubeola
Vaccines in the United States. In: First International Conference
on Vaccines Against Viral and Rickettsial Diseases of Man. Pan
American Health Organization, Scientific Publication No. 147,
1967, 295-300.
Fulginiti, V.A., Arthur, J., Pearlman, D.S., and Kempe, C.H.:
Serious Local Reactions Following Live Measles Virus Immuniza-
tion in Previous Killed-Vaccines Recipients. J. Pediat.,
69:891-892, 1966.
Katz, S.L. and Enders, J.F.: Measles Virus. In: Horsfall and
Tamm, Viral and Rickettsial Infections of Man, 4th Edition,
Philadelphia, J.B. Lippincott, 1965, 784-801.
Miller, G., Gale, K., Villarejos, V., James, W., Arteaga, C.,
Casey, H., and Henderson, D.A.: Edmonston B: A Further
Attenuated Measles Vaccine-A Placebo Controlled Double Blind
Comparison. Amer. J. Public Health, 57:1333-1340, 1967.
Nader, P.R., and Warren, R.J.: Reported Neurologic Disorders
Following Live Measles Vaccine. Pediatrics, 41:997-1001, 1968.
National Communicable Disease Center: Measles in Previously
Immunized Children, Governors Island, New York. Morbidity
and Mortality Weekly Report, 18:141-142, April 26, 1969.
Swartz, T., Klinberg, W., Nishmi, M., Goldblum, N.,
Gerichter, C., Yofe, Y., and Cockburn, W.C.: A Comparative
Study of Four Live Measles Vaccines in Israel. Bull. WHO,
39:285-292, 1968.


MUMPS VACCINE


INTRODUCTION
Mumps, one of the common communicable diseases,
is observed with greatest frequency in young school-age
children. However, approximately 15 percent of re-
ported cases occur after the onset of puberty.
Overt evidence of central nervous system disease with
sequelae is rare in mumps, although meningeal involve-
ment appears to be common. Orchitis has been reported
in up to 20 percent of clinical cases occurring in post-
pubertal males. Symptomatic involvement of other
glands and organs is observed less frequently. Nerve deaf-
ness is a very rare, but serious, complication of mumps.
All naturally acquired mumps infections, including
the estimated 30 percent which are subclinical, confer
durable immunity.


LIVE MUMPS VIRUS VACCINE*
Live mumps vaccine is prepared in chick embryo cell
culture. It produces an inapparent, non-communicable
infection following administration. Since its intro-
duction approximately 1 year ago, mumps vaccine has
been given to more than 1 million persons without re-
port of significant side reactions clearly attributable to
vaccination.
More than 95 percent of susceptible vaccinees
develop detectable antibodies after vaccination. Al-
though titers are lower than those induced by natural
infection, the pattern of antibody persistence parallels


*Official name: Mumps Virus Vaccine, Live





that seen following clinical mumps. The long-term dura-
tion of vaccine-induced immunity is unknown, but 3-year
observations show continuing protection against natural
infections and, in two small groups of children, antibody
levels which are persisting without decline.

VACCINE USAGE
General Recommendations
Age: Live mumps vaccine may be used at any age
from 12 months. It should not be administered to
children less than 12 months old because of possible
persistence of interfering maternal antibody. The vaccine
is of particular value in children approaching puberty,
adolescents, and adults, especially males, who have not
had mumps parotitis, either unilateral or bilateral.**
Since the Committee's initial statement on live, atten-
uated mumps vaccine in 1967, further experience with
the vaccine has been accumulated. In view of evidence
showing continued vaccine efficacy and safety, the Com-
mittee has modified its recommendation for limited vac-
cination of young children and now suggests that con-
sideration be given, to immunizing all susceptible chil-
dren over 1 year of age. The Committee reaffirms its
position, however, that mumps vaccination programs
should not be allowed to take priority over essential
ongoing health activities.
Dose: A single dose of vaccine should be administered
subcutaneously in the volume specified by the manu-
facturer.
Use of Vaccine Following Exposure
It is not known whether live mumps vaccine will pro-
vide protection when administered after exposure. There
is, however, no contraindication to its use at that time.t

Precautions
Severe febrile illnesses: Vaccination should be post-
poned until the patient is completely recovered.
Marked hypersensitivity to vaccine components:
Mumps vaccine is produced in chick embryo cell culture

**The mumps skin test with currently available antigens is an
unreliable indicator of immunity.
t Inactivated mumps vaccine and Mumps Immune Globulin
(Human) are of questionable effectiveness under these circum-
stances.


and should not be given to persons hypersensitive to
ingested egg proteins. Also, the vaccine contains small
amounts of neomycin, so it should not be given to in-
dividuals known to be sensitive to this antibiotic.
Altered immune states: Mumps vaccine virus infec-
tion might be potentiated by severe underlying diseases,
such as leukemia, lymphoma, or generalized malignancy,
and by lowered resistance, such as from therapy with
steroids, alkylating drugs, antimetabolites, or radiation;
therefore, vaccination of such patients should be
avoided.
Pregnancy: On theoretical grounds, it is reasonable to
avoid using live mumps vaccine during pregnancy.

Simultaneous Administration of Live Mumps
Virus Vaccine with Other Live Virus Vaccines
In order to evaluate the live mumps vaccine ade-
quately, its simultaneous administration with other vac-
cines should be deferred until results of controlled clini-
cal investigations are available. Until then, it is recom-
mended that mumps vaccination be separated from
other immunization procedures by about one month
whenever possible.

SURVEILLANCE
Careful surveillance of mumps is important. There is
need to improve reporting of mumps cases and their
complications, to demonstrate continuing vaccine effec-
tiveness, and to document patterns of vaccine use.

Published MMWR: Vol. 16, No. 51, 1967; revised, Vol. 17,
No.45,1968.


SELECTED BIBLIOGRAPHY
Gordon, J.E.: The Epidemiology of Mumps, Am. J. Med. Sci,
412-428, 1940.
Harris, R.W., et al.: Mumps in a Northeast Metropolitan Com-
munity. Am. J. Epidem., 88:224-233, 1968.
Hilleman, M.R., et al.: Live, Attenuated Mumps-Virus Vac-
cine. New Eng. J. Med., 278:227-232, 1968.
Sugg, W.C., et al.: Field Evaluation of Live Virus Mumps
Vaccine. J. Pediat., 72:461-466, 1968.
Weibel, R.E., et al.: Jeryl Lynn Strain Live Mumps Virus
Vaccine. JAMA, 207:1667-1670, 1969.
Witte, J.J. and Karchmer, A.W.: Surveillance of Mumps in the
United States as Background for Use of Vaccine. Pub. Health
Rep., 83:95-100, 1968.





PLAGUE VACCINE


INTRODUCTION
Plague is a sylvatic infection of rodents and their
ectoparasites in many parts of the world. In the western
United States, a few human cases occur each year fol-
lowing exposure to infected wild rodents. In some coun-
tries of Asia, Africa, and South America, epidemic
plague results when the domestic rat population be-
comes infected. Currently the area of most intensive epi-
demic and epizootic infection is Vietnam.

PLAGUE VACCINE
Plague vaccines have been used since the late nine-
teenth century, but it has never been possible to measure
their effectiveness precisely. Immunization with plague
vaccine, however, is known to reduce the incidence and
severity of disease.
The plague vaccine licensed for use in the United
States is prepared from Pasteurella pestis grown in arti-
ficial media, inactivated with formaldehyde, and pre-
served in 0.5 percent phenol.

VACCINE USAGE
General Recommendations
Routine vaccination is not indicated for persons sim-
ply living in plague enzootic areas of the western United
States or for travelers going to most of the countries
reporting cases.* Selective immunization is advisable for
the following:
1. All persons traveling to Vietnam, Cambodia, and
Laos.
2. All persons whose vocations or field work brings
them into frequent and regular contact with wild
rodents in plague enzootic areas of the western United
States, South America, Africa, or Asia.
3. All laboratory personnel working with the P.
pestis organism or with plague-infected rodents.
Primary Immunization
All injections should be given intramuscularly.
Adults and children over 10 years old: The primary
series consists of three doses of vaccine. The first two
doses, 0.5 ml each, should be administered 4 or more
weeks apart, followed by a third dose, 0.2 ml, 4 to 12
weeks after the second injection. When less time is avail-
able, satisfactory but less than optimal results can be
obtained with two 0.5 ml injections administered at least
3 weeks apart.
Children less than 10 years old: The primary series
also is three doses of vaccine, but the doses are smaller.
The manufacturer's guide to proportions of the adult
dose for children is: Infants under 1 year one-fifth
*For a current listing, consult the most recent issue of the World
Health Organization's Weekly Epidemiological Record


adult dose; 1-4 years two-fifths adult dose; 5-10
years three-fifths adult dose. The intervals between in-
jections are the same as for adults.

Booster Doses
Boosters should be given every 6 to 12 months while
individuals remain in an area where the risk of exposure
persists. Satisfactory doses for children and adults are
the same volumes suggested for the third dose in the
primary series. The primary series need never be re-
peated for booster doses to be effective.
Summary
The following table summarizes the recommended
doses for primary and booster vaccination:

Dose Age (Years)
Number Under 1 1-4 5-10 Over 10
1 & 2 0.1 ml 0.2 ml 0.3 ml 0.5 ml
3 & Boosters 0.04 ml 0.08 ml 0.12 ml 0.2 ml


Reactions
Mild reactions consisting of pain, reddening, and
swelling at the injection site are frequently recognized.
With repeated doses, systemic reactions of fever, head-
ache, and malaise occur more often and tend to become
more pronounced. Sterile abscesses are reported to occur
rarely. No fatal or disabling complications have been ob-
served.

Published MMWR: Vol. 17, No. 19, 1968.


SELECTED BIBLIOGRAPHY
Burmeister, R.W., Tigertt, W.D., and Overholt, E.L.: Labora-
tory Acquired Pneumonic Plague. Ann. Intern. Med.,
56:789-800, 1962.
Cavanaugh, D.C., et al.: Some Observations on the Current
Plague Outbreak in the Republic of Vietnam. Amer. J. Public
Health, 58:742-752, 1968.
Caten, J.L., and Kartman, L.: Human Plague in the United
States. JAMA, 205:333-336, 1968.
Cohen, R.J., and Stockard, J.I.: Pneumonic Plague in an Un-
treated Plague-Vaccinated Individual. JAMA, 202:365-366,
1967.
Meyer, K.F.: Pasteurella and Francisella. In: Dubos and
Hirsch, Bacterial and Mycotic Infections of Man. 4th Edition,
Philadelphia, J.B. Lippincott, 1965, 659-697.
Plague in the Americas, PAHO Scientific Publication No.
115:114-117, 1965.
Pollitzer, R.: Plague, No. 22, Monograph Series, Geneva:
World Health Organization, 1954, 1-698.
Pollitzer, R.: A Review of Recent Literature on Plague. Bull.
WHO, 23:313-400, 1960.
World Health Organization Expert Committee on Plague, 3rd
Report. Technical Report Series No. 165, 1959.





POLIOMYELITIS VACCINES


INTRODUCTION
Widespread use of poliovirus vaccines since 1955 has
resulted in the virtual elimination of paralytic polio-
myelitis in the United States. To ensure continued free-
dom from the disease, it is necessary to pursue regular
immunization of all children from early infancy.
Paralytic poliomyelitis declined from 18,308 cases in
1954 to 40 cases in 1967 and 48 cases in 1968. A
national survey in 1968 showed that 82 percent of
individuals 1-19 years old had received at least three
doses of oral poliovirus vaccine (OPV)*, inactivated
poliovirus vaccine (IPV)**, or both.
Nevertheless, low immunization rates still prevail in
certain disadvantaged urban and rural groups, particu-
larly for infants and young children born since the mass
immunization campaigns conducted between 1958 and
1962. Mosi of the cases of paralytic poliomyelitis in
recent years occurred in these populations.
With widespread use of poliovirus vaccine, laboratory
surveillance of enteroviruses indicates that circulation of
wild polioviruses has diminished markedly. It can be
assumed that inapparent infections with wild strains will
no longer contribute significantly to maintaining im-
munity; therefore, it is essential not only to continue
active immunization programs for infants and children
but also to make special efforts to raise the low immuni-
zation rates existing in certain other segments of the
population. Population groups requiring immunization
can be identified by immunization history and serologic
survey.

POLIOVIRUS VACCINES
Between 1955, when IPV was introduced, and 1962,
when live, attenuated vaccines became widely used,
more than 400 million doses of IPV were distributed in
the United States. Primary immunization with IPV plus
regular booster doses provided a high degree of protec-
tion against paralytic disease.
OPV has largely replaced IPV in this country because
it is easier to administer, requires no boosters, and pro-
duces an immune response like that induced by natural
poliovirus infection.
Monovalent OPV types 1, 2, and 3 were widely used
in the United States beginning in 1961, but they have
generally been supplanted by trivalent OPV because of
greater simplicity in scheduling and recordkeeping.
A primary series of three adequately spaced doses of
trivalent OPV will produce an immune response to the
three poliovirus types in well over 90 percent of recipi-
ents.



* Official names of the products in use: (1) Poliovirus Vaccine,
Live Oral, Type 1, (2) Poliovirus Vaccine, Live, Oral, Type 2, (3)
Poliovirus Vaccine, Live Oral, Type 3, (4) Poliovirus Vaccine,
Live, Oral Trivalent.
** Official name: Poliomyelitis Vaccine.


Very rarely, paralysis has occurred in recipients of
OPV or in their close contacts within 2 months of vac-
cine administration. Currently, for each 9 million doses
of OPV given, no more than one case of "vaccine associ-
ated" paralysis in recipients and two in recipient con-
tacts are reported.

VACCINE USAGE
Trivalent OPV-Primary Immunization
Infants: The three-dose immunization series should
be started at 6 to 12 weeks of age, commonly with the
first dose of DTP. The second dose should be given not
less than 6 and preferably 8 weeks later. The third dose
is an integral part of primary immunization and should
be administered 8 to 12 months after the second dose.
Children and adolescents: For unimmunized children
and adolescents through high school age, the primary
series is three doses. The first two should be given 6 to 8
weeks apart, and the third, 8 to 12 months after the
second. If circumstances do not permit the optimal
interval between the second and third doses, the third
may be given as early as 6 weeks after the second.
Adults: Routine poliomyelitis immunization for
adults residing in the continental United States is not
necessary because of the extreme unlikelihood of ex-
posure. However, an unimmunized adult at increased
risk through contact with a known case or travel to areas
where polio is epidemic or occurs regularly should re-
ceive trivalent OPV as indicated for children and
adolescents. Persons employed in hospitals, medical
laboratories, and sanitation facilities might also be at
increased risk, especially if poliomyelitis is occurring in
the area.
Pregnancy is not an indication for vaccine administra-
tion, nor is it a contraindication when protection is re-
quired.
Monovalent OPV-Primary Immunization
An alternative primary immunization is one dose of
each of the three types ofmonovalent OPV given at 6 to
8 week intervals, with a dose of trivalent OPV given 8 to
12 months after the third dose of monovalent OPV to
ensure adequate responses.
OPV-Booster Doses
Entering school: On entering kindergarten or first
grade, all children who have completed the primary
series of OPV should be given a single dose of trivalent
OPV; others should complete the primary series.
There is no indication for routine booster doses of
OPV beyond that given at the time of entering school.
Increased risk: A single dose of trivalent OPV can be
administered to anyone who has completed the full pri-
mary series because of travel or occupational hazard as
described above. The need for such an additional dose
has not been established, but if there is uncertainty
about the adequacy of existing protection, a single dose
of trivalent OPV should be given.





Contraindications
Altered immune states: Infection with live, atten-
uated polioviruses might be potentiated by severe under-
lying diseases, such as leukemia, lymphoma, or general-
ized malignancy, or by lowered resistance, such as from
therapy with steroids, alkylating drugs, antimetabolites,
or radiation; therefore, vaccination of such patients
should be avoided.

IPV-Primary Immunization
All ages: Four parenteral doses should be given, three
at approximately I-month intervals and the fourth 6 to
12 months after the third. This schedule can be inte-
grated with DTP immunization beginning at 6 to 12
weeks of age.
IPV-Booster Doses
A booster dose every 2 to 3 years is generally recom-
mended to ensure adequate levels of antibody. The need
for IPV boosters could be obviated by a full course of
OPV. For individuals at particular risk, as described pre-
viously, at least one dose of trivalent OPV, but prefera-
bly a full primary series, is recommended.

EPIDEMIC CONTROL
For operational purposes in the United States, an
"epidemic" of poliomyelitis is defined as two or more
cases caused by the same poliovirus type and occurring
within a 4-week period in a circumscribed population,
such as that of a city, county, or a metropolitan area. An
epidemic can be controlled with either trivalent OPV, or,
after identification of the responsible type of poliovirus,
homotypic monovalent OPV. Within the epidemic area,
all persons over 6 weeks of age who have not been com-
pletely immunized or whose immunization status is
unknown should promptly receive OPV.


SIMULTANEOUS ADMINISTRATION OF
LIVE VIRUS VACCINES
There are obvious practical advantages to adminis-
tering two or more live virus vaccines simultaneously.
Data from specific investigations are not yet sufficient to
develop comprehensive recommendations on simul-


taneous use, but a summary of current experience, atti-
tudes, and practices provides useful guidance.
It has been generally recommended that live virus vac-
cines be given at least 1 month apart whenever possible
- the rationale for this being that more frequent and
severe adverse reactions as well as diminished antibody
responses otherwise might result. Field observations indi-
cate, however, that with simultaneous administration of
certain live virus vaccines, results of this type have been
minimal or absent. (For example, the third dose of triva-
lent oral poliovirus vaccine, which is recommended
during the second year of life, is commonly given at the
same time as smallpox vaccination without evident dis-
advantage.)
If the theoretically desirable 1-month interval is not
feasible, as with the threat of concurrent exposures or
disruption of immunization programs, the vaccines
should preferably be given on the same day at dif-
ferent sites for parenteral products. An interval of about
2 days to 2 weeks should be avoided because inter-
ference between the vaccine viruses is most likely then.

Published: Supplement to the Poliomyelitis Surveillance Unit
Report No. 285, 1964; revised, MMWR, Vol. 16, No. 33, 1967.

SELECTED BIBLIOGRAPHY
Henderson, D.A., et a.: Paralytic Disease Associated with
Oral Polio Vaccines. JAMA, 190:41-48, 1964.
Hopkins, C.C., et al: Surveillance of Paralytic Poliomyelitis in
the United States. JAMA, in press.
Horstmann, D.M.: Enterovirus Infections of the Central Ner-
vous System. The Present and Future of Poliomyelitis, Med.
Clin. N. Amer., 51:681-692, 1967.
National Communicable Disease Center: Annual Poliomyelitis
Summary 1967. June 30, 1968.
National Communicable Disease Center: Annual Poliomyelitis
Summary 1968. June 1, 1969.
Report of Special Advisory Committee on Oral Poliomyelitis
Vaccines to the Surgeon General of the Public Health Service:
Oral Poliomyelitis Vaccines. JAMA, 190:49-51, 1964.
Sabin, A.B.: Commentary on Report on Oral Poliomyelitis
Vaccines. JAMA. 190:52-55, 1964.
Wehrle, P.F.: Immunization Against Poliomyelitis. Arch.
Environ. Health. 15:485-490, 1967.
World Health Organization, VIR/69.5: Report of the WHO
Consultation on Poliomyelitis with Special Reference to Type 3
Poliovirus.





RABIES PROPHYLAXIS


INTRODUCTION
Although cases of rabies in humans are rare in the
United States, thousands of persons receive rabies pro-
phylaxis each year. The following approach to pre-
vention is based on a contemporary interpretation of
both the risk of infection and the efficacy of treatment
and incorporates the basic concepts of the WHO Expert
Committee on Rabies.
The problem of whether or not to immunize those
bitten or scratched by animals suspected of being rabid
is a perplexing one for physicians. All available methods
of systemic treatment are complicated by numerous
instances of adverse reactions, a few of which have re-
sulted in death or permanent disability. Furthermore,
the decision must be made immediately, because the
longer treatment is postponed, the less likely it is to be
effective.
Accepted evidence of the efficacy of active and of
passive immunization after exposure was derived largely
from experimental studies in animals. Because rabies has
on occasion developed in humans who had received anti-
rabies prophylaxis, its value has been questioned. Evi-
dence from laboratory and field experience in many
areas of the world, however, indicates that post-exposure
prophylaxis is usually effective when appropriately used.

Rabies in the United States
Rabies in humans has decreased from an average of
22 cases per year in 1946-1950, to only one or two cases
per year since 1963. Rabies in domestic animals has
diminished similarly. In 1946, for example, there were
more than 8,000 cases of rabies in dogs, compared with
296 in 1968. Thus, the likelihood of humans' being
exposed to rabies by domestic animals has decreased
greatly, although bites by dogs and cats continue to be
responsible for the overwhelming majority of antirabies
treatments.
In contrast, the disease in wildlife-especially
skunks, foxes, and bats has become increasingly prom-
inent in recent years, accounting for more than 70 per-
cent of all reported cases of animal rabies in 1968. Wild
animals constitute the most important source of infec-
tion for man and domestic animals in the United States
today. In 1968, only three States reported no wildlife
rabies.

Antirabies Treatment in the United States
More than 30,000 persons receive post-exposure anti-
rabies treatment each year. However, there is no in-
formation on the number of persons actually exposed to
rabid animals.
In the United States, nervous tissue origin rabies vac-
cine of the Semple type (NTV) was used almost ex-
clusively until 1957, when duck embryo origin vaccine
(DEV) was licensed. More than 90 percent of those who
received rabies prophylaxis in the United States in 1968
were given DEV.


RABIES VACCINES
Duck Embryo Vaccine (DEV)
Prepared from embryonated duck eggs infected with
a fixed virus and inactivated with beta-propiolactone.
Nervous Tissue Vaccine (NTV)
Prepared from rabbit brain infected with a fixed virus
and inactivated with phenol (Semple type) or inactivated
with ultraviolet irradiation.
Antigenicity of Vaccines
The antigenicity of NTV is often higher than that of
DEV when tested in experimental animals. However, all
lots of both vaccines must pass minimum potency tests
established by the Division of Biologics Standards,
National Institutes of Health. There is evidence that the
serum antibody response in humans is detectable sooner
with DEV, but the eventual level of response is fre-
quently higher with NTV.
Effectiveness of Vaccines in Humans
In the United States, comparative effectiveness of
vaccines can be judged only by reported failures. During
the years 1957 through 1968 when both vaccines were
available, there were six rabies deaths among the
125,000 NTV-treated persons (1:20,800) and eight
among the 225,000 treated with DEV (1:28,100).
Reactions
Erythema, pruritis, pain, and tenderness at the site of
inoculation are common with both DEV and NTV.
Systemic responses including low-grade fever, or rarely
shock, may occasionally occur late in the course of
therapy with either vaccine, usually after five to eight
doses. In rare instances, serious reactions have occurred
after the first dose of DEV or NTV, particularly in per-
sons previously sensitized with vaccines containing avian
or rabbit brain tissue.
As described previously, neuroparalytic reactions
occur rarely with DEV. They much more frequently fol-
low NTV, especially after repeated courses of treatment
with this preparation.
Choice of Vaccine
Treatment-failure rates for the two vaccines are not
significantly different; therefore, the lower incidence of
central nervous system reaction with DEV makes it
preferable to NTV.

RATIONALE OF TREATMENT
EVERY EXPOSURE TO POSSIBLE RABIES IN-
FECTION MUST BE INDIVIDUALLY EVALUATED.
In the United States, the following factors should be
considered before specific antirabies treatment is
initiated:
Species of Biting Animal
Carnivorous animals (especially skunks, foxes,
coyotes, raccoons, dogs, and cats) and bats are more
likely to be infective than other animals. Bites of





rodents, including squirrels, chipmunks, rats, and mice,
seldom, if eier, call for specific rabies prophylaxis.
Circumstances of Biting Incident
An UNPROVOKED attack is more likely to mean
that the animal is rabid. (Bites during attempts to feed
or handle an apparently healthy animal should generally
be regarded as PROVOKED.)
Extent and Location of Bite Wound
The likelihood that rabies will result from a bite
varies with its extent and location. For convenience in
approaching management, two categories of exposure
are widely accepted:
Severe: Multiple or deep puncture wounds, or any
bites on the head, face, neck, hands, or fingers.
Mild: Scratches, lacerations, or single bites on areas of
the body other than the head, face, neck, hands, or
fingers. Open wounds, such as abrasions, suspected of
being contaminated with saliva also belong in this cate-
gory.
Vaccination Status of Biting Animal
An adult animal immunized properly with one or
more doses of rabies vaccine has only a minimal chance
of developing rabies and transmitting the virus.
Presence of Rabies in Region
If adequate laboratory and field records indicate that
there is no rabies infection in a domestic species within a
given region, local health officials may be justified in
taking this into consideration in making recommenda-
tions on antirabies treatment following a bite by that
species.

MANAGEMENT OF BITING ANIMALS
A dog or cat that bites a person should be captured,
confined, and observed by a veterinarian for at least 5
days, preferably 7 to 10. Any illness in the animal
should be reported immediately to the local health de-
partment. If the animal dies, the head should be re-
moved and shipped under refrigeration to a qualified
laboratory for examination. Clinical signs of rabies in
wild animals cannot be interpreted reliably; therefore,
any wild animal that bites or scratches a person should
be killed at once (without unnecessary damage to the
head) and the brain examined for evidence of rabies.

LOCAL TREATMENT OF WOUNDS
IMMEDIATE and thorough local treatment of all bite
wounds and scratches is perhaps the most effective
means of preventing rabies. Experimentally, the inci-
dence of rabies in animals can be markedly reduced by
local therapy alone.
First-Aid Treatment to be Carried out
Immediately
Copious flushing with water, soap and water, or
detergent and water.


Treatment by or Under Direction of Physician
1. Thorough flushing and cleansing into the wound
with soap solution. Quaternary ammonium compounds
may also be used.*
2. If antirabies serum is indicated, (See Passive
Immunization), some of the total dose should be thor-
oughly infiltrated around the wound. As in all instances
when horse serum is to be used, a careful history should
be taken and prior tests for hypersensitivity performed.
3. Tetanus prophylaxis and measures to control bac-
terial infection, as indicated.

POST-EXPOSURE PROPHYLAXIS
Active Immunization
Primary immunization: At least 14 daily injections of
vaccine in the dose recommended by the manufacturer.
They should be given subcutaneously in the abdomen,
lower back, or lateral aspect of thighs; rotation of sites is
recommended.
For severe exposure, 21 doses of vaccine are recom-
mended. These may be given as 21 daily doses or 14
doses in the first 7 days (either as two separate injections
or a double dose), and then seven daily doses.
Booster doses: Two booster doses, one 10 days and
the other at least 20 days after completion of the pri-
mary course. The two booster doses are particularly im-
portant if antirabies serum was used in the initial
therapy.
Precautions: When rabies vaccine must be given to a
person with a history of hypersensitivity, especially to
avian or rabbit tissues, antihistaminic drugs should be
given. Epinephrine is helpful in reactions of the ana-
phylactoid type. If serious allergic manifestations pre-
clude continuation of prophylaxis with one vaccine, the
other may be used.
When meningeal or neuroparalytic reactions develop,
vaccine treatment should be discontinued altogether.
Corticotrophin or corticosteroids are used for such com-
plications.
Passive Immunization
Hyperimmune serum has proved effective in pre-
venting rabies. Its use in combination with vaccine is
considered the best post-exposure prophylaxis. However,
the only preparation of antirabies serum now available in
the United States is of equine origin. Because horse
serum has induced serum sickness in at least 20 percent
of those who have received it, it should be used only
when indicated.
Hyperimmune serum is recommended for most ex-
posures classified as severe, and for ALL BITES by rabid
animals and UNPROVOKED BITES by wild carnivores


*All traces of soap should be removed before applying
quaternary ammonium compounds because soap neutralizes
their activity.





ANIMAL BITE TREATMENT CHECKLIST
(See text for Details)


FLUSH

WOUND

IMMEDIATELY

(FIRST AID)


CLEANSE
WOUND
THOROUGHLY
UNDER MEDICAL
SUPERVISION


ANTIRABIES
SERUM and/or
VACCINE
AS
INDICATED


TETANUS

PROPHYLAXIS

& ANTIBACTERIAL

WHEN REQUIRED


THE FOLLOWING RECOMMENDATIONS ARE INTENDED ONLY AS A GUIDE. THEY MAY BE MODIFIED
ACCORDING TO KNOWLEDGE OF THE SPECIES OF BITING ANIMAL AND CIRCUMSTANCES SUR-
ROUNDING THE BITING INCIDENT. (See text for details.)


ANIMAL BITE TREATMENT

STATUS AT EXPOSURE
SPECIES
TIME OF ATTACK NO LESION MILD* SEVERE*

healthy none none 1 S1
DOG signs suggestive of rabies none V 2 S+V 2
CAT escaped or unknown none V S+V
rabid none S+-V S+V

SKUNK
FOX
RACCOON REGARD AS RABID IN
COYOTE unprovoked attack none S+V SV
BAT

OTHER consider individually-see Rationale of Treatment in text

Code: = See definitions in text.
V = Rabies Vaccine.
S = Antirabies Serum.
1 = Begin vaccine at first sign of rabies in biting dog or cat during holding period (preferably 7 -10 days).
2 = Discontinue vaccine if biting dog or cat is healthy 5 days after exposure, or if acceptable laboratory negativity
has been demonstrated in animal killed at time of attack. If observed animal dies after 5 days and brain is
positive, resume treatment.





and bats. When indicated, antirabies serum should be
used regardless of the interval between exposure and
treatment.
The dose recommended is 1,000 units (one vial) per
40 pounds of body weight. A portion of the antiserum
should be used to infiltrate the wound, and the rest
administered intramuscularly. As previously noted, a
careful history must be obtained and appropriate tests
for hypersensitivity performed.*

PRE-EXPOSURE PROPHYLAXIS
The relatively low frequency of reactions to DEV has
made it more practical to offer pre-exposure immuniza-
tion to persons in high-risk groups: veterinarians, animal
handlers, certain laboratory workers, and individuals,
especially children, living in areas of the world where
rabies is a constant threat. Others whose vocational or
avocational pursuits result in frequent contact with dogs,
cats, foxes, skunks, or bats should also be considered for
pre-exposure prophylaxis.
Two 1.0 ml injections of DEV given subcutaneously
in the deltoid area 1 month apart should be followed by
a third dose 6 to 7 months after the second dose. This
series of three injections can be expected to have pro-
duced neutralizing antibody in 80 to 90 percent ofvac-
cinees by 1 month after the third dose.
For more rapid immunization, three 1.0 ml injections
ol DEV should be given at weekly intervals with a fourth
dose 3 months later. This schedule elicits an antibody
response in about 80 percent of the vaccinees.
All who receive the pre-exposure vaccination should
have their serum tested for neutralizing antibody 3 to 4
weeks after the last injection. Tests for rabies antibody
can be arranged with or through State health department
laboratories. If no antibody is detected, booster doses
should be given until a response is demonstrated. Persons
with continuing exposure should receive 1.0 ml boosters
every 2 to 3 years.
*A guide for use of animal serum is included in the recommenda-
tion for tetanus prophylaxis in wound management prepared by
the PHS Advisory Committee on Immunization Practices.


When an immunized individual with previously
demonstrated antibody is exposed to rabies, it is sug-
gested that for a mild exposure, one booster dose of
vaccine be given, and for a severe exposure, five daily
doses of vaccine plus a booster dose 20 days later. If it is
not known whether an exposed person had antibody,
the complete post-exposure antirabies treatment should
be given.

ACCIDENTAL INOCULATION WITH
LIVE RABIES VIRUS VACCINE
Persons inadvertently inoculated with attenuated
rabies vaccines for use in animals, such as the Flury
strain vaccine, are not considered at risk, and antirabies
prophylaxis is not indicated.

Published MMWR: Vol. 16, No. 19, 1967.



SELECTED BIBLIOGRAPHY
Farrar, W.E., Jr., Warner, A.R., Jr., and Vivona, S.: PFe-
exposure Immunization Against Rabies Using Duck Embryo
Vaccine. Milit. Med, 129:960-965, 1964.
Greenberg, M., and Childress, J.: Vaccination Against Rabies
with Duck-Embryo and Semple Vaccines. JAMA, 173:333-337,
1960.
Habel, K.: Rabies Antiserum Interference with Antigenicty
of Vaccine in Mice. Bull WHO, 17:933-936, 1957.
Johnson, H.N.: Rabies Virus. In: Horfall and Tamm, VbI
and Rickettsial Infections of Man. 4th Edition, JB. Lippincott,
Philadelphia, 1965, 814-840.
National Communicable Disease Center: NCDC Zoonoses Sur-
veillance Annual Rabies Reports, 1963-1968.
Peck, F.B., Jr., Powell, H.M., and Culbertson, C.G.: A New
Antirabies Vaccine for Human Use. J. Lab. Clin. Med.
45:679-683, 1955.
National Communicable Disease Center: Recommendation of
the Public Health Service Advisory Committee on Immunization
Practices: Diphtheria, Tetanus, and Pertussis Vaccine Tetanus
Prophylaxis in Wound Management. Morbidity and Mortality
Weekly Report, 15:416-418, December 3, 1966.
Technical Report Series No. 321, WHO Expert Committee on
Rabies, Fifth Report, 1966.
Tierkel, E.S., and Sikes, R.K.: Preexposure Prophylaxis
Against Rabies, JAMA, 201:911-914, 1967.






RUBELLA VIRUS VACCINE PRELICENSING STATEMENT


INTRODUCTION
The live, attenuated rubella virus vaccine* soon to
become available appears to be a highly effective im-
munizing agent and the first suitable method of con-
trolling rubella.
Rubella is generally a mild illness, but if the infection
is acquired by a woman in the early months of preg-
nancy, it poses a direct hazard to the fetus. Preventing
infection of the fetus is the principal objective of rubella
control. This can best be achieved by eliminating the
transmission of virus among children, who are the major
source of infection for susceptible pregnant women. Fur-
thermore, the live, attenuated rubella virus vaccine is
safe and protective for children, but not for pregnant
women because of an undetermined risk of the vaccine
virus for the fetus.
Rubella
Rubella is one of the common childhood exanthems.
Most cases occur in school-age children particularly
during the winter and spring. By early adulthood,
approximately 80 to 90 percent of individuals in the
United States have serological evidence of immunity.
Rubella is clinically variable, and its common fea-
tures, such as post-auricular and sub-occipital
lymphadenopathy and transient erythematous rash, are
often overlooked or misdiagnosed. A mild febrile illness
may not be recognizable as rubella, and moreover, sub-
clinical infection occurs, which further decreases the re-
liability of clinical history.
Complications of rubella are rare in children, but in
adults, particularly women, the illness is commonly
accompanied by transient polyarthritis. Far more impor-
tant is the frequent occurrence of fetal abnormalities
when a woman acquires rubella in the first trimester of
pregnancy.
Rubella Immunity
Immunity following rubella appears to be long
lasting, even after mild illness or clinically inapparent
infection. The only reliable evidence of immunity is a
positive serological test. However, because of the varia-
tion among reagents and technical procedures, results of
serological tests should be accepted only from labora-
tories of recognized competency that regularly perform
these tests.
At the present time, the hemagglutination-inhibition
(HI) antibody determination is particularly useful for
evaluating immunity.. It is a rapid and sensitive pro-
cedure. The complement fixation (CF) and other sero-
logical tests are less useful.



tRubella vaccine was licensed on June 9, 1969, for distribution
in the U.S.A. Revision of the ACIP recommendation awaits
accumulation of data based on experience.
*Official name: Rubella Virus Vaccine, Live.


LIVE RUBELLA VIRUS VACCINE
Live rubella virus vaccine is prepared in cell culture of
avian or mammalian tissues. It is administered as a single
subcutaneous injection. Although vaccinees shed virus
from the pharynx at times for 2 or more weeks after
vaccination, there is no clear evidence of communi-
cability. Approximately 95 percent of susceptible vac-
cinees develop antibodies, but titers are lower than those
observed following natural rubella infection. Recent
investigations have shown that vaccination affords pro-
tection against illness following either natural exposure
or artificial challenge.
Antibody levels have declined very little during the
3-year period of observation of children who were
among the first to be immunized with rubella vaccine.
Long-term protection is likely, but its exact duration can
be established only by continued observation.
More than 30,000 susceptible children have received
live rubella virus vaccine in field investigations, with
almost no untoward reactions. Only rarely has transient
arthralgia or evanescent rash been reported in children.
Many susceptible women have had lymphadenopathy,
arthralgia, and transient arthritis beginning 2 to 4 weeks
after vaccination; however, fever, rash, and other fea-
tures of naturally acquired rubella have occurred less
commonly. Not enough susceptible men have been vac-
cinated to show whether they experience comparable
reactions as frequently as women.

VACCINE USAGE
General Recommendations
Live rubella virus vaccine is recommended for boys
and girls between the age of I year and puberty. Vaccine
should not be administered to infants less than 1 year
old because of possible interference from persisting
maternal rubella antibody.
Children in kindergarten and the early grades of
elementary school deserve initial priority for vaccination
because they are commonly the major source of virus
dissemination in the community. A history of rubella
illness is usually not reliable enough to exclude children
from immunization.
Vaccination of adolescent or adult males is of much
lower priority because so few are susceptible. However,
the vaccine may be useful in preventing or controlling
outbreaks of rubella in circumscribed population groups.
Pregnant women should not be given live rubella virus
vaccine. It is not known to what extent infection of the
fetus with attenuated virus might take place following
vaccination, or whether damage to the fetus could result.
Therefore, routine immunization of adolescent girls and
adult women should not be undertaken because of the
danger of inadvertently administering vaccine before
pregnancy becomes evident.
Women of childbearing age may be considered for
vaccination only when the possibility of pregnancy in





the following 2 months is essentially nil; each case must
be considered individually. This cautious approach to
vaccinating postpubertal females is indicated for two
reasons: First. because of the theoretical risk of vaccina-
tion in pregnancy; and second, because significant con-
genital anomalies occur regularly in approximately 3 per-
cent of all births, and their fortuitous appearance after
vaccine had been given during pregnancy could lead to
serious misinterpretation.
If vaccination of a woman of childbearing age is con-
templated, the following steps are indicated:
Optimally, the woman should be tested by the HI test
for susceptibility to rubella (See Rubella Immunity).
If immune, she should be assured that vaccination is
unnecessary.
If susceptible, she may be vaccinated only if she
understands that it is imperative for her to avoid be-
coming pregnant for the following 2 months. (To ensure
this, a medically acceptable method for pregnancy pre-
vention should be followed. This precaution also applies
to women in the immediate postpartum period.) Addi-
tionally, she should be informed of the frequent occur-
rence of self-limited arthralgia and possible arthritis
beginning 2 to 4 weeks after vaccination.

Use of Vaccine Following Exposure
There is no evidence that live rubella virus vaccine
given after exposure will prevent illness. There is, how-
ever, no contraindication to vaccinating children already
exposed to natural rubella. For women exposed to ru-
bella, the concepts listed previously apply.
Precautions and Contraindications
Pregnancy: Live rubella virus vaccine is contra-
indicated. (See General Recommendations)
Altered immune states: Attenuated rubella virus
infection might be potentiated by severe underlying dis-
eases, such as leukemia, lymphoma, or generalized malig-
nancy, and when resistance has been lowered by therapy
with steroids, alkylating drugs, antimetabolites, or
radiation. Vaccination of such patients should be
avoided.
Severe febrile illnesses: Vaccination should be post-
poned until the patient has recovered.
Hypersensitivity to vaccine components: Rubella
vaccine is produced in cell culture. Care should be exer-


cised in administering vaccine to persons with known
hypersensitivity to the species from which the cells were
derived (indicated in the labeling). The vaccine contains
a small amount of neomycin and should not be given to
individuals known to be sensitive to this antibiotic.
Simultaneous Administration of Live Rubella
Virus Vaccine and Other Live Virus Vaccines
Simultaneous administration of live rubella virus vac-
cine and other live virus vaccines should be deferred
until results of controlled clinical investigate ions are avail-
able. Until then,.it is recommended that rubella vaccina-
tion be separated by at least 1 month from adminis-
tration of other live virus vaccines.

SURVEILLANCE
Careful surveillance of rubella infection is particularly
important with an effective vaccine in use. Emphasis
should be placed upon improved diagnosis and reporting
of rubella, of the congenital rubella syndrome, and of
complications of the disease. Competent laboratory in-
vestigation of all infants with birth defects suspected of
being due to rubella is essential. It will likewise be im-
portant to observe patterns of vaccine use and determine
their effectiveness.

Published MMWR: Vol. 18, No. 15, 1969.


SELECTED BIBLIOGRAPHY
Cooper, L.Z., et al.: Transient Arthritis After Rubella Vacci-
nation. Am. J. Dis. Child., 118:218-225, 1969.
Cooper, L.Z., and Krugman, S.: The Rubella Problem. Disease
A Month, Year Book Medical Publishers, Chicago, February
1969.
Dudgeon, J.A., et a.: Clinical and Laboratory Studies with
Rubella Vaccines in Adults. Brit. Med. J., 1:271-276, 1969.
Grayston, J.T., et al.: Field Trial of Live Attenuated Rubella
Virus Vaccine During an Epidemic in Taiwan. JAMA,
207:1107-1109, 1969.
Meyer, H.M., Jr., Parkman, P.D., and Hopps, H.E.: The Con-
trol of Rubella. Pediatrics, 44:5-23, 1969.
Parkman, P.D., and Meyer, H.M., Jr.: Prospects for a Rubella
Virus Vaccine. Progr. Med. Virol., 11:80-106, 1969.
Weibel, R.E., et al.: Live Attenuated Rubella Virus Vaccines
Prepared in Duck Embryo Cell Culture. JAMA, 205:82-86,
1968.
Witte, J.J., et al.: The Epidemiology of Rubella. Am. J. Di.
Child., 118:107-111, 1969.






SMALLPOX VACCINE


INTRODUCTION
In the United States, protection of the population
against smallpox through routine vaccination of infants
and revaccination of older children and adults represents
the principal mechanism of defense against the in-
digenous spread of the disease once introduced. This
approach to community protection, as with all practices
in preventive medicine, demands continuing reassess-
ment of the potential risk of the disease in comparison
with the efficacy and risk associated with preventive pro-
cedures.

THE RISK OF INTRODUCING SMALLPOX
While the current risk of introduction and subsequent
transmission of smallpox in the United States is difficult
to define, not one confirmed case of smallpox has
occurred since 1949 despite increased travel by United
States citizens and other nationals to and from smallpox
endemic areas. The reservoirs of endemic smallpox in
Asia, Africa, and South America are shrinking, and in
these areas many of the smallpox cases are now oc-
curring away from urban centers. Furthermore, recent
evidence suggests that the communicability of smallpox
through casual contact, as on common carriers, is quite
small.
It must be recognized, however, that quarantine
measures at ports of entry offer at best only partial pro-
tection against the introduction of smallpox. In almost
half of the 39 instances since 1950, when smallpox was
introduced into Western Europe, nationals of the coun-
try involved were responsible. Should smallpox be intro-
duced into the United States, it is similarly quite possi-
ble that a United States citizen returning from abroad
would introduce the disease.
Smallpox, particularly variola major, is a highly viru-
lent disease even with excellent medical care. The mor-
tality rate for unvaccinated persons was 40 percent in
Sweden and England in the outbreaks of 1962-63.
Because few physicians in practice today have seen
clinical smallpox, it is not surprising that in several re-
cent European outbreaks the disease went unrecognized
until the third generation of cases, or even later. During
a 1966 outbreak of variola minor in England, the diag-
nosis of smallpox was not made until the fourth cycle of
transmission, when 23 cases had already occurred -
more than 10 weeks after the first identifiable case.
Should the disease be introduced into the United States,
a similar course of events could occur.

SMALLPOX VACCINE
Effectiveness
The efficacy of smallpox vaccine has never been pre-
cisely measured in controlled trials. It is, however,
generally agreed that vaccination with fully potent vac-
cine confers a high level of protection for at least 3


years. Vaccination provides substantial but waning
immunity for 10 years or more, but appears to protect
against a fatal outcome of disease for an even longer
period, perhaps for decades.
Complications and Risks
It is recognized that with smallpox vaccination, as
with other medical procedures, there is a definite,
measurable risk of untoward reaction and rarely death.
Comprehensive national surveys to determine the fre-
quency of smallpox vaccine complications in the United
States were made in 1963 and 1968. In 1968, among
more than 5.6 million primary vaccinees and nearly 8.6
million revaccinees and their contacts, 16 cases of en-
cephalitis, 11 cases of vaccinia necrosum, and 126 cases
of eczema vaccinatum occurred in association with vac-
cination. Nine persons died. A substantial number of less
serious complications, some of which necessitated hos-
pitalization, were also recorded. All deaths and virtually
all complications occurred in primary vaccinees.
Survey data show clearly that more than half of the
complications from smallpox vaccination would not
have occurred if acknowledged contraindications to vac-
cination had been closely observed. Furthermore, com-
plication rates appear to be at least twice as high for
children under one year of age as for slightly older
children. Also primary vaccination of adolescents and
adults appears to carry a higher risk of adverse reactions
than vaccination of younger children.
Thus, with no introductions of smallpox into the
United States in 20 years and with a small but definite
risk of adverse reactions to smallpox vaccine, the justifi-
cation for its routine use must be examined regularly. In
weighing the relative risks, the consequences of having to
vaccinate persons for the first time as adults needing
protection against smallpox when entering military ser-
vice, traveling overseas, working in medical or allied
health professions, or being exposed in local outbreaks
must be considered.


OTHER PROPHYLACTIC AGENTS
In recent years, Vaccinia Immune Globulin (VIG) and
certain antiviral compounds have been found to be effec-
tive in conferring protection against smallpox when ad-
ministered shortly after exposure to the disease. At
present, none appears to be a satisfactory alternative to
vaccination, and more importantly, none confers more
than temporary protection. Thus, unless the first intro-
duced smallpox case could be promptly and correctly
diagnosed and all contacts quickly identified and
treated, interruption of subsequent transmission of the
disease by using these materials would be virtually im-
possible.
It is of added practical importance that antiviral com-
pounds have considerable gastrointestinal toxicity and
the supply of VIG is limited. Therefore, none of these





prophllactic agents is suitable for mass use as a substi-
tute for vaccination at the time of an actual or potential
outbreak.

CONCLUSIONS AND RATIONALE FOR
VACCINATION
In recent years, international travel has increased
dramatically, and while the reservoir of endemic small-
pox has decreased, the potential for introduction of
smallpox into the United States continues.
The 1966 World Health Assembly agreed to embark
on an intensive 10-year smallpox eradication program.
Vaccination campaigns in many of the developing coun-
tries have been very effective, so there is every reason to
anticipate success with this program. Eradication of
endemic smallpox represents the most direct attack on
the problem and the surest means of protecting the
United States.
Until eradication is achieved or, at least, nears realiza-
tion, vaccination, although not wholly without risk, now
represents the only suitable approach for community
protection in the United States. Comparing the risks of
smallpox spread in the United States and the risk of
primary vaccination complications for adults with the
risks of complications of vaccination of children, it
seems prudent for the present to continue the practice
of regular smallpox vaccination in early childhood and
subsequent periodic revaccination.

VACCINE USAGE
The following smallpox vaccination practices are
recommended for the United States:*
Primary Vaccination
Age: Within the second year of life (i.e., between first
and second birthdays) or at any age under conditions of
exposure or foreign travel.
Revaccination
School entrance: On entering kindergarten or ele-
mentary school.
Potential exposure: At 3-year intervals for persons
who conceivably might be exposed in endemic or poten-
tially endemic areas by virtue of international travel or
likely to be exposed by newly introduced infection into
the United States, in particular: hospital personnel,
including physicians, nurses, attendants, and laboratory
and laundry workers; other medical, public'health, and
allied professions; and morticians and other mortuary
workers.
Routine vaccination: At approximately 10-year inter-
vals for all others.

*All persons, regardless of age, entering the United States from
non-exempt areas are required to be vaccinated or revaccinated
within three years unless vaccination is medically contra-
indicated. The International Sanitary Regulations provide that
"if a vaccinator is of the opinion that vaccination is contra-
indicated on medical grounds, he should provide the persons
with written reasons underlying that opinion, which health
authorities may take into account."


Site of Vaccination
The skin over the insertion of the deltoid muscle or
the posterior aspect of the arm over the triceps muscle.
Methods of Vaccination
Multiple pressure: A small drop of vaccine is placed
on the dry, cleansed skin, and a series of pressures is
made in an area about 1/8-inch in diameter with the side
of a sharp, single pointed, sterile needle held tangentially
to the skin. The pressures are made with the side of the
needle. For primary vaccination, 10 pressures are ade-
quate; for revaccination, 30 pressures should be made.
(Proportionately fewer pressures are required with a
"bifurcated" needle.) The remaining vaccine should be
wiped off with dry, sterile gauze. Preferably, no dressing
should be applied to the site.
Jet injection: The recommended dose of vaccine
specifically manufactured for this purpose is injected
intradermally with a jet injection apparatus. Excess vac-
cine should be wiped off the arm with dry, sterile gauze.
Preferably, no dressing should be applied to the site.
Other techniques: Vaccination may be performed
with other devices and techniques shown to be equally
effective in assuring takes.
Interpretation of Responsest
Time of inspection: The vaccination site should be
inspected 6 to 8 days'after vaccination. The response at
this time should be interpreted.
Primary vaccination: A "successful" primary vac-
cination shows a typical Jennerian vesicle. If none is
observed, vaccination procedures should be checked and
vaccination repeated with vaccine from another lot unlil
a successful result is obtained.
Revaccination: Two types of revaccination response
are defined by the WHO Expert Committee on Small-
pox, eliminating use of older terms such as "accelerated"
and "immune." They are:
Major reaction A vesicular or pustular lesion or an
area of definite palpable induration or congestion sur-
rounding a central lesion which may be a crust or an
ulcer. This reaction indicates that virus multiplication
has taken place and that the revaccination is successful.
Equivocal reaction All reactions other than "major
reactions." They may be the consequences of immunity
adequate to suppress virus multiplication or may repre-
sent only allergic reactions to an inactive vaccine. If an
equivocal reaction is observed, revaccination procedures
should be checked and revaccination repeated with vac-
cine from another lot.
Types of Smallpox Vaccine
Smallpox vaccine is available both in the glycerinated
and the lyophilized form. Both forms, when properly
preserved and administered, afford excellent protection.
The glycerinated form requires constant refrigeration in
all stages of transport and storage at temperatures

t For purposes of validating an International Certificate of Vac-
cination, primary vaccination must be inspected. Although
desirable, inspection of revaccination is not mandatory.





recommended by the manufacturer. Comparatively
minor storage difficulties may reduce its potency enough
to decrease efficacy in vaccination and particularly in
revaccination. Even in excellent medical facilities, the
glycerinated vaccine is often stored under improper con-
ditions. Use of the much more stable lyophilized vaccine
would ensure more consistently effective vaccination.
Due care must be exercised to provide proper handling
of the lyophilized vaccine after reconstitution as di-
rected by the manufacturer
Contraindications
Skin disorders: Eczema and other forms of chronic
dermatitis in the individual to be vaccinated or in a
household contact. If vaccination is required for an
individual with dermatitis, because of potential exposure
in an endemic area, VIG should be administered to the
vaccinee. If there is real need to vaccinate an individual
who may thus create a hazard for a household contact
with dermatitis. consideration should be given to
separating the vaccinee from his contact until a crust has
developed.
Pregnancy- Vaccinia virus rarely may cross the
placental barrier at any stage of pregnancy and infect the
fetus. Virtually all cases of fetal vaccinia have followed
primary vaccination. If vaccination is indicated because
of potential exposure in an endemic area, Vaccinia
Immune Globulin should generally be given simul-
taneously with the vaccine, particularly in cases of pri-
mary vaccination. VIG will not prevent a take.
Altered immune states: Leukemia, lymphoma, and
other reticuloendothelial malignancies; d>sgammaglobu-
linemia; therapy with immunosuppressive drugs, such as
steroids and antimetabolites; or radiation. If exposure
should by chance occur, or if vaccination is absolutely
essential, persons with any of the above conditions
should be given Vaccinia Immune Globulin.

VACCINIA IMMUNE GLOBULIN
Prophylactic Use
Dose: 0.3 ml kg by the intramuscular route.


Therapeutic Use
Dose and indications. 0.6 ml kg by the intramuscular
route. For eczema vaccinatum, vaccinia (progressive vac-
cinia), or autoinoculation vaccinia of the eye, VIG may
be effective. For severe cases of generalized vaccinia,
VIG may be helpful in treatment, but such cases almost
invariably have a favorable outcome anyway. For mild
cases of generalized vaccinia or autoinoculation not
involving the eye, VIG is general. considered unneces-
sary. For postvaccinial encephalitis, VIG is of no proved
value.

THIOSEMICARBAZONES
Certain of the thiosemicarbazone derivatives re-
portedly have a short-term protective effect against
smallpox and possibly a therapeutic effect on individuals
with severe vaccinial complications These are still ex-
perimental drugs and are not available for general use.

Published MSWR: Vol. 15, No. 47, 1966.





S E L E CT ED BIBLIOGRAPHY
Bauer, D.J., Kempe, C.H., and Downie, A.W.: Prophylactic
Treatment of Smallpox Contacts with N-Methylisatin B-Thiose-
micarbazone iCompound 33T57, Marboran). Lancet, 2:494-496,
1963.
International Sanitaur Regulations, Article 98 (Footnote 9),
World Health Organization, Geneva, 1966.
Kempe, C.H., et al.: The Use of Vaccinia Hyperimmune
Gamma-Globulin in the Prophylaxis of Smallpox. Bull. WHO,
25:41-48, 1961.
Neff, J.M., et al.: Complications of Smallpox Vaccination. I.
National Survey in the United States. 1963. New Eng. J. Med.
276:125-132, 1967.
Neff, J.M., et al.: Complications of Smallpot Vaccination,
United States, 1963. II. Results Obtained by Four Statewide
Surveys. Pediatrics, 39:916-923, 1967.
Smallpox Surveillance, World Health Organization Weekly
Epidemiological Record, 27:433444, 1969.
Reports of the Scientific Group on Smallpox. WHO Technical
Report Series No. 393, Geneva, 1968.





TYPHOID VACCINE


INTRODUCTION
The incidence of typhoid fever has declined steadily
in the United States in the last half century, and in the
recent years fewer than 400 cases have been reported
annually. The continuing downward trend is due largely
to better sanitation and other control measures; vaccine
is not deemed to have played a significant role.

TYPHOID VACCINES
Although typhoid vaccines have been used for many
decades, only recently has definitive evidence of their
effectiveness been observed in well controlled field
investigations. Several different preparations of typhoid
vaccine have been shown to protect 70 to 90 percent of
recipients, depending in part on the degree of their sub-
sequent exposure.

VACCINE USAGE
Routine typhoid vaccination is no longer recom-
mended for persons in the United States. Selective
immunization is, however, indicated in the following
situations:
1. Intimate exposure to a known typhoid carrier, as
would occur with continued household contact.
2. Community or institutional outbreaks of typhoid
fever.
3. Foreign travel to areas where typhoid fever is
endemic.
Typhoid vaccination should not be interpreted as per-
mitting relaxation in careful selection of foods and water
in areas where typhoid infections are occurring.
Although typhoid vaccine was at one time suggested
for persons going to summer camps and those in areas
where flooding has occurred, there are no data to sup-
port the continuation of these practices.
Primary Immunization
On the basis of the field trials referred to above, the
following dosages of vaccines available in the USA are
recommended:
Adults and children over 10 years old: 0.5 ml sub-
cutaneously on two occasions, separated by 4 or more
weeks.
Children less than 10 years old*: 0.25 ml subcu-
taneously on two occasions, separated by 4 or more
weeks.
In instances where there is not sufficient time for two
doses to be administered at the interval specified, it has
been common practice to give three doses of the same
volumes listed above at weekly intervals recognizing that
this schedule may be less effective. When vaccine is to be

*Since febrile reactions to typhoid vaccine are common, an anti-
pyretic may be indicated.


administered for travel overseas under constraint of
time, a second dose may be administered en route at a
more suitable interval.
Booster Doses
Under conditions of continued or repeated exposure,
a booster dose should be given at least every 3 years.
Even when more than 3 years have elapsed since the
prior immunization, a single booster injection is suf-
ficient.
The following alternative routes and dosages of
booster immunization can be expected to produce com-
parable antibody responses; generally less reaction fol-
lows vaccination by the intradermal route (except when
acetone killed and dried vaccine is used. This vaccine
should not be given intradermally).
Adults and children over 10 years old: 0.5 ml sub-
cutaneously or 0.1 ml intradermally.
Children 6 months to 10 years*: 0.25 ml subcu-
taneously or 0.1 ml intradermally.

PARATYPHOID A AND B VACCINES

The effectiveness of paratyphoid A vaccine has never
been established, and recent field trials have shown that
available paratyphoid B vaccines are not effective, in the
usually small amounts contained in "TAB" vaccines.
Knowing this and recognizing that combining para-
typhoid A and B antigens with typhoid vaccine increases
the risk of vaccine reaction, paratyphoid A and B vac-
cines should not be used.

Published MMWR: Vol. 15, No. 29, 1966.


SELECTED BIBLIOGRAPHY
Ashcroft, M.T., et. al.: A Seven-Year Field Trial of Two
Typhoid Vaccines in Guyana. Lancet, 2:1056-1059, 1967.
Cvjetanovic, B. and Uemura, K.: The Present Status of Field
and Laboratory Studies of Typhoid and Paratyphoid Vaccine.
Bull. WHO, 32:29-36, 1965.
Hejfec, L.B., et. al.: Controlled Field Trials of Paratyphoid B
Vaccine and Evaluation of the Effectiveness of a Single Adminis-
tration of Typhoid Vaccine. Bull. WHO, 38:907-915, 1968.
Mallory, A., Belden, E., and Brachman, P.: The Current
Status of Typhoid Fever in the United States and a Description
of an Outbreak. J. Infect. D., 119:673-676, 1969.
Polish Typhoid Committee: Controlled Field Trials and
Laboratory Studies on the Effectiveness of Typhoid Vaccines in
Poland, 1961-64: Final Report. Bull. WHO, 34:211-222, 1966.
Schroeder, S.: The Interpretation of Serologic Tests for
Typhoid Fever. JAMA, 205:839-840, 1968.
Typhoid Vaccines. Lancet, 2:1075-1076, 1967.
Yugoslav Typhoid Commission: A Controlled Field Trial of
the Effectiveness of Acetone-Dried and Inactivated and Heat-
Phenol-Inactivated Typhoid Vaccines in Yugoslavia. Bull. WHO,
30:623-630, 1964.





TYPHUS VACCINE


INTRODUCTION
The United States has not experienced an outbreak of
louse-borne (epidemic) typhus since 1922. The last re-
ported case, 1950, did not result from an indigenous
source of infection.
Lousebore typhus was widespread in many countries
affected by World War II. Since 1945. reported cases
have declined steadily. Effective insecticides and gener-
ally improved standards of living have permitted many
populations to free themselves of louse infestation. A
human reservoir of latent infections persists in many
parts of the world, and resurgence of the disease might
occur under conditions of war or disaster. Vaccination of
any civilian population in the United States, however,
is unwarranted.

TYPHUS VACCINE
Typhus vaccines of the type available today were first
used widely in World War .I There were no deaths from
typhus among vaccinated persons during the North
African campaign, and incidence of disease in the vac-
cinated was reportedly lower than in the unvaccinated.
In unvaccinated adults, the case-fatair'. ratio is reported
to be 20 percent or higher.
Although no controlled studies of typhus vaccine
have been carried out in human populations, experience
from the field and the laboratory suggests that the inci-
dence and severity of typhus cases is diminished among
the vaccinated, especially if booster doses have been re-
ceived.
Typhus vaccine is prepared from formaldehyde in-
activated Rickettsia prow~:ekii grown in embryonated
eggs. This vaccine provides protection against only louse-
bore (epidemic) typhus; it does not protect against
marine or scrub typhus.

VACCINATION USAGE
Vaccination for International Travel
The rarity of epidemic typhus minimizes the need for
vaccination. Typhus is at present no threat to United
States residents visiting most other countries. This is true
even in places still reporting large numbers of cases if
travel is limited to urban areas with modern hotel
accommodations. It is only in mountainous. highland, or
areas where a cold climate and other local conditions
favor louse infestation that a potential threat exists.
Vaccination may be indicated for travelers to rural or
remote highland areas of Ethiopia. Raanda. Burundi,
Mexico. Ecuador. Bolivia, or Peru, and mountainous
areas of Asia. Even there, however, the risk of typhus for
US. travelers is extremely low. No typhus case in an
American traveler is known to have occurred in recent
years. Vaccination against typhus is not required by any
country as a condition for entry.
Typhus vaccination is suggested only for the follow-
ing special-risk groups:
1. Such persons as scienufic investigators (e.g., an-
thropologists. archaeologists, or geologists), oil-field and


construction workers, missionaries, and some goven-
ment workers who live in or visit areas where the disease
actually occurs and who will be in close contact with the
indigenous population in such areas.
2. Medical personnel. including nurses and atten-
dants, providing care for patients in areas in which louse-
borne (epidemic) t phus occurs.
3. Laboratory personnel working with Rickertsia
prowazekii
Primary Immunization
Two subcutaneous injections of vaccine 4 or more
weeks apart using the dose volume indicated by the
manufacturer for adults or for children.
Booster Doses
A single subcutaneous injection of vaccine at intervals
of 6 to 12 months for as long as opportunity for ex-
posure exists using the dose volume indicated by the
manufacturer for adults or for children. The primary
series need never be repeated for booster doses to be
effective.
Reactions
Pain and tenderness at the injection site should be
expected. A few individuals have reportedly experienced
exaggerated local reactions and fever, presumably a
manifestation of hypersensitivity.
Contraindications
As is the case for al vaccines propagated in eggs,
typhus vaccine should not be administered to anyone
who is hypersensitive to eggs.

Published MMWR: Vol. 17, No. 21, 1968.


SELECTED BIBLIOGRAPHY
Donovick, R., and yckoff R.W.G.: The Comparative Poten-
cies of Several Typhus Vaccines. Public Heath Rep..
60:605-612, 1945.
Ecke, RS., er aL: The Effect of Cox-Type Vaccine on Louse-
Borne Typhus Fever. An Account of 61 Cases of Naturally Oc-
curring Typhus Fever in Patients Who Had Previously Received
One or More Injections of Cox-Type Vaccine Am. Trop.
Mred. 25:447462, 1945.
Gilliam, A.G.: Efficacy of Cox-Type Vaccine in the Preven-
tion of Naturally Acquired Louse-Borne Typhus Fever. Am. .
Hyg.. 44.401410. 1946.
Sadusk, J.F.: Typhus Fever in the United States Army Fol-
lowing Immunzation. Incidence, Severity of Disease. Modifica-
tion of the Cinical Course and Serologic Dutnais. JAMA
133:1192-1199, 1947.
Smadel, J.E. Jackson, E-B.. and Campbell. JM.: Studies on
Epidemic Typhus Vaccine. Arch. Inst Part. Tunis 36:481-499,
1959.
Topping, N.H.: Typhus Fever. A Note on the Severity of the
Disease Among Unvaccinated and Vaccinated Laboratory Per-
sonnel at the National Institutes of Health. Am. J. Trop. Med,
24:5"-62. 1944.
isseman, CL., Jr.: The Present and Future of Immunization
Against the Typhus Feves. In: First International Conference on
Vaccines Against Viral and Rickettsial Diseases of Man. Pan
American Health Organization, Scientific Publication No. 147,
196" 523-527.





YELLOW FEVER VACCINE


INTRODUCTION
At present, cases of yellow fever are reported from
only Africa and South America. Two forms of yellow
fever- urban and jungle-are distinguishable epi-
demiologically. Clinically and etiologically. they are
identical.
Urban yellow fever is an epidemic viral disease of man
transmitted from infected to susceptible persons by a
vector, the Aedes aegypti mosquito. With the elimina-
tion of A. aegypti, urban yellow fever has disappeared
from previously epidemic foci.
Jungle yellow fever is an enzootic viral disease trans-
mitted among non-human hosts by a variety of mosquito
vectors. It is currently observed only in the jungles of
South America and Africa, but in the past it extended
into parts of Central America as well. Human cases occur
by chance. The disease can ostensibly disappear from an
area for years and then reappear. Delineation of areas
affected depends upon accurate diagnosis and prompt
reporting of all cases.
Urban yellow fever can be prevented by eradicating
A. aegypti mosquitoes. Jungle yellow fever can be pre-
vented in humans only by immunization. Because infec-
tion is from a non-human reservoir, prevention of human
cases requires vaccination of all persons at risk.

YELLOW FEVER VACCINE
Yellow fever vaccine is a live, attenuated virus
preparation made from one of two strains of virus: 17D
and Dakar (French neurotropic). The Dakar strain has
been associated with a significant (0.5 percent) incidence
of meningoencephalitic reactions and is not recom-
mended. The 17D strain has caused no significant com-
plications.
Licensed vaccine available in the United States is pre-
pared from the 17D strain, which is grown in chick
embryo inoculated with a fixed passage level seed virus.
The vaccine is freeze-dried supernate of centrifuged
embryo homogenate.
Vaccine should be stored at the temperature recom-
mended by the manufacturer until it is reconstituted by
the addition of sterile physiologic saline. Unused vaccine
should be discarded within approximately 1 hour of re-
constitution.

VACCINE USAGE
General Recommendations
Age: Persons 6 months of age or older traveling or
living in areas where yellow fever infection exists (cur-
rently Africa and South America. (See Vaccination for
International Travel).
Special risk: Laboratory personnel who might be ex-
posed to virulent yellow fever virus.

Vaccination for International Travel
To be acceptable for purposes of international travel,
yellow fever vaccines must be approved by the World
Health Organization and administered at a Yellow Fever


Vaccination Center listed with WHO. Vaccinees should
have an International Certificate of Vaccination filled in,
signed, and validated with the stamp of the.Center where
the vaccination is administered. (Yellow Fever Vaccina-
tion Centers in the United States are designated by the
Foreign Quarantine Program of the Public Health Ser-
vice.*)
Vaccination for international travel may be required
under circumstances other than those included in these
recommendations. A number of countries in Africa and
South America require evidence of vaccination from all
entering travelers; some may waive the requirements for
travelers coming from non-infected areas and staying less
than 2 weeks. These requirements may change, so all
travelers should seek current information from health
departments and travel agencies.
Some countries require an individual, even if only in
transit, to have a valid International Certificate of Vac-
cination if he has been in countries either known or
thought to harbor yellow fever virus. This applies par-
ticularly to travelers to South and Southeast Asia by
way of the Atlantic.
Primary Vaccination
A single subcutaneous injection of0.5 ml of reconsti-
tuted vaccine for both adults and children.
Revaccination
Yellow fever immunity following vaccination with
17D strain virus has been shown to persist for more than
10 years; the International Sanitary Regulations do not
require revaccination more frequently than every 10
years.
Reactions
The few reactions to 17D yellow fever vaccine that
occur are generally mild. Five to 10 percent ofvaccinees
have mild headache, myalgia, low-grade fever, or other
minor symptoms 5 to 10 days after vaccination.
Symptoms cause less than 0.2 percent to curtail regular
activities. Only two cases of encephalitis have been re-
ported in the United States, for more than 34 million
doses of vaccine distributed.
Because yellow fever vaccine is prepared from chick
embryos, it may induce reactions of varying degrees of
severity in individuals hypersensitive to eggs. Experience
in the Armed Forces suggests that allergy severe enough
to preclude vaccination is very uncommon and occurs
only in those who are actually unable to eat eggs.
Precautions and Contraindications
Pregnancy: Although specific information is not avail-
able concerning adverse effects of yellow fever vaccine
on the developing fetus, it is prudent on theoretical
grounds to avoid vaccinating pregnant women.

*For a list of such centers, see Immunization Information for
International Travel, PHS Publication No. 384, available from
the Supt. of Documents, U.S. Government Printing Office,
Washington, D.C. 20402 at 40 cents.





Altered iknmne states: Yellow fever vaccine virus
infection might be potentiated by severe underlying dis-
eases, such as leukemia, lymphoma, or generalized malig-
nancy, and by lowered resistance, such as from therapy
with steroids, alkylating drugs, aniimciabolites. or rad a-
tion; therefore, vaccination of such patients should be
avoided.
Allergy: Documented hypersensitivity to eggs can be
contraindication to vaccination. In making the decision
to vaccinate despite a history of egg allergy, a physician
must weigh three factors: 1) the nature of the history
and of the reported hypersensitivit), 2) the relative risk
of exposure to yellow fever, and 3), in the case of inter-
national travel, the possible inconvenience from dis-
rupted travel plans.
If international quarantine regulations are the only
reason to vaccinate a patient hypersensitive to eggs,
efforts should first be made to obtain a waiver. A
physician's letter which clearly states the contraindica-
tion to vaccination has been acceptable to some govern-
ments. Ideally, it should be written under his letterhead
and bear the authenicating stamp used by health depart-
ments and official immunization centers to validate
International Certificates ofVaccination ) Because this is
not uniformly true, however, it is prudent for the
traveler to obtain specific and authoritative advice from
the country or countries he plans to visit. Their em-
bassies or consulates may be contacted. Subsequent
waiver of requirements should be documented by appro-
priate letters.

SIMULTANEOUS ADMINISTRATION OF
LIVE VIRUS VACCINES
There are obvious practical advantages to adminis-
tering two or more live virus vaccines simultaneouslN.
Data from specific investigations are not yet sufficient to
develop comprehensive recommendations on simul-
taneous use, but a summary of current experience, atti-
tudes, and practices provides useful guidance.
It has been generally recommended that live virus vac-
cines be given at least 1 month apart whenever possible
- the rationale for this being that more frequent and


severe adverse reactions as well as diminished anybody
responses otherwise might result. Field observations nda-
cate, however, that with simultaneous administration of
certain live virus vaccines, results of this type have been
minimal or absent. IFor example, the third dose of triva-
lent oral poliovirus vaccine, which is recommended
during the second year of life, is commonly given at the
same time as smallpox vaccination without evident dis-
advantage.)
If the theoreucall) desirable 1-month interval is not
feasible, as with the threat of concurrent exposures or
disruption of immunization programs, the vaccines
should preferably be given on the same day- at dif-
ferent sites for parenteral products. An interval of about
2 days to 2 weeks should be avoided because inter-
ference between the vaccine viruses is most likely then.

Published MMWR: Vol. 18, No. 21, 1969


SELECTED BIBL IOG RAP HY
Burrus, H.W. and Hareet, M.V.: Yellow Fever Vaccine In-
activation Studies. Public Health Rep., 62:940-956, 1947.
Groot, H. and Ribeiro, RB.: Neutralizin and Hemagglutna-
tion-Inhibition Antibodies to Yello- Feter 1" 'ear Aiftei Vac-
cination with 17D Vaccine. Bull WHO. 27:699-707, 1962.
Harert. M.V., Burruss, K and Donovan, A.: Aqueous-
Base Yellow Fever Vaccine. Public Health Rep., 58:505-512,
1943.
Rosenzweig, E.C., Babione, R.W., and Wisseman, C.L, Jr.:
Immunological Studies with Group B Arthropod-Borne Viruses.
IV. Persistence of Yellow Feier Antibodies Followg Vaccina-
tion with 17D Strain Yellow Fever Vaccine. Amer. J. Trp.
Med. 12:230-235, 1963.
Smith, H.H.,Calderon-Cuerv.. H and Leyva, J.P.: A Conpari-
son of High and Low Subcultures of Yellow Fever Vaccine
(17D) in Human Groups. Amer. J Trop. Med, 21:579-58'.
1941.
Smithburn, G.K., etal.: Yellow Feer Vaccination. WHO
Mon oraph Series No. 30, Geneva, 1956.
Sutr.xe G.K. (ed.): Yellow Ferer. 1st Edtion. New York,
McGraw Hill, 1951.
Visseman, C.L. and Sweet B.H.: Immunological Studies with
Group B Arthropod-Borne Viruses. III. Response of Human Sub-
jects to Revaccination with 17D Strain Yellow Fever Vaccine.
Amer. J. Trop. Med. 11: 570-575, 1962.






APPENDIX


VOLUNTEER CONSULTANTS FOR THE DISTRIBUTION OF VACCINIA IMMUNE GLOBULIN

VIG can be obtained within a few hours from any of the
listed Regional Blood Centers of the American Red Cross
with a consultant's approval.


1. Moses Grossman, M.D.
Professor of Pediatrics
University of California Service
San Francisco General Hospital
San Francisco, California 94110
Office: (415) 648-8200, Ext. 441
Home: (415) 681-0475
2. Paul F. Wehrle, M.D.
Chief Physician, Children's Division
Los Angeles County General Hospital
Los Angeles, California 90033
Office: (213) 225-3115, Ext. 2825
Home: (213) 287-9858
Alternates:
John M. Leedom, M.D.
Office: (213) 225-3115, Ext. 2825
Home: (213) 289-7994
Allen W. Mathies, M.D.
Office: (213) 225-3115, Ext. 3283
Home: (213) 799-7006
3. C. Henry Kempe, M.D.
Professor and Chairman
Department of Pediatrics
University of Colorado School of Medicine
Denver, Colorado 80220
Office: (303) 394-8271
Home: (303) 322-4457
Alternate:
Ann S. Yeager, M.D.
Office: (303) 394-8501
Home: (303) 399-0839
4. Allen S. Chrisman, M.D.
Deputy Medical Director
Blood Program
The American National Red Cross
Washington, D.C. 20006
Office: (202) 737-8300, Ext. 472
Home: (301) 654-8418
Alternate:
Robert H. Parrott, M.D.
Clinical Professor of Pediatrics
Georgetown University School of Medicine
Director, The Children's Hospital of the District of Columbia
Washington, D.C. 20009
Office: (202) 3874220, Ext. 280
Home: (301) 365-0810
5. Andre J. Nahmias, M.D.
Associate Professor of Pediatrics and Preventive Medicine
Emory University School of Medicine
69 Butler Street, S.E.
Atlanta, Georgia 30303
Office: (404) 523-4711, Ext. 226
Home: (404) 634-9955
Alternate:
J. Michael Lane, M.D.
Chief, Domestic Operations
Smallpox Eradication Program
National Communicable Disease Center
Atlanta, Georgia 30333
Office: (404) 633-3311, Ext. 3525
Home: (404) 377-4834


6. Sharon Bintliff, M.D.
Office of the Medical Director
Kauikeolani Children's Hospital
Rehabilitation Center of Hawaii
226 North Kuakini Street, P.O. 3799
Honolulu, Hawaii 96817
Office: (808) 531-3511, Ext. 164
Home (808) 949-4245
Alternate:
Harry Shirkey, M.D.
Office: (808) 531-3511, Ext. 153
Home: (808) 373-4981
7. Irving Schulman, M.D.
Professor and Head
Department of Pediatrics
University of Illinois College of Medicine
Chicago, Illinois 60612
Office: (312) 633-6711
Home: (312) 835-0160
8. Abram S. Benenson, M.D.
Professor and Chairman
Department of Community Medicine
University of Kentucky College of Medicine
Lexington, Kentucky 40506
Office: (606) 233-5000, Ext. 5421
Home: (606) 266-0334
9. Margaret H.D. Smith, M.D.
Professor of Pediatrics and Epidemiology
Tulane University School of Medicine
New Orleans, Louisiana 70112
Office: (504) 523-3381, Ext. 254 or 531
Home: (504) 861-4304
Alternate:
Mark A. Belsey, M.D.
Office: (504) 523-3381, Ext. 254 or 531
Home: (504) 891-6550
10. John M. Neff, M.D.
Assistant Professor of Pediatrics
Division of Infectious Diseases
Johns Hopkins Hospital
Baltimore, Maryland 21205
Office: (301) 955-3271
Home: (301) 338-1173
11. Horace Hodes, M.D.
Professor and Chairman
Department of Pediatrics
Mount Sinai School of Medicine
New York, New York 10029
Office: (212) 877-1158
Home: (516)627-3691
Alternates:
Eugene Ainbender, M.D.
Office: (212) 877-1158
Home: (914) 762-1148
Julian B. Schorr, M.D.
Director, Clinical Services
Greater New York Blood Program
150 Amsterdam Avenue
New York, New York 10023
Office: (212) 861-7200, Ext. 293 & 294
Home: (914) 592-5721






Distribution to the Armed Forces
12. Edward L. Buescher, Lt. Col. MC
Chief, Department of Virus Diseases
Division of Communicable Disease and Immunology
Washington, D.C. 20012
Office: (202) 576-3757 or
(202) 723-1000, Ext 3757
Home: (301) 588-8835


Alternate:
Malcolm S. Artenstein, M.D.
Office: (202) 576-3758
Home: (301) 299-6211




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