# S MMWR
Septem ber 28, 1 984  This statem ent, a com pendium o f ACIP recom m endations, w ill n o t be updated regularly. The ACIP p e rio dica lly review s in d ivid u a l im m u n iza tio n statem ents, and revised statem e nts are pu b lish e d in the MMWR. The reader m u s t use the detailed, u p -to -d a te in d ivid u a l s ta te m en ts in conjunction w ith th is com pendium in order to keep abreast o f current inform ation.

# V A C C IN E-P R EV E N T A B LE D IS E A S E S AN D T H E IR

# IN TRO D U CTIO N
In general, immunization policies have been directed towards vaccinating infants, children, and adolescents. While immunization is a routine measure in pediatric practice, it is not usually routine in the practice of physicians who treat adults.
The widespread and successful implementation of childhood immunization programs has greatly reduced the occurrence of many vaccine-preventable diseases. However, successful childhood immunization alone will not necessarily eliminate specific disease problems. A sub stantial proportion of the remaining morbidity and mortality from vaccine-preventable dis eases now occurs in older adolescents and adults. Persons who escaped natural infection or were not immunized with vaccines and toxoids against diphtheria, tetanus, measles, mumps, rubella, and poliomyelitis may be at risk of these diseases and their complications.
To reduce further the unnecessary occurrence of these vaccine-preventable diseases, all those who provide health care to older adolescents and adults should provide immunizations as a routine part of their practice. In addition, the epidemiology of other vaccine-preventable diseases (e.g., hepatitis B, rabies, influenza, and pneumococcal disease) indicates that indi viduals in certain age, occupational, environmental, and lifestyle groups and individuals who have special health problems are at increased risk of these illnesses and should be immunized. Travelers to some countries may be at increased risk of exposure to vaccine-preventable ill nesses. Finally, foreign students, immigrants, and refugees may be susceptible to these diseases.
A system atic approach to immunization is necessary to ensure that every adult is appropri ately protected against vaccine-preventable diseases. Every visit by an adult to a health-care provider should be an opportunity to provide this protection. Several factors need to be con sidered before any patient is vaccinated. These include the susceptibility of the patient, the risk of exposure to the disease, the risk from the disease, and the benefits and risks from the immunizing agent. Physicians should maintain detailed information about previous vaccina tions received by each individual, including type of vaccination, date of receipt, and adverse events, if any, following vaccination. Information should also include the person's history of vaccine-preventable illnesses, occupation, and lifestyle. Vaccine histories ideally should be based on written documentation to ascertain whether vaccines and toxoids were administered at appropriate ages and at proper intervals. Close attention to factors such as military service and age may be helpful in determining whether any vaccines or toxoids are advisable for an in dividual. After the administration of any immunobiologic, the patient should be given written documentation of its receipt and information on which vaccines or toxoids will be needed in

# 2S

# MMWR
Septem ber 28, 1984 the future. For this purpose an immunization record form such as the suggested form found in Appendix 1 should be used routinely.
The patient or responsible person should be given information on the risks of immunobio logies as well as their major benefits in preventing disease both in individuals and in the com munity. No formal, legally acceptable statement has been universally adopted for the private medical sector. Thus, the ACIP recommends that there be ample opportunity for questions before each immunization. C D C has developed "Important Information Statem ents" for use with federally purchased vaccines given in public health clinics. Practitioners may wish to con sider these or similar materials for patients. Examples of "Important Information Statements" can be obtained from state and many local health departments.
Modern immunobiologies are extremely safe and effective, but not completely so. All im munobiologies have had adverse events reported after administration. These range from fre quent, minor, local reactions to extremely rare, severe system ic illness, such as paralysis asso ciated with oral poliovirus vaccine (OPV). It is frequently impossible to establish causeand-effect relationships when untoward events occur after vaccination since temporal asso ci ation alone does not necessarily indicate causation. To improve knowledge about adverse reactions, all temporally associated events severe enough to require the recipient to seek medical attention should be evaluated and reported in detail to local or state health officials and to the manufacturer of the immunobiologic.
General immunization considerations and recommendations are found in the ACIP state ment "General Recommendations on Immunization" ( 1).
The following recommendations apply generally to individuals in the indicated groups. For more detailed information on immunobiologies, including indications, side effects, adverse reactions, precautions, contraindications, dosage, and route of administration, providers are urged to refer to the following section on individual immunobiologies, the ACIP statements on specific immunobiologies (Appendix 2), and the tables and appendices at the back of this sup plement. Appendix 3 provides a list of vaccines, toxoids, and immune globulins available in the United States as of June 1 984.

# Age Groups
The following text and Table 1 summarize the vaccines and toxoids recommended for most adults in the specific age groups. The reader is referred to the section on specific immu nobiologies for essential information.

# A d u lts 1 8 -2 4 Years O ld
All young adults should complete a primary series of diphtheria and tetanus toxoids. A pri mary series for adults is three doses of preparations containing tetanus and diphtheria toxoids, with the first two doses given at least 4 weeks apart and the third dose given 6-1 2 months after the second. Those who have completed a primary series should receive a boos ter dose every 10 years. There is no need to repeat doses when the series schedule is delayed. The combined tetanus-diphtheria toxoids for adult use, Td, should be used to en hance protection against both diseases. Persons with unknown or uncertain histories of re ceiving tetanus or diphtheria toxoids should be considered unimmunized and should receive a full three-dose primary series of Td.
Young adults should also be immune to measles, rubella, and mumps. Persons are consid ered immune to measles and mumps if they have a dated record of vaccination with live vac cines on or after their first birthday, documentation of physician-diagnosed disease, or labora tory evidence of immunity. Persons vaccinated in the period 1 9 6 3 -1 9 6 7 with inactivated-measles-virus vaccine or with a measles vaccine of unknown type should be revaccinated with live-m easles-virus vaccine to prevent measles disease or atypical measles syndrome if exposed to wild measles virus. Persons are considered immune to rubella only if they have a record of vaccination with rubella vaccine on or after their first birthday or laboratory evidence of immunity. The combined measles, mumps, rubella (MMR) vaccine is the vaccine of choice if recipients are likely to be susceptible to more than one of the three diseases. Persons lacking adequate documentation as noted above should be vaccinated.

# A d u lts 2 5 -6 4 Years O ld
All adults 2 5 -6 4 years of age should complete a primary series of tetanus and diphtheria toxoids. A primary series for adults is three doses of preparations containing tetanus and diphtheria toxoids, with the first two doses given at least 4 weeks apart and the third dose given 6-1 2 months after the second. Those who have completed a primary series should re ceive a booster dose every 10 years. The combined toxoids for adult use, Td, should be used to enhance protection against both diseases. Persons with unknown or uncertain histories of receiving tetanus or diphtheria toxoids should be considered unimmunized and should receive a full three-dose primary series of Td.
Adults born in 1957 or later should receive measles vaccine unless they have a dated record of vaccination with live-measles vaccine on or after their first birthday, documentation of physician-diagnosed disease, or laboratory evidence of immunity. Adults born before 1 957 can be considered immune to measles, since measles was a universal infection before measles vaccine became available. While most adults are likely to have been infected naturally with mumps, mumps vaccine may be given to adults, especially males, who are considered susceptible. Unless proof of vaccination with rubella vaccine or laboratory evidence of im munity is available, rubella vaccine is recommended for women of childbearing age and for other adults who may find themselves in places where rubella transmission is likely to occur, such as hospitals, all types of schools, and other places where young people are likely to con gregate. The combined MMR vaccine is the vaccine of choice if recipients are likely to be su s ceptible to more than one of these three diseases.

# A d u lts 6 5 Years O ld o r O lder
All older adults should complete a primary series of tetanus and diphtheria toxoids. A pri mary series for adults is three doses of preparations containing tetanus and diphtheria toxoids, with the first two doses given at least 4 weeks apart and the third dose given 6-1 2 months after the second. Those who have completed a primary series should receive a boos ter dose every 10 years. The combined toxoids for adult use, Td, should be used to enhance protection against both diseases. Persons with unknown or uncertain histories of receiving tetanus or diphtheria toxoids should be considered unimmunized and should receive a full three-dose primary series of Td All older adults should receive influenza vaccine annually. They should also receive a single dose of pneumococcal polysaccharide vaccine.

# Special O ccupations
Persons in specific occupations may be at increased risk of exposure to certain vaccinepreventable illnesses. Such persons may need selected vaccines and toxoids in addition to those routinely recommended for their age group. Table 2 provides a summary of immunobio logies recommended for various special occupational groups. The reader is referred to the section on specific immunobiologies for essential information.

# MMWR
Septem ber 28, 1984

# H e a lth -R e la te d O ccu p a tio n s
Medical, dental, laboratory, and other support personnel who may have contact with blood or blood products should be immune to hepatitis B virus (HBV) infection. The groups at high est risk for acquiring HBV infection and for whom HB vaccine is recommended include medical technicians, operating room staff, phlebotomists, physicians (particularly surgeons and pa thologists), nurses (particularly intravenous-therapy nurses and nurses on oncology and dialy sis units), dentists and oral surgeons, laboratory and blood-bank technicians, and emergencyroom staff. Morticians and their assistants who have routine contact with blood and secre tions are also at high risk of HBV infection. Selected staff of institutions for the mentally retarded may be at increased risk of HBV infection because of exposure to bites and contact with skin lesions, saliva, and other potentially infected secretions in addition to blood.
Am ong health-care personnel with frequent exposure to blood, the prevalence of serologic evidence of HBV infection is estimated to range between 10% and 30%. Since the cost effec tiveness of serologic screening to detect susceptible individuals among health-care personnel depends on the prevalence of infection, each institution must decide whether serologic screening is cost effective. Vaccination of individuals who already have antibodies to HBV has not been shown to cause adverse effects.
The duration of protection from a three-dose series of HB vaccine or the need for booster doses has not yet been determined.
Transmission of rubella in health facilities (hospitals, physician or dentist offices, clinics, etc.) can disrupt hospital or office routines and cause considerable expense. Although no cases of congenital rubella syndrome (CRS) have been reported in association with rubella transmission in health facilities, therapeutic abortions have been sought by pregnant staff members following rubella infection (2). To prevent such situations, all medical, dental, laboratory, and other support health personnel, both male and female, who might be at risk of exposure to patients infected with rubella, or who might have contact with pregnant patients, should be immune. Rubella vaccine is recommended for all such personnel unless they have either proof of vaccination with rubella vaccine on or after their first birthday or laboratory evi dence of immunity. Combined MMR vaccine is the vaccine of choice if recipients are likely to be susceptible to measles and/or mumps as well as to rubella.
Measles transmission in health facilities can also be disruptive and costly. To prevent such situations, all health personnel born in 1957 or later who may have contact with patients in fected with measles should be immune. Such persons can be considered immune only if they have documentation of having received live-m easles vaccine on or after their first birthday, a record of physician-diagnosed measles, or laboratory evidence of immunity. Measles vaccine is recommended for all persons lacking such documentation. Combined MMR vaccine is the vaccine of choice if recipients are likely to be susceptible to rubella and/or mumps as well as to measles. Adults born before 1957 can be considered immune to measles since measles w as a universal infection before the availability of measles vaccine.
Poliovirus vaccine is not routinely recommended for persons older than high school age (18-19 years old). However, hospital personnel having close contact with patients who may be excreting wild polioviruses, and laboratory personnel handling specim ens that may contain wild polioviruses, should have completed a primary series of poliovirus vaccine. For personnel who do not have proof of having completed a primary series, completion is recommended with inactivated poliovirus vaccine (IPV). IPV is preferred because there is a slightly increased risk in adults of vaccine-associated paralysis following receipt of OPV. In addition, since v ac cine poliovirus may be excreted by O PV recipients for 30 or more days, the use of O PV in creases the risk of acquiring vaccine-associated paralytic poliomyelitis among susceptible im munocompromised contacts and susceptible close contacts of O PV recipients.

# MMWR 5 S
Sm allpox vaccination is indicated only for laboratory workers involved with orthopox viruses or in producing and testing smallpox vaccine. When indicated, smallpox vaccination should be given at least every years.
Plague vaccine is indicated for laboratory personnel working with Yersinia p e stis possibly resistant to antimicrobial agents and for persons performing Y. p e stis aerosol experiments.
Preexposure rabies vaccination is indicated for laboratory workers directly involved with testing or isolating rabies virus.

# Veterinarians an d A n im a l H a n d lers
Veterinarians and animal handlers are at risk of rabies exposure because of occupational contact with both domestic and wild animals. They should receive preexposure rabies-vaccine prophylaxis with human diploid cell rabies vaccine (HDCV). Preexposure vaccination against rabies does n o t eliminate the need for additional therapy after exposure to rabies; it does, however, simplify postexposure therapy by eliminating the need for human rabies immune globulin (HRIG) and by decreasing the number of postexposure doses of vaccine needed. Per sons at continued risk of frequent exposure should receive a booster dose of H D CV every 2 years or have their serum tested for rabies antibody every 2 years and, if the titer is inadequate ( < 5 by the rapid fluorescent-focus inhibition test), receive a booster dose.

# S e le c te d F ie ld P e rso n n e l
Plague vaccine is indicated for field personnel who cannot avoid regular exposure to poten tially plague-infected wild rodents and rabbits and their fleas.
Preexposure rabies vaccine prophylaxis should be considered for field personnel who are likely to have contact with potentially rabid dogs, cats, skunks, raccoons, bats, or other w ild life species.

# S e w a g e W orkers
Sew age workers, as all other adults, should be adequately vaccinated against diphtheria and tetanus.
Poliovirus and typhoid vaccines and immune globulin are not routinely recommended for sew age workers.

# Lifestyles
Various lifestyles may increase the risk of exposure to certain vaccine-preventable ill nesses. Persons with these lifestyles may require vaccines in addition to those routinely recommended for their age group. Table 2 provides a summary of the vaccines recommended.

# H o m o s e x u a lly A c t iv e M a le s
Homosexually active males are at high risk of HBV infection. Between 35% and 80o have serologic evidence of HBV infection. Susceptible homosexual males should be vaccinated with HB vaccine as early as possible after they begin homosexual activity because they can be expected to acquire HBV infection at a rate of 10% -20% per year. The duration of protection from a three-dose series of HB vaccine and the need for booster doses have not yet been determined. Because of the high prevalence of infection, prevaccination serologic screening of homosexual males may be cost effective regardless of their age or of how long they have been homosexually active.

# MMWR
Sep tem b er 28, 1 984

# U se rs o f Illic it In je cta b le D ru gs
Users of illicit injectable drugs are at high risk of HBV infection. Serologic evidence of HBV infection has been found in 60% -80% of these individuals. Efforts should be made to vaccinate susceptible users with HB vaccine as early as possible after their drug use begins because they can be expected to acquire HBV infection at a rate of 10% -20% per year. The duration of protection from a three-dose series of HB vaccine and the need for booster doses have not yet been determined Because of the high prevalence of infection, prevaccination serologic screening of users of illicit injectable drugs to avoid unnecessary immunization is cost effective.
These drug users are also at increased risk of tetanus, and their tetanus immunization status should be kept up to date with Td.

# Environmental Situations
Certain environments may place an individual at increased risk of certain vaccinepreventable diseases. Table 2 sum marizes additional vaccines recommended for persons in selected environments. The reader is referred to the section on specific immunobiologies for essential information.

# In m a te s o f Lo n g -Term C o rre ctio n a l F a c ilit ie s
Serologic evidence of HBV infection has been found in 10% -80% of male prisoners. A l though the frequency of transmission during imprisonment has not been documented, the en vironment of long-term correctional facilities may be associated with a high risk of transm is sion of HBV infection because of the frequency of use of illicit injectable drugs and of homo sexual behavior. In selected long-term institutional settings, prison officials may elect to un dertake serologic HBV screening and vaccination programs. The duration of protection from a three-dose series of HB vaccine and the need for booster doses have not yet been determined.

# R e s id e n ts o f In stitu tio n s fo r the M e n ta lly R e ta rd e d
Institutions for the mentally retarded provide a setting conducive to the transmission of HBV infection through bites and contact with blood, skin lesions, saliva, and other potentially infectious secretions. Serologic evidence of HBV infection has been found in 35% -80% of resi dents of such institutions. New adm issions to these institutions should be vaccinated as soon as possible. For current residents, screening and vaccination of susceptible residents is recom mended. Because of the high prevalence of infection, preimmunization serologic screening of those already institutionalized may be cost effective; however, screening of new admissions very likely will not be. Residents of group homes, foster homes, and similar settings who have household contact with a carrier of HBV should also be vaccinated. The duration of protection from a three-dose series of HB vaccine and the need for booster doses have not yet been determined.

# Travel
The risk of acquiring illness during international travel depends on the areas of the world to be visited and the extent to which the traveler is likely to be exposed to vaccine-preventable diseases. When considering travel, people often seek advice from health-care personnel on immunization. This provides a good opportunity to review the person's immunization status and administer primary series or booster doses, if needed.

# MMWR 7S
In most countries, measles, mumps, and rubella remain uncontrolled. Therefore, the risk of acquiring these diseases while traveling outside the United States is greater than the risk in curred within the United States. Approximately 50S, of imported measles cases reported for 1 980-1 9 8 3 occurred in citizens returning to the United States (3). To minimize importations by U.S. citizens, all travelers born in 1 957 or later should be immune to measles. Women trav elers of childbearing ages should be immune to rubella before leaving the United States.
In developed countries such as Japan, Canada, Australia, New Zealand, and the European countries, the risk of acquiring other vaccine-preventable diseases such as poliomyelitis, diphtheria, and tetanus is usually no greater than the risk incurred while traveling in the United States. In contrast, travelers to developing countries are, in general, at increased risk of expo sure to many infections, including wild polioviruses and diphtheria. Accordingly, such travelers should be immune to poliomyelitis and diphtheria, in particular.
For protection against poliomyelitis, unimmunized adults should receive at least two doses of IPV 1 month apart, and preferably a complete primary series, before traveling to a develop ing country. If an individual's travel plans do not permit this interval, then a single dose of OPV is recommended. For adults previously incompletely immunized with O PV or IPV, the remain ing doses of either vaccine required for completion of the primary series should be given, regardless of the interval since the last dose or the type of vaccine previously received. A single additional dose of either O PV or IPV should be given to travelers who have previously completed a primary series of O PV or IPV Selective immunization of travelers with vaccines against yellow fever, cholera, typhoid, plague, m eningococcal disease, rabies, or HBV infection or administration of immune globulin (IG) to prevent hepatitis A is recommended on the basis of known, or perceived, diseasespecific risks in the country(ies) to be visited and the type and duration of travel within a coun try. In the instances of cholera and yellow fever, vaccination requirements may have been es tablished by the country to be visited. Countries currently reporting yellow fever, cholera, and plague are identified biweekly in the S um m a ry o f H ealth Inform a tion fo r In tern ation al Travel. and information on known or probably infected areas is published annually in H ealth In fo rm a tion fo r In tern ation al Travel, which also lists specific requirements for cholera and yellow fever vaccinations for each country. All state health departments and many county and city health departments receive both publications. For entry into countries requiring yellow fever or cholera vaccination, travelers must have an International Certificate of Vaccination validat ed by an appropriate authority. State or local health departments can provide the addresses of persons or centers able to validate certificates.
More information on specific vaccine-preventable illnesses that a traveler might encounter is provided in the sections describing specific vaccines.

# Foreign Students, Im m igrants, and Refugees
In many countries children and adolescents are not routinely immunized against diphtheria, tetanus, measles, mumps, rubella, and poliomyelitis. A s a result, persons entering the United States to pursue college and postgraduate studies or as immigrants or refugees may be su s ceptible to one or more of these diseases.
Unless foreign students, immigrants, and refugees can provide a vaccination record docu menting the receipt of recommended vaccines or toxoids at appropriate ages and intervals or laboratory evidence of immunity, they should receive the appropriate vaccines for their age as noted in age-specific recommendations (see page 2S) and in

# Special Health Status
Som e vaccines may be contraindicated for persons with certain health problems; other vaccines may be indicated because of an underlying health condition. Table 3 provides a sum mary of immunobiologies indicated or contraindicated for persons with selected health problems.

# P re g n a n c y
When any vaccine or toxoid is to be given during pregnancy, waiting until the second or third trimester, when possible, is a reasonable precaution to minimize concern about possible teratogenicity.
Pregnant women not vaccinated previously against tetanus and diphtheria should receive two doses of Td properly spaced. Those who have previously received one or two doses of tetanus or diphtheria toxoid should complete their primary series during pregnancy. A primary series is three doses of preparations containing tetanus and diphtheria toxoids, with the first two doses given at least 4 weeks apart and the third dose given 6 -1 2 months after the second. Pregnant women who have completed a primary series should receive a booster dose of Td if 10 or more years have elapsed since their last dose.
Because of a theoretical risk to the developing fetus, live-virus vaccines should not usually be given to pregnant women or to those likely to become pregnant within 3 months. If, how ever, immediate protection against poliomyelitis or yellow fever is needed because of immi nent exposure, O PV or yellow fever vaccine may be given. If the only reason to vaccinate a pregnant woman with yellow fever vaccine is an international travel requirement, efforts should be made to obtain a waiver letter (see page 1 9S).
It is strongly recommended that rubella vaccine be administered in the postpartum period to women not known to be immune, preferably before discharge from the hospital.
Information about immunobiologies and vaccine-preventable diseases during pregnancy is summarized in Appendix 4.

# C o n d itio n s That C o m p ro m ise the Im m u n e S y s te m
Persons with conditions that compromise their immune responses (e.g., leukemia, lym pho ma, and generalized malignancy or immunosuppressive therapies) should receive annual in fluenza vaccination with the currently formulated vaccine. Persons with conditions associated with increased risk of pneumococcal disease or its complications should receive a single dose of pneumococcal polysaccharide vaccine. The effectiveness of these vaccines in such per sons may be limited, but the risk of disease is substantial and adverse reactions are minimal.
In general, live-virus vaccines should not be given to persons who are immunocompro mised as a result of immune deficiency diseases, leukemia, lymphoma, or generalized m alignancy or are immunosuppressed as a result of therapy with corticosteroids, alkylating drugs, antimetabolites, or radiation. However, susceptible patients with leukemia in remission who have not had chemotherapy for at least 3 months may receive live-virus vaccines. The exact interval between discontinuing im m unosuppressives and regaining the ability to respond to individual vaccines is not known. Estimates of experts vary from 3 months to 1 year.
Short-term (less than 2 weeks) corticosteroid therapy, topical steroid therapy (e.g., nasal or skin), and intraarticular, bursal, or tendon injections with corticosteroids should not be im munosuppressive and do not necessarily contraindicate vaccination with live-virus vaccines. Vaccination should be avoided if system ic immunosuppressive levels are achieved by topical application.

# MMWR 9S

# H e m o d ia ly sis
Persons receiving hemodialysis have been at high risk of infection with HBV, although envi ronmental control measures have reduced this risk during the past few years. Nationwide, an estimated 1 5% of hemodialysis patients have serologic evidence of HBV infection, and routine serologic screening of hemodialysis patients is currently recommended. Susceptible patients who will soon require or are currently receiving long-term hemodialysis should receive three double doses of HB vaccine as soon as possible. Double the normal dose is recommended for these patients because of lower vaccine immunogenicity in this group. Postvaccination screening to demonstrate antibody to hepatitis B surface antigen (HBsAg) is recommended in this group. Approximately 60% of hemodialysis patients who receive double doses of HB vac cine demonstrate antibodies against HBV. The duration of protection from a three-dose series of HB vaccine and the need for booster doses have not yet been determined.
Because persons with chronic renal disease are at increased risk of adverse consequences from infections of the lower respiratory tract, hemodialysis patients should receive annual in fluenza vaccination with the current formulated vaccine. These patients are also at increased risk of developing pneumococcal infection, as well as of experiencing more severe pneumo coccal disease, and should receive pneumococcal polysaccharide vaccine.

# S p le n ic D y sfu n c tio n or A n a to m ic A sp le n ia
Persons with splenic dysfunction or anatomic asplenia are known to be at increased risk of contracting fatal pneumococcal bacteremia and should receive pneumococcal polysaccharide vaccine. Persons scheduled for elective splenectomy should receive pneumococcal polysac charide vaccine at least 2 weeks before the operation.

# F a c to r V III a n d I X D e fic ie n c ie s
Patients with clotting disorders who receive factor VIII or IX concentrates have an in creased risk of HBV infection. Vaccination with HB vaccine is recommended for susceptible patients. The degree and duration of protection from a three-dose series of HB vaccine and the need for booster doses have not yet been determined.
Prevaccination serologic screening for HBV markers is recommended for patients who have already received multiple infusions of these products.

# C h ro n ic A lco h o lism
Persons with chronic alcoholism may be at increased risk of contracting a pneumococcal infection or having a more severe pneumococcal illness. Such persons, especially those with cirrhosis, should receive pneumococcal polysaccharide vaccine.

# H ig h -R is k D is e a s e s
Persons with disease conditions that increase the risk of adverse consequences from lower-respiratory-tract infections should receive annual influenza vaccination with the current formulated vaccine. These conditions include:
(a) Acquired or congenital heart disease with actual or potentially altered circulatory dynamics. (b) Any chronic disorder or condition that compromises pulmonary function. (c) Diabetes mellitus or other metabolic diseases that increase the likelihood that infections will be more severe than for persons without such conditions. (d) Chronic renal disease with azotemia or nephrotic syndrome. (e) Chronic, severe anemia, such as sickle cell disease. Som e chronic illnesses (e.g., chronic pulmonary disease, congestive heart failure, diabetes mellitis) predispose individuals to an increased risk of pneumococcal illness or its com plica tions. While data on the effectiveness of pneumococcal polysaccharide vaccine for chronical ly ill persons are not conclusive, such persons should receive the vaccine.

# V A C C IN E -P R E V E N T A B LE D IS E A S E S AN D TH EIR IM MU NO BIO LO G IC S
Vaccines, toxoids, and immune globulins are available for use in the prevention of a number of diseases. These diseases and their specific immunobiologies are presented in this section. For each immunobiologic, dosage, route of delivery, indications for use, side effects, adverse reactions, precautions, and contraindications to be considered before administration are described here and are summarized in Table 4.

# Toxoids

# D iphth eria
The occurrence of diphtheria has decreased dramatically in the United States, largely be cause of the widespread use of diphtheria toxoid. Only 11 cases of diphtheria were reported in the period 1 9 8 0 -1 9 8 2 . From 1977 through 1982 , 56% of the 34 reported cases of re spiratory diphtheria occurred in adults 20 years of age or older, and 24% of the cases o c curred in adults 50 years of age or older. The age distribution for persons who died from diphtheria w as similar. Diphtheria occurs primarily among unimmunized or inadequately immunized individuals. Limited serosurveys done since 1977 indicated that 62% of adults 1 8 -3 9 years of age and 41% -84% of those 60 years of age or older lacked protective levels of circulating antitoxin against diphtheria (4 -6 ).

# Diphtheria toxoid
Complete and appropriately timed immunization is at least 95% effective in preventing diphtheria. The combined preparation Td is recommended for use in adults since a large pro portion of adults lack protective levels of circulating antibody against tetanus (4)(5)(6). Further more, Td contains much less diphtheria toxoid than other diphtheria toxoid-containing pro ducts, and as a result, reactions to the diphtheria component are less likely. Immunization with toxoid does not, however, prevent or eliminate carriage of Corynebacterium diphtheriae.

# Toxoid indications
All adults lacking a completed primary series of tetanus and diphtheria toxoids should complete the series with Td. A primary series for adults is three doses of preparations con taining tetanus and diphtheria toxoids, with the first two doses given at least 4 weeks apart and the third dose given 6-1 2 months after the second. All adults for whom 10 years or more have elapsed since completion of their primary series or since their last booster dose should receive a dose of Td. Thereafter, a booster dose of Td should be administered every 1 0 years. There is no need to repeat doses if the schedule for the primary series or booster doses is delayed. (For toxoid side effects and adverse reactions, and precautions and contraindications, see page 1 2S).

# Tetanus
The occurrence of tetanus has decreased dramatically, largely because of the widespread use of tetanus toxoid. Nevertheless, the number of cases remained relatively constant from M M W R I I S 1 973 through 1 982, averaging 88 reported cases per year. Tetanus occurs almost exclusive ly in unimmunized or inadequately immunized individuals. Immune pregnant women confer temporary protection against tetanus to their infants through transplacental maternal anti body. In the period 1 977-1 982, persons 20 years of age or older accounted for 89% of the 50 4 reported tetanus cases for which patient ages were known; persons 60 years of age or older accounted for 55%. The age distribution of persons who died from tetanus w as similar. Serosurveys done since 1977 indicated that 110/-of adults 1 8 -3 9 years of age and 49 j-66% of those 60 years of age or older lacked protective levels of circulating antitoxin against tetanus (4-6).

# Tetanus toxoid
Complete and appropriately timed immunization is nearly 100% effective in preventing tetanus. The combined preparation, Td, is the preferred preparation for active tetanus immuni zation of adults since a large proportion of adults lack protective levels of circulating antitoxin against diphtheria (4-6).

# Toxoid indications
All adults lacking a complete primary series of tetanus and diphtheria toxoids should com plete the series with Td. A primary series for adults is three doses of preparations containing tetanus and diphtheria toxoids, with the first two doses given at least 4 weeks apart and the third dose given 6 -1 2 months after the second. All adults for whom 10 years or more have elapsed since completion of their primary series or since their last booster dose should receive a booster dose of Td. Thereafter, a booster dose of Td should be administered every 10 years. There is no need to repeat doses if the primary schedule for the series or booster doses is delayed.
The recommended pediatric schedule for DTP vaccine includes a booster dose at age 4 -6 years. The first Td booster is recommended at age 14-1 6 years (10 years after the dose at age 4 -6 years). One means of ensuring that persons continue to receive boosters every 10 years is to vaccinate persons routinely at mid-decade ages, e.g., 25 years, 35 years, etc.
For wound management the need for active immunization, with or without passive immuni zation, depends on the condition of the wound and the patient's immunization history. A sum mary of the indications for active and passive immunization is provided in Table 5. Only rarely have cases of tetanus occurred in persons with a documented primary series of toxoid injections.
Evidence indicates that complete primary immunization with tetanus toxoid provides longlasting protection-10 years or more in most recipients. Consequently, after complete primary tetanus immunization, boosters are recommended at 10-year intervals. For clean and minor wounds occurring during the 10-year interval no additional booster is recommended. For other wounds, a booster is appropriate if the patient has not received tetanus toxoid within the preceding 5 years. Antitoxin antibodies develop rapidly in persons who have previously re ceived at least two doses of tetanus toxoid.
Persons who have not completed a full primary series of injections or whose immunization status is unknown or uncertain may require tetanus toxoid and passive immunization at the time of wound cleaning and debridement. It is not sufficient to ascertain the interval since the most recent toxoid dose. A careful attempt should be made to determine whether a patient has previously completed primary immunization and, if not, how many doses have been given. Persons with unknown or uncertain previous immunization histories should be consid ered to have had no previous tetanus toxoid doses.
Td is the preferred preparation for active tetanus immunization in managing the wounds of adults. Td is used to enhance protection against diphtheria concurrently, since a large propor

# MMWR
Sep tem b er 28, 1 9 8 4 tion of adults are susceptible. Thus, if advantage is taken of visits for care of acute health problems, such as for wound management, some patients who otherwise would remain su s ceptible can be protected against both diseases. Primary immunization should ultimately be completed for persons documented to have received fewer than the recommended number of doses, including doses given as part of wound management. If passive immunization is needed, human tetanus immune globulin (TIG) is the product of choice. The currently recommended prophylactic dose of TIG for wounds of average severity is 2 5 0 units, intramuscularly (IM). When tetanus toxoid and TIG are given concurrently, separ ate syringes and separate sites should be used. Most experts consider the use of adsorbed toxoid mandatory in this situation.

# To xo id (Td) S id e E f f e c t s a n d A d v e rs e R e a ctio n s
Local reactions, generally erythema and induration with or without tenderness, can occur after the administration of Td. Fever and other system ic sym ptom s are less common.
Arthus-type hypersensitivity reactions characterized by severe local reactions generally starting 2 -8 hours after an injection and often associated with fever and malaise may occur, particularly in persons who have received multiple boosters of tetanus toxoid.
Rarely, severe system ic reactions such as generalized urticaria, anaphylaxis, or neurologic com plications have been reported after administration of tetanus and diphtheria toxoids. Peripheral neuropathy has been reported rarely after administration of tetanus toxoid, al though a causal relationship has not been established.

# To x o id (Td ) P re ca u tio n s an d C o n tra in d ica tio n s
Although there is no evidence that tetanus and diphtheria toxoids are teratogenic, waiting until the second trimester of pregnancy to administer Td is a reasonable precaution to mini mize any concern over teratogenicity.
A history of a neurologic reaction or a severe hypersensitivity reaction (e.g., generalized ur ticaria or anaphylaxis) following a previous dose is a contraindication to tetanus and diphtheria toxoids. Local side effects alone do not preclude continued use. If a prior system ic reaction is suspected of representing allergic hypersensitivity, appropriate skin testing to document im mediate hypersensitivity may be useful before tetanus toxoid immunization is discontinued (7). Mild, nonspecific skin-test reactivity to tetanus toxoid is common. Most vaccinees develop cutaneous delayed hypersensitivity to the toxoid.
Persons experiencing severe Arthus-type hypersensitivity reactions to a prior dose of tetanus toxoid usually have very high serum tetanus antitoxin levels and should not be given even emergency booster doses of Td more frequently than every 10 years.
Although a minor illness, such as a mild upper-respiratory infection, should not be cause for postponing vaccination, a severe febrile illness is reason to defer routine vaccination.

# Live-V irus Vaccines

# M e a sle s
In 1983, only 5.6% of the 3 ,1 3 9 counties in the United States reported cases of measles. Indigenous transmission of measles has been eliminated from most of the United States be cause of widespread vaccination. However, importations of disease are frequent (more than 1 0 0 each year), and there is a continued risk of exposure, particularly for young adults attend ing college or universities or traveling abroad.
In 1982, 1 1.7% of measles patients whose ages were reported were 20 years of age or older. Outbreaks continue to occur in universities and colleges and other places where young MMWR 13S
adults congregate. In the first half of 1983, 51% of reported cases were among college stu dents or were epidemiologically linked to cam pus outbreaks. It is estimated that as many as 20% of young adults lack detectable antibody and may be susceptible to measles. Encephalitis or death follows measles disease in approximately one case per 1,000. The risk of encephalitis is greatest in adult patients. Aside from infants, the highest measles casefatality ratio occurs in adults.
Measles illness during pregnancy increases rates of spontaneous abortion, premature labor, and low birth weight for infants. Although cases of congenital malformation following m easles infection during pregnancy have been reported, no consistent patterns have been demonstrated.

# M easles vaccine
Measles vaccine produces a mild or inapparent noncommunicable infection. A single sub cutaneously (SC) administered dose of live-m easles vaccine provides durable protection against measles illness in approximately 95% of vaccinees, extending probably for their life time. Combined MMR vaccine is the vaccine of choice if recipients are likely to be susceptible to rubella and/or mumps as well as to measles. Although reactions following measles, mumps, and rubella vaccines in persons previously immune have been reported, evidence and experience overwhelmingly suggest that vaccination with MMR of persons who were pre viously immune to one or more of its components is not associated with significant adverse effects.

# Vaccine indications
Measles vaccine is indicated for all persons born in 1 957 or later who lack documentation of receipt of live-m easles vaccine on or after their first birthday, physician-diagnosed measles, or laboratory evidence of immunity. Persons born before 1957 can generally be considered immune since measles w as a universal infection before measles vaccine became available. In dividuals who received vaccine before their first birthday, killed-measles vaccine, killedmeasles vaccine followed within 3 months by live-m easles vaccine, or a measles vaccine of unknown type in the period 1 9 6 3 -1 9 6 7 should be revaccinated. An estimated 6 0 0 ,0 0 0 -9 0 0 ,0 0 0 persons in the United States received killed-measles vaccine in the years 1 9 6 3 -1 9 6 7 .
Because the risk of acquiring measles outside the United States is greater than the risk in curred in the United States, travelers should be immune to measles before leaving the United States.
Generally, young adults who are exposed to measles and who have no or uncertain docu mentation of live-m easles vaccination on or after their first birthday, no record of physiciandiagnosed measles, and no laboratory evidence of immunity should be vaccinated within 72 hours after exposure, when vaccination is most likely to be protective. If the exposure did not result in infection, the vaccine should induce protection against subsequent measles infection. An acceptable alternative is to use IG, which can prevent or modify infection if administered within 6 days after exposure. IG is principally indicated when measles vaccine is contraindicat ed. IG should not be used in an attempt to control measles outbreaks. The recommended dose of IG is 0.25 ml/kg IM, not to exceed 1 5 ml. Live-m easles vaccine should be given 3 months after IG is administered, by which time the passive measles entibodies should have disappeared.

# Vaccine side effects and adverse reactions
Reactions to measles vaccine do not appear to be age related. About 5%-1 5% of vaccinees may develop a temperature of 103F (39.4C) or higher, generally beginning between days 5 and 12 after vaccination; fever usually lasts 1-2 days and, rarely, up to 5 days. Transient

# 14S MMWR
Sep tem b er 28, 1 984 rashes have been reported in approximately 5% of vaccinees. The incidence rate of encephali tis or encephalopathy following measles vaccination is lower than the observed background incidence rate of encephalitis of unknown etiology and much lower than that following natural measles.
Reactions after live-measles vaccination occur in 4% -55% of prior recipients of killedmeasles vaccine. The reactions are generally mild, consisting of a local reaction with or with out a low-grade fever of 1-2 days' duration. Such reactions are considerably milder than atypical measles syndrome, an illness which may affect prior recipients of killed-measles vac cine who are exposed to natural measles.

# Vaccine precautions and contraindications
Vaccination should not be postponed because of a minor illness, such as a mild upperrespiratory infection. However, vaccination of persons with severe febrile illnesses should be postponed until recovery. Vaccine should be given 14 days before or deferred for at least 6 weeks, and preferably 3 months, after a person has received IG, whole blood, or other blood products containing antibody.
Because of a theoretical risk to the developing fetus, measles vaccine should not be given to pregnant women.
Measles vaccine should not be given to persons who are immunocompromised as a result of immune deficiency diseases, leukemia, lymphoma, or generalized malignancy or are immunosuppressed as a result of therapy with corticosteroids, alkylating drugs, antimetabolites, or radiation. (See "Conditions That Com prom ise the Immune System ," page 8S.)
There is no evidence that live-measles vaccine exacerbates tuberculosis. If tuberculin skin testing is needed, it should be done on the day of vaccination and read 4 8 -7 2 hours later. For a recent vaccinee, it is prudent to wait 4 -6 weeks after receipt of measles vaccine before ad ministering a tuberculin skin test since measles vaccination may temporarily suppress tubercu lin reactivity.
Persons with a history of any sign or symptom of an anaphylactic reaction (i.e., hives, swelling of the mouth and throat, difficulty in breathing, hypotension, or shock) following in gestion of eggs or receipt of neomycin should be given measles vaccine only with extreme caution. Protocols have been developed for vaccinating such persons (S). Persons with reac tions that are not anaphylactic are not at increased risk and can be vaccinated.

# M u m p s
The occurrence of reported mumps cases in the United States has decreased steadily since the introduction of live-m um ps-virus vaccine. In 1983, a record low of 3,2 9 7 cases were reported provisionally; this number represented a 98% decline from the 1 85,691 cases reported in 1967, the year live-m umps vaccine w as licensed. In 1982, 5 ,2 7 0 cases were reported, of which 9% occurred in persons 20 years of age or older.
Although mumps disease is generally self-limiting, meningeal signs may appear in up to 1 5% of cases, and orchitis in up to 20% of clinical cases among postpubertal males. Sterility is a rare sequela of mumps orchitis among males. Deafness occurs at a rate of one case per 1 5 ,0 0 0 cases of mumps.
Serologic surveys indicate that most individuals have been infected with mumps by 20 years of age.

# M umps vaccine
Live-m um ps vaccine has been available since 1967. A single dose of live-m umps vaccine administered S C provides protective and long-lasting levels of antibody in over 90% of reci pients. Reported clinical vaccine efficacy ranges between 75% and 90%. MMR is the vaccine

# MMWR 15S
-f choice if recipients are likely to be susceptible to measles and/or rubella as well as to mumps. Although reactions following measles, mumps, and rubella vaccines in persons pre viously immune have been reported, evidence and experience overwhelmingly suggest that the vaccination with MMR of persons who were previously immune to one or more of its components is not associated with significant adverse effects.

# Vaccine indications
Mumps vaccine is indicated for all adults, particularly males, believed to be susceptible. Most adults are likely to have been infected naturally and generally can be considered immune, even if they did not have clinically recognizable mumps disease. Killed-m um ps vac cine w as available from 1 9 5 0 until 1 978. Persons who received killed-mumps vaccine might benefit from vaccination with live-mumps vaccine.

# Vaccine side e ffe cts and adverse reactions
Parotitis after vaccination has been reported rarely. Allergic reactions including rash, pru ritus, and purpura have been associated temporally with mumps vaccination but are uncom mon, usually mild, and of brief duration. The frequency of reported central nervous system (CNS) dysfunction following mumps vaccination is lower than the observed background inci dence rate in the general population.

# Vaccine precautions and contraindications
Vaccine should be given at least 14 days before or deferred for at least 6 weeks, and preferably 3 months, after a person has received IG, whole blood, or other blood products containing antibody.
Because of the theoretical risk of fetal damage following administration of a live-virus vac cine to a pregnant woman, it is prudent to avoid giving mumps vaccine to pregnant women.
Mumps vaccine should not be given to persons who are immunocompromised as a result of immune deficiency diseases, leukemia, lymphoma, or generalized m alignancy or are immunosuppressed as a result of therapy with corticosteroids, alkylating drugs, antimetabolites, or radiation. (See "Conditions That Com prom ise the Immune System ," page 8S.)
Persons with a history of any sign or symptom of an anaphylactic reaction (i.e., hives, swelling of the mouth and throat, difficulty in breathing, hypotension, or shock) following in gestion of eggs or receipt of neomycin should be vaccinated only with extreme caution. Proto cols have been developed for vaccinating persons with severe egg allergy (8). Persons with reactions that are not anaphylactic are not at increased risk and can be vaccinated.

# R u b e lla
Preventing fetal infection and consequent C R S are the objectives of rubella immunization. Fetal infection occurring during the first trimester of pregnancy can lead to C R S in up to 80% of fetuses. In addition, fetal wastage due to miscarriage or therapeutic abortion following m a ternal rubella disease or exposure during the first trimester remains a frequent occurrence.
The number of reported rubella cases has decreased steadily from over 5 6 ,0 0 0 cases in 1 9 69, the year rubella vaccine w as licensed, to 2 ,325 cases in 1 982. In 1 982, only 11.7% of the 3,1 37 counties in the United States reported cases of rubella. The 1 9 8 3 provisional total of 9 5 4 cases is an all-time low. Because, until recently, many adolescents and young adults had not been vaccinated, decreases in incidence rates of reported rubella were observed pri marily for children. Recent efforts to increase delivery of vaccine to cellege-age and older per sons have led to the current decline in the incidence rates for these age groups. However, an estimated 1 0%-1 5% of young adults remain susceptible to rubella, and limited outbreaks con tinue to be reported in universities, colleges, and places of employment-notably hospitals. Vaccination of young children has prevented widespread epidemics of rubella and of C R S and eventually will lead to the elimination of C R S as vaccinated cohorts enter the childbearing age. However, increased efforts to ensure that all women of childbearing age, in particular, are vaccinated will hasten the elimination of rubella and C R S in the United States. Additional aids to elimination of rubella and C R S include 1) achieving and maintaining high immunization levels, 2) maintaining vigorous surveillance, and 3) practicing aggressive outbreak control.

# Rubella vaccine
A single S C administered dose of live, attenuated rubella vaccine provides long-term, probably lifetime, immunity in approximately 95% of vaccinees. Moreover, there is no risk to susceptible contacts of vaccinees. MMR is the vaccine of choice if recipients are likely to be susceptible to measles and/or mumps as well as to rubella. Although reactions following ad ministration of measles, mumps, and rubella vaccines to persons previously immune have been reported, evidence and experience overwhelmingly suggest that the vaccination with MMR of persons who are already immune to one or more of its components is not associated with significant adverse effects.

# Vaccine indications
Rubella vaccine is recommended for adults, particularly females, unless proof of immunity is available (i.e., documented rubella vaccination on or after the first birthday or a positive serologic test) or unless the vaccine is specifically contraindicated. In particular, nonpregnant susceptible women of childbearing age should be provided rubella vaccination 1) during rou tine internal medicine and gynecologic outpatient care, 2) during routine care in a family plan ning clinic, 3) following premarital screening, 4) before discharge from a hospital for any reason, and 5) after childbirth or abortion. Ideally, any contact with the health-care system should be used as an opportunity to vaccinate susceptible women. In addition, evidence of rubella immunity should be required for all individuals in colleges and universities. Health-care programs in work places and in other places where women of childbearing age congregate should ensure that the rubella immune status of every employee is ascertained and that rubella immunization is made available. All hospital personnel (male and female) who might be at risk of exposure to patients infected with rubella or who might have contact with pregnant pa tients or personnel should be immune to rubella. Consideration should be given to making rubella immunity a condition for employment. Finally, since the risk of acquiring rubella while traveling outside the United States is greater than the risk incurred within the United States, all women travelers, particularly those of childbearing age, should be immune before leaving the United States.

# Vaccine side effects and adverse reactions
Up to 40% of susceptible adult vaccinees in large-scale field trials have had joint pain, usu ally of the small peripheral joints, after vaccination; frank arthritis is reported infrequently. A r thralgia and transient arthritis occur more frequently and tend to be more severe in susceptible women than in children. When joint sym ptom s or other types of pain and paresthesias do occur, they generally begin 3 -2 5 days after vaccination, persist for 1-11 days, and rarely recur. Adults with joint problems usually have not had to disrupt work activities. Complaints of transient peripheral neuritis such as paresthesias and pain in the arms and legs have o c curred very rarely and only in susceptible vaccinees.

# Vaccine precautions and contraindications
Rubella vaccine should be given at least 14 days before administration of IG or deferred for at least 6 weeks, and preferably 3 months, after administration. On the other hand, previ ous administration of whole blood or other blood products containing antibody (e.g., human anti-Rho  immune globulin) does not generally interfere with an immune response and is not a contraindication to postpartum vaccination. However, in this situation, serologic testing should be done 6 -8 weeks after vaccination to assure that seroconversion has occurred.

# MMWR 17S
Rubella vaccine should not be given to pregnant women or to those likely to become preg nant within 3 months after receiving the vaccine. Through 1 983, C D C monitored prospective ly 2 1 4 susceptible pregnant women who had received rubella vaccine within 3 months before or after conception and carried their pregnancies to term (94 received Cendehill or H PV-77, 11 9 received RA 27/3, and one received an unknown strain of vaccine). None of the infants had malformations compatible with C R S. The ACIP believes that the risk of vaccineassociated malformation is so small as to be negligible. Although a final decision must rest with the individual patient and her physician, the ACIP believes that rubella vaccination during pregnancy should not ordinarily be a reason to recommend interruption of pregnancy.
Because of the theoretical risk to the fetus, reasonable precautions should be taken before women of childbearing age are vaccinated. These precautions include 1) asking women if they are pregnant, 2) excluding those who say they are, and 3) explaining the theoretical risks of the vaccine to the others and counseling them not to become pregnant for 3 months after vaccination. If a pregnant woman is vaccinated or if a woman becomes pregnant within 3 months after vaccination, she should be counseled on the theoretical risks to the fetus. In stances of vaccination of k n o w n susceptible women who are pregnant or become pregnant within 3 months should be reported through state health departments to the Division of Im munization, CDC.
In general, rubella vaccine should not be given to persons who are immunocompromised as a result of immune deficiency diseases, leukemia, lymphoma, or generalized m alignancy or are immunosuppressed as a result of therapy with corticosteroids, alkylating drugs, antime tabolites, or radiation. (See "Conditions That Com prom ise the Immune System ," page 8S.)
Rubella vaccine is prepared in human diploid cell cultures and has not been reported to be associated with allergic reactions. The vaccine does contain trace amounts of neomycin to which patients may be allergic. Persons with a history of any sign or symptom of an anaphylactic reaction (i.e., hives, swelling of the mouth and throat, difficulty in breathing, hy potension, or shock) following receipt of neomycin should not receive rubella vaccine. Persons with reactions to neomycin that are not anaphylactic are not at increased risk and can be v ac cinated. Rubella vaccine does not contain penicillin.

# S m a llp o x
In May 1 9 80, the World Health Organization (WHO) declared the world free of smallpox. A smallpox vaccination certificate is not required by any country as a condition of entry for inter national travelers. In May 1983, the distribution of smallpox vaccine for civilian use in the United States w as discontinued.

# Vaccine indications
There is no evidence that smallpox vaccination has therapeutic value in the treatment of recurrent herpes simplex infection, warts, or any other disease. Sm allpox vaccine should never be used therapeutically for these or any other conditions.
Except for persons working with orthopox viruses or involved in producing and testing smallpox vaccine, there are no indications for the use of smallpox vaccine in civilian popula tions. When indicated, smallpox vaccination should be given at least every 3 years. For advice on vaccine administration and contraindications, contact the International Health Program Office, C D C , Atlanta, Georgia 30 3 3 3 .

# Y ello w F e v e r
C ases of yellow fever are reported only from Africa and South America. Two form s of yellow fever-urban and jungle -are distinguishable epidemiologically. Clinically and ecologi cally they are identical.

# 18S

# MMWR

# Septem ber 28, 1984
Urban yellow fever is an epidemic viral disease transmitted from infected to susceptible persons by the Aedes a e g yp ti mosquito. In areas where the A. a e g yp ti mosquito has been eliminated or suppressed, urban yellow fever has disappeared. In W est Africa, A. aegyptitransmitted epidemics involving town and village populations continue to occur at frequent intervals.
Jungle yellow fever is an enzootic viral disease transmitted among nonhuman hosts by a variety of mosquito vectors. It is currently observed only in forested areas of South America and forest-savannah zones of tropical Africa, but occasionally extends into Central America and the Caribbean. In tropical America 2 0 0 -4 0 0 cases are recognized annually, mainly among persons with occupational exposure to the vector in forested areas; the disease is, however, believed to be greatly underreported. In Africa, epidemics that are spread by forest mosquito vectors affect tens of thousands of persons every few years, but few cases are officially reported. The jungle yellow fever cycle may be active but unrecognized in forested areas of countries within the zone with endemic yellow fever (Figure 1).

# Yellow fever vaccine
The yellow fever vaccine available in the United States is an attenuated, live-virus vaccine prepared from the 1 7D strain of virus grown in chick embryo. Immunity is induced by a single S C injection of 0.5 ml of reconstituted vaccine and persists for more than 10 years.
Yellow fever vaccines must be approved by W HO and administered at an approved Yellow Fever Vaccination Center. Centers can be identified by contacting state and local health departments. Vaccinees should have an International Certificate of Vaccination filled out, dated, signed, and validated with the stamp of the center where the vaccine is given. Vaccine must be received 6 days to 10 years before travel in order for the certificate to be valid.

# Vaccine indications
Vaccination is recommended for persons traveling or living in areas where yellow fever in fection o ccu rs-currently parts of Africa and South America. tries currently reporting yellow fever are noted biweekly in S um m ary o f H ealth In fo rm a tio n fo r In te rn a tio n a l Travel. All state health departments and many county and city health depart ments receive these publications. It should be emphasized that the actual areas of yellow fever activity far exceed the zones officially reported to be infected. Vaccination is also recommended for laboratory personnel who might be exposed to virulent yellow fever virus. Booster doses are needed at 1 O-year intervals. Som e countries, especially in Africa, require evidence of vaccination from all entering trav elers. Other countries may waive the requirements for travelers coming from noninfected areas and staying less than 2 weeks. Som e countries require a traveler, even if only in transit, to have a valid certificate if the traveler has visited any country thought to harbor yellow fever virus. Requirements of individual countries may change, and the most current information is published biweekly in S um m ary o f H ealth In fo rm a tio n fo r In tern ation al Travel and summarized annually in H ealth Inform a tion fo r Intern ation al Travel.

# Vaccine side effects and adverse reactions
Reactions to 17D yellow fever vaccine are generally mild. From 2% to 5% of vaccinees have mild headache, myalgia, low-grade fever, or other minor sym ptom s 5 -1 0 days after vac cination. Fewer than 0.2% curtail regular activities. Immediate hypersensitivity reactions, char acterized by rash, urticaria, and/or asthma, are extremely uncommon and occur principally in persons with a history of egg allergy. Although more than 34 million doses of vaccines have been distributed, only two cases of encephalitis temporally associated with vaccinations have been reported in the United States; in one fatal case, 1 7D virus w as isolated from the brain.

# Vaccine precautions and contraindications
Yellow fever vaccine should not be given to persons who are immunocompromised as a result of immune deficiency diseases, leukemia, lymphoma, or generalized m alignancy or are immunosuppressed as a result of therapy with corticosteroids, alkylating drugs, antimetabo lites, or radiation. (See "Conditions That Com prom ise the Immune System ," page 8S.)
Although specific information is not available on adverse effects of yellow fever vaccine on the developing fetus, it is prudent on theoretical grounds to avoid vaccinating pregnant women and to advise that they postpone travel to areas where yellow fever occurs until after delivery. Pregnant women who must travel to areas where the risk of yellow fever is high should be vaccinated. It is believed that under these circum stances, the risk of yellow fever in fection far outweighs the small theoretical risk to mother and fetus from vaccination. Howev er, if international travel regulations constitute the only reason to vaccinate a pregnant woman or a patient hypersensitive to eggs, efforts should be made to obtain a letter of waiver from a physician clearly stating the contraindication to vaccination. Ideally, this letter should be writ ten on letterhead stationery and bear the stamp used by health departments and official im munization centers to validate the International Certificates of Vaccination. Such a letter of waiver has been acceptable to some governments. Under these conditions, it is also useful for the traveler to obtain specific, authoritative advice from the country or countries he or she plans to visit. Their em bassies or consulates may be contacted, and a letter substantiating the waiver of requirements obtained.
Since live yellow fever vaccine is produced in chick embryos, persons with a history of any signs or sym ptom s of an anaphylactic reaction (i.e., hives, swelling of the mouth and throat, difficulty in breathing, hypotension, or shock) after eating eggs should not receive yellow fever vaccine. If vaccination of an individual with a questionable history of egg hypersensitivity is considered essential because of a high risk of exposure, an intradermal (ID) test dose may be administered under close medical supervision. Specific directions for skin testing are found in the package insert. Som e data have indicated that persons given yellow fever and cholera vaccines simultane ously or 1-3 weeks apart had lower-than-normal antibody responses to both vaccines. Unless there are time constraints, cholera and yellow fever vaccines should be administered at a minimal interval of 3 weeks. If the vaccines cannot be administered at least 3 weeks apart, then they should preferably be given simultaneously.
Yellow fever vaccine and commercially available IG may be given simultaneously.

# Both Live-V irus and Inactivated-Virus Vaccines

# P o lio m y e litis
The risk of poliomyelitis is very small in the United States; however, epidemics could occur if the high immunity level of the general population is not maintained by immunizing children routinely or if wild poliovirus is introduced into susceptible populations in communi ties with low immunization levels. In the United States inapparent infection with wild poliovirus strains no longer contributes significantly to establishing or maintaining immunity. Most adults are already immune.

# Poliovirus vaccines
Two types of poliovirus vaccines are currently licensed in the United States: O PV and IPV. A primary vaccination series with either vaccine produces immunity to all three types of polio virus in more than 95% of recipients. The primary series of O PV consists of three doses: two doses given 6 -8 weeks apart and a third dose given at least 6 weeks and customarily 6 -1 2 months after the second. The primary series for IPV consists of four doses: three doses each given 4 -8 weeks apart and a fourth dose given 6 -1 2 months after the third. In general, it is not necessary to give a primary vaccine series to adults living in the United States who have not had a primary series as children. However, for adults who have not had a primary series and who are at greater risk than the general population of exposure to wild polioviruses be cause of foreign travel or health occupation, IPV is preferred since the risk of O PV-associated paralysis is slightly higher in adults than in children.
Poliovirus vaccine is not routinely recommended for persons older than high school age (1 8 -1 9 years old).

# Vaccine indications
Travelers to areas where wild poliovirus is epidemic or endemic should have completed a primary series of poliovirus vaccine. For previously unimmunized persons, IPV is indicated. However, if less than 4 weeks are available before protection is needed, a single dose of OPV is recommended. Travelers who have previously received less than a full primary course of O PV or IPV should be given the remaining required doses of either vaccine, regardless of the interval since the last dose and the type of vaccine previously received. Travelers to develop ing countries who have previously completed a primary series of O PV should receive a single dose of OPV. Additional booster doses of O PV are probably not necessary. Those who have previously received a primary series of IPV should receive a dose of either O PV or IPV. If IPV is used exclusively, an additional dose may be given every 5 years if exposure continues or recurs, although the need for these boosters has not been established.
Health-care personnel in close contact with patients who may be excreting wild poliovi ruses, and laboratory personnel handling specim ens that may contain wild polioviruses, should have completed a primary series of poliovirus vaccine. IPV is indicated because of the slightly increased risk to adults of vaccine-associated paralysis after O PV administration; also, virus may be shed after receipt of O PV vaccine and inadvertently expose susceptible im munocompromised contacts to live vaccine virus.

# MMWR

# 21S

# Vaccine adverse reactions
In a ctiva te d po lio viru s vaccine. No serious side effects of currently available IPV have been documented. Since IPV contains trace amounts of streptomycin and neomycin, hypersensitivi ty reactions are possible in individuals sensitive to these antibiotics. Persons with signs and sym ptom s of an anaphylactic reaction (i.e., hives, swelling of mouth and throat, difficulty in breathing, hypotension, or shock) following receipt of streptomycin or neomycin should not receive IPV. Persons with reactions that are not anaphylactic are not at increased risk and can be vaccinated.
O ral p o lio viru s vaccine. In rare instances, administration of O PV has been associated with paralysis in healthy recipients and their contacts. Although the risk of vaccine-associated paralytic poliomyelitis is extremely small for immunologically normal vaccinees (approximate ly one case per 9 million doses distributed) and their susceptible, immunologically normal household contacts (approximately one case per 7 million doses distributed), vaccinees should be informed of this risk.

# Vaccine precautions and contraindications
In a ctiva te d p o lio viru s vaccine. There is no convincing evidence of adverse effects of IPV for the pregnant woman or developing fetus; regardless, it is prudent on theoretical grounds to avoid vaccinating pregnant women. However, if immediate protection against poliomyelitis is needed. OPV, not IPV, is recommended.
O ral po lio viru s vaccine. Unlike other live-virus vaccines, which are administered parenteral ly, O PV is administered orally. IG and other antibody-containing blood products do not appear to interfere with the immune response to OPV.
OPV should not be given to persons who are or may be immunocompromised as a result of immune deficiency diseases, leukemia, lymphoma, or generalized malignancy or immunosuppressed as a result of therapy with corticosteroids, alkylating drugs, antimetabolites, or ra diation. (See "Conditions That Com prom ise the Immune System ," page 8S.) If immunization against poliomyelitis is indicated in such persons, IPV should be used, and some protection may result.
OPV should not be used for immunizing household contacts of patients immunocompro mised as a result of immune deficiency disease, leukemia, lymphoma, or generalized malignancy or immunosuppressed as a result of therapy with corticosteroids, alkylating drugs, antimetabolites, or radiation. If protection is indicated, IPV should be used for immuniz ing household contacts of such patients. O PV should not be given to anyone in a family with a known family history of immunodeficiency until the immune status of all family members is documented.
When children in the household are given O PV, adults who are not adequately immunized against poliomyelitis are at a very small risk of contracting O PV-associated paralytic polio myelitis. Because of the overriding importance of ensuring prompt and complete immunization of the child and the extreme rarity of O PV-associated disease in contacts of vaccinees, the ACIP recommends the administration of O PV to a child regardless of the poliovirus-vaccine status of adult household contacts. This is the usual practice in the United States. The re sponsible adult should be informed of the small risk involved and of precautions to be taken, such as hand washing after changing a diaper. An acceptable alternative, if there is strong assurance that ultimate, full immunization of the child will not be jeopardized or unduly delayed, is to immunize adults with IPV or OPV, as appropriate to their immunity status, before giving O PV to the child.

# Inactivated-Virus Vaccines

# H e p a titis B Virus In fe ctio n
The estimated lifetime risk of acquiring HBV infection in the United States is approximately 5% for the population as a whole but may approach 100% for the highest risk groups. Annual ly, an estimated 1 0 0 ,0 0 0 sym ptom atic cases of hepatitis B disease occur in the United States, leading to approximately 10,000 hospitalizations and 190 fulminant cases. Threefourths of persons with fulminant disease die.
In 1982, 88% of hepatitis B cases for which patient age w as known occurred in persons 20 years of age or older. Between 6% and 10% of adults with HBV infection become carriers. The United States currently has 4 0 0 ,0 0 0 -8 0 0 ,0 0 0 carriers. Chronic active hepatitis occurs in 25% of carriers. Each year in the United States, approximately 4 ,0 0 0 persons die of HBVrelated cirrhosis, and 8 00, of HBV-related liver cancer.

# Hepatitis B vaccine
A series of three 1 -ml IM doses of HB vaccine, each containing 20 /ug/ml of HBsAg protein, provides protective antibody in over 90% of healthy adult recipients and is 80% -95% effective in preventing infection for at least 2 years. The first two doses should be given 1 month apart, and the third dose, 5 months after the second. The duration of vaccine-induced protection and the need for booster doses are not yet known. For susceptible hem odialysis patients, three 2-m l doses given at the above intervals are recommended. Because the prevalence of HBV varies widely among various population groups, serologic screening to detect susceptible individuals before vaccination may or may not be cost effective. Cost effectiveness depends on the known or perceived risk of infection, the cost of screening, and the cost of HB vaccine.

# Vaccine indications
Immunization is recommended for adults at increased risk of occupational, social, family, environmental, or illness-related exposure to HBV. These include homosexual males, users of illicit injectable drugs, household and sexual contacts of HBV carriers, workers in healthrelated occupations requiring frequent exposure to blood, residents and staff of institutions for the mentally retarded, hemodialysis patients, recipients of factor VIII or IX concentrates, and morticians and their assistants. Inmates in some long-term correctional facilities may also be candidates for vaccination.
Vaccination should also be considered for persons who plan to reside for more than 6 months in areas with high levels of endemic HBV and who will have close contact with the local population and for travelers intending a short stay who are likely to have contact with blood from or sexual contact with residents of areas with high levels of endemic disease (par ticularly areas of eastern Asia and Sub-Saharan Africa). Such persons should allow 6 months before travel in order to complete the HB vaccine primary series.
HB vaccine is intended primarily for preexposure prophylaxis. However, it has recently been recommended for postexposure use in certain situations, particularly for persons who belong to a high-risk group for whom preexposure administration of vaccine is recommended ( 3 ). HB vaccine in combination with HBIG provides sustained protective levels of antibody and obviates the need for a second dose of HBIG in such exposures. Therefore, a normal series of HB vaccine, combined with a single dose (0.06 ml/kg or 5 ml for adults) of HBIG given at a dif ferent site, is recommended for postexposure prophylaxis of health workers following acci dental percutaneous or mucous-membrane exposure to blood containing HBsAg, and of su s ceptible homosexual men following sexual exposure to an H BsAg-positive man. HBIG alone (in the same dose) is recommended for postexposure prophylaxis of persons with heterosexu al exposures. - Vaccine side effects and adverse reactions
In vaccine trials, soreness at the site of injection w as the only side effect that occurred more frequently for vaccinees than for controls. Since its licensure in 1981 through August 1 983, HB vaccine is estimated to have been administered to over 3 5 0 ,0 0 0 individuals in the United States. A s of May 1 984, adverse events following immunization had been reported for 8 9 0 vaccinees. The reported adverse events represent temporal associations with vaccination and are not necessarily caused by the vaccine. Forty-eight persons had serious events such as transverse myelitis, grand mal seizures, aseptic meningitis, erythema multiforme, or Guillain-Barre syndrome (GBS).

# Vaccine precautions and contraindications
Pregnancy should not be considered a contraindication to vaccinating women who are oth erwise candidates for receiving HB vaccine. While data are not available on the safety of the vaccine for the developing fetus, HB vaccine contains only noninfectious HBsAg particles and should pose no risk to the fetus. In contrast, HBV infection in a pregnant woman may result in a severe disease for the mother and chronic infection for the newborn.
Since HB vaccine is made from human plasma, the possibility that it may contain an etiologic agent of acquired immunodeficiency syndrome (AIDS) has been raised. The purification and inactivation process used in preparing HB vaccine inactivates representatives of all known groups of viruses. There are no microbiologic, epidemiologic, or empiric data to suggest that the HB vaccine carries any etiologic risk for AIDS.

# In flu e n za
Influenza viruses have continually demonstrated the ability to cause major epidem ics of re spiratory disease. High attack rates of acute illness and the frequent occurrence of lowerrespiratory-tract complications usually result in dramatic rises in visits to physicians' offices and hospital emergency rooms. Furthermore, influenza frequently infects individuals who, be cause of their age or underlying health status, are poorly able to cope with the disease and often require medical attention, including hospitalization. Such persons are considered to be medically at "high risk" in epidemics. In one recent study, for example, rates of hospitalization for adults with "high-risk" medical conditions increased during major epidemics by about two-to fivefold in different age groups, reaching a maximum rate of about 8 0 0 per 1 0 0 ,0 0 0 population.
Influenza epidemics cause excess mortality, which is attributable not only to influenza pneumonia, but also to cardiopulmonary disease. Fifteen times in the years 1 9 5 7 -1 9 8 2 , epidemics have been associated with 10 ,0 0 0 or more excess deaths; in 1983, excess mor tality again exceeded the epidemic threshold.
The greatest impact of influenza is normally seen when new strains appear against which most of the population lacks immunity. In these circum stances (e.g., 1957 and 1968), pandemics occur. During pandemics, a quarter or more of the United States population have been affected over a period of 2 -3 months.
Because the proportion of elderly persons in the United States is increasing, and because age and its associated chronic diseases are risk factors for severe influenza illness, the toll of influenza may also increase unless control measures are used more vigorously than in the past.

# Influenza vaccine
Influenza A viruses are classified into subtypes on the basis of two antigens: hemagglutinin (H) and neuraminidase (N). Three subtypes of hemagglutinin (H1, H2, H3) and two subtypes of neuraminidases (N1, N2) are recognized among influenza A viruses that have caused w ide spread human disease. Immunity to these antigens, especially hemagglutinin, reduces the likelihood of infection and the severity of disease if a person does become infected. However, there may be sufficient antigenic variation (antigenic drift) within the same subtype overtime, so that infection or vaccination with one strain may not induce immunity to distantly related strains of the same subtype. Although influenza B viruses have shown much more antigenic stability than influenza A viruses, antigenic variation does occur. A s a consequence, the an tigenic characteristics of current strains provide the basis for selecting virus strains to be included in the vaccine for a given year. Potency of present vaccines is such that nearly all vaccinated young adults develop hemagglutination-inhibition antibody titers that are likely to protect them against infection by strains like those in the vaccine, and often by related variants that emerge. The elderly, the very young, and patients with certain chronic diseases may develop lower postvaccination an tibody titers than do young adults. Under these circum stances, influenza vaccine may be more effective in preventing lower-respiratory-tract involvement, or other complications of in fluenza, than in preventing upper-respiratory-tract involvement. Influenza vaccine will not pre vent primary illnesses caused by other respiratory pathogens.

# Vaccine indications
Use of inactivated influenza vaccine is the single most important measure in the prevention and/or attenuation of influenza infection. Since 1 963, annual vaccination against influenza has been recommended for individuals at high risk of lower-respiratory-tract complications and death following influenza infection (i.e., the elderly and persons with chronic disorders of the cardiovascular, pulmonary, and/or renal system s; metabolic diseases; severe anemia; and/or compromised immune function). These groups have been identified primarily by review of death certificate data, supported by hospital-based or population-based studies. W ithin each broadly defined "high-risk" category, however, some persons are more likely than others to suffer severe complications from influenza infection.
Am ong nursing-home residents, chronic diseases and other debilitating conditions are common, and spread of influenza can often be explosive, with attack rates as high as 60% and case-fatality ratios up to 30% or higher. In addition, recent retrospective studies of nonin stitutionalized patients suggest that chronic underlying diseases, particularly those that affect the cardiovascular and pulmonary system s, may contribute more to the severity of illness than does age alone.
Medical personnel may transmit influenza infections to their high-risk patients while they are themselves incubating an infection, undergoing a subclinical infection, or working while they have mild sym ptom s. Nosocom ial outbreaks of influenza are reported. The potential for introducing influenza to a high-risk group such as patients with severely compromised cardio pulmonary or immune system s or infants in neonatal intensive care units should be reduced by targeted vaccination programs of medical personnel.
Based on these observations, the previous, broadly defined "high-risk" adult groups have been further assigned priority for receiving vaccine in order that special efforts can be directed at providing vaccine to those who may derive the greatest benefit.
1. Adults at high risk of severe influenza illness who most warrant active, targeted v acci nation efforts: (a) Adults with chronic disorders of the cardiovascular or pulmonary system s that are severe enough to require regular medical follow-up or to have caused hospitalization during the preceding year.
(b) Residents of nursing homes and other chronic-care facilities (e.g., institutions hous ing patients of any age with chronic medical conditions). Achievement of high vacci nation rates (e.g., 80%) may induce herd immunity in such populations and thereby MMVIIR 2 5 S lower the frequency of outbreaks, as well as reducing the frequency of severe illness when outbreaks do occur. 2. Physicians, nurses, and other personnel who have extensive contact with high-risk pa tients (e.g., primary-care and certain specialty clinicians and staff of intensive-care units). These persons should receive influenza vaccination annually to reduce the po ssi bility for nosocomial spread of influenza to high-risk patients. 3. Other adults who are at moderately increased risk of serious illness compared with the general population. Special programs to make vaccine readily available to these groups should also be given high priority:
(a) Healthy individuals over 65 years of age.
(b) Adults with a chronic metabolic disease (including diabetes mellitus), renal dysfunc tion (including those in chronic dialysis), anemia, immunosuppression, or asthma that is severe enough to require regular medical follow-up or to have caused hospi talization during the preceding year. In addition, influenza vaccine may be offered to persons who provide essential community service or to any adult who w ishes to reduce the likelihood of an influenza infection.
Effective programs for giving influenza vaccine are needed in nursing homes and other chronic-care facilities, in physicians' offices, and in hospital settings. Residents of nursing homes and chronic-care facilities should receive routine annual vaccination. Other adult highpriority groups should receive influenza vaccine at the time of regular medical follow -ups in the fall, or should be notified to come in specifically to receive the vaccine. Patients with high risk conditions who are hospitalized during the fall should be considered for influenza vaccine before discharge from the hospital.
There is considerable overlap in the target groups for influenza vaccination and those for pneumococcal polysaccharide vaccine. Pneum ococcal polysacchraride vaccine and influenza vaccine can be given at the same time at different sites without an increase in side effects; however, it should be emphasized that whereas influenza vaccine is given annually, pneumo coccal polysaccharide vaccine should be given only once to adults. Detailed immunization records should be provided to each patient to help ensure that additional doses of pneumo coccal polysaccharide vaccine are not given.
Amantadine hydrochloride, an antiviral drug, can prevent influenza A or be used therapeuti cally to reduce sym ptom s of influenza A infections. It is n o t a substitute for vaccine. Specific circum stances in which amantadine prophylaxis is recommended are described in the ACIP recommendations on prevention and control of influenza.

# Vaccine side effects and adverse reactions
Vaccines used in recent years have generally been associated with only a few reactions. Fewer than one-third of vaccinees have been reported to develop local redness or induration for 1 or 2 days at the site of injection.
System ic reactions have been of two types. First, malaise, myalgia, and other system ic sym ptom s of toxicity, although infrequent, most often affect those who have had no experi ence with the influenza virus antigens contained in the vaccine. These reactions, which begin 6 -1 2 hours after vaccination and persist for 1-2 days, are usually attributed to the influenza antigens (even though the virus is inactivated) and constitute most of the system ic side ef fects of influenza vaccination.
Second, immediate, presumably allergic, responses such as flare and wheal or various respiratory-tract sym ptom s of hypersensitivity occur extremely rarely after influenza vaccina tion. These sym ptom s probably result from sensitivity to some vaccine component -most likely residual egg protein. Although current influenza vaccines contain only a small quantity of egg protein, on rare occasions vaccine can induce hypersensitivity reactions. Unlike the MMWR Septem ber 28, 1984
1 976 swine influenza vaccine, vaccines used subsequently have not been associated with an increased frequency of GBS.

# Vaccine precautions and contraindications
Pregnancy has not been demonstrated to be a risk factor for severe influenza infection except in the largest pandemics of 1 9 1 8 -1 9 1 9 and 1 957-1 958. Influenza vaccine is consid ered to be generally safe for pregnant women. Nonetheless, when vaccine is to be given during pregnancy, waiting until the second or third trimester is a reasonable precaution to minimize any concern over theoretical teratogenicity.
Persons with a history of any signs or sym ptom s of an anaphylactic reaction (i.e., hives, swelling of the mouth and throat, difficulty in breathing, hypotension, or shock) after eating eggs should not be given inactivated influenza vaccine.
Persons with acute febrile illnesses normally should not be vaccinated until their temporary sym ptom s have abated.

# R a b ie s
Although rabies rarely affects humans in the United States, thousands of persons receive rabies vaccine every year, principally for postexposure prophylaxis. The likelihood of human exposure to rabies from domestic animals has decreased greatly in recent years. In every year since 1 976, more than 85% of all reported cases of animal rabies have been among wild ani mals, the most important source of possible infection for humans in the United States. How ever, for persons traveling overseas to developing countries with endemic rabies, the dog re mains the animal most likely to transmit rabies.

# Rabies vaccine
Both whole-virion and subvirion human diploid cell rabies vaccines (HDCV) are available. For preexposure rabies prophylaxis a three-dose series of H D CV of either type given as 1 -ml doses IM on days 0, 7, and 28 provides adequate antibody levels in virtually all recipients (10). The C D C currently accepts a titer of 5 by the rapid fluorescent-focus inhibition test as adequate.
The whole-virion H D CV produced by the Merieux Institute has been used for preexposure immunization in a regimen of three 0 .1 -ml doses given intradermally (ID) in the lateral aspect of the upper arm in the deltoid area, one dose on each of days 0, 7, and 28. Experience gained with over 2 ,0 0 0 persons vaccinated in the United States by the ID route has shown that anti body is produced in all recipients, although the mean response is somewhat lower and may be of shorter duration than with comparable IM immunization. Except for persons suspected of being immunosuppressed, postvaccination serology is not necessary following IM or ID im munization in the United States. Antibody response in some groups vaccinated ID outside the United States has been found to be inadequate for reasons not yet determined (11). Prelimi nary data suggest that concurrent administration of malaria chem oprophylaxis may be a factor in the lowered immunologic response of persons vaccinated overseas. It should be noted that Merieux Institute, the manufacturer, has not yet met the packaging and labeling re quirements necessary to obtain approval by the FDA for the ID route of administration. The 1 -ml vial presently available is intended for IM use and contains no preservatives. To minimize the risk of contamination and loss of vaccine potency, the reconstituted vaccine must be used immediately. Data on ID immunization are not available for W yeth Laboratories vaccine.
Proper postexposure rabies prophylaxis is determined by whether or not the person has had previous preexposure or postexposure prophylaxis. 1) Persons who (a) have previously received postexposure prophylaxis with HDCV, (b) have received a three-dose IM preexposure regimen of HDCV, (c) have received a three-dose ID preexposure regimen of H D CV in the United States, or (d) have a previously documented adequate rabies titer should receive two 1-ml IM doses of H D C V -one dose on each of days 0 and 3. HRIG is not recommended in these circum stances. 2) Persons not meeting the above criteria should be treated with a single, 20-international units (IU)/kg dose of HRIG and five 1-ml doses IM of H D CV -one on each of days 0, 3, 7, 14, and 28. HRIG should be administered at the beginning of H D CV post exposure prophylaxis but can be given up to the eighth day after the first dose of H D CV was given. The HRIG dose should be divided; up to half should be infiltrated into the area of the wound, if possible, and the rest administered IM, but not in the same site as HDCV. O nly IM ad ministration of HD CV is indicated for postexposure prophylaxis.

# Vaccine indications
Preexposure immunization should be considered for high-risk groups: animal handlers, cer tain laboratory workers and field personnel, and persons planning to be in countries or areas of countries for more than 1 month where rabies is a constant threat. Persons whose voca tions or avocations bring them into contact with potentially rabid animals should also be con sidered for preexposure immunization. Persons with continuing risk of exposure should re ceive a booster dose every 2 years or have their serum tested for rabies antibody every 2 years and, if the titer is inadequate, be given a booster dose. If there is substantial risk of expo sure to rabies, preexposure rabies prophylaxis may be indicated during pregnancy.
The decision to provide specific postexposure antirabies treatment should include the fol lowing considerations:
1 Type of exposure-rabies is transmitted primarily by the bite of infected animals. It may also be transmitted by introducing the virus into open cuts or wounds in skin or via m ucous membranes by saliva or other potentially infectious material from a rabid animal and, rarely, by aerosol exposure. 2. Species of biting animal -carnivorous wild animals (especially skunks, raccoons, and foxes) and bats are most commonly infected with rabies in the United States. Elsewhere in the world, dogs, cats, carnivorous wildlife, and bats are the major vectors. The likeli hood that domestic cats or dogs in the United States will be infected varies from region to region. Rodents are rarely infected. Consultations with the state or local health department may be helpful. 3. Circum stances of biting incident -an unprovoked attack is more indicative of a rabid animal than a provoked attack.
- Vaccine side effects and adverse reactions Following postexposure prophylaxis, local reactions, such as pain, erythema, and swelling or itching at the injection site, are very common, and mild system ic reactions, such as head ache, nausea, abdominal pain, muscle aches, and dizziness, are reported by about 20% of reci pients. System ic allergic reactions ranging from hives to anaphylaxis occur in an estimated 11 per 10,000 vaccinees. Mild immune-complex-like hypersensitivity reactions consisting of hives, itching, and angio-edema have occurred 2-21 days after booster doses of H D CV and are the most frequently reported allergic reactions ( 12 ). Four cases of transient neuroparalytic illness have been temporally associated with H D CV administration: two following administra tion of whole-virion vaccine and two following administration of subvirion vaccine (13). No permanent sequelae or deaths have been associated with administration of HDCV.

# Vaccine precautions and contraindications
Corticosteroids and other immunosuppressive agents can interfere with the development of active immunity and should not be administered during preexposure therapy. When rabies postexposure prophylaxis is administered to persons known or suspected of being immunosuppressed, or to those who are receiving steroids or immunosuppressive therapy, it is espe cially important that serum be tested to ensure an adequate rabies antibody response. If a person experiences an anaphylactic reaction (i.e., hives, swelling of the mouth and throat, difficulty in breathing, hypotension, or shock) after receiving HDCV, no further preex posure doses of H D CV should be given. By contrast, if a person needing postexposure therapy has had a previous anaphylactic reaction to H D CV or has such a reaction during the postexpo sure course, H D CV therapy should continue; however, the person should receive the required doses in an appropriate medical setting.

# Inactivated-Bacteria Vaccines

# Ch o le ra
Cholera continues to be a health risk in Africa and Asia. Countries currently reporting chol era are listed in the biweekly publication S um m a ry o f H ealth Inform a tion fo r In tern ation al Travel. All state health departments and many county and city health departments receive this publication. Persons who follow the usual tourist itinerary and who use tourist accom m o dations in countries affected by cholera are at virtually no risk of infection. The traveler's best protection against cholera is avoiding food and water that might be contaminated.

# Cholera vaccine
The vaccine may be administered as a 0.5-m l dose S C or IM or as a 0.2-m l dose ID. A l though a single dose of vaccine is sufficient for entry into most countries, some countries may require evidence of a complete primary series of two doses given 1 week to 1 month or more apart, or a booster dose within 6 months before arrival.
The currently available cholera vaccine has been shown in field trials to be only about 50% effective in preventing clinical illness for a period of 3 -6 months. The vaccine does not prevent transmission of infection. The risk of cholera to most U.S. travelers is so low that it is doubtful that vaccination is of benefit. W HO no longer recommends cholera vaccination for travel to or from cholera-infected areas. However, some countries affected or threatened by cholera re quire evidence of cholera vaccination as a condition of entry. Current information on choleravaccination requirements of individual countries is published annually in H ealth Inform a tion fo r International. Travel. All state health departments and many county and city health depart ments receive this publication. Travelers to countries with cholera-vaccination requirements should have an International Certificate of Vaccination filled in, dated, signed, and validated showing receipt of the vaccine 6 days to 6 months before entry into the country. Most city, county, and state health departments can validate certificates. Failure to secure validation may cause travelers to be revaccinated or quarantined

# Vaccine indications
Cholera vaccine is indicated only for travelers to countries requiring evidence of cholera vaccination for entry. Boosters may be given every 6 months if required by a country.

# Vaccine side effects and adverse reactions
Vaccination often results in 1 -2 days of pain, erythema, and induration at the site of injec tion. The local reaction may be accompanied by fever, malaise, and headache. Serious reac tions, including neurologic reactions, following cholera vaccination are extremely rare.

# Vaccine precautions and contraindications
No specific information is available on the safety of cholera vaccine during pregnancy. Be cause cholera disease during pregnancy is a serious illness, whether to use cholera vaccine should be determined in individual circum stances based on the actual risk of disease and the probable benefits of the vaccine.
The only contraindication to cholera vaccine is a history of a severe reaction following a previous dose. Most governments will permit an unvaccinated traveler to enter the country if
MMWR 2 9 S
he or she carries a physician's statement of medical contraindication. However, some coun tries may quarantine such unvaccinated persons or place them under surveillance if they come from areas with cholera. Som e data have indicated that persons given yellow fever and cholera vaccines simultane ously or 1-3 weeks apart had lower-than-normal antibody responses to both vaccines. Unless there are time constraints, cholera and yellow fever vaccines should be administered at a minimal interval of 3 weeks. If the vaccines cannot be administered at least 3 weeks apart, then they should preferably be given simultaneously.

# M e n in g o co cca l D is e a s e
Meningococcal disease is endemic throughout the world but may also occur in epidemics. Am ong U.S. civilians, m eningococcal disease occurs primarily as single, isolated cases or, in frequently, in small, localized clusters. A third of all cases of m eningococcal disease occur in patients 20 years old or older. Serogroup B strains cause the majority of U.S. cases, with serogroups C and W1 35 strains accounting for most of the remainder.

# M eningococcal polysaccharide vaccine
Two m eningococcal polysaccharide vaccines, bivalent A -C and quadrivalent A, C, Y, and W1 35 vaccines, are available for use in the United States. Each is given as a single dose, and each induces specific serogroup immunity. The duration of immunity conferred by the v ac cines is not known.

# Vaccine indications
Vaccine may be of benefit as an adjunct to antibiotic chem oprophylaxis for household and other close contacts of persons with m eningococcal disease caused by serogroups A, C, Y, and W 1 3 5 and for travelers to areas with epidemic m eningococcal disease. The need for booster doses has not been established.
Routine vaccination of U.S. civilians with m eningococcal polysaccharide vaccine is not recommended because of the lack of availability of a group B vaccine and the low risk of in fection in the United States.

# Vaccine side effects and adverse reactions
Adverse reactions to meningococcal polysaccharide vaccines are infrequent and mild, con sisting principally of localized erythema lasting 1 -2 days.

# Vaccine precautions and contraindications
The safety of meningococcal polysaccharide vaccines for pregnant women has not been established. On theoretical grounds, it is prudent not to use them unless there is a substantial risk of infection.

# P lagu e
Plague is a natural infection of rodents and their fleas. In the United States a few human cases occur yearly in humans exposed in the Western states to infected animals, primarily ro dents, and their fleas. Other countries currently reporting plague infections are noted in the biweekly publication S um m a ry o f H ealth In fo rm a tio n fo r In tern ation al Travel. All state health departments and many county and city health departments receive this publication. A number of countries in Africa, Asia, and South America continue to report sporadic, epidemic, and epi zootic infection. In most of these countries, the risk of exposure exists primarily in rural or semirural areas.
- Plague vaccine A primary series of plague vaccine consists of three IM doses. The first dose, 1 ml, is fol lowed in 4 weeks by a second dose of 0.2 ml. The third dose, also 0.2 ml, is administered 5 months after the second. The effectiveness of a primary series of plague vaccine has never been measured precisely. Field experience indicates that vaccination with plague vaccine reduces the incidence and severity of disease resulting from the bite of infected fleas. The degree of protection offered against primary pneumonic infection is unknown. Since plague vaccination may only ameliorate illness, prophylactic antibiotics may be indicated whenever a person, vaccinated or not, has a definite exposure.

# Vaccine indications
Vaccination is indicated for certain vocational groups. These include all laboratory and field personnel working with Yersinia pe stis organisms that may be resistant to antimicro bials, persons engaged in aerosol experiments with Y. pestis, and field personnel engaged in operations in areas with enzootic or epidemic plague where preventing exposure to rodents and fleas is impossible. Plague vaccination should be considered for laboratory personnel regularly working with Y. p e stis or plague-infected rodents and for persons whose vocation regularly exposes them to wild rodents or rabbits in areas with enzootic plague.
Vaccine may also be considered for travelers to areas known to have endemic plague in countries reporting plague, particularly if travel will not be limited to urban areas with tourist hotel accommodations.
For persons with continuing exposure, three booster doses, each 0.1-0.2 ml, should be given at approximately 6-m onth intervals. Thereafter, booster doses at 1-to 2-year intervals should provide good protection.

# Vaccine side e ffe cts and adverse reactions
For about 10% of recipients, primary vaccination may result in general malaise, headache, fever, mild lymphadenopathy, and/or erythema and induration at the injection site. These reactions occur more commonly with repeated injections. Sterile abscesses occur rarely. Se n sitivity reactions manifested by urticarial and asthmatic phenomena have occasionally been reported.

# Vaccine precautions and contraindications
Neither the safety nor efficacy of vaccination with plague vaccine during pregnancy has been determined; therefore, it should not be used unless there is a substantial risk of infection.
Plague vaccine should not be administered to anyone with a known hypersensitivity to any of its constituents (beef protein, soy, casein, and phenol). Patients who have had severe local or system ic reactions to plague vaccine should not be revaccinated.

# P n e u m o c o c c a l D is e a s e
Precise data on the occurrence of serious pneumococcal disease in the United States are not available: however, the annual incidence rate of pneumococcal pneumonia is estimated to be 68 cases to 2 6 0 cases per 1 0 0 ,0 0 0 population, and of bacteremia, 7 -2 5 /1 0 0 ,0 0 0 . The incidence of pneumococcal pneumonia, which causes a substantial number of deaths annual ly, increases in those over 4 0 years old, and show s a twofold increase in those over 60 years of age. Mortality from pneumococcal disease is highest among patients who have bacteremia or meningitis, patients with underlying medical conditions, and older persons.
Patients with certain underlying conditions are clearly at increased risk both of contracting pneumococcal infection and of experiencing more severe pneumococcal illness. These condi tions include sickle cell anemia, multiple myeloma, cirrhosis, alcoholism, nephrotic syndrome, renal failure, splenic dysfunction, anatomic asplenia, and organ transplant. Persons suffering from diabetes mellitus, chronic pulmonary disease, cardiovascular disease, or conditions asso ciated with immunosuppression may be at increased risk of contracting pneumococcal infec tion or of having more severe illness.

# MMWR 3 1 S - Pneum ococcal polysaccharide vaccine
The pneumococcal polysaccharide vaccine currently available contains purified capsular materials of the 23 types of S treptococcus pneum oniae responsible for 87% of recent bacteremic pneumococcal disease in the United States. Most healthy adults show a twofold rise in type-specific antibody 2-3 weeks after administration of a single dose of vaccine. The titer of antibody that is protective against each serotype has not been determined.
The duration of vaccine-induced immunity is unknown. Studies of persistence of vaccineinduced antibody show elevated titers 3 -5 years after immunization. Booster doses are not recommended because of increased adverse reactions to subsequent doses.
Patients who have received the earlier pneumococcal polysaccharide vaccine containing capsular material from only 14 types of S. pneum oniae should not receive a dose of the 2 3valent pneumococcal polysaccharide vaccine since the modest increase in coverage does not warrant the increased risk of adverse reactions.

# Vaccine indications
Newly available data regarding vaccine efficacy support the broader use of pneumococcal polysaccharide vaccine in the United States. Vaccination is particularly recommended for the following:
1) Adults with chronic illnesses, especially those with cardiovascular disease and chronic pulmonary disease, who sustain increased morbidity with respiratory infections. 2) Adults with chronic illnesses specifically associated with an increased risk of pneumo coccal disease or its complications. These include splenic dysfunction or anatomic asplenia, Hodgkins' disease, multiple myeloma, cirrhosis, alcoholism, renal failure (including those on chronic dialysis), cerebrospinal-fluid leaks, and conditions associat ed with immunosuppression. 3) Older adults, especially those age 65 and over, who are healthy. Program s for vaccine delivery in the recommended high-risk groups need to be developed further. Specifically, more effective programs are needed for giving vaccine in physicians' of fices, in hospitals, and in nursing homes and other chronic-care facilities.
Since two-thirds of persons with serious pneumococcal disease have been hospitalized within 5 years before the pneumococcal illness ( 14), vaccine should be given to hospitalized patients in the high-risk groups before discharge, in order to prevent future adm issions for pneumococcal disease. In addition, persons with chronic conditions who visit physicians fre quently are probably at higher risk of pneumococcal infection than those who require infre quent visits. Office-based programs to identify and immunize patients requiring frequent medical care should help prevent pneumococcal illness. Furthermore, pneumococcal polysac charide vaccine and influenza vaccine can be given at different sites at the same time without an increase in side effects (7 5 ).
Medicare has partially reimbursed the cost of pneumococcal polysaccharide vaccination since 1981. It has been determined that hospitals may be reimbursed for pneumococcal im munization of Medicare recipients independent of reimbursement based on system s of pros pective payments.

# Vaccine side e ffe cts and adverse reactions
About half of the persons given pneumococcal polysaccharide vaccine experience mild side effects such as erythema and pain at the site of injection. Fever and m yalgias have been reported by fewer than 1% of those given pneumococcal polysaccharide vaccine (7 6).
Severe adverse effects such as anaphylactic reactions have rarely been reported -about five cases per million doses administered.
Arthus reactions and system ic reactions have been common among adults given second doses (1 7). They are thought to result from localized antigen-antibody reactions involving an tibody induced by previous vaccination. Therefore, second, or "booster," doses are not recommended.

# Vaccine precautions and contraindications
The safety of pneumococcal polysaccharide vaccine in pregnant women has not been evaluated. It should not be given to healthy pregnant women. Women at high risk of pneumo coccal disease ideally should be vaccinated before pregnancy.
Because of a marked increase in adverse reactions with second injections of pneumococcal polysaccharide vaccine, second, or "booster," doses should not be given. However, when there is doubt or no information on whether a person in one of the high-risk groups has ever received pneumococcal polysaccharide vaccine, vaccine should be given. Complete records of vaccination can help to avoid repeat doses.

# Typhoid
The occurrence of typhoid fever remained constant in the period 1 9 7 2 -1 9 8 2 , with an average of 4 8 6 cases reported annually. During the years 1 9 7 8 -1 9 8 2 , 57% of cases for which the patient's age w as known occurred in patients 20 years of age or older. Approxi mately 62% of typhoid cases reported in the United States during 1 977-1 979 were acquired by travelers to other countries, and an additional 27% occurred in contacts of typhoid carriers.

# Typhoid vaccine
A primary series of two 0.5-m l doses of typhoid vaccine given S C 4 weeks apart has been shown to protect 70% -90% of recipients.

# Vaccine indications
Immunization is indicated for travelers to areas where a recognized risk of exposure to ty phoid exists. It should be emphasized that even after typhoid vaccination, food and water should be selected carefully in these areas. Typhoid vaccination is not recommended in the United States or in areas of natural disaster. Booster doses should be given at least every 3 years to persons with continued or repeated exposure; these may be given S C (0.5 ml) or ID (0.1 ml). The acetone-killed and -dried vaccine should not be given ID. This preparation is available only to the U.S. Armed Forces.

# Vaccine side effects and adverse reactions
Typhoid vaccination often results in 1-2 days of discom fort at the site of injection. The local reaction may be accompanied by fever, malaise, and headache.

# Vaccine precautions and contraindications
The only contraindication to typhoid vaccine is a history of a severe local or system ic reac tion following a previous dose.

# Live-Bacteria V accines T u b e rcu lo sis
The number of tuberculosis cases in the United States has declined steadily since reporting began in the 1 9th century. Between 1 972 and 1 9 82, the annual incidence of tuberculosis de clined from 15.8 cases per 1 0 0 ,0 0 0 population to 1 1 .0/100 ,000, a decrease of 30%. In 1 982, approximately 92% of 2 5 ,0 5 9 reported cases with patient ages known occurred in per sons 20 years of age or older. Reported cases usually are typical postprimary pulmonary dis ease. The risk of infection is greatest for those who have repeated exposure to persons with unrecognized or untreated sputum -positive pulmonary tuberculosis. In the United States, ef forts to control tuberculosis are directed toward early identification and treatment of cases.

# MMWR 33 S
preventive therapy with isoniazid for infected persons at high risk of developing disease, and prevention of transmission to others.

# BCG vaccine
Although BCG vaccine is widely used in many areas of the world, results of a recent largescale field trial in India have raised questions about its efficacy (18). BCG vaccines currently available in the United States differ from the products used in the published field trials, and their efficacy has not been demonstrated directly. In the United States, vaccines for ID and for percutaneous administration are licensed. (For percutaneous administration, one drop of vac cine is placed on the skin and introduced through the skin by multiple punctures with a bifurcated or other needle.) Vaccination should be only by the route indicated on the package labeling.

# Vaccine indications
In the United States the only situations in which BCG might be considered are 1) for indi viduals in prolonged close contact with patients with active tuberculosis that is untreated, ineffectually treated, or resistant to treatment; 2) for health-worker groups, such as hospital staffs, with an annual new-infection rate of 1% or higher in spite of other tuberculosis control measures; and 3) for other groups in which an excessive rate of new infection can be demonstrated and the usual surveillance and treatment programs have failed or are not feasible. - Vaccine side effects and adverse reactions BCG has been associated with severe or prolonged ulceration at the vaccination site, re gional adenitis, disseminated BCG infection, and osteitis. Severe ulceration and adenitis occur in approximately 1 % -10% of vaccinees, and disseminated infections and osteitis are quite rare (1-10 per million doses).

# Vaccine precautions and contraindications
Although no harmful effects of BCG on the fetus have been observed, it is prudent to avoid vaccination during pregnancy unless there is immediate excessive risk of exposure to in fective tuberculosis.
Since BCG is a live-bacteria vaccine, it should not be given to persons immunocompro mised as a result of immune deficiency diseases, leukemia, lymphoma, or generalized m alignancy or to persons immunosuppressed as a result of therapy with corticosteroids, alkylating drugs, antimetabolites, or radiation. (See "Conditions That Com prom ise the Immune System ," page 8S.)

# Other Licensed Vaccines

# A d e n o v iru s a n d A d e n o v iru s V a ccin e
Adenovirus types 4 and 7 have frequently been the cause of outbreaks of acute, febrile, respiratory-tract disease in young adults during military training. Live, oral adenovirus vaccines for types 4 and 7 are available for immunization of military populations. Use of the vaccines in other populations is not recommended.

# A n th ra x an d A n th ra x V a ccin e
Anthrax is infrequently encountered. Anthrax vaccine is recommended only for individuals who come in contact with imported animal hides, furs, bonemeal, wool, animal hair (especially goat hair), and bristles in the workplace and for individuals undertaking investigational studies involving Bacillus anthracis.
Primary immunization consists of six S C 0.5-m l injections, the first three at 2-w eek inter vals and the other three at 6-m onth intervals. Booster doses of 0.5-m l S C are recommended at 1-year intervals. The vaccine is only available from the Biologic Products Program, Michi

# P e rtu ss is a n d P e rtu s s is V a ccin e
Pertussis disease in adults is generally milder than in children and is not known to result in death. Pertussis can be transmitted from adult patients to close contacts, especially unimmu nized children. Such transmission may occur in the household and in hospitals, where chains of transmission have involved patients and staff.
In general, pertussis vaccine is not recommended for adults because both local and sy s temic reactions are thought to be more frequent and severe than in children under 7 years of age and because the disease itself is less severe in adults. In specific situations, such as docu mented transmission to and from personnel in a hospital, single-antigen pertussis vaccine in a 0.2-m l IM dose has been given as a part of control efforts. Single-antigen pertussis vaccine, adsorbed, is available only from the Biologic Products Program, Michigan Department of Public Health.

# Immune Globulins
IG and specific immune globulins, i.e., HBIG, TIG, HRIG, and varicella zoster immune globulin (VZIG), are indicated for use in order to prevent or modify certain diseases in specific circumstances.

# Im m u n e G lobulin fo r In tra m u scu la r U se
IG is given IM for preexposure prophylaxis against hepatitis A to travelers in areas where contact with potentially contaminated food and water is unavoidable. For travelers at risk for 2-3 months, a single IM dose of 0.02 ml/kg is recommended. For more prolonged travel 0.06 ml/kg should be given every 5 months. IG is also indicated for postexposure prophylaxis for close household and sexual contacts of persons with hepatitis A, staff and attendees of day care centers and household contacts of diapered children in day-care centers in which hepati tis A transmission is occurring, selected staff and clients of custodial institutions in which an outbreak is occurring, and co-workers of food handlers with hepatitis A. For such contacts a single dose of 0.02 ml/kg of IG is recommended as soon as possible after exposure. IG should be given within 2 weeks after exposure.
IG can be used to prevent or modify measles disease in susceptible contacts of persons with measles, especially those for whom measles vaccine is contraindicated, if given within 6 days after exposure. The recommended dose is 0.25 ml/kg (maximum dose = 15 ml). IG should not be used to control measles outbreaks.

# Im m u n e G lobulin fo r In tra ve n o u s U se
IG modified for IV administration may be given to prevent acute infections in patients with defective antibody synthesis or as prophylaxis against hepatitis A for patients for whom the IM preparation is contraindicated because of thrombocytopenia or disorders that can cause IM hemorrhage. ONLY IG MODIFIED FOR IN TRAVENO US U SE CAN BE GIVEN INTRAVE NOUSLY. The IV dose is 100 mg/kg, given slowly. The IV preparation is supplied in 50-m l vials containing 2.5 g of IG.

# H e p a titis B Im m u n e G lobulin
HBIG, alone or in combination with HB vaccine, is used for postexposure prophylaxis of HBV infection. For percutaneous or mucous membrane exposure to blood known to be HBsAg positive or from a bite by an HBV carrier, a single dose of HBIG (0.06 ml/kg or 5 ml for adults) should be given as soon as possible, and a series of three doses of HB vaccine begun within 1 week after exposure. Vaccine and HBIG may be given simultaneously, but in different sites.
For those who choose not to take HB vaccine, a second identical dose of HBIG should be given 1 month later. Following percutaneous exposure to blood from individuals at high risk of being HBsAg positive (such as persons with acute, unconfirmed viral hepatitis) or from patients at high risk of being infected with hepatitis B (such as male homosexuals, users of illicit IV drugs, and hemodialysis patients), IG should be given immediately to the exposed person as an IM dose of 0.06 ml/kg. Then serologic confirmation of the HBsAg status of the suspected high-risk patient should be obtained as soon as possible, and certainly within 7 days. If the suspected high-risk patient is HBsAg positive, the exposed person should immediately receive HBIG and hepatitis B vaccine according to the schedule above. The value of HBIG given beyond 7 days after exposure is unclear.
For homosexual exposure to HBsAg-positive males (known carriers or persons with acute cases), a single dose of HBIG should be given to susceptible contacts within 1 4 days after the last sexual exposure. Since HB vaccine is routinely recommended for male homosexuals, an HB vaccine series should be started within 7 days after HBIG administration.
For heterosexual exposures to persons with acute cases of hepatitis B, a single dose of HBIG (0.06 ml/kg or 5 ml for adults) should be given within 14 days of the last sexual contact. If the index case remains HBsAg positive at 3 months and exposure continues, the contact should be given a second dose of HBIG. If the index case becomes an HBV carrier (HGsAg positive for 6 months), the HB vaccine series should be given to the contact.

# Tetanus Im m u n e G lobulin
TIG is indicated in tetanus prophylaxis as part of the management of wounds other than clean, minor wounds in persons 1) whose previous tetanus toxoid immunization status is un known or uncertain, 2) who have received fewer than two previous tetanus toxoid doses, or 3) who have received only two previous tetanus toxoid doses and whose wound is more than 24 hours old. The currently recommended prophylactic dose for wounds of average severity is 2 5 0 units IM Td should be given at the same time but at a separate site.
A summary of the indications for active and passive immunization in the management of wounds is provided in Table 5.

# H um an R a b ie s Im m u n e G lobulin
Postexposure prophylaxis for rabies should always include HRIG with one exception: per sons who have been previously immunized with the recommended preexposure or postexpo sure regimens of HD CV or have been immunized with other types of rabies vaccines and have a history of documented adequate rabies antibody titer should not receive HRIG (Table 4). The recommended dose of HRIG is 20 Ill/kg body weight. If anatomically feasible, up to onehalf the dose of HRIG should be thoroughly infiltrated in the area around the wound, the rest should be administered IM.

# V a rice lla -Z o s te r Im m u n e G lobulin
Most adults (85%-95%) with negative or unknown histories of varicella disease (chickenpox) are likely to be immune. (Susceptibility rates for adults raised in some tropical areas, par ticularly remote areas, may be somewhat higher.) Rates of complications and death for immu nocompromised adults who contract varicella are likely to be substantially greater than for normal adults. After careful, individual evaluation, an immunocompromised patient who is be lieved to be susceptible and who has had significant exposure to varicella should receive VZIG to prevent complications. Significant exposure to a person with varicella includes household contact, close contact indoors of longer than 1 hour, sharing the same two-to four-bed hospital room, or prolonged, direct, face-to-face contact such as occurs with nurses or doctors who take care of the patient.
Chickenpox can be more severe in adults than in normal children. The decision to adminis ter VZIG to a normal adult should be made on an individual basis. The objective of VZIG use for normal adults is to modify rather than prevent illness in hopes of inducing lifelong immuni ty. When deciding whether to administer VZIG , the clinician should consider the patient's health status, the type of exposure, and the likelihood of previous infection. It is likely that adults who were older siblings in large families or whose children have had varicella are immune. If, after careful evaluation, a normal adult with significant exposure to varicella is be lieved to be susceptible, VZIG may be administered. Pregnant women and potentially su s ceptible hospital personnel should be evaluated in the same way as other adults. Supplies of V ZIG are limited, and indiscriminate administration of VZIG to normal adults would quickly ex haust supplies and prevent prophylaxis for known high-risk individuals. The cost of a five-vial adult dose is approximately $ 3 7 5 .
VZIG, available through some American Red C ro ss distribution centers (Appendix 5), is supplied in vials containing 1 25 units. W hereas 1 25 units/1 0 kg of body weight up to a m axi mum of 625 units generally is considered likely to prevent or modify varicella in normal adults, higher doses may be necessary for the immunocompromised adult. However, the ap propriate dose for immunocompromised adults has not been determined. VZIG should be ad ministered IM as directed by the manufacturer. While the duration of protection is unknown, it seems reasonable that protection should last for at least one half-life of the immune globulin, that is, approximately 3 weeks.

# Im m u n e G lo bu lin S id e E f f e c t s a n d A d v e rs e R e a c tio n s
Serious adverse effects have been rare from immune globulins administered as recommended.

# Im m u n e G lo bu lin P re ca u tio n s a n d C o n tra in d ica tio n s
Immune globulins, if needed, are not contraindicated for pregnant women. Except for the IV preparation of IG, immune globulins are prepared for IM use and should no t be given IV. The various preparations intended for IM use should not be given to patients with severe thrombocytopenia or other coagulation disorders that would ordinarily contraindicate IM in jections unless the expected benefits outweigh the risks.
Parenterally administered live-virus vaccines (e.g., MMR or other combinations) should be given at least 1 4 days before or at least 6 weeks, and preferably 3 months, after the adminis tration of immune globulins. If an immune globulin must be administered within 14 days after the administration of most live-virus vaccines, the vaccine should be administered again 3 months after the immune globulin is given. If the interval between vaccine receipt and immune globulin receipt is longer, the vaccine need not be readministered.
Preliminary data indicate that immune globulins do not interfere with the immune response to either O PV or yellow fever vaccine.
In Ju ly 1983 , a W HO Consultative Group reviewed data on both normal and specific immune globulins prepared from plasma collected mainly in the United States, including dona "Several other vaccines, toxoids, and immune globulins are licensed and available. These are noted in Appendix 3. In addition, the following antitoxins are licensed and available: (1) botulism antitoxin, trivalent (ABE) equine (distributed by C D C only), (2) tetanus antitoxin (equine), (3) diphtheria antitoxin (equine), and (4) rabies antitoxin (equine). Several vaccines and toxoids are in "Investigation of New Drug" (IND) status and available only through the Division of Host Factors, Center for Infectious Disease, CD C. These are: (1) pentavalent (ABCDE) botulinum toxoid, (2) eastern equine encephalitis (EEE) vaccine, (3) Venezualan equine encephalitis (VEE) vaccine, and (4) tularemia vaccine When any vaccine or toxoid is indicated during pregnancy, waiting until the second or the third trimester, when possible, is a reasonable precaution that minimizes concern about teratogenicity.
Persons immunocompromised because of immune deficiency diseases, leukemia, lymphoma or generalized m alignancy or immunosuppressed as a result of therapy with corticosteroids, alkylating drugs, antimetabolites or radiation.  Although a protective immune response to IPV in the immunocompromised individual cannot be assured, the vaccine is safe and some protection may result from its administration. 'Several other vaccines, toxoids, and immune globulins are licensed and available. These are noted in Appendix 3. In addition, the following antitoxins are licensed and available: (1) botulism antitoxin, trivalent (ABE) equine (distributed by CD C only), (2) tetanus antitoxin (equine), (3) diphtheria antitoxin (equine), and (4) rabies antitoxin (equine). Several vaccines and toxoids are in "Investigation of New Drug" (IND) status and available only through the Division of Host Factors, Center for Infectious Disease, CD C. These are: (1) pentavalent (ABCDE) botulinum toxoid, (2) eastern equine encephalitis (EEE) vaccine, (3) Venezualan equine encephalitis (VEE) vaccine, and (4) tularemia vaccine When any vaccine or toxoid is indicated during pregnancy, waiting until the second or the third trimester, when possible, is a reasonable precaution that minimizes concern about teratogenicity.

# L IV E -V IR U S A N D IN A C TIV A TED -V IR U S V A C C IN ES

# IN A C T IV A T ED -V IR U S V A C C IN ES
Persons immunocompromised because of immune deficiency diseases, leukemia, lymphoma or generalized m alignancy or immunosuppressed as a result of therapy with corticosteroids, alkylating drugs, antimetabolites or radiation.  "Several other vaccines, toxoids, and immune globulins are licensed and available. These are noted in Appendix 3. In addition, the following antitoxins are licensed and available: (1) botulism antitoxin, trivalent (ABE) equine (distributed by CD C only), (2) tetanus antitoxin (equine), (3) diphtheria antitoxin (equine), and (4) rabies antitoxin (equine). Several vaccines and toxoids are in "Investigation of New Drug" (IND) status and available only through the Division of Host Factors, Center for Infectious Disease, CD C. These are: (1) pentavalent (ABCDE) botulinum toxoid, (2) eastern equine encephalitis (EEE) vaccine, (3) Venezuelan equine encephalitis (VEE) vaccine, and (4) tularemia vaccine When any vaccine or toxoid is indicated during pregnancy, waiting until the second or the third trimester, when possible, is a reasonable precaution that minimizes concern about teratogenicity.  'Several other vaccines, toxoids, and immune globulins are licensed and available. These are noted in Appendix 3. In addition, the following antitoxins are licensed and available: (1) botulism antitoxin, trivalent (ABE) equine (distributed by C D C only), (2) tetanus antitoxin (equine), (3) diphtheria antitoxin (equine), and (4) rabies antitoxin (equine). Several vaccines and toxoids are in "Investigation of New D rug" (IND) status and available only through the Division of Host Factors, Center for Infectious Disease, CD C. These are: (1) pentavalent (ABCDE) botulinum toxoid, (2) eastern equine encephalitis (EEE) vaccine, (3) Venezualan equine encephalitis (VEE) vaccine, and (4) tularemia vaccine When any vaccine or toxoid is indicated during pregnancy, waiting until the second or the third trimester, when possible, is a reasonable precaution that minimizes concern about teratogenicity.
Persons immunocompromised because of immune deficiency diseases, leukemia, lymphoma or generalized m alignancy or immunosuppressed as a result of therapy with corticosteroids, alkylating drugs, antimetabolites or radiation Although preferable to be given with the 1 st dose of vaccine, can be given up to the 8th day after the 1 st dose of vaccine.
Varicella-zoster immune globulin (VZIG) '
Persons ^ 50 kg: 125 units/10kg IM; persons > 50 kg: 6 25 u n its"
Immunocompromised patients known or likely to be su s ceptible with close and pro longed exposure to a house hold contact case or to an infectious hospital staff member or hospital roommate.N O TE: Refer to text on specific vaccines or toxoids for further details on indications, contraindications, precautions, dosages, side effects, and adverse reactions, and special considerations and individual ACIP statements (see list of published ACIP statements in Appendix 2). ' Several other vaccines, toxoids, and immune globulins are licensed and available. These are noted in Appendix 3. In addition, the following antitoxins are licensed and available: (1) botulism antitoxin, trivalent (ABE) equine (distributed by CD C only), (2) tetanus antitoxin (equine), (3) diphtheria antitoxin (equine), and (4) rabies antitoxin (equine).
Several vaccines and toxoids are in "Investigation of New Drug" (IND) status and available only through the Division of Host Factors, Center for Infectious Disease, CDC. These are: (1) pentavalent (ABCDE) botulinum toxoid, (2) eastern equine encephalitis (EEE) vaccine, (3) Venezualan equine encephalitis (VEE) vaccine, and (4) tularemia vaccine When any vaccine or toxoid is indicated during pregnancy, waiting until the second or the third trimester, when possible, is a reasonable precaution that minimizes concern about teratogenicity.
Persons immunocompromised because of immune deficiency diseases, leukemia, lymphoma or generalized m alignancy or immunosuppressed as a result of therapy with corticosteroids, alkylating drugs, antimetabolites or radiation.

# MMWR 37 S
tions from homosexuals. The data indicated that although about 19.5 million 2-m l to 10-m l doses of immune globulin had been prepared during the preceding 4 years, no transmission of hepatitis B or any other infectious agents and no cases of A ID S had been reported in persons observed for 1-4 years after receiving immune globulin. Therefore, the Consultative Group confirmed that, at present, there is no evidence of risk attached to the use of normal or specif ic immune globulins prepared by the universally accepted methods ( 19).
R eferences 1. Immunization Practices Advisory Committee, General recommendations on immunizations. MMWR 1 9 8 3 ;3 2 :1 -8 , 13-7. 2. CD C. Rubella in hospitals -California. MMWR 1 9 8 3 ;3 2 :3 7 -9 . 3. Amler RW, Bloch AB, Orenstein WA, Bart K J, Turner PM Jr, Hinman AR. Imported m easles in the United States. JA M A 1 9 8 2 ;2 4 8 :2 1 2 9 -3 3 . 4. W eiss BP, Strassburg MA, Feeley J C . Tetanus and diphtheria immunity in an elderly population in Los Angeles County, Am J Pub Health 1 9 8 3 ;7 3 :8 0 2 -4 . 5. Crossley K, Irvine P, Warren JB , Lee BK, Mead K. Tetanus and diphtheria immunity in urban Min nesota adults. JA M A 1 9 7 9 :2 4 2 :2 2 9 8 -3 0 0 0 . 6. Ruben FL, Nagel J , Fireman P Antitoxin responses in the elderly to tetanus-diphtheria (Td) immuni zation. Am J Epidemiol 1978; 1 0 8 :1 4 5 -9 . 7. Ja c o b s RL, Lowe RS, Lanier BQ. Adverse reactions to tetanus toxoid. JA M A 1 9 8 2 :2 4 7 :40-2. 8. Herman J J , Radin R, Schneiderm an R. Allergic reactions to m easles (rubeola) vaccine in patients hy persensitive to egg protein. J Pediatr 1 983; 1 0 2 :1 9 6 -9 . 9. CD C. Postexposure prophylaxis of hepatitis B. MMWR 1 9 8 4 ;3 3 :2 8 5 -9 0 . 10. Turner G S, Nicholson KG, Tyrrell D A J, Akoi FY. Evaluation of a human diploid cell strain rabies va c cine: final report of a three year study of pre-exposure immunization. J Hyg 1 9 8 2 ;8 9 :1 0 1 -1 0 . 1 1. CD C. Field evaluations of pre-exposure use of human diploid cell rabies vaccine. MMWR 1 9 8 3 :3 2 :6 0 1 -3 . 12. C D C System ic allergic reactions following immunization with human diploid cell rabies vaccine.
MMWR 1 9 8 4 ;3 3 :1 8 5 -7 . 13. Bernard KW , Sm ith PW, Kader F J, Moran MJ. Neuroparalytic illness and human diploid cell rabies vaccine. JA M A 1 9 8 2 :2 4 8 :3 1 36 -8 14. Fedson DS, Chiarello LA. Previous hospital care and pneum ococcal bacteremia: importance for pneum ococcal immunization. Arch Intern Med 1 9 83; 1 4 3 :8 8 5 -9 . 1 5. DeStefano F, Goodman RA, Noble GR, et al. Sim ultaneous administration of influenza and pneumo coccal vaccines. JA M A 1 9 8 2 ;2 4 7 :2 5 5 1 -4. 16. Sem el JD , Seskind C. Severe febrile reaction to pneum ococcal vaccine. JA M A 1 9 7 9 :2 4 1 :1 792.   General recommendations on immunizations 1 9 8 3 :3 2 :1 -8 ,1 3 -7 Diphtheria, tetanus, and pertussis. 1 9 8 1 :3 0 :3 9 2 -9 6 ,4 0 1 -7 guidelines for vaccine prophylaxis and Erratum. 1 981 ;3 0 :4 2 0 other preventive measures M easles prevention 1 9 8 2 ;3 1 :2 1 7 -2 4 ,2 2 9 -3 1
Mumps vaccine 1 9 8 2 :3 1 :6 1 7 -2 0 ,6 2 5
Rubella prevention 1 9 8 4 :3 3 :3 0 1 -1 0 ,3 1 5 -8
Yellow fever vaccine 1 9 8 4 :3 2 :6 7 9 -8 2 ,6 8 7 -8
Poliomyelitis prevention 1 9 82;31 22-6,31 -4
Prevention and control of influenza- 1 9 8 4 :3 3 :2 5 3 -6 0 ,2 6 5 -6
Inactivated hepatitis B virus vaccine 1 9 8 2 :3 1 :3 1 7 -2 2 ,3 2 7 -8
Postexposure prophylaxis of hepatitis B 1 9 8 4 :3 3 :2 8 5 -9 0
Rabies prevention Supplem entary statement on rabies vaccine and serologic testing 1 9 8 1 ;3 0 :5 3 5 -6 Rabies 1 9 8 4 ;3 3 :3 9 3 -4 0 2 ,4 0 7 -8
Supplem entary statement on 1 9 8 2 :3 1 :2 7 9 -8 0 ,2 8 5 pre-exposure rabies prophylaxis by the intradermal route Cholera vaccine 1 9 7 8 :2 7 :1 7 3 -4 M eningococcal polysaccharide vaccine 1 9 7 8 :2 7 :3 2 7 -9
Plague vaccine 1 9 8 2 ;3 1 :3 0 1 -4
Update: Pneum ococcal polysaccharide vaccine 1 9 8 4 :3 3 :2 7 3 -6 ,8 1 usage -United States Typhoid vaccine 1 9 7 8 ;2 7 :2 3 1 -3 BCG vaccines 1 9 7 9 ;2 8 :2 4 1 -4
Immune globulins for protection against viral hepatitis 1 9 8 1 :3 0 :4 2 3 -8 ,4 3 3 -5
Varicella-zoster immune globulin for the prevention of chickenpox 1 9 8 4 :3 3 :8 4 -9 0 ,9 5 -1 0 0 'T h e Immunization Practices A dvisory Committee (ACIP) periodically reviews recommendations on v a c cination and prophylaxis. W hen recommendations are revised, they are published individually in the MMWR.
Each year influenza vaccine recommendations are reviewed and amended to reflect updated informa tion on influenza activity in the United States for the preceding influenza season and to provide inform a tion on the vaccine available for the upcoming influenza season. These recommendations are published in the MMWR annually, usually during June or July.           The Greater New York Blood Program 1 50 Am sterdam Ave. New York, NY 10023 (212) 5 7 0 -3 0 6 7 (212) 5 7 0 -3 0 6 8 (night) Am erican Red Cross Blood Services Northeastern New York Region Hackett Blvd. at Clara Barton Dr. Albany, N Y 12208 (518) 4 4 9 -5 0 2 0 (518) 4 6 2 -7 4 6 1 (518) 4 6 2 -6 9 6 4 (night) Am erican Red Cross Blood Services Greater Buffalo Chapter 786 Delaware Ave. Buffalo, NY 1 4209  (716) 8 8 6 -7 5 0 6 3 1 0 8  (314) 6 5 8 -2 0 0 0  (314) 6 5 8 -2 1 3 6 (

# IN A C T IV A TE D -V IR U S V A C C IN ES

# IN A C T IV A T E D -B A C T E R IA V A C C IN ES