From: Subject: General Recommendations on Immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP) Date: Sun, 30 May 2004 19:30:59 +0200 MIME-Version: 1.0 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: file://C:\Documents%20and%20Settings\Ferrando\Impostazioni%20locali\Temporary%20Internet%20Files\OLK54\caccavale%203.htm X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2800.1409 General Recommendations on Immunization: = Recommendations of the Advisory Committee on Immunization Practices = (ACIP) and the American Academy of Family Physicians (AAFP)

3D"

General Recommendations = on=20 Immunization

Recommendations of the Advisory Committee on = Immunization=20 Practices (ACIP) and the American Academy of Family Physicians=20 (AAFP)

Prepared by
William L. Atkinson, M.D.¹Larry = K.=20 Pickering, M.D.²Benjamin Schwartz,=20 M.D.³Bruce G. Weniger, M.D.³John K.=20 Iskander, M.D.³John C. Watson,=20 M.D.^4
1Immunization Services=20 Division²Office of the = Director³Epidemiology=20 and Surveillance Division
National Immunization=20 Program⁴Division of Parasitic Diseases
National = Center=20 for Infectious Diseases

The material in this report was prepared for publication = by the=20 National Immunization Program, Walter A. Orenstein, M.D., = Director; and=20 the Immunization Services Division, Lance E. Rodewald, M.D.,=20 Director.

Summary

This report is a revision of General Recommendations on = Immunization=20 and updates the 1994 statement by the Advisory Committee on = Immunization=20 Practices (ACIP) (CDC. General recommendations on = immunization:=20 recommendations of the Advisory Committee on Immunization = Practices=20 [ACIP]. MMWR 1994;43[No. RR-1]:1--38). The principal changes = include=20 expansion of the discussion of vaccination spacing and timing,=20 recommendations for vaccinations administered by an incorrect = route,=20 information regarding needle-free injection technology, = vaccination of=20 children adopted from countries outside the United States, timing = of=20 live-virus vaccination and tuberculosis screening, expansion of = the=20 discussion and tables of contraindications and precautions = regarding=20 vaccinations, and addition of a directory of immunization = resources. These=20 recommendations are not comprehensive for each vaccine. The most = recent=20 ACIP recommendations for each specific vaccine should be consulted = for=20 additional details. This report, ACIP recommendations for each = vaccine,=20 and other information regarding immunization can be accessed at = CDC's=20 National Immunization Program website at http://www.cdc.gov/nip = (accessed October=20 11, 2001).=20

Introduction

This report provides technical guidance regarding common = immunization=20 concerns for health-care providers who administer vaccines to = children,=20 adolescents, and adults. Vaccine recommendations are based on=20 characteristics of the immunobiologic product, scientific = knowledge=20 regarding the principles of active and passive immunization, the=20 epidemiology and burden of diseases (i.e., morbidity, mortality, = costs of=20 treatment, and loss of productivity), the safety of vaccines, and = the cost=20 analysis of preventive measures as judged by public health = officials and=20 specialists in clinical and preventive medicine.

Benefits and risks are associated with using all = immunobiologics. No=20 vaccine is completely safe or 100% effective. Benefits of = vaccination=20 include partial or complete protection against the consequences of = infection for the vaccinated person, as well as overall benefits = to=20 society as a whole. Benefits include protection from symptomatic = illness,=20 improved quality of life and productivity, and prevention of = death.=20 Societal benefits include creation and maintenance of herd = immunity=20 against communicable diseases, prevention of disease outbreaks, = and=20 reduction in health-care--related costs. Vaccination risks range = from=20 common, minor, and local adverse effects to rare, severe, and=20 life-threatening conditions. Thus, recommendations for = immunization=20 practices balance scientific evidence of benefits for each person = and to=20 society against the potential costs and risks of vaccination = programs.=20

Standards for child and adolescent immunization practices and = standards=20 for adult immunization practices (1,2)= =20 have been published to assist with implementing vaccination = programs and=20 maximizing their benefits. Any person or institution that provides = vaccination services should adopt these standards to improve = immunization=20 delivery and protect children, adolescents, and adults from=20 vaccine-preventable diseases.

To maximize the benefits of vaccination, this report provides = general=20 information regarding immunobiologics and provides practical = guidelines=20 concerning vaccine administration and technique. To minimize risk = from=20 vaccine administration, this report delineates situations that = warrant=20 precautions or contraindications to using a vaccine. These = recommendations=20 are intended for use in the United States because vaccine = availability and=20 use, as well as epidemiologic circumstances, differ in other = countries.=20 Individual circumstances might warrant deviations from these=20 recommendations. The relative balance of benefits and risks can = change as=20 diseases are controlled or eradicated. For example, because wild=20 poliovirus transmission has been interrupted in the United States = since=20 1979, the only indigenous cases of paralytic poliomyelitis = reported since=20 that time have been caused by live oral poliovirus vaccine (OPV). = In 1997,=20 to reduce the risk for vaccine-associated paralytic polio (VAPP),=20 increased use of inactivated poliovirus vaccine (IPV) was = recommended in=20 the United States (3)= .=20 In 1999, to eliminate the risk for VAPP, exclusive use of IPV was=20 recommended for routine vaccination in the United States (4)= ,=20 and OPV subsequently became unavailable for routine use. However, = because=20 of superior ability to induce intestinal immunity and to prevent = spread=20 among close contacts, OPV remains the vaccine of choice for areas = where=20 wild poliovirus is still present. Until worldwide eradication of=20 poliovirus is accomplished, continued vaccination of the U.S. = population=20 against poliovirus will be necessary.=20

Timing and Spacing of=20 Immunobiologics

General Principles for Vaccine Scheduling

Optimal response to a vaccine depends on multiple factors, = including=20 the nature of the vaccine and the age and immune status of the = recipient.=20 Recommendations for the age at which vaccines are administered are = influenced by age-specific risks for disease, age-specific risks = for=20 complications, ability of persons of a certain age to respond to = the=20 vaccine, and potential interference with the immune response by = passively=20 transferred maternal antibody. Vaccines are recommended for = members of the=20 youngest age group at risk for experiencing the disease for whom = efficacy=20 and safety have been demonstrated.

Certain products, including inactivated vaccines, toxoids, = recombinant=20 subunit and polysaccharide conjugate vaccines, require = administering=20 >2 doses for development of an adequate and persisting = antibody=20 response. Tetanus and diphtheria toxoids require periodic = reinforcement or=20 booster doses to maintain protective antibody concentrations. = Unconjugated=20 polysaccharide vaccines do not induce T-cell memory, and booster = doses are=20 not expected to produce substantially increased protection. = Conjugation=20 with a protein carrier improves the effectiveness of = polysaccharide=20 vaccines by inducing T-cell--dependent immunologic function. = Vaccines that=20 stimulate both cell-mediated immunity and neutralizing antibodies = (e.g.,=20 live attenuated virus vaccines) usually can induce prolonged, = often=20 lifelong immunity, even if antibody titers decline as time = progresses=20 (5). Subsequent exposure to infection usually does not lead = to=20 viremia but to a rapid anamnestic antibody response.

Approximately 90%--95% of recipients of a single dose of a = parenterally=20 administered live vaccine at the recommended age (i.e., measles, = mumps,=20 rubella [MMR], varicella, and yellow fever), develop protective = antibody=20 within 2 weeks of the dose. However, because a limited proportion = of=20 recipients (<5%) of MMR vaccine fail to respond to one = dose, a=20 second dose is recommended to provide another opportunity to = develop=20 immunity (6)= .=20 The majority of persons who fail to respond to the first dose of = MMR=20 respond to a second dose (7). Similarly, approximately 20% = of=20 persons aged >13 years fail to respond to the first dose = of=20 varicella vaccine; 99% of recipients seroconvert after two doses = (8)= .=20

The recommended childhood vaccination schedule is revised = annually and=20 is published each January. Recommendations for vaccination of = adolescents=20 and adults are revised less frequently, except for influenza = vaccine=20 recommendations, which are published annually. Physicians and = other=20 health-care providers should always ensure that they are following = the=20 most up-to-date schedules, which are available from CDC's National = Immunization Program website at http://www.cdc.gov/nip = (accessed October=20 11, 2001).=20

Spacing of Multiple Doses of the Same Antigen

Vaccination providers are encouraged to adhere as closely as = possible=20 to the recommended childhood immunization schedule. Clinical = studies have=20 reported that recommended ages and intervals between doses of = multidose=20 antigens provide optimal protection or have the best evidence of = efficacy.=20 Recommended vaccines and recommended intervals between doses are = provided=20 in this report (Table= =20 1).

In certain circumstances, administering doses of a multidose = vaccine at=20 shorter than the recommended intervals might be necessary. This = can occur=20 when a person is behind schedule and needs to be brought = up-to-date as=20 quickly as possible or when international travel is impending. In = these=20 situations, an accelerated schedule can be used that uses = intervals=20 between doses shorter than those recommended for routine = vaccination.=20 Although the effectiveness of all accelerated schedules has not = been=20 evaluated in clinical trials, the Advisory Committee on = Immunization=20 Practices (ACIP) believes that the immune response when = accelerated=20 intervals are used is acceptable and will lead to adequate = protection. The=20 accelerated, or minimum, intervals and ages that can be used for=20 scheduling catch-up vaccinations is provided in this report (Table= =20 1). Vaccine doses should not be administered at intervals less = than=20 these minimum intervals or earlier than the minimum age.*

In clinical practice, vaccine doses occasionally are = administered at=20 intervals less than the minimum interval or at ages younger than = the=20 minimum age. Doses administered too close together or at too young = an age=20 can lead to a suboptimal immune response. However, administering a = dose a=20 limited number of days earlier than the minimum interval or age is = unlikely to have a substantially negative effect on the immune = response to=20 that dose. Therefore, ACIP recommends that vaccine doses = administered=20 <4 days before the minimum interval or age be counted as = valid.⁼⁸⁶ However, because of its unique schedule, this = recommendation does not apply to rabies vaccine (9)= .=20 Doses administered >5 days earlier than the minimum = interval or=20 age should not be counted as valid doses and should be repeated as = age-appropriate. The repeat dose should be spaced after the = invalid dose=20 by the recommended minimum interval as provided in this report (Table= =20 1). For example, if Haemophilus influenzae type b (Hib) = doses=20 one and two were administered only 2 weeks apart, dose two is = invalid and=20 should be repeated. The repeat dose should be administered = >4=20 weeks after the invalid (second) dose. The repeat dose would be = counted as=20 the second valid dose. Doses administered >5 days before = the=20 minimum age should be repeated on or after the child reaches the = minimum=20 age and >4 weeks after the invalid dose. For example, if = varicella vaccine were administered at age 10 months, the repeat = dose=20 would be administered no earlier than the child's first birthday. =

Certain vaccines produce increased rates of local or systemic = reactions=20 in certain recipients when administered too frequently (e.g., = adult=20 tetanus-diphtheria toxoid [Td], pediatric diphtheria-tetanus = toxoid [DT],=20 and tetanus toxoid) (10,11). Such reactions are thought to = result=20 from the formation of antigen-antibody complexes. Optimal record = keeping,=20 maintaining patient histories, and adhering to recommended = schedules can=20 decrease the incidence of such reactions without adversely = affecting=20 immunity.=20

Simultaneous Administration

Experimental evidence and extensive clinical experience have=20 strengthened the scientific basis for administering vaccines=20 simultaneously (i.e., during the same office visit, not combined = in the=20 same syringe). Simultaneously administering all vaccines for which = a=20 person is eligible is critical, including for childhood = vaccination=20 programs, because simultaneous administration increases the = probability=20 that a child will be fully immunized at the appropriate age. A = study=20 conducted during a measles outbreak demonstrated that = approximately one=20 third of measles cases among unvaccinated but vaccine-eligible = preschool=20 children could have been prevented if MMR had been administered at = the=20 same visit when another vaccine was administered (12). = Simultaneous=20 administration also is critical when preparing for foreign travel = and if=20 uncertainty exists that a person will return for further doses of = vaccine.=20

Simultaneously administering the most widely used live and = inactivated=20 vaccines have produced seroconversion rates and rates of adverse = reactions=20 similar to those observed when the vaccines are administered = separately=20 (13--16). Routinely administering all vaccines = simultaneously is=20 recommended for children who are the appropriate age to receive = them and=20 for whom no specific contraindications exist at the time of the = visit.=20 Administering combined MMR vaccine yields results similar to = administering=20 individual measles, mumps, and rubella vaccines at different = sites.=20 Therefore, no medical basis exists for administering these = vaccines=20 separately for routine vaccination instead of the preferred MMR = combined=20 vaccine (6)= .=20 Administering separate antigens would result in a delay in = protection for=20 the deferred components. Response to MMR and varicella vaccines=20 administered on the same day is identical to vaccines administered = a month=20 apart (17). No evidence exists that OPV interferes with=20 parenterally administered live vaccines. OPV can be administered=20 simultaneously or at any interval before or after parenteral live=20 vaccines. No data exist regarding the immunogenicity of oral Ty21a = typhoid=20 vaccine when administered concurrently or within 30 days of live = virus=20 vaccines. In the absence of such data, if typhoid vaccination is=20 warranted, it should not be delayed because of administration of = virus=20 vaccines (18= ).=20

Simultaneously administering pneumococcal polysaccharide = vaccine and=20 inactivated influenza vaccine elicits a satisfactory antibody = response=20 without increasing the incidence or severity of adverse reactions=20 (19). Simultaneously administering pneumococcal = polysaccharide=20 vaccine and inactivated influenza vaccine is strongly recommended = for all=20 persons for whom both vaccines are indicated.

Hepatitis B vaccine administered with yellow fever vaccine is = as safe=20 and immunogenic as when these vaccines are administered separately = (20). Measles and yellow fever vaccines have been = administered=20 safely at the same visit and without reduction of immunogenicity = of each=20 of the components (21,22= ).=20

Depending on vaccines administered in the first year of life, = children=20 aged 12--15 months can receive <7 injections during a = single=20 visit (MMR, varicella, Hib, pneumococcal conjugate, diphtheria and = tetanus=20 toxoids and acellular pertussis [DTaP], IPV, and hepatitis B = vaccines). To=20 help reduce the number of injections at the 12--15-month visit, = the IPV=20 primary series can be completed before the child's first birthday. = MMR and=20 varicella vaccines should be administered at the same visit that = occurs as=20 soon as possible on or after the first birthday. The majority of = children=20 aged 1 year who have received two (polyribosylribitol=20 phosphate-meningococcal outer membrane protein [PRP-OMP]) or three = (PRP-tetanus [PRP-T], diphtheria CRM₁₉₇ [CRM, = cross-reactive=20 material] protein conjugate [HbOC]) prior doses of Hib vaccine, = and three=20 prior doses of DTaP and pneumococcal conjugate vaccine have = developed=20 protection (23,24= ).=20 The third (PRP-OMP) or fourth (PRP-T, HbOC) dose of the Hib = series, and=20 the fourth doses of DTaP and pneumococcal conjugate vaccines are = critical=20 in boosting antibody titer and ensuring continued protection = (24--26= ).=20 However, the booster dose of the Hib or pneumococcal conjugate = series can=20 be deferred until ages 15--18 months for children who are likely = to return=20 for future visits. The fourth dose of DTaP is recommended to be=20 administered at ages 15--18 months, but can be administered as = early as=20 age 12 months under certain circumstances (25= ).=20 For infants at low risk for infection with hepatitis B virus = (i.e., the=20 mother tested negative for hepatitis B surface antigen [HBsAg] at = the time=20 of delivery and the child is not of Asian or Pacific Islander = descent),=20 the hepatitis B vaccine series can be completed at any time during = ages=20 6--18 months. Recommended spacing of doses should be maintained = (Table= =20 1).

Use of combination vaccines can reduce the number of injections = required at an office visit. Licensed combination vaccines can be = used=20 whenever any components of the combination are indicated and its = other=20 components are not contraindicated. Use of licensed combination = vaccines=20 is preferred over separate injection of their equivalent component = vaccines (27= ).=20 Only combination vaccines approved by the Food and Drug = Administration=20 (FDA) should be used. Individual vaccines must never be mixed in = the same=20 syringe unless they are specifically approved for mixing by FDA. = Only one=20 vaccine (DTaP and PRP-T Hib vaccine, marketed as = TriHIBit^=AE=20 [manufactured by Aventis Pasteur]) is FDA-approved for mixing in = the same=20 syringe. This vaccine should not be used for primary vaccination = in=20 infants aged 2, 4, and 6 months, but it can be used as a booster = after any=20 Hib vaccine.=20

Nonsimultaneous Administration

Inactivated vaccines do not interfere with the immune response = to other=20 inactivated vaccines or to live vaccines. An inactivated vaccine = can be=20 administered either simultaneously or at any time before or after = a=20 different inactivated vaccine or live vaccine (Table= =20 2).

The immune response to one live-virus vaccine might be impaired = if=20 administered within 30 days of another live-virus vaccine = (28,29).=20 Data are limited concerning interference between live vaccines. In = a study=20 conducted in two U.S. health maintenance organizations, persons = who=20 received varicella vaccine <30 days after MMR vaccination had = an=20 increased risk for varicella vaccine failure (i.e., varicella = disease in a=20 vaccinated person) of 2.5-fold compared with those who received = varicella=20 vaccine before or >30 days after MMR (30= ).=20 In contrast, a 1999 study determined that the response to yellow = fever=20 vaccine is not affected by monovalent measles vaccine administered = 1--27=20 days earlier (21). The effect of nonsimultaneously = administering=20 rubella, mumps, varicella, and yellow fever vaccines is unknown. =

To minimize the potential risk for interference, parenterally=20 administered live vaccines not administered on the same day should = be=20 administered >4 weeks apart whenever possible (Table= =20 2). If parenterally administered live vaccines are separated = by <4=20 weeks, the vaccine administered second should not be counted as a = valid=20 dose and should be repeated. The repeat dose should be = administered=20 >4 weeks after the last, invalid dose. Yellow fever = vaccine can=20 be administered at any time after single-antigen measles vaccine. = Ty21a=20 typhoid vaccine and parenteral live vaccines (i.e., MMR, = varicella, yellow=20 fever) can be administered simultaneously or at any interval = before or=20 after each other, if indicated.=20

Spacing of Antibody-Containing Products and Vaccines =

Live Vaccines

Ty21a typhoid and yellow fever vaccines can be administered at = any time=20 before, concurrent with, or after administering any immune = globulin or=20 hyperimmune globulin (e.g., hepatitis B immune globulin and rabies = immune=20 globulin). Blood (e.g., whole blood, packed red blood cells, and = plasma)=20 and other antibody-containing blood products (e.g., immune = globulin,=20 hyperimmune globulin, and intravenous immune globulin [IGIV]) can = inhibit=20 the immune response to measles and rubella vaccines for = >3=20 months (31,32). The effect of blood and immune globulin=20 preparations on the response to mumps and varicella vaccines is = unknown,=20 but commercial immune globulin preparations contain antibodies to = these=20 viruses. Blood products available in the United States are = unlikely to=20 contain a substantial amount of antibody to yellow fever vaccine = virus.=20 The length of time that interference with parenteral live = vaccination=20 (except yellow fever vaccine) can persist after the = antibody-containing=20 product is a function of the amount of antigen-specific antibody = contained=20 in the product (31--33). Therefore, after an = antibody-containing=20 product is received, parenteral live vaccines (except yellow fever = vaccine) should be delayed until the passive antibody has degraded = (Table= =20 3). Recommended intervals between receipt of various blood = products=20 and measles-containing vaccine and varicella vaccine are listed in = this=20 report (Table= =20 4). If a dose of parenteral live-virus vaccine (except yellow = fever=20 vaccine) is administered after an antibody-containing product but = at an=20 interval shorter than recommended in this report, the vaccine dose = should=20 be repeated unless serologic testing indicates a response to the = vaccine.=20 The repeat dose or serologic testing should be performed after the = interval indicated for the antibody-containing product (Table= =20 4).

Although passively acquired antibodies can interfere with the = response=20 to rubella vaccine, the low dose of anti-Rho(D) globulin = administered to=20 postpartum women has not been demonstrated to reduce the response = to the=20 RA27/3 strain rubella vaccine (34). Because of the = importance of=20 rubella immunity among childbearing-age women (6,35= ),=20 the postpartum vaccination of rubella-susceptible women with = rubella or=20 MMR vaccine should not be delayed because of receipt of = anti-Rho(D)=20 globulin or any other blood product during the last trimester of = pregnancy=20 or at delivery. These women should be vaccinated immediately after = delivery and, if possible, tested >3 months later to = ensure=20 immunity to rubella and, if necessary, to measles (6)= .=20

Interference can occur if administering an antibody-containing = product=20 becomes necessary after administering MMR, its individual = components, or=20 varicella vaccine. Usually, vaccine virus replication and = stimulation of=20 immunity will occur 1--2 weeks after vaccination. Thus, if the = interval=20 between administering any of these vaccines and subsequent = administration=20 of an antibody-containing product is <14 days, vaccination = should be=20 repeated after the recommended interval (Table= s=20 3,4= ),=20 unless serologic testing indicates that antibodies were produced. =

A humanized mouse monoclonal antibody product (palivizumab) is=20 available for prevention of respiratory syncytial virus infection = among=20 infants and young children. This product contains only antibody to = respiratory syncytial virus; hence, it will not interfere with = immune=20 response to live or inactivated vaccines.

Inactivated Vaccines

Antibody-containing products interact less with inactivated = vaccines,=20 toxoids, recombinant subunit, and polysaccharide vaccines than = with live=20 vaccines (36). Therefore, administering inactivated = vaccines and=20 toxoids either simultaneously with or at any interval before or = after=20 receipt of an antibody-containing product should not substantially = impair=20 development of a protective antibody response (Table= =20 3). The vaccine or toxoid and antibody preparation should be=20 administered at different sites by using the standard recommended = dose.=20 Increasing the vaccine dose volume or number of vaccinations is = not=20 indicated or recommended.=20

Interchangeability of Vaccines from Different = Manufacturers=20

Numerous vaccines are available from different ma00048610.h= tmnufacturers,=20 and these vaccines usually are not identical in antigen content or = amount=20 or method of formulation. Manufacturers use different production=20 processes, and their products might contain different = concentrations of=20 antigen per dose or different stabilizers or preservatives.

Available data indicate that infants who receive sequential = doses of=20 different Hib conjugate, hepatitis B, and hepatitis A vaccines = produce a=20 satisfactory antibody response after a complete primary series=20 (37--40). All brands of Hib conjugate, hepatitis = B,^=A7 and=20 hepatitis A vaccines are interchangeable within their respective = series.=20 If different brands of Hib conjugate vaccine are administered, a = total of=20 three doses is considered adequate for the primary series among = infants.=20 After completing the primary series, any Hib conjugate vaccine can = be used=20 for the booster dose at ages 12--18 months.

Data are limited regarding the safety, immunogenicity, and = efficacy of=20 using acellular pertussis (as DTaP) vaccines from different = manufacturers=20 for successive doses of the pertussis series. Available data from = one=20 study indicate that, for the first three doses of the DTaP series, = one or=20 two doses of Tripedia^=AE (manufactured by Aventis = Pasteur)=20 followed by Infanrix^=AE (manufactured by = GlaxoSmithKline) for the=20 remaining doses(s) is comparable to three doses of Tripedia with = regard to=20 immunogenicity, as measured by antibodies to diphtheria, tetanus, = and=20 pertussis toxoid, and filamentous hemagglutinin (41). = However, in=20 the absence of a clear serologic correlate of protection for = pertussis,=20 the relevance of these immunogenicity data for protection against=20 pertussis is unknown. Whenever feasible, the same brand of DTaP = vaccine=20 should be used for all doses of the vaccination series; however,=20 vaccination providers might not know or have available the type of = DTaP=20 vaccine previously administered to a child. In this situation, any = DTaP=20 vaccine should be used to continue or complete the series. = Vaccination=20 should not be deferred because the brand used for previous doses = is not=20 available or is unknown (25,42= ).=20

Lapsed Vaccination Schedule

Vaccination providers are encouraged to administer vaccines as = close to=20 the recommended intervals as possible. However, = longer-than-recommended=20 intervals between doses do not reduce final antibody = concentrations,=20 although protection might not be attained until the recommended = number of=20 doses has been administered. An interruption in the vaccination = schedule=20 does not require restarting the entire series of a vaccine or = toxoid or=20 the addition of extra doses.=20

Unknown or Uncertain Vaccination Status

Vaccination providers frequently encounter persons who do not = have=20 adequate documentation of vaccinations. Providers should only = accept=20 written, dated records as evidence of vaccination. With the = exception of=20 pneumococcal polysaccharide vaccine (43= ),=20 self-reported doses of vaccine without written documentation = should not be=20 accepted. Although vaccinations should not be postponed if records = cannot=20 be found, an attempt to locate missing records should be made by=20 contacting previous health-care providers and searching for a = personally=20 held record. If records cannot be located, these persons should be = considered susceptible and should be started on the = age-appropriate=20 vaccination schedule. Serologic testing for immunity is an = alternative to=20 vaccination for certain antigens (e.g., measles, mumps, rubella,=20 varicella, tetanus, diphtheria, hepatitis A, hepatitis B, and = poliovirus)=20 (see Vaccination of Internationally Adopted Children).=20

Contraindications and=20 Precautions

Contraindications and precautions to vaccination dictate = circumstances=20 when vaccines will not be administered. The majority of = contraindications=20 and precautions are temporary, and the vaccination can be = administered=20 later. A contraindication is a condition in a recipient that = increases the=20 risk for a serious adverse reaction. A vaccine will not be = administered=20 when a contraindication is present. For example, administering = influenza=20 vaccine to a person with an anaphylactic allergy to egg protein = could=20 cause serious illness in or death of the recipient.

National standards for pediatric immunization practices have = been=20 established and include true contraindications and precautions to=20 vaccination (Table= =20 5) (1)= .=20 The only true contraindication applicable to all vaccines is a = history of=20 a severe allergic reaction after a prior dose of vaccine or to a = vaccine=20 constituent (unless the recipient has been desensitized). Severely = immunocompromised persons should not receive live vaccines. = Children who=20 experience an encephalopathy <7 days after = administration of a=20 previous dose of diphtheria and tetanus toxoids and whole-cell = pertussis=20 vaccine (DTP) or DTaP not attributable to another identifiable = cause=20 should not receive further doses of a vaccine that contains = pertussis.=20 Because of the theoretical risk to the fetus, women known to be = pregnant=20 should not receive live attenuated virus vaccines (see Vaccination = During=20 Pregnancy).

A precaution is a condition in a recipient that might increase = the risk=20 for a serious adverse reaction or that might compromise the = ability of the=20 vaccine to produce immunity (e.g., administering measles vaccine = to a=20 person with passive immunity to measles from a blood transfusion). = Injury=20 could result, or a person might experience a more severe reaction = to the=20 vaccine than would have otherwise been expected; however, the risk = for=20 this happening is less than expected with a contraindication. = Under normal=20 circumstances, vaccinations should be deferred when a precaution = is=20 present. However, a vaccination might be indicated in the presence = of a=20 precaution because the benefit of protection from the vaccine = outweighs=20 the risk for an adverse reaction. For example, caution should be = exercised=20 in vaccinating a child with DTaP who, within 48 hours of receipt = of a=20 prior dose of DTP or DTaP, experienced fever >40.5C = (105F); had=20 persistent, inconsolable crying for >3 hours; collapsed = or=20 experienced a shock-like state; or had a seizure <3 days = after=20 receiving the previous dose of DTP or DTaP. However, administering = a=20 pertussis-containing vaccine should be considered if the risk for=20 pertussis is increased (e.g., during a pertussis outbreak) (25= ).=20 The presence of a moderate or severe acute illness with or without = a fever=20 is a precaution to administration of all vaccines. Other = precautions are=20 listed in this report (Table= =20 5).

Physicians and other health-care providers might = inappropriately=20 consider certain conditions or circumstances to be true = contraindications=20 or precautions to vaccination. This misconception results in = missed=20 opportunities to administer recommended vaccines (44). = Likewise,=20 physicians and other health-care providers might fail to = understand what=20 constitutes a true contraindication or precaution and might = administer a=20 vaccine when it should be withheld. This practice can result in an = increased risk for an adverse reaction to the vaccine. Conditions = often=20 inappropriately regarded as contraindications to vaccination are = listed in=20 this report (Table= =20 5). Among the most common are diarrhea and minor = upper-respiratory=20 tract illnesses (including otitis media) with or without fever, = mild to=20 moderate local reactions to a previous dose of vaccine, current=20 antimicrobial therapy, and the convalescent phase of an acute = illness.=20

The decision to administer or delay vaccination because of a = current or=20 recent acute illness depends on the severity of symptoms and the = etiology=20 of the disease. All vaccines can be administered to persons with = minor=20 acute illness (e.g., diarrhea or mild upper-respiratory tract = infection=20 with or without fever). Studies indicate that failure to vaccinate = children with minor illnesses can seriously impede vaccination = efforts=20 (45--47). Among persons whose compliance with medical care = cannot=20 be ensured, use of every opportunity to provide appropriate = vaccinations=20 is critical.

The majority of studies support the safety and efficacy of = vaccinating=20 persons who have mild illness (48--50). For example, in the = United=20 States, >97% of children with mild illnesses produced measles = antibody=20 after vaccination (51). Only one limited study has reported = a lower=20 rate of seroconversion (79%) to the measles component of MMR = vaccine among=20 children with minor, afebrile upper-respiratory tract infections=20 (52). Therefore, vaccination should not be delayed because = of the=20 presence of mild respiratory tract illness or other acute illness = with or=20 without fever.

Persons with moderate or severe acute illness should be = vaccinated as=20 soon as they have recovered from the acute phase of the illness. = This=20 precaution avoids superimposing adverse effects of the vaccine on = the=20 underlying illness or mistakenly attributing a manifestation of = the=20 underlying illness to the vaccine.

Routine physical examinations and measuring temperatures are = not=20 prerequisites for vaccinating infants and children who appear to = be=20 healthy. Asking the parent or guardian if the child is ill and = then=20 postponing vaccination for those with moderate to severe illness, = or=20 proceeding with vaccination if no contraindications exist, are = appropriate=20 procedures in childhood immunization programs.

A family history of seizures or other central nervous system = disorders=20 is not a contraindication to administration of pertussis or other=20 vaccines. However, delaying pertussis vaccination for infants and = children=20 with a history of previous seizures until the child's neurologic = status=20 has been assessed is prudent. Pertussis vaccine should not be = administered=20 to infants with evolving neurologic conditions until a treatment = regimen=20 has been established and the condition has stabilized (25= ).=20

Vaccine = Administration=20

Infection Control and Sterile Technique

Persons administering vaccines should follow necessary = precautions to=20 minimize risk for spreading disease. Hands should be washed with = soap and=20 water or cleansed with an alcohol-based waterless antiseptic hand = rub=20 between each patient contact. Gloves are not required when = administering=20 vaccinations, unless persons administering vaccinations are likely = to come=20 into contact with potentially infectious body fluids or have open = lesions=20 on their hands. Syringes and needles used for injections must be = sterile=20 and disposable to minimize the risk of contamination. A separate = needle=20 and syringe should be used for each injection. Changing needles = between=20 drawing vaccine from a vial and injecting it into a recipient is=20 unnecessary. Different vaccines should never be mixed in the same = syringe=20 unless specifically licensed for such use.

Disposable needles and syringes should be discarded in labeled, = puncture-proof containers to prevent inadvertent needle-stick = injury or=20 reuse. Safety needles or needle-free injection devices also can = reduce the=20 risk for injury and should be used whenever available (see = Occupational=20 Safety Regulations).=20

Recommended Routes of Injection and Needle Length

Routes of administration are recommended by the manufacturer = for each=20 immunobiologic. Deviation from the recommended route of = administration=20 might reduce vaccine efficacy (53,54) or increase local = adverse=20 reactions (55--57). Injectable immunobiologics should be=20 administered where the likelihood of local, neural, vascular, or = tissue=20 injury is limited. Vaccines containing adjuvants should be = injected into=20 the muscle mass; when administered subcutaneously or = intradermally, they=20 can cause local irritation, induration, skin discoloration, = inflammation,=20 and granuloma formation.

Subcutaneous Injections

Subcutaneous injections usually are administered at a 45-degree = angle=20 into the thigh of infants aged <12 months and in the = upper-outer=20 triceps area of persons aged >12 months. Subcutaneous = injections=20 can be administered into the upper-outer triceps area of an = infant, if=20 necessary. A 5/8-inch, 23--25-gauge needle should be inserted into = the=20 subcutaneous tissue.

Intramuscular Injections

Intramuscular injections are administered at a 90-degree angle = into the=20 anterolateral aspect of the thigh or the deltoid muscle of the = upper arm.=20 The buttock should not be used for administration of vaccines or = toxoids=20 because of the potential risk of injury to the sciatic nerve = (58).=20 In addition, injection into the buttock has been associated with = decreased=20 immunogenicity of hepatitis B and rabies vaccines in adults, = presumably=20 because of inadvertent subcutaneous injection or injection into = deep fat=20 tissue (53,59).

For all intramuscular injections, the needle should be long = enough to=20 reach the muscle mass and prevent vaccine from seeping into = subcutaneous=20 tissue, but not so long as to involve underlying nerves and blood = vessels=20 or bone (54,60--62). Vaccinators should be familiar with = the=20 anatomy of the area into which they are injecting vaccine. An = individual=20 decision on needle size and site of injection must be made for = each person=20 on the basis of age, the volume of the material to be = administered, the=20 size of the muscle, and the depth below the muscle surface into = which the=20 material is to be injected.

Although certain vaccination specialists advocate aspiration = (i.e., the=20 syringe plunger pulled back before injection), no data exist to = document=20 the necessity for this procedure. If aspiration results in blood = in the=20 needle hub, the needle should be withdrawn and a new site should = be=20 selected.

Infants (persons aged <12 months). Among the = majority=20 of infants, the anterolateral aspect of the thigh provides the = largest=20 muscle mass and is therefore the recommended site for injection. = For the=20 majority of infants, a 7/8--1-inch, 22--25-gauge needle is = sufficient to=20 penetrate muscle in the infant's thigh.

Toddlers and Older Children (persons aged >12=20 months--18 years). The deltoid muscle can be used if the = muscle=20 mass is adequate. The needle size can range from 22 to 25 gauge = and from=20 7/8 to 1=BC inches, on the basis of the size of the muscle. For = toddlers,=20 the anterolateral thigh can be used, but the needle should be = longer,=20 usually 1 inch.

Adults (persons aged >18 years). For adults, = the=20 deltoid muscle is recommended for routine intramuscular = vaccinations. The=20 anterolateral thigh can be used. The suggested needle size is = 1--1=BD inches=20 and 22--25 gauge.

Intradermal Injections

Intradermal injections are usually administered on the volar = surface of=20 the forearm. With the bevel facing upwards, a 3/8--3/4-inch, = 25--27-gauge=20 needle can be inserted into the epidermis at an angle parallel to = the long=20 axis of the forearm. The needle should be inserted so that the = entire=20 bevel penetrates the skin and the injected solution raises a small = bleb.=20 Because of the small amounts of antigen used in intradermal = vaccinations,=20 care must be taken not to inject the vaccine subcutaneously = because it can=20 result in a suboptimal immunologic response.=20

Multiple Vaccinations

If >2 vaccine preparations are administered or if = vaccine and=20 an immune globulin preparation are administered simultaneously, = each=20 preparation should be administered at a different anatomic site. = If=20 >2 injections must be administered in a single limb, the = thigh=20 is usually the preferred site because of the greater muscle mass; = the=20 injections should be sufficiently separated (i.e., >1 = inch) so=20 that any local reactions can be differentiated (55,63). For = older=20 children and adults, the deltoid muscle can be used for multiple=20 intramuscular injections, if necessary. The location of each = injection=20 should documented in the person's medical record.=20

Jet Injection

Jet injectors (JIs) are needle-free devices that drive liquid=20 medication through a nozzle orifice, creating a narrow stream = under high=20 pressure that penetrates skin to deliver a drug or vaccine into=20 intradermal, subcutaneous, or intramuscular tissues = (64,65).=20 Increasing attention to JI technology as an alternative to = conventional=20 needle injection has resulted from recent efforts to reduce the = frequency=20 of needle-stick injuries to health-care workers (66) and to = overcome the improper reuse and other drawbacks of needles and = syringes in=20 economically developing countries (67--69). JIs have been = reported=20 safe and effective in administering different live and inactivated = vaccines for viral and bacterial diseases (69). The immune=20 responses generated are usually equivalent to, and occasionally = greater=20 than, those induced by needle injection. However, local reactions = or=20 injury (e.g., redness, induration, pain, blood, and ecchymosis at = the=20 injection site) can be more frequent for vaccines delivered by JIs = compared with needle injection (65,69).

Certain JIs were developed for situations in which substantial = numbers=20 of persons must be vaccinated rapidly, but personnel or supplies = are=20 insufficient to do so with conventional needle injection. Such=20 high-workload devices vaccinate consecutive patients from the same = nozzle=20 orifice, fluid pathway, and dose chamber, which is refilled = automatically=20 from attached vials containing <50 doses each. Since the = 1950s,=20 these devices have been used extensively among military recruits = and for=20 mass vaccination campaigns for disease control and eradication=20 (64). An outbreak of hepatitis B among patients receiving=20 injections from a multiple-use--nozzle JI was documented (70,71<= /I>),=20 and subsequent laboratory, field, and animal studies demonstrated = that=20 such devices could become contaminated with blood = (69,72,73).

No U.S.-licensed, high-workload vaccination devices of = unquestioned=20 safety are available to vaccination programs. Efforts are under = way for=20 the research and development of new high-workload JIs using=20 disposable-cartridge technology that avoids reuse of any = unsterilized=20 components having contact with the medication fluid pathway or = patient's=20 blood. Until such devices become licensed and available, the use = of=20 existing multiple-use--nozzle JIs should be limited. Use can be = considered=20 when the theoretical risk for bloodborne disease transmission is=20 outweighed by the benefits of rapid vaccination with limited = personnel in=20 responding to serious disease threats (e.g., pandemic influenza or = bioterrorism event), and by any competing risks of iatrogenic or=20 occupational infections resulting from conventional needles and = syringes.=20 Before such emergency use of multiple-use--nozzle JIs, health-care = workers=20 should consult with local, state, national, or international = health=20 agencies or organizations that have experience in their use.

In the 1990s, a new generation of low-workload JIs were = introduced with=20 disposable cartridges serving as dose chambers and nozzle = (69).=20 With the provision of a new sterile cartridge for each patient and = other=20 correct use, these devices avoid the safety concerns described = previously=20 for multiple-use--nozzle devices. They can be used in accordance = with=20 their labeling for intradermal, subcutaneous, or intramuscular=20 administration.=20
Methods for Alleviating Discomfort and Pain Associated with = Vaccination

Comfort measures and distraction techniques (e.g., playing = music or=20 pretending to blow away the pain) might help children cope with = the=20 discomfort associated with vaccination. Pretreatment (30-60 = minutes before=20 injection) with 5% topical lidocaine-prilocaine emulsion = (EMLA^=AE=20 cream or disk [manufactured by AstraZeneca LP]) can decrease the = pain of=20 vaccination among infants by causing superficial anesthesia=20 (74,75). Preliminary evidence indicates that this cream = does not=20 interfere with the immune response to MMR (76). Topical=20 lidocaine-prilocaine emulsion should not be used on infants aged = <12=20 months who are receiving treatment with methemoglobin-inducing = agents=20 because of the possible development of methemoglobinemia = (77).=20 Acetaminophen has been used among children to reduce the = discomfort and=20 fever associated with vaccination (78). However, = acetaminophen can=20 cause formation of methemoglobin and, thus, might interact with=20 lidocaine-prilocaine cream, if used concurrently (77). = Ibuprofen or=20 other nonaspirin analgesic can be used, if necessary. Use of a = topical=20 refrigerant (vapocoolant) spray can reduce the short-term pain = associated=20 with injections and can be as effective as lidocaine-prilocaine = cream=20 (79). Administering sweet-tasting fluid orally immediately = before=20 injection can result in a calming or analgesic effect among = certain=20 infants.=20
Nonstandard Vaccination Practices

Recommendations regarding route, site, and dosage of = immunobiologics=20 are derived from data from clinical trials, from practical = experience, and=20 from theoretical considerations. ACIP strongly discourages = variations from=20 the recommended route, site, volume, or number of doses of any = vaccine.=20

Variation from the recommended route and site can result in = inadequate=20 protection. The immunogenicity of hepatitis B vaccine and rabies = vaccine=20 is substantially lower when the gluteal rather than the deltoid = site is=20 used for administration (53,59). Hepatitis B vaccine = administered=20 intradermally can result in a lower seroconversion rate and final = titer of=20 hepatitis B surface antibody than when administered by the deltoid = intramuscular route (80,81). Doses of rabies vaccine = administered=20 in the gluteal site should not be counted as valid doses and = should be=20 repeated. Hepatitis B vaccine administered by any route or site = other than=20 intramuscularly in the anterolateral thigh or deltoid muscle = should not be=20 counted as valid and should be repeated, unless serologic testing=20 indicates that an adequate response has been achieved.

Live attenuated parenteral vaccines (e.g., MMR, varicella, or = yellow=20 fever) and certain inactivated vaccines (e.g., IPV, pneumococcal=20 polysaccharide, and anthrax) are recommended by the manufacturers = to be=20 administered by subcutaneous injection. Pneumococcal = polysaccharide and=20 IPV are approved for either intramuscular or subcutaneous = administration.=20 Response to these vaccines probably will not be affected if the = vaccines=20 are administered by the intramuscular rather then subcutaneous = route.=20 Repeating doses of vaccine administered by the intramuscular route = rather=20 than by the subcutaneous route is unnecessary.

Administering volumes smaller than those recommended (e.g., = split=20 doses) can result in inadequate protection. Using larger than the=20 recommended dose can be hazardous because of excessive local or = systemic=20 concentrations of antigens or other vaccine constituents. Using = multiple=20 reduced doses that together equal a full immunizing dose or using = smaller=20 divided doses is not endorsed or recommended. Any vaccination = using less=20 than the standard dose should not be counted, and the person = should be=20 revaccinated according to age, unless serologic testing indicates = that an=20 adequate response has been achieved.=20
Preventing Adverse Reactions

Vaccines are intended to produce active immunity to specific = antigens.=20 An adverse reaction is an untoward effect that occurs after a = vaccination=20 that is extraneous to the vaccine's primary purpose of producing = immunity.=20 Adverse reactions also are called vaccine side effects. =

All vaccines might cause adverse reactions (82= ).=20 Vaccine adverse reactions are classified by three general = categories:=20 local, systemic, and allergic. Local reactions are usually the = least=20 severe and most frequent. Systemic reactions (e.g., fever) occur = less=20 frequently than local reactions. Serious allergic reactions (e.g., = anaphylaxis) are the most severe and least frequent. Severe = adverse=20 reactions are rare.

The key to preventing the majority of serious adverse reactions = is=20 screening. Every person who administers vaccines should screen = patients=20 for contraindications and precautions to the vaccine before it is=20 administered (Table= =20 5). Standardized screening questionnaires have been developed = and are=20 available from certain state immunization programs and other = sources=20 (e.g., the Immunization Action Coalition at http://www.immunize.org/ = [accessed=20 October 31, 2001]).

Severe allergic reactions after vaccination are rare. However, = all=20 physicians and other health-care providers who administer vaccines = should=20 have procedures in place for the emergency management of a person = who=20 experiences an anaphylactic reaction. All vaccine providers should = be=20 familiar with the office emergency plan and be certified in=20 cardiopulmonary resuscitation.

Syncope (vasovagal or vasodepressor reaction) can occur after=20 vaccination, most commonly among adolescents and young adults. = During=20 1990--August 2001, a total of 2,269 reports to the Vaccine Adverse = Event=20 Reporting system were coded as syncope. Forty percent of these = episodes=20 were reported among persons aged 10--18 years (CDC, unpublished = data,=20 2001). Approximately 12% of reported syncopal episodes resulted in = hospitalization because of injury or medical evaluation. Serious = injury,=20 including skull fractures and cerebral bleeding, have been = reported to=20 result from syncopal episodes after vaccination. A published = review of=20 syncope after vaccination reported that 63% of syncopal episodes = occurred=20 <5 minutes after vaccination, and 89% occurred within 15 = minutes=20 after vaccination (83). Although syncopal episodes are = uncommon and=20 serious allergic reactions are rare, certain vaccination = specialists=20 recommend that persons be observed for 15--20 minutes after being=20 vaccinated, if possible (84). If syncope develops, patients = should=20 be observed until the symptoms resolve.=20
Managing Acute Vaccine Reactions

Although rare after vaccination, the immediate onset and=20 life-threatening nature of an anaphylactic reaction require that = personnel=20 and facilities providing vaccinations be capable of providing = initial care=20 for suspected anaphylaxis. Epinephrine and equipment for = maintaining an=20 airway should be available for immediate use.

Anaphylaxis usually begins within minutes of vaccine = administration.=20 Rapidly recognizing and initiating treatment are required to = prevent=20 possible progression to cardiovascular collapse. If flushing, = facial=20 edema, urticaria, itching, swelling of the mouth or throat, = wheezing,=20 difficulty breathing, or other signs of anaphylaxis occur, the = patient=20 should be placed in a recumbent position with the legs elevated. = Aqueous=20 epinephrine (1:1000) should be administered and can be repeated = within=20 10--20 minutes (84). A dose of diphenhydramine = hydrochloride might=20 shorten the reaction, but it will have little immediate effect.=20 Maintenance of an airway and oxygen administration might be = necessary.=20 Arrangements should be made for immediate transfer to an emergency = facility for further evaluation and treatment.=20
Occupational Safety Regulations

Bloodborne diseases (e.g., hepatitis B and C and human = immunodeficiency=20 virus [HIV]) are occupational hazards for health-care workers. In = November=20 2000, to reduce the incidence of needle-stick injuries among = health-care=20 workers and the consequent risk for bloodborne diseases acquired = from=20 patients, the Needlestick Safety and Prevention Act was signed = into law.=20 The act directed the Occupational Safety and Health Administration = (OSHA)=20 to strengthen its existing bloodborne pathogen standards. Those = standards=20 were revised and became effective in April 2001 (66). These = federal=20 regulations require that safer injection devices (e.g., = needle-shielding=20 syringes or needle-free injectors) be used for parenteral = vaccination in=20 all clinical settings when such devices are appropriate, = commercially=20 available, and capable of achieving the intended clinical purpose. = The=20 rules also require that records be kept documenting the incidence = of=20 injuries caused by medical sharps (except in workplaces with = <10=20 employees) and that nonmanagerial employees be involved in the = evaluation=20 and selection of safer devices to be procured.

Needle-shielding or needle-free devices that might satisfy the=20 occupational safety regulations for administering parenteral = injections=20 are available in the United States and are listed at multiple = websites=20 (69,85--87).^=B6 Additional information regarding = implementation and enforcement of these regulations is available = at the=20 OSHA website at http://www.osha-slc.gov/nee= dlesticks=20 (accessed October 31, 2001).=20
Storage and Handling = of=20 Immunobiologics

Failure to adhere to recommended specifications for storage and = handling of immunobiologics can reduce potency, resulting in an = inadequate=20 immune response in the recipient. Recommendations included in a = product's=20 package insert, including reconstitution of the vaccine, should be = followed carefully. Vaccine quality is the shared responsibility = of all=20 parties from the time the vaccine is manufactured until = administration.=20 All vaccines should be inspected upon delivery and monitored = during=20 storage to ensure that the cold chain has been maintained. = Vaccines should=20 continue to be stored at recommended temperatures immediately upon = receipt. Certain vaccines (e.g., MMR, varicella, and yellow fever) = are=20 sensitive to increased temperature. All other vaccines are = sensitive to=20 freezing. Mishandled vaccine usually is not distinguishable from = potent=20 vaccine. When in doubt regarding the appropriate handling of a = vaccine,=20 vaccination providers should contact the manufacturer. Vaccines = that have=20 been mishandled (e.g., inactivated vaccines and toxoids that have = been=20 exposed to freezing temperatures) or that are beyond their = expiration date=20 should not be administered. If mishandled or expired vaccines are=20 administered inadvertently, they should not be counted as valid = doses and=20 should be repeated, unless serologic testing indicates a response = to the=20 vaccine.

Live attenuated virus vaccines should be administered promptly = after=20 reconstitution. Varicella vaccine must be administered = <30=20 minutes after reconstitution. Yellow fever vaccine must be used=20 <1 hour after reconstitution. MMR vaccine must be = administered=20 <8 hours after reconstitution. If not administered = within these=20 prescribed time periods after reconstitution, the vaccine must be=20 discarded.

The majority of vaccines have a similar appearance after being = drawn=20 into a syringe. Instances in which the wrong vaccine inadvertently = was=20 administered are attributable to the practice of prefilling = syringes or=20 drawing doses of a vaccine into multiple syringes before their = immediate=20 need. ACIP discourages the routine practice of prefilling syringes = because=20 of the potential for such administration errors. To prevent = errors,=20 vaccine doses should not be drawn into a syringe until immediately = before=20 administration. In certain circumstances where a single vaccine = type is=20 being used (e.g., in advance of a community influenza vaccination=20 campaign), filling multiple syringes before their immediate use = can be=20 considered. Care should be taken to ensure that the cold chain is=20 maintained until the vaccine is administered. When the syringes = are=20 filled, the type of vaccine, lot number, and date of filling must = be=20 carefully labeled on each syringe, and the doses should be = administered as=20 soon as possible after filling.

Certain vaccines are distributed in multidose vials. When = opened, the=20 remaining doses from partially used multidose vials can be = administered=20 until the expiration date printed on the vial or vaccine = packaging,=20 provided that the vial has been stored correctly and that the = vaccine is=20 not visibly contaminated.=20
Special = Situations=20

Concurrently Administering Antimicrobial Agents and = Vaccines=20

With limited exceptions, using an antibiotic is not a = contraindication=20 to vaccination. Antimicrobial agents have no effect on the = response to=20 live attenuated vaccines, except live oral Ty21a typhoid vaccine, = and have=20 no effect on inactivated, recombinant subunit, or polysaccharide = vaccines=20 or toxoids. Ty21a typhoid vaccine should not be administered to = persons=20 receiving antimicrobial agents until >24 hours after any = antibiotic dose (18= ).=20

Antiviral drugs used for treatment or prophylaxis of influenza = virus=20 infections have no effect on the response to inactivated influenza = vaccine=20 (88= ).=20 Antiviral drugs active against herpesviruses (e.g., acyclovir or=20 valacyclovir) might reduce the efficacy of live attenuated = varicella=20 vaccine. These drugs should be discontinued >24 hours = before=20 administration of varicella vaccine, if possible.

The antimalarial drug mefloquine (Lariam^=AE = [manufactured by=20 Roche Laboratories, Inc.]) could affect the immune response to = oral Ty21a=20 typhoid vaccine if both are taken simultaneously (89,90). = To=20 minimize this effect, administering Ty21a typhoid vaccine = >24=20 hours before or after a dose of mefloquine is prudent.=20
Tuberculosis Screening and Skin Test Reactivity

Measles illness, severe acute or chronic infections, HIV = infection, and=20 malnutrition can create an anergic state during which the = tuberculin skin=20 test (usually known as purified protein derivative = [PPD]=20 skin test) might give a false negative reaction (91--93). = Although=20 any live attenuated measles vaccine can theoretically suppress PPD = reactivity, the degree of suppression is probably less than that = occurring=20 from acute infection from wild measles virus. Although routine PPD = screening of all children is no longer recommended, PPD screening = is=20 sometimes needed at the same time as administering a = measles-containing=20 vaccine (e.g., for well-child care, school entrance, or for = employee=20 health reasons), and the following options should be considered: =

PPD and measles-containing vaccine can be administered at = the same=20 visit (preferred option). Simultaneously administering PPD and=20 measles-containing vaccine does not interfere with reading the = PPD=20 result at 48--72 hours and ensures that the person has received = measles=20 vaccine.=20
If the measles-containing vaccine has been administered = recently,=20 PPD screening should be delayed >4 weeks after = vaccination. A=20 delay in performing PPD will remove the concern of any = theoretical but=20 transient suppression of PPD reactivity from the vaccine.=20
PPD screening can be performed and read before administering = the=20 measles-containing vaccine. This option is the least favored = because it=20 will delay receipt of the measles-containing vaccine.

No data exist for the potential degree of PPD suppression that = might be=20 associated with other parenteral live attenuated virus vaccines = (e.g.,=20 varicella or yellow fever). Nevertheless, in the absence of data,=20 following guidelines for measles-containing vaccine when = scheduling PPD=20 screening and administering other parenteral live attenuated virus = vaccines is prudent. If a risk exists that the opportunity to = vaccinate=20 might be missed, vaccination should not be delayed only because of = these=20 theoretical considerations.

Mucosally administered live attenuated virus vaccines (e.g., = OPV and=20 intranasally administered influenza vaccine) are unlikely to = affect the=20 response to PPD. No evidence has been reported that inactivated = vaccines,=20 polysaccharide vaccines, recombinant, or subunit vaccines, or = toxoids=20 interfere with response to PPD.

PPD reactivity in the absence of tuberculosis disease is not a=20 contraindication to administration of any vaccine, including = parenteral=20 live attenuated virus vaccines. Tuberculosis disease is not a=20 contraindication to vaccination, unless the person is moderately = or=20 severely ill. Although no studies have reported the effect of MMR = vaccine=20 on persons with untreated tuberculosis, a theoretical basis exists = for=20 concern that measles vaccine might exacerbate tuberculosis (6)= .=20 Consequently, before administering MMR to persons with untreated = active=20 tuberculosis, initiating antituberculosis therapy is advisable = (6)= .=20 Ruling out concurrent immunosuppression (e.g., immunosuppression = caused by=20 HIV infection) before administering live attenuated vaccines is = also=20 prudent.=20
Severe Allergy to Vaccine Components

Vaccine components can cause allergic reactions among certain=20 recipients. These reactions can be local or systemic and can = include mild=20 to severe anaphylaxis or anaphylactic-like responses (e.g., = generalized=20 urticaria or hives, wheezing, swelling of the mouth and throat, = difficulty=20 breathing, hypotension, and shock). Allergic reactions might be = caused by=20 the vaccine antigen, residual animal protein, antimicrobial = agents,=20 preservatives, stabilizers, or other vaccine components = (94). An=20 extensive listing of vaccine components, their use, and the = vaccines that=20 contain each component has been published (95) and is also=20 available from CDC's National Immunization Program website at http://www.cdc.gov/nip = (accessed=20 October 31, 2001).

The most common animal protein allergen is egg protein, which = is found=20 in vaccines prepared by using embryonated chicken eggs (influenza = and=20 yellow fever vaccines). Ordinarily, persons who are able to eat = eggs or=20 egg products safely can receive these vaccines; persons with = histories of=20 anaphylactic or anaphylactic-like allergy to eggs or egg proteins = should=20 not be administered these vaccines. Asking persons if they can eat = eggs=20 without adverse effects is a reasonable way to determine who might = be at=20 risk for allergic reactions from receiving yellow fever and = influenza=20 vaccines. A regimen for administering influenza vaccine to = children with=20 egg hypersensitivity and severe asthma has been developed = (96).=20

Measles and mumps vaccine viruses are grown in chick embryo = fibroblast=20 tissue culture. Persons with a serious egg allergy can receive = measles- or=20 mumps-containing vaccines without skin testing or desensitization = to egg=20 protein (6)= .=20 Rubella and varicella vaccines are grown in human diploid cell = cultures=20 and can safely be administered to persons with histories of severe = allergy=20 to eggs or egg proteins. The rare serious allergic reaction after = measles=20 or mumps vaccination or MMR are not believed to be caused by egg = antigens,=20 but to other components of the vaccine (e.g., gelatin) = (97--100).=20 MMR, its component vaccines, and other vaccines contain hydrolyzed = gelatin=20 as a stabilizer. Extreme caution should be exercised when = administering=20 vaccines that contain gelatin to persons who have a history of an=20 anaphylactic reaction to gelatin or gelatin-containing products. = Before=20 administering gelatin-containing vaccines to such persons, skin = testing=20 for sensitivity to gelatin can be considered. However, no specific = protocols for this approach have been published.

Certain vaccines contain trace amounts of antibiotics or other=20 preservatives (e.g., neomycin or thimerosal) to which patients = might be=20 severely allergic. The information provided in the vaccine package = insert=20 should be reviewed carefully before deciding if the rare patient = with such=20 allergies should receive the vaccine. No licensed vaccine contains = penicillin or penicillin derivatives.

Certain vaccines contain trace amounts of neomycin. Persons who = have=20 experienced anaphylactic reactions to neomycin should not receive = these=20 vaccines. Most often, neomycin allergy is a contact dermatitis, a=20 manifestation of a delayed type (cell-mediated) immune response, = rather=20 than anaphylaxis (101,102). A history of delayed type = reactions to=20 neomycin is not a contraindication for administration of these = vaccines.=20

Thimerosal is an organic mercurial compound in use since the = 1930s and=20 added to certain immunobiologic products as a preservative. A = joint=20 statement issued by the U.S. Public Health Service and the = American=20 Academy of Pediatrics (AAP) in 1999 (103)=20 and agreed to by the American Academy of Family Physicians (AAFP) = later in=20 1999, established the goal of removing thimerosal as soon as = possible from=20 vaccines routinely recommended for infants. Although no evidence = exists of=20 any harm caused by low levels of thimerosal in vaccines and the = risk was=20 only theoretical (104), this goal was established as a=20 precautionary measure.

The public is concerned about the health effects of mercury = exposure of=20 any type, and the elimination of mercury from vaccines was judged = a=20 feasible means of reducing an infant's total exposure to mercury = in a=20 world where other environmental sources of exposure are more = difficult or=20 impossible to eliminate (e.g., certain foods). Since mid-2001, = vaccines=20 routinely recommended for children have been manufactured without=20 thimerosal as a preservative and contain either no thimerosal or = only=20 trace amounts. Thimerosal as a preservative is present in certain = other=20 vaccines (e.g., Td, DT, one of two adult hepatitis B vaccines, and = influenza vaccine). A trace thimerosal formulation of one brand of = influenza vaccine was licensed by FDA in September 2001.

Receiving thimerosal-containing vaccines has been believed to = lead to=20 induction of allergy. However, limited scientific basis exists for = this=20 assertion (94). Hypersensitivity to thimerosal usually = consists of=20 local delayed type hypersensitivity reactions (105--107).=20 Thimerosal elicits positive delayed type hypersensitivity patch = tests in=20 1%--18% of persons tested, but these tests have limited or no = clinical=20 relevance (108,109). The majority of patients do not = experience=20 reactions to thimerosal administered as a component of vaccines = even when=20 patch or intradermal tests for thimerosal indicate = hypersensitivity=20 (109). A localized or delayed type hypersensitivity = reaction to=20 thimerosal is not a contraindication to receipt of a vaccine that = contains=20 thimerosal.=20
Latex Allergy

Latex is liquid sap from the commercial rubber tree. Latex = contains=20 naturally occurring impurities (e.g., plant proteins and = peptides), which=20 are believed to be responsible for allergic reactions. Latex is = processed=20 to form natural rubber latex and dry natural rubber. Dry natural = rubber=20 and natural rubber latex might contain the same plant impurities = as latex=20 but in lesser amounts. Natural rubber latex is used to produce = medical=20 gloves, catheters, and other products. Dry natural rubber is used = in=20 syringe plungers, vial stoppers, and injection ports on = intravascular=20 tubing. Synthetic rubber and synthetic latex also are used in = medical=20 gloves, syringe plungers, and vial stoppers. Synthetic rubber and=20 synthetic latex do not contain natural rubber or natural latex, = and=20 therefore, do not contain the impurities linked to allergic = reactions.=20

The most common type of latex sensitivity is contact-type (type = 4)=20 allergy, usually as a result of prolonged contact with = latex-containing=20 gloves (110). However, injection-procedure--associated = latex=20 allergies among patients with diabetes have been described=20 (111--113). Allergic reactions (including anaphylaxis) = after=20 vaccination procedures are rare. Only one report of an allergic = reaction=20 after administering hepatitis B vaccine in a patient with known = severe=20 allergy (anaphylaxis) to latex has been published (114). =

If a person reports a severe (anaphylactic) allergy to latex, = vaccines=20 supplied in vials or syringes that contain natural rubber should = not be=20 administered, unless the benefit of vaccination outweighs the risk = of an=20 allergic reaction to the vaccine. For latex allergies other than=20 anaphylactic allergies (e.g., a history of contact allergy to = latex=20 gloves), vaccines supplied in vials or syringes that contain dry = natural=20 rubber or natural rubber latex can be administered.=20
Vaccination of Premature Infants

In the majority of cases, infants born prematurely, regardless = of birth=20 weight, should be vaccinated at the same chronological age and = according=20 to the same schedule and precautions as full-term infants and = children.=20 Birth weight and size are not factors in deciding whether to = postpone=20 routine vaccination of a clinically stable premature infant=20 (115--117), except for hepatitis B vaccine. The full = recommended=20 dose of each vaccine should be used. Divided or reduced doses are = not=20 recommended (118).

Studies demonstrate that decreased seroconversion rates might = occur=20 among certain premature infants with low birth weights (i.e., = <2,000=20 grams) after administration of hepatitis B vaccine at birth = (119).=20 However, by chronological age 1 month, all premature infants, = regardless=20 of initial birth weight or gestational age are as likely to = respond as=20 adequately as older and larger infants (120--122). A = premature=20 infant born to HBsAg-positive mothers and mothers with unknown = HBsAg=20 status must receive immunoprophylaxis with hepatitis B vaccine and = hepatitis B immunoglobulin (HBIG) <12 hours after birth. = If=20 these infants weigh <2,000 grams at birth, the initial vaccine = dose=20 should not be counted towards completion of the hepatitis B = vaccine=20 series, and three additional doses of hepatitis B vaccine should = be=20 administered, beginning when the infant is age 1 month. The = optimal timing=20 of the first dose of hepatitis B vaccine for premature infants of=20 HBsAg-negative mothers with a birth weight of <2,000 grams has = not been=20 determined. However, these infants can receive the first dose of = the=20 hepatitis B vaccine series at chronological age 1 month. Premature = infants=20 discharged from the hospital before chronological age 1 month can = also be=20 administered hepatitis B vaccine at discharge, if they are = medically=20 stable and have gained weight consistently.=20
Breast-Feeding and Vaccination

Neither inactivated nor live vaccines administered to a = lactating woman=20 affect the safety of breast-feeding for mothers or infants. = Breast-feeding=20 does not adversely affect immunization and is not a = contraindication for=20 any vaccine. Limited data indicate that breast-feeding can enhance = the=20 response to certain vaccine antigens (123). Breast-fed = infants=20 should be vaccinated according to routine recommended schedules=20 (124--126).

Although live vaccines multiply within the mother's body, the = majority=20 have not been demonstrated to be excreted in human milk. Although = rubella=20 vaccine virus might be excreted in human milk, the virus usually = does not=20 infect the infant. If infection does occur, it is well-tolerated = because=20 the viruses are attenuated (127). Inactivated, recombinant, = subunit, polysaccharide, conjugate vaccines and toxoids pose no = risk for=20 mothers who are breast-feeding or for their infants.=20
Vaccination During Pregnancy

Risk to a developing fetus from vaccination of the mother = during=20 pregnancy is primarily theoretical. No evidence exists of risk = from=20 vaccinating pregnant women with inactivated virus or bacterial = vaccines or=20 toxoids (128,129). Benefits of vaccinating pregnant women = usually=20 outweigh potential risks when the likelihood of disease exposure = is high,=20 when infection would pose a risk to the mother or fetus, and when = the=20 vaccine is unlikely to cause harm.

Td toxoid is indicated routinely for pregnant women. Previously = vaccinated pregnant women who have not received a Td vaccination = within=20 the last 10 years should receive a booster dose. Pregnant women = who are=20 not immunized or only partially immunized against tetanus should = complete=20 the primary series (130).=20 Depending on when a woman seeks prenatal care and the required = interval=20 between doses, one or two doses of Td can be administered before = delivery.=20 Women for whom the vaccine is indicated, but who have not = completed the=20 recommended three-dose series during pregnancy, should receive = follow-up=20 after delivery to ensure the series is completed.

Women in the second and third trimesters of pregnancy have been = demonstrated to be at increased risk for hospitalization from = influenza=20 (131). Therefore, routine influenza vaccination is = recommended for=20 healthy women who will be beyond the first trimester of pregnancy = (i.e.,=20 >14 weeks of gestation) during influenza season (usually = December--March in the United States) (88= ).=20 Women who have medical conditions that increase their risk for=20 complications of influenza should be vaccinated before the = influenza=20 season, regardless of the stage of pregnancy.

IPV can be administered to pregnant women who are at risk for = exposure=20 to wild-type poliovirus infection (4)= .=20 Hepatitis B vaccine is recommended for pregnant women at risk for=20 hepatitis B virus infection (132).=20 Hepatitis A, pneumococcal polysaccharide, and meningococcal = polysaccharide=20 vaccines should be considered for women at increased risk for = those=20 infections (43,133,134).=20

Pregnant women who must travel to areas where the risk for = yellow fever=20 is high should receive yellow fever vaccine, because the limited=20 theoretical risk from vaccination is substantially outweighed by = the risk=20 for yellow fever infection (22,135= ).=20 Pregnancy is a contraindication for measles, mumps, rubella, and = varicella=20 vaccines. Although of theoretical concern, no cases of congenital = rubella=20 or varicella syndrome or abnormalities attributable to fetal = infection=20 have been observed among infants born to susceptible women who = received=20 rubella or varicella vaccines during pregnancy (6,136<= /I>).=20 Because of the importance of protecting women of childbearing age = against=20 rubella, reasonable practices in any immunization program include = asking=20 women if they are pregnant or intend to become pregnant in the = next 4=20 weeks, not vaccinating women who state that they are pregnant, = explaining=20 the potential risk for the fetus to women who state that they are = not=20 pregnant, and counseling women who are vaccinated not to become = pregnant=20 during the 4 weeks after MMR vaccination (6,35,137).=20 Routine pregnancy testing of women of childbearing age before=20 administering a live-virus vaccine is not recommended (6)= .=20 If a pregnant woman is inadvertently vaccinated or if she becomes = pregnant=20 within 4 weeks after MMR or varicella vaccination, she should be = counseled=20 regarding the theoretical basis of concern for the fetus; however, = MMR or=20 varicella vaccination during pregnancy should not ordinarily be a = reason=20 to terminate pregnancy (6,8)= .=20

Persons who receive MMR vaccine do not transmit the vaccine = viruses to=20 contacts (6)= .=20 Transmission of varicella vaccine virus to contacts is rare (138).=20 MMR and varicella vaccines should be administered when indicated = to the=20 children and other household contacts of pregnant women (6,8)= .=20

All pregnant women should be evaluated for immunity to rubella = and be=20 tested for the presence of HBsAg (6,35,132).=20 Women susceptible to rubella should be vaccinated immediately = after=20 delivery. A woman known to be HBsAg-positive should be followed = carefully=20 to ensure that the infant receives HBIG and begins the hepatitis B = vaccine=20 series <12 hours after birth and that the infant = completes the=20 recommended hepatitis B vaccine series (132).=20 No known risk exists for the fetus from passive immunization of = pregnant=20 women with immune globulin preparations.=20
Vaccination of Internationally Adopted Children

The ability of a clinician to determine that a person is = protected on=20 the basis of their country of origin and their records alone is = limited.=20 Internationally adopted children should receive vaccines according = to=20 recommended schedules for children in the United States. Only = written=20 documentation should be accepted as evidence of prior vaccination. = Written=20 records are more likely to predict protection if the vaccines, = dates of=20 administration, intervals between doses, and the child's age at = the time=20 of immunization are comparable to the current U.S. = recommendations.=20 Although vaccines with inadequate potency have been produced in = other=20 countries (139,140), the majority of vaccines used = worldwide are=20 produced with adequate quality control standards and are potent. =

The number of American families adopting children from outside = the=20 United States has increased substantially in recent years = (141).=20 Adopted children's birth countries often have immunization = schedules that=20 differ from the recommended childhood immunization schedule in the = United=20 States. Differences in the U.S. immunization schedule and those = used in=20 other countries include the vaccines administered, the recommended = ages of=20 administration, and the number and timing of doses.

Data are inconclusive regarding the extent to which an = internationally=20 adopted child's immunization record reflects the child's = protection. A=20 child's record might indicate administration of MMR vaccine when = only=20 single-antigen measles vaccine was administered. A study of = children=20 adopted from the People's Republic of China, Russia, and Eastern = Europe=20 determined that only 39% (range: 17%--88% by country) of children = with=20 documentation of >3 doses of DTP before adoption had protective = levels=20 of diphtheria and tetanus antitoxin (142). However, = antibody=20 testing was performed by using a hemagglutination assay, which = tends to=20 underestimate protection and cannot directly be compared with = antibody=20 concentration (143). Another study measured antibody to = diphtheria=20 and tetanus toxins among 51 children who had records of having = received=20 >2 doses of DTP. The majority of the children were from = Russia,=20 Eastern Europe, and Asian countries, and 78% had received all = their=20 vaccine doses in an orphanage. Overall, 94% had evidence of = protection=20 against diphtheria (EIA > 0.1 IU/mL). A total of 84% had = protection=20 against tetanus (enzyme-linked immunosorbent assay [ELISA] > = 0.5=20 IU/mL). Among children without protective tetanus antitoxin = concentration,=20 all except one had records of >3 doses of vaccine, and = the=20 majority of nonprotective concentrations were categorized as = indeterminate=20 (ELISA =3D 0.05--0.49 IU/mL) (144). Reasons for the = discrepant=20 findings in these two studies probably relate to different = laboratory=20 methodologies; the study using a hemagglutination assay might have = underestimated the number of children who were protected. = Additional=20 studies using standardized methodologies are needed. Data are = likely to=20 remain limited for countries other than the People's Republic of = China,=20 Russia, and Eastern Europe because of the limited number of = adoptees from=20 other countries.

Physicians and other health-care providers can follow one of = multiple=20 approaches if a question exists regarding whether vaccines = administered to=20 an international adoptee were immunogenic. Repeating the = vaccinations is=20 an acceptable option. Doing so is usually safe and avoids the need = to=20 obtain and interpret serologic tests. If avoiding unnecessary = injections=20 is desired, judicious use of serologic testing might be helpful in = determining which immunizations are needed. This report provides = guidance=20 on possible approaches to evaluation and revaccination for each = vaccine=20 recommended universally for children in the United States (see Table= =20 6 and the following sections).

MMR Vaccine

The simplest approach to resolving concerns regarding MMR = immunization=20 among internationally adopted children is to revaccinate with one = or two=20 doses of MMR vaccine, depending on the child's age. Serious = adverse events=20 after MMR vaccinations are rare (6)= .=20 No evidence indicates that administering MMR vaccine increases the = risk=20 for adverse reactions among persons who are already immune to = measles,=20 mumps, or rubella as a result of previous vaccination or natural = disease.=20 Doses of measles-containing vaccine administered before the first = birthday=20 should not be counted as part of the series (6)= .=20 Alternatively, serologic testing for immunoglobulin G (IgG) = antibody to=20 vaccine viruses indicated on the vaccination record can be = considered.=20 Serologic testing is widely available for measles and rubella IgG=20 antibody. A child whose record indicates receipt of monovalent = measles or=20 measles-rubella vaccine at age >1 year and who has = protective=20 antibody against measles and rubella should receive a single dose = of MMR=20 as age-appropriate to ensure protection against mumps (and rubella = if=20 measles vaccine alone had been used). If a child whose record = indicates=20 receipt of MMR at age >12 months has a protective = concentration=20 of antibody to measles, no additional vaccination is needed unless = required for school entry.

Hib Vaccine

Serologic correlates of protection for children vaccinated = >2 months=20 previously might be difficult to interpret. Because the number of=20 vaccinations needed for protection decreases with age and adverse = events=20 are rare (24= ),=20 age-appropriate vaccination should be provided. Hib vaccination is = not=20 recommended routinely for children aged >5 years.

Hepatitis B Vaccine

Serologic testing for HBsAg is recommended for international = adoptees,=20 and children determined to be HBsAg-positive should be monitored = for the=20 development of liver disease. Household members of HBsAg-positive = children=20 should be vaccinated. A child whose records indicate receipt of=20 >3 doses of vaccine can be considered protected, and = additional=20 doses are not needed if >1 doses were administered at = age=20 >6 months. Children who received their last hepatitis B = vaccine=20 dose at age <6 months should receive an additional dose at age=20 >6 months. Those who have received <3 doses should = complete=20 the series at the recommended intervals and ages (Table= =20 1).

Poliovirus Vaccine

The simplest approach is to revaccinate internationally adopted = children with IPV according to the U.S. schedule. Adverse events = after IPV=20 are rare (4)= .=20 Children appropriately vaccinated with three doses of OPV in = economically=20 developing countries might have suboptimal seroconversion, = including to=20 type 3 poliovirus (125). Serologic testing for neutralizing = antibody to poliovirus types 1, 2, and 3 can be obtained = commercially and=20 at certain state health department laboratories. Children with = protective=20 titers against all three types do not need revaccination and = should=20 complete the schedule as age-appropriate. Alternately, because the = booster=20 response after a single dose of IPV is excellent among children = who=20 previously received OPV (3)= , a=20 single dose of IPV can be administered initially with serologic = testing=20 performed 1 month later.

DTaP Vaccine

Vaccination providers can revaccinate a child with DTaP vaccine = without=20 regard to recorded doses; however, one concern regarding this = approach is=20 that data indicate increased rates of local adverse reactions = after the=20 fourth and fifth doses of DTP or DTaP (42= ).=20 If a revaccination approach is adopted and a severe local reaction = occurs,=20 serologic testing for specific IgG antibody to tetanus and = diphtheria=20 toxins can be measured before administering additional doses. = Protective=20 concentration** indicates that further doses are unnecessary and=20 subsequent vaccination should occur as age-appropriate. No = established=20 serologic correlates exist for protection against pertussis.

For a child whose record indicates receipt of >3 = doses of DTP=20 or DTaP, serologic testing for specific IgG antibody to both = diphtheria=20 and tetanus toxin before additional doses is a reasonable = approach. If a=20 protective concentration is present, recorded doses can be = considered=20 valid, and the vaccination series should be completed as = age-appropriate.=20 Indeterminate antibody concentration might indicate immunologic = memory but=20 antibody waning; serology can be repeated after a booster dose if = the=20 vaccination provider wishes to avoid revaccination with a complete = series.=20

Alternately, for a child whose records indicate receipt of = >3=20 doses, a single booster dose can be administered, followed by = serologic=20 testing after 1 month for specific IgG antibody to both diphtheria = and=20 tetanus toxins. If a protective concentration is obtained, the = recorded=20 doses can be considered valid and the vaccination series completed = as=20 age-appropriate. Children with indeterminate concentration after a = booster=20 dose should be revaccinated with a complete series.

Varicella Vaccine

Varicella vaccine is not administered in the majority of = countries. A=20 child who lacks a reliable medical history regarding prior = varicella=20 disease should be vaccinated as age-appropriate (8)= .=20

Pneumococcal Vaccines

Pneumococcal conjugate and pneumococcal polysaccharide vaccines = are not=20 administered in the majority of countries and should be = administered as=20 age-appropriate or as indicated by the presence of underlying = medical=20 conditions (26,43= ).=20
Altered Immunocompetence

ACIP's statement regarding vaccinating immunocompromised = persons=20 summarizes recommendations regarding the efficacy, safety, and use = of=20 specific vaccines and immune globulin preparations for = immunocompromised=20 persons (145).=20 ACIP statements regarding individual vaccines or immune globulins = contain=20 additional information regarding those concerns.

Severe immunosuppression can be the result of congenital=20 immunodeficiency, HIV infection, leukemia, lymphoma, generalized=20 malignancy or therapy with alkylating agents, antimetabolites, = radiation,=20 or a high dose, prolonged course of corticosteroids. The degree to = which a=20 person is immunocompromised should be determined by a physician. = Severe=20 complications have followed vaccination with live-virus vaccines = and live=20 bacterial vaccines among immunocompromised patients (146--153).=20 These patients should not receive live vaccines except in certain=20 circumstances that are noted in the following paragraphs. MMR = vaccine=20 viruses are not transmitted to contacts, and transmission of = varicella=20 vaccine virus is rare (6,138).=20 MMR and varicella vaccines should be administered to susceptible = household=20 and other close contacts of immunocompromised patients when = indicated.=20

Persons with HIV infection are at increased risk for severe=20 complications if infected with measles. No severe or unusual = adverse=20 events have been reported after measles vaccination among = HIV-infected=20 persons who did not have evidence of severe immunosuppression=20 (154--157). As a result, MMR vaccination is recommended for = all=20 HIV-infected persons who do not have evidence of severe=20 immunosuppression⁼⁸⁶⁼⁸⁶ and for whom measles = vaccination would=20 otherwise be indicated.

Children with HIV infection are at increased risk for = complications of=20 primary varicella and for herpes zoster, compared with = immunocompetent=20 children (138,15= 8).=20 Limited data among asymptomatic or mildly symptomatic HIV-infected = children (CDC class N1 or A1, age-specific CD4⁺ = lymphocyte=20 percentages of >25%) indicate that varicella vaccine is=20 immunogenic, effective, and safe (138,159).=20 Varicella vaccine should be considered for asymptomatic or mildly=20 symptomatic HIV-infected children in CDC class N1 or A1 with = age-specific=20 CD4⁺ T lymphocyte percentages of >25%. = Eligible=20 children should receive two doses of varicella vaccine with a = 3-month=20 interval between doses (138).=20

HIV-infected persons who are receiving regular doses of IGIV = might not=20 respond to varicella vaccine or MMR or its individual component = vaccines=20 because of the continued presence of passively acquired antibody. = However,=20 because of the potential benefit, measles vaccination should be = considered=20 approximately 2 weeks before the next scheduled dose of IGIV (if = not=20 otherwise contraindicated), although an optimal immune response is = unlikely to occur. Unless serologic testing indicates that = specific=20 antibodies have been produced, vaccination should be repeated (if = not=20 otherwise contraindicated) after the recommended interval (Table= =20 4). An additional dose of IGIV should be considered for = persons on=20 maintenance IGIV therapy who are exposed to measles >3 = weeks=20 after administering a standard dose (100--400 mg/kg body weight) = of IGIV.=20

Persons with cellular immunodeficiency should not receive = varicella=20 vaccine. However, ACIP recommends that persons with impaired = humoral=20 immunity (e.g., hypogammaglobulinemia or dysgammaglobulinemia) = should be=20 vaccinated (138,16= 0).=20

Inactivated, recombinant, subunit, polysaccharide, and = conjugate=20 vaccines and toxoids can be administered to all immunocompromised=20 patients, although response to such vaccines might be suboptimal. = If=20 indicated, all inactivated vaccines are recommended for = immunocompromised=20 persons in usual doses and schedules. In addition, pneumococcal,=20 meningococcal, and Hib vaccines are recommended specifically for = certain=20 groups of immunocompromised patients, including those with = functional or=20 anatomic asplenia (145,161).=20

Except for influenza vaccine, which should be administered = annually=20 (88= ),=20 vaccination during chemotherapy or radiation therapy should be = avoided=20 because antibody response is suboptimal. Patients vaccinated while = receiving immunosuppressive therapy or in the 2 weeks before = starting=20 therapy should be considered unimmunized and should be = revaccinated=20 >3 months after therapy is discontinued. Patients with = leukemia=20 in remission whose chemotherapy has been terminated for = >3=20 months can receive live-virus vaccines.

Corticosteroids

The exact amount of systemically absorbed corticosteroids and = the=20 duration of administration needed to suppress the immune system of = an=20 otherwise immunocompetent person are not well-defined. The = majority of=20 experts agree that corticosteroid therapy usually is not a=20 contraindication to administering live-virus vaccine when it is = short-term=20 (i.e., <2 weeks); a low to moderate dose; long-term, = alternate-day=20 treatment with short-acting preparations; maintenance physiologic = doses=20 (replacement therapy); or administered topically (skin or eyes) or = by=20 intra-articular, bursal, or tendon injection (145).=20 Although of theoretical concern, no evidence of increased severity = of=20 reactions to live vaccines has been reported among persons = receiving=20 corticosteroid therapy by aerosol, and such therapy is not a = reason to=20 delay vaccination. The immunosuppressive effects of steroid = treatment=20 vary, but the majority of clinicians consider a dose equivalent to = either=20 >2 mg/kg of body weight or a total of 20 mg/day of = prednisone or=20 equivalent for children who weigh >10 kg, when administered for = >2 weeks as sufficiently immunosuppressive to raise = concern=20 regarding the safety of vaccination with live-virus vaccines = (84,145).=20 Corticosteroids used in greater than physiologic doses also can = reduce the=20 immune response to vaccines. Vaccination providers should wait=20 >1 month after discontinuation of therapy before = administering a=20 live-virus vaccine to patients who have received high systemically = absorbed doses of corticosteroids for >2 weeks.=20
Vaccination of Hematopoietic Stem Cell Transplant = Recipients=20

Hematopoietic stem cell transplant (HSCT) is the infusion of=20 hematopoietic stem cells from a donor into a patient who has = received=20 chemotherapy and often radiation, both of which are usually bone = marrow=20 ablative. HSCT is used to treat a variety of neoplastic diseases,=20 hematologic disorders, immunodeficiency syndromes, congenital = enzyme=20 deficiencies, and autoimmune disorders. HSCT recipients can = receive either=20 their own cells (i.e., autologous HSCT) or cells from a donor = other than=20 the transplant recipient (i.e., allogeneic HSCT). The source of = the=20 transplanted stem cells can be from either a donor's bone marrow = or=20 peripheral blood or harvested from the umbilical cord of a newborn = infant=20 (162).=20

Antibody titers to vaccine-preventable diseases (e.g., tetanus, = poliovirus, measles, mumps, rubella, and encapsulated bacteria) = decline=20 during the 1--4 years after allogeneic or autologous HSCT if the = recipient=20 is not revaccinated (163--167). HSCT recipients are at = increased=20 risk for certain vaccine-preventable diseases, including those = caused by=20 encapsulated bacteria (i.e., pneumococcal and Hib infections). As = a=20 result, HSCT recipients should be routinely revaccinated after = HSCT,=20 regardless of the source of the transplanted stem cells. = Revaccination=20 with inactivated, recombinant, subunit, polysaccharide, and Hib = vaccines=20 should begin 12 months after HSCT (162).=20 An exception to this recommendation is for influenza vaccine, = which should=20 be administered at >6 months after HSCT and annually for = the=20 life of the recipient thereafter. MMR vaccine should be = administered 24=20 months after transplantation if the HSCT recipient is presumed to = be=20 immunocompetent. Varicella, meningococcal, and pneumococcal = conjugate=20 vaccines are not recommended for HSCT recipients because of = insufficient=20 experience using these vaccines among HSCT recipients (162).=20 The household and other close contacts of HSCT recipients and = health-care=20 workers who care for HSCT recipients, should be appropriately = vaccinated,=20 including against influenza, measles, and varicella. Additional = details of=20 vaccination of HSCT recipients and their contacts can be found in = a=20 specific CDC report on this topic (162).=20
Vaccinating Persons with Bleeding Disorders and Persons = Receiving=20 Anticoagulant Therapy

Persons with bleeding disorders (e.g., hemophilia) and persons=20 receiving anticoagulant therapy have an increased risk for = acquiring=20 hepatitis B and at least the same risk as the general population = of=20 acquiring other vaccine-preventable diseases. However, because of = the risk=20 for hematoma formation after injections, intramuscular injections = are=20 often avoided among persons with bleeding disorders by using the=20 subcutaneous or intradermal routes for vaccines that are = administered=20 normally by the intramuscular route. Hepatitis B vaccine = administered=20 intramuscularly to 153 persons with hemophilia by using a 23-gauge = needle,=20 followed by steady pressure to the site for 1--2 minutes, resulted = in a 4%=20 bruising rate with no patients requiring factor supplementation=20 (168). Whether antigens that produce more local reactions = (e.g.,=20 pertussis) would produce an equally low rate of bruising is = unknown.

When hepatitis B or any other intramuscular vaccine is = indicated for a=20 patient with a bleeding disorder or a person receiving = anticoagulant=20 therapy, the vaccine should be administered intramuscularly if, in = the=20 opinion of a physician familiar with the patient's bleeding risk, = the=20 vaccine can be administered with reasonable safety by this route. = If the=20 patient receives antihemophilia or similar therapy, intramuscular=20 vaccinations can be scheduled shortly after such therapy is = administered.=20 A fine needle (<23 gauge) should be used for the = vaccination and=20 firm pressure applied to the site, without rubbing, for = >2=20 minutes. The patient or family should be instructed concerning the = risk=20 for hematoma from the injection.=20
Vaccination = Records=20

Consent to Vaccinate

The National Childhood Vaccine Injury Act of 1986 (42 U.S.C. = =A7=20 300aa-26) requires that all health-care providers in the United = States who=20 administer any vaccine covered by the act^=A7=A7 must = provide a copy=20 of the relevant, current edition of the vaccine information = materials that=20 have been produced by CDC before administering each dose of the = vaccine.=20 The vaccine information material must be provided to the parent or = legal=20 representative of any child or to any adult to whom the physician = or other=20 health-care provider intends to administer the vaccine. The Act = does not=20 require that a signature be obtained, but documentation of consent = is=20 recommended or required by certain state or local authorities.=20
Provider Records

Documentation of patient vaccinations helps ensure that persons = in need=20 of a vaccine receive it and that adequately vaccinated patients = are not=20 overimmunized, possibly increasing the risk for local adverse = events=20 (e.g., tetanus toxoid). Serologic test results for = vaccine-preventable=20 diseases (e.g., those for rubella screening) as well as documented = episodes of adverse events also should be recorded in the = permanent=20 medical record of the vaccine recipient.

Health-care providers who administer vaccines covered by the = National=20 Childhood Vaccine Injury Act are required to ensure that the = permanent=20 medical record of the recipient (or a permanent office log or = file)=20 indicates the date the vaccine was administered, the vaccine = manufacturer,=20 the vaccine lot number, and the name, address, and title of the = person=20 administering the vaccine. Additionally, the provider is required = to=20 record the edition date of the vaccine information materials = distributed=20 and the date those materials were provided. Regarding this Act, = the term=20 health-care provider is defined as any licensed health-care = professional, organization, or institution, whether private or = public=20 (including federal, state, and local departments and agencies), = under=20 whose authority a specified vaccine is administered. ACIP = recommends that=20 this same information be kept for all vaccines, not just for those = required by the National Childhood Vaccine Injury Act.=20
Patients' Personal Records

Official immunization cards have been adopted by every state,=20 territory, and the District of Columbia to encourage uniformity of = records=20 and to facilitate assessment of immunization status by schools and = child=20 care centers. The records also are key tools in immunization = education=20 programs aimed at increasing parental and patient awareness of the = need=20 for vaccines. A permanent immunization record card should be = established=20 for each newborn infant and maintained by the parent or guardian. = In=20 certain states, these cards are distributed to new mothers before=20 discharge from the hospital. Using immunization record cards for=20 adolescents and adults also is encouraged.=20
Registries

Immunization registries are confidential, population-based,=20 computerized information systems that collect vaccination data for = as many=20 children as possible within a geographic area. Registries are a = critical=20 tool that can increase and sustain increased vaccination coverage = by=20 consolidating vaccination records of children from multiple = providers,=20 generating reminder and recall vaccination notices for each child, = and=20 providing official vaccination forms and vaccination coverage = assessments=20 (169).=20 A fully operational immunization registry also can prevent = duplicate=20 vaccinations, limit missed appointments, reduce vaccine waste, and = reduce=20 staff time required to produce or locate immunization records or=20 certificates. The National Vaccine Advisory Committee strongly = encourages=20 development of community- or state-based immunization registry = systems and=20 recommends that vaccination providers participate in these = registries=20 whenever possible (170,171).=20 A 95% participation of children aged <6 years in fully = operational=20 population-based immunization registries is a national health = objective=20 for 2010 (172).=20
Reporting Adverse = Events After=20 Vaccination

Modern vaccines are safe and effective; however, adverse events = have=20 been reported after administration of all vaccines (82= ).=20 These events range from frequent, minor, local reactions to = extremely=20 rare, severe, systemic illness (e.g., encephalopathy). = Establishing=20 evidence for cause-and-effect relationships on the basis of case = reports=20 and case series alone is impossible because temporal association = alone=20 does not necessarily indicate causation. Unless the syndrome that = occurs=20 after vaccination is clinically or pathologically distinctive, = more=20 detailed epidemiologic studies to compare the incidence of the = event among=20 vaccinees with the incidence among unvaccinated persons are often=20 necessary. Reporting adverse events to public health authorities,=20 including serious events, is a key stimulus to developing studies = to=20 confirm or refute a causal association with vaccination. More = complete=20 information regarding adverse reactions to a specific vaccine can = be found=20 in the ACIP recommendations for that vaccine and in a specific = statement=20 on vaccine adverse reactions (82= ).=20

The National Childhood Vaccine Injury Act requires health-care=20 providers to report selected events occurring after vaccination to = the=20 Vaccine Adverse Event Reporting System (VAERS). Events for which = reporting=20 is required appear in the Vaccine Injury Table.^=B6=B6 = Persons other=20 than health-care workers also can report adverse events to VAERS. = Adverse=20 events other than those that must be reported or that occur after=20 administration of vaccines not covered by the act, including = events that=20 are serious or unusual, also should be reported to VAERS, even if = the=20 physician or other health-care provider is uncertain they are = related=20 causally. VAERS forms and instructions are available in the FDA = Drug=20 Bulletin, by calling the 24-hour VAERS Hotline at 800-822-7967, or = from=20 the VAERS website at http://www.vaers.org/ (accessed = November=20 7, 2001).=20
Vaccine Injury Compensation Program

The National Vaccine Injury Compensation Program, established = by the=20 National Childhood Vaccine Injury Act, is a no-fault system in = which=20 persons thought to have suffered an injury or death as a result of = administration of a covered vaccine can seek compensation. The = program,=20 which became operational on October 1, 1988, is intended as an = alternative=20 to civil litigation under the traditional tort system in that = negligence=20 need not be proven. Claims arising from covered vaccines must = first be=20 adjudicated through the program before civil litigation can be = pursued.=20

The program relies on a Vaccine Injury Table listing the = vaccines=20 covered by the program as well as the injuries, disabilities, = illnesses,=20 and conditions (including death) for which compensation might be = awarded.=20 The table defines the time during which the first symptom or = substantial=20 aggravation of an injury must appear after vaccination. Successful = claimants receive a legal presumption of causation if a condition = listed=20 in the table is proven, thus avoiding the need to prove actual = causation=20 in an individual case. Claimants also can prevail for conditions = not=20 listed in the table if they prove causation. Injuries after = administration=20 of vaccines not listed in the legislation authorizing the program = are not=20 eligible for compensation through the program. Additional = information is=20 available from the following:

National Vaccine Injury Compensation Program
Health = Resources and=20 Services Administration
Parklawn Building, Room 8-46
5600 = Fishers=20 Lane
Rockville, MD 20857
Telephone: 800-338-2382 (24-hour=20 recording)
Internet: http://www.hrsa.gov/bhpr/vicp = (accessed November 7, 2001)

Persons wishing to file a claim for vaccine injury should call = or write=20 the following:

U.S. Court of Federal Claims
717 Madison Place,=20 N.W.
Washington, D.C. 20005
Telephone: 202-219-9657=20

Benefit and Risk Communication

Parents, guardians, legal representatives, and adolescent and = adult=20 patients should be informed regarding the benefits and risks of = vaccines=20 in understandable language. Opportunity for questions should be = provided=20 before each vaccination. Discussion of the benefits and risks of=20 vaccination is sound medical practice and is required by law.

The National Childhood Vaccine Injury Act requires that vaccine = information materials be developed for each vaccine covered by the = Act.=20 These materials, known as Vaccine Information Statements, = must be=20 provided by all public and private vaccination providers each time = a=20 vaccine is administered. Copies of Vaccine Information Statements = are=20 available from state health authorities responsible for = immunization, or=20 they can be obtained from CDC's National Immunization Program = website at=20 http://www.cdc.gov/nip = (accessed=20 November 7, 2001). Translations of Vaccine Information Statements = into=20 languages other than English are available from certain state = immunization=20 programs and from the Immunization Action Coalition website at http://www.immunize.org/ = (accessed=20 November 7, 2001).

Health-care providers should anticipate that certain parents or = patients will question the need for or safety of vaccination, = refuse=20 certain vaccines, or even reject all vaccinations. A limited = number of=20 persons might have religious or personal objections to = vaccinations.=20 Others wish to enter into a dialogue regarding the risks and = benefits of=20 certain vaccines. Having a basic understanding of how patients = view=20 vaccine risk and developing effective approaches in dealing with = vaccine=20 safety concerns when they arise is imperative for vaccination = providers.=20

Each person understands and reacts to vaccine information on = the basis=20 of different factors, including prior experience, education, = personal=20 values, method of data presentation, perceptions of the risk for = disease,=20 perceived ability to control those risks, and their risk = preference.=20 Increasingly, through the media and nonauthoritative Internet = sites,=20 decisions regarding risk are based on inaccurate information. Only = through=20 direct dialogue with parents and by using available resources, = health-care=20 professionals can prevent acceptance of media reports and = information from=20 nonauthoritative Internet sites as scientific fact.

When a parent or patient initiates discussion regarding a = vaccine=20 controversy, the health-care professional should discuss the = specific=20 concerns and provide factual information, using language that is=20 appropriate. Effective, empathetic vaccine risk communication is = essential=20 in responding to misinformation and concerns, although recognizing = that=20 for certain persons, risk assessment and decision-making is = difficult and=20 confusing. Certain vaccines might be acceptable to the resistant = parent.=20 Their concerns should then be addressed in the context of this=20 information, using the Vaccine Information Statements and offering = other=20 resource materials (e.g., information available on the National=20 Immunization Program website).

Although a limited number of providers might choose to exclude = from=20 their practice those patients who question or refuse vaccination, = the more=20 effective public health strategy is to identify common ground and = discuss=20 measures that need to be followed if the patient's decision is to = defer=20 vaccination. Health-care providers can reinforce key points = regarding each=20 vaccine, including safety, and emphasize risks encountered by = unimmunized=20 children. Parents should be advised of state laws pertaining to = school or=20 child care entry, which might require that unimmunized children = stay home=20 from school during outbreaks. Documentation of these discussions = in the=20 patient's record, including the refusal to receive certain = vaccines (i.e.,=20 informed refusal), might reduce any potential liability if a=20 vaccine-preventable disease occurs in the unimmunized patient.=20
Vaccination = Programs=20

The best way to reduce vaccine-preventable diseases is to have = a highly=20 immune population. Universal vaccination is a critical part of = quality=20 health care and should be accomplished through routine and = intensive=20 vaccination programs implemented in physicians' offices and in = public=20 health clinics. Programs should be established and maintained in = all=20 communities to ensure vaccination of all children at the = recommended age.=20 In addition, appropriate vaccinations should be available for all=20 adolescents and adults.

Physicians and other pediatric vaccination providers should = adhere to=20 the standards for child and adolescent immunization practices = (1)= .=20 These standards define appropriate vaccination practices for both = the=20 public and private sectors. The standards provide guidance on = practices=20 that will result in eliminating barriers to vaccination. These = include=20 practices aimed at eliminating unnecessary prerequisites for = receiving=20 vaccinations, eliminating missed opportunities to vaccinate, = improving=20 procedures to assess vaccination needs, enhancing knowledge = regarding=20 vaccinations among parents and providers, and improving the = management and=20 reporting of adverse events. Additionally, the standards address = the=20 importance of recall and reminder systems and using assessments to = monitor=20 clinic or office vaccination coverage levels among patients.

Standards of practice also have been published to increase = vaccination=20 coverage among adults (2)= .=20 Persons aged >65 years and all adults with medical = conditions=20 that place them at risk for pneumococcal disease should receive=20 >1 doses of pneumococcal polysaccharide vaccine. All = persons=20 aged >50 years and those with medical conditions that = increase=20 the risk for complications from influenza should receive annual = influenza=20 vaccination. All adults should complete a primary series of = tetanus and=20 diphtheria toxoids and receive a booster dose every 10 years. = Adult=20 vaccination programs also should provide MMR and varicella = vaccines=20 whenever possible to anyone susceptible to measles, mumps, = rubella, or=20 varicella. Persons born after 1956 who are attending college (or = other=20 posthigh school educational institutions), who are employed in=20 environments that place them at increased risk for measles = transmission=20 (e.g., health-care facilities), or who are traveling to areas with = endemic=20 measles, should have documentation of having received two doses of = MMR on=20 or after their first birthday or other evidence of immunity (6,173).=20 All other adults born after 1956 should have documentation of = >1=20 doses of MMR vaccine on or after their first birthday or have = other=20 evidence of immunity. No evidence indicates that administering MMR = vaccine=20 increases the risk for adverse reactions among persons who are = already=20 immune to measles, mumps, or rubella as a result of previous = vaccination=20 or disease. Widespread use of hepatitis B vaccine is encouraged = for all=20 persons who might be at increased risk (e.g., adolescents and = adults who=20 are either in a group at high risk or reside in areas with = increased rates=20 of injection-drug use, teenage pregnancy, or sexually transmitted=20 disease).

Every visit to a physician or other health-care provider can be = an=20 opportunity to update a patient's immunization status with needed=20 vaccinations. Official health agencies should take necessary = steps,=20 including developing and enforcing school immunization = requirements, to=20 ensure that students at all grade levels (including college) and = those in=20 child care centers are protected against vaccine-preventable = diseases.=20 Agencies also should encourage institutions (e.g., hospitals and = long-term=20 care facilities) to adopt policies regarding the appropriate = vaccination=20 of patients, residents, and employees (173).=20

Dates of vaccination (day, month, and year) should be recorded = on=20 institutional immunization records (e.g., those kept in schools = and child=20 care centers). This record will facilitate assessments that a = primary=20 vaccination series has been completed according to an appropriate = schedule=20 and that needed booster doses have been administered at the = appropriate=20 time.

The independent, nonfederal Task Force on Community Preventive = Services=20 (the Task Force) gives public health decision-makers = recommendations on=20 population-based interventions to promote health and prevent = disease,=20 injury, disability, and premature death. The recommendations are = based on=20 systematic reviews of the scientific literature regarding = effectiveness=20 and cost-effectiveness of these interventions. In addition, the = Task Force=20 identifies critical information regarding the other effects of = these=20 interventions, as well as the applicability to specific = populations and=20 settings and the potential barriers to implementation. This = information is=20 available through the Internet at http://www.thecommunityguide.o= rg/=20 (accessed November 7, 2001).

Beginning in 1996, the Task Force systematically reviewed = published=20 evidence on the effectiveness and cost-effectiveness of = population-based=20 interventions to increase coverage of vaccines recommended for = routine use=20 among children, adolescents, and adults. A total of 197 articles = were=20 identified that evaluated a relevant intervention, met inclusion = criteria,=20 and were published during 1980--1997. Reviews of 17 specific = interventions=20 were published in 1999 (174--176). Using the results of = their=20 review, the Task Force made recommendations regarding the use of = these=20 interventions (177). A number of interventions were = identified and=20 recommended on the basis of published evidence. The interventions = and the=20 recommendations are summarized in this report (Table= =20 7).=20
Vaccine Information=20 Sources

In addition to these general recommendations, other sources are = available that contain specific and updated vaccine information.=20
National Immunization Information Hotline

The National Immunization Information Hotline is supported by = CDC's=20 National Immunization Program and provides vaccination information = for=20 health-care providers and the public, 8:00 am--11:00 pm, = Monday--Friday:=20

Telephone (English): 800-232-2522
Telephone (Spanish):=20 800-232-0233
Telephone (TTY): 800-243-7889
Internet: http://www.ashastd.org/ = (accessed=20 November 7, 2001)

CDC's National Immunization Program

CDC's National Immunization Program website provides direct = access to=20 immunization recommendations of the Advisory Committee on = Immunization=20 Practices (ACIP), vaccination schedules, vaccine safety = information,=20 publications, provider education and training, and links to other=20 immunization-related websites. It is located at http://www.cdc.gov/nip = (accessed=20 November 7, 2001).=20
Morbidity and Mortality Weekly Report

ACIP recommendations regarding vaccine use, statements of = vaccine=20 policy as they are developed, and reports of specific disease = activity are=20 published by CDC in the Morbidity and Mortality Weekly = Report=20 (MMWR) series. Electronic subscriptions are free and = available at=20 http://www.cdc.gov/subscribe.h= tml=20 (accessed November 7, 2001). Printed subscriptions are available = at

Superintendent of Documents
U.S. Government Printing=20 Office
Washington, D.C. 20402-9235

American Academy of Pediatrics (AAP)

Every 3 years, AAP issues the Red Book: Report of the = Committee on=20 Infectious Diseases, which contains a composite summary of AAP = recommendations concerning infectious diseases and immunizations = for=20 infants, children, and adolescents.

Telephone: 888-227-1770
Internet: http://www.aap.org/ (accessed = November 7,=20 2001)

American Academy of Family Physicians (AAFP)

Information from the professional organization of family = physicians is=20 available at http://www.aafp.org/=20 (accessed November 7, 2001).=20
Immunization Action Coalition

This source provides extensive free provider and patient = information,=20 including translations of Vaccine Information Statements into = multiple=20 languages. The Internet address is http://www.immunize.org/ = (accessed=20 November 7, 2001).=20
National Network for Immunization Information

This information source is provided by the Infectious Diseases = Society=20 of America, Pediatric Infectious Diseases Society, AAP, American = Nurses=20 Association, and other professional organizations. It provides = objective,=20 science-based information regarding vaccines for the public and = providers.=20 The Internet site is http://www.immunizationinfo.org= /=20 (accessed November 7, 2001).=20
Vaccine Education Center

Located at the Children's Hospital of Philadelphia, this source = provides patient and provider information. The Internet address is = http://www.vaccine.chop.edu/=20 (accessed November 7, 2001).=20
Institute for Vaccine Safety

Located at Johns Hopkins University School of Public Health, = this=20 source provides information regarding vaccine safety concerns and=20 objective and timely information to health-care providers and = parents. It=20 is available at http://www.vaccinesafety.edu/ = (accessed November 7, 2001).=20
National Partnership for Immunization

This national organization encourages greater acceptance and = use of=20 vaccinations for all ages through partnerships with public and = private=20 organizations. Their Internet address is http://www.partnersforim= munization.org/=20 (accessed November 7, 2001).=20
State and Local Health Departments

State and local health departments provide technical advice = through=20 hotlines, electronic mail, and Internet sites, including printed=20 information regarding vaccines and immunization schedules, = posters, and=20 other educational materials.

Acknowledgments

The members of the Advisory Committee on Immunization Practices = are=20 grateful for the contributions of Margaret Hostetter, M.D., Yale = Child=20 Health Research Center; Mary Staat, M.D., Children's Hospital = Medical=20 Center of Cincinnati; Deborah Wexler, M.D., Immunization Action = Coalition;=20 and John Grabenstein, Ph.D., U.S. Army Medical Command.=20
References

CDC.=20 Standards for pediatric immunization practices: recommended by = the=20 National Vaccine Advisory Committee; approved by the U.S. Public = Health=20 Service. MMWR 1993;42(No. RR-5):1--13.***=20
CDC.=20 Health objectives for the nation public health burden of=20 vaccine-preventable diseases among adults: standards for adult=20 immunization practice. MMWR 1990;39:725--9.***=20
CDC.=20 Poliomyelitis prevention in the United States: introduction of a = sequential vaccination schedule of inactivated poliovirus = vaccine=20 followed by oral poliovirus vaccine; recommendations of the = Advisory=20 Committee on Immunization Practices (ACIP). MMWR 1997;46(No.=20 RR-3):1--25.=20
CDC.=20 Poliomyelitis prevention in the United States: updated = recommendations=20 of the Advisory Committee on Immunization Practices (ACIP). MMWR = 2000;49(No. RR-5):1--22.=20
Plotkin SA. Immunologic correlates of protection induced by=20 vaccination. Pediatr Infect Dis J 2001;20:63--75.=20
CDC.=20 Measles, mumps, and rubella---vaccine use and strategies for = elimination=20 of measles, rubella, and congenital rubella syndrome and control = of=20 mumps: recommendations of the Advisory Committee on Immunization = Practices (ACIP). MMWR 1998;47(No. RR-8):1--57.=20
Watson JC, Pearson JA, Markowitz LE, et al. Evaluation of = measles=20 revaccination among school-entry-aged children. Pediatrics=20 1996;97:613--8.=20
CDC.=20 Prevention of varicella: recommendations of the Advisory = Committee on=20 Immunization Practices (ACIP). MMWR 1996;45(No. RR-11):8.=20
CDC.=20 Human rabies prevention---United States, 1999: recommendations = of the=20 Advisory Committee on Immunization Practices (ACIP). MMWR = 1999;48(No.=20 RR-1):1--21.=20
Levine L, Edsall G. Tetanus toxoid: what determines reaction = proneness [Letter]? J Infect Dis 1981;144:376.=20
Edsall, G, Elliot MW, Peebles TC, Levine L, Eldred MC. = Excessive use=20 of tetanus toxoid boosters. JAMA 1967;202:17--9.=20
Hutchins SS, Escolan J, Markowitz LE, et al. Measles = outbreak among=20 unvaccinated preschool-age children: opportunities missed by = health care=20 providers to administer measles vaccine. Pediatrics = 1989;83:369--74.=20
Deforest A, Long SS, Lischner HW, et al. Simultaneous = administration=20 of measles-mumps-rubella vaccine with booster doses of=20 diphtheria-tetanus-pertussis and poliovirus vaccines. Pediatrics = 1988;81:237--46.=20
King GE, Hadler SC. Simultaneous administration of childhood = vaccines: an important public health policy that is safe and=20 efficacious. Pediatr Infect Dis J 1994;13:394--407.=20
Dashefsky B, Wald E, Guerra N, Byers C. Safety, = tolerability, and=20 immunogenicity of concurrent administration of Haemophilus=20 influenzae type B conjugate vaccine (meningococcal protein=20 conjugate) with either measles-mumps-rubella vaccine or=20 diphtheria-tetanus-pertussis and oral poliovirus vaccines in 14- = to=20 23-month-old infants. Pediatrics 1990;85(4 Pt 2):682--9.=20
Giammanco G, Li Volti S, Mauro L, et al. Immune response to=20 simultaneous administration of a recombinant DNA hepatitis B = vaccine and=20 multiple compulsory vaccines in infancy. Vaccine 1991;9:747--50. =
Shinefield HR, Black SB, Staehle BO, et al. Safety, = tolerability and=20 immunogenicity of concomitant injections in separate locations = of=20 M-M-R^=AE_II, VARIVAX^=AE and=20 TETRAMUNE^=AE in healthy children vs. concomitant = injections of=20 M-M-R^=AE_II and TETRAMUNE^=AE = followed six=20 weeks later by VARIVAX^=AE. Pediatr Infect Dis J = 1998;17:980--5.=20
CDC.=20 Typhoid immunization: recommendations of the Advisory Committee = on=20 Immunization Practices (ACIP). MMWR 1994;43(No. RR-14):1--7. =
DeStefano F, Goodman RA, Noble GR, McClary GD, Smith SJ, = Broome CV.=20 Simultaneous administration of influenza and pneumococcal = vaccines. JAMA=20 1982;247:2551--4.=20
Yvonnet B, Coursaget P, Deubel V, Diop-Mar I, Digoutte JP, = Chiron J.=20 Simultaneous administration of hepatitis B and yellow fever=20 vaccinations. J Med Virol 1986;19:307--11.=20
Stefano I, Sato HK, Pannuti CS, et al. Recent immunization = against=20 measles does not interfere with the sero-response to yellow = fever=20 vaccine. Vaccine 1999;17:1042--6.=20
CDC.=20 Yellow fever vaccine: recommendations of the Immunization = Practices=20 Advisory Committee (ACIP). MMWR 1990;39(No. RR-6):1--6.=20
Shinefield HR, Black S, Ray P, et al. Safety and = immunogenicity of=20 heptavalent pneumococcal CRM₁₉₇ conjugate vaccine in = infants=20 and toddlers. Pediatr Infect Dis J 1999;18:757--63.=20
CDC.=20 Haemophilus b conjugate vaccines for prevention of = Haemophilus=20 influenzae type b disease among infants and children two = months of=20 age and older: recommendations of the Immunization Practices = Advisory=20 Committee (ACIP). MMWR 1991;40(No. RR-1):1--7.=20
CDC.=20 Pertussis vaccination: use of acellular pertussis vaccines among = infants=20 and young children: recommendations of the Advisory Committee on = Immunization Practices (ACIP). MMWR 1997;46(No. RR-7):1--25. =
CDC.=20 Preventing pneumococcal disease among infants and young = children:=20 recommendations of the Advisory Committee on Immunization = Practices=20 (ACIP). MMWR 2000;49(No. RR-9):1--35.=20
CDC.=20 Combination vaccines for childhood immunization: recommendations = of the=20 Advisory Committee on Immunization Practices (ACIP), the = American=20 Academy of Pediatrics (AAP), and the American Academy of Family=20 Physicians (AAFP). MMWR 1999;48(No. RR-5):5.=20
Petralli JK, Merigan TC, Wilbur JR. Action of endogenous = interferon=20 against vaccinia infection in children. Lancet 1965;2:401--5.=20
Petralli, JK, Merigan TC, Wilbur JR. Circulating interferon = after=20 measles vaccination. N Eng J Med 1965;273:198--201.=20
CDC.=20 Simultaneous administration of varicella vaccine and other = recommended=20 childhood vaccines---United States, 1995--1999. MMWR=20 2001;50:1058--61.=20
Siber GR, Werner BC, Halsey NA, et al. Interference of = immune=20 globulin with measles and rubella immunization. J Pediatr=20 1993;122:204--11.=20
Mason W, Takahashi M, Schneider T. Persisting passively = acquired=20 measles antibody following gamma globulin therapy for Kawasaki = disease=20 and response to live virus vaccination [Abstract 311]. Presented = at the=20 32^nd meeting of the Interscience Conference on = Antimicrobial=20 Agents and Chemotherapy, Los Angeles, California, October 1992.=20
Kaplan JE, Nelson DB, Schonberger LB, et al. Effect of = immune=20 globulin on the response to trivalent oral poliovirus and yellow = fever=20 vaccinations. Bull World Health Organ 1984;62:585--90.=20
Black NA, Parsons A, Kurtz JB, McWhinney N, Lacey A, = Mayon-White RT.=20 Post-partum rubella immunization: a controlled trial of two = vaccines.=20 Lancet 1983;2:990--2.=20
CDC.=20 Control and prevention of rubella: evaluation and management of=20 suspected outbreaks, rubella in pregnant women, and surveillance = for=20 congenital rubella syndrome. MMWR 2001;50(No. RR-12):1--24.=20
Siber GR, Snydman DR. Use of immune globulin in the = prevention and=20 treatment of infections. In: Remington J, Swartz M, eds. Current = clinical topics in infectious diseases, vol 12. Oxford: = Blackwell=20 Scientific, 1992.=20
Greenberg DP, Lieberman JM, Marcy SM, et al. Enhanced = antibody=20 responses in infants given different sequences of heterogeneous=20 Haemophilus influenzae type B conjugate vaccines. J = Pediatr=20 1995;126:206--11.=20
Anderson EL, Decker MD, Englund JA, et al. = Interchangeability of=20 conjugated Haemophilus influenzae type b vaccines in = infants.=20 JAMA 1995;273:849--53.=20
Piazza M, Abrescia N, Picciotto L, et al. Demonstration of = the=20 interchangeability of 2 types of recombinant anti-hepatitis-B = vaccine.=20 Boll Soc Ital Biol Sper 1993;69:273--80.=20
Bryan JP, Henry CH, Hoffman AG, et al. Randomized, = cross-over,=20 controlled comparison of two inactivated hepatitis A vaccines. = Vaccine=20 2000;19:743--50.=20
Greenberg DP, Pickering LK, Senders SD, et al. = Interchangeability of=20 two diphtheria-tetanus-acellular pertussis vaccines in infancy.=20 Pediatrics 2002 (in press).=20
CDC.=20 Use of diphtheria toxoid-tetanus toxoid-acellular pertussis = vaccine as a=20 five-dose series: supplemental recommendations of the Advisory = Committee=20 on Immunization Practices (ACIP). MMWR 2000;49(No. = RR-13):1--8.=20
CDC.=20 Prevention pneumococcal disease: recommendations of the Advisory = Committee on Immunization Practices (ACIP). MMWR 1997;46(No.=20 RR-8):1--24.=20
Szilagyi PG, Rodewald LE. Missed opportunities for = immunizations: a=20 review of the evidence. Journal of Public Health Management = Practice=20 1996;2:18--25.=20
Wald ER, Dashefsky B, Byers C, Guerra N, Taylor F. Frequency = and=20 severity of infections in day care. J Pediatr 1988;112:540--6.=20
Lewis T, Osborn LM, Lewis K, Brockert J, Jacobsen J, Cherry = JD.=20 Influence of parental knowledge and opinions on 12-month = diphtheria,=20 tetanus, and pertussis vaccination rates. Am J Dis Child=20 1988;142:283--6.=20
Farizo KM, Stehr-Green PA, Markowitz LE, Patriarca PA. = Vaccination=20 levels and missed opportunities for measles vaccination: a = record audit=20 in a public pediatric clinic. Pediatrics 1992;89:589--92.=20
Halsey NA, Boulos R, Mode F, et al. Response to measles = vaccine in=20 Haitian infants 6 to 12 months old: influence of maternal = antibodies,=20 malnutrition, and concurrent illnesses. N Engl J Med = 1985;313:544--9.=20
Ndikuyeze A, Munoz A, Stewart S, et al. Immunogenicity and = safety of=20 measles vaccine in ill African children. Int J Epidemiol=20 1988;17:448--55.=20
Lindegren ML, Reynolds S, Atkinson W, Davis A, Falter K, = Patriarca=20 P. Adverse events following measles vaccination of ill = preschool-aged=20 children [Abstract 270]. Abstracts of the 31^st = Interscience=20 Conference on Antimicrobial Agents and Chemotherapy, September=20 29--October 2, 1991, Chicago, Illinois:144.=20
Atkinson W, Markowitz L, Baughman A, et al. Serologic = response to=20 measles vaccination among ill children [Abstract 422]. Abstracts = of the=20 32^nd Interscience Conference on Antimicrobial Agents = and=20 Chemotherapy, October 1992, Anaheim, California:181.=20
Krober MS, Stracener LE, Bass JW. Decreased measles antibody = response after measles-mumps-rubella vaccine in infants with = colds. JAMA=20 1991;265:2095--6.=20
Shaw FE Jr, Guess HA, Roets JM, et al. Effect of anatomic = injection=20 site, age and smoking on the immune response to hepatitis B = vaccination.=20 Vaccine 1989;7:425--30.=20
Zuckerman JN. Importance of injecting vaccines into muscle:=20 different patients need different needle sizes. Brit Med J=20 2000;321:1237--8.=20
Ipp MM, Gold R, Goldback M, et al. Adverse reactions to = diphtheria,=20 tetanus, pertussis-polio vaccination at 18 months of age: effect = of=20 injection site and needle length. Pediatrics 1989;83:679--82.=20
Michaels L, Poole RW. Injection granuloma of the buttock. = Can Med=20 Assoc J 1970;102:626--8.=20
Haramati N, Lorans R, Lutwin M, Kaleya RN. Injection = granulomas:=20 intramuscle or intrafat? Arch Fam Med 1994;3:146--8.=20
Giles FH, French JH. Postinjection sciatic nerve palsies in = infants=20 and children. J Pediatr 1961;58:195--204.=20
Fishbein DB, Sawyer LA, Reid-Sanden FL, Weir EH. = Administration of=20 human diploid-cell rabies vaccine in the gluteal area [Letter]. = N Engl J=20 Med 1988;318:124--5.=20
Bergeson PS, Singer SA, Kaplan AM. Intramuscular injections = in=20 children. Pediatrics 1982;70:944--8.=20
Poland GA, Borrund A, Jacobson RM, et al. Determination of = deltoid=20 fat pad thickness: implications for needle length in adult = immunization.=20 JAMA 1997;277:1709--11.=20
Groswasser J, Kahn A, Bouche B, Hanquinet S, Perlmuter N, = Hessel L.=20 Needle length and injection technique for efficient = intramuscular=20 vaccine delivery in infants and children evaluated through an=20 ultrasonographic determination of subcutaneous and muscle layer=20 thickness. Pediatrics 1997;100:400--3.=20
Scheifele D, Bjornson G, Barreto L, Meekison W, Guasparini = R.=20 Controlled trial of Haemophilus influenzae type b = diphtheria=20 toxoid conjugate combined with diphtheria, tetanus and pertussis = vaccines, in 18-month-old children, including comparison of arm = versus=20 thigh injection. Vaccine 1992;10:455--60.=20
Hingson RA, Davis HS, Rosen M. Historical development of jet = injection and envisioned uses in mass immunization and mass = therapy=20 based upon two decades' experience. Mil Med 1963;128:516--24.=20
Reis EC, Jacobson RM, Tarbell S, Weniger BG. Taking the = sting out of=20 shots: control of vaccination-associated pain and adverse = reactions.=20 Pediatric Ann 1998;27:375--85.=20
Occupational Safety and Health Administration. Occupational = exposure=20 to bloodborne pathogens; needlestick and other sharps injuries; = final=20 rule (29 CFR Part 1910). Federal Register 2001;66:5318--25. = Available at=20 http://= www.osha-slc.gov/FedReg_osha_pdf/FED20010118A.pdf.=20 Accessed November 8, 2001.=20
Simonsen L, Kane A, Lloyd J, Zaffran M, Kane M. Unsafe = injections in=20 the developing world and transmission of bloodborne pathogens: a = review.=20 Bull World Health Organ 1999;77:789--800.=20
Kane A, Lloyd J, Zaffran M, Simonsen L, Kane M. Transmission = of=20 hepatitis B, hepatitis C and human immunodeficiency viruses = through=20 unsafe injections in the developing world: model-based regional=20 estimates. Bull World Health Organ 1999;77:801--7.=20
CDC. Needle-free injection technology. Atlanta, GA: US = Department of=20 Health and Human Services, CDC, National Immunization Program, = 2001.=20 Available at <www.cdc.gov/nip/dev/jet= inject.htm.=20 Accessed November 8, 2001.=20
CDC.=20 Hepatitis B associated with jet gun injection---California=20 [Epidemiologic notes and reports]. MMWR 1986;35:373--6.=20
Canter J, Mackey K, Good LS, et al. Outbreak of hepatitis B=20 associated with jet injections in a weight reduction clinic. = Arch Intern=20 Med 1990;150:1923--7.=20
Brito GS, Chen RT, Stefano IC, Campos AM, Oselka G. Risk of=20 transmission of HIV and other blood-born diseases via jet = injectors=20 during immunization mass campaigns in Brazil [Abstract PC0132].=20 10^th International Conference on AIDS, Yokohama, = 7--12 August=20 1994;10:301. Available at http:/= /www.aegis.com/pubs/aidsline/1994/dec/m94c3258.html.=20 Accessed November 8, 2001.=20
Hoffman PN, Abuknesha RA, Andrews NJ, Samuel D, Lloyd JS. = Model to=20 assess the infection potential of jet injectors used in mass=20 immunization. Vaccine 2001;19:4020--7.=20
Taddio A, Nulman I, Goldbach M, Ipp M, Koren G. Use of=20 lidocaine-prilocain cream for vaccination pain in infants. J = Pediatr=20 1994;124:643--8.=20
Uhari M. Eutectic mixture of lidocaine and prolocaine for=20 alleviating vaccination pain in infants. Pediatrics = 1993;92:719--21.=20
Halperin SA, McGrath P, Smith B, Houston T. = Lidocaine-prilocaine=20 patch decreases the pain associated with subcutaneous = administration of=20 measles-mumps-rubella vaccine but does not adversely affect the = antibody=20 response. J Pediatr 2000;136:789--94.=20
Frayling IM, Addison GM, Chatterge K, Meakin G. = Methaemoglobinaemia=20 in children treated with prilocaine-lignocaine cream. Br Med J=20 1990;301:153--4.=20
Lewis K, Cherry JD, Sachs MH, et al. Effect of prophylactic=20 acetaminophen administration on reactions to DTP vaccination. Am = J Dis=20 Child 1988;142:62--5.=20
Reis E, Holubkov R. Vapocoolant spray is equally effective = as EMLA=20 cream in reducing immunization pain in school-aged children. = Pediatrics=20 1997;100:e5. Available at http://www.p= ediatrics.org/cgi/content/full/100/6/e5.=20 Accessed November 8, 2001.=20
Redfield RR, Innis BL, Scott RM, Cannon HG, Bancroft WH. = Clinical=20 evaluation of low-dose intradermally administered hepatitis B = vaccine: a=20 cost reduction strategy. JAMA 1985;254:3203--6.=20
Coleman PJ, Shaw FE, Serovich J, Hadler SC, Margolis HS. = Intradermal=20 hepatitis B vaccination in a large hospital employee population. = Vaccine=20 1991;9:723--7.=20
CDC.=20 Update: vaccine side effects, adverse reactions, = contraindications, and=20 precautions: recommendations of the Advisory Committee on = Immunization=20 Practices (ACIP). MMWR 1996;45(No. RR-12):1--35.=20
Braun MM, Patriarca PA, Ellenberg SS. Syncope after = immunization.=20 Arch Pediatr Adolesc Med 1997;151:255--9.=20
American Academy of Pediatrics. Active immunization. In: = Pickering=20 LK, ed. 2000 red book: report of the Committee on Infectious = Diseases.=20 25^th ed. Elk Grove Village, IL: American Academy of=20 Pediatrics, 2000.=20
International Health Care Worker Safety Center. List of=20 safety-engineered sharp devices and other products designed to = prevent=20 occupational exposures to bloodborne pathogens. Charlottesville, = VA:=20 University of Virginia, 2001. Available at http://www.med.virginia.edu/medcntr/centers/epinet/safetydevice.html= .=20 Accessed November 8, 2001.=20
California Department of Health Services. California list of = needleless systems and needles with engineered sharps injury = protection.=20 Sacramento, CA: California Department of Health Services, 2001.=20 Available at http://www.dh= s.cahwnet.gov/ohb/SHARPS/disclaim.htm.=20 Accessed November 8, 2001.=20
National Alliance for the Primary Prevention of Sharps = Injuries.=20 NAPPSI: National Alliance for the Primary Prevention of Sharps = Injuries.=20 Carlsbad, CA: NAPPSI, 2001. Available at http://www.nappsi.org/. = Accessed=20 November 13, 2001.=20
CDC.=20 Prevention and control of influenza: recommendations of the = Advisory=20 Committee on Immunization Practices (ACIP). MMWR 2001;50(No.=20 RR-4):1--44.=20
Ambrosch F, Hirschl A, Kollaritsch H, et al. Immunologic=20 investigations with oral live typhoid vaccine Ty21a strain. In: = Steffen=20 R, Lobel HO, Bradley DJ, eds. Travel medicine: proceedings of = the first=20 Conference on International Travel Medicine. Berlin, Germany:=20 Springer-Verlog, 1989:248--53.=20
Horowitz H, Carbonaro CA. Inhibition of the Salmonella = typhi=20 oral vaccine strain, Ty21a, by mefloquine and chloroquine = [Letter]. J=20 Infect Dis 1992;166:1462--4.=20
Starr S, Berkovich S. Effects of measles, = gamma-globulin-modified=20 measles and vaccine measles on the tuberculin test. N Engl J Med = 1964;270:386--91.=20
Brickman HF, Beaudry PH, Marks MI. Timing of tuberculin = tests in=20 relation to immunization with live viral vaccines. Pediatrics=20 1975;55:392--6.=20
Berkovich S, Starr S. Effects of live type 1 poliovirus = vaccine and=20 other viruses on the tuberculin test. N Engl J Med = 1966;274:67--72.=20
Grabenstein JD. Clinical management of hypersensitivities to = vaccine=20 components. Hospital Pharmacy 1997;32:77--87.=20
Grabenstein JD. ImmunoFacts: vaccines & immunologic = drugs. St.=20 Louis, MO: Wolters Kluwer Co, Facts and Comparisons, 2001:K1--5. =
Murphy KR, Strunk RC. Safe administration of influenza = vaccine in=20 asthmatic children hypersensitive to egg proteins. J Pediatr=20 1985;106:931--3.=20
Kelso JM, Jones RT, Yunginger JW. Anaphylaxis to measles, = mumps, and=20 rubella vaccine mediated by IgE to gelatin. J Allergy Clin = Immunol=20 1993;91:867--72.=20
Sakaguchi M, Ogura H, Inouye S. IgE antibody to gelatin in = children=20 with immediate-type reactions to measles and mumps vaccines. J = Allergy=20 Clin Immunol 1995;96:563--5.=20
Sakaguchi M, Yamanaka T, Ikeda K, et al. IgE-mediated = systemic=20 reactions to gelatin included in the varicella vaccine. J = Allergy Clin=20 Immunol 1997;99:263--4.=20
Sakaguchi M, Nakayama T, Inouye S. Food allergy to gelatin = in=20 children with systemic immediate-type reactions, including = anaphylaxis,=20 to vaccines. J Allergy Clin Immunol 1996;98:1058--61.=20
Reitschel RL, Bernier R. Neomycin sensitivity and the MMR = vaccine=20 [Letter]. JAMA 1981;245:571.=20
Elliman D, Dhanraj B. Safe MMR vaccination despite neomycin = allergy=20 [Letter]. Lancet 1991;337:365.=20
CDC.=20 Thimerosal in vaccines: a joint statement of the American = Academy of=20 Pediatrics and the Public Health Service [Notice to readers]. = MMWR=20 1999;48:563--5.=20
Ball LK, Ball R, Pratt RD. Assessment of thimerosal use in = childhood=20 vaccines. Pediatrics 2001;107:1147--54.=20
Aberer W. Vaccination despite thimerosal sensitivity. = Contact=20 Dermatitis 1991;24:6--10.=20
Kirkland LR. Ocular sensitivity to thimerosal: a problem = with=20 hepatitis B vaccine? South Med J 1990;83:497--9.=20
Cox NH, Forsyth A. Thiomersal allergy and vaccination = reactions.=20 Contact Dermatitis 1988;18:229--33.=20
M=F6ller H. All these positive tests to thimerosal. Contact = Dermatitis=20 1994;31:209--13.=20
Wantke F, Demmer CM, G=F6tz M, Jarisch R. Contact dermatitis = from=20 thimerosal: 2 year's experience with ethylmercuric chloride in = patch=20 testing thimerosal-sensitive patients. Contact Dermatitis=20 1994;30:115--8.=20
Slater JE. Latex allergy. J Allergy Clin Immunol = 1994;94:139--49.=20
Towse A, O'Brien M, Twarog FJ, Braimon J, Moses A. Local = reaction=20 secondary to insulin injection: a potential role for latex = antigens in=20 insulin vials and syringes [Short reports]. Diabetes Care=20 1995;18:1195--7.=20
Bastyr EJ. Latex allergen allergic reactions [Letter]. = Diabetes Care=20 1996;19:546.=20
MacCracken J, Stenger P, Jackson T. Latex allergy in = diabetic=20 patients: a call for latex-free insulin tops [Letter]. Diabetes = Care=20 1996;19:184.=20
Lear JT, English JSC. Anaphylaxis after hepatitis B = vaccination=20 [Letter]. Lancet 1995;345:1249.=20
Bernbaum JC, Daft A, Anolik R, et al. Response of preterm = infants to=20 diphtheria-tetanus- pertussis immunizations. J Pediatr = 1985;107:184--8.=20
Koblin BA, Townsend TR, Munoz A, Onorato I, Wilson M, Polk = BF.=20 Response of preterm infants to diphtheria-tetanus-pertussis = vaccine.=20 Pediatr Infect Dis J 1988;7:704--11.=20
Smolen P, Bland R, Heiligenstein E, et al. Antibody response = to oral=20 polio vaccine in premature infants. J Pediatr 1983;103:917--9.=20
Bernbaum J, Daft A, Samuelson J, Polin RA. Half-dose = immunization=20 for diphtheria, tetanus, pertussis: response of preterm infants. = Pediatrics 1989;83:471--6.=20
Lau YL, Tam AY, Ng KW, et al. Response of preterm infants to = hepatitis B vaccine. J Pediatr 1992;121:962--5.=20
Patel DM, Butler J, Feldman S, Graves GR, Rhodes PG. = Immunogenicity=20 of hepatitis B vaccine in healthy very low birth weight infants. = J=20 Pediatr 1997;131:641--3.=20
Kim SC, Chung EK, Hodinka RL, et al. Immunogenicity of = hepatitis B=20 vaccine in preterm infants. Pediatrics 1997;99:534--6.=20
Losonsky GA, Wasserman SS, Stephens I, et al. Hepatitis B=20 vaccination of premature infants: a reassessment of current=20 recommendations for delayed immunization. Pediatrics = 1999;103:E14.=20
Pickering LK, Granoff DM, Erickson JR, et al. Modulation of = the=20 immune system by human milk and infant formula containing = nucleotides.=20 Pediatrics 1998;101:242--9.=20
Kim-Farley R, Brink E, Orenstein W, Bart K. Vaccination and = breast=20 feeding [Letter]. JAMA 1982;248:2451--2.=20
Patriaca PA, Wright PF, John TJ. Factors affecting the=20 immunogenicity of oral polio vaccine in developing countries: = review.=20 Rev Infect Dis 1991;13:926--39.=20
Hahn-Zoric M, Fulconis F, Minoli I, et al. Antibody = responses to=20 parenteral and oral vaccines are impaired by conventional and=20 low-protein formulas as compared to breast feeding. Acta = Paediatr Scand=20 1990;79:1137--42.=20
Krogh V, Duffy LC, Wong D, Rosenband M, Riddlesberger KR, = Ogra PL.=20 Postpartum immunization with rubella virus vaccine and antibody = response=20 in breast-feeding infants. J Lab Clin Med 1989;113:695--9.=20
Koren G, Pastuszak A, Ito S. Drugs in pregnancy. N Eng J Med = 1998;338:1128--37.=20
Grabenstein JD. Vaccines and antibodies in relation to = pregnancy and=20 lactation. Hospital Pharmacy 1999;34:949--60.=20
CDC.=20 Diphtheria, tetanus, and pertussis: recommendations for vaccine = use and=20 other preventive measures; recommendations of the Immunization = Practices=20 Advisory Committee (ACIP). MMWR 1991;40(No. RR-10):1--28.=20
Neuzil KM, Reed GW, Mitchel EF, Simonsen L, Griffin MR. = Impact of=20 influenza on acute cardiopulmonary hospitalizations in pregnant = women.=20 Am J Epidemiol 1998;148:1094--102.=20
CDC.=20 Hepatitis B virus: a comprehensive strategy for eliminating = transmission=20 in the United States through universal childhood vaccination;=20 recommendations of the Immunization Practices Advisory Committee = (ACIP).=20 MMWR 1991;40(No. RR-13):1--25.=20
CDC.=20 Prevention of hepatitis A through active or passive = immunization:=20 recommendations of the Advisory Committee on Immunization = Practices=20 (ACIP). MMWR 1999;48(No. RR-12):1--37.=20
CDC.=20 Prevention and control of meningococcal disease and = meningococcal=20 disease and college students: recommendations of the Advisory = Committee=20 on Immunization Practices (ACIP). MMWR 2000;49(No. = RR-7):1--20.=20
Tsai TF, Paul R, Lynberg MC, Letson GW. Congenital yellow = fever=20 virus infection after immunization in pregnancy. J Infect Dis=20 1993;168:1520--3.=20
Shields KE, Galil K, Seward J, Sharrar RG, Cordero JF, = Slater E.=20 Varicella vaccine exposure during pregnancy: data from the first = 5 years=20 of the pregnancy registry. Obstet Gynecol 2001;98:14--9.=20
CDC.=20 Revised ACIP recommendation for avoiding pregnancy after = receiving a=20 rubella-containing vaccine [Notice to readers]. MMWR = 2001;50:1117.=20
CDC.=20 Prevention of varicella: update recommendations of the Advisory=20 Committee on Immunization Practices (ACIP). MMWR 1999;48(No.=20 RR-6):1--5.=20
Hlady WG, Bennett JV, Samadi AR, et al. Neonatal tetanus in = rural=20 Bangladesh: risk factors and toxoid efficacy. Am J Publ Health=20 1992;82:1365--9.=20
de Quadros CA, Andrus JK, Olive J-M, de Macedo CG. Polio = eradication=20 from the Western Hemisphere. Ann Rev Publ Health = 1992;13:239--52.=20
U.S. Department of State. International adoptions. = Washington, DC:=20 US Department of State, 2001. Available at http://www.travel.state.g= ov/adopt.html.=20 Accessed November 13, 2001.=20
Hostetter MK, Johnson DE. Immunization status of adoptees = from=20 China, Russia, and Eastern Europe [Abstract 851]. Presented at = the 1998=20 Pediatric Academic Societies Annual Meeting, New Orleans, May 5, = 1998.=20
Kriz B, Burian V, Sladky K, et al. Comparison of titration = results=20 of diphtheric antitoxic antibody obtained by means of Jensen's = method=20 and the method of tissue cultures and haemagglutination. J Hyg = Epidemiol=20 Microbiol Immunol 1978;22:485--93.=20
Staat MA, Daniels D. Immunization verification in = internationally=20 adopted children [Abstract]. Pediatr Res 2001;49(4):468a.=20
CDC.=20 Recommendations of the Advisory Committee on Immunization = Practices=20 (ACIP): use of vaccines and immune globulins in persons with = altered=20 immunocompetence. MMWR 1993;42(No. RR-4):1--18.=20
Sixbey JW. Routine immunization of the immunocompromised = child. Adv=20 Pediatr Infect Dis 1987;2:79--114.=20
Wright PF, Hatch MH, Kasselberg AG, Lowry SP, Wadlington WB, = Karzon=20 DT. Vaccine-associated poliomyelitis in a child with sex-linked=20 agammaglobulinemia. J Pediatr 1977;91:408--12.=20
Wyatt HV. Poliomyelitis in hypogammaglobulinemics. J Infect = Dis=20 1973;128:802--6.=20
Davis LE, Bodian D, Price D, Butler IJ, Vickers JH. Chronic=20 progressive poliomyelitis secondary to vaccination of an = immunodeficient=20 child. N Engl J Med 1977;297:241--5.=20
CDC.=20 Disseminated Mycobacterium bovis infection from BCG = vaccination=20 of a patient with acquired immunodeficiency syndrome = [Epidemiologic=20 notes and reports]. MMWR 1985;34:227--8.=20
Ninane J, Grymonprez A, Burtonboy G, Francois A, Cornu G.=20 Disseminated BCG in HIV infection. Arch Dis Child = 1988;63:1268--9.=20
Redfield RR, Wright DC, James WD, Jones TS, Brown C, Burke = DS.=20 Disseminated vaccinia in a military recruit with human = immunodeficiency=20 virus (HIV) disease. N Engl J Med 1987;316:673--6.=20
CDC.=20 Measles pneumonitis following measles-mumps-rubella vaccination = of a=20 patient with HIV infection, 1993. MMWR 1996;45:603--6.=20
Sprauer MA, Markowitz LE, Nicholson JKA, et al. Response of = human=20 immunodeficiency virus-infected adults to measles-rubella = vaccination. J=20 Acquir Immune Defic Syndr 1993;6:1013--6.=20
McLaughlin M, Thomas P, Onorato I, et al. Live virus = vaccines in=20 human immunodeficiency virus-infected children: a retrospective = survey.=20 Pediatrics 1988;82:229--33.=20
Onorato IM, Markowitz LE, Oxtoby MJ. Childhood immunization, = vaccine-preventable diseases and infection with human = immunodeficiency=20 virus. Pediatr Infect Dis J 1988;6:588--95.=20
Palumbo P, Hoyt L, Demasio K, Oleske J, Connor E. = Population-based=20 study of measles and measles immunization in human = immunodeficiency=20 virus-infected children. Pediatr Infect Dis J 1992;11:1008--14.=20
Derryck A, LaRussa P, Steinberg S, Capasso M, Pitt J, = Gershon AA.=20 Varicella and zoster infection in children with human = immunodeficiency=20 virus infection. Pediatr Infect Dis J 1998;17:931--3.=20
CDC.=20 1994 revised classification system for human immunodeficiency = virus=20 infection in children less than 13 years of age. MMWR = 1994;43(No.=20 RR-12):1--10.=20
Levin MJ, Gershon AA, Weinberg A, et al. Immunization of=20 HIV-infected children with varicella vaccine. J Pediatr=20 2001;139:305--10.=20
CDC.=20 Update on adult immunization recommendations of the Immunization = Practices Advisory Committee (ACIP). MMWR 1991;40(No. = RR-12):1--94.=20
CDC.=20 Guidelines for preventing opportunistic infections among = hematopoietic=20 stem cell transplant recipients: recommendations of CDC, the = Infectious=20 Disease Society of America, and the American Society of Blood = and Marrow=20 Transplantation. MMWR 2000;49(No. RR-10):1--128.=20
Guinan EC, Molrine DC, Antin JH, et al. Polysaccharide = conjugate=20 vaccine responses in bone marrow transplant patients. = Transplantation=20 1994;57:677--84.=20
Pauksen K, Hammarstrom V, Ljungman P, et al. Immunity to = poliovirus=20 and immunization with inactivated poliovirus vaccine after = autologous=20 bone marrow transplantation. Clin Infect Dis 1994;18:547--52.=20
Pauksen K, Duraj V, Ljungman P, et al. Immunity to and = immunization=20 against measles, rubella and mumps in patients after autologous = bond=20 marrow transplantation. Bone Marrow Transplant 1992;9:427--32.=20
Ljungman P, Wiklund-Hammarsten M, Duraj V, et al. Response = to=20 tetanus toxoid immunization after allogeneic bone marrow=20 transplantation. J Infect Dis 1990;162:496--500.=20
Ljungman P, Fridell E, Lonnqvist B, et al. Efficacy and = safety of=20 vaccination of marrow transplant recipients with a live = attenuated=20 measles, mumps, and rubella vaccine. J Infect Dis = 1989;159:610--5.=20
Evans DI, Shaw A. Safety of intramuscular injection of = hepatitis B=20 vaccine in haemophiliacs, BMJ 1990;300:1694--5.=20
CDC.=20 Progress in development of immunization registries---United = States,=20 2000. MMWR 2001;50:3--7.=20
National Vaccine Advisory Committee (NVAC). Development of=20 community- and state-based immunization registries; approved = January 12,=20 1999. Atlanta, GA: US Department of health and Human Services, = CDC,=20 1999. Available at http://www.cdc.gov/nip/= registry/nvac.htm.=20 Accessed November 13, 2001.=20
CDC.=20 Development of community- and state-based immunization = registries: CDC=20 response to a report from the National Vaccine Advisory = Committee. MMWR=20 2001;50(No. RR-17):1--17.=20
U.S. Department of Health and Human Services. Immunization = and=20 infectious diseases [Goal 14-26]. In: Healthy People 2010 = (conference=20 ed, vol 1). Washington, DC: US Government Printing Office, 2000. = Available at http://www.health.gov/healthypeople/Document/H= TML/Volume1/14Immunization.htm#_Toc494510242.=20 Accessed November 13, 2001.=20
CDC.=20 Immunization of health-care workers: recommendations of the = Advisory=20 Committee on Immunization Practices (ACIP) and the Hospital = Infection=20 Control Practices Advisory Committee (HICPAC). MMWR 1997;46(No.=20 RR-18):1--42.=20
Shefer A, Briss P, Rodewald L, et al. Improving immunization = coverage rates: an evidence-based review of the literature. = Epidemiol=20 Rev 1999;21:96--142.=20
CDC.=20 Vaccine-preventable diseases: improving vaccination coverage in=20 children, adolescents, and adults; a report on recommendations = of the=20 Task Force on Community Preventive Services. MMWR 1999;48(No.=20 RR-8):1--15.=20
Briss PA, Rodewald LE, Hinman AR, et al. and the Task Force = on=20 Community Preventive Services. Reviews of evidence regarding=20 interventions to improve vaccination coverage in children, = adolescents,=20 and adults. Am J Prev Med 2000;18(1 Suppl):97--140.=20
Task Force on Community Preventive Services. Recommendations = regarding interventions to improve vaccination coverage in = children,=20 adolescents, and adults.. Am J Prev Med 2000;18(1 Suppl):92--6.=20

* During measles outbreaks, if cases are occurring among = infants aged=20 <12 months, measles vaccination of infants as young as 6 months = can be=20 undertaken as an outbreak control measure. However, doses = administered at=20 ages <12 months should not be counted as part of the series=20 (Source: CDC. Measles, mumps, and rubella vaccine use and=20 strategies for elimination of measles, rubella, and congenital = rubella=20 syndrome and control of mumps: recommendations of the Advisory = Committee=20 on Immunization Practices [ACIP]. MMWR 1998;47[No. RR-8]:157). =

⁼⁸⁶ In certain situations, local or state = requirements might=20 mandate that doses of selected vaccines be administered on or = after=20 specific ages. For example, a school entry requirement might not = accept a=20 dose of MMR or varicella vaccine administered before the child's = first=20 birthday. ACIP recommends that physicians and other health-care = providers=20 comply with local or state vaccination requirements when = scheduling and=20 administering vaccines.

^=A7 The exception is the two-dose hepatitis B = vaccination=20 series for adolescents aged 1115 years. Only Recombivax = HB^=AE=20 (Merck Vaccine Division) should be used in this schedule.=20 Engerix-B^=AE is not approved by FDA for this schedule. =

^=B6 Internet sites with device listings are = identified for=20 information purposes only. CDC, the U.S. Public Health Service, = and the=20 Department of Health and Human Services do not endorse any = specific device=20 or imply that the devices listed would all satisfy the = needle-stick=20 prevention regulations.

** Toxin neutralization testing is reliable but not readily = available.=20 Enzyme immunoassay tests are the most readily available, although = passive=20 hemagglutination is available in certain areas. Physicians should = contact=20 the laboratory performing the test for interpretive standards and=20 limitations. Protective concentrations for diphtheria are defined = as=20 >0.1 IU/mL and for tetanus as >0.10.2 IU/mL. =

⁼⁸⁶⁼⁸⁶ As defined by a low age-specific total = CD4⁺ T=20 lymphocyte count or a low CD4⁺T lymphocyte count as a=20 percentage of total lymphocytes. ACIP recommendations for using = MMR=20 vaccine contain additional details regarding the criteria for = severe=20 immunosuppression in persons with HIV infection (Source: = CDC.=20 Measles, mumps, and rubella vaccine use and strategies for = elimination of=20 measles, rubella, and congenital rubella syndrome and control of = mumps:=20 recommendations of the Advisory Committee on Immunization = Practices=20 [ACIP]. MMWR 1998;47[No. RR-8]:157).

^=A7=A7 As of January 2002, vaccines covered by the = act include=20 diphtheria, tetanus, pertussis, measles, mumps, rubella, = poliovirus,=20 hepatitis B, Hib, varicella, and pneumococcal conjugate.

^=B6=B6 The Vaccine Injury Table can be obtained from = the Vaccine=20 Injury Compensation Program Internet site at <http://www.hrsa.dhh= s.gov/bhpr/vicp/table.htm>=20 (accessed November 7, 2001).

*** Standards for pediatric, adolescent, and adult immunization = practices are being revised and will be posted on CDC's National=20 Immunization Program Interne site (http://www.cdc.gov/nip; = accessed=20 November 7, 2001) as soon as the updates are available. =

Abbreviations Used in = This=20 Publication

AAFP=20
American Academy of Family Physicians=20
AAP=20
American Academy of Pediatrics=20
ACIP=20
Advisory Committee on Immunization Practices=20
DT=20
pediatric diphtheria-tetanus toxoid=20
DTaP=20
diphtheria and tetanus toxoids and acellular pertussis = vaccine=20
DTP=20
diphtheria and tetanus toxoids and whole-cell pertussis = vaccine=20
EIA/ELISA=20
enzyme immunoassay=20
FDA=20
Food and Drug Administration=20
GBS=20
Guillain-Barr=E9 syndrome=20
HBIG=20
hepatitis B immune globulin=20
HbOC=20
diphtheria CRM₁₉₇ (CRM, cross-reactive material) = protein=20 conjugate=20
HBsAg=20
hepatitis B surface antigen=20
Hib=20
Haemophilus influenzae type b=20
HIV=20
human immunodeficiency virus=20
HSCT=20
hematopoietic stem cell transplant=20
IgG=20
immunoglobulin G=20
IGIV=20
intravenous immune globulin=20
IPV=20
inactivated poliovirus vaccine=20
JIs=20
jet injectors=20
MMR=20
measles, mumps, rubella vaccine=20
OPV=20
oral poliovirus vaccine=20
OSHA=20
Occupational Safety and Health Administration=20
PCV=20
pneumococcal conjugate vaccine=20
PPD=20
purified protein derivative=20
PRP-OMP=20
polyribosylribitol phosphate-meningococcal outer membrane = protein=20
PRP-T=20
PRP-tetanus=20
PPV=20
pneumococcal polysaccharide vaccine=20
Td=20
adult tetanus-diphtheria toxoid=20
VAERS=20
Vaccine Adverse Event Reporting System=20
VAPP=20
vaccine-associated paralytic polio

Definitions Used in = This=20 Report

Adverse event. An untoward event that occurs after a = vaccination=20 that might be caused by the vaccine product or vaccination = process. It=20 includes events that are 1) vaccine-induced: caused by the = intrinsic=20 characteristic of the vaccine preparation and the individual = response of=20 the vaccinee; these events would not have occurred without = vaccination=20 (e.g., vaccine-associated paralytic poliomyelitis); 2)=20 vaccine-potentiated: would have occurred anyway, but were = precipitated by=20 the vaccination (e.g., first febrile seizure in a predisposed = child); 3)=20 programmatic error: caused by technical errors in vaccine = preparation,=20 handling, or administration; 4) coincidental: associated = temporally with=20 vaccination by chance or caused by underlying illness. Special = studies are=20 needed to determine if an adverse event is a reaction or the = result of=20 another cause (Sources: Chen RT. Special methodological issues in=20 pharmacoepidemiology studies of vaccine safety. In: Strom BL, ed.=20 Pharmacoepidemiology. 3^rd ed. Sussex, England: John = Wiley &=20 Sons, 2000:707--32; and Fenichel GM, Lane DA, Livengood JR, = Horwitz SJ,=20 Menkes JH, Schwartz JF. Adverse events following immunization: = assessing=20 probability of causation. Pediatr Neurol 1989;5:287--90).

Adverse reaction. An undesirable medical condition that = has been=20 demonstrated to be caused by a vaccine. Evidence for the causal=20 relationship is usually obtained through randomized clinical = trials,=20 controlled epidemiologic studies, isolation of the vaccine strain = from the=20 pathogenic site, or recurrence of the condition with repeated = vaccination=20 (i.e., rechallenge); synonyms include side effect and adverse = effect).=20

Immunobiologic. Antigenic substances (e.g., vaccines and = toxoids) or antibody-containing preparations (e.g., globulins and=20 antitoxins) from human or animal donors. These products are used = for=20 active or passive immunization or therapy. The following are = examples of=20 immunobiologics:

Vaccine. A suspension of live (usually attenuated) or=20 inactivated microorganisms (e.g., bacteria or viruses) or = fractions=20 thereof administered to induce immunity and prevent infectious = disease=20 or its sequelae. Some vaccines contain highly defined antigens = (e.g.,=20 the polysaccharide of Haemophilus influenzae type b or = the=20 surface antigen of hepatitis B); others have antigens that are = complex=20 or incompletely defined (e.g., killed Bordetella = pertussis or=20 live attenuated viruses).

Toxoid. A modified bacterial toxin that has been made=20 nontoxic, but retains the ability to stimulate the formation of=20 antibodies to the toxin.

Immune globulin. A sterile solution containing = antibodies,=20 which are usually obtained from human blood. It is obtained by = cold=20 ethanol fractionation of large pools of blood plasma and = contains=20 15%--18% protein. Intended for intramuscular administration, = immune=20 globulin is primarily indicated for routine maintenance of = immunity=20 among certain immunodeficient persons and for passive protection = against=20 measles and hepatitis A.

Intravenous immune globulin. A product derived from = blood=20 plasma from a donor pool similar to the immune globulin pool, = but=20 prepared so that it is suitable for intravenous use. Intravenous = immune=20 globulin is used primarily for replacement therapy in primary=20 antibody-deficiency disorders, for treatment of Kawasaki = disease, immune=20 thrombocytopenic purpura, hypogammaglobulinemia in chronic = lymphocytic=20 leukemia, and certain cases of human immunodeficiency virus = infection=20 (Table= =20 2).

Hyperimmune globulin (specific). Special preparations = obtained=20 from blood plasma from donor pools preselected for a high = antibody=20 content against a specific antigen (e.g., hepatitis B immune = globulin,=20 varicella-zoster immune globulin, rabies immune globulin, = tetanus immune=20 globulin, vaccinia immune globulin, cytomegalovirus immune = globulin,=20 respiratory syncytial virus immune globulin, botulism immune = globulin).=20

Monoclonal antibody. An antibody product prepared from = a=20 single lymphocyte clone, which contains only antibody against a = single=20 microorganism.

Antitoxin. A solution of antibodies against a toxin. = Antitoxin=20 can be derived from either human (e.g., tetanus antitoxin) or = animal=20 (usually equine) sources (e.g., diphtheria and botulism = antitoxin).=20 Antitoxins are used to confer passive immunity and for = treatment.=20

Vaccination and Immunization. The terms vaccine = and=20 vaccination are derived from vacca, the Latin term = for cow.=20 Vaccine was the term used by Edward Jenner to describe = material=20 used (i.e., cowpox virus) to produce immunity to smallpox. The = term=20 vaccination was used by Louis Pasteur in the = 19^th=20 century to include the physical act of administering any vaccine = or=20 toxoid. Immunization is a more inclusive term, denoting the = process=20 of inducing or providing immunity by administering an = immunobiologic.=20 Immunization can be active or passive. Active immunization = is the=20 production of antibody or other immune responses through = administration of=20 a vaccine or toxoid. Passive immunization means the = provision of=20 temporary immunity by the administration of preformed antibodies. = Four=20 types of immunobiologics are administered for passive = immunization: 1)=20 pooled human immune globulin or intravenous immune globulin, 2)=20 hyperimmune globulin (specific) preparations, 3) monoclonal = antibody=20 preparations, and 4) antitoxins from nonhuman sources. Although = persons=20 often use the terms vaccination and immunization=20 interchangeably in reference to active immunization, the terms are = not=20 synonymous because the administration of an immunobiologic cannot = be=20 equated automatically with development of adequate immunity.

Table 1

Return= to=20 top.
Table 2

Return= to=20 top.
Table 3

Return= to=20 top.
Table 4

Return= to=20 top.
Table 5

Return= to=20 top.
Table 6

Return= to=20 top.
Table 7

Return= to=20 top.

Advisory Committee on Immunization=20 Practices
Membership List, June 2001=20
Chairman: John F. Modlin, M.D., Professor of Pediatrics = and=20 Medicine, Dartmouth Medical School, Lebanon, New Hampshire.=20
Executive Secretary: Dixie E. Snider, Jr., M.D., = Associate=20 Director for Science, Centers for Disease Control and Prevention, = Atlanta,=20 Georgia.=20
Members: Dennis A. Brooks, M.D., Johnson Medical Center, = Baltimore, Maryland; Richard D. Clover, M.D., University of = Louisville=20 School of Medicine, Louisville, Kentucky; Jaime Deseda-Tous, M.D., = San=20 Jorge Children's Hospital, San Juan, Puerto Rico; Charles M. = Helms, M.D.,=20 Ph.D., University of Iowa Hospital and Clinics, Iowa City, Iowa ; = David R.=20 Johnson, M.D., Michigan Department of Community Health, Lansing, = Michigan=20 ; Myron J. Levin, M.D., University of Colorado School of Medicine, = Denver,=20 Colorado; Paul A. Offit, M.D., Children's Hospital of = Philadelphia,=20 Philadelphia, Pennsylvania; Margaret B. Rennels, M.D., University = of=20 Maryland School of Medicine, Baltimore, Maryland; Natalie J. = Smith, M.D.,=20 California Department of Health Services, Berkeley, California; = Lucy S.=20 Tompkins, M.D., Ph.D., Stanford University Medical Center, = Stanford,=20 California; Bonnie M. Word, M.D., Monmouth Junction, New Jersey.=20
Ex-Officio Members: James Cheek, M.D., Indian Health = Service,=20 Albuquerque, New Mexico; Carole Heilman, M.D., National Institutes = of=20 Health, Bethesda, Maryland; Karen Midthun, M.D., Food and Drug=20 Administration, Bethesda, Maryland; Martin G. Myers, M.D., = National=20 Vaccine Program Office, Atlanta, Georgia; Kristin Lee Nichol, = M.D., VA=20 Medical Center, Minneapolis, Minnesota; Col. Benedict M. Didiega, = M.D.,=20 Department of Defense, Falls Church, Virginia; Geoffrey S. Evans, = M.D.,=20 Health Resources and Services Administration, Rockville, Maryland; = T.=20 Randolph Graydon, Health Care Financing Administration, Baltimore, = Maryland.=20
Liaison Representatives: American Academy of Family = Physicians,=20 Martin Mahoney, M.D., Ph.D., Clarence, New York; Richard = Zimmerman, M.D.,=20 Pittsburgh, Pennsylvania; American Academy of Pediatrics, Jon = Abramson,=20 M.D., Winston-Salem, North Carolina; Gary Overturf, M.D., = Albuquerque, New=20 Mexico; American Association of Health Plans, Eric K. France, = M.D.,=20 Denver, Colorado; American College of Obstetricians and = Gynecologists,=20 Stanley A. Gall, M.D., Louisville, Kentucky; American College of=20 Physicians, Kathleen M. Neuzil, M.D., Seattle, Washington; = American=20 Hospital Association, William Schaffner, M.D., Nashville, = Tennessee;=20 American Medical Association, H. David Wilson, M.D., Grand Forks, = North=20 Dakota; Association of Teachers of Preventive Medicine, W. Paul = McKinney,=20 M.D. Louisville, Kentucky; Canadian National Advisory Committee on = Immunization, Victor Marchessault, M.D., Cumberland, Ontario, = Canada;=20 Hospital Infection Control Practices Advisory Committee, Jane D. = Siegel,=20 M.D., Dallas, Texas; Infectious Diseases Society of America, = Samuel L.=20 Katz, M.D., Durham, North Carolina; London Department of Health, = David M.=20 Salisbury, M.D., London, United Kingdom; National Immunization = Council and=20 Child Health Program, Mexico, Jose Ignacio Santos, M.D., Mexico = City,=20 Mexico; National Medical Association, Rudolph E. Jackson, M.D., = Atlanta,=20 Georgia; National Vaccine Advisory Committee, Georges Peter, M.D., = Providence, Rhode Island; Pharmaceutical Research and = Manufacturers of=20 America, Kevin Reilly, Radnor, Pennsylvania.=20
Members of the General Recommendations on = Immunization=20 Working Group

Advisory Committee on Immunization Practices (ACIP), Lucy = Tompkins,=20 M.D.; Chinh Le, M.D.; Richard Clover, M.D.; Natalie Smith, M.D. = ACIP=20 Liaison and Ex-Officio Members, David H. Trump, M.D., Office of = the=20 Assistant Secretary of Defense (Health Affairs); Pierce Gardner, = M.D.,=20 American College of Physicians; Georges Peter, M.D., National = Vaccine=20 Advisory Committee; Victor Marchessault, M.D., Canadian National = Advisory=20 Committee on Immunization; Goeffrey Evans, M.D., Health Resources = and=20 Services Administration; Richard Zimmerman, M.D., American Academy = of=20 Family Physicians; Larry Pickering, M.D., American Academy of = Pediatrics;=20 CDC staff member, William L. Atkinson, M.D.; other members and=20 consultants, Margaret Hostetter, M.D., Yale Child Health Research = Center;=20 Mary Staat, M.D., Children's Hospital Medical Center of = Cincinnati;=20 Deborah Wexler, M.D., Immunization Action Coalition; John = Grabenstein,=20 Ph.D., U.S. Army Medical Command; Thomas Vernon, M.D., Merck = Vaccine=20 Division; and Fredrick Ruben, M.D., Aventis-Pasteur.=20

Use of trade names and commercial sources is for=20 identification only and does not imply endorsement by the = U.S.=20 Department of Health and Human Services.

References = to=20 non-CDC sites on the Internet are provided as a service to=20 MMWR readers and do not constitute or imply = endorsement of=20 these organizations or their programs by CDC or the U.S. = Department=20 of Health and Human Services. CDC is not responsible for the = content=20 of pages found at these = sites.

Disclaimer=20 All MMWR HTML versions of articles are = electronic=20 conversions from ASCII text into HTML. This conversion may have = resulted=20 in character translation or format errors in the HTML version. = Users=20 should not rely on this HTML document, but are referred to the = electronic=20 PDF version and/or the original MMWR paper copy for the = official=20 text, figures, and tables. An original paper copy of this issue = can be=20 obtained from the Superintendent of Documents, U.S. Government = Printing=20 Office (GPO), Washington, DC 20402-9371; telephone: (202) = 512-1800.=20 Contact GPO for current prices.
**Questions or messages = regarding errors in formatting should be addressed to mmwrq@cdc.gov.=20
Page converted: 2/6/2002

=20

Print=20 Help

MMWR = Home | MMWR = Search |=20 Help | Contact=20 Us

CDC Home | Search | Health = Topics=20 A-Z

This page=20 last reviewed 2/6/2002

Centers for Disease Control and = Prevention=20
Morbidity and Mortality Weekly = Report

General Recommendations = on=20 Immunization

Recommendations of the Advisory Committee on = Immunization=20 Practices (ACIP) and the American Academy of Family Physicians=20 (AAFP)

Introduction

Timing and Spacing of=20 Immunobiologics

General Principles for Vaccine Scheduling

Spacing of Multiple Doses of the Same Antigen

Simultaneous Administration

Nonsimultaneous Administration

Spacing of Antibody-Containing Products and Vaccines =

Interchangeability of Vaccines from Different = Manufacturers=20

Lapsed Vaccination Schedule

Unknown or Uncertain Vaccination Status

Contraindications and=20 Precautions

Vaccine = Administration=20

Infection Control and Sterile Technique

Recommended Routes of Injection and Needle Length

Multiple Vaccinations

Jet Injection

Methods for Alleviating Discomfort and Pain Associated with = Vaccination

Nonstandard Vaccination Practices

Preventing Adverse Reactions

Managing Acute Vaccine Reactions

Occupational Safety Regulations

Storage and Handling = of=20 Immunobiologics

Special = Situations=20

Concurrently Administering Antimicrobial Agents and = Vaccines=20

Tuberculosis Screening and Skin Test Reactivity

Severe Allergy to Vaccine Components

Latex Allergy

Vaccination of Premature Infants

Breast-Feeding and Vaccination

Vaccination During Pregnancy

Vaccination of Internationally Adopted Children

Altered Immunocompetence

Vaccination of Hematopoietic Stem Cell Transplant = Recipients=20

Vaccinating Persons with Bleeding Disorders and Persons = Receiving=20 Anticoagulant Therapy

Vaccination = Records=20

Consent to Vaccinate

Provider Records

Patients' Personal Records

Registries

Reporting Adverse = Events After=20 Vaccination

Vaccine Injury Compensation Program

Benefit and Risk Communication

Vaccination = Programs=20

Vaccine Information=20 Sources

National Immunization Information Hotline

CDC's National Immunization Program

Morbidity and Mortality Weekly Report

American Academy of Pediatrics (AAP)

American Academy of Family Physicians (AAFP)

Immunization Action Coalition

National Network for Immunization Information

Vaccine Education Center

Institute for Vaccine Safety

National Partnership for Immunization

State and Local Health Departments

Acknowledgments

References

Abbreviations Used in = This=20 Publication

Definitions Used in = This=20 Report