General Recommendations on Immunization · General Recommendations on Immunization ... immunization concerns for health-care providers who admin- ... age-specific risks for disease,

INSIDE Continuing Education Examination

Morbidity and Mortality Weekly Report

Recommendations and Reports February 8 2002 Vol 51 No RR-2

Centers for Disease Control and PreventionCenters for Disease Control and PreventionCenters for Disease Control and PreventionCenters for Disease Control and PreventionCenters for Disease Control and PreventionSAFER bull HEALSAFER bull HEALSAFER bull HEALSAFER bull HEALSAFER bull HEALTHIER bull PEOPLETHIER bull PEOPLETHIER bull PEOPLETHIER bull PEOPLETHIER bull PEOPLETM

General Recommendations on Immunization

Recommendations of the Advisory Committeeon Immunization Practices (ACIP)

and the American Academy of Family Physicians (AAFP)

CONTENTSIntroduction 1Timing and Spacing of Immunobiologics 2

General Principles for Vaccine Scheduling 2Spacing of Multiple Doses of the Same Antigen 2Simultaneous Administration 4Nonsimultaneous Administration 5Spacing of Antibody-Containing Products and Vaccines 6Interchangeability of Vaccines from Different Manufacturers 8Lapsed Vaccination Schedule 8Unknown or Uncertain Vaccination Status 8

Contraindications and Precautions 8Vaccine Administration 11

Infection Control and Sterile Technique 11Recommended Routes of Injection and Needle Length 12Multiple Vaccinations 12Jet Injection 13Methods for Alleviating Discomfort and Pain Associated

with Vaccination 13Nonstandard Vaccination Practices 13Preventing Adverse Reactions 14Managing Acute Vaccine Reactions 14Occupational Safety Regulations 15

Storage and Handling of Immunobiologics 15Special Situations 16

Concurrently Administering Antimicrobial Agentsand Vaccines 16

Tuberculosis Screening and Skin Test Reactivity 16Severe Allergy to Vaccine Components 16Latex Allergy 17Vaccination of Premature Infants 18Breast-Feeding and Vaccination 18Vaccination During Pregnancy 18Vaccination of Internationally Adopted Children 19Altered Immunocompetence 22Vaccination of Hematopoietic Stem Cell Transplant

Recipients 23Vaccinating Persons with Bleeding Disorders

and Persons Receiving Anticoagulant Therapy 23Vaccination Records 24

Consent to Vaccinate 24Provider Records 24Patientsrsquo Personal Records 24Registries 24

Reporting Adverse Events After Vaccination 24Vaccine Injury Compensation Program 25Benefit and Risk Communication 25

Vaccination Programs 26Vaccine Information Sources 28

National Immunization Information Hotline 28CDCrsquos National Immunization Program 28Morbidity and Mortality Weekly Report 28American Academy of Pediatrics (AAP) 28American Academy of Family Physicians (AAFP) 28Immunization Action Coalition 28National Network for Immunization Information 28Vaccine Education Center 28Institute for Vaccine Safety 28National Partnership for Immunization 28State and Local Health Departments 28

References 29Abbreviations Used in This Publication 34Definitions Used in This Report 34Continuing Education Examination CE-1

SUGGESTED CITATIONCenters for Disease Control and Prevention Generalrecommendations on immunization recom-mendations of the Advisory Committee onImmunization Practices and the American Academyof Family Physicians MMWR 200251(No RR-2)[inclusive page numbers]

The MMWR series of publications is published by theEpidemiology Program Office Centers for DiseaseControl and Prevention (CDC) US Department ofHealth and Human Services Atlanta GA 30333

Centers for Disease Control and Prevention

Jeffrey P Koplan MD MPHDirector

David W Fleming MDDeputy Director for Science and Public Health

Dixie E Snider Jr MD MPHAssociate Director for Science

Epidemiology Program Office

Stephen B Thacker MD MScDirector

Office of Scientific and Health Communications

John W Ward MDDirector

Editor MMWR Series

Suzanne M Hewitt MPAManaging Editor

C Kay Smith-Akin MEdProject Editor

Beverly J HollandVisual Information Specialist

Michele D RenshawErica R Shaver

Information Technology Specialists

On the Cover Detail from illustration of Edward JennerVaccinating James Phipps artist and date unknown Photographcopy 2002 BettmanCorbis Reproduced with permission

On May 14 1796 Edward Jenner an English physicianinoculated James Phipps age 8 with material from a cowpoxlesion on the hand of a milkmaid Jenner subsequently dem-onstrated that the child was protected against smallpox Thisprocedure became known as vaccination which resulted in theglobal eradication of smallpox 181 years later

Vol 51 RR-2 Recommendations and Reports 1

The material in this report was prepared for publication by the NationalImmunization Program Walter A Orenstein MD Director and theImmunization Services Division Lance E Rodewald MD Director

IntroductionThis report provides technical guidance regarding common

immunization concerns for health-care providers who admin-ister vaccines to children adolescents and adults Vaccine rec-ommendations are based on characteristics of theimmunobiologic product scientific knowledge regarding theprinciples of active and passive immunization the epidemiol-ogy and burden of diseases (ie morbidity mortality costs oftreatment and loss of productivity) the safety of vaccinesand the cost analysis of preventive measures as judged by pub-lic health officials and specialists in clinical and preventivemedicine

Benefits and risks are associated with using allimmunobiologics No vaccine is completely safe or 100 ef-fective Benefits of vaccination include partial or completeprotection against the consequences of infection for the vacci-nated person as well as overall benefits to society as a wholeBenefits include protection from symptomatic illness im-

proved quality of life and productivity and prevention of deathSocietal benefits include creation and maintenance of herd im-munity against communicable diseases prevention of diseaseoutbreaks and reduction in health-carendashrelated costs Vacci-nation risks range from common minor and local adverseeffects to rare severe and life-threatening conditions Thusrecommendations for immunization practices balance scien-tific evidence of benefits for each person and to society againstthe potential costs and risks of vaccination programs

Standards for child and adolescent immunization practicesand standards for adult immunization practices (12) have beenpublished to assist with implementing vaccination programsand maximizing their benefits Any person or institution thatprovides vaccination services should adopt these standards toimprove immunization delivery and protect children adoles-cents and adults from vaccine-preventable diseases

To maximize the benefits of vaccination this report pro-vides general information regarding immunobiologics andprovides practical guidelines concerning vaccine administra-tion and technique To minimize risk from vaccine adminis-tration this report delineates situations that warrantprecautions or contraindications to using a vaccine These rec-ommendations are intended for use in the United States be-

General Recommendations on ImmunizationRecommendations of the Advisory Committee on Immunization Practices

(ACIP) and the American Academy of Family Physicians (AAFP)Prepared by

William L Atkinson MD1

Larry K Pickering MD2

Benjamin Schwartz MD3

Bruce G Weniger MD3

John K Iskander MD3

John C Watson MD4

1Immunization Services Division2Office of the Director

3Epidemiology and Surveillance DivisionNational Immunization Program

4Division of Parasitic DiseasesNational Center for Infectious Diseases

Summary

This report is a revision of General Recommendations on Immunization and updates the 1994 statement by the AdvisoryCommittee on Immunization Practices (ACIP) (CDC General recommendations on immunization recommendations ofthe Advisory Committee on Immunization Practices [ACIP] MMWR 199443[No RR-1]1ndash38) The principal changesinclude expansion of the discussion of vaccination spacing and timing recommendations for vaccinations administered by anincorrect route information regarding needle-free injection technology vaccination of children adopted from countries outside theUnited States timing of live-virus vaccination and tuberculosis screening expansion of the discussion and tables of contraindicationsand precautions regarding vaccinations and addition of a directory of immunization resources These recommendations are notcomprehensive for each vaccine The most recent ACIP recommendations for each specific vaccine should be consulted for addi-tional details This report ACIP recommendations for each vaccine and other information regarding immunization can beaccessed at CDCrsquos National Immunization Program website at httpwwwcdcgovnip (accessed October 11 2001)

2 MMWR February 8 2002

cause vaccine availability and use as well as epidemiologiccircumstances differ in other countries Individual circum-stances might warrant deviations from these recommenda-tions The relative balance of benefits and risks can changeas diseases are controlled or eradicated For example be-cause wild poliovirus transmission has been interrupted inthe United States since 1979 the only indigenous cases ofparalytic poliomyelitis reported since that time have beencaused by live oral poliovirus vaccine (OPV) In 1997 toreduce the risk for vaccine-associated paralytic polio (VAPP)increased use of inactivated poliovirus vaccine (IPV) wasrecommended in the United States (3) In 1999 to elimi-nate the risk for VAPP exclusive use of IPV was recommendedfor routine vaccination in the United States (4) and OPVsubsequently became unavailable for routine use Howeverbecause of superior ability to induce intestinal immunityand to prevent spread among close contacts OPV remainsthe vaccine of choice for areas where wild poliovirus is stillpresent Until worldwide eradication of poliovirus is accom-plished continued vaccination of the US population againstpoliovirus will be necessary

Timing and Spacingof Immunobiologics

General Principlesfor Vaccine Scheduling

Optimal response to a vaccine depends on multiple fac-tors including the nature of the vaccine and the age andimmune status of the recipient Recommendations for theage at which vaccines are administered are influenced byage-specific risks for disease age-specific risks for complica-tions ability of persons of a certain age to respond to thevaccine and potential interference with the immune re-sponse by passively transferred maternal antibody Vaccinesare recommended for members of the youngest age groupat risk for experiencing the disease for whom efficacy andsafety have been demonstrated

Certain products including inactivated vaccines toxoidsrecombinant subunit and polysaccharide conjugate vaccinesrequire administering gt2 doses for development of an adequateand persisting antibody response Tetanus and diphtheria tox-oids require periodic reinforcement or booster doses to main-tain protective antibody concentrations Unconjugatedpolysaccharide vaccines do not induce T-cell memory andbooster doses are not expected to produce substantially in-creased protection Conjugation with a protein carrier improvesthe effectiveness of polysaccharide vaccines by inducing T-cellndashdependent immunologic function Vaccines that stimulate both

cell-mediated immunity and neutralizing antibodies (eglive attenuated virus vaccines) usually can induce prolongedoften lifelong immunity even if antibody titers decline astime progresses (5) Subsequent exposure to infection usu-ally does not lead to viremia but to a rapid anamnesticantibody response

Approximately 90ndash95 of recipients of a single dose of aparenterally administered live vaccine at the recommended age(ie measles mumps rubella [MMR] varicella and yellowfever) develop protective antibody within 2 weeks of the doseHowever because a limited proportion of recipients (lt5) ofMMR vaccine fail to respond to one dose a second dose isrecommended to provide another opportunity to develop im-munity (6) The majority of persons who fail to respond tothe first dose of MMR respond to a second dose (7) Similarlyapproximately 20 of persons aged gt13 years fail to respondto the first dose of varicella vaccine 99 of recipientsseroconvert after two doses (8)

The recommended childhood vaccination schedule is re-vised annually and is published each January Recommen-dations for vaccination of adolescents and adults are revisedless frequently except for influenza vaccine recommenda-tions which are published annually Physicians and otherhealth-care providers should always ensure that they arefollowing the most up-to-date schedules which are avail-able from CDCrsquos National Immunization Program websiteat httpwwwcdcgovnip (accessed October 11 2001)

Spacing of Multiple Dosesof the Same Antigen

Vaccination providers are encouraged to adhere as closelyas possible to the recommended childhood immunizationschedule Clinical studies have reported that recommendedages and intervals between doses of multidose antigens pro-vide optimal protection or have the best evidence of effi-cacy Recommended vaccines and recommended intervalsbetween doses are provided in this report (Table 1)

In certain circumstances administering doses of amultidose vaccine at shorter than the recommended inter-vals might be necessary This can occur when a person isbehind schedule and needs to be brought up-to-date asquickly as possible or when international travel is impend-ing In these situations an accelerated schedule can be usedthat uses intervals between doses shorter than those recom-mended for routine vaccination Although the effectivenessof all accelerated schedules has not been evaluated in clini-cal trials the Advisory Committee on Immunization Prac-tices (ACIP) believes that the immune response whenaccelerated intervals are used is acceptable and will lead toadequate protection The accelerated or minimum inter-

TABLE 1 Recommended and minimum ages and intervals between vaccine dosesVaccine Recommended age Minimum age Recommended Minimumand dose number for this dose for this dose interval to next dose interval to next dose

Hepatitis B1dagger Birthndash2 mos Birth 1ndash4 mos 4 wks

Hepatitis B2 1ndash4 mos 4 weeks 2ndash17 mos 8 wks

Hepatitis B3sect 6ndash18 mos 6 mospara mdash mdash

Diphtheria and tetanus 2 mos 6 wks 2 mos 4 wkstoxoids and acellularpertussis (DTaP)1

DTaP2 4 mos 10 wks 2 mos 4 wks

DTaP3 6 mos 14 wks 6ndash12 mos 6 mospara

DTaP4 15ndash18 mos 12 mos 3 yrs 6 mospara

DTaP5 4ndash6 yrs 4 yrs mdash mdash

Haemophilus influenzae 2 mos 6 wks 2 mos 4 wkstype b (Hib)1dagger daggerdagger

Hib2 4 mos 10 wks 2 mos 4 wks

Hib3sectsect 6 mos 14 wks 6ndash9 mos 8 wks

Hib4 12ndash15 mos 12 mos mdash mdash

Inactivated poliovirus 2 mos 6 wks 2 mos 4 wksvaccine (IPV)1

IPV2 4 mos 10 wks 2ndash14 mos 4 wks

IPV3 6ndash18 mos 14 wks 35 yrs 4 wks

IPV4 4ndash6 yrs 18 wks mdash mdash

Pneumococcal conjugate 2 mos 6 wks 2 mos 4 wksvaccine (PCV)1daggerdagger

PCV2 4 mos 10 wks 2 mos 4 wks

PCV4 12ndash15 mos 12 mos mdash mdash

Measles mumps and 12ndash15 mosparapara 12 mos 3ndash5 yrs 4 wksrubella (MMR)1

MMR2 4ndash6 yrs 13 mos mdash mdash

Varicella 12ndash15 mos 12 mos 4 wks 4 wks

Hepatitis A1 gt2 yrs 2 yrs 6ndash18 mospara 6 mospara

Hepatitis A2 gt30 mos 30 mos mdash mdash

Influenzadaggerdaggerdagger mdash 6 mospara 1 mo 4 wks

pneumococcal mdash 2 yrs 5 yrssectsectsect 5 yrspolysaccharide (PPV)1

PPV2 mdash 7 yrssectsectsect mdash mdash

Combination vaccines are available Using licensed combination vaccines is preferred over separate injections of their equivalent component vaccines (Source CDC Combi-nation vaccines for childhood immunization recommendations of the Advisory Committee on Immunization Practices (ACIP) the American Academy of Pediatrics (AAP) andthe American Academy of Family Physicians (AAFP) MMWR 199948[No RR-5]5) When administering combination vaccines the minimum age for administration is theoldest age for any of the individual components the minimum interval between doses is equal to the greatest interval of any of the individual antigens

dagger A combination hepatitis B-Hib vaccine is available (Comvaxreg manufactured by Merck Vaccine Division) This vaccine should not be administered to infants aged lt6 weeksbecause of the Hib component

sect Hepatitis B3 should be administered gt8 weeks after Hepatitis B2 and 16 weeks after Hepatitis B1 and it should not be administered before age 6 monthspara Calendar months

The minimum interval between DTaP3 and DTaP4 is recommended to be gt6 months However DTaP4 does not need to be repeated if administered gt4 months after DTaP3daggerdagger For Hib and PCV children receiving the first dose of vaccine at age gt7 months require fewer doses to complete the series (see CDC Haemophilus b conjugate vaccines for

prevention of Haemophilus influenzae type b disease among infants and children two months of age and older recommendations of the ACIP MMWR 199140[No RR-1]1ndash7and CDC Preventing pneumococcal disease among infants and young children recommendations of the Advisory Committee on Immunization Practices [ACIP] MMWR200049[No RR-9]1ndash35)

sectsect For a regimen of only polyribosylribitol phosphate-meningococcal outer membrane protein (PRP-OMP PedvaxHibreg manufactured by Merck) a dose administered at age 6months is not required

parapara During a measles outbreak if cases are occurring among infants aged lt12 months measles vaccination of infants aged gt6 months can be undertaken as an outbreak controlmeasure However doses administered at age lt12 months should not be counted as part of the series (Source CDC Measles mumps and rubella mdash vaccine use andstrategies for elimination of measles rubella and congenital rubella syndrome and control of mumps recommendations of the Advisory Committee on Immunization Practices[ACIP] MMWR 199847[No RR-8]1ndash57)

Children aged 12 monthsndash13 years require only one dose of varicella vaccine Persons aged gt13 years should receive two doses separated by gt4 weeksdaggerdaggerdagger Two doses of inactivated influenza vaccine separated by 4 weeks are recommended for children aged 6 monthsndash9 years who are receiving the vaccine for the first time

Children aged 6 monthsndash9 years who have previously received influenza vaccine and persons aged gt9 years require only one dose per influenza seasonsectsectsect Second doses of PPV are recommended for persons at highest risk for serious pneumococcal infection and those who are likely to have a rapid decline in pneumococcal antibody

concentration Revaccination 3 years after the previous dose can be considered for children at highest risk for severe pneumococcal infection who would be aged lt10 years at thetime of revaccination (see CDC Prevention of pneumococcal disease recommendations of the Advisory Committee on Immunization Practices [ACIP] MMWR 199746[NoRR-8]1ndash24)

vals and ages that can be used for scheduling catch-up vac-cinations is provided in this report (Table 1) Vaccine dosesshould not be administered at intervals less than these mini-mum intervals or earlier than the minimum age

In clinical practice vaccine doses occasionally are admin-istered at intervals less than the minimum interval or atages younger than the minimum age Doses administeredtoo close together or at too young an age can lead to a sub-optimal immune response However administering a dosea limited number of days earlier than the minimum inter-val or age is unlikely to have a substantially negative effecton the immune response to that dose Therefore ACIP rec-ommends that vaccine doses administered lt4 days beforethe minimum interval or age be counted as validdagger How-ever because of its unique schedule this recommendationdoes not apply to rabies vaccine (9) Doses administeredgt5 days earlier than the minimum interval or age shouldnot be counted as valid doses and should be repeated asage-appropriate The repeat dose should be spaced after theinvalid dose by the recommended minimum interval asprovided in this report (Table 1) For example if Haemophilusinfluenzae type b (Hib) doses one and two were adminis-tered only 2 weeks apart dose two is invalid and should berepeated The repeat dose should be administered gt4 weeksafter the invalid (second) dose The repeat dose would becounted as the second valid dose Doses administered gt5days before the minimum age should be repeated on orafter the child reaches the minimum age and gt4 weeks afterthe invalid dose For example if varicella vaccine were ad-ministered at age 10 months the repeat dose would beadministered no earlier than the childrsquos first birthday

Certain vaccines produce increased rates of local or systemicreactions in certain recipients when administered too frequently(eg adult tetanus-diphtheria toxoid [Td] pediatricdiphtheria-tetanus toxoid [DT] and tetanus toxoid) (1011)Such reactions are thought to result from the formation ofantigen-antibody complexes Optimal record keeping main-taining patient histories and adhering to recommended sched-

ules can decrease the incidence of such reactions withoutadversely affecting immunity

Simultaneous AdministrationExperimental evidence and extensive clinical experience

have strengthened the scientific basis for administering vac-cines simultaneously (ie during the same office visit notcombined in the same syringe) Simultaneously adminis-tering all vaccines for which a person is eligible is criticalincluding for childhood vaccination programs because si-multaneous administration increases the probability that achild will be fully immunized at the appropriate age Astudy conducted during a measles outbreak demonstratedthat approximately one third of measles cases among un-vaccinated but vaccine-eligible preschool children could havebeen prevented if MMR had been administered at the samevisit when another vaccine was administered (12) Simulta-neous administration also is critical when preparing for for-eign travel and if uncertainty exists that a person will returnfor further doses of vaccine

Simultaneously administering the most widely used live andinactivated vaccines have produced seroconversion rates andrates of adverse reactions similar to those observed when thevaccines are administered separately (13ndash16) Routinely ad-ministering all vaccines simultaneously is recommended forchildren who are the appropriate age to receive them and forwhom no specific contraindications exist at the time of thevisit Administering combined MMR vaccine yields resultssimilar to administering individual measles mumps and ru-bella vaccines at different sites Therefore no medical basisexists for administering these vaccines separately for routinevaccination instead of the preferred MMR combined vaccine(6) Administering separate antigens would result in a delay inprotection for the deferred components Response to MMRand varicella vaccines administered on the same day is identi-cal to vaccines administered a month apart (17) No evidenceexists that OPV interferes with parenterally administered livevaccines OPV can be administered simultaneously or at anyinterval before or after parenteral live vaccines No data existregarding the immunogenicity of oral Ty21a typhoid vaccinewhen administered concurrently or within 30 days of live vi-rus vaccines In the absence of such data if typhoid vaccina-tion is warranted it should not be delayed because ofadministration of virus vaccines (18)

Simultaneously administering pneumococcal polysaccharidevaccine and inactivated influenza vaccine elicits a satisfactoryantibody response without increasing the incidence or severityof adverse reactions (19) Simultaneously administering pneu-mococcal polysaccharide vaccine and inactivated influenza

During measles outbreaks if cases are occurring among infants aged lt12months measles vaccination of infants as young as 6 months can be undertakenas an outbreak control measure However doses administered at ages lt12months should not be counted as part of the series (Source CDC Measlesmumps and rubella mdash vaccine use and strategies for elimination of measlesrubella and congenital rubella syndrome and control of mumpsrecommendations of the Advisory Committee on Immunization Practices[ACIP] MMWR 199847[No RR-8]1ndash57)

dagger In certain situations local or state requirements might mandate that doses ofselected vaccines be administered on or after specific ages For example aschool entry requirement might not accept a dose of MMR or varicella vaccineadministered before the childrsquos first birthday ACIP recommends that physiciansand other health-care providers comply with local or state vaccinationrequirements when scheduling and administering vaccines

vaccine is strongly recommended for all persons for whomboth vaccines are indicated

Hepatitis B vaccine administered with yellow fever vaccineis as safe and immunogenic as when these vaccines are admin-istered separately (20) Measles and yellow fever vaccineshave been administered safely at the same visit and withoutreduction of immunogenicity of each of the components(2122)

Depending on vaccines administered in the first year of lifechildren aged 12ndash15 months can receive lt7 injections duringa single visit (MMR varicella Hib pneumococcal conjugatediphtheria and tetanus toxoids and acellular pertussis [DTaP]IPV and hepatitis B vaccines) To help reduce the number ofinjections at the 12ndash15-month visit the IPV primary seriescan be completed before the childrsquos first birthday MMR andvaricella vaccines should be administered at the same visit thatoccurs as soon as possible on or after the first birthday Themajority of children aged 1 year who have received two(polyribosylribitol phosphate-meningococcal outer membraneprotein [PRP-OMP]) or three (PRP-tetanus [PRP-T] diph-theria CRM

197 [CRM cross-reactive material] protein conju-

gate [HbOC]) prior doses of Hib vaccine and three prior dosesof DTaP and pneumococcal conjugate vaccine have developedprotection (2324) The third (PRP-OMP) or fourth (PRP-THbOC) dose of the Hib series and the fourth doses of DTaPand pneumococcal conjugate vaccines are critical in boostingantibody titer and ensuring continued protection (24ndash26)However the booster dose of the Hib or pneumococcal con-jugate series can be deferred until ages 15ndash18 months for chil-dren who are likely to return for future visits The fourth doseof DTaP is recommended to be administered at ages 15ndash18months but can be administered as early as age 12 monthsunder certain circumstances (25) For infants at low risk forinfection with hepatitis B virus (ie the mother tested nega-tive for hepatitis B surface antigen [HBsAg] at the time ofdelivery and the child is not of Asian or Pacific Islander de-scent) the hepatitis B vaccine series can be completed at anytime during ages 6ndash18 months Recommended spacing of dosesshould be maintained (Table 1)

Use of combination vaccines can reduce the number ofinjections required at an office visit Licensed combinationvaccines can be used whenever any components of the com-bination are indicated and its other components are notcontraindicated Use of licensed combination vaccines ispreferred over separate injection of their equivalent compo-nent vaccines (27) Only combination vaccines approvedby the Food and Drug Administration (FDA) should beused Individual vaccines must never be mixed in the samesyringe unless they are specifically approved for mixing byFDA Only one vaccine (DTaP and PRP-T Hib vaccine

marketed as TriHIBitreg [manufactured by Aventis Pasteur])is FDA-approved for mixing in the same syringe This vac-cine should not be used for primary vaccination in infantsaged 2 4 and 6 months but it can be used as a boosterafter any Hib vaccine

Nonsimultaneous AdministrationInactivated vaccines do not interfere with the immune

response to other inactivated vaccines or to live vaccinesAn inactivated vaccine can be administered either simulta-neously or at any time before or after a different inactivatedvaccine or live vaccine (Table 2)

The immune response to one live-virus vaccine might beimpaired if administered within 30 days of another live-virus vaccine (2829) Data are limited concerning inter-ference between live vaccines In a study conducted in twoUS health maintenance organizations persons who receivedvaricella vaccine lt30 days after MMR vaccination had anincreased risk for varicella vaccine failure (ie varicella dis-ease in a vaccinated person) of 25-fold compared with thosewho received varicella vaccine before or gt30 days after MMR(30) In contrast a 1999 study determined that the re-sponse to yellow fever vaccine is not affected by monova-lent measles vaccine administered 1ndash27 days earlier (21)The effect of nonsimultaneously administering rubellamumps varicella and yellow fever vaccines is unknown

To minimize the potential risk for interference parenter-ally administered live vaccines not administered on the sameday should be administered gt4 weeks apart whenever pos-sible (Table 2) If parenterally administered live vaccinesare separated by lt4 weeks the vaccine administered sec-ond should not be counted as a valid dose and should berepeated The repeat dose should be administered gt4 weeksafter the last invalid dose Yellow fever vaccine can be ad-ministered at any time after single-antigen measles vaccineTy21a typhoid vaccine and parenteral live vaccines (ie

TABLE 2 Guidelines for spacing of live and inactivatedantigens

Antigen Recommended minimum intervalcombination between doses

gt2 inactivated None can be administered simultaneouslyor at any interval between doses

Inactivated and live None can be administered simultaneouslyor at any interval between doses

gt2 live parenteral 4-week minimum interval if not administered simultaneously

Live oral vaccines (eg Ty21a typhoid vaccine oral polio vaccine) can beadministered simultaneously or at any interval before or after inactivatedor live parenteral vaccines

MMR varicella yellow fever) can be administered simul-taneously or at any interval before or after each other ifindicated

Spacing of Antibody-ContainingProducts and VaccinesLive Vaccines

Ty21a typhoid and yellow fever vaccines can be adminis-tered at any time before concurrent with or after adminis-tering any immune globulin or hyperimmune globulin (eghepatitis B immune globulin and rabies immune globu-lin) Blood (eg whole blood packed red blood cells andplasma) and other antibody-containing blood products(eg immune globulin hyperimmune globulin and in-travenous immune globulin [IGIV]) can inhibit the im-mune response to measles and rubella vaccines for gt3 months(3132) The effect of blood and immune globulin prepa-rations on the response to mumps and varicella vaccines isunknown but commercial immune globulin preparationscontain antibodies to these viruses Blood products avail-able in the United States are unlikely to contain a substan-tial amount of antibody to yellow fever vaccine virus Thelength of time that interference with parenteral live vacci-nation (except yellow fever vaccine) can persist after the an-tibody-containing product is a function of the amount ofantigen-specific antibody contained in the product (31ndash33) Therefore after an antibody-containing product is re-ceived parenteral live vaccines (except yellow fever vaccine)

should be delayed until the passive antibody has degraded(Table 3) Recommended intervals between receipt of vari-ous blood products and measles-containing vaccine andvaricella vaccine are listed in this report (Table 4) If a doseof parenteral live-virus vaccine (except yellow fever vaccine)is administered after an antibody-containing product butat an interval shorter than recommended in this report thevaccine dose should be repeated unless serologic testing in-dicates a response to the vaccine The repeat dose or sero-logic testing should be performed after the interval indicatedfor the antibody-containing product (Table 4)

Although passively acquired antibodies can interfere withthe response to rubella vaccine the low dose of anti-Rho(D)globulin administered to postpartum women has not beendemonstrated to reduce the response to the RA273 strain ru-bella vaccine (34) Because of the importance of rubella im-munity among childbearing-age women (635) thepostpartum vaccination of rubella-susceptible women withrubella or MMR vaccine should not be delayed because ofreceipt of anti-Rho(D) globulin or any other blood prod-uct during the last trimester of pregnancy or at deliveryThese women should be vaccinated immediately after de-livery and if possible tested gt3 months later to ensureimmunity to rubella and if necessary to measles (6)

Interference can occur if administering an antibody-containing product becomes necessary after administeringMMR its individual components or varicella vaccine Usu-ally vaccine virus replication and stimulation of immunity willoccur 1ndash2 weeks after vaccination Thus if the interval be-

TABLE 3 Guidelines for administering antibody-containing products and vaccinesSimultaneous administration

Combination Recommended minimum interval between doses

Antibody-containing products and inactivated antigen None can be administered simultaneously at different sites or at anytime between doses

Antibody-containing products and live antigen Should not be administered simultaneouslydagger If simultaneousadministration of measles-containing vaccine or varicella vaccine isunavoidable administer at different sites and revaccinate or test forseroconversion after the recommended interval (see Table 4)

Nonsimultaneous administration

Product administered

First Second Recommended minimum interval between doses

Antibody-containing products Inactivated antigen None

Inactivated antigen Antibody-containing products None

Antibody-containing products Live antigen Dose-relateddaggersect

Live antigen Antibody-containing products 2 weeks

Blood products containing substantial amounts of immunoglobulin including intramuscular and intravenous immune globulin specific hyperimmune globulin(eg hepatitis B immune globulin tetanus immune globulin varicella zoster immune globulin and rabies immune globulin) whole blood packed red cellsplasma and platelet products

daggerYellow fever and oral Ty21a typhoid vaccines are exceptions to these recommendations These live attenuated vaccines can be administered at any timebefore after or simultaneously with an antibody-containing product without substantially decreasing the antibody response

sectThe duration of interference of antibody-containing products with the immune response to the measles component of measles-containing vaccine andpossibly varicella vaccine is dose-related (see Table 4)

tween administering any of these vaccines and subsequentadministration of an antibody-containing product is lt14days vaccination should be repeated after the recommendedinterval (Tables 34) unless serologic testing indicates thatantibodies were produced

A humanized mouse monoclonal antibody product(palivizumab) is available for prevention of respiratory syn-cytial virus infection among infants and young childrenThis product contains only antibody to respiratory syncy-tial virus hence it will not interfere with immune responseto live or inactivated vaccines

Inactivated VaccinesAntibody-containing products interact less with inacti-

vated vaccines toxoids recombinant subunit and polysac-charide vaccines than with live vaccines (36) Thereforeadministering inactivated vaccines and toxoids either simul-taneously with or at any interval before or after receipt of anantibody-containing product should not substantially im-pair development of a protective antibody response (Table3) The vaccine or toxoid and antibody preparation shouldbe administered at different sites by using the standard rec-

TABLE 4 Suggested intervals between administration of antibody-containing products for different indications and measles-containing vaccine and varicella vaccine

Dose including mg Recommended intervalimmunoglobulin G (IgG)kg before measles or varicella

ProductIndication body weight vaccination (months)

Respiratory syncytial virus immune globulin 15 mgkg intramuscularly (IM) None(IG) monoclonal antibody (Synagistrade)dagger

Tetanus IG 250 units (10 mg IgGkg) IM 3

Hepatitis A IG

Contact prophylaxis 002 mLkg (33 mg IgGkg) IM 3

International travel 006 mLkg (10 mg IgGkg) IM 3

Hepatitis B IG 006 mLkg (10 mg IgGkg) IM 3

Rabies IG 20 IUkg (22 mg IgGkg) IM 4

Varicella IG 125 units10 kg (20ndash40 mg IgGkg) IM 5maximum 625 units

Measles prophylaxis IG

Standard (ie nonimmuno-compromised) contact 025 mLkg (40 mg IgGkg) IM 5

Immunocompromised contact 050 mLkg (80 mg IgGkg) IM 6

Blood transfusion

Red blood cells (RBCs) washed 10 mLkg negligible IgGkg Noneintravenously (IV)

RBCs adenine-saline added 10 mLkg (10 mg IgGkg) IV 3

Packed RBCs (hematocrit 65)sect 10 mLkg (60 mg IgGkg) IV 6

Whole blood (hematocrit 35ndash50)sect 10 mLkg (80ndash100 mg IgGkg) IV 6

Plasmaplatelet products 10 mLkg (160 mg IgGkg) IV 7

Cytomegalovirus intravenous immune 150 mgkg maximum 6globulin (IGIV)

Respiratory syncytial virus prophylaxis IGIV 750 mgkg 9

Replacement therapy for immune deficienciespara 300ndash400 mgkg IVpara 8

Immune thrombocytopenic purpura 400 mgkg IV 8

Kawasaki disease 2 gramskg IV 11

This table is not intended for determining the correct indications and dosages for using antibody-containing products Unvaccinated persons might not befully protected against measles during the entire recommended interval and additional doses of immune globulin or measles vaccine might be indicatedafter measles exposure Concentrations of measles antibody in an immune globulin preparation can vary by manufacturerrsquos lot Rates of antibody clearanceafter receipt of an immune globulin preparation might vary also Recommended intervals are extrapolated from an estimated half-life of 30 days forpassively acquired antibody and an observed interference with the immune response to measles vaccine for 5 months after a dose of 80 mg IgGkg(Source Mason W Takahashi M Schneider T Persisting passively acquired measles antibody following gamma globulin therapy for Kawasaki diseaseand response to live virus vaccination [Abstract 311] Presented at the 32

nd meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy

Los Angeles California October 1992)dagger

Contains antibody only to respiratory syncytial virussect

Assumes a serum IgG concentration of 16 mgmLpara

Measles and varicella vaccination is recommended for children with asymptomatic or mildly symptomatic human immunodeficiency virus (HIV) infection butis contraindicated for persons with severe immunosuppression from HIV or any other immunosuppressive disorder

ommended dose Increasing the vaccine dose volume ornumber of vaccinations is not indicated or recommended

Interchangeability of Vaccinesfrom Different Manufacturers

Numerous vaccines are available from different manufac-turers and these vaccines usually are not identical in anti-gen content or amount or method of formulationManufacturers use different production processes and theirproducts might contain different concentrations of antigenper dose or different stabilizers or preservatives

Available data indicate that infants who receive sequen-tial doses of different Hib conjugate hepatitis B and hepa-titis A vaccines produce a satisfactory antibody response aftera complete primary series (37ndash40) All brands of Hib con-jugate hepatitis Bsect and hepatitis A vaccines are interchange-able within their respective series If different brands of Hibconjugate vaccine are administered a total of three doses isconsidered adequate for the primary series among infantsAfter completing the primary series any Hib conjugate vac-cine can be used for the booster dose at ages 12ndash18 months

Data are limited regarding the safety immunogenicityand efficacy of using acellular pertussis (as DTaP) vaccinesfrom different manufacturers for successive doses of the per-tussis series Available data from one study indicate thatfor the first three doses of the DTaP series one or two dosesof Tripediareg (manufactured by Aventis Pasteur) followed byInfanrixreg (manufactured by GlaxoSmithKline) for the re-maining doses(s) is comparable to three doses of Tripediawith regard to immunogenicity as measured by antibodiesto diphtheria tetanus and pertussis toxoid and filamen-tous hemagglutinin (41) However in the absence of a clearserologic correlate of protection for pertussis the relevanceof these immunogenicity data for protection against per-tussis is unknown Whenever feasible the same brand ofDTaP vaccine should be used for all doses of the vaccina-tion series however vaccination providers might not knowor have available the type of DTaP vaccine previously ad-ministered to a child In this situation any DTaP vaccineshould be used to continue or complete the series Vaccina-tion should not be deferred because the brand used for pre-vious doses is not available or is unknown (2542)

Lapsed Vaccination ScheduleVaccination providers are encouraged to administer vac-

cines as close to the recommended intervals as possible

However longer-than-recommended intervals betweendoses do not reduce final antibody concentrations althoughprotection might not be attained until the recommendednumber of doses has been administered An interruption inthe vaccination schedule does not require restarting the entireseries of a vaccine or toxoid or the addition of extra doses

Unknown or UncertainVaccination Status

Vaccination providers frequently encounter persons whodo not have adequate documentation of vaccinations Pro-viders should only accept written dated records as evidenceof vaccination With the exception of pneumococcal polysac-charide vaccine (43) self-reported doses of vaccine withoutwritten documentation should not be accepted Althoughvaccinations should not be postponed if records cannot befound an attempt to locate missing records should be madeby contacting previous health-care providers and searchingfor a personally held record If records cannot be locatedthese persons should be considered susceptible and shouldbe started on the age-appropriate vaccination schedule Se-rologic testing for immunity is an alternative to vaccinationfor certain antigens (eg measles mumps rubella vari-cella tetanus diphtheria hepatitis A hepatitis B and po-liovirus) (see Vaccination of Internationally AdoptedChildren)

Contraindications and PrecautionsContraindications and precautions to vaccination dictate

circumstances when vaccines will not be administered Themajority of contraindications and precautions are temporaryand the vaccination can be administered later A contraindica-tion is a condition in a recipient that increases the risk for aserious adverse reaction A vaccine will not be administeredwhen a contraindication is present For example administer-ing influenza vaccine to a person with an anaphylactic allergyto egg protein could cause serious illness in or death of therecipient

National standards for pediatric immunization practiceshave been established and include true contraindicationsand precautions to vaccination (Table 5) (1) The only truecontraindication applicable to all vaccines is a history of asevere allergic reaction after a prior dose of vaccine or to avaccine constituent (unless the recipient has been desensi-tized) Severely immunocompromised persons should notreceive live vaccines Children who experience an encephal-opathy lt7 days after administration of a previous dose ofdiphtheria and tetanus toxoids and whole-cell pertussis vac-

sect The exception is the two-dose hepatitis B vaccination series for adolescentsaged 11ndash15 years Only Recombivax HBreg (Merck Vaccine Division) shouldbe used in this schedule Engerix-Breg is not approved by FDA for this schedule

TABLE 5 Guide to contraindications and precautions to commonly used vaccines Vaccine True contraindications and precautions Untrue (vaccines can be administered)

General for all vaccines includingdiphtheria and tetanus toxoidsand acellular pertussis vaccine(DTaP) pediatric diphtheria-tetanus toxoid (DT) adult tetanus-diphtheria toxoid (Td) inactivatedpoliovirus vaccine (IPV) measles-mumps-rubella vaccine (MMR)Haemophilus influenzae type bvaccine (Hib) hepatitis A vaccinehepatitis B vaccine varicellavaccine pneumococcal conjugatevaccine (PCV) influenza vaccineand pneumococcal polysaccha-ride vaccine (PPV)

ContraindicationsSerious allergic reaction (eg anaphylaxis) after aprevious vaccine dose

Serious allergic reaction (eg anaphylaxis) to a vaccinecomponent

PrecautionsModerate or severe acute illness with or without fever

Mild acute illness with or without fever

Mild to moderate local reaction (ie swelling rednesssoreness) low-grade or moderate fever after previousdose

Lack of previous physical examination in well-appearingperson

Current antimicrobial therapy

Convalescent phase of illness

Premature birth (hepatitis B vaccine is an exception incertain circumstances)dagger

Recent exposure to an infectious disease

History of penicillin allergy other nonvaccine allergiesrelatives with allergies receiving allergen extractimmunotherapy

ContraindicationsSevere allergic reaction after a previous dose or to avaccine component

Encephalopathy (eg coma decreased level ofconsciousness prolonged seizures) within 7 days ofadministration of previous dose of DTP or DTaP

Progressive neurologic disorder including infantilespasms uncontrolled epilepsy progressive encephal-opathy defer DTaP until neurologic status clarified andstabilized

PrecautionsFever of gt405degC lt48 hours after vaccination with aprevious dose of DTP or DTaP

Collapse or shock-like state (ie hypotonichyporesponsive episode) lt48 hours after receiving aprevious dose of DTPDTaP

Seizure lt3 days of receiving a previous dose of DTPDTaPsect

Persistent inconsolable crying lasting gt3 hours lt48hours after receiving a previous dose of DTPDTaP

Moderate or severe acute illness with or without fever

Temperature of lt405degC fussiness or mild drowsinessafter a previous dose of diphtheria toxoid-tetanustoxoid-pertussis vaccine (DTP)DTaP

Family history of seizuressect

Family history of sudden infant death syndrome

Family history of an adverse event after DTP or DTaPadministration

Stable neurologic conditions (eg cerebral palsy well-controlled convulsions developmental delay)

PrecautionsGuillain-Barreacute syndrome lt6 weeks after previous doseof tetanus toxoid-containing vaccine

MMRpara

ContraindicationsSevere allergic reaction to previous dose or vaccinecomponent

PrecautionsPregnancy

Pregnancy

Known severe immunodeficiency (eg hematologicand solid tumors congenital immunodeficiency long-term immunosuppressive therapy or severelysymptomatic human immunodeficiency virus [HIV]infection)

PrecautionsRecent (lt11 months) receipt of antibody-containingblood product (specific interval depends on product)sectsect

History of thrombocytopenia or thrombocytopenicpurpura

Positive tuberculin skin test

Simultaneous TB skin testingdaggerdagger

Breast-feeding

Pregnancy of recipientrsquos mother or other close orhousehold contact

Recipient is child-bearingndashage female

Immunodeficient family member or household contact

Asymptomatic or mildly symptomatic HIV infectionAllergy to eggs

cine (DTP) or DTaP not attributable to another identifi-able cause should not receive further doses of a vaccine thatcontains pertussis Because of the theoretical risk to thefetus women known to be pregnant should not receive liveattenuated virus vaccines (see Vaccination DuringPregnancy)

A precaution is a condition in a recipient that might in-crease the risk for a serious adverse reaction or that mightcompromise the ability of the vaccine to produce immu-nity (eg administering measles vaccine to a person withpassive immunity to measles from a blood transfusion) In-jury could result or a person might experience a more se-

ContraindicationSevere allergic reaction after a previous dose or to avaccine component

PrecautionsInfant weighing lt2000 gramsdagger

Events or conditions listed as precautions should be reviewed carefully Benefits and risks of administering a specific vaccine to a person under these circumstances should beconsidered If the risk from the vaccine is believed to outweigh the benefit the vaccine should not be administered If the benefit of vaccination is believed to outweigh the risk thevaccine should be administered Whether and when to administer DTaP to children with proven or suspected underlying neurologic disorders should be decided on a case-by-casebasis

dagger Hepatitis B vaccination should be deferred for infants weighing lt2000 grams if the mother is documented to be hepatitis B surface antigen (HbsAg)-negative at the time of theinfantrsquos birth Vaccination can commence at chronological age 1 month For infants born to HbsAg-positive women hepatitis B immunoglobulin and hepatitis B vaccine should beadministered at or soon after birth regardless of weight See text for details

sect Acetaminophen or other appropriate antipyretic can be administered to children with a personal or family history of seizures at the time of DTaP vaccination and every 4ndash6 hoursfor 24 hours thereafter to reduce the possibility of postvaccination fever (Source American Academy of Pediatrics Active immunization In Pickering LK ed 2000 red book reportof the Committee on Infectious Diseases 25th ed Elk Grove Village IL American Academy of Pediatrics 2000)

para MMR and varicella vaccines can be administered on the same day If not administered on the same day these vaccines should be separated by gt28 days Substantially immunosuppressive steroid dose is considered to be gt2 weeks of daily receipt of 20 mg or 2 mgkg body weight of prednisone or equivalentdaggerdagger Measles vaccination can suppress tuberculin reactivity temporarily Measles-containing vaccine can be administered on the same day as tuberculin skin testing If testing cannot

be performed until after the day of MMR vaccination the test should be postponed for gt4 weeks after the vaccination If an urgent need exists to skin test do so with theunderstanding that reactivity might be reduced by the vaccine

sectsect See text for detailsparapara If a vaccinee experiences a presumed vaccine-related rash 7ndash25 days after vaccination avoid direct contact with immunocompromised persons for the duration of the rash

Immunodeficient family member or household contactparapara

Asymptomatic or mildly symptomatic HIV infection

Humoral immunodeficiency (eg agammaglobulinemia)

TABLE 5 (Continued ) Guide to contraindications and precautions to commonly used vaccines Vaccine True contraindications and precautions Untrue (vaccines can be administered)

Hepatitis B

mdashContraindicationsSevere allergic reaction after a previous dose or to avaccine component

Age lt6 weeks

PrecautionModerate or severe acute illness with or without fever

Hepatitis A

Pregnancy

Autoimmune disease (eg systemic lupuserythematosis or rheumatoid arthritis)

Moderate or severe acute illness with or without feverVaricellapara Contraindications

Severe allergic reaction after a previous dose or to avaccine component

Substantial supression of cellular immunity

Pregnancy

PCV ContraindicationSevere allergic reaction after a previous dose or to avaccine component

Nonsevere (eg contact) allergy to latex or thimerosal

Concurrent administration of coumadin or aminophyl-line

Influenza

ContraindicationSevere allergic reaction to previous dose or vaccinecomponent including egg protein

PPV mdashContraindicationSevere allergic reaction after a previous dose or to avaccine component

vere reaction to the vaccine than would have otherwise beenexpected however the risk for this happening is less thanexpected with a contraindication Under normal circum-stances vaccinations should be deferred when a precautionis present However a vaccination might be indicated inthe presence of a precaution because the benefit of protec-tion from the vaccine outweighs the risk for an adverse re-action For example caution should be exercised invaccinating a child with DTaP who within 48 hours ofreceipt of a prior dose of DTP or DTaP experienced fevergt405C (105F) had persistent inconsolable crying for gt3hours collapsed or experienced a shock-like state or had aseizure lt3 days after receiving the previous dose of DTP orDTaP However administering a pertussis-containing vac-cine should be considered if the risk for pertussis is in-creased (eg during a pertussis outbreak) (25) The presenceof a moderate or severe acute illness with or without a feveris a precaution to administration of all vaccines Other pre-cautions are listed in this report (Table 5)

Physicians and other health-care providers might inap-propriately consider certain conditions or circumstances tobe true contraindications or precautions to vaccination Thismisconception results in missed opportunities to adminis-ter recommended vaccines (44) Likewise physicians andother health-care providers might fail to understand whatconstitutes a true contraindication or precaution and mightadminister a vaccine when it should be withheld This prac-tice can result in an increased risk for an adverse reaction tothe vaccine Conditions often inappropriately regarded ascontraindications to vaccination are listed in this report (Table5) Among the most common are diarrhea and minor upper-respiratory tract illnesses (including otitis media) with or with-out fever mild to moderate local reactions to a previous doseof vaccine current antimicrobial therapy and the convales-cent phase of an acute illness

The decision to administer or delay vaccination because ofa current or recent acute illness depends on the severity ofsymptoms and the etiology of the disease All vaccines can beadministered to persons with minor acute illness (eg diar-rhea or mild upper-respiratory tract infection with or withoutfever) Studies indicate that failure to vaccinate children withminor illnesses can seriously impede vaccination efforts (45ndash47) Among persons whose compliance with medical care can-not be ensured use of every opportunity to provideappropriate vaccinations is critical

The majority of studies support the safety and efficacy ofvaccinating persons who have mild illness (48ndash50) For ex-ample in the United States gt97 of children with mildillnesses produced measles antibody after vaccination (51)Only one limited study has reported a lower rate of

seroconversion (79) to the measles component of MMRvaccine among children with minor afebrile upper-respira-tory tract infections (52) Therefore vaccination should notbe delayed because of the presence of mild respiratory tractillness or other acute illness with or without fever

Persons with moderate or severe acute illness should bevaccinated as soon as they have recovered from the acutephase of the illness This precaution avoids superimposingadverse effects of the vaccine on the underlying illness ormistakenly attributing a manifestation of the underlyingillness to the vaccine

Routine physical examinations and measuring tempera-tures are not prerequisites for vaccinating infants and chil-dren who appear to be healthy Asking the parent or guardianif the child is ill and then postponing vaccination for thosewith moderate to severe illness or proceeding with vacci-nation if no contraindications exist are appropriate proce-dures in childhood immunization programs

A family history of seizures or other central nervous systemdisorders is not a contraindication to administration of per-tussis or other vaccines However delaying pertussis vaccina-tion for infants and children with a history of previousseizures until the childrsquos neurologic status has been assessedis prudent Pertussis vaccine should not be administered toinfants with evolving neurologic conditions until a treat-ment regimen has been established and the condition hasstabilized (25)

Vaccine AdministrationInfection Control and SterileTechnique

Persons administering vaccines should follow necessary pre-cautions to minimize risk for spreading disease Hands shouldbe washed with soap and water or cleansed with an alcohol-based waterless antiseptic hand rub between each patient con-tact Gloves are not required when administering vaccinationsunless persons administering vaccinations are likely to comeinto contact with potentially infectious body fluids or haveopen lesions on their hands Syringes and needles used forinjections must be sterile and disposable to minimize the riskof contamination A separate needle and syringe should beused for each injection Changing needles between drawingvaccine from a vial and injecting it into a recipient is unneces-sary Different vaccines should never be mixed in the samesyringe unless specifically licensed for such use

Disposable needles and syringes should be discarded inlabeled puncture-proof containers to prevent inadvertentneedle-stick injury or reuse Safety needles or needle-freeinjection devices also can reduce the risk for injury and

should be used whenever available (see Occupational SafetyRegulations)

Recommended Routes of Injectionand Needle Length

Routes of administration are recommended by the manu-facturer for each immunobiologic Deviation from the rec-ommended route of administration might reduce vaccineefficacy (5354) or increase local adverse reactions (55ndash57)Injectable immunobiologics should be administered wherethe likelihood of local neural vascular or tissue injury islimited Vaccines containing adjuvants should be injectedinto the muscle mass when administered subcutaneouslyor intradermally they can cause local irritation indurationskin discoloration inflammation and granuloma formation

Subcutaneous InjectionsSubcutaneous injections usually are administered at a 45-

degree angle into the thigh of infants aged lt12 months andin the upper-outer triceps area of persons aged gt12 monthsSubcutaneous injections can be administered into the up-per-outer triceps area of an infant if necessary A 58-inch23ndash25-gauge needle should be inserted into the subcuta-neous tissue

Intramuscular InjectionsIntramuscular injections are administered at a 90-degree

angle into the anterolateral aspect of the thigh or the del-toid muscle of the upper arm The buttock should not beused for administration of vaccines or toxoids because ofthe potential risk of injury to the sciatic nerve (58) In ad-dition injection into the buttock has been associated withdecreased immunogenicity of hepatitis B and rabies vac-cines in adults presumably because of inadvertent subcu-taneous injection or injection into deep fat tissue (5359)

For all intramuscular injections the needle should be longenough to reach the muscle mass and prevent vaccine fromseeping into subcutaneous tissue but not so long as to in-volve underlying nerves and blood vessels or bone (5460ndash62) Vaccinators should be familiar with the anatomy ofthe area into which they are injecting vaccine An individualdecision on needle size and site of injection must be madefor each person on the basis of age the volume of the mate-rial to be administered the size of the muscle and the depthbelow the muscle surface into which the material is to beinjected

Although certain vaccination specialists advocate aspira-tion (ie the syringe plunger pulled back before injection)no data exist to document the necessity for this procedure

If aspiration results in blood in the needle hub the needleshould be withdrawn and a new site should be selected

Infants (persons aged lt12 months) Among the ma-jority of infants the anterolateral aspect of the thighprovides the largest muscle mass and is therefore the rec-ommended site for injection For the majority of infants a78ndash1-inch 22ndash25-gauge needle is sufficient to penetratemuscle in the infantrsquos thigh

Toddlers and Older Children (persons aged gt12monthsndash18 years) The deltoid muscle can be used if themuscle mass is adequate The needle size can range from 22to 25 gauge and from 78 to 1frac14 inches on the basis of thesize of the muscle For toddlers the anterolateral thigh canbe used but the needle should be longer usually 1 inch

Adults (persons aged gt18 years) For adults the del-toid muscle is recommended for routine intramuscular vac-cinations The anterolateral thigh can be used The suggestedneedle size is 1ndash1frac12 inches and 22ndash25 gauge

Intradermal InjectionsIntradermal injections are usually administered on the volar

surface of the forearm With the bevel facing upwards a 38ndash34-inch 25ndash27-gauge needle can be inserted into the epider-mis at an angle parallel to the long axis of the forearm Theneedle should be inserted so that the entire bevel penetratesthe skin and the injected solution raises a small bleb Becauseof the small amounts of antigen used in intradermal vaccina-tions care must be taken not to inject the vaccine subcutane-ously because it can result in a suboptimal immunologicresponse

Multiple VaccinationsIf gt2 vaccine preparations are administered or if vaccine and

an immune globulin preparation are administered simulta-neously each preparation should be administered at a differ-ent anatomic site If gt2 injections must be administered in asingle limb the thigh is usually the preferred site because ofthe greater muscle mass the injections should be sufficientlyseparated (ie gt1 inch) so that any local reactions can be dif-ferentiated (5563) For older children and adults the deltoidmuscle can be used for multiple intramuscular injections ifnecessary The location of each injection should documentedin the personrsquos medical record

Jet InjectionJet injectors (JIs) are needle-free devices that drive liquid

medication through a nozzle orifice creating a narrow streamunder high pressure that penetrates skin to deliver a drug orvaccine into intradermal subcutaneous or intramuscular tis-

sues (6465) Increasing attention to JI technology as analternative to conventional needle injection has resulted fromrecent efforts to reduce the frequency of needle-stick inju-ries to health-care workers (66) and to overcome the im-proper reuse and other drawbacks of needles and syringesin economically developing countries (67ndash69) JIs have beenreported safe and effective in administering different liveand inactivated vaccines for viral and bacterial diseases (69)The immune responses generated are usually equivalent toand occasionally greater than those induced by needle in-jection However local reactions or injury (eg rednessinduration pain blood and ecchymosis at the injectionsite) can be more frequent for vaccines delivered by JIs com-pared with needle injection (6569)

Certain JIs were developed for situations in which substan-tial numbers of persons must be vaccinated rapidly but per-sonnel or supplies are insufficient to do so with conventionalneedle injection Such high-workload devices vaccinate con-secutive patients from the same nozzle orifice fluid pathwayand dose chamber which is refilled automatically from attachedvials containing lt50 doses each Since the 1950s these deviceshave been used extensively among military recruits and formass vaccination campaigns for disease control and eradica-tion (64) An outbreak of hepatitis B among patients receiv-ing injections from a multiple-usendashnozzle JI was documented(7071) and subsequent laboratory field and animal studiesdemonstrated that such devices could become contaminatedwith blood (697273)

No US-licensed high-workload vaccination devices ofunquestioned safety are available to vaccination programsEfforts are under way for the research and development ofnew high-workload JIs using disposable-cartridge technologythat avoids reuse of any unsterilized components having con-tact with the medication fluid pathway or patientrsquos blood Untilsuch devices become licensed and available the use of existingmultiple-usendashnozzle JIs should be limited Use can be consid-ered when the theoretical risk for bloodborne disease trans-mission is outweighed by the benefits of rapid vaccination withlimited personnel in responding to serious disease threats (egpandemic influenza or bioterrorism event) and by any com-peting risks of iatrogenic or occupational infections resultingfrom conventional needles and syringes Before such emer-gency use of multiple-usendashnozzle JIs health-care workersshould consult with local state national or internationalhealth agencies or organizations that have experience intheir use

In the 1990s a new generation of low-workload JIs wereintroduced with disposable cartridges serving as dose cham-bers and nozzle (69) With the provision of a new sterile

cartridge for each patient and other correct use these de-vices avoid the safety concerns described previously formultiple-usendashnozzle devices They can be used in accor-dance with their labeling for intradermal subcutaneous orintramuscular administration

Methods for Alleviating Discomfortand Pain Associated with Vaccination

Comfort measures and distraction techniques (eg play-ing music or pretending to blow away the pain) might helpchildren cope with the discomfort associated with vaccina-tion Pretreatment (30-60 minutes before injection) with5 topical lidocaine-prilocaine emulsion (EMLAreg creamor disk [manufactured by AstraZeneca LP]) can decreasethe pain of vaccination among infants by causing superfi-cial anesthesia (7475) Preliminary evidence indicates thatthis cream does not interfere with the immune response toMMR (76) Topical lidocaine-prilocaine emulsion shouldnot be used on infants aged lt12 months who are receivingtreatment with methemoglobin-inducing agents becauseof the possible development of methemoglobinemia (77)Acetaminophen has been used among children to reducethe discomfort and fever associated with vaccination (78)However acetaminophen can cause formation of methemo-globin and thus might interact with lidocaine-prilocainecream if used concurrently (77) Ibuprofen or othernonaspirin analgesic can be used if necessary Use of a topi-cal refrigerant (vapocoolant) spray can reduce the short-term pain associated with injections and can be as effectiveas lidocaine-prilocaine cream (79) Administering sweet-tasting fluid orally immediately before injection can resultin a calming or analgesic effect among certain infants

Nonstandard Vaccination PracticesRecommendations regarding route site and dosage of

immunobiologics are derived from data from clinical trialsfrom practical experience and from theoretical considerationsACIP strongly discourages variations from the recommendedroute site volume or number of doses of any vaccine

Variation from the recommended route and site can re-sult in inadequate protection The immunogenicity of hepa-titis B vaccine and rabies vaccine is substantially lower whenthe gluteal rather than the deltoid site is used for adminis-tration (5359) Hepatitis B vaccine administered intrad-ermally can result in a lower seroconversion rate and finaltiter of hepatitis B surface antibody than when adminis-tered by the deltoid intramuscular route (8081) Doses ofrabies vaccine administered in the gluteal site should not

be counted as valid doses and should be repeated Hepati-tis B vaccine administered by any route or site other thanintramuscularly in the anterolateral thigh or deltoid muscleshould not be counted as valid and should be repeatedunless serologic testing indicates that an adequate responsehas been achieved

Live attenuated parenteral vaccines (eg MMR varicellaor yellow fever) and certain inactivated vaccines (eg IPVpneumococcal polysaccharide and anthrax) are recom-mended by the manufacturers to be administered by sub-cutaneous injection Pneumococcal polysaccharide and IPVare approved for either intramuscular or subcutaneous ad-ministration Response to these vaccines probably will notbe affected if the vaccines are administered by the intra-muscular rather then subcutaneous route Repeating dosesof vaccine administered by the intramuscular route ratherthan by the subcutaneous route is unnecessary

Administering volumes smaller than those recommended(eg split doses) can result in inadequate protection Us-ing larger than the recommended dose can be hazardousbecause of excessive local or systemic concentrations of an-tigens or other vaccine constituents Using multiple reduceddoses that together equal a full immunizing dose or usingsmaller divided doses is not endorsed or recommended Anyvaccination using less than the standard dose should not becounted and the person should be revaccinated accordingto age unless serologic testing indicates that an adequateresponse has been achieved

Preventing Adverse ReactionsVaccines are intended to produce active immunity to spe-

cific antigens An adverse reaction is an untoward effect thatoccurs after a vaccination that is extraneous to the vaccinersquosprimary purpose of producing immunity Adverse reactionsalso are called vaccine side effects

All vaccines might cause adverse reactions (82) Vaccine ad-verse reactions are classified by three general categories localsystemic and allergic Local reactions are usually the least se-vere and most frequent Systemic reactions (eg fever) occurless frequently than local reactions Serious allergic reactions(eg anaphylaxis) are the most severe and least frequent Se-vere adverse reactions are rare

The key to preventing the majority of serious adverse reac-tions is screening Every person who administers vaccinesshould screen patients for contraindications and precautionsto the vaccine before it is administered (Table 5) Standard-ized screening questionnaires have been developed and areavailable from certain state immunization programs and

other sources (eg the Immunization Action Coalition athttpwwwimmunizeorg [accessed October 31 2001])

Severe allergic reactions after vaccination are rare How-ever all physicians and other health-care providers whoadminister vaccines should have procedures in place for theemergency management of a person who experiences ananaphylactic reaction All vaccine providers should be fa-miliar with the office emergency plan and be certified incardiopulmonary resuscitation

Syncope (vasovagal or vasodepressor reaction) can occur af-ter vaccination most commonly among adolescents and youngadults During 1990ndashAugust 2001 a total of 2269 reports tothe Vaccine Adverse Event Reporting system were coded assyncope Forty percent of these episodes were reported amongpersons aged 10ndash18 years (CDC unpublished data 2001)Approximately 12 of reported syncopal episodes resulted inhospitalization because of injury or medical evaluation Seri-ous injury including skull fractures and cerebral bleeding havebeen reported to result from syncopal episodes after vacci-nation A published review of syncope after vaccination re-ported that 63 of syncopal episodes occurred lt5 minutesafter vaccination and 89 occurred within 15 minutes af-ter vaccination (83) Although syncopal episodes are un-common and serious allergic reactions are rare certainvaccination specialists recommend that persons be observedfor 15ndash20 minutes after being vaccinated if possible (84)If syncope develops patients should be observed until thesymptoms resolve

Managing Acute Vaccine ReactionsAlthough rare after vaccination the immediate onset and

life-threatening nature of an anaphylactic reaction require thatpersonnel and facilities providing vaccinations be capable ofproviding initial care for suspected anaphylaxis Epinephrineand equipment for maintaining an airway should be availablefor immediate use

Anaphylaxis usually begins within minutes of vaccine ad-ministration Rapidly recognizing and initiating treatment arerequired to prevent possible progression to cardiovascular col-lapse If flushing facial edema urticaria itching swelling ofthe mouth or throat wheezing difficulty breathing or othersigns of anaphylaxis occur the patient should be placed in arecumbent position with the legs elevated Aqueous epineph-rine (11000) should be administered and can be repeatedwithin 10ndash20 minutes (84) A dose of diphenhydramine hy-drochloride might shorten the reaction but it will havelittle immediate effect Maintenance of an airway and oxy-gen administration might be necessary Arrangements should

be made for immediate transfer to an emergency facility forfurther evaluation and treatment

Occupational Safety RegulationsBloodborne diseases (eg hepatitis B and C and human

immunodeficiency virus [HIV]) are occupational hazards forhealth-care workers In November 2000 to reduce the in-cidence of needle-stick injuries among health-care workersand the consequent risk for bloodborne diseases acquiredfrom patients the Needlestick Safety and Prevention Actwas signed into law The act directed the Occupational Safetyand Health Administration (OSHA) to strengthen its ex-isting bloodborne pathogen standards Those standards wererevised and became effective in April 2001 (66) These fed-eral regulations require that safer injection devices (egneedle-shielding syringes or needle-free injectors) be usedfor parenteral vaccination in all clinical settings when suchdevices are appropriate commercially available and capableof achieving the intended clinical purpose The rules alsorequire that records be kept documenting the incidence ofinjuries caused by medical sharps (except in workplaces withlt10 employees) and that nonmanagerial employees be in-volved in the evaluation and selection of safer devices to beprocured

Needle-shielding or needle-free devices that might satisfy theoccupational safety regulations for administering parenteralinjections are available in the United States and are listed atmultiple websites (6985ndash87)para Additional information regard-ing implementation and enforcement of these regulations isavailable at the OSHA website at httpwwwosha-slcgovneedlesticks (accessed October 31 2001)

Storage and Handlingof Immunobiologics

Failure to adhere to recommended specifications for stor-age and handling of immunobiologics can reduce potencyresulting in an inadequate immune response in the recipi-ent Recommendations included in a productrsquos packageinsert including reconstitution of the vaccine should befollowed carefully Vaccine quality is the shared responsi-bility of all parties from the time the vaccine is manufac-tured until administration All vaccines should be inspectedupon delivery and monitored during storage to ensure that

the cold chain has been maintained Vaccines should con-tinue to be stored at recommended temperatures immedi-ately upon receipt Certain vaccines (eg MMR varicellaand yellow fever) are sensitive to increased temperature Allother vaccines are sensitive to freezing Mishandled vaccineusually is not distinguishable from potent vaccine Whenin doubt regarding the appropriate handling of a vaccinevaccination providers should contact the manufacturer Vac-cines that have been mishandled (eg inactivated vaccinesand toxoids that have been exposed to freezing tempera-tures) or that are beyond their expiration date should notbe administered If mishandled or expired vaccines are ad-ministered inadvertently they should not be counted asvalid doses and should be repeated unless serologic testingindicates a response to the vaccine

Live attenuated virus vaccines should be administeredpromptly after reconstitution Varicella vaccine must be ad-ministered lt30 minutes after reconstitution Yellow fever vac-cine must be used lt1 hour after reconstitution MMR vaccinemust be administered lt8 hours after reconstitution If notadministered within these prescribed time periods after recon-stitution the vaccine must be discarded

The majority of vaccines have a similar appearance afterbeing drawn into a syringe Instances in which the wrongvaccine inadvertently was administered are attributable tothe practice of prefilling syringes or drawing doses of a vac-cine into multiple syringes before their immediate needACIP discourages the routine practice of prefilling syringesbecause of the potential for such administration errors Toprevent errors vaccine doses should not be drawn into asyringe until immediately before administration In certaincircumstances where a single vaccine type is being used (egin advance of a community influenza vaccination campaign)filling multiple syringes before their immediate use can beconsidered Care should be taken to ensure that the coldchain is maintained until the vaccine is administered Whenthe syringes are filled the type of vaccine lot number anddate of filling must be carefully labeled on each syringeand the doses should be administered as soon as possibleafter filling

Certain vaccines are distributed in multidose vials Whenopened the remaining doses from partially used multidosevials can be administered until the expiration date printed onthe vial or vaccine packaging provided that the vial has beenstored correctly and that the vaccine is not visibly contami-nated

para Internet sites with device listings are identified for information purposes onlyCDC the US Public Health Service and the Department of Health andHuman Services do not endorse any specific device or imply that the deviceslisted would all satisfy the needle-stick prevention regulations

Special SituationsConcurrently AdministeringAntimicrobial Agents and Vaccines

With limited exceptions using an antibiotic is not a con-traindication to vaccination Antimicrobial agents have no ef-fect on the response to live attenuated vaccines except liveoral Ty21a typhoid vaccine and have no effect on inactivatedrecombinant subunit or polysaccharide vaccines or toxoidsTy21a typhoid vaccine should not be administered to per-sons receiving antimicrobial agents until gt24 hours afterany antibiotic dose (18)

Antiviral drugs used for treatment or prophylaxis of influ-enza virus infections have no effect on the response to inacti-vated influenza vaccine (88) Antiviral drugs active againstherpesviruses (eg acyclovir or valacyclovir) might reduce theefficacy of live attenuated varicella vaccine These drugs shouldbe discontinued gt24 hours before administration of varicellavaccine if possible

The antimalarial drug mefloquine (Lariamreg [manufacturedby Roche Laboratories Inc]) could affect the immune responseto oral Ty21a typhoid vaccine if both are taken simultaneously(8990) To minimize this effect administering Ty21a typhoidvaccine gt24 hours before or after a dose of mefloquine isprudent

Tuberculosis Screeningand Skin Test Reactivity

Measles illness severe acute or chronic infections HIVinfection and malnutrition can create an anergic state dur-ing which the tuberculin skin test (usually known as puri-fied protein derivative [PPD] skin test) might give a falsenegative reaction (91ndash93) Although any live attenuatedmeasles vaccine can theoretically suppress PPD reactivitythe degree of suppression is probably less than that occur-ring from acute infection from wild measles virus Althoughroutine PPD screening of all children is no longer recom-mended PPD screening is sometimes needed at the sametime as administering a measles-containing vaccine (egfor well-child care school entrance or for employee healthreasons) and the following options should be considered

bull PPD and measles-containing vaccine can be adminis-tered at the same visit (preferred option) Simultaneouslyadministering PPD and measles-containing vaccine doesnot interfere with reading the PPD result at 48ndash72 hoursand ensures that the person has received measles vaccine

bull If the measles-containing vaccine has been administeredrecently PPD screening should be delayed gt4 weeksafter vaccination A delay in performing PPD will re-

move the concern of any theoretical but transient sup-pression of PPD reactivity from the vaccine

bull PPD screening can be performed and read before ad-ministering the measles-containing vaccine This op-tion is the least favored because it will delay receipt ofthe measles-containing vaccine

No data exist for the potential degree of PPD suppressionthat might be associated with other parenteral live attenuatedvirus vaccines (eg varicella or yellow fever) Nevertheless inthe absence of data following guidelines for measles-containing vaccine when scheduling PPD screening and ad-ministering other parenteral live attenuated virus vaccinesis prudent If a risk exists that the opportunity to vaccinatemight be missed vaccination should not be delayed onlybecause of these theoretical considerations

Mucosally administered live attenuated virus vaccines (egOPV and intranasally administered influenza vaccine) are un-likely to affect the response to PPD No evidence has beenreported that inactivated vaccines polysaccharide vaccinesrecombinant or subunit vaccines or toxoids interfere withresponse to PPD

PPD reactivity in the absence of tuberculosis disease is not acontraindication to administration of any vaccine includingparenteral live attenuated virus vaccines Tuberculosis dis-ease is not a contraindication to vaccination unless the per-son is moderately or severely ill Although no studies havereported the effect of MMR vaccine on persons with un-treated tuberculosis a theoretical basis exists for concernthat measles vaccine might exacerbate tuberculosis (6)Consequently before administering MMR to persons withuntreated active tuberculosis initiating antituberculosistherapy is advisable (6) Ruling out concurrent immuno-suppression (eg immunosuppression caused by HIV in-fection) before administering live attenuated vaccines is alsoprudent

Severe Allergy to VaccineComponents

Vaccine components can cause allergic reactions among cer-tain recipients These reactions can be local or systemic andcan include mild to severe anaphylaxis or anaphylactic-likeresponses (eg generalized urticaria or hives wheezing swell-ing of the mouth and throat difficulty breathing hypoten-sion and shock) Allergic reactions might be caused by thevaccine antigen residual animal protein antimicrobial agentspreservatives stabilizers or other vaccine components (94)An extensive listing of vaccine components their use and thevaccines that contain each component has been published (95)and is also available from CDCrsquos National Immunization

Program website at httpwwwcdcgovnip (accessed Oc-tober 31 2001)

The most common animal protein allergen is egg pro-tein which is found in vaccines prepared by using embryo-nated chicken eggs (influenza and yellow fever vaccines)Ordinarily persons who are able to eat eggs or egg prod-ucts safely can receive these vaccines persons with historiesof anaphylactic or anaphylactic-like allergy to eggs or eggproteins should not be administered these vaccines Askingpersons if they can eat eggs without adverse effects is a rea-sonable way to determine who might be at risk for allergicreactions from receiving yellow fever and influenza vaccinesA regimen for administering influenza vaccine to childrenwith egg hypersensitivity and severe asthma has been de-veloped (96)

Measles and mumps vaccine viruses are grown in chickembryo fibroblast tissue culture Persons with a serious eggallergy can receive measles- or mumps-containing vaccineswithout skin testing or desensitization to egg protein (6) Ru-bella and varicella vaccines are grown in human diploid cellcultures and can safely be administered to persons with histo-ries of severe allergy to eggs or egg proteins The rare seriousallergic reaction after measles or mumps vaccination or MMRare not believed to be caused by egg antigens but to othercomponents of the vaccine (eg gelatin) (97ndash100) MMR itscomponent vaccines and other vaccines contain hydrolyzedgelatin as a stabilizer Extreme caution should be exercised whenadministering vaccines that contain gelatin to persons who havea history of an anaphylactic reaction to gelatin or gelatin-containing products Before administering gelatin-containing vaccines to such persons skin testing forsensitivity to gelatin can be considered However no spe-cific protocols for this approach have been published

Certain vaccines contain trace amounts of antibiotics orother preservatives (eg neomycin or thimerosal) to whichpatients might be severely allergic The information providedin the vaccine package insert should be reviewed carefully be-fore deciding if the rare patient with such allergies should re-ceive the vaccine No licensed vaccine contains penicillin orpenicillin derivatives

Certain vaccines contain trace amounts of neomycin Per-sons who have experienced anaphylactic reactions to neomy-cin should not receive these vaccines Most often neomycinallergy is a contact dermatitis a manifestation of a delayedtype (cell-mediated) immune response rather than anaphy-laxis (101102) A history of delayed type reactions to neomy-cin is not a contraindication for administration of thesevaccines

Thimerosal is an organic mercurial compound in use sincethe 1930s and added to certain immunobiologic products as a

preservative A joint statement issued by the US PublicHealth Service and the American Academy of Pediatrics(AAP) in 1999 (103) and agreed to by the American Acad-emy of Family Physicians (AAFP) later in 1999 establishedthe goal of removing thimerosal as soon as possible fromvaccines routinely recommended for infants Although noevidence exists of any harm caused by low levels of thimero-sal in vaccines and the risk was only theoretical (104) thisgoal was established as a precautionary measure

The public is concerned about the health effects of mer-cury exposure of any type and the elimination of mercuryfrom vaccines was judged a feasible means of reducing aninfantrsquos total exposure to mercury in a world where otherenvironmental sources of exposure are more difficult or im-possible to eliminate (eg certain foods) Since mid-2001vaccines routinely recommended for children have beenmanufactured without thimerosal as a preservative and con-tain either no thimerosal or only trace amounts Thimero-sal as a preservative is present in certain other vaccines (egTd DT one of two adult hepatitis B vaccines and influ-enza vaccine) A trace thimerosal formulation of one brandof influenza vaccine was licensed by FDA in September2001

Receiving thimerosal-containing vaccines has been believedto lead to induction of allergy However limited scientific ba-sis exists for this assertion (94) Hypersensitivity to thimerosalusually consists of local delayed type hypersensitivity reactions(105ndash107) Thimerosal elicits positive delayed type hypersen-sitivity patch tests in 1ndash18 of persons tested but thesetests have limited or no clinical relevance (108109) The ma-jority of patients do not experience reactions to thimerosaladministered as a component of vaccines even when patch orintradermal tests for thimerosal indicate hypersensitivity (109)A localized or delayed type hypersensitivity reaction to thime-rosal is not a contraindication to receipt of a vaccine that con-tains thimerosal

Latex AllergyLatex is liquid sap from the commercial rubber tree La-

tex contains naturally occurring impurities (eg plant pro-teins and peptides) which are believed to be responsiblefor allergic reactions Latex is processed to form natural rub-ber latex and dry natural rubber Dry natural rubber andnatural rubber latex might contain the same plant impuri-ties as latex but in lesser amounts Natural rubber latex isused to produce medical gloves catheters and other prod-ucts Dry natural rubber is used in syringe plungers vialstoppers and injection ports on intravascular tubing Syn-thetic rubber and synthetic latex also are used in medical

gloves syringe plungers and vial stoppers Synthetic rub-ber and synthetic latex do not contain natural rubber ornatural latex and therefore do not contain the impuritieslinked to allergic reactions

The most common type of latex sensitivity is contact-type (type 4) allergy usually as a result of prolonged contactwith latex-containing gloves (110) However injection-procedurendashassociated latex allergies among patients withdiabetes have been described (111ndash113) Allergic reactions(including anaphylaxis) after vaccination procedures are rareOnly one report of an allergic reaction after administeringhepatitis B vaccine in a patient with known severe allergy(anaphylaxis) to latex has been published (114)

If a person reports a severe (anaphylactic) allergy to latexvaccines supplied in vials or syringes that contain naturalrubber should not be administered unless the benefit ofvaccination outweighs the risk of an allergic reaction to thevaccine For latex allergies other than anaphylactic allergies(eg a history of contact allergy to latex gloves) vaccinessupplied in vials or syringes that contain dry natural rub-ber or natural rubber latex can be administered

Vaccination of Premature InfantsIn the majority of cases infants born prematurely re-

gardless of birth weight should be vaccinated at the samechronological age and according to the same schedule andprecautions as full-term infants and children Birth weightand size are not factors in deciding whether to postponeroutine vaccination of a clinically stable premature infant(115ndash117) except for hepatitis B vaccine The full recom-mended dose of each vaccine should be used Divided orreduced doses are not recommended (118)

Studies demonstrate that decreased seroconversion ratesmight occur among certain premature infants with low birthweights (ie lt2000 grams) after administration of hepatitisB vaccine at birth (119) However by chronological age 1month all premature infants regardless of initial birth weightor gestational age are as likely to respond as adequately as olderand larger infants (120ndash122) A premature infant born toHBsAg-positive mothers and mothers with unknownHBsAg status must receive immunoprophylaxis with hepa-titis B vaccine and hepatitis B immunoglobulin (HBIG)lt12 hours after birth If these infants weigh lt2000 gramsat birth the initial vaccine dose should not be counted to-wards completion of the hepatitis B vaccine series and threeadditional doses of hepatitis B vaccine should be adminis-tered beginning when the infant is age 1 month The opti-mal timing of the first dose of hepatitis B vaccine forpremature infants of HBsAg-negative mothers with a birth

weight of lt2000 grams has not been determined How-ever these infants can receive the first dose of the hepatitisB vaccine series at chronological age 1 month Prematureinfants discharged from the hospital before chronologicalage 1 month can also be administered hepatitis B vaccine atdischarge if they are medically stable and have gained weightconsistently

Breast-Feeding and VaccinationNeither inactivated nor live vaccines administered to a lac-

tating woman affect the safety of breast-feeding for mothersor infants Breast-feeding does not adversely affect immuniza-tion and is not a contraindication for any vaccine Limiteddata indicate that breast-feeding can enhance the responseto certain vaccine antigens (123) Breast-fed infants shouldbe vaccinated according to routine recommended sched-ules (124ndash126)

Although live vaccines multiply within the motherrsquos bodythe majority have not been demonstrated to be excreted inhuman milk Although rubella vaccine virus might be excretedin human milk the virus usually does not infect the infant Ifinfection does occur it is well-tolerated because the viruses areattenuated (127) Inactivated recombinant subunit polysac-charide conjugate vaccines and toxoids pose no risk for motherswho are breast-feeding or for their infants

Vaccination During PregnancyRisk to a developing fetus from vaccination of the mother

during pregnancy is primarily theoretical No evidence existsof risk from vaccinating pregnant women with inactivated vi-rus or bacterial vaccines or toxoids (128129) Benefits of vac-cinating pregnant women usually outweigh potential riskswhen the likelihood of disease exposure is high when in-fection would pose a risk to the mother or fetus and whenthe vaccine is unlikely to cause harm

Td toxoid is indicated routinely for pregnant women Pre-viously vaccinated pregnant women who have not received aTd vaccination within the last 10 years should receive a boosterdose Pregnant women who are not immunized or only par-tially immunized against tetanus should complete the primaryseries (130) Depending on when a woman seeks prenatal careand the required interval between doses one or two doses ofTd can be administered before delivery Women for whomthe vaccine is indicated but who have not completed the rec-ommended three-dose series during pregnancy should receivefollow-up after delivery to ensure the series is completed

Women in the second and third trimesters of pregnancy havebeen demonstrated to be at increased risk for hospitalizationfrom influenza (131) Therefore routine influenza vaccina-

tion is recommended for healthy women who will be be-yond the first trimester of pregnancy (ie gt14 weeks ofgestation) during influenza season (usually DecemberndashMarch in the United States) (88) Women who have medi-cal conditions that increase their risk for complications ofinfluenza should be vaccinated before the influenza seasonregardless of the stage of pregnancy

IPV can be administered to pregnant women who are atrisk for exposure to wild-type poliovirus infection (4) Hepa-titis B vaccine is recommended for pregnant women at riskfor hepatitis B virus infection (132) Hepatitis A pneumo-coccal polysaccharide and meningococcal polysaccharidevaccines should be considered for women at increased riskfor those infections (43133134)

Pregnant women who must travel to areas where the riskfor yellow fever is high should receive yellow fever vaccinebecause the limited theoretical risk from vaccination is sub-stantially outweighed by the risk for yellow fever infection(22135) Pregnancy is a contraindication for measlesmumps rubella and varicella vaccines Although of theo-retical concern no cases of congenital rubella or varicellasyndrome or abnormalities attributable to fetal infectionhave been observed among infants born to susceptiblewomen who received rubella or varicella vaccines duringpregnancy (6136) Because of the importance of protect-ing women of childbearing age against rubella reasonablepractices in any immunization program include askingwomen if they are pregnant or intend to become pregnantin the next 4 weeks not vaccinating women who state thatthey are pregnant explaining the potential risk for the fe-tus to women who state that they are not pregnant andcounseling women who are vaccinated not to become preg-nant during the 4 weeks after MMR vaccination (635137)Routine pregnancy testing of women of childbearing agebefore administering a live-virus vaccine is not recommended(6) If a pregnant woman is inadvertently vaccinated or ifshe becomes pregnant within 4 weeks after MMR or vari-cella vaccination she should be counseled regarding thetheoretical basis of concern for the fetus however MMR orvaricella vaccination during pregnancy should not ordinarilybe a reason to terminate pregnancy (68)

Persons who receive MMR vaccine do not transmit the vac-cine viruses to contacts (6) Transmission of varicella vaccinevirus to contacts is rare (138) MMR and varicella vaccinesshould be administered when indicated to the children andother household contacts of pregnant women (68)

All pregnant women should be evaluated for immunity torubella and be tested for the presence of HBsAg (635132)Women susceptible to rubella should be vaccinated immedi-

ately after delivery A woman known to be HBsAg-positiveshould be followed carefully to ensure that the infant re-ceives HBIG and begins the hepatitis B vaccine series lt12hours after birth and that the infant completes the recom-mended hepatitis B vaccine series (132) No known riskexists for the fetus from passive immunization of pregnantwomen with immune globulin preparations

Vaccination of InternationallyAdopted Children

The ability of a clinician to determine that a person isprotected on the basis of their country of origin and theirrecords alone is limited Internationally adopted childrenshould receive vaccines according to recommended sched-ules for children in the United States Only written docu-mentation should be accepted as evidence of priorvaccination Written records are more likely to predict pro-tection if the vaccines dates of administration intervalsbetween doses and the childrsquos age at the time of immuni-zation are comparable to the current US recommenda-tions Although vaccines with inadequate potency have beenproduced in other countries (139140) the majority of vac-cines used worldwide are produced with adequate qualitycontrol standards and are potent

The number of American families adopting children fromoutside the United States has increased substantially in recentyears (141) Adopted childrenrsquos birth countries often have im-munization schedules that differ from the recommended child-hood immunization schedule in the United States Differencesin the US immunization schedule and those used in othercountries include the vaccines administered the recommendedages of administration and the number and timing of doses

Data are inconclusive regarding the extent to which aninternationally adopted childrsquos immunization record reflectsthe childrsquos protection A childrsquos record might indicate ad-ministration of MMR vaccine when only single-antigenmeasles vaccine was administered A study of childrenadopted from the Peoplersquos Republic of China Russia andEastern Europe determined that only 39 (range 17ndash88 by country) of children with documentation of gt3doses of DTP before adoption had protective levels of diph-theria and tetanus antitoxin (142) However antibody test-ing was performed by using a hemagglutination assay whichtends to underestimate protection and cannot directly becompared with antibody concentration (143) Anotherstudy measured antibody to diphtheria and tetanus toxinsamong 51 children who had records of having received gt2doses of DTP The majority of the children were from Rus-sia Eastern Europe and Asian countries and 78 had re-

ceived all their vaccine doses in an orphanage Overall 94had evidence of protection against diphtheria (EIA gt 01IUmL) A total of 84 had protection against tetanus (en-zyme-linked immunosorbent assay [ELISA] gt 05 IUmL)Among children without protective tetanus antitoxin con-centration all except one had records of gt3 doses of vac-cine and the majority of nonprotective concentrations werecategorized as indeterminate (ELISA = 005ndash049 IUmL)(144) Reasons for the discrepant findings in these two stud-ies probably relate to different laboratory methodologiesthe study using a hemagglutination assay might have un-derestimated the number of children who were protectedAdditional studies using standardized methodologies areneeded Data are likely to remain limited for countries otherthan the Peoplersquos Republic of China Russia and EasternEurope because of the limited number of adoptees fromother countries

Physicians and other health-care providers can follow oneof multiple approaches if a question exists regarding whethervaccines administered to an international adoptee were im-

munogenic Repeating the vaccinations is an acceptable op-tion Doing so is usually safe and avoids the need to obtainand interpret serologic tests If avoiding unnecessary injec-tions is desired judicious use of serologic testing might behelpful in determining which immunizations are neededThis report provides guidance on possible approaches toevaluation and revaccination for each vaccine recommendeduniversally for children in the United States (see Table 6and the following sections)

MMR VaccineThe simplest approach to resolving concerns regarding

MMR immunization among internationally adopted chil-dren is to revaccinate with one or two doses of MMR vac-cine depending on the childrsquos age Serious adverse eventsafter MMR vaccinations are rare (6) No evidence indicatesthat administering MMR vaccine increases the risk for ad-verse reactions among persons who are already immune tomeasles mumps or rubella as a result of previous vaccina-tion or natural disease Doses of measles-containing vaccine

Measles mumps and rubella (MMR)

Haemophilus influenzae type b (Hib)

Hepatitis B

Poliovirus

Diphtheria and tetanus toxoids and acellularpertussis (DTaP)

Varicella

Pneumococcal

Revaccinate with MMR

Age-appropriate revaccination

Serological testing for hepatitis Bsurface antigen

Revaccinate with inactivated poliovirusvaccine (IPV)

Revaccination with DTaP with serologictesting for specific IgG antibody to tetanusand diphtheria toxins in the event of asevere local reaction

Age-appropriate vaccination of children wholack a reliable history of previous varicelladisease

Age-appropriate vaccination

Serologic testing for immunoglobulin G (IgG)antibody to vaccine viruses indicated byvaccination record

Serologic testing for neutralizing antibody topoliovirus types 1 2 and 3 (limited availability)or administer single dose of IPV followed byserologic testing for neutralizing antibody topoliovirus types 1 2 and 3

Children whose records indicate receipt of gt3doses serologic testing for specific IgG antibodyto diphtheria and tetanus toxins before adminis-tering additional doses (see text) or administera single booster dose of DTaP followed byserological testing after 1 month for specific IgGantibody to diphtheria and tetanus toxins withrevaccination as appropriate (see text)

TABLE 6 Approaches to the evaluation and vaccination of internationally adopted children

Vaccine Recommended approach Alternative approach

administered before the first birthday should not be countedas part of the series (6) Alternatively serologic testing forimmunoglobulin G (IgG) antibody to vaccine viruses indi-cated on the vaccination record can be considered Sero-logic testing is widely available for measles and rubella IgGantibody A child whose record indicates receipt of monova-lent measles or measles-rubella vaccine at age gt1 year andwho has protective antibody against measles and rubellashould receive a single dose of MMR as age-appropriate toensure protection against mumps (and rubella if measlesvaccine alone had been used) If a child whose record indi-cates receipt of MMR at age gt12 months has a protectiveconcentration of antibody to measles no additional vacci-nation is needed unless required for school entry

Hib VaccineSerologic correlates of protection for children vaccinated

gt2 months previously might be difficult to interpret Be-cause the number of vaccinations needed for protectiondecreases with age and adverse events are rare (24) age-appropriate vaccination should be provided Hib vaccinationis not recommended routinely for children aged gt5 years

Hepatitis B VaccineSerologic testing for HBsAg is recommended for interna-

tional adoptees and children determined to be HBsAg-positive should be monitored for the development of liverdisease Household members of HBsAg-positive childrenshould be vaccinated A child whose records indicate re-ceipt of gt3 doses of vaccine can be considered protectedand additional doses are not needed if gt1 doses were ad-ministered at age gt6 months Children who received theirlast hepatitis B vaccine dose at age lt6 months should re-ceive an additional dose at age gt6 months Those who havereceived lt3 doses should complete the series at the recom-mended intervals and ages (Table 1)

Poliovirus VaccineThe simplest approach is to revaccinate internationally

adopted children with IPV according to the US scheduleAdverse events after IPV are rare (4) Children appropri-ately vaccinated with three doses of OPV in economicallydeveloping countries might have suboptimal seroconversionincluding to type 3 poliovirus (125) Serologic testing forneutralizing antibody to poliovirus types 1 2 and 3 can beobtained commercially and at certain state health depart-ment laboratories Children with protective titers againstall three types do not need revaccination and should com-plete the schedule as age-appropriate Alternately becausethe booster response after a single dose of IPV is excellentamong children who previously received OPV (3) a single

dose of IPV can be administered initially with serologictesting performed 1 month later

DTaP VaccineVaccination providers can revaccinate a child with DTaP

vaccine without regard to recorded doses however one con-cern regarding this approach is that data indicate increasedrates of local adverse reactions after the fourth and fifth dosesof DTP or DTaP (42) If a revaccination approach is adoptedand a severe local reaction occurs serologic testing for spe-cific IgG antibody to tetanus and diphtheria toxins can bemeasured before administering additional doses Protectiveconcentration indicates that further doses are unneces-sary and subsequent vaccination should occur as age-appropriate No established serologic correlates exist forprotection against pertussis

For a child whose record indicates receipt of gt3 doses ofDTP or DTaP serologic testing for specific IgG antibody toboth diphtheria and tetanus toxin before additional dosesis a reasonable approach If a protective concentration ispresent recorded doses can be considered valid and thevaccination series should be completed as age-appropriateIndeterminate antibody concentration might indicate im-munologic memory but antibody waning serology can berepeated after a booster dose if the vaccination providerwishes to avoid revaccination with a complete series

Alternately for a child whose records indicate receipt ofgt3 doses a single booster dose can be administered fol-lowed by serologic testing after 1 month for specific IgGantibody to both diphtheria and tetanus toxins If a pro-tective concentration is obtained the recorded doses canbe considered valid and the vaccination series completed asage-appropriate Children with indeterminate concentra-tion after a booster dose should be revaccinated with a com-plete series

Varicella VaccineVaricella vaccine is not administered in the majority of

countries A child who lacks a reliable medical history re-garding prior varicella disease should be vaccinated as age-appropriate (8)

Pneumococcal VaccinesPneumococcal conjugate and pneumococcal polysaccha-

ride vaccines are not administered in the majority of coun-

Toxin neutralization testing is reliable but not readily available Enzymeimmunoassay tests are the most readily available although passivehemagglutination is available in certain areas Physicians should contact thelaboratory performing the test for interpretive standards and limitations Protectiveconcentrations for diphtheria are defined as gt01 IUmL and for tetanus asgt01ndash02 IUmL

tries and should be administered as age-appropriate or asindicated by the presence of underlying medical conditions(2643)

Altered ImmunocompetenceACIPrsquos statement regarding vaccinating immuno-

compromised persons summarizes recommendations regard-ing the efficacy safety and use of specific vaccines andimmune globulin preparations for immunocompromisedpersons (145) ACIP statements regarding individual vac-cines or immune globulins contain additional informationregarding those concerns

Severe immunosuppression can be the result of congeni-tal immunodeficiency HIV infection leukemia lymphomageneralized malignancy or therapy with alkylating agentsantimetabolites radiation or a high dose prolonged courseof corticosteroids The degree to which a person isimmunocompromised should be determined by a physi-cian Severe complications have followed vaccination withlive-virus vaccines and live bacterial vaccines amongimmunocompromised patients (146ndash153) These patientsshould not receive live vaccines except in certain circum-stances that are noted in the following paragraphs MMRvaccine viruses are not transmitted to contacts and trans-mission of varicella vaccine virus is rare (6138) MMR andvaricella vaccines should be administered to susceptiblehousehold and other close contacts of immunocompromisedpatients when indicated

Persons with HIV infection are at increased risk for severecomplications if infected with measles No severe or un-usual adverse events have been reported after measles vacci-nation among HIV-infected persons who did not haveevidence of severe immunosuppression (154ndash157) As aresult MMR vaccination is recommended for all HIV-infected persons who do not have evidence of severe immu-nosuppressiondaggerdagger and for whom measles vaccination wouldotherwise be indicated

Children with HIV infection are at increased risk for com-plications of primary varicella and for herpes zoster com-pared with immunocompetent children (138158) Limiteddata among asymptomatic or mildly symptomatic HIV-infected children (CDC class N1 or A1 age-specific CD4+

lymphocyte percentages of gt25) indicate that varicellavaccine is immunogenic effective and safe (138159) Va-ricella vaccine should be considered for asymptomatic ormildly symptomatic HIV-infected children in CDC classN1 or A1 with age-specific CD4+ T lymphocyte percent-ages of gt25 Eligible children should receive two doses ofvaricella vaccine with a 3-month interval between doses(138)

HIV-infected persons who are receiving regular doses ofIGIV might not respond to varicella vaccine or MMR or itsindividual component vaccines because of the continuedpresence of passively acquired antibody However becauseof the potential benefit measles vaccination should be con-sidered approximately 2 weeks before the next scheduleddose of IGIV (if not otherwise contraindicated) althoughan optimal immune response is unlikely to occur Unlessserologic testing indicates that specific antibodies have beenproduced vaccination should be repeated (if not otherwisecontraindicated) after the recommended interval (Table 4)An additional dose of IGIV should be considered for per-sons on maintenance IGIV therapy who are exposed tomeasles gt3 weeks after administering a standard dose (100ndash400 mgkg body weight) of IGIV

Persons with cellular immunodeficiency should not re-ceive varicella vaccine However ACIP recommends thatpersons with impaired humoral immunity (eghypogammaglobulinemia or dysgammaglobulinemia)should be vaccinated (138160)

Inactivated recombinant subunit polysaccharide andconjugate vaccines and toxoids can be administered to allimmunocompromised patients although response to suchvaccines might be suboptimal If indicated all inactivatedvaccines are recommended for immunocompromised per-sons in usual doses and schedules In addition pneumo-coccal meningococcal and Hib vaccines are recommendedspecifically for certain groups of immunocompromised pa-tients including those with functional or anatomic asplenia(145161)

Except for influenza vaccine which should be adminis-tered annually (88) vaccination during chemotherapy orradiation therapy should be avoided because antibody re-sponse is suboptimal Patients vaccinated while receivingimmunosuppressive therapy or in the 2 weeks before start-ing therapy should be considered unimmunized and shouldbe revaccinated gt3 months after therapy is discontinuedPatients with leukemia in remission whose chemotherapyhas been terminated for gt3 months can receive live-virusvaccines

daggerdagger As defined by a low age-specific total CD4+ T lymphocyte count or a low CD4+

T lymphocyte count as a percentage of total lymphocytes ACIP recommendationsfor using MMR vaccine contain additional details regarding the criteria forsevere immunosuppression in persons with HIV infection (Source CDCMeasles mumps and rubella mdash vaccine use and strategies for elimination ofmeasles rubella and congenital rubella syndrome and control of mumpsrecommendations of the Advisory Committee on Immunization Practices [ACIP]MMWR 199847[No RR-8]1ndash57)

CorticosteroidsThe exact amount of systemically absorbed corticoster-

oids and the duration of administration needed to suppressthe immune system of an otherwise immunocompetentperson are not well-defined The majority of experts agreethat corticosteroid therapy usually is not a contraindica-tion to administering live-virus vaccine when it is short-term (ie lt2 weeks) a low to moderate dose long-termalternate-day treatment with short-acting preparationsmaintenance physiologic doses (replacement therapy) oradministered topically (skin or eyes) or by intra-articularbursal or tendon injection (145) Although of theoreticalconcern no evidence of increased severity of reactions tolive vaccines has been reported among persons receivingcorticosteroid therapy by aerosol and such therapy is not areason to delay vaccination The immunosuppressive effectsof steroid treatment vary but the majority of clinicians con-sider a dose equivalent to either gt2 mgkg of body weightor a total of 20 mgday of prednisone or equivalent for chil-dren who weigh gt10 kg when administered for gt2 weeksas sufficiently immunosuppressive to raise concern regard-ing the safety of vaccination with live-virus vaccines(84145) Corticosteroids used in greater than physiologicdoses also can reduce the immune response to vaccinesVaccination providers should wait gt1 month after discon-tinuation of therapy before administering a live-virus vac-cine to patients who have received high systemicallyabsorbed doses of corticosteroids for gt2 weeks

Vaccination of HematopoieticStem Cell Transplant Recipients

Hematopoietic stem cell transplant (HSCT) is the infu-sion of hematopoietic stem cells from a donor into a patientwho has received chemotherapy and often radiation bothof which are usually bone marrow ablative HSCT is usedto treat a variety of neoplastic diseases hematologic disor-ders immunodeficiency syndromes congenital enzymedeficiencies and autoimmune disorders HSCT recipientscan receive either their own cells (ie autologous HSCT)or cells from a donor other than the transplant recipient(ie allogeneic HSCT) The source of the transplanted stemcells can be from either a donorrsquos bone marrow or periph-eral blood or harvested from the umbilical cord of a new-born infant (162)

Antibody titers to vaccine-preventable diseases (eg teta-nus poliovirus measles mumps rubella and encapsulatedbacteria) decline during the 1ndash4 years after allogeneic or au-tologous HSCT if the recipient is not revaccinated (163ndash167)HSCT recipients are at increased risk for certain vaccine-pre-

ventable diseases including those caused by encapsulatedbacteria (ie pneumococcal and Hib infections) As a re-sult HSCT recipients should be routinely revaccinated af-ter HSCT regardless of the source of the transplanted stemcells Revaccination with inactivated recombinant subunitpolysaccharide and Hib vaccines should begin 12 monthsafter HSCT (162) An exception to this recommendationis for influenza vaccine which should be administered atgt6 months after HSCT and annually for the life of the re-cipient thereafter MMR vaccine should be administered24 months after transplantation if the HSCT recipient ispresumed to be immunocompetent Varicella meningo-coccal and pneumococcal conjugate vaccines are not rec-ommended for HSCT recipients because of insufficientexperience using these vaccines among HSCT recipients(162) The household and other close contacts of HSCTrecipients and health-care workers who care for HSCT re-cipients should be appropriately vaccinated includingagainst influenza measles and varicella Additional detailsof vaccination of HSCT recipients and their contacts canbe found in a specific CDC report on this topic (162)

Vaccinating Persons with BleedingDisorders and Persons ReceivingAnticoagulant Therapy

Persons with bleeding disorders (eg hemophilia) andpersons receiving anticoagulant therapy have an increasedrisk for acquiring hepatitis B and at least the same risk asthe general population of acquiring other vaccine-preventable diseases However because of the risk for he-matoma formation after injections intramuscular injectionsare often avoided among persons with bleeding disordersby using the subcutaneous or intradermal routes for vac-cines that are administered normally by the intramuscularroute Hepatitis B vaccine administered intramuscularly to153 persons with hemophilia by using a 23-gauge needlefollowed by steady pressure to the site for 1ndash2 minutesresulted in a 4 bruising rate with no patients requiringfactor supplementation (168) Whether antigens that pro-duce more local reactions (eg pertussis) would producean equally low rate of bruising is unknown

When hepatitis B or any other intramuscular vaccine isindicated for a patient with a bleeding disorder or a personreceiving anticoagulant therapy the vaccine should be ad-ministered intramuscularly if in the opinion of a physicianfamiliar with the patientrsquos bleeding risk the vaccine can beadministered with reasonable safety by this route If thepatient receives antihemophilia or similar therapy intra-muscular vaccinations can be scheduled shortly after such

therapy is administered A fine needle (lt23 gauge) shouldbe used for the vaccination and firm pressure applied to thesite without rubbing for gt2 minutes The patient or fam-ily should be instructed concerning the risk for hematomafrom the injection

Vaccination RecordsConsent to Vaccinate

The National Childhood Vaccine Injury Act of 1986 (42USC sect 300aa-26) requires that all health-care providersin the United States who administer any vaccine covered bythe actsectsect must provide a copy of the relevant current edi-tion of the vaccine information materials that have beenproduced by CDC before administering each dose of thevaccine The vaccine information material must be providedto the parent or legal representative of any child or to anyadult to whom the physician or other health-care providerintends to administer the vaccine The Act does not requirethat a signature be obtained but documentation of con-sent is recommended or required by certain state or localauthorities

Provider RecordsDocumentation of patient vaccinations helps ensure that

persons in need of a vaccine receive it and that adequatelyvaccinated patients are not overimmunized possibly increas-ing the risk for local adverse events (eg tetanus toxoid)Serologic test results for vaccine-preventable diseases (egthose for rubella screening) as well as documented episodesof adverse events also should be recorded in the permanentmedical record of the vaccine recipient

Health-care providers who administer vaccines coveredby the National Childhood Vaccine Injury Act are requiredto ensure that the permanent medical record of the recipi-ent (or a permanent office log or file) indicates the date thevaccine was administered the vaccine manufacturer thevaccine lot number and the name address and title of theperson administering the vaccine Additionally the provideris required to record the edition date of the vaccine infor-mation materials distributed and the date those materialswere provided Regarding this Act the term health-care pro-vider is defined as any licensed health-care professional or-ganization or institution whether private or public(including federal state and local departments and agen-cies) under whose authority a specified vaccine is adminis-

tered ACIP recommends that this same information bekept for all vaccines not just for those required by the Na-tional Childhood Vaccine Injury Act

Patientsrsquo Personal RecordsOfficial immunization cards have been adopted by every

state territory and the District of Columbia to encourageuniformity of records and to facilitate assessment of immu-nization status by schools and child care centers The recordsalso are key tools in immunization education programs aimedat increasing parental and patient awareness of the need forvaccines A permanent immunization record card shouldbe established for each newborn infant and maintained bythe parent or guardian In certain states these cards aredistributed to new mothers before discharge from the hos-pital Using immunization record cards for adolescents andadults also is encouraged

RegistriesImmunization registries are confidential population-

based computerized information systems that collect vac-cination data for as many children as possible within ageographic area Registries are a critical tool that can in-crease and sustain increased vaccination coverage by con-solidating vaccination records of children from multipleproviders generating reminder and recall vaccination no-tices for each child and providing official vaccination formsand vaccination coverage assessments (169) A fully opera-tional immunization registry also can prevent duplicate vac-cinations limit missed appointments reduce vaccine wasteand reduce staff time required to produce or locate immu-nization records or certificates The National Vaccine Advi-sory Committee strongly encourages development ofcommunity- or state-based immunization registry systemsand recommends that vaccination providers participate inthese registries whenever possible (170171) A 95 par-ticipation of children aged lt6 years in fully operationalpopulation-based immunization registries is a nationalhealth objective for 2010 (172)

Reporting Adverse EventsAfter Vaccination

Modern vaccines are safe and effective however adverseevents have been reported after administration of all vaccines(82) These events range from frequent minor local reactionsto extremely rare severe systemic illness (eg encephalopa-thy) Establishing evidence for cause-and-effect relationshipson the basis of case reports and case series alone is impos-

sect sectAs of January 2002 vaccines covered by the act include diphtheria tetanuspertussis measles mumps rubella poliovirus hepatitis B Hib varicella andpneumococcal conjugate

sible because temporal association alone does not necessar-ily indicate causation Unless the syndrome that occurs af-ter vaccination is clinically or pathologically distinctive moredetailed epidemiologic studies to compare the incidence ofthe event among vaccinees with the incidence among un-vaccinated persons are often necessary Reporting adverseevents to public health authorities including serious eventsis a key stimulus to developing studies to confirm or refutea causal association with vaccination More complete infor-mation regarding adverse reactions to a specific vaccine canbe found in the ACIP recommendations for that vaccineand in a specific statement on vaccine adverse reactions (82)

The National Childhood Vaccine Injury Act requireshealth-care providers to report selected events occurring af-ter vaccination to the Vaccine Adverse Event Reporting Sys-tem (VAERS) Events for which reporting is required appearin the Vaccine Injury Tableparapara Persons other than health-care workers also can report adverse events to VAERS Ad-verse events other than those that must be reported or thatoccur after administration of vaccines not covered by theact including events that are serious or unusual also shouldbe reported to VAERS even if the physician or other health-care provider is uncertain they are related causally VAERSforms and instructions are available in the FDA Drug Bul-letin by calling the 24-hour VAERS Hotline at 800-822-7967 or from the VAERS website at httpwwwvaersorg(accessed November 7 2001)

Vaccine Injury Compensation ProgramThe National Vaccine Injury Compensation Program es-

tablished by the National Childhood Vaccine Injury Act is ano-fault system in which persons thought to have suffered aninjury or death as a result of administration of a covered vac-cine can seek compensation The program which became op-erational on October 1 1988 is intended as an alternative tocivil litigation under the traditional tort system in that negli-gence need not be proven Claims arising from covered vac-cines must first be adjudicated through the program beforecivil litigation can be pursued

The program relies on a Vaccine Injury Table listing the vac-cines covered by the program as well as the injuries disabili-ties illnesses and conditions (including death) for whichcompensation might be awarded The table defines the timeduring which the first symptom or substantial aggravation ofan injury must appear after vaccination Successful claimantsreceive a legal presumption of causation if a condition listed in

the table is proven thus avoiding the need to prove actualcausation in an individual case Claimants also can prevail forconditions not listed in the table if they prove causation Inju-ries after administration of vaccines not listed in the legisla-tion authorizing the program are not eligible forcompensation through the program Additional informa-tion is available from the following

National Vaccine Injury Compensation ProgramHealth Resources and Services AdministrationParklawn Building Room 8-465600 Fishers LaneRockville MD 20857Telephone 800-338-2382 (24-hour recording)Internet http wwwhrsagovbhprvicp (accessed

November 7 2001)Persons wishing to file a claim for vaccine injury should

call or write the followingUS Court of Federal Claims717 Madison Place NWWashington DC 20005Telephone 202-219-9657

Benefit and Risk CommunicationParents guardians legal representatives and adolescent

and adult patients should be informed regarding the ben-efits and risks of vaccines in understandable language Op-portunity for questions should be provided before eachvaccination Discussion of the benefits and risks of vaccina-tion is sound medical practice and is required by law

The National Childhood Vaccine Injury Act requires thatvaccine information materials be developed for each vaccinecovered by the Act These materials known as Vaccine In-formation Statements must be provided by all public andprivate vaccination providers each time a vaccine is admin-istered Copies of Vaccine Information Statements are avail-able from state health authorities responsible forimmunization or they can be obtained from CDCrsquos Na-tional Immunization Program website at httpwwwcdcgovnip (accessed November 7 2001) Transla-tions of Vaccine Information Statements into languages otherthan English are available from certain state immunizationprograms and from the Immunization Action Coalitionwebsite at httpwwwimmunizeorg (accessed November 72001)

Health-care providers should anticipate that certain par-ents or patients will question the need for or safety of vacci-nation refuse certain vaccines or even reject all vaccinationsA limited number of persons might have religious or per-sonal objections to vaccinations Others wish to enter into

para paraThe Vaccine Injury Table can be obtained from the Vaccine Injury CompensationProgram Internet site at lthttpwwwhrsadhhsgovbhprvicptablehtmgt(accessed November 7 2001)

a dialogue regarding the risks and benefits of certain vac-cines Having a basic understanding of how patients viewvaccine risk and developing effective approaches in dealingwith vaccine safety concerns when they arise is imperativefor vaccination providers

Each person understands and reacts to vaccine informa-tion on the basis of different factors including prior experi-ence education personal values method of datapresentation perceptions of the risk for disease perceivedability to control those risks and their risk preference In-creasingly through the media and nonauthoritative Internetsites decisions regarding risk are based on inaccurate infor-mation Only through direct dialogue with parents and byusing available resources health-care professionals can pre-vent acceptance of media reports and information fromnonauthoritative Internet sites as scientific fact

When a parent or patient initiates discussion regarding avaccine controversy the health-care professional should dis-cuss the specific concerns and provide factual informationusing language that is appropriate Effective empatheticvaccine risk communication is essential in responding tomisinformation and concerns although recognizing that forcertain persons risk assessment and decision-making is dif-ficult and confusing Certain vaccines might be acceptableto the resistant parent Their concerns should then be ad-dressed in the context of this information using the Vac-cine Information Statements and offering other resourcematerials (eg information available on the National Im-munization Program website)

Although a limited number of providers might choose toexclude from their practice those patients who question orrefuse vaccination the more effective public health strategyis to identify common ground and discuss measures thatneed to be followed if the patientrsquos decision is to defer vac-cination Health-care providers can reinforce key points re-garding each vaccine including safety and emphasize risksencountered by unimmunized children Parents should beadvised of state laws pertaining to school or child care en-try which might require that unimmunized children stayhome from school during outbreaks Documentation of thesediscussions in the patientrsquos record including the refusal toreceive certain vaccines (ie informed refusal) might re-duce any potential liability if a vaccine-preventable diseaseoccurs in the unimmunized patient

Vaccination ProgramsThe best way to reduce vaccine-preventable diseases is to

have a highly immune population Universal vaccination is

a critical part of quality health care and should be accom-plished through routine and intensive vaccination programsimplemented in physiciansrsquo offices and in public health clin-ics Programs should be established and maintained in allcommunities to ensure vaccination of all children at therecommended age In addition appropriate vaccinationsshould be available for all adolescents and adults

Physicians and other pediatric vaccination providersshould adhere to the standards for child and adolescent im-munization practices (1) These standards define appropri-ate vaccination practices for both the public and privatesectors The standards provide guidance on practices thatwill result in eliminating barriers to vaccination These in-clude practices aimed at eliminating unnecessary prerequi-sites for receiving vaccinations eliminating missedopportunities to vaccinate improving procedures to assessvaccination needs enhancing knowledge regarding vacci-nations among parents and providers and improving themanagement and reporting of adverse events Additionallythe standards address the importance of recall and remindersystems and using assessments to monitor clinic or officevaccination coverage levels among patients

Standards of practice also have been published to increasevaccination coverage among adults (2) Persons aged gt65years and all adults with medical conditions that place themat risk for pneumococcal disease should receive gt1 doses ofpneumococcal polysaccharide vaccine All persons aged gt50years and those with medical conditions that increase therisk for complications from influenza should receive annualinfluenza vaccination All adults should complete a primaryseries of tetanus and diphtheria toxoids and receive a boosterdose every 10 years Adult vaccination programs also shouldprovide MMR and varicella vaccines whenever possible toanyone susceptible to measles mumps rubella or varicellaPersons born after 1956 who are attending college (or otherposthigh school educational institutions) who are employedin environments that place them at increased risk for measlestransmission (eg health-care facilities) or who are travel-ing to areas with endemic measles should have documen-tation of having received two doses of MMR on or aftertheir first birthday or other evidence of immunity (6173)All other adults born after 1956 should have documenta-tion of gt1 doses of MMR vaccine on or after their first birth-day or have other evidence of immunity No evidenceindicates that administering MMR vaccine increases therisk for adverse reactions among persons who are alreadyimmune to measles mumps or rubella as a result of previ-ous vaccination or disease Widespread use of hepatitis Bvaccine is encouraged for all persons who might be at in-

creased risk (eg adolescents and adults who are either in agroup at high risk or reside in areas with increased rates ofinjection-drug use teenage pregnancy or sexually trans-mitted disease)

Every visit to a physician or other health-care providercan be an opportunity to update a patientrsquos immunizationstatus with needed vaccinations Official health agenciesshould take necessary steps including developing and en-forcing school immunization requirements to ensure thatstudents at all grade levels (including college) and those inchild care centers are protected against vaccine-preventablediseases Agencies also should encourage institutions (eghospitals and long-term care facilities) to adopt policies re-garding the appropriate vaccination of patients residentsand employees (173)

Dates of vaccination (day month and year) should berecorded on institutional immunization records (eg thosekept in schools and child care centers) This record willfacilitate assessments that a primary vaccination series hasbeen completed according to an appropriate schedule andthat needed booster doses have been administered at theappropriate time

The independent nonfederal Task Force on CommunityPreventive Services (the Task Force) gives public healthdecision-makers recommendations on population-based in-

terventions to promote health and prevent disease injurydisability and premature death The recommendations arebased on systematic reviews of the scientific literature re-garding effectiveness and cost-effectiveness of these inter-ventions In addition the Task Force identifies criticalinformation regarding the other effects of these interven-tions as well as the applicability to specific populationsand settings and the potential barriers to implementationThis information is available through the Internet athttpwwwthecommunityguideorg (accessed November 72001)

Beginning in 1996 the Task Force systematically reviewedpublished evidence on the effectiveness and cost-effectivenessof population-based interventions to increase coverage of vac-cines recommended for routine use among children ado-lescents and adults A total of 197 articles were identifiedthat evaluated a relevant intervention met inclusion crite-ria and were published during 1980ndash1997 Reviews of 17specific interventions were published in 1999 (174ndash176)Using the results of their review the Task Force made rec-ommendations regarding the use of these interventions(177) A number of interventions were identified and rec-ommended on the basis of published evidence The inter-ventions and the recommendations are summarized in thisreport (Table 7)

TABLE 7 Summary of recommendations regarding interventions to improve coverage of vaccines recommended for routine useamong children adolescents and adults

Intervention Recommendation

Interventions that increase community demand for immunizationsClient reminder or recall systems Strongly recommended

Multicomponent interventions including education Strongly recommended

School- child care- and college-entry requirements Recommended

Community education alone Insufficient evidence

Clinic-based education Insufficient evidence

Patient or family incentives or sanctions Insufficient evidence

Client-held medical records Insufficient evidence

Interventions that enhance access to vaccination servicesReducing out-of-pocket costs Strongly recommended

Enhancing access through the US Department of RecommendedAgriculturersquos Women Infants and Children program

Home visits outreach and case management Recommended

Enhancing access at child care centers Insufficient evidence

Enhancing access at schools Insufficient evidence

Expanding access in health-care settings Recommended as part of multicomponent interventions only

Interventions that target providersReminder or recall systems Strongly recommended

Assessment and feedback Strongly recommended

Standing orders Strongly recommended

Provider education alone Insufficient evidence

Adapted from Task Force on Community Preventive Services Recommendations regarding interventions to improve vaccination coverage in childrenadolescents and adults Am J Prev Med 200018(1 Suppl)92ndash6

Vaccine Information SourcesIn addition to these general recommendations other

sources are available that contain specific and updated vac-cine information

National Immunization InformationHotline

The National Immunization Information Hotline is sup-ported by CDCrsquos National Immunization Program and pro-vides vaccination information for health-care providers andthe public 800 amndash1100 pm MondayndashFriday

Telephone (English) 800-232-2522Telephone (Spanish) 800-232-0233Telephone (TTY) 800-243-7889Internet httpwwwashastdorg

(accessed November 7 2001)

CDCrsquos National Immunization ProgramCDCrsquos National Immunization Program website provides

direct access to immunization recommendations of the Advi-sory Committee on Immunization Practices (ACIP) vaccina-tion schedules vaccine safety information publicationsprovider education and training and links to otherimmunization-related websites It is located at httpwwwcdcgovnip (accessed November 7 2001)

Morbidity and Mortality Weekly ReportACIP recommendations regarding vaccine use statements

of vaccine policy as they are developed and reports of specificdisease activity are published by CDC in the Morbidity andMortality Weekly Report (MMWR) series Electronicsubscriptions are free and available at httpwwwcdcgovsubscribehtml (accessed November 7 2001) Printed sub-scriptions are available at

Superintendent of DocumentsUS Government Printing OfficeWashington DC 20402-9235

American Academy of Pediatrics (AAP)Every 3 years AAP issues the Red Book Report of the Com-

mittee on Infectious Diseases which contains a composite sum-mary of AAP recommendations concerning infectious diseasesand immunizations for infants children and adolescents

Telephone 888-227-1770Internet httpwwwaaporg

American Academy of FamilyPhysicians (AAFP)

Information from the professional organization of familyphysicians is available at httpwwwaafporg (accessed No-vember 7 2001)

Immunization Action CoalitionThis source provides extensive free provider and patient

information including translations of Vaccine InformationStatements into multiple languages The Internet addressis httpwwwimmunizeorg (accessed November 7 2001)

National Network for ImmunizationInformation

This information source is provided by the Infectious Dis-eases Society of America Pediatric Infectious Diseases SocietyAAP American Nurses Association and other professionalorganizations It provides objective science-based informationregarding vaccines for the public and providers The Internetsite is httpwwwimmunizationinfoorg (accessed November7 2001)

Vaccine Education CenterLocated at the Childrenrsquos Hospital of Philadelphia this source

provides patient and provider information The Internet ad-dress is httpwwwvaccinechopedu (accessed November 72001)

Institute for Vaccine SafetyLocated at Johns Hopkins University School of Public

Health this source provides information regarding vaccinesafety concerns and objective and timely information to health-care providers and parents It is available at httpwwwvaccinesafetyedu (accessed November 7 2001)

National Partnership for ImmunizationThis national organization encourages greater acceptance and

use of vaccinations for all ages through partnerships with pub-lic and private organizations Their Internet address is httpwwwpartnersforimmunizationorg (accessed November 72001)

State and Local Health DepartmentsState and local health departments provide technical advice

through hotlines electronic mail and Internet sites includ-ing printed information regarding vaccines and immunizationschedules posters and other educational materials

AcknowledgmentsThe members of the Advisory Committee on

Immunization Practices are grateful for the contributionsof Margaret Hostetter MD Yale Child Health ResearchCenter Mary Staat MD Childrenrsquos Hospital MedicalCenter of Cincinnati Deborah Wexler MD ImmunizationAction Coalition and John Grabenstein PhD US ArmyMedical Command

References1 CDC Standards for pediatric immunization practices recommended

by the National Vaccine Advisory Committee approved by the USPublic Health Service MMWR 199342(No RR-5)1ndash13

2 CDC Health objectives for the nation public health burden of vac-cine-preventable diseases among adults standards for adult immuni-zation practice MMWR 199039725ndash9

3 CDC Poliomyelitis prevention in the United States introduction of asequential vaccination schedule of inactivated poliovirus vaccine fol-lowed by oral poliovirus vaccine recommendations of the AdvisoryCommittee on Immunization Practices (ACIP) MMWR 199746(NoRR-3)1ndash25

4 CDC Poliomyelitis prevention in the United States updated recom-mendations of the Advisory Committee on Immunization Practices(ACIP) MMWR 200049(No RR-5)1ndash22

5 Plotkin SA Immunologic correlates of protection induced by vaccina-tion Pediatr Infect Dis J 20012063ndash75

6 CDC Measles mumps and rubellamdashvaccine use and strategies forelimination of measles rubella and congenital rubella syndrome andcontrol of mumps recommendations of the Advisory Committee onImmunization Practices (ACIP) MMWR 199847(No RR-8)1ndash57

7 Watson JC Pearson JA Markowitz LE et al Evaluation of measlesrevaccination among school-entry-aged children Pediatrics199697613ndash8

8 CDC Prevention of varicella recommendations of the Advisory Com-mittee on Immunization Practices (ACIP) MMWR 199645(NoRR-11)8

9 CDC Human rabies preventionmdashUnited States 1999 recommen-dations of the Advisory Committee on Immunization Practices (ACIP)MMWR 199948(No RR-1)1ndash21

10 Levine L Edsall G Tetanus toxoid what determines reaction prone-ness [Letter] J Infect Dis 1981144376

11 Edsall G Elliot MW Peebles TC Levine L Eldred MC Excessiveuse of tetanus toxoid boosters JAMA 196720217ndash9

12 Hutchins SS Escolan J Markowitz LE et al Measles outbreak amongunvaccinated preschool-age children opportunities missed by healthcare providers to administer measles vaccine Pediatrics198983369ndash74

13 Deforest A Long SS Lischner HW et al Simultaneous administra-tion of measles-mumps-rubella vaccine with booster doses ofdiphtheria-tetanus-pertussis and poliovirus vaccines Pediatrics198881237ndash46

14 King GE Hadler SC Simultaneous administration of childhood vac-cines an important public health policy that is safe and efficaciousPediatr Infect Dis J 199413394ndash407

15 Dashefsky B Wald E Guerra N Byers C Safety tolerability andimmunogenicity of concurrent administration of Haemophilus influenzaetype B conjugate vaccine (meningococcal protein conjugate) with ei-ther measles-mumps-rubella vaccine or diphtheria-tetanus-pertussisand oral poliovirus vaccines in 14- to 23-month-old infants Pediatrics199085(4 Pt 2)682ndash9

16 Giammanco G Li Volti S Mauro L et al Immune response to simul-taneous administration of a recombinant DNA hepatitis B vaccine andmultiple compulsory vaccines in infancy Vaccine 19919747ndash50

17 Shinefield HR Black SB Staehle BO et al Safety tolerability andimmunogenicity of concomitant injections in separate locations ofM-M-Rreg

II VARIVAXreg and TETRAMUNEreg in healthy children vs

concomitant injections of M-M-RregII and TETRAMUNEreg followed

six weeks later by VARIVAXreg Pediatr Infect Dis J 199817980ndash518 CDC Typhoid immunization recommendations of the Advisory Com-

mittee on Immunization Practices (ACIP) MMWR 199443(NoRR-14)1ndash7

19 DeStefano F Goodman RA Noble GR McClary GD Smith SJBroome CV Simultaneous administration of influenza and pneumo-coccal vaccines JAMA 19822472551ndash4

20 Yvonnet B Coursaget P Deubel V Diop-Mar I Digoutte JP ChironJ Simultaneous administration of hepatitis B and yellow fever vacci-nations J Med Virol 198619307ndash11

21 Stefano I Sato HK Pannuti CS et al Recent immunization againstmeasles does not interfere with the sero-response to yellow fever vac-cine Vaccine 1999171042ndash6

22 CDC Yellow fever vaccine recommendations of the ImmunizationPractices Advisory Committee (ACIP) MMWR 199039(No RR-6)1ndash6

23 Shinefield HR Black S Ray P et al Safety and immunogenicity ofheptavalent pneumococcal CRM

197 conjugate vaccine in infants and

toddlers Pediatr Infect Dis J 199918757ndash6324 CDC Haemophilus b conjugate vaccines for prevention of Haemophilus

influenzae type b disease among infants and children two months ofage and older recommendations of the Immunization Practices Advi-sory Committee (ACIP) MMWR 199140(No RR-1)1ndash7

25 CDC Pertussis vaccination use of acellular pertussis vaccines amonginfants and young children recommendations of the Advisory Com-mittee on Immunization Practices (ACIP) MMWR 199746(NoRR-7)1ndash25

26 CDC Preventing pneumococcal disease among infants and youngchildren recommendations of the Advisory Committee on Immuniza-tion Practices (ACIP) MMWR 200049(No RR-9)1ndash35

27 CDC Combination vaccines for childhood immunization recom-mendations of the Advisory Committee on Immunization Practices(ACIP) the American Academy of Pediatrics (AAP) and the AmericanAcademy of Family Physicians (AAFP) MMWR 199948(No RR-5)5

28 Petralli JK Merigan TC Wilbur JR Action of endogenous interferonagainst vaccinia infection in children Lancet 19652401ndash5

29 Petralli JK Merigan TC Wilbur JR Circulating interferon aftermeasles vaccination N Eng J Med 1965273198ndash201

30 CDC Simultaneous administration of varicella vaccine and other rec-ommended childhood vaccinesmdashUnited States 1995ndash1999 MMWR2001501058ndash61

Standards for pediatric adolescent and adult immunization practices are beingrevised and will be posted on CDCrsquos National Immunization Program Internesite (httpwwwcdcgovnip accessed November 7 2001) as soon as theupdates are available

31 Siber GR Werner BC Halsey NA et al Interference of immuneglobulin with measles and rubella immunization J Pediatr1993122204ndash11

32 Mason W Takahashi M Schneider T Persisting passively acquiredmeasles antibody following gamma globulin therapy for Kawasaki dis-ease and response to live virus vaccination [Abstract 311] Presentedat the 32nd meeting of the Interscience Conference on AntimicrobialAgents and Chemotherapy Los Angeles California October 1992

33 Kaplan JE Nelson DB Schonberger LB et al Effect of immune globulinon the response to trivalent oral poliovirus and yellow fever vaccina-tions Bull World Health Organ 198462585ndash90

34 Black NA Parsons A Kurtz JB McWhinney N Lacey A Mayon-White RT Post-partum rubella immunization a controlled trial oftwo vaccines Lancet 19832990ndash2

35 CDC Control and prevention of rubella evaluation and managementof suspected outbreaks rubella in pregnant women and surveillancefor congenital rubella syndrome MMWR 200150(No RR-12)1ndash24

36 Siber GR Snydman DR Use of immune globulin in the preventionand treatment of infections In Remington J Swartz M eds Currentclinical topics in infectious diseases vol 12 Oxford Blackwell Scien-tific 1992

37 Greenberg DP Lieberman JM Marcy SM et al Enhanced antibodyresponses in infants given different sequences of heterogeneousHaemophilus influenzae type B conjugate vaccines J Pediatr1995126206ndash11

38 Anderson EL Decker MD Englund JA et al Interchangeability ofconjugated Haemophilus influenzae type b vaccines in infants JAMA1995273849ndash53

39 Piazza M Abrescia N Picciotto L et al Demonstration of the inter-changeability of 2 types of recombinant anti-hepatitis-B vaccine BollSoc Ital Biol Sper 199369273ndash80

40 Bryan JP Henry CH Hoffman AG et al Randomized cross-overcontrolled comparison of two inactivated hepatitis A vaccines Vac-cine 200019743ndash50

41 Greenberg DP Pickering LK Senders SD et al Interchangeability oftwo diphtheria-tetanus-acellular pertussis vaccines in infancy Pediat-rics 2002 (in press)

42 CDC Use of diphtheria toxoid-tetanus toxoid-acellular pertussis vac-cine as a five-dose series supplemental recommendations of the Advi-sory Committee on Immunization Practices (ACIP) MMWR200049(No RR-13)1ndash8

43 CDC Prevention pneumococcal disease recommendations of theAdvisory Committee on Immunization Practices (ACIP) MMWR199746(No RR-8)1ndash24

44 Szilagyi PG Rodewald LE Missed opportunities for immunizationsa review of the evidence Journal of Public Health Management Prac-tice 1996218ndash25

45 Wald ER Dashefsky B Byers C Guerra N Taylor F Frequency andseverity of infections in day care J Pediatr 1988112540ndash6

46 Lewis T Osborn LM Lewis K Brockert J Jacobsen J Cherry JDInfluence of parental knowledge and opinions on 12-month diphtheriatetanus and pertussis vaccination rates Am J Dis Child 1988142283ndash6

47 Farizo KM Stehr-Green PA Markowitz LE Patriarca PA Vaccina-tion levels and missed opportunities for measles vaccination a recordaudit in a public pediatric clinic Pediatrics 199289589ndash92

48 Halsey NA Boulos R Mode F et al Response to measles vaccine inHaitian infants 6 to 12 months old influence of maternal antibodiesmalnutrition and concurrent illnesses N Engl J Med 1985313544ndash9

49 Ndikuyeze A Munoz A Stewart S et al Immunogenicity and safety ofmeasles vaccine in ill African children Int J Epidemiol 198817448ndash55

50 Lindegren ML Reynolds S Atkinson W Davis A Falter K PatriarcaP Adverse events following measles vaccination of ill preschool-agedchildren [Abstract 270] Abstracts of the 31st Interscience Conferenceon Antimicrobial Agents and Chemotherapy September 29ndashOctober 21991 Chicago Illinois144

51 Atkinson W Markowitz L Baughman A et al Serologic response tomeasles vaccination among ill children [Abstract 422] Abstracts of the32nd Interscience Conference on Antimicrobial Agents and Chemo-therapy October 1992 Anaheim California181

52 Krober MS Stracener LE Bass JW Decreased measles antibody re-sponse after measles-mumps-rubella vaccine in infants with coldsJAMA 19912652095ndash6

53 Shaw FE Jr Guess HA Roets JM et al Effect of anatomic injectionsite age and smoking on the immune response to hepatitis B vaccina-tion Vaccine 19897425ndash30

54 Zuckerman JN Importance of injecting vaccines into muscle differ-ent patients need different needle sizes Brit Med J 20003211237ndash8

55 Ipp MM Gold R Goldback M et al Adverse reactions to diphtheriatetanus pertussis-polio vaccination at 18 months of age effect of in-jection site and needle length Pediatrics 198983679ndash82

56 Michaels L Poole RW Injection granuloma of the buttock Can MedAssoc J 1970102626ndash8

57 Haramati N Lorans R Lutwin M Kaleya RN Injection granulomasintramuscle or intrafat Arch Fam Med 19943146ndash8

58 Giles FH French JH Postinjection sciatic nerve palsies in infants andchildren J Pediatr 196158195ndash204

59 Fishbein DB Sawyer LA Reid-Sanden FL Weir EH Administrationof human diploid-cell rabies vaccine in the gluteal area [Letter]N Engl J Med 1988318124ndash5

60 Bergeson PS Singer SA Kaplan AM Intramuscular injections in chil-dren Pediatrics 198270944ndash8

61 Poland GA Borrund A Jacobson RM et al Determination of deltoidfat pad thickness implications for needle length in adult immuniza-tion JAMA 19972771709ndash11

62 Groswasser J Kahn A Bouche B Hanquinet S Perlmuter N HesselL Needle length and injection technique for efficient intramuscularvaccine delivery in infants and children evaluated through anultrasonographic determination of subcutaneous and muscle layer thick-ness Pediatrics 1997100400ndash3

63 Scheifele D Bjornson G Barreto L Meekison W Guasparini R Con-trolled trial of Haemophilus influenzae type b diphtheria toxoid conju-gate combined with diphtheria tetanus and pertussis vaccines in18-month-old children including comparison of arm versus thigh in-jection Vaccine 199210455ndash60

64 Hingson RA Davis HS Rosen M Historical development of jet in-jection and envisioned uses in mass immunization and mass therapybased upon two decadesrsquo experience Mil Med 1963128516ndash24

65 Reis EC Jacobson RM Tarbell S Weniger BG Taking the sting out ofshots control of vaccination-associated pain and adverse reactionsPediatric Ann 199827375ndash85

66 Occupational Safety and Health Administration Occupationalexposure to bloodborne pathogens needlestick and other sharps inju-ries final rule (29 CFR Part 1910) Federal Register 2001665318ndash25 Available at httpwwwosha-slcgovFedReg_osha_pdfFED20010118Apdf Accessed November 8 2001

67 Simonsen L Kane A Lloyd J Zaffran M Kane M Unsafe injectionsin the developing world and transmission of bloodborne pathogens areview Bull World Health Organ 199977789ndash800

68 Kane A Lloyd J Zaffran M Simonsen L Kane M Transmission ofhepatitis B hepatitis C and human immunodeficiency viruses throughunsafe injections in the developing world model-based regional esti-mates Bull World Health Organ 199977801ndash7

69 CDC Needle-free injection technology Atlanta GA US Depart-ment of Health and Human Services CDC National ImmunizationProgram 2001 Available at ltwwwcdcgovnipdevjetinjecthtm Ac-cessed November 8 2001

70 CDC Hepatitis B associated with jet gun injectionmdashCalifornia [Epi-demiologic notes and reports] MMWR 198635373ndash6

71 Canter J Mackey K Good LS et al Outbreak of hepatitis B associ-ated with jet injections in a weight reduction clinic Arch Intern Med19901501923ndash7

72 Brito GS Chen RT Stefano IC Campos AM Oselka G Risk oftransmission of HIV and other blood-born diseases via jet injectorsduring immunization mass campaigns in Brazil [Abstract PC0132]10th International Conference on AIDS Yokohama 7ndash12 August199410301 Available at httpwwwaegiscompubsaidsline1994decm94c3258html Accessed November 8 2001

73 Hoffman PN Abuknesha RA Andrews NJ Samuel D Lloyd JSModel to assess the infection potential of jet injectors used in massimmunization Vaccine 2001194020ndash7

74 Taddio A Nulman I Goldbach M Ipp M Koren G Use of lidocaine-prilocain cream for vaccination pain in infants J Pediatr 1994124643ndash8

75 Uhari M Eutectic mixture of lidocaine and prolocaine for alleviatingvaccination pain in infants Pediatrics 199392719ndash21

76 Halperin SA McGrath P Smith B Houston T Lidocaine-prilocainepatch decreases the pain associated with subcutaneous administra-tion of measles-mumps-rubella vaccine but does not adversely affectthe antibody response J Pediatr 2000136789ndash94

77 Frayling IM Addison GM Chatterge K Meakin GMethaemoglobinaemia in children treated with prilocaine-lignocainecream Br Med J 1990301153ndash4

78 Lewis K Cherry JD Sachs MH et al Effect of prophylactic acetami-nophen administration on reactions to DTP vaccination Am J DisChild 198814262ndash5

79 Reis E Holubkov R Vapocoolant spray is equally effective as EMLAcream in reducing immunization pain in school-aged children Pediat-rics 1997100e5 Available at httpwwwpediatricsorgcgicontentfull1006e5 Accessed November 8 2001

80 Redfield RR Innis BL Scott RM Cannon HG Bancroft WH Clini-cal evaluation of low-dose intradermally administered hepatitis B vac-cine a cost reduction strategy JAMA 19852543203ndash6

81 Coleman PJ Shaw FE Serovich J Hadler SC Margolis HS Intrad-ermal hepatitis B vaccination in a large hospital employee populationVaccine 19919723ndash7

82 CDC Update vaccine side effects adverse reactions contraindicationsand precautions recommendations of the Advisory Committee on Im-munization Practices (ACIP) MMWR 199645(No RR-12)1ndash35

83 Braun MM Patriarca PA Ellenberg SS Syncope after immunizationArch Pediatr Adolesc Med 1997151255ndash9

84 American Academy of Pediatrics Active immunization In PickeringLK ed 2000 red book report of the Committee on Infectious Dis-eases 25th ed Elk Grove Village IL American Academy of Pediatrics2000

85 International Health Care Worker Safety Center List of safety-engi-neered sharp devices and other products designed to prevent occupa-tional exposures to bloodborne pathogens Charlottesville VAUniversity of Virginia 2001 Available at httpwwwmedvirginiaedumedcntrcentersepinetsafetydevicehtml Accessed November 82001

86 California Department of Health Services California list of needlelesssystems and needles with engineered sharps injury protection Sacra-mento CA California Department of Health Services 2001 Avail-able at httpwwwdhscahwnetgovohbSHARPSdisclaimhtmAccessed November 8 2001

87 National Alliance for the Primary Prevention of Sharps InjuriesNAPPSI National Alliance for the Primary Prevention of Sharps Inju-ries Carlsbad CA NAPPSI 2001 Available at httpwwwnappsiorgAccessed November 13 2001

88 CDC Prevention and control of influenza recommendations of theAdvisory Committee on Immunization Practices (ACIP) MMWR200150(No RR-4)1ndash44

89 Ambrosch F Hirschl A Kollaritsch H et al Immunologic investiga-tions with oral live typhoid vaccine Ty21a strain In Steffen R LobelHO Bradley DJ eds Travel medicine proceedings of the first Confer-ence on International Travel Medicine Berlin Germany Springer-Verlog 1989248ndash53

90 Horowitz H Carbonaro CA Inhibition of the Salmonella typhi oralvaccine strain Ty21a by mefloquine and chloroquine [Letter] J In-fect Dis 19921661462ndash4

91 Starr S Berkovich S Effects of measles gamma-globulin-modifiedmeasles and vaccine measles on the tuberculin test N Engl J Med1964270386ndash91

92 Brickman HF Beaudry PH Marks MI Timing of tuberculin tests inrelation to immunization with live viral vaccines Pediatrics197555392ndash6

93 Berkovich S Starr S Effects of live type 1 poliovirus vaccine and otherviruses on the tuberculin test N Engl J Med 196627467ndash72

94 Grabenstein JD Clinical management of hypersensitivities to vaccinecomponents Hospital Pharmacy 19973277ndash87

95 Grabenstein JD ImmunoFacts vaccines amp immunologic drugs StLouis MO Wolters Kluwer Co Facts and Comparisons 2001K1ndash5

96 Murphy KR Strunk RC Safe administration of influenza vaccine inasthmatic children hypersensitive to egg proteins J Pediatr1985106931ndash3

97 Kelso JM Jones RT Yunginger JW Anaphylaxis to measles mumpsand rubella vaccine mediated by IgE to gelatin J Allergy Clin Immunol199391867ndash72

98 Sakaguchi M Ogura H Inouye S IgE antibody to gelatin in childrenwith immediate-type reactions to measles and mumps vaccines J Al-lergy Clin Immunol 199596563ndash5

99 Sakaguchi M Yamanaka T Ikeda K et al IgE-mediated systemicreactions to gelatin included in the varicella vaccine J Allergy ClinImmunol 199799263ndash4

100 Sakaguchi M Nakayama T Inouye S Food allergy to gelatin in chil-dren with systemic immediate-type reactions including anaphylaxisto vaccines J Allergy Clin Immunol 1996981058ndash61

101 Reitschel RL Bernier R Neomycin sensitivity and the MMR vaccine[Letter] JAMA 1981245571

102 Elliman D Dhanraj B Safe MMR vaccination despite neomycin al-lergy [Letter] Lancet 1991337365

103 CDC Thimerosal in vaccines a joint statement of the American Acad-emy of Pediatrics and the Public Health Service [Notice to readers]MMWR 199948563ndash5

104 Ball LK Ball R Pratt RD Assessment of thimerosal use in childhoodvaccines Pediatrics 20011071147ndash54

105 Aberer W Vaccination despite thimerosal sensitivity Contact Der-matitis 1991246ndash10

106 Kirkland LR Ocular sensitivity to thimerosal a problem with hepa-titis B vaccine South Med J 199083497ndash9

107 Cox NH Forsyth A Thiomersal allergy and vaccination reactionsContact Dermatitis 198818229ndash33

108 Moumlller H All these positive tests to thimerosal Contact Dermatitis199431209ndash13

109 Wantke F Demmer CM Goumltz M Jarisch R Contact dermatitis fromthimerosal 2 yearrsquos experience with ethylmercuric chloride in patch test-ing thimerosal-sensitive patients Contact Dermatitis 199430115ndash8

110 Slater JE Latex allergy J Allergy Clin Immunol 199494139ndash49111 Towse A OrsquoBrien M Twarog FJ Braimon J Moses A Local reaction

secondary to insulin injection a potential role for latex antigens in insulinvials and syringes [Short reports] Diabetes Care 1995181195ndash7

112 Bastyr EJ Latex allergen allergic reactions [Letter] Diabetes Care199619546

113 MacCracken J Stenger P Jackson T Latex allergy in diabetic pa-tients a call for latex-free insulin tops [Letter] Diabetes Care199619184

114 Lear JT English JSC Anaphylaxis after hepatitis B vaccination [Let-ter] Lancet 19953451249

115 Bernbaum JC Daft A Anolik R et al Response of preterm infants todiphtheria-tetanuspertussis immunizations J Pediatr 1985107184ndash8

116 Koblin BA Townsend TR Munoz A Onorato I Wilson M Polk BFResponse of preterm infants to diphtheria-tetanus-pertussis vaccinePediatr Infect Dis J 19887704ndash11

117 Smolen P Bland R Heiligenstein E et al Antibody response to oralpolio vaccine in premature infants J Pediatr 1983103917ndash9

118 Bernbaum J Daft A Samuelson J Polin RA Half-dose immunizationfor diphtheria tetanus pertussis response of preterm infants Pediat-rics 198983471ndash6

119 Lau YL Tam AY Ng KW et al Response of preterm infants tohepatitis B vaccine J Pediatr 1992121962ndash5

120 Patel DM Butler J Feldman S Graves GR Rhodes PG Immunoge-nicity of hepatitis B vaccine in healthy very low birth weight infants JPediatr 1997131641ndash3

121 Kim SC Chung EK Hodinka RL et al Immunogenicity of hepatitisB vaccine in preterm infants Pediatrics 199799534ndash6

122 Losonsky GA Wasserman SS Stephens I et al Hepatitis B vaccina-tion of premature infants a reassessment of current recommendationsfor delayed immunization Pediatrics 1999103E14

123 Pickering LK Granoff DM Erickson JR et al Modulation of theimmune system by human milk and infant formula containing nucle-otides Pediatrics 1998101242ndash9

124 Kim-Farley R Brink E Orenstein W Bart K Vaccination and breastfeeding [Letter] JAMA 19822482451ndash2

125 Patriaca PA Wright PF John TJ Factors affecting the immunogenic-ity of oral polio vaccine in developing countries review Rev InfectDis 199113926ndash39

126 Hahn-Zoric M Fulconis F Minoli I et al Antibody responses toparenteral and oral vaccines are impaired by conventional and low-protein formulas as compared to breast feeding Acta Paediatr Scand1990791137ndash42

127 Krogh V Duffy LC Wong D Rosenband M Riddlesberger KR OgraPL Postpartum immunization with rubella virus vaccine and antibodyresponse in breast-feeding infants J Lab Clin Med 1989113695ndash9

128 Koren G Pastuszak A Ito S Drugs in pregnancy N Eng J Med19983381128ndash37

129 Grabenstein JD Vaccines and antibodies in relation to pregnancy andlactation Hospital Pharmacy 199934949ndash60

130 CDC Diphtheria tetanus and pertussis recommendations for vac-cine use and other preventive measures recommendations of the Im-munization Practices Advisory Committee (ACIP) MMWR199140(No RR-10)1ndash28

131 Neuzil KM Reed GW Mitchel EF Simonsen L Griffin MR Impactof influenza on acute cardiopulmonary hospitalizations in pregnantwomen Am J Epidemiol 19981481094ndash102

132 CDC Hepatitis B virus a comprehensive strategy for eliminating trans-mission in the United States through universal childhood vaccinationrecommendations of the Immunization Practices Advisory Commit-tee (ACIP) MMWR 199140(No RR-13)1ndash25

133 CDC Prevention of hepatitis A through active or passive immuniza-tion recommendations of the Advisory Committee on ImmunizationPractices (ACIP) MMWR 199948(No RR-12)1ndash37

134 CDC Prevention and control of meningococcal disease and meningo-coccal disease and college students recommendations of the AdvisoryCommittee on Immunization Practices (ACIP) MMWR 200049(NoRR-7)1ndash20

135 Tsai TF Paul R Lynberg MC Letson GW Congenital yellow fevervirus infection after immunization in pregnancy J Infect Dis19931681520ndash3

136 Shields KE Galil K Seward J Sharrar RG Cordero JF Slater EVaricella vaccine exposure during pregnancy data from the first 5 yearsof the pregnancy registry Obstet Gynecol 20019814ndash9

137 CDC Revised ACIP recommendation for avoiding pregnancy afterreceiving a rubella-containing vaccine [Notice to readers] MMWR2001501117

138 CDC Prevention of varicella update recommendations of the Advi-sory Committee on Immunization Practices (ACIP) MMWR199948(No RR-6)1ndash5

139 Hlady WG Bennett JV Samadi AR et al Neonatal tetanus in ruralBangladesh risk factors and toxoid efficacy Am J Publ Health1992821365ndash9

140 de Quadros CA Andrus JK Olive J-M de Macedo CG Polio eradica-tion from the Western Hemisphere Ann Rev Publ Health199213239ndash52

141 US Department of State International adoptions Washington DCUS Department of State 2001 Available at httpwwwtravelstategovadopthtml Accessed November 13 2001

142 Hostetter MK Johnson DE Immunization status of adoptees fromChina Russia and Eastern Europe [Abstract 851] Presented at the1998 Pediatric Academic Societies Annual Meeting New OrleansMay 5 1998

143 Kriz B Burian V Sladky K et al Comparison of titration results ofdiphtheric antitoxic antibody obtained by means of Jensenrsquos methodand the method of tissue cultures and haemagglutination J HygEpidemiol Microbiol Immunol 197822485ndash93

144 Staat MA Daniels D Immunization verification in internationallyadopted children [Abstract] Pediatr Res 200149(4)468a

145 CDC Recommendations of the Advisory Committee on Immuniza-tion Practices (ACIP) use of vaccines and immune globulins in per-sons with altered immunocompetence MMWR 199342(NoRR-4)1ndash18

146 Sixbey JW Routine immunization of the immunocompromised childAdv Pediatr Infect Dis 1987279ndash114

147 Wright PF Hatch MH Kasselberg AG Lowry SP Wadlington WBKarzon DT Vaccine-associated poliomyelitis in a child with sex-linkedagammaglobulinemia J Pediatr 197791408ndash12

148 Wyatt HV Poliomyelitis in hypogammaglobulinemics J Infect Dis1973128802ndash6

149 Davis LE Bodian D Price D Butler IJ Vickers JH Chronic progres-sive poliomyelitis secondary to vaccination of an immunodeficientchild N Engl J Med 1977297241ndash5

150 CDC Disseminated Mycobacterium bovis infection from BCG vaccina-tion of a patient with acquired immunodeficiency syndrome [Epide-miologic notes and reports] MMWR 198534227ndash8

151 Ninane J Grymonprez A Burtonboy G Francois A Cornu G Dis-seminated BCG in HIV infection Arch Dis Child 1988631268ndash9

152 Redfield RR Wright DC James WD Jones TS Brown C Burke DSDisseminated vaccinia in a military recruit with human immunodefi-ciency virus (HIV) disease N Engl J Med 1987316673ndash6

153 CDC Measles pneumonitis following measles-mumps-rubella vaccina-tion of a patient with HIV infection 1993 MMWR 199645603ndash6

154 Sprauer MA Markowitz LE Nicholson JKA et al Response of hu-man immunodeficiency virus-infected adults to measles-rubella vacci-nation J Acquir Immune Defic Syndr 199361013ndash6

155 McLaughlin M Thomas P Onorato I et al Live virus vaccines inhuman immunodeficiency virus-infected children a retrospective sur-vey Pediatrics 198882229ndash33

156 Onorato IM Markowitz LE Oxtoby MJ Childhood immunizationvaccine-preventable diseases and infection with human immunodefi-ciency virus Pediatr Infect Dis J 19886588ndash95

157 Palumbo P Hoyt L Demasio K Oleske J Connor E Population-based study of measles and measles immunization in human immuno-deficiency virus-infected children Pediatr Infect Dis J1992111008ndash14

158 Derryck A LaRussa P Steinberg S Capasso M Pitt J Gershon AAVaricella and zoster infection in children with human immunodefi-ciency virus infection Pediatr Infect Dis J 199817931ndash3

159 CDC 1994 revised classification system for human immunodeficiencyvirus infection in children less than 13 years of age MMWR199443(No RR-12)1ndash10

160 Levin MJ Gershon AA Weinberg A et al Immunization of HIV-infected children with varicella vaccine J Pediatr 2001139305ndash10

161 CDC Update on adult immunization recommendations of the Immu-nization Practices Advisory Committee (ACIP) MMWR 199140(NoRR-12)1ndash94

162 CDC Guidelines for preventing opportunistic infections among he-matopoietic stem cell transplant recipients recommendations of CDCthe Infectious Disease Society of America and the American Societyof Blood and Marrow Transplantation MMWR 200049(No RR-10)1ndash128

163 Guinan EC Molrine DC Antin JH et al Polysaccharide conjugatevaccine responses in bone marrow transplant patients Transplantation199457677ndash84

164 Pauksen K Hammarstrom V Ljungman P et al Immunity to poliovi-rus and immunization with inactivated poliovirus vaccine after autolo-gous bone marrow transplantation Clin Infect Dis 199418547ndash52

165 Pauksen K Duraj V Ljungman P et al Immunity to and immunizationagainst measles rubella and mumps in patients after autologous bondmarrow transplantation Bone Marrow Transplant 19929427ndash32

166 Ljungman P Wiklund-Hammarsten M Duraj V et al Response totetanus toxoid immunization after allogeneic bone marrow transplan-tation J Infect Dis 1990162496ndash500

167 Ljungman P Fridell E Lonnqvist B et al Efficacy and safety of vacci-nation of marrow transplant recipients with a live attenuated measlesmumps and rubella vaccine J Infect Dis 1989159610ndash5

168 Evans DI Shaw A Safety of intramuscular injection of hepatitis Bvaccine in haemophiliacs BMJ 19903001694ndash5

169 CDC Progress in development of immunization registriesmdashUnitedStates 2000 MMWR 2001503ndash7

170 National Vaccine Advisory Committee (NVAC) Development of com-munity- and state-based immunization registries approved January12 1999 Atlanta GA US Department of health and Human Ser-vices CDC 1999 Available at httpwwwcdcgovnipregistrynvachtm Accessed November 13 2001

171 CDC Development of community- and state-based immunizationregistries CDC response to a report from the National Vaccine Advi-sory Committee MMWR 200150(No RR-17)1ndash17

172 US Department of Health and Human Services Immunization andinfectious diseases [Goal 14-26] In Healthy People 2010 (conferenceed vol 1) Washington DC US Government Printing Office 2000Available at httpwwwhealthgovhealthypeopleDocumentHTMLVolume114Immunizationhtm_Toc494510242 Accessed Novem-ber 13 2001

173 CDC Immunization of health-care workers recommendations of theAdvisory Committee on Immunization Practices (ACIP) and the Hos-pital Infection Control Practices Advisory Committee (HICPAC)MMWR 199746(No RR-18)1ndash42

174 Shefer A Briss P Rodewald L et al Improving immunization coveragerates an evidence-based review of the literature Epidemiol Rev19992196ndash142

175 CDC Vaccine-preventable diseases improving vaccination coveragein children adolescents and adults a report on recommendations ofthe Task Force on Community Preventive Services MMWR199948(No RR-8)1ndash15

176 Briss PA Rodewald LE Hinman AR et al and the Task Force onCommunity Preventive Services Reviews of evidence regarding inter-ventions to improve vaccination coverage in children adolescents andadults Am J Prev Med 200018(1 Suppl)97ndash140

177 Task Force on Community Preventive Services Recommendationsregarding interventions to improve vaccination coverage in childrenadolescents and adults Am J Prev Med 200018(1 Suppl)92ndash6

nical errors in vaccine preparation handling or adminis-tration 4) coincidental associated temporally with vacci-nation by chance or caused by underlying illness Specialstudies are needed to determine if an adverse event is a reac-tion or the result of another cause (Sources Chen RT Spe-cial methodological issues in pharmacoepidemiology studiesof vaccine safety In Strom BL ed Pharmacoepidemiology3rd ed Sussex England John Wiley amp Sons 2000707ndash32 and Fenichel GM Lane DA Livengood JR HorwitzSJ Menkes JH Schwartz JF Adverse events following im-munization assessing probability of causation PediatrNeurol 19895287ndash90)

Adverse reaction An undesirable medical condition thathas been demonstrated to be caused by a vaccine Evidencefor the causal relationship is usually obtained through ran-domized clinical trials controlled epidemiologic studiesisolation of the vaccine strain from the pathogenic site orrecurrence of the condition with repeated vaccination (ierechallenge) synonyms include side effect and adverse ef-fect)

Immunobiologic Antigenic substances (eg vaccines andtoxoids) or antibody-containing preparations (eg globu-lins and antitoxins) from human or animal donors Theseproducts are used for active or passive immunization ortherapy The following are examples of immunobiologics

Vaccine A suspension of live (usually attenuated) orinactivated microorganisms (eg bacteria or viruses) orfractions thereof administered to induce immunity andprevent infectious disease or its sequelae Some vaccinescontain highly defined antigens (eg the polysaccha-ride of Haemophilus influenzae type b or the surfaceantigen of hepatitis B) others have antigens that arecomplex or incompletely defined (eg killed Bordetellapertussis or live attenuated viruses)

Toxoid A modified bacterial toxin that has beenmade nontoxic but retains the ability to stimulate theformation of antibodies to the toxin

Immune globulin A sterile solution containing an-tibodies which are usually obtained from human bloodIt is obtained by cold ethanol fractionation of large poolsof blood plasma and contains 15ndash18 protein In-tended for intramuscular administration immuneglobulin is primarily indicated for routine maintenanceof immunity among certain immunodeficient personsand for passive protection against measles andhepatitis A

Intravenous immune globulin A product derivedfrom blood plasma from a donor pool similar to theimmune globulin pool but prepared so that it is suit-

Abbreviations Usedin This Publication

AAFP American Academy of Family PhysiciansAAP American Academy of PediatricsACIP Advisory Committee on Immunization PracticesDT pediatric diphtheria-tetanus toxoidDTaP diphtheria and tetanus toxoids and acellular

pertussis vaccineDTP diphtheria and tetanus toxoids and whole-cell

pertussis vaccineEIAELISA enzyme immunoassayFDA Food and Drug AdministrationGBS Guillain-Barreacute syndromeHBIG hepatitis B immune globulinHbOC diphtheria CRM

197 (CRM cross-reactive

material) protein conjugateHBsAg hepatitis B surface antigenHib Haemophilus influenzae type bHIV human immunodeficiency virusHSCT hematopoietic stem cell transplantIgG immunoglobulin GIGIV intravenous immune globulinIPV inactivated poliovirus vaccineJIs jet injectorsMMR measles mumps rubella vaccineOPV oral poliovirus vaccineOSHA Occupational Safety and Health AdministrationPCV pneumococcal conjugate vaccinePPD purified protein derivativePRP-OMP polyribosylribitol phosphate-meningococcal

outer membrane proteinPRP-T PRP-tetanusPPV pneumococcal polysaccharide vaccineTd adult tetanus-diphtheria toxoidVAERS Vaccine Adverse Event Reporting SystemVAPP vaccine-associated paralytic polio

Definitions Used in This ReportAdverse event An untoward event that occurs after a vac-

cination that might be caused by the vaccine product orvaccination process It includes events that are 1) vaccine-induced caused by the intrinsic characteristic of the vac-cine preparation and the individual response of the vaccineethese events would not have occurred without vaccination(eg vaccine-associated paralytic poliomyelitis) 2) vaccine-potentiated would have occurred anyway but were pre-cipitated by the vaccination (eg first febrile seizure in apredisposed child) 3) programmatic error caused by tech-

able for intravenous use Intravenous immune globulinis used primarily for replacement therapy in primaryantibody-deficiency disorders for treatment of Kawasakidisease immune thrombocytopenic purpurahypogammaglobulinemia in chronic lymphocytic leu-kemia and certain cases of human immunodeficiencyvirus infection (Table 2)

Hyperimmune globulin (specific) Special prepara-tions obtained from blood plasma from donor poolspreselected for a high antibody content against a spe-cific antigen (eg hepatitis B immune globulin vari-cella-zoster immune globulin rabies immune globulintetanus immune globulin vaccinia immune globulincytomegalovirus immune globulin respiratory syncy-tial virus immune globulin botulism immune globu-lin)

Monoclonal antibody An antibody product preparedfrom a single lymphocyte clone which contains onlyantibody against a single microorganism

Antitoxin A solution of antibodies against a toxinAntitoxin can be derived from either human (eg teta-nus antitoxin) or animal (usually equine) sources (egdiphtheria and botulism antitoxin) Antitoxins are usedto confer passive immunity and for treatment

Vaccination and Immunization The terms vaccine andvaccination are derived from vacca the Latin term for cowVaccine was the term used by Edward Jenner to describematerial used (ie cowpox virus) to produce immunity tosmallpox The term vaccination was used by Louis Pasteurin the 19th century to include the physical act of adminis-tering any vaccine or toxoid Immunization is a more inclu-sive term denoting the process of inducing or providingimmunity by administering an immunobiologic Immuni-zation can be active or passive Active immunization is theproduction of antibody or other immune responses throughadministration of a vaccine or toxoid Passive immunizationmeans the provision of temporary immunity by the admin-istration of preformed antibodies Four types ofimmunobiologics are administered for passive immuniza-tion 1) pooled human immune globulin or intravenousimmune globulin 2) hyperimmune globulin (specific)preparations 3) monoclonal antibody preparations and 4)antitoxins from nonhuman sources Although persons of-ten use the terms vaccination and immunization inter-changeably in reference to active immunization the termsare not synonymous because the administration of animmunobiologic cannot be equated automatically with de-velopment of adequate immunity

Continuing Education Activity Sponsored by CDCGeneral Recommendations on Immunization Recommendations of the Advisory Committee on

Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP)

ACCREDITATIONContinuing Medical Education (CME) CDC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuingmedical education for physicians CDC designates this educational activity for a maximum of 20 hours in category 1 credit toward the AMA Physicianrsquos RecognitionAward Each physician should claim only those hours of credit that heshe actually spent in the educational activity

Continuing Education Unit (CEU) CDC has been approved as an authorized provider of continuing education and training programs by the InternationalAssociation for Continuing Education and Training and awards 02 Continuing Education Unit (CEUs)

Continuing Nursing Education (CNE) This activity for 23 contact hours is provided by CDC which is accredited as a provider of continuing education innursing by the American Nurses Credentialing Centerrsquos Commission on Accreditation

Certified Health Education Specialist (CHES) CDC is a designated provider of continuing education contact hours in health education by the NationalCommission for Health Education Credentialing Inc This program is a designated event for CHES to receive 20 hours in category 1 credit in health education CDCprovider number GA0082

By Internet1 Read this MMWR (Vol 51 RR-2) which contains the correct answers to the

questions beginning on the next page2 Go to the MMWR Continuing Education Internet site at lthttp

wwwcdcgovmmwrcmecontedhtmlgt3 Select which exam you want to take and select whether you want to register for

CME CEU CNE or CHES credit4 Fill out and submit the registration form5 Select exam questions To receive continuing education credit you must

answer all of the questions Questions with more than one correct answer willinstruct you to ldquoIndicate all that applyrdquo

6 Submit your answers no later than February 8 20057 Immediately print your Certificate of Completion for your records

By Mail or Fax1 Read this MMWR (Vol 51 RR-2) which contains the correct answers to the

questions beginning on the next page2 Complete all registration information on the response form including your

name mailing address phone number and e-mail address if available3 Indicate whether you are registering for CME CEU CNE or CHES credit4 Select your answers to the questions and mark the corresponding letters on

the response form To receive continuing education credit you must answerall of the questions Questions with more than one correct answer will instructyou to ldquoIndicate all that applyrdquo

5 Sign and date the response form or a photocopy of the form and send no laterthan February 8 2005 toFax 404-639-4198 Mail MMWR CE Credit

Office of Scientific and Health CommunicationsEpidemiology Program Office MS C-08Centers for Disease Control and Prevention1600 Clifton Rd NEAtlanta GA 30333

6 Your Certificate of Completion will be mailed to you within 30 days

INSTRUCTIONS

You must complete and return the response form electronically or by mail byFebruary 8 2005 to receive continuing education credit If you answer all ofthe questions you will receive an award letter for 20 hours Continuing MedicalEducation (CME) credit 02 Continuing Education Unit (CEUs) 23 contacthours Continuing Nursing Education (CNE) credit or 20 hours Certified Health

EXPIRATION mdash February 8 2005Education Specialist (CHES) credit If you return the form electronically you willreceive educational credit immediately If you mail the form you will receiveeducational credit in approximately 30 days No fees are charged for participatingin this continuing education activity

CE-2 MMWR February 8 2002

1 Which of the following is not a vaccination provider requirement asspecified by the National Childhood Vaccine Injury Act of 1986A Provide a copy of the relevant current edition of the Vaccine

Information Statement before each dose of vaccineB Obtain a signed consent before administration of vaccineC Record information regarding the vaccine in the recipientrsquos permanent

medical recordD Report certain vaccine adverse events to the Vaccine Adverse Event

Reporting System (VAERS)E All of the above are required by the National Childhood Vaccine

Injury Act of 1986

2 What is the preferred option for spacing of tuberculin skin testing(purified protein derivative [PPD]) and administration of measles-containing vaccineA PPD and measles-containing vaccine administered at the same visitB PPD administered 72 hours before measles-containing vaccineC PPD administered 4 weeks before measles-containing vaccineD Measles-containing vaccine administered 72 hours before PPDE Measles-containing vaccine administered 4 weeks before PPD

3 What is the minimum age for administration of the second dose ofinactivated poliovirus vaccineA Four weeksB Six weeksC Ten weeksD Sixteen weeksE Twenty-four weeks

4 A recent transfusion of whole blood is most likely to interfere with theresponse to which of the following vaccinesA Inactivated poliovirus vaccineB Yellow fever vaccineC Hepatitis B vaccineD Measles vaccineE Adult formulation of tetanus-diphtheria toxoid

5 Which of the following is a valid contraindication to theadministration of varicella vaccineA PregnancyB Child who is being breast-fedC Immunodeficient sibling living in the householdD Current antibiotic therapyE All of the above are valid contraindications to the administration of

varicella vaccine

6 What action is recommended if varicella vaccine is inadvertentlyadministered 10 days after a dose of measles-mumps-rubella (MMR)vaccineA Repeat both vaccines gt4 weeks after the varicella vaccine was

administeredB Repeat only the MMR vaccine gt4 weeks after the varicellaC Repeat only the varicella vaccine gt4 weeks after the inadvertently

administered dose of varicella vaccineD Repeat only the varicella vaccine gt6 months after the inadvertently

administered dose of varicella vaccineE No action is recommended both doses are counted as valid

Goal and ObjectivesThis MMWR provides general guidelines on immunizations These recommendations were developed by CDC staff the Advisory Committee on Immunization Practices(ACIP) and the American Academy of Family Physicians (AAFP) The goal of this report is to improve vaccination practices in the United States Upon completion of thisactivity the reader should be able to a) identify valid contraindications and precautions for commonly used vaccines b) locate the minimum age and minimum spacingbetween doses for vaccines routinely used in the United States c) describe recommended methods for administration of vaccines and d) list requirements for vaccinationproviders as specified by the National Childhood Vaccine Injury Act of 1986

To receive continuing education credit please answer all of the following questions

7 What is the minimum needle length recommended for intramuscularinjection of an infantA frac12 inchB 58 inchC 78 inchD 1 inchE 1frac14 inch

8 Which of the following approaches is recommended for thevaccination of a person with substantial immunodeficiencyA Inactivated vaccine should be administered as indicated without

regard to the immunodeficiencyB Live attenuated viral vaccines should generally not be administered to

persons with severe immunodeficiencyC Persons with humoral immunodeficiency should receive varicella

vaccine if indicatedD Live attenuated viral vaccines should be administered to susceptible

household contacts of immunodeficient personsE All of the above are approaches recommended for the vaccination of a

person with substantial immunodeficiency

9 What action is recommended if the interval between doses of hepatitisB vaccine is longer than the recommended intervalA Add one additional doseB Add two additional dosesC Restart the series from the beginningD Perform a serologic test to determine if a response to the vaccine has

been obtainedE Continue the series ignoring the prolonged interval

10 Indicate your work settingA Statelocal health departmentB Other public health settingC Hospital clinicprivate practiceD Managed care organizationE Academic institutionF Other work setting

11 Which best describes your professional activitiesA Patient care mdash emergency or urgent careB Patient care mdash inpatientC Patient care mdash primary care clinic or officeD Laboratory or pharmacyE Public healthF Other

12 I plan to use these recommendations as the basis for (Indicate allthat apply)A health education materialsB insurance reimbursement policiesC local practice guidelinesD public policyE other uses

13 Have you administered gt1 doses of vaccine in the last 12 monthsA YesB No

Vol 51 No RR-2 Recommendations and Reports CE-3

Detach or photocopy

receiv

8 2005

ese it

plicati

te I C

14 How much time did you spend reading this report and completing theexam and evaluationA Less than 2 hoursB 2ndash25 hoursC 25ndash3 hoursD More than 3 hours

15 After reading this report I am confident I can identify validcontraindications and precautions for commonly used vaccinesA Strongly agreeB AgreeC Neither agree nor disagreeD DisagreeE Strongly disagree

16 After reading this report I am confident I can locate the minimum ageand minimum spacing between doses for vaccines routinely used inthe United StatesA Strongly agreeB AgreeC Neither agree nor disagreeD DisagreeE Strongly disagree

17 After reading this report I am confident I can describe recommendedmethods for administration of vaccinesA Strongly agreeB AgreeC Neither agree nor disagreeD DisagreeE Strongly disagree

18 After reading this report I am confident I can list requirements forvaccination providers as specified by the National Childhood VaccineInjury Act of 1986A Strongly agreeB AgreeC Neither agree nor disagreeD DisagreeE Strongly disagree

19 The objectives are relevant to the goal of this reportA Strongly agreeB AgreeC Neither agree nor disagreeD DisagreeE Strongly disagree

20 The tables are usefulA Strongly agreeB AgreeC Neither agree nor disagreeD DisagreeE Strongly disagree

21 Overall the format of the report enhanced my ability to understandthe materialA Strongly agreeB AgreeC Neither agree nor disagreeD DisagreeE Strongly disagree

Correct answers for questions 1ndash91 B 2 A 3 C 4 D 5 A 6 C 7 C 8 E 9 E

22 These recommendations will affect my practiceA Strongly agreeB AgreeC Neither agree nor disagreeD DisagreeE Strongly disagree

23 The availability of continuing education credit influenced my decisionto read this reportA Strongly agreeB AgreeC Neither agree nor disagreeD DisagreeE Strongly disagree

24 How did you learn about this continuing education activityA InternetB Advertisement (eg fact sheet MMWR cover newsletter or journal)C CoworkersupervisorD Conference presentationE MMWR subscriptionF Other

References to non-CDC sites on the Internet are provided as a service to MMWR readers and do not constitute or imply endorsement ofthese organizations or their programs by CDC or the US Department of Health and Human Services CDC is not responsible for thecontent of these sites

Use of trade names and commercial sources is for identification only and does not imply endorsement by the US Department of Healthand Human Services

All MMWR references are available on the Internet at httpwwwcdcgovmmwr Use the search function to find specific articles

Advisory Committee on Immunization PracticesMembership List June 2001

Chairman John F Modlin MD Professor of Pediatrics and Medicine Dartmouth Medical School Lebanon New HampshireExecutive Secretary Dixie E Snider Jr MD Associate Director for Science Centers for Disease Control and Prevention Atlanta GeorgiaMembers Dennis A Brooks MD Johnson Medical Center Baltimore Maryland Richard D Clover MD University of Louisville School of MedicineLouisville Kentucky Jaime Deseda-Tous MD San Jorge Childrenrsquos Hospital San Juan Puerto Rico Charles M Helms MD PhD University of IowaHospital and Clinics Iowa City Iowa David R Johnson MD Michigan Department of Community Health Lansing Michigan Myron J Levin MDUniversity of Colorado School of Medicine Denver Colorado Paul A Offit MD Childrenrsquos Hospital of Philadelphia Philadelphia Pennsylvania MargaretB Rennels MD University of Maryland School of Medicine Baltimore Maryland Natalie J Smith MD California Department of Health ServicesBerkeley California Lucy S Tompkins MD PhD Stanford University Medical Center Stanford California Bonnie M Word MD MonmouthJunction New JerseyEx-Officio Members James Cheek MD Indian Health Service Albuquerque New Mexico Carole Heilman MD National Institutes of Health BethesdaMaryland Karen Midthun MD Food and Drug Administration Bethesda Maryland Martin G Myers MD National Vaccine Program Office AtlantaGeorgia Kristin Lee Nichol MD VA Medical Center Minneapolis Minnesota Col Benedict M Didiega MD Department of Defense Falls ChurchVirginia Geoffrey S Evans MD Health Resources and Services Administration Rockville Maryland T Randolph Graydon Health Care FinancingAdministration Baltimore MarylandLiaison Representatives American Academy of Family Physicians Martin Mahoney MD PhD Clarence New York Richard Zimmerman MDPittsburgh Pennsylvania American Academy of Pediatrics Jon Abramson MD Winston-Salem North Carolina Gary Overturf MD Albuquerque NewMexico American Association of Health Plans Eric K France MD Denver Colorado American College of Obstetricians and Gynecologists Stanley AGall MD Louisville Kentucky American College of Physicians Kathleen M Neuzil MD Seattle Washington American Hospital Association WilliamSchaffner MD Nashville Tennessee American Medical Association H David Wilson MD Grand Forks North Dakota Association of Teachers ofPreventive Medicine W Paul McKinney MD Louisville Kentucky Canadian National Advisory Committee on Immunization Victor Marchessault MDCumberland Ontario Canada Hospital Infection Control Practices Advisory Committee Jane D Siegel MD Dallas Texas Infectious Diseases Society ofAmerica Samuel L Katz MD Durham North Carolina London Department of Health David M Salisbury MD London United Kingdom NationalImmunization Council and Child Health Program Mexico Jose Ignacio Santos MD Mexico City Mexico National Medical Association Rudolph EJackson MD Atlanta Georgia National Vaccine Advisory Committee Georges Peter MD Providence Rhode Island Pharmaceutical Research andManufacturers of America Kevin Reilly Radnor Pennsylvania

Members of the General Recommendations on Immunization Working GroupAdvisory Committee on Immunization Practices (ACIP) Lucy Tompkins MD Chinh Le MD Richard Clover MD Natalie Smith MD ACIP Liaisonand Ex-Officio Members David H Trump MD Office of the Assistant Secretary of Defense (Health Affairs) Pierce Gardner MD American College ofPhysicians Georges Peter MD National Vaccine Advisory Committee Victor Marchessault MD Canadian National Advisory Committee on ImmunizationGoeffrey Evans MD Health Resources and Services Administration Richard Zimmerman MD American Academy of Family Physicians Larry PickeringMD American Academy of Pediatrics CDC staff member William L Atkinson MD other members and consultants Margaret Hostetter MD YaleChild Health Research Center Mary Staat MD Childrenrsquos Hospital Medical Center of Cincinnati Deborah Wexler MD Immunization Action CoalitionJohn Grabenstein PhD US Army Medical Command Thomas Vernon MD Merck Vaccine Division and Fredrick Ruben MD Aventis-Pasteur

The Morbidity and Mortality Weekly Report (MMWR) series is prepared by the Centers for Disease Control and Prevention (CDC) andis available free of charge in electronic format and on a paid subscription basis for paper copy To receive an electronic copy on Friday ofeach week send an e-mail message to listservlistservcdcgov The body content should read SUBscribe mmwr-toc Electronic copy also isavailable from CDCrsquos Internet server at httpwwwcdcgovmmwr or from CDCrsquos file transfer protocol server at ftpftpcdcgovpubPublicationsmmwr To subscribe for paper copy contact Superintendent of Documents US Government Printing Office WashingtonDC 20402 telephone 202-512-1800

Data in the weekly MMWR are provisional based on weekly reports to CDC by state health departments The reporting weekconcludes at close of business on Friday compiled data on a national basis are officially released to the public on the following FridayAddress inquiries about the MMWR series including material to be considered for publication to Editor MMWR Series Mailstop C-08CDC 1600 Clifton Rd NE Atlanta GA 30333 telephone 888-232-3228

All material in the MMWR series is in the public domain and may be used and reprinted without permission however citation of thesource is appreciated

US Government Printing Office 2002-733-10069005 Region IV

Introduction

Timing and Spacing of 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

Lapsed Vaccination Schedule

Unknown or Uncertain Vaccination Status

Contraindications and Precautions

Vaccine Administration

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 Immunobiologics

Special Situations

Concurrently Administering Antimicrobial Agents and Vaccines

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

Vaccinating Persons with Bleeding Disorders and Persons Receiving Anticoagulant Therapy

Vaccination Records

Consent to Vaccinate

Provider Records

Patientsrsquo Personal Records

Registries

Reporting Adverse Events After Vaccination

Vaccine Injury Compensation Program

Benefit and Risk Communication

Vaccination Programs

Vaccine Information Sources

National Immunization Information Hotline

CDCrsquos National Immunization Program


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

References

Abbreviations Used in This Publication

Definitions Used in This Report

Continuing Education Examination