This report is a revision o f the General Recomm endations on Im m unization a?id updates the 2 0 0 6 statement by the Advisory Committee on Im m unization Practices (ACIP) (CDC. General recommendations on im m unization: recommendations o f the Advisory Committee on Im m unization Practices , M M W R 2006;55, M M W R 1991;40); the assessment a n d feedback strategy to increase vaccination rates (CDC. Recommendations o f the Advisory Committee on Im m unization Practices: programmatic strategies to increase vaccination rates-assessment a nd feedback o f provider-based vaccination coverage information.#
C D C , our planners, and our content experts wish to disclose that they have no financial interests or other relationships w ith the manufacturers o f commercial products, sup pliers o f commercial services, or commercial supporters. This report w ill not include any discussion o f the unlabeled use o f a product or a product under investigational use w ith the exception o f the follow ing situations:
1. The nonsimultaneous administration o f yellow fever (YF) vaccine and inactivated vaccines. A tla n ta , G A 3 0 3 3 3 . Telephone: 4 0 4 -6 3 9 -1 9 5 8 ; Fax: 4 0 4 -6 3 9 -8 8 2 8 ; E -m a il: aok2@ cdc.gov.
T h e guidance in this report will help vaccination provid ers to assess vaccine benefits and risks, use reco m m ended ad m inistratio n and storage practices, u n d erstan d the m ost effective strategies for ensuring that vaccination coverage in the p o pulatio n rem ains high, and com m unicate the im portance o f vaccination to reduce the effects o f vaccine-preventable disease. T hese recom m endations are in ten d ed for use in the U nited States; vaccine availability, use, and epidem iologic cir cum stances m ight differ in o th er countries and m ight w arrant different recom m endations.

# M ethods
T h e Advisory C om m ittee on Im m unization Practices (ACIP) General Recom mendations W ork G roup (GRW G) revises the General Recommendations on Im m unization every 3 to 5 years. Relevant topics are those identified by A C IP as topics that relate to all vaccines, including tim ing and spacing o f doses, vaccine administration, and vaccine storage and handling. N ew topics often are added w hen A C IP decides that previous A C IP state ments on general issues such as com bination vaccines, adolescent vaccination, or adult vaccination should be revised and combined with the General Recommendations on Immunization.
T h e recom m endations in this rep o rt are based n o t only on available scientific evidence b u t also o n expertise th a t comes directly from a diverse group o f health-care providers and public h ealth officials. G R W G includes professionals from academ ic m ed icin e (pediatrics, fam ily practice, and pharm acy); international (C anada), federal, and state public health professionals; and a m em ber from the nongovernm ental Im m unization A ction C oalition. G R W G , w hich m et m onthly beginning June 2007, form ed subgroups o n the basis o f in ter est in topics such tim in g and spacing, vaccine adm inistration, and storage and handling. T hese subgroups also m et m onthly, conducted literature reviews, and co n trib u ted expert opinion on the need for revisions to specific language. In O ctober 2008, G R W G consulted A C IP to determ ine the best m echanism for approving the resulting docum ent. A C IP concluded that the docum ent could be approved and finalized increm entally w ith a final vote on the entire docum ent.
Revisions to the following sections were approved through con sensus vote in O ctober 2008 (i.e., were approved as a part o f the entire docum ent and not through separate votes on each section): l)T im in g and Spacing oflm munobiologics; 2) Contraindications and Precautions; 3) Preventing and M anaging Adverse Reactions; 4) Reporting Vaccine Adverse Events; 5) the N ational Vaccine Injury Com pensation Program; and 6) Vaccine Administration. In February 2009, revisions were made to Storage and H andling o f Immunobiologies, and A C IP approved the section. In June 2009, A CIP voted to incorporate the contents of a 1999 ACIP statem ent on com bination vaccines. T he statem ent was revised by G RW G and the A C IP C om bination Vaccines W ork Group. A C IP also approved m inor changes to the section on Special Situations and the section on Vaccination Records. In O ctober 2009, ACIP voted to revise the entire General Recommendations on Immunization, which incorporated ACIP recommendations on adolescent vaccination (1996) and adult vaccination (1991) into the section on Vaccination Programs. Three votes were taken to approve various sections o f the docum ent, and one vote was taken to approve the entire docum ent. At this final meeting, ACIP also discussed concerns about the lack o f evidence that supports use o f antipyretics before or at the time o f vaccination for the prevention o f fever.

# Tim ing and Spacing of Im m unobiologies

# General Principles for Vaccine Scheduling
O ptim al response to a vaccine depends on m ultiple factors, including the type o f vaccine, age o f the recipient, and im m une status o f the recipient. R ecom m endations for the age at w hich vaccines are adm inistered are influenced by age-specific risks for disease, age-specific risks for com plications, age-specific responses to vaccination, and potential interference w ith the im m une response by passively transferred m aternal antibodies. Vaccines are recom m ended for m em bers o f the youngest age group at risk for experiencing the disease for w hich efficacy and safety have been dem onstrated.
C ertain products, including inactivated vaccines, toxoids, recombinant subunit vaccines, polysaccharide conjugate vaccines, and live vaccines, require >2 doses to elicit an adequate antibody response. Tetanus and diphtheria toxoids require booster doses to m aintain protective antibody concentrations. Unconjugated polysaccharide vaccines do not induce T-cell memory, and addi tional doses (although they elicit the same or a lower antibody concentration) might increase the level o f protection. Conjugation w ith a protein carrier improves the effectiveness o f polysaccharide vaccines by inducing T-lymphocyte-dependent im m unologic function. M any vaccines th at stim ulate b o th cell-m ediated im m unity and neutralizing antibodies (e.g., live, attenuated virus vaccines) usually can induce prolonged immunity, even if antibody titers decline over time (7). Subsequent exposure to such viruses usually results in a rapid anamnestic antibody response w ithout viremia.
A pproxim ately 9 0 % -95% o f recipients o f a single dose o f certain live vaccines adm inistered by injection at the recom m ended age (i.e., measles, rubella, and yellow fever vaccines) develop protective antibodies, generally w ith in 14 days o f the dose. For varicella and m um ps vaccines, 8 0% -85% o f vaccinees are protected after a single dose. However, because a lim ited p roportion (5% -15% ) o f measles, m um ps, and rubella (M M R ) or varicella vaccinees fail to respond to 1 dose, a sec ond dose is recom m ended to provide another o p p o rtu n ity to develop im m u n ity (2). O f those w ho do n o t respond to the first dose o f M M R or varicella vaccine, 9 7 % -99% respond to a second dose (3,4).
T h e Recommended Im m unization Schedules fo r Persons Aged 0 Through 18 Years and the Recommended A d u lt Im m unization Schedule are revised annually. Physicians and oth er health-care providers should ensure th at they are following the m ost upto-date schedules, w hich are available from C D C at h ttp :// www.cdc.gov/vaccines.

# Spacing of Multiple Doses of the Same Antigen
V accination providers should adhere as closely as possible to recom m ended vaccination schedules (Table 1). A dm inistration at recom m ended ages and in accordance w ith recom m ended intervals betw een doses o f m ultidose antigens provide optim al protection.
A dm inistration o f doses o f a m ultidose vaccine using inter vals th at are shorter th an recom m ended m ight be necessary in certain circum stances, such as im pending international travel or w hen a person is behind schedule on vaccinations but needs rapid protection. In these situations, an accelerated schedule can be im plem ented using intervals betw een doses that are shorter than intervals recom m ended for rou tin e vaccination.
T h e accelerated or m in im u m intervals and ages for schedul ing catch-up vaccinations are available at  w w .cdc.gov/ vaccines. Vaccine doses should not be adm inistered at intervals less than these m in im u m intervals or at an age th at is younger th an the m in im u m age.- - D u rin g measles outbreaks, i f cases are occurring among infants aged 5 days earlier than the m inim um interval or age should n o t be counted as valid doses and should be repeated as age appropriate. T h e repeat dose should be spaced after the invalid dose by the recom m ended m inim um interval (Table 1). For example, if the first and second doses o f Haemophilus influenzae type b (H ib) were adm inistered only 14 days apart, the second dose w ould be invalid and need to be repeated because the m in im u m interval from dose 1 to dose 2 is 4 weeks. T h e repeat dose should be adm inistered >4 weeks after the invalid dose (in this case, the second). T h e repeat dose is counted as the valid second dose.
If the first dose in a series is given >5 days before the recom m ended m in im u m age, the dose should be repeated on or after the date w hen the child reaches at least the m in im u m age. If the vaccine is a live vaccine, ensuring that a m in im u m interval o f 28 days has elapsed from the invalid dose is recom m ended. For example, if the first dose o f varicella vaccine were inadver tently adm inistered at age 10 m onths, the repeat dose w ould be adm inistered no earlier than the child's first birthday (the m in im u m age for the first dose). I f the first dose o f varicella vaccine were adm inistered at age 11 m onths and 2 weeks, the repeat dose should be adm inistered no earlier than 4 weeks thereafter, w hich w ould occur after the first birthday.
C ertain vaccines (e.g., adult tetanus and d iphtheria toxoids , pediatric diphtheria and tetanus toxoids ; and teta nus toxoid) produce increased rates o f local or systemic reac tions in certain recipients w hen adm inistered m ore frequently than recom m ended (6,/) . Careful record keeping, m aintenance In certain situations, local o r state requirem ents m ig h t m andate th a t doses o f selected vaccines be adm inistered o n o r after specific ages. F or example, a school e n try re quirem ent m ig h t n o t accept a dose o f M M R o r varicella vaccine ad m inistered before the c h ild 's firs t birthday. A C IP recommends th a t physicians and other health-care providers co m p ly w ith local o r state vaccination require m ents w hen scheduling and a d m inistering vaccines.
-f patient histories, use o f im m u n izatio n inform ation systems (IISs), and adherence to recom m ended schedules can decrease the incidence o f such reactions w ith o u t adversely affecting im m u n ity

# Sim ultaneous Administration
S im u lta n e o u s a d m in is tra tio n o f vaccines is d efin ed as adm inistering m ore th an one vaccine on the same clinic day, at different anatom ic sites, and n o t com bined in the same syringe. Experim ental evidence and extensive clinical experi ence provide the scientific basis for adm inistering vaccines sim ultaneously Sim ultaneously adm inistering all vaccines for w hich a person is eligible at the tim e o f a visit increases the probability th a t a child, adolescent, or adult will be vaccinated fully by the appropriate age (8). A stu d y conducted during a measles outbreak dem onstrated th at approxim ately one third o f measles cases am o n g unvaccinated b u t vaccine-eligible preschool children m ight have been prevented if M M R had been adm inistered at the same visit w hen another vaccine was adm inistered (9). Sim ultaneous adm inistration also is criti cal w hen preparing for foreign travel and w hen a health-care provider is u ncertain th at a p atien t will retu rn for additional doses o f vaccine. W ith som e exceptions, sim ultaneously adm inistering the m ost w idely used live and inactivated vaccines has produced seroconversion rates and rates for adverse reactions sim ilar to those observed w hen the vaccines are adm inistered separately {10-13). R outine adm in istratio n o f all age-appropriate doses o f vaccines sim ultaneously is recom m ended for children for w hom no specific contraindications exist at the tim e o f the visit. M M R and varicella vaccine can be adm inistered sim ul taneously. Live, atten u ated influenza vaccine (LAIV) does n o t interfere w ith the im m u n e response to M M R or varicella vaccines adm inistered at the sam e visit. N o data exist about the im m u n o g e n ic ity o f oral T y21a ty p h o id vaccine w hen ad m inistered concurrently or w ith in 30 days o f live virus vac cines. In the absence o f such data, if typhoid vaccination is w arranted, adm inistration should n o t be delayed because o f recent adm inistration o f live, attenuated virus vaccines (14). Sim ultaneous ad m inistration of pneum ococcal polysaccharide vaccine (PPSV) and inactivated influenza vaccine elicits a satis factory antib o d y response w ith o u t increasing the incidence or severity o f adverse reactions (75). Sim ultaneous adm inistration o f PPSV and inactivated influenza vaccine is recom m ended for all persons for w h o m b o th vaccines are indicated. Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) and trivalent inactivated influenza vaccine (TIV) can be adm in istered sim ultaneously (76). H epatitis B vaccine adm inistered w ith yellow fever vaccine is as safe and im m unogenic as w hen these vaccines are adm inistered separately (77). Measles and yellow fever vaccines have been adm inistered safely at the same visit and w ith o u t reduction o f im m unogenicity o f either o f the com ponents (18,19).
D epending on w hich vaccines are adm inistered during the first year o f life, a child m ight receive up to nine injections at the 12-through 1 5 -m o n th visit (M M R , varicella, H ib, pneum ococcal conjugate vaccine , pediatric diphtheria and tetanus toxoids and acellular pertussis , inacti vated poliovirus , hepatitis A, hepatitis B, and influenza vaccines). A lthough there is no exact lim it on the n u m b er o f injections, w ith a little flexibility, a provider can ensure that the prim ary series doses are given w ith o u t adm inistering too m any injections at each visit. To reduce the n um ber o f injec tions at the 12-through 15-m onth visit, the hepatitis B series and 3 doses o f IP V (20) can be adm inistered before the child's first birthday.
T h ere are m any o ther examples o f ways the vaccination schedule provides flexibility. T h e m ajority o f children aged 1 year w'ho have received 2 H ib vaccine doses (polyribosylribitol phosphate-m eningococcal o u te r m em brane p ro te in ) or 3 H ib vaccine doses (PR P-tetanus ' P R P -T ) and 3 previous doses o f D TaP and P C V have protection against H ib, diphtheria, pertussis, tetanus, and pneum ococcus, w hich lasts th ro u g h o u t infancy (21,22). T h e third (P R P -O M P ) or fourth (PR P-T ) dose o f the H ib series and the fo u rth doses o f D TaP and P C V are critical in boosting antibody titer and ensuring continued protection (22-25). T he fourth dose o f D TaP is rec om m ended at age 15-18 m onths b u t m ay be adm inistered as early as age 12 m onths if 6 m onths have elapsed since the third dose and if there is concern that the child m ight n o t return by age 18 m onths (23). For infants at low risk for infection w ith hepatitis B virus (i.e., m other tested negative for hepatitis B surface antigen  at the tim e o f delivery and is not in a high risk group), the hepatitis B series can be com pleted at any tim e for children aged 6-18 m onths (26). T h e m inim um age for adm inistration o f com bination vaccines is the oldest m inim um age for any o f the individual com ponents; the m ini m um interval betw een doses is equal to the greatest m inim um interval o f any o f the individual com ponents. W ith use o f the com bination H ib-hepatitis B vaccine, the m in im u m age o f adm inistration o f the final dose is 12 m onths because o f the m inim um age requirem ent for the last dose o f the H ib series (26). R ecom m ended spacing o f doses should be m aintained (Table 1).

# Com bination Vaccines

# Licensed Com bination Vaccines
In this report, a com b in atio n vaccine is defined as a p ro d uct containing com ponents that can be divided equally into indepen d en tly available routine vaccines. A dash ( -) between vaccine products indicates th at products are supplied in their final form by the m anufacturer and do n o t require mixing or reconstitution by the user. A slash ( / ) indicates th at the products m ust be mixed or reconstituted by the user. Seven com bination vaccines for w hich separate antigens or antigen com binations exist have been licensed by F D A since 1996 in the U nited States (Table 2) (39-45). In the future, com bina tion vaccines m ight include increasing num bers o f com ponents in different arrays to protect against these and other diseases. Situations m ight arise in w hich one com p o n en t o f a com bination vaccine is specifically preferred to another com po nen t in that same vaccine. Future research considerations for new ly licensed com bination vaccines should focus on safety o f doses th a t are n o t needed because a p atient is already vac cinated against the agents, w hether the com bination vaccine w ill im prove the tim eliness o f v accination, and p o ten tial reduced costs from disease prevention resulting from timely vaccination.

# C om bination Vaccines and FDA Licensure
O n ly com bination vaccines licensed by FD A should be used. V accination providers should not com bine separate vaccines into the same syringe to adm inister together unless m ixing is indicated for the p a tie n t's age and is explicitly specified on the FD A -approved p ro duct label inserts. O n ly two com bination vaccines (D T aP -IP V /H ib vaccine, m arketed as Pentacel, and D T aP /H ib , m arketed as T riH ibit) contain separate antigen com ponents for w hich FD A approves m ixing by the user. T h e safety, im m unogenicity, and effectiveness of unlicensed com binations are unknow n.

# Interchangeability o f Form ulations
F D A generally licenses a co m b in atio n vaccine based on studies dem onstrating th at the p ro d u ct's im m unogenicity (or efficacy) and safety are com parable or equivalent to m onova lent or com bination products licensed previously (46). FD A licensure also generally indicates that a com bination vaccine m ay be used interchangeably w ith m onovalent form ulations and o th e r co m b in atio n p ro d u cts w ith sim ilar c o m p o n en t antigens produced by the same m anufacturer to continue the vaccination series. For example, DTaP, D T aP /H ib , and future D T aP vaccines th at contain sim ilar acellular pertussis antigens from the same m anufacturer m ay be used interchangeably if licensed and indicated for the p atien t's age (45).

# In terch an geability o f Com bination Vaccines from D ifferen t M anufacturers
Licensure o f a vaccine by F D A does n o t necessarily indicate th at the vaccine is interchangeable w ith products from other m anufacturers. Such data are ascertained and interpreted more readily for diseases w ith know n correlates o f protective im m u nity (e.g., specific serologic m arkers). For diseases w ith o u t such surrogate laboratory m arkers, prelicensure field vaccine efficacy (phase III) trials or postlicensure surveillance generally are required to determ ine pro tectio n (47). A C IP prefers that doses o f vaccine in a series com e from the sam e m anufacturer; however, if this is n o t possible or if the m anufacturer of doses given previously is u n k now n, provid ers should adm inister the vaccine th at they have available.

# Vaccine Supply
A lth o u g h v accin atio n providers should stock sufficient quantities o f com bination and m onovalent vaccines needed to vaccinate children, adolescents, and adults against all diseases for w hich vaccines are recom m ended (20,28), all available types o r b rand-nam e products need n o t be stocked. Potential advantages o f stocking a lim ited n u m b er o f vaccines include 1) reducing confusion and p otential errors w hen staff m em bers m ust handle re d u n d a n t products and form ulations, 2) m inim izing waste w hen less com m only used products expire, 3) decreasing cold storage capacity requirem ents, and 4) m ini m izing adm inistrative costs related to accounting, purchasing, and handling.

# Extra Doses o f Vaccine Antigens
A dm inistering extra antigens contained in a com bination vaccine should be avoided in m ost situations. Using com bina tion vaccines containing certain antigens n o t indicated at the tim e o f adm in istratio n to a patient m ight be justified w hen 1) the extra antigen is n o t contraindicated, 2) products th at contain only the needed antigens are n o t readily available, and 3) potential benefits to the patient outw eigh the potential risk for adverse events associated w ith the extra antigens. An extra dose o f m any live-virus vaccines and H ib or hepatitis B vaccine has n o t been found to be harm ful (48). However, the risk for an adverse event m ight increase w hen extra doses are adm inistered at an earlier tim e than the recom m ended interval for certain vaccines (e.g., tetanus toxoid vaccines and PPSV) (16,24,49).
A vaccination provider m ight n o t have vaccines available th at contain only the antigens needed as indicated by a child's vaccination history. Alternatively, although the indicated vac cines m ight be available, the provider m ight prefer to use a com bination vaccine to red uce the required n u m b er o f injec tions. In such cases, the benefits and risks o f adm inistering the com bination vaccine w ith an unneeded antigen should be care fully considered and discussed w ith the patient or parent. W h e n inactivated (i.e., killed), or particularly su b u n it vac cines (which are often adsorbed to alum inum -salt adjuvants), are adm inistered, the reactogenicity o f the vaccine m ust be considered in balancing the benefits and risks o f extra doses. Because clinical experience suggests low reactogenicity, an extra dose o f H ib or hepatitis B vaccine m ay be adm inistered as part o f a com bination vaccine to com plete a vaccination series for another com ponent o f the com bination. A dm inistration o f extra doses o f tetanus toxoid vaccines earlier than the recom m ended intervals can increase the risk for hypersensitivity reactions (16,24,50). Examples o f such vaccines include DTaP, D T aP /H ib, D T (for ch ild ren ),T d (for adolescents and adults), and T dap. Extra doses o f tetanus-toxoid-containing vaccines m ight be appropriate for certain patients, including for children w ho previously received D T o r T d vaccine and need protec tio n from pertussis (in D TaP or T dap) or for im m igrants w ith u ncertain vaccination histories.

# C onjugate Vaccine Carrier Proteins
C ertain carrier proteins in existing conjugated H ib vaccines also are used as com ponents o f other vaccines (e.g., p n eu m o coccal and m eningococcal vaccines) (51). Protein conjugates used in H ib conjugate vaccines produced in the U nited States include an outer m em brane protein com plex from Neisseria m eningitidis (in P R P -O M P ), and tetanus toxoid (in PR P-T ). Sim ultaneous adm inistration o f quadrivalent m eningococcal conjugate vaccine (M C V 4), PCV, and T d ap , all o f w hich con tain diphtheria toxoid, is n o t associated w ith reduced im m u nogenicity or an increase in local adverse events (24,51).

# Nonsim ultaneous Administration
T here is no evidence th at inactivated vaccines interfere w'ith the im m une response to o th er inactivated vaccines or to live vaccines. A ny inactivated vaccine can be adm inistered either sim ultaneously or at any tim e before or after a different inac tivated vaccine or live vaccine (Table 3).
Lim ited data are available regarding interference between live vaccines used in the U nited States. T h e im m une response to one live-virus vaccine m ight be im paired if adm inistered w ithin 28 days (i.e., 4 weeks) o f another live-virus vaccine (52,53). In a study conducted in two U.S. health m aintenance organiza tions, the risk for varicella vaccine failure (i.e., varicella d isease in a vaccinated person) am ong persons wrho received varicella vaccine w ith in 28 days o f M M R vaccination was threefold higher than am ong persons w ho received varicella vaccine >28 days after M M R vaccination (54). A no th er stu d y determ ined th at the response to yellow fever vaccine is n o t affected by m onovalent measles vaccine adm inistered 1-27 days earlier (18). T h e effect ofn o n sim u ltan eo u s adm inistration o f rubella, m um ps, varicella, and yellow fever vaccines is unknow n.
To m inim ize the potential risk for interference, injectable or nasally adm inistered live vaccines not adm inistered on the same day should be adm inistered >4 weeks apart (Table 3). If injectable or nasally adm inistered live vaccines are separated by 4 weeks after the last invalid dose. O ral vaccines (Ty21a typhoid vaccine and rotavirus) can be adm inistered sim ultaneously or at any interval before or after other live vaccines (injectable or intranasal) if indicated.

# Spacing of Vaccines and Antibody-Containing Products

# Live Vaccines
Ty21a typhoid, yellow fever, LAIV, zoster, and rotavirus vaccines m ay be adm inistered at any tim e before, concurrent w ith, o r after adm inistration o f any im m u n e globulin, hyper im m un e globulin, or intravenous im m une globulin (IGIV ) (55). Blood (e.g., w hole blood, packed red blood cells, and plasma) and oth er an tibody-containing blood products (e.g., im m un e globulin, h y p erim m u n e globulin, and IG IV ) can in hibit the im m u n e response to measles and rubella vaccines for >3 m onths. T h e effect o f blood and im m u n e globulin preparations on the response to m um ps and varicella vaccines is unknow n; however, commercial im m une globulin preparations contain antibodies to these viruses. Blood prod ucts available in the U nited States are unlikely to contain a substantial am ount of antib o d y to yellow fever vaccine virus. T h e length o f tim e th at interference w ith injectable live-virus vaccine (other th an yellow' fever) can persist after the antibody-containing product is a function of the am o u n t o f antigen-specific antib ody con tained in the p ro d u ct (56-58). T herefore, after an antibodycontaining prod u ct is received, live vaccines (other th an yellow fever, o ralT y 2 1 a typhoid, LAIV, zoster, and rotavirus) should be delayed u n til the passive antib o d y has degraded (Table 4). I f a dose o f injectable live-virus vaccine (other than yellow fever and zoster) is adm inistered after an an tibody-containing p roduct b u t at an interval shorter than recom m ended in this report, the vaccine dose should be repeated unless serologic testing is feasible and indicates a response to the vaccine. T h e repeat dose o r serologic testing should be perform ed after the interval indicated for the an tibody-containing p roduct (Table 5).
A lthough passively acquired antibodies can interfere w ith the response to rubella vaccine, the low dose o f anti-R ho(D ) globulin adm inistered to p o stp artu m w om en has n o t been dem onstrated to reduce the response to the RA 27/3 strain rubella vaccine (59). Because o f the im portance o f rubella and varicella im m u n ity am ong w om en o f child-bearing age (4,60), the postpartum vaccination o f w om en w ithout evidence o f im m u n ity to rubella or varicella w ith M M R , varicella, or M M R V vaccines should n o t be delayed because o f receipt o f anti-R ho(D ) globulin or any other blood p ro d u ct during the last trim ester o f pregnancy or at delivery. T hese w om en should be vaccinated im m ediately after giving b irth and, if possible, tested >3 m onths later to ensure im m u n ity to rubella and, if appropriate, to measles (2).
Interference m ight occur if adm inistration o f an antibodycontaining p ro d u ct becomes necessary after adm inistration o f M M R or varicella vaccines. Usually, vaccine virus replication and stim ulation o f im m u n ity occurs 1-2 weeks after vaccina tion. If the interval between adm inistration o f any o f these vac cines and subsequent adm inistration o f an antibody-containing product is <14 days, vaccination should be repeated after the recom m ended interval (Tables 4 and 5) unless serologic testing indicates a protective antibody response.
A hum anized m ouse m onoclonal antibody p ro d u ct (palivizum ab) is available as prophylaxis for serious lower respiratory tract disease from respiratory syncytial virus am ong infants and young children. T his p ro d u ct contains only antibody to respi ratory syncytial virus and does n o t interfere w ith the im m une response to licensed live or inactivated vaccines.

# Inactivated Vaccines
A ntibody-containing products interact less w ith inactivated vaccines, toxoids, recom binant su bunit, and polysaccharide vaccines th an w ith live vaccines (61). Therefore, adm inistering inactivated vaccines and toxoids either sim ultaneously w ith or at any interval before or after receipt o f an antibody-containing p ro d u c t should n o t substantially im pair developm ent o f a protective antibody response (Table 4). T h e vaccine or toxoid and antibody preparation should be adm inistered at different sites using the standard recom m ended dose. Increasing the vaccine dose volum e or num ber o f vaccinations is n o t indicated or recom m ended.

# Interchangeability of Single-Com ponent Vaccines from Different M anufacturers
C ertain vaccines th at provide p ro tectio n from the same diseases are available from different m anufacturers, and these vaccines usually are n o t identical in antigen co n ten t or in am o u n t or m ethod o f form ulation. M anufacturers use differ ent production processes, and their products m ight contain different co ncentrations o f antigen per dose or a different stabilizer or preservative.
Available data indicate th at infants w ho receive sequential doses o f different H ib conjugate, hepatitis B, and hepatitis A vaccines produce a satisfactory antib o d y response after a com plete prim ary series (62-65)-All brands o f H ib conju gate, hepatitis B ,i hepatitis A, rotavirus, and quadrivalent m eningococcal conjugate vaccines are interchangeable w ithin their respective series. I f different brands o f a particular vaccine require a different nu m b er o f doses for series com pletion (e.g., H ib and rotavirus vaccines) and a provider mixes brands, the higher n u m b er o f doses is recom m ended for series com pletion (e.g., 3 doses o f either rotavirus or H ib vaccines).
Lim ited data are available about the safety, im m unogenicity, and efficacy of using acellular pertussis (e.g., DTaP) vaccines from different m anufacturers for successive doses o f the per tussis series. D ata from one study indicate th at for the first 3 doses of the D TaP series, 1 -2 doses ofT ripedia (Sanofi Pasteur) followed by Infanrix (GlaxoSmithKline) for the rem aining dose (or doses) is com parable to 3 doses o fT rip ed ia w ith regard to im m unogenicity, as m easured by antibodies to diphtheria, tetanus, and pertussis toxoids, and filam entous hem agglutinin (66). However, in the absence o f a clear serologic correlate o f protectio n for pertussis, the relevance o f these im m unogenic ity data for protectio n against pertussis is unknow n. W h e n feasible, the same bran d o f D TaP vaccine should be used for all doses of the vaccination series. I f vaccination providers do n o t know or have available the type o f D TaP vaccine previ ously adm inistered to a child, any D TaP vaccine m ay be used to continue or com plete the series. For a child w ho needs 2 doses o f influenza vaccine (T IV or LAIV), it is preferable to use the sam e type o f vaccine for both doses. However, if the child is eligible for either T IV or LAIV, and the type o f vaccine used for the first dose is n o t available, either vaccine can be used for the second dose. For vaccines in general, vaccination should n o t be deferred because the brand used for previous doses is n o t available or is u n k n o w n (23,67).

# Lapsed Vaccination Schedule
V accination providers should adm inister vaccines as close to the recom m ended intervals as possible. However, intervals betw een doses th at are longer than recom m ended typically do n o t reduce final antibody concentrations, although protection m ight n o t be attained until the recom m ended num ber o f doses has been adm inistered. W ith exception o f oral typhoid vaccine, an in terru p tio n in the vaccination schedule does n o t require restarting the entire series o f a vaccine or toxoid or addition o f extra doses.

# Unknown or Uncertain Vaccination Status
V accination providers frequently encounter persons w ho do n o t have adequate d o cum entation o f vaccinations. W ith the exception o f influenza vaccine and PPSV, providers should only accept w ritten, dated records as evidence o f vaccination; self-reported doses o f influenza vaccine and PPSV are accept able (49,68). A lthough vaccinations should n o t be postponed if records cannot be found, an attem pt to locate missing records should be m ade by contacting previous health-care providers, reviewing state or local IISs, and searching for a personally held record. If records cannot be located w ithin a reasonable tim e, these persons should be considered susceptible and started on the age-appropriate vaccination sched ule. Serologic testing for im m u n ity is an alternative to vaccination for certain antigens (e.g., measles, rubella, hepatitis A, and tetanus). However, com m ercial serologic testing m ight n o t always be sufficiently sensitive o r standardized for detectio n o f vaccine-induced im m unity (with the exception o f hepatitis B vaccination at 1-2 m onths after the final dose), and research laboratory testing m ight not be readily available.

# Contraindications and Precautions
C ontraindications and precautions to vaccination are con ditions under w hich vaccines should n o t or likely should not be adm inistered. Because the m ajority o f contraindications and precautions are tem porary, vaccinations often can be adm inistered later if one or m ore exist. A con traindication is a condition in a recipient th at increases the risk for a serious adverse reaction. A vaccine should n o t be adm inistered w hen a c o n tra in d ica tio n is present; for exam ple, M M R vaccine should n o t be adm inistered to severely im m unocom prom ised persons. In contrast, certain conditions are com m only misperceived as contraindications (i.e., are n o t valid reasons to defer vaccination).
N ational standards for pediatric vaccination practices have been established and include descriptions o f valid contraindica tions and precautions to vaccination. Persons w ho adm inister vaccines sh o u ld screen p atien ts for c o n train d icatio n s and p recautions to the vaccine before each dose o f vaccine is adm inistered (Table 6). Screening is facilitated by consistent use o f screening questionnaires, w hich are available from certain sta te v a c c in a tio n p ro g ram s a n d o th e r so u rces (e.g., th e Im m unization Action Coalition,  w w .im m unize.org).
T h e only co n train d icatio n applicable to all vaccines is a history o f a severe allergic reaction (i.e., anaphylaxis) after a previous dose o f vaccine or to a vaccine co m p o n en t (unless the recipient has been desensitized; see Special Situations section). In addition, severely im m uno co m p ro m ised persons generally should n o t receive live vaccines. C hild ren w ho experienced encephalopathy w ith in 7 days after adm inistration o f a pre vious dose o f d ip h th eria and tetanus toxoids and whole-cell pertussis vaccine (D T P ), DTaP, or T d ap n o t attributable to another identifiable cause should n o t receive additional doses of a vaccine th a t contains pertussis. Because of the theoreti cal risk to the fetus, w om en know n to be p regnant generally should n o t receive live, attenuated virus vaccines (see Special Situations section).
A precaution is a condition in a recipient that m ight increase the risk for a serious adverse reaction or that m ight com prom ise the ability o f the vaccine to produce im m u n ity (e.g., adm in istering measles vaccine to a person w ith passive im m u n ity to measles from a blood transfusion or adm inistering influenza vaccine to som eone w ith a history o f G uillain-Barre syndrom e w ithin 6 weeks o f a previous influenza vaccination). A person m ight experience a m ore severe reaction to the vaccine than w ould have otherw ise been expected; however, the risk for this happening is less than the risk expected w ith a contraindication. In general, vaccinations should be deferred w hen a precaution is present. However, a vaccination m ight be indicated in the presence o f a p recaution if the benefit o f pro tectio n from the vaccine outweighs the risk for an adverse reaction. For example a dose o f D T aP should be considered for a person in a com m u n ity w ith a pertussis outbreak even if th at person previously developed G uillain-B arre syndrom e after a dose.
T h e presence o f a m oderate or severe acute illness w ith or w ith o u t a fever is a precaution to adm inistration of all vaccines (Table 6). A personal or family history o f seizures is a precaution for M M R V vaccination. A recent study found an increased risk for febrile seizures in children w ho receive M M R V com pared w ith M M R and varicella vaccine (35).
Clinicians or other health-care providers m ight misperceive certain conditions or circumstances as valid contraindications or precautions to vaccination when they actually do not preclude vaccination (Table 7). These m isperceptions result in missed opportunities to administer recom m ended vaccines (69). Among the m ost com m on conditions mistakenly considered to be con traindications are diarrhea, m inor upper respiratory tract illnesses (including otitis media) w ith or w ithout fever, mild to moderate local reactions to a previous dose o f vaccine, current antimicrobial therapy, and being in the convalescent phase o f an acute illness. Routine physical exam inations and procedures (e.g., measur ing tem peratures) are n o t prerequisites for vaccinating persons w ho appear to be healthy. T h e provider should ask the parent or guardian if the child is ill. I f the child has a m oderate or severe illness, the vaccination should be postponed.

# Preventing and M anaging
Adverse R eactions

# Benefit and Risk Com munication
Parents, guardians, legal representatives, and adolescent and adult patients should be inform ed about the benefits of and risks from vaccines in language th at is culturally sensitive and at an appropriate educational level. O p p o rtu n ity for questions should be provided before each vaccination. D iscussion o f the benefits o f and risks from vaccination is sound medical practice and is required by law.
T h e N atio n al C h ild h o o d Vaccine In ju ry A ct o f 1 9 8 6 : : requires th at vaccine inform ation m aterials be developed for each vaccine covered by the act. T hese m aterials, know n as vaccine inform ation statem ents (VI Ss), m ust be provided by all public and private vaccination providers each tim e a vaccine is adm inistered. Copies ofV ISs are available from state health authorities responsible for vaccination and from C D C (h ttp :// www.cdc.gov/vaccines). Translations o fV IS s into languages o th er th an English are available from certain state vaccination programs and from the Im m unization A ction C oalition website ( w w .im m unize.org). T h e act does n o t require th at a signature be obtained; however, d o cu m en tatio n o f consent m ight be recom m ended or required by certain state or local h ealth authorities or school authorities. C ertain parents or patients question the need for or safety o f vaccinations and w ant to discuss the risks from and benefits o f certain vaccines. Some refuse certain vaccines or reject all vaccinations for personal or religious reasons. H aving a basic understanding of how patients and parents o f patients view vac cine risk and developing effective approaches to address vaccine safety concerns are im perative for vaccination providers.
Each person understands and reacts to vaccine inform ation on the basis o f different factors, including previous experience, education, personal values, m eth o d o f data presentation, per ceptions o f the risk for disease and perceived ability to control these risks, and risk preference. Increasingly, decisions about vaccination are based o n inaccurate inform ation about risk provided by the m edia and certain websites. W ebsites and other sources o f vaccine info rm atio n m ight be inaccurate or incom plete. H ealth-care providers can be a pivotal source o f science-based credible inform ation by discussing w ith parents and patients the risks from and benefits o f vaccines, w hich helps patients m ake inform ed decisions. W h e n a parent or p atien t initiates a discussion about a per ceived vaccine adverse reaction, the health-care provider should discuss the specific concerns and provide factual inform ation, using appropriate language. Effective, em pathetic vaccine risk com m u n icatio n is essential in responding to m isinform ation and concerns, w'ith health-care providers recognizing that risk assessment and decision-making can be difficult and confusing. C ertain vaccines m ight be acceptable to a parent who is resistant to other vaccines. This partial acceptance can be used to facilitate additional communication. T heir concerns can be addressed using the VIS and offering other resource materials (e.g., vaccination inform ation from C D C : ).
T h e A m erican A cadem y o f Pediatrics (AAP) does n o t rec om m en d th at providers exclude from their practice patients whose parents or guardians question or refuse vaccination. A lim ited nu m b er o f providers m ight exclude patients on this basis; however, an effective public health strategy is to identify com m on ground and discuss measures that need to be followed if the decision is to defer vaccination. H ealth-care providers should reinforce key p o in ts ab o u t each vaccine, including safety, and emphasize risks for disease am ong unvaccinated children. Parents should be advised o f state laws regarding entry to schools or child-care facilities, w hich m ight require th at unvaccinated children be excluded from the facility d u r ing outbreaks. T hese discussions should be docum ented in the patient's medical record, including the refusal to receive certain vaccines (i.e., inform ed refusal).

# Preventing Adverse Reactions
Vaccines are intended to produce active im m u n ity to spe cific antigens. A n adverse reaction is an undesirable side effect th at occurs after a vaccination. Vaccine adverse reactions are classified as 1) local, 2) system ic, or 3) allergic (additional inform ation available at  w w .fda.gov). Local reactions (e.g., redness) are usually the least severe and m ost frequent. Systemic reactions (e.g., fever) occur less frequently th an local reactions, and severe allergic reactions (e.g., anaphylaxis) are the least frequent reactions. Severe adverse reactions are rare.
Syncope (vasovagal or vasodepressor reaction) can occur after vaccination and is m ost com m on am ong adolescents and young adults. In 2005, the Vaccine Adverse Event R eporting System (VAERS) began detecting a trend o f increasing syncope reports th at coincided w ith the licensure o f three vaccines for adolescents: h u m an papillom avirus (H PV ), M C V 4, and T dap (77). O f particular concern am ong adolescents has been the risk for serious secondary injuries, including skull fracture and cerebral hem orrhage. O f 463 VAERS reports o f syncope during January 1, 2005, to July 31, 2007, a total o f 41 listed syncope w ith secondary injury w ith inform ation on the tim ing after vaccination, and the m ajority o f these syncope reports (76% ) occurred am ong adolescents. A m ong all age groups, 80% o f reported syncope episodes occur w ithin 15 m inutes o f vaccine ad m in istratio n (additional in fo rm atio n available at h ttp :// w w w .cdc.gov/vaccinesafety/concern/syncope.htm ). Providers should take appropriate measures to prevent injuries if a patient becom es weak or dizzy or loses consciousness. Adolescents and adults should be seated or lying dow n during vaccination. Vaccine providers, particularly w hen vaccinating adolescents, should consider observing patients (with patients seated or lying down) for 15 m inutes after vaccination to decrease the risk for injury should they faint (77). I f syncope develops, patients should be observed until the sym ptom s resolve.

# Managing Acute Vaccine Reactions
A lthough anaphylactic reactions are rare after vaccination, their im m ediate onset and life-threatening nature require that all personnel and facilities providing vaccinations have proce dures in place for anaphylaxis m anagem ent. All vaccination providers should be fam iliar w ith the office em ergency plan and be currently certified in cardiopulm onary resuscitation. Epinephrine and equipm ent for m aintaining an airway should be available for im m ediate use.
A naphylaxis usually begins w ith in m in u te s o f vaccine adm inistration (78-80). Rapid recognition and initiation o f treatm ent are required to prevent possible progression to car diovascular collapse. If flushing, facial edema, urticaria, itching, swelling o f the m o u th or throat, w heezing, dyspnea, or other signs or sym ptom s o f anaphylaxis occur, the patient should be placed in a recum bent position w ith the legs elevated if possible (81,82). A d m inistration o f epinephrine is the m anagem ent o f choice. A dditional drugs also m ight be indicated (Table 8) (83). M aintenance o f the airway and oxygen adm inistration m ight be necessary. A fter the p atien t is stabilized, arrangem ents should be m ade for im m ediate transfer to an em ergency facility for additional evaluation and treatm ent.

# Reporting Adverse Events After Vaccination
M o d ern vaccines are safe and effective; however, adverse events have been reported after adm inistration o f all vaccines (84). M ore com plete inform ation about adverse reactions to a specific vaccine is available in the package insert for each vac cine and from C D C at  w w .cdc.gov/vaccines/vac-gen/ side-effects.htm . An adverse event is an untow ard event that occurs after a vaccination th at m ight be caused by the vaccine p roduct or vaccination process. These events range from com m on, m inor, local reactions to rare, severe, allergic reactions (e.g., anaphylaxis). Establishing evidence for cause and effect on the basis o f case reports and case series alone is usually n o t possible because health problem s that have a tem poral associa tion w ith vaccination do n o t necessarily indicate causality.
M an y adverse events require m ore detailed epidem iologic studies to com pare th e incidence o f the event am ong vaccinees to the in cidence am o n g u n v accinated persons. R ep o rtin g adverse events, including serious events, to VAERS is a key m echanism for identifying p o tential vaccine safety concerns. Potential causal associations betw een reported adverse events after vaccination can be assessed th ro u g h epidem iologic or clinical studies.
T h e N a tio n a l C h ild h o o d V accin e In ju ry A ct requires health-care providers and vaccine m anufacturers to report to VAERS specific adverse events th at occur after vaccination. T h e reporting requirem ents are different for m anufacturers and health-care providers. M anufacturers are required to report all adverse events th at occur after vaccination to VAERS, whereas health-care providers are required to report events th at appear in the reportable events table on the VAERS website at http:/./ vaers.hhs.gov/reportable.htm .
In add itio n to the m andated reporting o f events listed on the reportable events table, health-care providers should report to VAERS all events listed in p ro d u ct inserts as contraindica tions, as well as all clinically significant adverse events, even if they are u ncertain th at the adverse event is related causally to vaccination. Persons other than health-care providers also can report adverse events to VAERS.

# National Vaccine Injury Com pensation Program
T h e N a tio n a l V accine In ju ry C o m p e n sa tio n P rogram , established by the N ational C hild h o o d Vaccine In ju ry A ct o f 1986, is a no-fault system in w hich persons th o u g h t to have experienced an injury or to have died as a result o f adm inistra tion o f a covered vaccine can seek com pensation. T h e program became operational on O ctober 1, 1988, and is intended as an alternative to civil litigation un d er the traditional to rt system in th at negligence need n o t be proven. C laim s arising from covered vaccines m ust first be adjudicated through the program before civil litigation can be pursued.
T h e program relies on the Vaccine In ju ry Table, w hich lists the vaccines covered by the program and the injuries (including death), disabilities, illnesses, and conditions for w hich com pensation m ight be awarded. T he table defines the tim e during w hich the first sym ptom or substantial aggravation o f an injury m ust appear after vaccination to be eligible. Successful claim ants receive a legal presum ption o f causation if a condition listed in the table is proven, thus avoiding the need to prove actual causation in an individual case. C laim ants also can prevail for conditions n o t listed in the reportable events table if they prove causation for covered vaccines. A dditional inform ation is avail able from the H ealth Resources and Services A dm inistration (H RSA ) (h ttp  w w .h rsa.

# V accine Administration

# Infection Control and Sterile Technique

# General Precautions

# Needles and Syringes
Needles and syringes used for vaccine injections m ust be sterile and disposable. A separate needle and syringe should be used for each injection. C hanging needles betw een draw ing vaccine from a vial and injecting it into a recipient is not necessary unless the needle has been dam aged or contam i nated. D ifferent vaccines should never be mixed in the same syringe unless specifically licensed for such use, and no attem pt should be m ade to transfer betw een syringes. Single-dose vials and m anufacturer-filled syringes are designed for single-dose adm inistration and should be discarded if vaccine has been w ithdraw n or reconstituted and subsequently n o t used w ithin the tim e fram e specified by the m anufacturer. T h is typically is no longer th an th e sam e clinic day (typically recom m ended as a m axim um for inactivated vaccines).
Som etim es providers prefill syringes themselves. A C IP dis courages the routine practice o f prefilling syringes because o f the potential for adm inistration errors and vaccine wastage. Because the m ajority o f vaccines have a similar appearance after being draw n into a syringe, prefilling m ight result in adm inis tration errors. In certain circum stances in w hich a single vac cine type is being used (e.g., in p reparation for a co m m u n ity influenza vaccination cam paign), filling a small n u m b er o f syringes m ay be considered. Vaccine doses should n o t be drawn into a syringe u n til im m ediately before adm inistration. W h e n syringes are filled, the type o f vaccine, lot num ber, and date o f filling m ust be labeled on each syringe, and the doses should be adm inistered as soon as possible after filling. U nused syringes filled by the end user (i.e., n o t filled by the m anufacturer) should be discarded at the end o f the vaccination session. In ad ditio n to adm inistration errors, prefilling o f syringes is a concern because F D A does n o t license adm inistration syringes for vaccine storage. U nused syringes th at are prefilled by the m anufacturer and activated (i.e., syringe cap removed or needle attached) should be discarded at the end o f the clinic day. T h e act directed O S H A to strengthen its existing bloodborne pathogen standards. T h e revised standards becam e effective in 2001 (86). These federal regulations require th at safetyengineered injection devices (e.g., needle-shielding syringes or needle-free injectors) be used for injectable vaccination in all clinical settings. T h e regulations also require m aintenance o f records docum enting injuries caused by needles and other m edical sharp objects and th at nonm anagerial employees be involved in the evaluation and selection o f safety-engineered devices before they are procured.
Safety-engineered needles and syringes or needle-free injec tion devices are preferred and should be encouraged to reduce risk for injury. To prevent inadvertent needle-stick injury or reuse, safety m echanism s should be deployed after use and needles and syringes sh o u ld be discarded im m ed iately in labeled, p u n c tu re -p ro o f containers located in the same room w'here the vaccine is adm inistered. Used needles should never be recapped .
N eedle-shielding or needle-free devices th at m ight satisfy the occupational safety regulations for adm inistering injectable vaccines are available in the U nited States (87-89). A dditional inform ation about im plem entation and enforcem ent of these regulations is available from O S H A ( w w .osha.gov).

# Route of Administration

# Oral Route
Rotavirus and oral typhoid vaccines are the only vaccines adm inistered orally in the U nited States. O ral typhoid capsules should be adm inistered as directed by the m anufacturer. T h e capsules should n o t be opened or mixed w ith any other sub stance. Rotavirus vaccines are licensed for infants. T here are two brands o f rotavirus vaccine, and they have different types o f applicators. Providers should consult the package insert for details. A dose of rotavirus vaccine need n o t be repeated if the vaccine is spit up or vom ited. T h e infant should receive the rem aining recom m ended doses o f rotavirus vaccine following the routine schedule.

# Intranasal Route
LAIV is licensed for healthy nonpregnant persons aged 2-A9 years and is the only vaccine administered by the intranasal route. T he adm inistration device is a nasal sprayer w ith a dose-divider clip that allows introduction o f one 0.1 -m L spray into each naris. T he tip should be inserted slightly into the naris before adm in istration. Even if the person coughs or sneezes immediately after adm inistration or the dose is expelled any other way, the vaccine dose need not be repeated . Introduction o f low levels o f vaccine viruses into the environm ent likely is unavoidable w hen adminis tering LAIV; however, no instances have been reported o f illness or attenuated vaccine virus infections am ong inadvertently exposed health-care providers or im m unocom prom ised patients. T h e risk for acquiring vaccine viruses from the environm ent is unknow n but is likely low; in addition, vaccine viruses are cold-adapted and attenuated and unlikely to cause sym ptom atic influenza. Severely immunosuppressed persons should not administer LAIV However, other persons at higher risk for influenza complications can adm inister LAIV. These include persons w ith underlying medical conditions placing them at higher risk or w ho are likely to be at risk, including pregnant w om en, persons w ith asthma, and persons aged >50 years (68).

# Injectable Route
W ith the exception o f bacille C alm ette-G uerin (BCG ) vac cine and sm allpox vaccine, injectable vaccines are adm inistered by the intram uscular or subcutaneous route. T h e m ethod o f adm inistratio n o f injectable vaccines is determ ined, in part, by the presence o f adjuvants in som e vaccines. A n adjuvant is a vaccine co m p o n en t d istinct from the antigen th at enhances the im m u n e response to th e antigen. Inactivated vaccines c o n tain in g an ad ju v an t sh o u ld be injected in to a m uscle because adm inistration subcutaneously or intraderm ally can cause local irritation, induration, skin discoloration, inflam m a tion, and granulom a form ation. Routes o f adm inistration are recom m ended by the m anufacturer for each im m unobiologic (Table 9). D eviation from the recom m ended route o f adm in istration m ight reduce vaccine efficacy (90, 91) or increase the risk for local adverse reactions (92)(93)(94).

# Intramuscular Injections

# N ee d le Length
Injectable im m unobiologies should be adm inistered where local, neural, vascular, or tissue injury is unlikely. Use o f longer needles has been associated w ith less redness or swelling than occurs w ith shorter needles because o f injection into deeper muscle mass (92). A ppropriate needle length depends on age and body mass. Injection technique is the m ost im p o rtan t param eter to ensure efficient intram uscular vaccine delivery.
F or all in tra m u sc u la r in jectio n s, th e need le sh o u ld be long enough to reach the m uscle mass and prevent vaccine from seeping into subcutaneous tissue, b u t not so long as to involve underlying nerves, blood vessels, or bone (91,(95)(96)(97). Vaccinators should be fam iliar w ith the anatom y o f the area into w hich they are injecting vaccine. Intram uscular injections are adm inistered at a 90-degree angle to the skin, prefer ably into the anterolateral aspect o f the thigh or the deltoid muscle o f the upper arm , depending on the age o f the patient (Table 10).
A decision on needle size and site o f injection m ust be m ade for each person on the basis o f the size o f the muscle, the thickness o f adipose tissue at the injection site, the volum e o f the m aterial to be adm inistered, injection technique, and the depth below the muscle surface into w hich the m aterial is to be injected (Figure 1). A spiration before injection o f vaccines or toxoids (i.e., pulling back on the syringe plunger after needle insertion b u t before injection) is n o t necessary because no large blood vessels are present at the recom m ended injection sites, and a process th at includes aspiration m ight be m ore painful for infants (98).

# In fan ts (Aged < 1 2 M on th s)
For the m ajority o f infants, the anterolateral aspect o f the thigh is the recom m ended site for injection because it provides a large m uscle mass (Figure 2). In certain circum stances (e.g., physical obstruction to other sites and no reasonable indication to defer doses), the gluteal muscle can be used. I f the gluteal muscle m ust be used, care should be taken to define the ana tom ic la n d m a r k s .I n je c tio n technique is the m ost im portant param eter to ensure efficient intram uscular vaccine delivery. I f the subcutaneous and m uscle tissue are bunched to m inim ize the chance o f striking bone (95), a 1-inch needle is required to ensure intram uscular adm inistration in infants aged >1 m onth. For the m ajority o f infants, a 1-inch, 22-to 25-gauge needle is sufficient to penetrate the thigh muscle. For neonates (first 28 days o f life) and preterm infants, a % -inch needle usually is adequate if the skin is stretched flat between the th u m b and forefinger and the needle is inserted at a 90-degree angle to the skin (97).

# Toddlers (Aged 12 M o n th s -2 Years)
For toddlers, the anterolateral thigh muscle is preferred, and if used, the needle should be at least 1 inch long. T h e deltoid muscle can be used if the muscle mass is adequate. A % -inch needle is adequate only for the deltoid m uscle and only if the skin is stretched flat betw een th u m b and forefinger and the needle is inserted at a 90-degree angle to the skin.

# C hildren (Aged 3 -1 8 Years)
T h e deltoid m uscle is preferred for children aged 3-18 years (Figure 3); the needle size for deltoid site injections can range from 22 to 25 gauge and from Vs to 1 inch on the basis o f tech nique. Knowledge o f body mass can be useful for estim ating the appropriate needle length (99)', however, neither a physical exam ination n o r m easurem ent o f body mass is necessary to adm inister vaccines. M ost children in this age range require a %-or 1-inch needle (or interm ediate size, if available).

# A dults (Aged > 1 9 Years)
For adults, the deltoid muscle is recom m ended for routine intram uscular vaccinations. T h e anterolateral thig h also can be used. For m en and w om en w ho weigh 200 lbs (>90 kg) or m en w ho w eigh >260 lbs (> 1 18 kg), a 1 Vi-inch needle is recom m ended (Table 10) (96).

# Subcutaneous Injections
Subcutaneous injections are adm inistered at a 45-degree angle, usually into the thigh for infants aged 12 m onths. Subcutaneous injections m ay be adm inistered into the upperouter triceps area o f an infant if necessary. A % -inch, 23-to 25-gauge needle should be inserted into the subcutaneous tissue (Figures 4 and 5).

# Multiple Injections
I f m ultiple vaccines are adm inistered at a single visit, adm in ister each preparation at a different anatom ic site. For infants and younger children, if m ore th an tw o vaccines are injected in a single lim b, the thigh is the preferred site because o f the greater muscle mass; the injections should be sufficiently sepa rated (i.e., >1 inch if possible) so th at any local reactions can be differentiated (92,100)

# Jet Injections
Jet injectors are needle-free devices th at pressurize liquid m edication, forcing it th ro u g h a nozzle orifice into a narrow' stream capable o f penetrating skin to deliver a drug or vac cine into intraderm al, subcutaneous, or intram uscular tissues (101,102). Jet injectors prevent needle-stick injuries to health care providers (86) and can overcome im proper, unsterile reuse and other drawbacks o f needles and syringes in developing countries (87, . Im m u n e responses generated by jet injectors against b o th attenuated and inactivated viral and bacterial antigens are usually equivalent to, and occasionally greater than, im m une responses induced by needle injection. However, local reactions or injuries are som etim es m ore fre quent on delivery o f vaccine by jet injectors com pared w'ith needle injection, depending on the inherent irritability o f the vaccine and operator technique (102). Jet injectors that use the same nozzle for consecutive injections w ithout intervening sterilization were used in mass vaccination cam paigns from the 1950s through the 1990s (102); however, these were found to be unsafe because o f the possibility o f bloodborne pathogen transm ission (105-108) and should n o t be used. A new gen eration o f jet injectors w ith disposable cartridges and syringes has been developed since the 1990s. W ith a new, sterile dose cham ber and nozzle for each p atien t and correct use, these devices do n o t have the same safety concerns as m ultiple-use nozzle jet injectors. Several o f the new er devices have been approved by FD A for sale in the U nited States (102).

# M ethods for Alleviating Discomfort and Pain Associated with Vaccination
C o m fort measures, such as distraction (e.g., playing m usic or p re ten d in g to blow away the pain), ingestion o f sweet liquids, breastfeeding, cooling of the injection site, and topi cal analgesia, can help infants or children cope w ith the dis com fort associated w ith vaccination (109,110). P retreatm ent (30-60 m inutes before injection) w ith a 5% topical lidocaineprilocaine em ulsion m ight decrease the pain o f vaccination by causing superficial anesthesia (111,112)

# Nonstandard Vaccination Practices
Recommendations for route, site, and dosage o f immunobiolog ies are derived from data from clinical trials, practical experience, norm al periodicity o f health-care visits, and theoretical consider ations. A CIP discourages variations from the recommend ed route, site, volume, or num ber o f doses o f any vaccine.
Variation from the recom m ended route and site can result in inadequate protection. In adults (but not in infants) (117), the im m unogenicity o f hepatitis B is substantially lower w hen the gluteal rather than the deltoid site is used for adm inistration (90). Hepatitis B administered intraderm ally might result in a lower seroconversion rate and final titer o f hepatitis B surface antibody than w hen administered by the deltoid intramuscular route (118,119). Hepatitis B administered by any route other than intramuscular, or in adults at any site other than the deltoid or anterolateral thigh, should not be counted as valid and should be repeated. Similarly, doses o f rabies vaccine administered in the gluteal site should not be counted as valid doses and should be repeated (120). M C V 4 should be administered intram uscu larly; however, revaccination is not necessary if a vaccine dose is administered subcutaneously (121). Inactivated influenza vaccine is im m unogenic w hen administered in a lower than standard dose by the intraderm al route to healthy adult volunteers (122). However, the im m unogenicity for persons aged >60 years is inadequate, and varying the recom m ended route and dose is not recomm ended.
Live, attenuated injectable vaccines (e.g., M M R , varicella, and yellow fever) and certain inactivated vaccines (e.g., meningococ cal polysaccharide) are recom m ended by the manufacturers to be adm inistered by subcutaneous injection. PPSV and IPV are recom m ended by the m anufacturer to be administered by the subcutaneous or intram uscular route. Response to vaccines rec om m ended by the subcutaneous route are unlikely to be affected if the vaccines are administered by the intram uscular rather than subcutaneous route. Repeating doses o f vaccine administered by the intram uscular route w hen recom m ended to be by the subcutaneous route is not necessary.
Adm inistering volumes smaller than recom m ended (e.g., inap propriately divided doses) m ight result in inadequate protection. Using reduced doses administered at m ultiple vaccination visits that equal a full dose or using smaller divided doses is not recom mended. Any vaccination using less than the standard dose should not be counted, and the person should be revaccinated according to age unless serologic testing indicates that an adequate response has developed. If less than a full recommended dose o f a parenteral vaccine is administered because o f syringe or needle leakage, the dose should be repeated. Using larger than recommended dosages can be hazardous because o f excessive local or systemic concentra tions of antigens or other vaccine constituents.

# Storage and Handling of Im m unobiologies

# Storage Temperature
Vaccines licensed for refrigerator storage should be stored at 35F-46F (2C-8C). L iquid vaccines containing an alum i num adjuvant perm anently lose potency w hen exposed to freez ing tem peratures. Live, attenuated virus vaccines th at should be frozen lose potency w'hen exposed to higher tem peratures because the viruses degrade m ore quickly at storage tem pera tures th at are w arm er than recom m ended (Table 11).

# Storage Units
Refrigerators and freezers used for vaccine storage m ust m aintain the required tem perature range year-round, be large enough to hold the year's largest inventory, and be dedicated to storage o f vaccines. Vaccine storage units m ust be carefully selected, used properly, and consistently m onitored to ensure that recom m ended tem peratures are m aintained. Refrigerators w ithout freezers and stand-alone freezers (either m anual defrost or autom atic defrost) are usually the m ost effective at m aintain ing the precise tem peratures required for vaccine storage. Such single-purpose units sold for hom e use are less expensive alter natives to medical specialty equipm ent (123) and are preferable to com bination units. A com bination refrigerator-freezer unit sold for hom e use m ight be adequate for storing lim ited qu an tities o f vaccines if the refrigerator and freezer com partm ents have separate external doors. Before using the refrigerator for vaccine storage, the tem perature should be allowed to stabilize and then be m easured in various locations w ithin the refrigera tor co m p artm en t to d o cum ent th at a consistent tem perature can be m aintained w ithin the co m p artm en t (Table 11) (124). N ew units m ight need >2 days o f operation to establish a stable operating tem perature; vaccine should n o t be stored in the unit until the u n it m aintains an appropriate and stable storage tem perature. Refrigerator tem peratures are m ost reflective o f the actual co m p artm en t tem perature after the door has rem ained closed and u n d istu rb ed for several hours (e.g., overnight). T h e refrigerator tem perature should be set at the m idpoint o f the recom m ended range (i.e., 40F ) (125,126). A storage u n it should be sufficiently sized so that vaccines can be placed away from the walls in the p art o f the u n it best able to m aintain the constant, required tem perature. C o m bination units, w ith separate com partm ents o f sm aller size, can only be used to store lim ited quantities o f vaccines. Frequent opening and closing o f doors can cause fluctuations in com partm ent tem perature; food, beverages, and clinical specimens should n o t be stored in vaccine storage units. I f it becomes necessary to store clinical specim ens in the same u n it as vaccines, the clinical specim ens should be o n a shelf below the vaccine to prevent co n tam in atio n should the specim en leak.

# Temperature Monitoring
Tem perature m onitoring is a critical com ponent o f tem pera ture m anagem ent. All office and clinical staff m em bers should be aware o f vaccine vulnerabilities and storage requirem ents. Assigning one person in the office the prim ary responsibility for m aintaining and reviewing tem perature logs (Figure 6) gener ally is m ost effective, w ith a second person assigned as backup. Tem peratures for b o th the refrigerator and freezer should be docum ented twice a day and recorded. T h e backup person should review the log at least once each week. Tem perature logs should be m aintained for 3 years unless state or local authorities require a longer tim e. A n autom ated m onitoring system th at alerts staff w hen a tem perature deviation occurs is optim al. However, even if an autom ated m o n ito ring system is used, tem peratures still should be m anually checked and recorded twice each day.
T o f the m anufacturing process, this recom m endation refers to a second calibration process that occurs after m anufacturing b u t before m arketing and is docum ented w ith a certificate that comes w ith the product. Some products (e.g., continuous chart recorder therm om eters) usually include a m anufacturerdefined schedule for additional recalibration. For m any types o f therm om eters, replacem ent m ight be less expensive than recalibration. T herm om eters that require batteries need to have the batteries changed; review the d o cum entation th at comes w ith the p ro duct for guidance.

# Response to Out-of-Range
Temperature Reading
A n o u t-o f-ra n g e te m p e ra tu re re a d in g sh o u ld p ro m p t im m ediate action. A plan should be d eveloped ahead o f tim e to address various types o f emergencies th at m ight require removal o f vaccine from the original storage unit. Transfer o f vaccines to a predesignated alternative em ergency storage site m ight be necessary if a tem perature problem cannot be resolved im m ediately (e.g., plugging in an unplugged unit or closing a door th a t has been left open). Vaccine should be m arked "do n o t use" and moved to the alternate site after verifying that the alternate u n it is at the proper tem perature. After the vac cine has been moved, determ ine w hether the vaccine is still useable by contacting the state or local health d epartm ent or m anufacturer. D am age to the im m unogenicity o f a vaccine exposed to tem peratures outside o f the recom m ended range m ight n o t be apparent visually. As a general rule, vaccines that have been stored at inappropriate tem peratures should not be adm inistered. I f such vaccines already have been adm inis tered, guidance is available from the state health departm ent or C D C . Vaccine exposed to inappropriate tem peratures that is inadvertently adm inistered should generally be repeated. Clinicians should consult w ith state or local health depart m ents in these situations.

# Expiration Dates and Windows
All vaccines have an expiration date determ in ed by the m anufacturer th at m ust be observed. Providers should record the vaccine expiration dates and lot num bers on a stock or inventory record for each vaccine vial w hen a sh ip m en t is received. W h e n vaccines are rem oved from storage, clinicians and other health-care providers should note w hether an expira tion w indow exists for vaccine stored at room tem perature or at an interm ediate tem perature. For example, single-com ponent varicella vaccine th at is stored frozen m ust be discarded after 72 hours o f storage at refrigerator tem perature. Vaccine trans p o rt betw een the storage site and the adm inistration clinic is discouraged unless the cold chain is m aintained, and vaccine tran sp o rt by th e p a tie n t (e.g., tra n sp o rtin g zoster vaccine from a p harm acy to a clinic) is particularly discouraged. A n expiration w indow also applies to vaccines th a t have been reconstituted. For example, after reconstitution, M M R vac cine should be k ept at refrigerator tem perature and m ust be adm inistered w ithin 8 hours. Doses o f expired vaccines that are adm inistered inadvertently generally should n o t be counted as valid and should be repeated. Inactivated vaccines should be repeated as soon as possible. Live vaccines should be repeated after a 28-day interval from the invalid dose to reduce the risk for interference from interferon on the subsequent doses. A dditional inform ation about expiration dates is available at  w w .cdc. gov/ vaccines/recs/storage.

# Multidose Vials
C ertain vaccines (i.e., quadrivalent m eningococcal poly saccharide vaccine , PPSV, TIV, IPV, and yellow fever) are available in m ultidose vials. Because several doses are w ithdraw n from the sam e vial, p roper technique m ust be followed to prevent contam ination. For m ultidose vials that do n o t require reconstitution, doses th at rem ain after w ith drawal of a dose can be adm inistered until the expiration date p rin ted on the vial or vaccine packaging if the vial has been stored correctly and the vaccine is n o t visibly contam inated, unless otherwise specified by the m anufacturer. M ultidose vials that require reco n stitu tio n m ust be used w ith in the interval specified by the m anufacturer. A fter reconstitution, the new expiration date should be w ritten on the vial.

# Altered Im m unocom petence

# General Principles
A ltered im m u n o co m p eten ce, a term often used synony m ously w ith im m unosuppression and im m unocom prom ise, can be classified as prim ary or secondary. Prim ary im m unodefi ciencies generally are inherited and include conditions defined by an absence or quantitative deficiency o f cellular or hum oral com ponents or both that provide im m unity. Examples include congenital im m unodeficiency diseases such as X -linked agam m aglobulinem ia, severe com bined im m unodeficiency disease, and chronic granulom atous disease. Secondary im m unodefi ciency generally is acquired and is defined by loss or qualitative deficiency in cellular or hum oral im m u n e com ponents that occurs as a result o f a disease process or its therapy. Examples o f sec o n d a ry im m u n o d e fic ie n c y in c lu d e H IV in fe c tio n , hem atopoietic m alignancies, treatm en t w ith radiation, and treatm ent w ith im m unosuppressive drugs including alkylating agents and antim etabolites. T h e degree to w hich im m u n o su p pressive drugs cause clinically significant im m unodeficiency generally is dose related and varies by drug. Prim ary and sec ondary im m unodeficiencies m ight include a com bination o f deficits in both cellular and hum oral im m unity. In this report, the general term altered im m unocom petence also is used to include conditions such as asplenia and chronic renal disease, and treatm ents w ith therapeutic m onoclonal antibodies (spe cifically, the tu m o r necrosis factor inhibitors) (127-132) and prolonged adm inistration o f high-dose corticosteroids.
D eterm in atio n o f altered im m un o co m p eten ce is im p o r tan t to the vaccine provider because incidence or severity o f som e vaccine-preventable diseases is higher in persons w ith altered im m unocom petence; therefore, certain vaccines (e.g., inactivated influenza vaccine and pneum ococcal vaccines) are recom m ended specifically for persons w ith these diseases (28,68). Vaccines m ight be less effective during the period o f altered im m unocom petence. Live vaccines m ight need to be deferred u n til im m une function has im proved. Inactivated vaccines adm inistered during the period o f altered im m u n o com petence m ight need to be repeated after im m une function has im proved. In ad d itio n , persons w ith altered im m u n o com petence m ight be at increased risk for an adverse reaction after adm inistration o f live, attenuated vaccines because o f uninhibited replication.
T he degree o f altered im m unocom petence in a patient should be determ ined by a physician. T h e challenge for clinicians and other health-care providers is assessing the safety and effective ness o f vaccines for conditions associated w ith prim ary or sec ondary im m unodeficiency, especially w hen new therapeutic modalities are being used and inform ation about the safety and effectiveness o f vaccines has not been characterized fully in persons receiving these drugs (Table 13). Laboratory studies can be useful for assessing the effects o f a disease or drug on the im m une system. Tests useful to assess hum oral im m unity include im m unoglobulin (and im m unoglobulin subset) levels and spe cific antibody levels (e.g., tetanus and diphtheria). Tests that dem onstrate the status o f cellular im m unity include lymphocyte num bers (i.e., a com plete blood count with differential), a test that delineates concentrations and proportions o f lymphocyte subsets (i.e., B and T lymphocytes, C D 4 + T versus C D 8+ T lym phocytes), and tests th at measure T-cell proliferation in response to specific or nonspecific stimuli (e.g., lym phocyte proliferation assays) (133,134). T he ability to characterize a drug or disease condition as affecting cellular or hum oral im m unity is only the first step; using this inform ation to draw inferences about w hether particular vaccines are indicated or w hether cau tion is advised w ith use o f live or inactivated vaccines is more com plicated and m ight require consultation w ith an infectious disease or im m unology specialist.

# Altered Im m unocom petence as an Indication to Receive a Vaccine

# Vaccination with Inactivated Vaccines
All inactivated vaccines can be adm inistered safely to per sons w ith altered im m unocom petence w hether the vaccine is a killed w hole-organism or a recom binant, subunit, toxoid, polysaccharide, or polysaccharide protein-conjugate vaccine. If inactivated vaccines are indicated for persons w ith altered im m unocom petence, the usual doses and schedules are rec om m ended. However, the effectiveness o f such vaccinations m ight be suboptim al.
Except for inactivated influenza vaccine, vaccination during chem otherapy or radiation therapy should be avoided if pos sible because antibody response m ight be suboptim al. Patients vaccinated w ithin 14 days before starting im m unosuppressive therapy or while receiving im m unosuppressive therapy should be considered unim m unized and should be revaccinated at least 3 m onths after therapy is discontinued if im m une com petence has been restored.

# Vaccination with Live, Attenuated Viral and Bacterial Vaccines
Severe

# Recipients of Hematopoietic Cell Transplants
A hem atopoietic cell transplant (H C T ) results in im m u nosuppression because o f the hem atopoietic ablative therapy adm inistered before the transplant, drugs used to prevent or treat graft-versus-host disease, and, in som e cases, from the underlying disease process necessitating transplantation (152)(153)(154)

# Conditions or Drugs that Might Cause Im m unodeficiencies
Asplenia and use o f corticosteroids or certain drugs have the potential to be im m unosuppressive and are presum ed to cause som e degree o f altered im m unocom petence.

# A natom ic or Functional Asplenia
Persons w ith anatom ic asplenia (e.g., surgical removal or congenital absence o f the spleen) or functional asplenia (as occurs in persons w ith sickle cell disease) are at increased risk for infection by encapsulated bacteria, especially by S. Pneumococcal, m eningococcal, and H ib vaccinations should be adm inistered at least 14 days before elective splenectomy, if possible. If the vaccinations are n o t adm inistered before surgery, they should be adm inistered after the procedure as soon as the p atien t's condition is stable.

# Corticosteroids
T he am ount o f systemically absorbed corticosteroids and the duration o f adm inistration needed to suppress the im m une system o f an otherw ise im m u n o co m p eten t person are n o t well defined. C orticosteroid therapy usually is n o t a contraindica tion to adm inistering live-virus vaccine w hen adm inistration is 1) short term (i.e., 2 m g/kg o f body w eight or >20 m g/day o f prednisone or equivalent for persons w ho weigh >10 kg w hen adm inistered for >14 days as sufficiently im m unosuppressive to raise concern about the safety o f vaccination w ith live-virus vaccines (154). C orticosteroids used in greater than physiologic doses also can reduce the im m une response to vaccines. Vaccination providers should defer live-virus vaccination for at least 1 m o n th after discon tin u atio n of high-dose systemically absorbed corticos teroid therapy adm inistered for >14 days.

# Other Immunosuppressive Drugs
W h e n feasible, clinicians should adm inister all indicated vac cines to all persons before initiatio n o f chem otherapy, before treatm en t w ith oth er im m unosuppressive drugs, and before radiation or splenectom y. Persons receiving chem otherapy or radiation for leukem ia and other hem atopoietic m alignancies, for solid tum ors, or after solid organ tran sp lan t should be assumed to have altered im m unocom petence.

# S pecial Situations

# Concurrent Administration of Antimicrobial Agents and Vaccines
W ith a few exceptions, use o f an antim icrobial agent is not a contraindication to vaccination. A ntibacterial agents have no effect on the response to live, attenuated vaccines, except live o ra lT y 2 la typhoid vaccine, and have no effect on inactivated, recom binant subunit, or polysaccharide vaccines or toxoids. T y 2 la typhoid vaccine should not be adm inistered to persons receiving antim icrobial agents until 24 hours after the last dose o f antim icrobial (14). I f feasible, to avoid a possible reduction in vaccine effectiveness, antibacterial drugs should n o t be started or resum ed until 1 week after the last dose ofT y21a.
A n tiv ira l d ru g s used for tre a tm e n t o r p ro p h y lax is o f influenza virus infections have no effect on the response to inactivated influenza vaccine (68). However, live, attenuated influenza vaccine should n o t be adm inistered u n til 48 hours after cessation o f therapy w ith antiviral influenza drugs. If feasible, to avoid possible reduction in vaccine effectiveness, antiviral m edication should n o t be adm inistered for 14 days after LAIV adm inistration (68). A ntiviral drugs active against herpesviruses (e.g., acyclovir or valacyclovir) m ight reduce the efficacy o f live, attenuated varicella and zoster vaccines (4,55). These drugs should be discontinued at least 24 hours before adm inistration o f vaccines containing varicella zoster virus, including zoster vaccine, if possible. D elay use or resum ption o f antiviral therapy for 14 days after vaccination. N o data exist to suggest that com m only used antiviral drugs have an effect on rotavirus vaccine or M M R .

# Tuberculosis Screening and Skin Test Reactivity
Measles illness, severe acute or chronic infections, H IV infection, and m aln u tritio n can create a relatively anergic state during w hich the tuberculin skin test (TST) m ight have a falsenegative reaction (156-158). A lthough any live, attenuated measles vaccine theoretically can suppress T S T reactivity, the degree o f suppression is likely less th an that occurring from acute infection from wild-type measles virus. A lthough routine T S T screening o f all children is no longer recom m ended, T S T screening is som etim es needed (e.g., for well child care, school entrance, or employee health reasons) at the same tim e as adm inistration o f a m easles-containing vaccine.
T h e T S T and m easles-containing vaccine can be adm in istered at the same visit (preferred option). Sim ultaneously adm inistering the T S T and m easles-containing vaccine does n o t interfere w ith reading the T S T result at 4 8 -7 2 hours and ensures that the person has received measles vaccine.
I f th e m easles-containing vaccine has been adm inistered recently, T S T screening should be delayed for at least 4 weeks after vaccination. A delay in perform ing the T S T removes the concern o f any theoretical b u t transient suppression o f T S T reactivity from the vaccine.
T S T screening can be perform ed and read before adm inis tration of the m easles-containing vaccine. T h is o p tion is the least favored because it delays receipt o f the m easles-containing vaccine. If a person is suspected to have tuberculosis, n o t only should the M M R vaccine be w ithheld before the TST, it should be w ithheld u n til after treatm en t has been initiated because a person w ith active tuberculosis w ho is m oderately or severely ill should n o t receive M M R vaccine. In a general screening situation in w hich tuberculosis is n o t suspected, a T S T may be adm inistered sim ultaneously w ith live vaccines or should be deferred for 28 days after vaccination.
N o data exist regarding the poten tial degree o f T S T sup pression that m ight be associated w ith other live, attenuated virus vaccines (e.g., varicella or yellow fever). However, in the absence o f data, following guidelines for m easles-containing vaccine w hen scheduling T S T screening and adm inistering other live, attenuated virus vaccines is p ru d en t. I f the oppor tu n ity to vaccinate m ight be missed, vaccination should not be delayed only because o f these theoretical considerations.

# Because o f sim ilar concerns about sm allpox vaccine and T S T suppression, a T S T should n o t be perform ed until 4 weeks after sm allpox vaccination ( 1.59).
A m ore specific test for diagnosis o f tuberculosis or latent tuberculosis infection was licensed in 2005-T h e interferon gam m a release assay (IGRA) requires only one visit to com plete and is less sensitive to the effects o f previous B C G vaccination (160). T h e same tim in g guidelines that apply to the interval betw een a live vaccine and T S T apply to IG R A (i.e., 28 days betw een live vaccine and IG R A if they do n o t occur on the same day), because IG R A (like T S T ) m ig h t be suppressed th ro u g h im m unologic m echanism s.
T h e p o tential for T S T to cause boosting o f results should be considered in adults w ho m ight have latent tuberculosis and have a negative in itia lT S T (160). T h e tw o-step tuberculin test is recom m ended for certain situations (160). Because this test consists o f two TSTs (or a T S T followed by IGRA) separated by an interval o f 1-3 weeks, there is a greater w indow o f tim e during which live vaccine replication could suppress reactivity. If a live vaccine is adm inistered, the first dose o f a two-step T S T should be delayed for 4 weeks, and if additional doses of live vaccines are indicated thereafter, they should be delayed until the second T S T (or the IG R A after an initial T ST ).
T S T or IG RA reactivity in the absence o f tuberculosis disease is n o t a contraindication to adm inistration o f any vaccine, including live, attenuated virus vaccines. Tuberculosis disease is n o t a contraindication to vaccination, unless the person is m oderately or severely ill. A lthough no studies have reported on the effects o f M M R vaccine on persons w ith untreated tuberculosis, a theoretical basis exists for concern that measles vaccine m ight exacerbate tuberculosis disease (2). As a result, before adm inistering M M R to persons w ith untreated active tuberculosis, initiating antituberculosis therapy is advisable (2). C onsidering w hether concurrent im m unosuppression (e.g., im m unosuppression caused by H IV infection) is a concern before adm inistering live, attenuated vaccines also is prudent.

# Severe Allergy to Vaccine Com ponents
Vaccine co m ponents can cause allergic reactions am ong certain recipients. T hese reactions can be local or systemic and can include anaphylaxis or anaphylactic-like responses (e.g., generalized urticaria or hives, wheezing, swelling o f the m outh and throat, dyspnea, hypotension, and shock). Allergic reactions m ight be caused by the vaccine antigen, residual anim al protein, antim icrobial agents, preservatives, stabiliz ers, or o th er vaccine com ponents (161). C hildren w ho have had an apparent severe allergic reaction to a vaccine should be evaluated by an allergist to determ ine the responsible allergen and to m ake recom m endations regarding future vaccination. C o m ponents o f each vaccine are listed in the respective pack age insert. A n extensive list o f vaccine com ponents and their use, as well as the vaccines th at contain each com ponent, has been published (162) and also is available from C D C (h ttp :// www.cdc. gov/ vaccines).
T h e m ost com m on anim al p rotein allergen is egg protein, w hich is found in influenza and yellow fever vaccines because they are prepared using em bryonated chicken eggs. Ordinarily, persons w ho are able to eat eggs or egg products safely can receive these vaccines; persons w ho have had an anaphylactic or anaphylactic-like allergy to eggs or egg proteins generally should n o t receive these vaccines. Asking persons if they can eat eggs w ith o u t adverse effects is a reasonable way to determ ine w hich persons m ight be at risk for allergic reactions from yel low fever and influenza vaccines. A regim en for adm inistering influenza vaccine to children w ith egg hypersensitivity and severe asthm a has been developed (163,164)

# Latex Allergy
Latex is sap from the com m ercial rubber tree. Latex contains naturally occurring im purities (e.g., plant proteins and pep tides) th at m ight be responsible for allergic reactions. Latex is processed to form natural rubber latex and dry, natural rubber. N atural rubber latex and dry, natural rubber m ight contain the same plant im purities as latex b u t in lesser am ounts. N atural ru b b er latex is used to p ro d u ce m edical gloves, catheters, and other products. Dry, natural rubber is used in the tip o f syringe plungers, the tip on prefilled syringes, vial stoppers, and injection ports on intravascular tubing. Synthetic rubber and synthetic latex also are used in m edical gloves, syringe plungers, and vial stoppers. Synthetic rubber and synthetic latex do n o t contain natural rubber or natural latex and do n o t contain im purities linked to allergic reactions. Latex or dry, natural rubber used in vaccine packaging generally is noted in the m anufacturers' package inserts.
T he most com m on type o f latex sensitivity is a contact-type (type 4) allergy, usually as a result o f prolonged contact w ith latex-containing gloves (176). However, latex allergies associated w ith injection procedures have been described am ong patients w ith diabetes mellitus (177-179)-Allergic reactions (including anaphylaxis) after vaccinations are rare. A review o f reports to VAERS identified only 28 cases o f possible im m ediate-type anaphylactic reactions among more than 160,000 vaccine adverse event reports (180).
If a person reports a severe (anaphylactic) allergy to latex, vaccines supplied in vials or syringes th at co ntain natural rubber latex should n o t be adm inistered unless the benefit o f vaccination clearly outweighs the risk for a potential allergic reaction. In these cases, providers should be prepared to treat patients w ho are having an allergic reaction. For latex allergies other th an anaphylactic allergies (e.g., a history o f contact allergy to latex gloves), vaccines supplied in vials or syringes th at contain dry, natural rubber or natural rubber latex may be adm inistered.

# Vaccination of Preterm Infants
In the m ajority o f cases, preterm infants (infants born before 37 weeks' gestation), regardless o f b irth w eight, should be vaccinated at the same chronological age and according to the same schedule and using the same precautions as for full-term I f a child aged at least 6 weeks has been in the hospital since birth, deferral o f rotavirus vaccine is recom m ended until the tim e of discharge (136). T h e rotavirus vaccine series should n o t be initiated for infants aged >15 weeks, 0 days.

# Breastfeeding and Vaccination
N eith er inactivated n o r live-virus vaccines adm inistered to a lactating w om an affect the safety o f breastfeeding for w om en or their infants. A lthough live viruses in vaccines can replicate in vaccine recipients (i.e., the m other), the m ajority o f live viruses in vaccines have been d em onstrated n o t to be excreted in hu m an milk. Varicella vaccine virus has n o t been found in h u m an m ilk (190). A lthough rubella vaccine virus m ight be excreted in h u m a n m ilk, the virus usually does n o t infect the infant. If infection does occur, it is well tolerated because the virus is attenuated (191). Inactivated, recom binant, subunit, polysaccharide, and conjugate vaccines, as well as toxoids, pose no risk for m others w ho are breastfeeding or for their infants. Breastfeeding is a contraindication for sm allpox vaccination o f the m o th er because o f the theoretical risk for contact trans m ission from m o th er to infant. Yellow fever vaccine should be avoided in breastfeeding w om en (19). However, w hen nursing m others can n o t avoid or postpone travel to areas endem ic for yellow fever in w hich risk for acquisition is high, these w om en should be vaccinated.
Lim ited data indicate that breastfeeding can enhance the response to certain vaccine antigens (192). T here are no data to suggest th at passive transfer o f antibodies in h u m a n m ilk can affect the efficacy o f live-virus vaccines. Breastfed infants should be vaccinated according to the recom m ended schedule (1 9 3 -1 9 5 ).

# Vaccination During Pregnancy
Risk to a developing fetus from vaccination o f the m other during pregnancy is theoretical. N o evidence exists o f risk to the fetus from vaccinating pregnant w om en w ith inactivated virus or bacterial vaccines or toxoids (196,197). Live vaccines adm inistered to a pregnant w om an pose a theoretical risk to the fetus; therefore, live, attenuated virus and live bacterial vac cines generally are contraindicated during pregnancy. Benefits o f vaccinating pregnant w om en usually outw eigh potential risks w hen the likelihood o f disease exposure is high, w hen infection would pose a risk to the m other or fetus, and w hen the vaccine is unlikely to cause harm . R ecom m endations for vaccination d u rin g pregnancy are developed using A C IP 's G uiding Principles fo r Development o fA C IP Recommendations fo r Vaccination D uring Pregnancy a n d Breastfeeding (198). Because vaccinating against influenza before the season begins is critical, and because predicting exactly w hen the season will begin is im possible, routine influenza vaccination is recom m ended for all w om en w ho are or will be pregnant (in any trim ester) durin g influenza season, w hich in the U nited States is usually early O cto b er th ro u g h late M arch (68).
IPV can be adm inistered to p regnant w om en who are at risk for exposure to w ild -ty p e poliovirus in fectio n (201). H epatitis A, pneum ococcal polysaccharide, m eningococcal conjugate, and m eningococcal polysaccharide vaccines should be considered for w om en at increased risk for those infections (49,51,202). Pregnant w om en w ho m ust travel to areas where the risk for yellow fever is high should receive yellow fever vaccine because the lim ited theoretical risk from vaccination is outw eighed substantially by the risk for yellow fever infec tion (19,203). H epatitis B vaccine is n o t contraindicated in pregnancy and should be given to a pregnant w o m an w ho has an indication for hepatitis B vaccine (26,204).
Pregnancy is a contraindication for sm allpox (vaccinia) vac cine and measles-, m um ps-, rubella-, and varicella-containing vaccines. Sm allpox vaccine is the only vaccine know n to harm a fetus w hen adm inistered to a pregnant w om an. In addition, sm allpox vaccine should n o t be adm inistered to a household contact o f a preg n an t w om an (159). However, antibody testing was perform ed by using a hem ag glutination assay, w hich tends to underestim ate protection and cannot directly be com pared w ith antibody concentration (210). D ata are likely to rem ain lim ited for areas other than the People's Republic o f C hina, Russia, and E astern Europe. Health-care providers should ensure that household contacts o f international adoptees are vaccinated adequately, particularly for measles, hepatitis A, and hepatitis B (211).
H ealth-care providers m ay use one o f m ultiple approaches if the im m unogenicity o f vaccines adm inistered to persons outside the U nited States is in question. Repeating the vaccina tions is an acceptable o p tio n that usually is safe and prevents the need to obtain and interp ret serologic tests. If avoiding unnecessary injections is desired, judicious use o f serologic testing m ight help determ ine w hich vaccinations are needed.
For som e vaccines, the m ost readily available serologic tests cannot d o cu m en t protection against infection. These recom m endations provide guidance on possible approaches to evalu ation and revaccination for each vaccine recom m ended in the U nited States (Table 14). b u t w aning antibody; serologic testing can be repeated after a booster dose if the vaccination provider w ants to avoid revac cination w ith a com plete series.

# DTaP Vaccine
A lternately, for a child whose records indicate receipt o f >3 doses, a single booster dose can be adm inistered followed by serologic testing after 1 m o n th for specific IgG antibody to both diphtheria and tetanus toxins. I f the child has a protective concentration, the recorded doses are considered valid, and the vaccination series should be com pleted as age appropriate. C hildren w ith an indeterm inate concentration after a booster dose should be revaccinated w ith a com plete series.

# Hepatitis A Vaccine

# Poliovirus Vaccine
T h e sim plest approach to vaccinating w ith poliovirus vaccine is to revaccinate persons aged <18 years w ith IPV according to the U.S. schedule. Adverse events after IP V are rare {201). C hildren appropriately vaccinated w ith 3 doses o f O P V in econom ically developing countries m ig h t have suboptim al seroconversion, including to type 3 poliovirus {201). Serologic testing for neutralizing antib o d y to poliovirus types 1, 2, and 3 can be obtained com m ercially and at certain state health departm en t laboratories. Persons w ith protective titers against all three types do n o t need to repeat doses b u t should com plete the schedule as age appropriate.

# Rotavirus Vaccine
Rotavirus vaccination should not be initiated for infants aged >15 weeks, 0 days. Infants w ho began the rotavirus vaccine series outside the U n ited States b u t who did n o t com plete the series and w ho are still aged <8 m onths, 0 days, should follow the routine schedule and receive doses to com plete the series. I f the brand o f a previously adm inistered dose is RV5 or unknow n, a total o f 3 doses o f rotavirus vaccine should be do cu m en ted for series com pletion. All doses should be adm inistered by age 8 m onths, 0 days.

# Td and Tdap Vaccines
C hildren aged >7 years w ho need the prim ary series doses o f tetanus-toxoid-containing vaccine should receive T d or T dap as age appropriate.

# Varicella Vaccine

# Varicella vaccine is n o t available in the m ajority o f countries. A person w ho lacks reliable evidence o f varicella im m u n ity should be vaccinated as age appropriate {4,20).

# Zoster Vaccine
Zoster vaccination is recom m ended for all persons aged >60 years who have no contraindications, including persons who report a previous episode o f zoster or who have chronic medical conditions. T he vaccine should be offered at the patients first clinical encounter w ith the health-care provider. T h e vaccine is administered as a single 0.65-m L subcutaneous dose. Zoster vac cination is not indicated to treat acute zoster, to prevent persons with acute zoster from developing postherpetic neuralgia, or to treat ongoing postherpetic neuralgia. Before adm inistration o f zoster vaccine, patients do not need to be asked about their history o f varicella or to have serologic testing conducted to determ ine zoster immunity.

# Vaccinating Persons with Bleeding Disorders
Because o f the risk for hem atom a form ation after injections, intram uscular injections are often avoided am ong persons w ith bleeding disorders by using the subcutaneous or intraderm al routes for vaccines th a t norm ally are adm inistered intram us cularly. In one study, hepatitis B vaccine was adm inistered intram uscularly to 153 persons w ith hem ophilia. T h e vac cination was adm inistered w ith a 23-gauge or sm aller caliber needle, followed by application o f steady pressure to the site for 1-2 m inutes. T h e vaccinations resulted in a low (4%) bruising rate, and no patients required factor supplem entation {213). W h e th er antigens that produce m ore local reactions (e.g., pertussis) w ould produce an equally low rate o f bruising is unknow'n. W h en hepatitis B or any other intram uscularly adm inistered vaccine is indicated for a p atien t w ith a bleeding disorder, the vaccine should be adm inistered intram uscularly if a physician fam iliar w ith the p atien ts bleeding risk determ ines th at the vaccine can be adm inistered by this ro u te w ith reasonable safety I f the patien t receives antihem ophilia or sim ilar therapy intram uscularly adm inistered vaccinations can be scheduled shortly after such therapy is adm inistered. A fine-gauge needle (23 gauge or smaller caliber) should be used for the vaccina tion, followed by firm pressure on the site, w ith o u t rubbing, for at least 2 m inutes. T h e p atien t or family should be given in form atio n o n the risk for h em ato m a from the injection. Patients receiving anticoagulation therapy presum ably have the same bleeding risk as patients w ith clotting factor disor ders and should follow the sam e guidelines for intram uscular adm inistration. tered, the vaccine m anufacturer, the vaccine lot num ber, and the nam e, address, and title of the person adm inistering the vaccine. In addition, the provider is required to record the edition date of the V IS distributed and the date those m ateri als were provided. T h e act considers a health-care provider to be any licensed health-care professional, organization, or institutio n , w hether private or public (including federal, state, and local departm ents and agencies), und er w hose authority a specified vaccine is adm inistered. T his inform ation should be kept for all vaccines, n o t just for those required by the act. Providers and staff m em bers also should system atically update patient's perm anent medical records to reflect any docum ented episodes of adverse events after vaccination and any serologic test results related to vaccine-preventable diseases (e.g., those for rubella screening and antib o d y to HBsAg).

# Vaccination R ecords

# Records of Health-Care Providers

# Personal Records of Patients
Official childhood vaccination records have been adopted by every state and territory and the D istrict o f C o lum bia to encourage u n iform ity o f records and to facilitate assessment o f vaccination status by schools and child-care centers. T h e records also are key tools in vaccination education program s aim ed at increasing parental and patient awareness o f the need for vaccines. A perm an en t vaccination record card should be established for each new born infant and m aintained by the parent or guardian. T h e parent or guardian should be educated about the im portance o f keeping the record up to date and instructed to keep the record indefinitely as part o f the child's perm anent medical record. These cards should be distributed to new m others before discharge from the hospital. Using vaccina tion record cards for adolescents and adults also is encouraged. Standardized adult vaccination records are available at h ttp :// w w w .im m unize.org.

# Immunization Information Systems

# Vaccination of Children and Adolescents
Physicians and other pediatric vaccination providers should adhere to the standards for child and adolescent vaccination practices (8). T hese standards were published by the N ational Vaccine A dvisory C o m m ittee and define appropriate vaccina tion practices for both public and private sectors. T h e standards provide guidance on practices that elim inate barriers to vaccina tion, including elim inating unnecessary prerequisites for receiv ing vaccinations, elim inating missed opportunities to vaccinate, im proving procedures to assess vaccination needs, enhancing knowledge about vaccinations am ong parents and providers, and im proving m anagem ent and reporting of adverse events. In addition, the standards address the im portance o f recall and rem inder systems and using assessments to m o n ito r clinic or office vaccination coverage levels. E nsuring adolescents receive rou tin e and catch-up vaccina tion and increasing vaccination coverage in this age group pres ent challenges. In general, adolescents do n o t visit health-care providers frequently. H ealth-care providers should prom ote annual preventive visits (217), including one specifically for adolescents aged 11 and 12 years. T h e annual visits should be used as o pportunities to provide routinely recom m ended vac cine doses, additional catch-up doses needed for lapsed vaccine series, vaccines recom m ended for high-risk groups, additional doses th at m ight have been recently recom m ended, and other recom m ended health-care services.
All vaccine doses should be adm inistered according to A C IP vaccine-specific statem ents and w ith the m ost recent schedules for b o th routine and catch-up vaccination. Before leaving any visit for m edical care, adolescents should be encouraged to schedule retu rn visits for any additional vaccine doses needed. D u rin g visits that occur outside o f influenza season, providers should discuss and recom m end seasonal influenza vaccination and m ake explicit plans for vaccination, including tim ing and anticipated setting (e.g., health-care provider's office, school, or pharm acy). C atch-up vaccination w ith m ultidose adolescent vaccines generally can occur according to the rou tine dosing schedule for these vaccines, although in some circumstances the clinician or health-care provider m ight use m in im u m intervals for vaccine doses. T hese circum stances include an outbreak th at increases risk for disease o r the likelihood th at doses will be missed in the future (e.g., because o f an im pending loss o f health-care coverage or tran sp o rtatio n challenges). Because o f lack o f efficacy data for H P V vaccine adm inistration using m inim um intervals, providers are encouraged, w h en possible, to use routine dosing intervals for females aged 11-26 years w ho have n o t yet received 3 H P V vaccine doses as recom m ended (20,28).
O n e o f the challenges o f adolescent vaccination is ensur ing that current, com plete vaccination histories are available. Insurers, covered services, or reim bursem ent levels can change, and these changes m ight affect reim bursem ent for vaccine doses and vaccination services directly w hile also causing disruptions in an adolescent's access to vaccination providers or venues. In circum stances in w hich a vaccination record is unavailable, vaccination providers should attem p t to obtain this inform a tio n from various sources (e.g., parent, previous providers, or school records). M ore detail about how to obtain these records is available at from C D C at  w w .cdc.gov/vaccines/ recs/im m uniz-records.htm . W ith the exception o f influenza and pneum ococcal polysaccharide vaccines, if d o cu m en ta tio n o f a vaccine dose is n o t available, the adolescent should be considered unvaccinated for th at dose. Regardless o f the venue in w hich an adolescent receives a dose o f vaccine, that vaccine dose should be docum ented in the p atien t's chart or in an office log, and the inform ation should be entered into an IIS. T h e adolescent also should be provided w ith a record card th at docum ents the vaccination history.

# Adult Vaccination
T h e incidence o f vaccine-preventable diseases in adults in the U nited States is high. A pproxim ately 4 5,000 adults die each year from vaccine-preventable diseases, the m ajority from influenza (222). In 2008, an estim ated 44,000 cases ofinvasive pneum ococcal disease were reported w ith approxim ately 4,500 deaths, the m ajority occurring am ong persons aged >35 years ( w w .cdc.gov/abcs/survreports/spneu08.htm ). Because o f recent licensure o f new vaccines approved for ad ults and new A C IP recom m endations for the use o f m any vaccines in adults, providers o f adult health care now share a greater responsibility for p u tting these recom m endations into practice. In 2009, an estim ated 4,070 deaths were caused by infection w ith the H P V strains causing the m ajority o f cervical cancers in this co untry th at are preventable w ith H P V vaccine and routine Papanicolaou sm ear testing ( w w .cancer.org/ docroot/hom e/index.asp). H erpes zoster causes considerable m orbidity in adults aged >50 years (55). A painful com plica tion o f herpes zoster infection is postherpetic neuralgia, w hich is characterized by severe pain that can persist for up to a year after the herpes zoster rash has subsided. A vaccine to prevent herpes zoster was licensed in 2006.
In Vaccination w ith vaccines recommended for all adults or for those in specific age groups is generally cost-effective, if n o t costsaving, for society. T h e N ational Com m ission on Prevention Priorities (N CPP) ranked clinical preventive services based on clinically preventable disease effects and cost-effectiveness (223) In the N C P P report, influenza vaccination for adults aged >50 years and pneumococcal vaccination for adults aged >65 years ranked high, w ith 8 o f 10 possible points in the scoring system used. M ost other studies have found influenza vaccination reduces or minimizes health care, societal, and individual costs or the pro ductivity losses and absenteeism associated w ith influenza illness {224-226). Economic analyses am ong adults aged >65 years have found influenza vaccination to be cost-effective (225)(226)(227).
A 2008 study o f the cost-effectiveness o f PPSV dem onstrated that vaccination resulted in a gain o f $3,341 per quality-adjusted life year; the result is sensitive to vaccine uptake assumptions (228). PPSV administered at ages 50-65 years m ight be clini cally favorable and, depending on cost-effectiveness criteria used, economically favorable (228).
H epatitis B vaccine is n o t recom m ended routinely for all adults. However, m ultiple studies have established the costeffectiveness o f providing hepatitis B vaccinations at counseling and testing sites for H IV and other sexually tran sm itted dis eases, correctional institutions, drug-abuse treatm en t centers, and other settings serving adults at risk for hepatitis B virus infection (229-230).
Four studies have estim ated the cost-effectiveness o f a rou tine herpes zoster vaccination program o f im m u n o com petent persons aged >60 years (231-234). At a vaccine cost o f $150 per dose, the societal costs o f ro utinely vaccinating im m u n o com p eten t persons aged >60 years range from $27,000 to $ 112,000 per quality-adjusted life year gained (231-234). T he estim ated cost per quality-adjusted life year for zoster vaccina tion covers a wide range th at appears acceptable com pared with either standard thresholds or oth er established interventions b u t is at the interm ediate to high end o f that range.
Vaccination rates in adults are considered suboptimal (235-238). Healthy People 2010 goals for adult vaccination coverage with influenza and pneumococcal polysaccharide vaccines are 90% for each vaccine. For the 2007-2008 season, influenza vaccination coverage am ong adults aged 50-64 years was 34% , and cover age am ong adults aged >65 years was 66% (67). In 2008, 60% o f adults aged >65 years received a dose o f PPSV ( w w cdc.gov/nchs/data/hestat/vaccine_coverage.htm ). N ew Healthy People2 0 2 0 goals for influenza and pneumococcal polysaccharide vaccines include specific subsets o f adults, including institutional ized adults aged >18 years (for both influenza and pneumococcal polysaccharide vaccines) and noninstitutionalized adults at high risk aged >18 years (for pneumococcal polysaccharide vaccine) ( ?id=30&topicarea=immunization+and+infectious+diseases).
T h e m ost substantial barrier to vaccination coverage is lack o f knowledge about these vaccines am ong adult patients and adult A com m on challenge for health-care providers is vaccinating adults w ith unknow n vaccination records. In general (except for influenza and pneum ococcal polysaccharide vaccines), adults should receive a vaccine dose if the dose is recom m ended and no record o f previous adm inistration exists. If an adult has a record of military service and does n o t have records available, providers can assume that the person has received all vaccines recom m ended by the military at the time o f service entry. Serologic testing m ight be helpful in clarifying im m une status if questions remain because at different times and depending on military assignments, there m ight be interservice and individual differences.  15).

# Evidence-Based Interventions to Increase Vaccination Coverage
In 1997, the task force categorized as a recom m ended strat egy vaccination requirem ents for child care, school, and college (236). W hen appropriate, health agencies should take necessary steps to develop and enforce these requirem ents. Since 1995, all states receiving federal funds for vaccination program s have been required to cond u ct annual assessments of vaccination rates both in public health clinics and in pri vate provider offices. Prim arily to aid local and state health departm ents in their efforts to cond u ct assessments and assist providers, C D C has developed num erous software applications to m easure vaccination rates in provider practices.

# Other General Programmatic Issues
P ro g ram m atic challenges, evolving issues, and effective in te rv e n tio n s related to a d u lt and adolescent v accination program s have been described by oth er advisory groups and expert groups. Ad ditional evidence-based approaches are being developed for certain issues (e.g., settings for adolescent vac cination delivery) th ro u g h ongoing research and evaluation. A m ong current program m atic challenges, vaccine financing is especially difficult because certain problem s and solutions differ m arkedly from one state to another. Practitioners interested in beginning or contin u in g to provide vaccinations to patients are encouraged to consult w ith local and state public health vaccination program s to learn about publicly funded program s th at m ight be available in their areas for patients w ho need vac cination but have insufficient health insurance coverage and no financial resources. I f n o t already participating, providers wrho care for adolescents and children aged <19 years should enroll in the Vaccines for C hild ren Program ( w w .cdc.gov/ vaccines/program s/vfc/default.htm ). T h ro u g h this program 's provision o f A C IP-recom m ended, federally purchased vaccines, participating providers are able to fully vaccinate eligible chil dren w hose parents m ight n o t otherw ise be able to afford the vaccinations. Interested providers are encouraged to w ork w ith insurers, state and specialty-specific medical organizations, vac cine m anufacturers, and other stakeholders to address financial barriers to achieving high vaccination coverage. W ith avail ability o f safe and effective vaccines for 17 vaccine-preventable diseases, the capacity for realizing the potential benefits o f these products in the U nited States depends on reaching children, adolescents, and adults through dedicated, knowledgeable vac cination providers and efficient, strong vaccination program s at local, state, and federal levels.

# V accine Information S ources
In addition to these general recom m endations, the following sources contain specific and updated vaccine inform ation.

# CDC-INFO Contact Center
T h e C D C -IN F O contact center is supported by C D C and provides public health-related inform ation, including vaccina tion inform ation, for health-care providers and the public, 24 hours a day, 7 days a week (telephone : 800-232-4636; telephone : 800-232-6348).

# CDC's National Center for immunization and Respiratory Diseases

# American Academy of Family Physicians (AAFP)
Inform ation from the professional organization o f family physicians is available at  w w .aafp.org.

# Immunization Action Coalition

# National Network for Immunization Information

# Vaccine Education Center
Located at the C h ild re n 's H o sp ital o f P h iladelphia, the Vaccine E ducation C en ter provides p atien t and provider vac cine inform ation ( w w .vaccine.chop.edu).

# Institute for Vaccine Safety
Located at Johns H o p k in s U niversity S chool o f Public H ealth, the In stitute for Vaccine Safety provides inform ation about vaccine safety concerns and objective and tim ely infor m ation to physicians and health-care providers and parents ( w w .vaccinesafety.edu).

# Group on Immunization Education of the Society of Teachers of Family Medicine

# State and Local Health Departments

# TABLE 1. (Continued) R ecom m en ded and m in im u m ages a n d intervals b e tw e e n vaccine doses'1 '
Abbreviations: DTaP = diphtheria and tetanus toxoids and acellular pertussis; HepA = hepatitis A; HepB = hepatitis B; Hib = Haemophilus influenzae type b; IHPV = human papillomavirus; IPV = inactivated poliovirus; LAIV= live, attenuated influenza vaccine; MCV4 = quadrivalent meningococcal conjugate vaccine; MMR = measles, mumps, and rubella; MMRV= measles, mumps, rubella, and varicella; MPSV4 = quadrivalent meningococcal polysaccharide vaccine; PCV= pneumococcal conjugate vaccine; PPSV = pneumococcal polysaccharide vaccine; PRP-OMB = polyribosylribitol phosphate-meningococcal outer membrane protein conjugate; Td = tetanus and diphtheria toxoids;TIV = trivalent inactiated influenza vaccine;Tdap = tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis; Var = varicella vaccine. - Combination vaccines are available. Use o f licensed combination vaccines is generally preferred to separate injections o f their equivalent com ponent vaccines. When administering combination vaccines, the minim um age for administration is the oldest age for any o f the individual components; the m inimum interval between doses is equal to the greatest interval o f any o f the individual components. f Information on travel vaccines, including typhoid, Japanese encephalitis, and yellow fever, is available at . Information on other vaccines that are licensed in the United States but not distributed, including anthrax and smallpox, is available at . 5 Combination vaccines containing the hepatitis B component are available (see Table 2). These vaccines should not be administered to infants aged 7 months require fewer doses to complete the series. 1111 If PRP-OMP (Pedvax-Hib, Merck Vaccine Division) was administered at ages 2 and 4 months, a dose at age 6 months is not necessary. * A fourth dose is not needed if the third dose was administered at >4 years and at least 6 months after the previous dose.   - Although MMR, DTaP, DT,Td, and Tdap are combination vaccines, they are not included on this list because they are not available in the United States as single-antigen products. f A dash ( -) between vaccine products indicates that products are supplied in their final form by the manufacturer and do not require mixing or reconstitution by the user. A slash ( / ) indicates that the products must be mixed or reconstituted by the user.

# TABLE 3. G uidelines for spacing o f live and ina c tiv ate d antigen s Antigen com bination Recomm ended m inim um interval betw een doses
Two or more inactivated- May be administered simultaneously or at any interval between doses Inactivated and live May be administered simultaneously or at any interval between doses Two or more live injectable1 28 days m inimum interval, if not administered simultaneously Source: American Academy o f Pediatrics. Pertussis. In: Pickering LK, Baker, CJ, Kimberlin DW, Long SS, eds. Red book: 2009 report o f the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy o f Pediatrics; 2009:22. - Certain experts suggest a 28-day interval between tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine and tetravalent meningococcal conjugate vaccine if they are not administered simultaneously. T Live oral vaccines (e.g.,Ty2la typhoid vaccine and rotavirus vaccine) may be administered simultaneously or at any interval before or after inactivated or live inject able vaccines.

# TABLE 4 . G uidelines for ad m in is te rin g a n tib o d y -c o n ta in in g p ro d u cts - and vaccines Type o f adm inistration Products adm inistered Recomm ended m inim um interval betw een doses
Simultaneous (during the same office visit)

# Nonsimultaneous
Antibody-containing products and inactivated antigen Antibody-containing products and live antigen

# Adm inistered first
Antibody-containing products Inactivated antigen Antibody-containing products Live antigen

# Adm inistered second

# Inactivated antigen Antibody-containing products Live antigen Antibody-containing products
Can be administered simultaneously at different anatomic sites or at any tim e interval between doses Should not be administered simultaneously.1 ' If simultaneous administration o f measles-containing vaccine or varicella vaccine is unavoidable, administer at different sites and revaccinate or test for seroconversion after the recommend ed interval (see Table 5)

# No interval necessary
No interval necessary Dose related1-5 2 weeks1 " - Blood products containing substantial amounts o f immune globulin include intramuscular and intravenous immune globulin, specific hyperimmune globulin (e.g., hepatitis B immune globulin, tetanus immune globulin, varicella zoster immune globulin, and rabies immune globulin), whole blood, packed red blood cells, plasma, and platelet products. 1 Yellow fever vaccine; rotavirus vaccine; oralTy2la typhoid vaccine; live, attenuated influenza vaccine; and zoster vaccine are exceptions to these recommendations.
These live, attenuated vaccines can be administered at any tim e before or after or simultaneously with an antibody-containing product. 5 The duration o f interference o f antibody-containing products with the immune response to the measles com ponent o f measles-containing vaccine, and possibly varicella vaccine, is dose related (see Table 5).  - Events or conditions listed as precautions should be reviewed carefully. Benefits o f and risks for administering a specific vaccine to a person under these circum stances should be considered. If the risk from the vaccine is believed to outweigh the benefit, the vaccine should not be administered. If the benefit o f vaccination is believed to outweigh the risk, the vaccine should be administered. Whether and when to administer DTaP to children w ith proven or suspected underlying neurologic disorders should be decided on a case-by-case basis. I HIV-infected children may receive varicella and measles vaccine if CD4+ T-lymphocyte count is >15%. (Source: Adapted from American Academy o f Pediatrics.

# TABLE 5. R ecom m en ded intervals b e tw e e n a d m in is tra tio n o f a n tib o d y -c o n ta in in g p roducts and m easles-or varicella-con tain ing vaccine, by p ro d u ct and ind icatio n for vaccination
Passive immunization. In: Pickering LK, ed. Red book: 2009 report o f the comm ittee on infectious diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics: 2009.) 5 MMR and varicella vaccines can be administered on the same day. If not administered on the same day, these vaccines should be separated by at least 28 days. II Substantially immunosuppressive steroid dose is considered to be >2 weeks o f daily receipt o f 20 mg or 2 m g/kg body weight o f prednisone or equivalent.  See text and Table 5 for details. t f Measles vaccination m ight 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 o f MMR vaccination, the test should be postponed for >4 weeks after the vaccination. If an urgent need exists to skin test, do so w ith the understanding that reactivity m ight be reduced by the vaccine. 55 Hepatitis B vaccination should be deferred for infants weighing <2,000 g if the mother is documented to be HBsAg-negative at the tim e o f the infant's birth.
Vaccination can commence at chronological age 1 month or at hospital discharge. For infants born to HBsAg-positive women, hepatitis B immune globulin and hepatitis B vaccine should be administered w ithin 12 hours after birth, regardless o f weight. 1111 Vaccine should be deferred for the appropriate interval if replacement im mune globulin products are being administered (see Table 5). R e co m m e n d a tio n s a nd Reports

# TABLE 7. C onditions com m o nly m isperceived as con traind ication s to vaccination Vaccine

# Conditions com m only misperceived as contraindications (i.e., vaccination may be adm inistered under these conditions)
General for all vaccines, including Mild acute illness w ith or w ithout fever DTaP, pediatric DT, adult Td, Mild-to-moderate local reaction (i.e., swelling, redness, soreness); low-grade or moderate fever after previous dose adolescent- - Antibacterial drugs m ight interfere w ith Ty21a oral typhoid vaccine, and certain antiviral drugs m ight interfere with varicella-containing vaccines and LAIV. + Hepatitis B vaccination should be deferred for infants weighing <2,000 g if the mother is documented to be HBsAg-negative at the tim e o f the infant's birth.
Vaccination can commence at chronological age 1 month or at hospital discharge. For infants born to HBsAg-positive women, hepatitis B immune globulin and hepatitis B vaccine should be administered w ithin 12 hours after birth, regardless o f weight. 5 MMR and varicella vaccines can be administered on the same day. If not administered on the same day, these vaccines should be separated by at least 28 days.
HIV-infected children should receive im mune globulin after exposure to measles. HIV-infected children can receive varicella and measles vaccine if CD4+T-lymphocyte count is >15%. If testing cannot be performed until after the day o f MMR vaccination, the test should be postponed for at least 4 weeks after the vaccination. If an urgent need exists to skin test, do so with the understanding that reactivity m ight be reduced by the vaccine. f t If a vaccinee experiences a presumed vaccine-related rash 7-25 days after vaccination, the person should avoid direct contact with im munocompromised persons for the duration o f the rash.            J M e d V ir o l 1 9 8 6 ;1 9 :3 0 7 -1 1 .
18. S tefano I, Sato H K , P a n n u ti CS, e t al. R ecent im m u n iz a tio n against measles does n o t inte rfere w ith the sero-response to y e llo w fever vaccine.
V a ccine 1 9 9 9 ;1 7 :1 0 4 2 -6 .

# G lossary
Adverse event. An untoward event that occurs after a vaccination that might be caused by the vaccine product or vaccination process. Adverse events include those that have the following characteristics: 1) vaccine induced (caused by the intrinsic characteristic of the vaccine preparation and the individual response of the vaccinee): these events would not have occurred w ithout vaccination (e.g., vaccine-associated paralytic poliomyelitis); 2) vaccine potentiated: the events would have occurred anyway but were precipitated by the vaccination (e.g., first febrile seizure in a predisposed child); 3) programmatic error: the event was caused by technical errors in vaccine preparation, handling, or administration; and 4) coin cidental: the event was associated temporally with vaccination by chance or caused by underlying illness. Special studies are needed to determine whether an adverse event is a reaction to the vaccine or the result of another cause (Sources: Chen RT. Special m eth odological issues in pharmacoepidemiology studies o f vaccine safety. In: Strom BL, ed. Pharmacoepidemiology. 3rd ed. Sussex, England: John Wiley & Sons; 2000:707-32; and Fenichel GM, Lane DA, Livengood JR, Horwitz SJ, Menkes JH , Schwartz JF. Adverse events following immunization: assessing probability of causation. Pediatr Neurol 1989;5:287-90).
Adverse reaction. An undesirable medical condition that has been demonstrated to be caused by a vaccine. Evidence for the causal relation is usually obtained through randomized clinical trials, controlled epidemiologic studies, isolation of the vaccine strain from the pathogenic site, or recurrence of the condition with repeated vaccination (i.e., rechallenge); synonyms include side effect and adverse effect.
A djuvant. A vaccine com ponent distinct from the antigen that enhances the immune reponse to the antigen.
A ntitoxin. A solution of antibodies against a toxin. Antitoxin can be derived from either hum an (e.g., tetanus im m une globulin) or animal (usually equine) sources (e.g., diphtheria and botulism antitoxin). Antitoxins are used to confer passive im m unity and for treatment.
H y p e rim m u n e g lo b u lin (sp e c ific ). Special preparations obtained from blood plasma from donor pools preselected for a high antibody content against a specific antigen (e.g., hepatitis B immune globulin, varicella-zoster immune globulin, rabies immune globulin, tetanus im m une globulin, vaccinia immune globulin, cytomegalovirus im mune globulin, botulism im m une globulin).
Im m u n e globulin. A sterile solution containing antibodies, which are usually obtained from hum an blood. It is obtained by cold ethanol fractionation of large pools of blood plasma and contains 15%-18% protein. Intended for intramuscular adminis tration, immune globulin is primarily indicated for routine main tenance of im m unity among certain immunodeficient persons and for passive protection against measles and hepatitis A.
Im m u n o b io lo g ic. Antigenic substances (e.g., vaccines and toxoids) or antibody-containing preparations (e.g., globulins and antitoxins) from hum an or animal donors. These prod ucts are used for active or passive immunization or therapy. Examples of im m u nobiologies include antitoxin, immune globulin and hyperimmune globulin, monoclonal antibodies, toxoids, and vaccines.
Intravenous im m une globulin. A product derived from blood plasma from a donor pool similar to the imm une globulin pool, but prepared so that it is suitable for intravenous use. Intravenous im m une globulin is used primarily for replacement therapy in primary antibody-deficiency disorders, for treatment of Kawasaki disease, imm une thrombocytopenic purpura, hypogammaglobu linemia in chronic lymphocytic leukemia, and certain cases of hum an immunodeficiency virus infection (Table 5).
M onoclonal antibody. An antibody product prepared from a single lymphocyte clone, which contains only antibody against a single antigen.
S im ultaneous. In the context of vaccine timing and spacing, occurring on the same clinic day, at different anatomic sites, and not combined in the same syringe.
Toxoid. A modified bacterial toxin that has been made nontoxic, but retains the ability to stimulate the formation of antibodies to the toxin.
Vaccination and im m unization. The terms vaccine and vaccina tion are derived from rncca, the Latin term for cow. Vaccine was the term used by Edward Jenner to describe material used (i.e., cowpox virus) to produce im m unity to smallpox. The term vaccination was used by Louis Pasteur in the 19th century to include the physical act of administering any vaccine or toxoid. Immunization is a more inclusive term, denoting the process of ind ucing or providing im m unity by administering an immunobiologic. Immunization can be active or passive. Active immunization is the production of antibody or other immune responses through administration of a vaccine or toxoid. Passive immunization means the provi sion of temporary im m unity by the administration of preformed antibodies. Although persons often use the terms vaccination and immunization interchangeably in reference to active immunization, the terms are not synonymous because the administration of an immunobiologic cannot be equated automatically with develop m ent of adequate immunity.
Vaccine. A suspension of live (usually attenuated) or inactivated microorganisms (e.g., bacteria or viruses) or fractions thereof administered to induce im m unity and prevent infectious disease or its sequelae. Some vaccines contain highly defined antigens (e.g., the polysaccharide of Haemophilus influenzae type b or the surface antigen of hepatitis B); others have antigens that are complex or incompletely defined (e.g., Bordetella pertussis antigens or live, attenuated viruses).

# Advisory Committee on Immunization

# TABLE 14. Approaches to evalu atio n a n d vaccination o f persons vaccinated o utsid e th e U n ite d States w h o have no (or q uestio nab le) vaccina tio n records