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Immunizations in children and adolescents 

Updated 2013 Jun 12 03:12:00 PM: quadrivalent inactivated influenza vaccine (Fluzone) FDA approved for prevention of seasonal influenza in persons ≥ 6 months old (Manufacturer Press Release 2013 Jun 10) view updateShow more updates

Related Summaries: 

Immunizations in adults

2013 Recommended Immunization Schedule 

charts from Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) o for routine immunizations PDF ages 0-18 years o for catch-up chart PDF ages 4 months to 18 years federal law requires provision of federal Vaccine Information Statements (VISs) to parents, VISs may be downloaded from CDC

Routine immunizations by age:   

birth - hepatitis B (first dose)(1) age 1 month - hepatitis B (second dose), or at age 2 months(1) age 2 months(1) o hepatitis B (second dose), if not received at age 1 month o rotavirus (first dose) o DTaP (first dose) - diphtheria, tetanus, and pertussis o Haemophilus influenzae type B (Hib) (first dose) o pneumococcal conjugate (PCV13) (first dose) o inactivated poliovirus (first dose) age 4 months(1) o rotavirus (second dose) o DTaP (second dose) o Hib (second dose) o PCV13 (second dose o inactivated poliovirus (second dose) age 6 months(1) o hepatitis B (third dose), or anytime age 6-18 months o rotavirus (third dose), if using 3-dose RV-5 series or any dose in series was unknown


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DTaP (third dose) Hib (third dose), not indicated If PRP-OMP (PedvaxHiB or Comvax) given at age 2 and 4 months o PCV13 (third dose) o inactivated poliovirus (third dose), or anytime age 6-18 months o inactivated influenza vaccine yearly until age 2 years - give 2 doses separated by ≥ 4 weeks to children < 8 years old who are receiving influenza vaccine for first time age 12-15 months(1) o hepatitis B (third dose), or anytime age 6-18 months if not given earlier o Hib (third or fourth dose) as booster o PCV13 (fourth dose) o inactivated poliovirus (third dose), or anytime age 6-18 months if not given earlier o inactivated influenza vaccine yearly until age 2 years - give 2 doses separated by ≥ 4 weeks to children < 8 years old who are receiving influenza vaccine for first time o measles, mumps, rubella (MMR) (first dose) o varicella (first dose) o hepatitis A (first dose at age 12-23 months) age 15-18 months(1) o DTaP (fourth dose) o inactivated influenza vaccine yearly until age 2 years - give 2 doses separated by ≥ 4 weeks to children < 8 years old who are receiving influenza vaccine for first time age 18-23 months(1) o hepatitis A (second dose 6-18 months after first dose) o inactivated influenza vaccine yearly until age 2 years - give 2 doses separated by ≥ 4 weeks to children < 8 years old who are receiving influenza vaccine for first time age 2-3 years - influenza yearly (inactivated influenza vaccine or live, attenuated influenza vaccine)(1) age 4-6 years(1) o DTaP (fifth dose) o inactivated poliovirus (fourth dose) o influenza yearly (inactivated influenza vaccine or live, attenuated influenza vaccine) o MMR (second dose) o varicella (second dose) age 11-12 years(1) o Tdap - tetanus, diphtheria, and pertussis o influenza yearly (inactivated influenza vaccine or live, attenuated influenza vaccine) o human papillomavirus 3-dose series o meningococcal age 16 years - meningococcal booster(1)


Changes to immunization schedule from 2012: 

2013 changes from 2012 include o immunization schedule now extended to ages 0-18 years o meningococcal conjugate vaccine (MCV4) extended down to age 6 weeks reflecting licensure of HiB-MenCY vaccine o extended hepatitis A vaccine recommendations for older children o recommendations for pneumococcal polysaccharide vaccine (PPSV23) added for certain high-risk groups o updated recommendations for diphtheria, tetanus, and acellular pertussis  DTaP < 7 years old  Tdap  ≥ 7 years old, including children ages 7-10 years not fully immunized with the childhood DTaP  single dose to pregnant adolescents during each pregnancy o updated influenza vaccine recommendations for children aged 6 months to 8 years for 2012-13 and 2013-14 influenza seasons

Specific Vaccinations (Including Catch-Up Schedules) Hepatitis B vaccine (HepB):   

minimum age for first dose - birth(1) 0.5 mL intramuscularly (anterolateral thigh muscle or deltoid muscle of arm) (3) routine vaccination(1) o give first dose at birth  for all newborns, give monovalent HepB vaccine before hospital discharge.  for infants born to hepatitis B surface antigen (HBsAg)-positive mothers  give vaccine plus hepatitis B immune globulin (HBIG) 0.5 mL within 12 hours of birth  test for HBsAg and HBsAg antibody 1-2 months after completion of series (age 9-18 months [preferably at next well-child visit])  for infants born to mothers with unknown HBsAg status  give HepB vaccine within 12 hours of birth regardless of birth weight  if infant weighs < 2,000 g also give HBIG within 12 hours of birth regardless of mother's HBsAg status  if infant weighs ≥ 2,000 g and mother determined to be HBsAg-positive, give HBIG before age 1 week o give second dose at age 1-2 months (use monovalent HepB vaccine for doses given before age 6 weeks) catch-up vaccination(1) o for infants who did not receive birth dose


give first dose as soon as possible, second dose at 1-2 months, and third dose at 6 months  give third or fourth dose (4 doses recommended if combination vaccine given after birth dose) > 16 weeks after first dose and no earlier than age 24 weeks o for unvaccinated persons in general, give 3-dose series with minimal intervals of 4 weeks between first and second dose and 8 weeks between second and third dose o for children aged 11-15 years, consider 2-dose series (2 doses with minimum interval of 4 months) of adult formulation Recombivax HB see Hepatitis B Vaccine Recombinant for additional information

Hepatitis A vaccine (HepA):   

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minimum age for first dose - age 12 months(1) 0.5 mL intramuscularly (anterolateral thigh muscle or deltoid muscle of arm) (3) routine vaccination(1) o start 2-dose series at age 12-23 months o give second dose 6-18 months after first dose (minimum interval 6 months) catch-up vaccination - give 2 doses of HepA vaccine separated by 6-18 months to anyone ≥ 2 years old desiring immunity against hepatitis A virus infection (1) special populations(1) o give 2 doses of HepA vaccine ≥ 6 months apart to children who are  previously unvaccinated and living in areas where vaccination programs target older children  at increased risk for hepatitis A infection see Hepatitis A Virus Vaccine Inactivated for additional information

Diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP):   

minimum age for first dose - age 6 weeks(1) 0.5 mL intramuscularly (anterolateral thigh muscle or deltoid muscle of arm) (3) routine vaccination(1) o 5-dose series at ages 2, 4, 6, 15-18 months, and 4-6 years o fourth dose may be given at age 12 months if ≥ 6 months since third dose catch-up vaccination for children aged 4 months to 6 years(1) o 5-dose series with minimal intervals of  4 weeks between first and second dose  4 weeks between second and third dose  6 months between third and fourth dose  6 months between fourth and fifth dose o fifth dose not needed if fourth dose given at age 4 years or older same brand of DTaP vaccine for all 3 doses of primary vaccination series generally recommended, but starting series with Tripedia for 1-2 doses and ending with Infanrix for 1-2 doses appears as safe and immunogenic as using Tripedia for all 3 doses (level 3 [lacking direct] evidence) o based on randomized trial without clinical outcomes


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449 healthy infants aged 6-12 weeks randomized to 1 of 3 groups  Tripedia at ages 2, 4, and 6 months  Tripedia at ages 2 and 4 months and Infanrix at 6 months old  Tripedia at 2 months old and Infanrix at ages 4 and 6 months o no significant differences in antibody concentrations or seroprotection o Reference - Pediatrics 2002 Apr;109(4):666 additional DTaP vaccination at age 2-14 days associated with lower immune response to pertussis at age 6-18 months (level 3 [lacking direct] evidence) o based on small randomized trial without clinical outcomes o 50 healthy full-term infants aged 2-14 days randomized to DTaP plus hepatitis B vaccination vs. hepatitis B vaccination alone, followed by standard vaccination schedule o early DTaP associated with  significantly lower geometric mean antibody titers (GMAT) for all pertussis antigens (pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae 2 and 3) at ages 6 months, 7 months, and 8 months  significantly lower GMAT for  fimbriae at ages 6, 7, 17, and 18 months  filamentous hemagglutinin at 18 months o no significant differences in local or systemic reactions o Reference - J Pediatr 2008 Sep;153(3):327,editorial can be found in J Pediatr 2008 Sep;153(3):305 see Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed for additional information

Tetanus and diphtheria toxoids and acellular pertussis vaccine (Tdap): 

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minimum age(1) o age 10 years for Boostrix o age 11 years for Adacel 0.5 mL intramuscularly (deltoid muscle of arm or anterolateral thigh muscle) (3) routine vaccination(1) o give 1 dose to all adolescents aged 11-12 years o can be given regardless of interval since last tetanus and diphtheria toxoidcontaining vaccine o give 1 dose to pregnant adolescents during each pregnancy  27-36 weeks gestation preferred  give regardless of number of years from prior tetanus and diphtheria toxoids (Td) or Tdap vaccination catch-up vaccination(1) o if child aged 7-10 years was not fully immunized with childhood DTaP vaccine series  give 1 dose of Tdap vaccine  give Td vaccine if additional doses needed  do not give adolescent Tdap vaccine o if child aged 11-18 years has not received Tdap vaccine


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give 1 dose of Tdap vaccine give Td booster every 10 years o if inadvertent dose of DTaP vaccine given to child aged 7-10 years, count as part of catch-up series  can count as adolescent Tdap dose or  child can receive Tdap booster dose at age 11-12 years Tdap vaccine can be safely administered at any interval (at least 18 months) after previous tetanus/diphtheria vaccine, based on local side effect rates < 10% in cohort of 7,156 children and adolescents (Pediatr Infect Dis J 2006 Mar;25(3):195) see Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed for additional information

Meningococcal vaccines: 

commercially available formulations in United States contain purified capsular polysaccharide antigens A, C, Y, and W-135 extracted from Neisseria meningitidis o meningococcal conjugate quadrivalent vaccines (MCV4)  2 available MCV4 vaccines considered interchangeable by Centers for Disease Control and Prevention (CDC)  MenACWY-D (Menactra) licensed for use at age 9 months to 55 years  MenACWY-CRM (Menveo) licensed for use at age 2-55 years  both have antigens conjugated to diphtheria toxoid protein  given by intramuscular injection  contraindications  MenACWY-D contraindicated if hypersensitivity to any ingredient, latex sensitivity  MenACWY-CRM contraindicated if allergic reaction to any component, or any other CRM197, diphtheria toxoid, or meningococcal-containing vaccine  contraindication for history of Guillain Barre syndrome removed by The Advisory Committee on Immunization Practices (ACIP) in June 2010 o meningococcal polysaccharide quadrivalent vaccine - 1 available: MPSV4 (Menomune)  has unconjugated antigens  given by subcutaneous injection  only vaccine licensed for use in persons ≥ 56 years old  contraindicated if hypersensitivity to any ingredient or any acute illness o bivalent meningococcal polysaccharide protein conjugate vaccine (serogroups C and Y) combined with Haemophilus influenzae type B (HibMenCY-TT [MenHibrix]) licensed for use in children aged 6 weeks to 18 months CDC recommendations for meningococcal vaccination o routine vaccination of adolescents with MenACWY vaccine


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first dose at age 11-12 years booster dose at age 16 years catch-up vaccination if missing routine timing  first dose at age 13-18 years if not previously vaccinated  if first dose at age 13-15 years  booster dose at age 16-18 years  minimum interval between doses 8 weeks  booster not needed if first dose is administered ≥ 16 years old, unless at increased risk of meningococcal disease  booster dose may be given at age 19-21 years if no dose after age 16 years for persons with anatomic or functional asplenia (including sickle cell disease)  for infants - 4-dose primary series of Hib-MenCY-TT at ages 2, 4, 6, and 12-15 months  infants aged 19-23 months not receiving Hib-MenCY-TT should defer vaccination with MenACWY until age 2 years and completion of pneumococcal conjugate vaccine (PCV)-13 series  if age 2-55 years without complete series of Hib-MenCY-TT  2 primary doses of either MenACWY vaccine 8-12 weeks apart  give only ≥ 4 weeks after completion of all PCV-13 doses  booster doses every 5 years (except first booster dose in 3 years for children who had primary series before age 7 years) for persons with persistent complement component deficiency (C3, C5-9, Properdin, Factor D, and Factor H)  for infants - 4-dose primary series of Hib-MenCY-TT at ages 2, 4, 6, and 12-15 months  for persons aged 9 months to 55 years - 2-dose primary series of MenACWY given 8-12 weeks apart  booster doses every 5 years (except first booster dose in 3 years for children who had primary series before age 7 years) for persons with HIV infection  HIV infection is not an indication for routine meningococcal vaccination  for persons with HIV infection who are otherwise candidates for meningococcal vaccination, 2-dose primary series (given 8-12 weeks) apart recommended instead of single dose for travel to or residence in countries where meningococcal disease Is hyperendemic or epidemic, particularly with prolonged contact with local population  recommended for visiting parts of sub-Saharan Africa known as "meningitis belt" during dry season (December-June)  for persons aged 9 months to 55 years - 2-dose primary series of MenACWY given 8-12 weeks apart  booster dose of MenACWY  if last dose ≥ 5 years before date of travel


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if last dose > 3 years before date of travel for all travelers to Mecca during annual Hajj  infants and children receiving prior dose of Hib-MenCY-TT traveling to high endemic areas are not protected against serogroups A and W and prior to travel should receive  MenACWY-D (Menactra) 12 weeks apart if aged 9-23 months or  1 dose of MenACWY if ≥ 2 years old o during community outbreak attributable to vaccine serogroup - follow ageand formulation-appropriate series of MenACWY or Hib-MenCY-TT o for first-year college students living in residence halls  at least 1 dose of MenACWY before college entry ≥ 16 years old  booster dose before enrollment if previous dose < 16 years old o for microbiologists routinely exposed to isolates of N. meningitidis  1 dose of MenACWY  booster dose every 5 years if exposure is ongoing o for persons ≥ 56 years old meeting criteria for vaccination  MenACWY preferred if previously vaccinated with MenACWY  MPSV4 preferred if no prior meningococcal vaccine exposure o Reference - MMWR Recomm Rep 2013 Mar 22;62(RR-2):1 New York City Health Department recommends meningococcal vaccination for men who have sex with men met through website, digital application, bar or party, or men with HIV infection who have sex with men (NYC Health 2013 Mar 6 PDF) MCV4 more immunogenic than MPSV4 at 1 and 6 months (level 3 [lacking direct] evidence) other meningococcal vaccines with established clinical efficacy, but not licensed in United States o meningococcal C conjugate vaccine (MenC) is monovalent vaccine used in United Kingdom and Canada; meningococcal C conjugate vaccines appear effective against severe meningococcus type C disease (level 2 [mid-level] evidence) o 4-component meningococcal serogroup B vaccine (Bexsero) approved in European Union and appears immunogenic in healthy infants and adolescents (level 3 [lacking direct] evidence) o meningococcal A conjugate vaccine (MenAfriVac) appears immunogenic in children and adults in Africa (level 3 [lacking direct] evidence) and can be stored for up to 4 days without cold chain o polysaccharide serogroup A vaccine protected against serogroup A meningococcal meningitis for at least 1 year in persons > 5 years old (level 1 [likely reliable] evidence) see Meningococcal Vaccine for details

Inactivated poliovirus vaccine (IPV): 

IPV has replaced OPV in settings where risk of vaccine-associated paralytic poliomyelitis (VAPP) exceeds risk of wild polio


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0.5 mL intramuscularly (deltoid muscle of arm) or subcutaneously (fatty tissue over anterolateral thigh muscle or triceps) (Centers for Disease Control and Prevention (CDC) PDF) minimum age 6 weeks old routine vaccination  4 dose series at ages 2, 4, 6-18 months and 4-6 years  final dose ≥ 4 years old and at least 6 months after previous dose catch-up vaccination  4 dose series with minimal intervals of  4 weeks between first and second dose  4 weeks between second and third dose  6 months between third and fourth dose  minimum age and minimum intervals are only recommended if child ≤ 6 months is at risk for imminent exposure to circulating poliovirus (travel to polio-endemic region or during outbreak)  if ≥ 4 doses administered < 4 years old additional dose needed age 46 years  fourth dose not necessary if third dose ≥ 4 years old and at least 6 months after previous dose  if both OPV and IPV were administered as part of series 4 doses should be administered regardless of child’s current age  IPV is not routinely recommended for U.S. residents ≥ 18 years old Reference - MMWR Surveill Summ 2013 Feb 1;62 Suppl 1:2 American Academy of Pediatrics recommendations on poliovirus vaccination  IPV should be administered to immunocompromised and immunodeficient children using standard schedule  recommendations for poliovirus vaccination schedule for specific combination vaccines  when DTaP-IPV/Hib used to provide first 4 doses, additional booster of IPV-containing vaccine (IPV or DTaP-IPV) should be administered on or after fourth birthday  minimum interval from dose 4 to dose 5 ≥ 6 months  Reference - Pediatrics 2011 Oct;128(4):805 Advisory Committee on Immunization Practices updated recommendations on routine poliovirus vaccination  Advisory Committee on Immunization Practices (ACIP) recommends all-IPV schedule for routine childhood polio vaccination in United States (as of 1999 June 17)  no OPV distributed in United States since 1999  recommendations for poliovirus vaccination schedule for specific combination vaccines  when DTaP-IPV/Hib (Pentacel) used to provide 4 doses (ages 2, 4, 6, and 15-18 months) additional booster of ageappropriate IPV-containing vaccine (IPV [Ipol] or DTaP-IPV [Kinrix]) should be administered at age 4-6 years (this 5-dose IPV vaccine series considered acceptable by ACIP)


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DTaP-IPV/Hib not indicated for booster dose at age 4-6 years minimum interval from dose 4 to dose 5 ≥ 6 months if IPV dose at age 4-6 years missed, booster dose should be given as soon as feasible  Reference - ACIP updated recommendations on routine poliovirus vaccination (MMWR Morb Mortal Wkly Rep 2009 Aug 7;58(30):829 ) cases of vaccine-associated paralytic polio have been eliminated in United States with change to all-IPV schedule (JAMA 2004 Oct 13;292(14):1696), editorial can be found in JAMA 2004 Oct 13;292(14):1749 IPV may be at least as immunogenic as OPV (level 3 [lacking direct] evidence)  based on randomized trial without clinical outcomes  500 infants randomized to 3 groups according to polio vaccine type given at standard dosing intervals  DTaP/IPV/Hib combination vaccine (Pentaxim) plus Hib vaccine (EngerixB)  DTwP-HB/Hib combination vaccine (TritanrixB and Hiberix), IPV (Imovax Polio) for first 2 doses and OPV for subsequent 2 doses  DTwP-HB/Hib combination vaccine (TritanrixB and Hiberix) plus OPV for all 4 doses  comparing rates of seropositivity of polio types 1, 2, and 3 for IPV vs. OPV  98%-100% vs. 92.1%-99.3% 2 months after second dose (p < 0.001)  100% vs. 97%-100% (not significant)  IPV only had higher geometric mean titers than OPV only  Reference - J Infect Dis 2007 Sep 1;196(5):692 fractional dose of poliovaccine for resource limited settings  fractional dose of inactivated poliovirus vaccine may have similar and high immune response compared to full dose (level 3 [lacking direct] evidence)  based on randomized trial without clinical outcomes  320 infants in Cuba randomized to IPV fractional dose (0.1 mL, or one-fifth of full dose) intradermally vs. full dose intramuscularly at ages 4 and 8 months  priming immune response defined as meeting 1 of 2 criteria  absence of seroconversion after first dose of IPV and antibody titer at 8 months 7 days 4 times as high as titer at 8 months  nondetectable reciprocal titer at 8 months and detectable reciprocal titer at 8 months 7 days  priming immune response comparing fractional IPV dose vs. full IPV dose  90.8% vs. 97.6% for poliovirus type 1 (p = 0.1)  94% vs. 98.2% for poliovirus type 2 (not significant)


 89.6% vs. 98.1% for poliovirus type 3 (p = 0.01) cumulative 2-dose seroconversion comparing fractional IPV dose vs. full IPV dose  93.6% vs. 100% for poliovirus type 1 (p = 0.002)  98.1% vs. 100% for poliovirus type 2 (not significant)  93% vs. 99.3% for poliovirus type 3 (p = 0.006)  Reference - N Engl J Med 2013 Jan 31;368(5):416  DynaMed Commentary -- while statistically lower immune response for poliovirus type 3, the clinical difference may not be significant and may be useful for resource limited areas  IPV associated with similar and high seroconversion rate in type 2 poliovirus and significantly lower titers when administered as fractional dose compared to full dose (level 3 [lacking direct] evidence)  based on randomized trial without clinical outcomes  400 infants in Oman randomized at birth to IPV fractional dose (0.1 mL, one-fifth of full dose) intradermally vs. full dose intramuscularly at age 2, 4, and 6 months  seroconversion at 7 months comparing IPV in fractional dose vs. full dose  97.3% vs. 100% for type 1 poliovirus (not significant)  95.7% vs. 100% for type 2 poliovirus (p = 0.01)  97.9% vs. 100% for type 3 poliovirus (not significant)  median titers lower with fractional dose vs. full dose (p < 0.001 for all poliovirus serotypes)  type 1 poliovirus excreted at 7 months in 74.8% with fractional dose vs. 63.1% with full dose (p = 0.03)  42 hospitalizations reported (not significant between groups)  Reference - N Engl J Med 2010 Jun 24;362(25):2351, editorial can be found in N Engl J Med 2010 Jun 24;362(25):2346 oral polio vaccine (OPV) - attenuated Sabin vaccine o given routinely at ages 2, 4, 6-18 months, 4-6 years o OPV is trivalent - Types 1, 2, and 3 o produces IgA response o side effects - rarely paralysis in healthy persons, greatest risk with first dose o storage - freezer at less than 0 degrees C (32 degrees F), may be thawed and refrozen several times under specific conditions o bivalent OPV may have improved seroconversion compared to trivalent OPV and may be similar to monovalent type 1 or type 3 OPV for types 1 and 3 poliovirus (level 3 [lacking direct] evidence)  based on randomized trial without clinical outcomes  900 children randomized at birth to 1 of 5 polio vaccines given at birth and at 30 days  monovalent type 1 OPV  monovalent type 2 OPV  monovalent type 3 OPV 


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trivalent types 1, 2 and 3 OPV bivalent types 1 and 3 OPV non-inferiority defined as < 20% difference in seroconversion between bivalent OPV and types 1 and 3 OPV Cumulative 2-dose Seroconversion at 60 Days: To Poliovirus To Poliovirus To Poliovirus Vaccine Type 1 Type 2 Type 3 Monovalent type 90%* 13% 8% 1 OPV Monovalent type 17% 90% 5% 2 OPV Monovalent type 13% 13% 84%* 3 OPV Trivalent OPV 63% 91% 52% Bivalent OPV 86%* 11% 74%* Abbreviations: OPV, oral polio vaccine; NA, not applicable. * p < 0.0001 vs. trivalent OPV.

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no significant differences among treatments in adverse events Reference - Lancet 2010 Nov 13;376(9753):1682, correction can be found in Lancet 2010 Nov 13;376(9753):1646, editorial can be found in Lancet 2010 Nov 13;376(9753):1624 monovalent oral poliovirus type 1 vaccine (mOPV1) more effective than trivalent OPV in case-control studies  mOPV1 developed in 2005  mOPV1 appears more effective than trivalent OPV  based on case-control study with 2,076 cases in India  Reference - Lancet 2007 Apr 21;369(9570):1356, editorials can be found in Lancet 2007 Apr 21;369(9570):1321, 1322, correction can be found in Lancet 2007 May 26;369(9575):1790, commentary can be found in Lancet 2007 Jul 14;370(9582):129  mOPV1 appears more effective compared to trivalent OPV in Nigeria  based on case-control study  1,174 children with type 1 poliomyelitis, 502 children with type 3 poliomyelitis and matched controls were compared for number of doses of oral poliovirus vaccine (as reported by parent/guardian)  efficacy against type 1 paralytic poliomyelitis 67% with mOPV1 and 16% with trivalent oral poliovirus vaccine  estimated efficacy per dose of trivalent oral poliovirus vaccine against type 3 paralytic poliomyelitis 18%


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insufficient use of monovalent type 3 to estimate efficacy Reference - N Engl J Med 2008 Oct 16;359(16):1666, editorial can be found in N Engl J Med 2008 Oct 16;359(16):1726 mOPV1 appears more effective compared to trivalent OPV in newborns in Egypt  based on case-control study  530 newborns randomized to mOPV1 1 dose vs. trivalent oral poliovirus vaccine at birth  79% completed trial  single challenge dose of monovalent type 1 oral poliovirus vaccine given at 30 days of age  seroconversion to type 1 poliovirus was 55.4% with monovalent vaccine vs. 32.1% with trivalent vaccine (p < 0.001)  Reference - N Engl J Med 2008 Oct 16;359(16):1655, editorial can be found in N Engl J Med 2008 Oct 16;359(16):1726

advice for travelers o primary series of inactivated polio vaccine (IPV) should be given to anyone traveling to tropical or developing countries outside Western Hemisphere who have not previously been immunized o booster dose should be given if no previous booster dose o single dose of IPV or OPV recommended if protection needed within 4 weeks, OPV can rarely cause vaccine-induced polio in previously unimmunized adults o Reference - The Medical Letter 1999 Apr 23;41(1051);39, summary in Am Fam Physician 1999 Sep 15;60(4):1225 o editorial discussion regarding global eradication of polio can be found in N Engl J Med 2000 Sep 14;343(11):806

see Poliovirus Vaccine Inactivated for additional information

Measles, mumps, and rubella vaccine (MMR):   

minimum age for routine vaccination - 12 months(1) 0.5 mL subcutaneously (fatty tissue over anterolateral thigh or triceps) (3) routine vaccination(1) o give first dose at age 12-15 months o give second dose at age 4-6 years (may be given in child < 4 years old if at least 4 weeks from first dose routine vaccination if traveling internationally from United States(1) o in infants aged 6-11 months  give 1 dose before departure  revaccinate with 2 additional doses


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first dose at age 12-15 months (age 12 months if child remains in area with high disease risk)  second dose at least 4 weeks later o in children ≥ 12 months old - give 2 doses before departure, at least 4 weeks apart catch-up vaccination - ensure all school-aged children and adolescents have had 2 doses of MMR vaccine, given at least 4 weeks apart (1) ProQuad is combination vaccine with MMR vaccine and varicella virus vaccine vitamin A 100,000 units supplementation at time of 9-month measles vaccination increases protective antibody levels through age 6-8 years based on randomized trial of 462 children in Guinea-Bissau (Lancet 2002 Apr 13;359(9314):1313) see Measles, Mumps, and Rubella Vaccine for additional information

Pneumococcal vaccines (PCV13, PPSV23): 

pneumococcal vaccine o 2 commercially available formulations in United States  both vaccines contain capsular antigens extracted from Streptococcus pneumoniae  pneumococcal 13-valent conjugate vaccine (PCV13, Prevnar 13), replacing pneumococcal 7-valent conjugate vaccine (diphtheria cross-reactive material protein) (PCV7, Prevnar)  pneumococcal 23-valent polysaccharide vaccine (PPV23, Pneumovax 23) o PCV7 and PCV13 administered by intramuscular (IM) injection, PPV23 administered by intramuscular or subcutaneous injection o do not administer PCV7 and PPV23 at same time o contraindicated if hypersensitivity to any ingredient in formulation (including diphtheria toxoid for PCV7 and PCV13) o World Health Organization (WHO) considers 7-valent pneumococcal conjugate vaccine a priority for national immunization programs, especially in countries with > 50,000 child deaths per year or in which mortality among children < 5 years old is > 50 per 1,000 live births o Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunizations Practices (ACIP) recommendations  PCV13 should replace use of PCV7 (PCV7 can be used if only vaccine available until supply exhausted)  13-valent pneumococcal conjugate vaccine recommended for all children aged 2-59 months and children aged 60-71 months with medical conditions associated with increased risk of invasive pneumococcal disease or complications  4-dose series at age 2, 4, 6 and 12-15 months (same as PCV7)  complete immunization series with PCV13 in infants and children who received ≥ 1 doses of PCV7  pneumococcal vaccine recommended for cochlear implant candidates and recipients


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American Diabetes Association (ADA) recommends pneumococcal polysaccharide vaccine for all patients with diabetes ≥ 2 years old see Pneumococcal Vaccine for details

Haemophilus b conjugate vaccine (Hib):   

minimum age for first dose - 6 weeks(1) 0.5 mL intramuscularly (anterolateral thigh muscle or deltoid muscle of arm) (3) routine vaccination(1) o give Hib vaccine primary series at ages 2, 4, and 6 months (dose at 6 months not needed if PRP-OMP [PedvaxHib or Comvax] given at 2 and 4 months) o give booster dose age 12-15 months (use PRP-T [Hiberixc] for booster dose in children aged 1-4 years who received at least 1 dose of Hib) catch-up vaccination(1) o if first dose given at age 7-11 months, give second dose ≥ 4 weeks later and final dose at age 12-15 months, regardless of HiB vaccine (PRP-T or PRPOMP) used for first dose o if first 2 doses were PRP-OMP (PedvaxHi or Comvax) and were given to infant ≤ 11 months old, give third (and final) dose at age 12-15 months (at least 8 weeks after second dose) o if first dose given at age 12-24 months, give booster (as final dose) at least 8 weeks after first dose o if child ≥ 15 months not vaccinated, give 1 dose only o not routinely recommended in children > 5 years old in children ≥ 5 years old with immunocompromise, give 1 dose if unvaccinated or partially vaccinated (for example, children with leukemia, malignant neoplasms, HIV infection, anatomic or functional asplenia [including sickle cell disease])(1) see Haemophilus b Conjugate Vaccine for additional information

Varicella vaccine (VAR):   

minimum age for first dose - 12 months(1) 0.5 mL subcutaneously (fatty tissue over anterolateral thigh muscle or fatty tissue over triceps)(3) routine vaccination(1) o give first dose at age 12-15 months o give second dose at age 4-6 years  may be given to child < 40 years old if at least 3 months after first dose  second dose considered valid if given at least 4 weeks after first dose catch-up vaccination - ensure all children aged 7-18 years without evidence of immunity have 2 doses of varicella vaccine (1) o in children aged 7-12 years, 3 months is minimum interval between doses (second dose considered valid if given at least 4 weeks after first dose) o if ≥ 13 years old, 4 weeks is minimum interval between doses ProQuad is combination vaccine with VAR vaccine and measles, mumps, and rubella vaccine


see Varicella Virus Vaccine Live for additional information

Human papillomavirus vaccines (HPV): 

human papillomavirus vaccines (Gardasil, Cervarix) o quadrivalent human papillomavirus (HPV) recombinant vaccine against HPV types 6, 11, 16, and 18 (Gardasil)  Gardasil 0.5 mL intramuscular injections into deltoid or anterolateral thigh given at 0, 2, and 6 months; costs about $155 per dose or $465 for full course  approvals include  FDA approved for  females aged 9-26 years to prevent cervical cancer, vaginal and vulvar cancer, anal cancer, precancerous genital lesions, and genital warts  males aged 9-26 years to prevent anal cancer and genital warts (condyloma acuminata)  Gardasil approved by Health Canada for use in females aged 9-26 years  United Kingdom Department of Health approved routine HPV vaccination for girls aged 12-13 years with 2-year catch-up for girls up to 18 years old  European Union approved indication is prevention of premalignant genital lesions (cervical, vulvar, and vaginal), cervical cancer, and external genital warts due to HPV types 6, 11, 16, and 18; based on demonstration of efficacy in women aged 16-26 years and immunogenicity in girls aged 915 years  efficacy of quadrivalent HPV vaccine established in women aged 1526 years for reducing high-grade cervical lesions (level 3 [lacking direct] evidence) and anogenital warts (level 1 [likely reliable] evidence)  quadrivalent HPV vaccine reduces 3-year incidence of HPV 16/18-related cervical intraepithelial neoplasia grade 2 (CIN 2) and cervical intraepithelial neoplasia grade 3 (CIN 3) (level 3 [lacking direct] evidence)  NNT 125 for any high-grade cervical lesion (CIN 2, CIN 3, or adenocarcinoma in situ)  NNT 100 for high-grade cervical lesion due to HPV 16 or HPV 18  quadrivalent HPV vaccine reduces 3-year incidence of anogenital warts (level 1 [likely reliable] evidence)  NNT 53 for any external anogenital or vaginal lesion  NNT 37 for external anogenital or vaginal lesion due to HPV 6, HPV 11, HPV 16, or HPV 18  adverse effects include injection-site event (erythema, pain, pruritus, or swelling) (NNH 10) and fever (NNH 30)


quadrivalent HPV vaccine induces immunogenicity in children aged 9-15 years (level 3 [lacking direct] evidence)  quadrivalent HPV vaccine is effective in preventing cervical and external genital disease in women aged 24-45 years (level 1 [likely reliable] evidence) but may not be cost-effective  quadrivalent HPV vaccine associated with decreased genital lesions related to HPV 6 and HPV 11 in men aged 16-26 years (level 2 [midlevel] evidence) o bivalent HPV recombinant vaccine against HPV 16/18 vaccine (Cervarix)  Cervarix FDA approved for girls aged 10-25 years for prevention of cervical cancer and cervical precancer  HPV 16/18 vaccine appears to reduce incidence of CIN associated with HPV 16 or HPV 18 (level 3 [lacking direct] evidence)  HPV 16/18 vaccine does not accelerate viral clearance in patients with HPV infection (level 3 [lacking direct] evidence) o Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP), American Cancer Society (ACS), American Academy of Pediatrics (AAP), and American College of Obstetricians and Gynecologists (ACOG) recommend  for females  routine HPV vaccination for girls aged 11-12 years (can be started at age 9 years)  consideration of HPV vaccination for unvaccinated females aged 13-26 years (or those without complete series) (ACIP recommends vaccination in this population)  vaccination does not eliminate need for routine cervical cancer screening  for males  CDC/ACIP recommends  routine quadrivalent HPV vaccination for boys aged 11-12 years (can be started at 9 years)  quadrivalent HPV vaccination for unvaccinated males aged 13-21 years (or those without complete series)  consideration of quadrivalent HPV vaccination for males aged 22-26 years  ACS does not currently recommend HPV vaccination for males and ACOG makes no recommendation o pregnancy category B, recommended to delay vaccine series until after pregnancy completed o alternative HPV vaccines in development  monovalent HPV 16 L1 vaccine reduces incidence of cervical HPV 16 infection and related CIN (level 3 [lacking direct] evidence), but not commercially available o DynaMed commentary -- prevention of CIN classified as surrogate outcome (level 3 [lacking direct] evidence) see Human papillomavirus vaccine for details


Rotavirus vaccine:  

minimum for first dose - 6 weeks for both RV-1 (Rotarix) and RV-5 (RotaTeq)(1) oral dosing o 1 mL for Rotarix o 2 mL for RotaTeq routine vaccination(1) o Rotarix - give 2-dose series at age 2 and 4 months o RotaTeq - give 3-dose series at age 2, 4, and 6 months o give total of 3 doses any dose in series was RotaTeq or vaccine product unknown for any dose in series catch-up vaccination(1) o maximum age for first dose is 14 weeks, 6 days (do not give if ≥ 15 weeks old) o maximum age for final dose is 8 months, 0 days o 4 weeks is minimal interval between doses see Rotavirus Vaccine Live Oral for additional information

Influenza vaccines: 

 

minimum age(1) o 6 months for trivalent inactivated influenza vaccine o 2 years for live, attenuated influenza vaccine trivalent inactivated influenza vaccine given intramuscularly (anterolateral thigh muscle or deltoid muscle of arm)(3) o 0.25 mL in infants and children aged 6-35 months o 0.5 mL in children > 3 years old live, attenuated influenza vaccine given intranasally (0.2 mL) (3) routine vaccination(1) o give annually to all children beginning at age 6 months  in children aged 6 months to 8 years receiving influenza vaccine for first time, give 2 doses (separated by at least 4 weeks) in 2012-2013 season  in children ≥ 9 years old, give 1 dose o live, attenuated influenza vaccine or trivalent inactivated influenza vaccine can be used for most healthy, nonpregnant persons aged 2-49 years o do not give live, attenuated influenza vaccine to  children with asthma  children aged 2-4 years with wheezing in past 12 months  children with underlying medical conditions predisposing them to influenza complications  children with other contraindications to use of LAIV quadrivalent inactivated influenza vaccine (Fluzone) FDA approved for prevention of seasonal influenza in persons ≥ 6 months old (Manufacturer Press Release 2013 Jun 10) see Influenza vaccines in children for additional information


Bacille Calmette-Guérin vaccine (BCG):  

 

BCG is attenuated strain of Mycobacterium bovis BCG vaccine is controversial, and global policies and practices vary widely o 157 countries currently recommend universal BCG vaccination with 16 countries also recommending boosters o 23 countries stopped BCG vaccination or recommend selective vaccination of at-risk groups o Reference - PLoS Med 2011 Mar;8(3):e1001012 information on BCG policies and practices in > 180 countries can be found at World Atlas of BCG Policies and Practices initial immunization o efficacy of BCG vaccine varies across controlled trials, with differences in vaccine strains and study populations (Control Clin Trials 1994 Aug;15(4):247 in JAMA 2004 May 5;291(17):2086 ) o BCG vaccine may be protective against disseminated forms of tuberculosis (TB) in young children with protective estimate of  73% (range 67%-79%) against TB meningitis  77% (range 58%-87%) against miliary TB  Reference - Clin Infect Dis 2010 May 15;50 Suppl 3:S184 o vaccine efficacy in BCG trials has been high (65% to 90%) in protecting against severe disease in infants but duration of efficacy variable (0% to > 80%) in older children and adults (JAMA 2004 May 5;291(17):2127) o appears effective at preventing miliary or disseminated tuberculosis (TB) in children o need for tuberculin testing before BCG vaccination has been questioned (BMJ 2003 Aug 2;327(7409):243 ), commentary can be found in BMJ 2003 Oct 18;327(7420):932 o genetic changes in BCG cultures used for vaccine production may result in reduced immunogenicity (Proc Natl Acad Sci U S A 2007 Mar 27;104(13):5596 ) o BCG vaccination appears protective against TB infection (level 2 [midlevel] evidence)  based on observational study of 979 child household contacts of 414 adult patients with pulmonary TB in Turkey  patients tested with enzyme-linked immunosorbent spot test (ELISPOT) and tuberculin skin test (TST), patients with positive ELISPOT all considered to have TB infection  test results compared in patients with and without BCG vaccination scars  ELISPOT positive in 40% of patients with BCG vaccination vs. 53% without (p < 0.0001)  Reference - Lancet 2005 Oct 22;366(9495):1443, editorial can be found in Lancet 2005 Oct 22;366(9495):1414, commentary can be found in Lancet 2006 Feb 4;367(9508):391


o

intradermal and percutaneous BCG appear similarly effective in reducing incidence of TB in infants vaccinated at birth in South Africa (level 2 [mid-level] evidence)  based on quasi-randomized trial  11,680 newborns receiving Tokyo 172 BCG vaccine within 24 hours of birth were randomized to percutaneous route vs. intradermal route  patients followed for 2 years  no significant differences in definite, probable, or possible TB or adverse events  Reference - BMJ 2008 Nov 13;337:a2052 o BCG vaccine associated with reduced infant mortality (level 2 [midlevel] evidence)  based on prospective study of 8,752 children in West Africa  at age 6 months, mortality in vaccinated children 3.8% vs. mortality 4.9% in nonvaccinated children, mortality ratio was 0.72 (95% CI 0.54-0.96)  similar benefit also seen with measles vaccination, and authors speculate BCG and measles vaccination provide beneficial activation of immune system  Reference - BMJ 2000 Dec 9;321(7274):1435 , editorial can be found in BMJ 2000 Dec 9;321(7274):1423 , BMJ 2000 Dec 9;321(7274):1439, commentary can be found in BMJ 2001 Feb 10;322(7282):360, 361 o BCG at birth associated with reduced mortality at 4 weeks, but not at 12 months compared to later BCG among low-birth-weight (LBW) infants in West Africa (level 2 [mid-level] evidence)  based on randomized trial with high loss to follow-up  2,320 LBW infants (< 2.5 kg [5.5 lbs]) in Bissau randomized to BCG vaccination immediately after birth vs. later (current practice, median, 7.7 weeks) and were visited at home at day 3 following enrollment, and at ages 2, 6, and 12 months  follow-up at 12 months in 67%  birth weight < 1.5 kg (3.3 lbs) in 7%  mortality at 12 months (primary outcome) 8.9% with BCG at birth vs. 10.7% with BCG later (not significant)  early BCG associated with decreased mortality  at 4 weeks (mortality rate ratio 0.55, 95% CI 0.34-0.89)  at 12 months among children with birth weight < 1.5 kg (3.3 lbs) (mortality rate ratio 0.43, 95% CI 0.21-0.85)  Reference - J Infect Dis 2011 Jul;204(2):245, editorial can be found in J Infect Dis 2011 Jul;204(2):182 recommendations o Centers for Disease Control and Prevention (CDC) guidelines  consider for infant or child who has negative TST result if either of the following  continual exposure to an untreated or ineffectively treated patient with infectious pulmonary TB, and child cannot be


separated from infectious patient or given long-term primary preventive therapy  continual exposure to patient with infectious pulmonary TB caused by M. tuberculosis strains resistant to isoniazid and rifampin, and child cannot be separated from infectious patient  BCG vaccination is not recommended for children with HIV infection or adults in United States  Reference - MMWR Recomm Rep 1996 Apr 26;45(RR-4):1 duration of efficacy o BCG vaccination in infancy may induce immunologic response for at least 14 years (level 3 [lacking direct] evidence)  based on cohort study without clinical outcomes  16 adolescents who received infant BCG vaccination and 16 unvaccinated controls were tested for interferon-gamma response to Mycobacterium tuberculosis purified protein derivative (PPD)  detectable interferon-gamma response to TB PPD occurred in 13 (81%) vaccinated vs. 6 (38%) unvaccinated adolescents (p = 0.012, NNT 3)  Reference - BMC Infect Dis 2008 Jan 25;8:9 o BCG vaccine may be effective for up to 60 years (level 2 [mid-level] evidence)  based on retrospective cohort study  3,025 American Indian and Alaskan-native children aged 1 month to 20 years were alternately assigned to BCG vaccine vs. placebo as single intracutaneous dose between 1935 and 1938  exclusion criteria included reaction to high-dose (250 units) of tuberculin PPD or abnormal chest x-ray  2,792 participants (92%) were followed up with prospective case finding of TB since 1948, participants not aware of treatment assignment until follow-up from 1992 to 1998  comparing BCG vaccine vs. placebo  TB developed in 2.43% vs. 5.04% (p value not reported)  overall incidence of TB 66 vs. 138 per 100,000 person-years (estimated vaccine efficacy 52%, 95% CI 27%-69%)  possible waning of vaccine efficacy after 30 years, but not statistically significant  Reference - JAMA 2004 May 5;291(17):2086 , editorial can be found in JAMA 2004 May 5;291(17):2127 revaccination o BCG revaccination in children may not provide additional benefits (level 2 [mid-level] evidence)  based on 2 randomized trials without blinding  BCG revaccination when school-aged may not reduce incidence of TB in Brazil (level 2 [mid-level] evidence)  based on cluster-randomized trial without blinding


200,771 school-aged children at 767 schools randomized by school to BCG revaccination vs. no revaccination and followed for 4-5 years  children all had BCG vaccine as infants  crude incidence of TB 29.3 vs. 30.2 per 100,000 person-years (not significant)  Reference - Lancet 2005 Oct 8;366(9493):1290, editorial can be found in Lancet 2005 Oct 8;366(9493):1240  BCG revaccination at age 19 months does not appear to reduce mortality or hospital admission in Africa (level 2 [mid-level] evidence)  based on randomized trial without blinding  2,871 children aged 19 months in Guinea-Bissau (where most children had BCG vaccination by age 1 year) with Mantoux tuberculin test reaction < 15 mm were randomized to BCG revaccination vs. no additional vaccination and followed until aged 5 years  77 children died  trial terminated early due to increased risk of mortality with BCG vaccination in interim analysis, based on higher mortality during autumn 2003  BCG revaccination not significantly associated with overall mortality or hospital admission in final analysis  in subgroup analysis BCG vaccination associated with reduced mortality in children who previously received diphtheria-tetanus-pertussis (DTP) booster vaccination at baseline and increased mortality in children who had not received DTP booster vaccination at baseline  Reference - BMJ 2010 Mar 15;340:c671 , editorial can be found in BMJ 2010 Mar 15;340:c809 effects other than in TB o BCG vaccination may be associated with reduced risk of asthma (level 2 [mid-level] evidence)  based on systematic review limited by heterogeneity  systematic review of 17 studies evaluating association of BCG vaccination and risk of sensitization, eczema/atopic dermatitis, allergic rhinoconjunctivitis, asthma, and other allergic conditions  BCG vaccination associated with decreased risk of asthma in analysis of 12 studies, limited by heterogeneity  odds ratio (OR) 0.73 (95% CI 0.56-0.95)  NNT 27-243 assuming asthma in 9% in controls  BCG vaccination not associated with decreased risk of  sensitization to common allergens (by immunoglobulin E [IgE] or skin prick testing) in analysis of 9 studies  atopic eczema/dermatitis in analysis of 9 studies  allergic rhinoconjunctivitis in analysis of 9 studies  Reference - J Allergy Clin Immunol 2011 Jan;127(1):246


effect of prior BCG vaccination on tuberculin skin test (TST) results in children o BCG vaccination, particularly after infancy, appears associated with false positive PPDs within first 10-15 years of vaccination (level 2 [midlevel] evidence)  based on 2 systematic reviews of cohort studies  26 prospective cohort studies comparing PPD results for latent TB between patients with history of BCG vaccination and patients without  studies were excluded if they included known contacts to active TB cases  patients with BCG vaccination more likely to have indurations > 10 mm than patients without history of vaccination, 25.2% vs. 19%, in 20 trials with 49,510 patients (relative risk [RR] 2.12, 95% CI 1.5-3)  no association between history of BCG vaccination in patients with positive skin test defined as induration > 15 mm  no association between history of BCG vaccination and positive TST after 15 years  BCG associated with boosting (false positive test caused by multiple TSTs) in 17.4% vs.10.8% in 4 studies with 4,783 patients (RR 1.61, 95% CI 1.35-1.94)  Reference - Thorax 2002 Sep;57(9):804 , correction can be found in Thorax. 2003 Feb;58(2):188, commentary can be found in Thorax 2003 Apr;58(4):367  31 cohort studies with 240,203 patients  positive TSTs > 10 mm in 8.5% of patients vaccinated as infants but only 1% were positive if tested ≥ 10 years after BCG vaccination  false positive rates among BCG vaccinated patients  calculated as difference between positive rate in vaccinated patients minus rate in nonvaccinated, assuming all TSTs in nonvaccinated patients were true positive  in 12 studies with 12,728 children vaccinated after aged 12 months, 41.8% had false positive TST  43.4% of false positives were positive within 10 years of testing, and 21.2% had false positive TST ≥ 10 years later  Reference - Int J Tuberc Lung Dis 2006 Nov;10(11):1192 o BCG vaccination associated with increased risk of indurations > 10 mm from TST in children aged 1-6 years  based on cross-sectional study  1,145 children received TST  children with BCG vaccinations significantly more likely to have indurations and more likely to have larger indurations  Reference - Acta Paediatr 2002;91(2):235


o

o

BCG vaccination associated with increased size of induration from TST in children aged 7-11 years  based on cross-sectional study  970 children aged 7-11 years received TST and were evaluated based on presence of BCG scar  mean size of induration  3.7 mm in children with no BCG scar  6.5 mm in children with 1 BCG scar (p < 0.05 vs. children with no scar)  9.2 mm in children with 2 BCG scars (p < 0.05 vs. children with no scar)  Reference - Acta Paediatr 2004 Aug;93(8):1033 BCG vaccine in first month of life may not be associated with TST induration > 10 mm in children aged 3 years (level 2 [mid-level] evidence)  based on cohort study  birth cohort of 69 healthy term infants in Peru who received BCG vaccine in first month of life  80% had TST 3 years later  3 children had induration > 10 mm and all 3 had known TB contact at home  Reference - Pediatrics 2003 Oct;112(4):e298

Combination VaccinesVaccination in High-Risk Populations Preterm and low birth weight infants:  

preterm (< 37 weeks gestation) and low birth weight (< 2.5 kg) infants have increased risk of morbidity from vaccine-preventable diseases(4) hepatitis B vaccine (HepB) (4) o if born to hepatitis B surface antigen (HBsAg)-positive mother  give HepB and hepatitis B immune globulin (HBIG) within 12 hours of birth (regardless of birth weight or gestational age)  if birth weight < 2 kg, give additional 3 doses of HepB starting at age 1 month (in addition to birth dose)  screen infants for anti-HBs antibody and HBsAG after completing HepB vaccine series (age 9-15 months) o if maternal antibody to hepatitis B surface antigen (HBsAG) status unknown  if birth weight > 2 kg, can wait up to 7 days for mother's HBsAg test results before giving HBIG  if birth weight < 2 kg, give HBIG within 12 hours of birth start routine immunization schedule at age 2 months if medically stable, regardless of birth weight or gestational age(4) o diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) o Haemophilus b conjugate vaccine (Hib) o Inactivated poliovirus vaccine (IPV) o pneumococcal 13-valent conjugate vaccine (PCV13)


routine influenza vaccination starting at age 6 months (if receiving vaccine for first time, give 2 doses 1 month apart)(4)

Primary immunodeficiencies:   

  

primary immunodeficiencies associated with increased susceptibility to infection (4) safety and efficacy of vaccines in immunocompromised patients depends on degree of immunosuppression(4) inactivated vaccines generally recommended at same dose and schedule as for immunocompetent children(4) o immune response may be inadequate o higher and additional doses may be needed (especially for patients having transplant) give inactivated influenza vaccine annually to all children with primary immunodeficiences (safety and efficacy of live influenza vaccine not known) (4) safety and efficacy of rotavirus vaccine not known(4) specific primary immunodeficiencies(4) o patients with B-lymphocyte disorders  consider measles and varicella vaccines  response may be suboptimal  IV immunoglobulin may interfere with immune response  other live vaccines contraindicated (except in children with immunoglobulin A deficiency), such as  smallpox  live influenza  Bacille Calmette-Guérin vaccine (BCG)  oral typhoid  yellow fever o patients with T-lymphocyte dysfunction, all live vaccines contraindicated o patients with compromised phagocytic or complement function  live virus vaccines may be safe  give all vaccines except for live bacterial vaccines (for example BCG, oral typhoid)

Solid organ transplant recipients: 

transplant candidates and recipients have increased risk of infectious complications(4) o ensure that transplant candidates, household members, and healthcare providers have received all recommended vaccines before transplant o vaccinate transplant candidates early in course of disease (immune response to many vaccines suboptimal in organ failure) o vaccines will be more immunogenic before transplant (immunosuppressive medications after transplant can affect number and/or function of B- and Tlymphocytes guidelines for vaccination of solid organ transplant candidates and recipients (4)


o o o o

give all recommended vaccines before transplant if possible including BCG if indicated for potential high-risk exposure live attenuated influenza vaccine, smallpox, and anthrax not recommended revaccination after transplant with inactivated influenza, hepatitis A and B, DPT, inactivated polio, Hib, pneumococcal, MCV4, and HPV vaccines monitor vaccine titers after transplant for hepatitis A and B, tetanus, Hib, pneomococcus, varicella, and MMR vaccines

Children with cancer:  

immunocompromise can occur due to primary underlying malignancy or treatment with chemotherapy and/or radiation(4) in patients who have not started or not completed routine vaccination schedule at time of cancer diagnosis(4) o measles, mumps, and rubella vaccine (MMR) - if no doses given, give 2 doses at least 3 months apart when off-therapy for 6 months o varicella vaccine  in patients in continuous remission for ≥ 1 year with lymphocyte count > 700/mcL and platelet count > 100,000/mcL, give 2 doses at least 3 months apart  if patient still being treated in an endemic period, stop drug administration 1 week before and 1 week after vaccination o diphtheria, tetanus, pertussis, inactivated poliovirus, Haemophilus influenzae type b (Hib), pneumococcal, meningococcal vaccines - follow primary schedule in patients off-therapy for 3 months o inactivated influenza - give 2 doses if ever vaccinated or < 9 years old, otherwise 1 dose regardless of chemotherapy o hepatitis A - give 2 doses at least 6 months apart if epidemic risk, regardless of chemotherapy o hepatitis B - give at age 0, 1, 2-6, and 12 months if epidemic risk, regardless of chemotherapy in patients who have completed routine vaccination schedule at time of cancer diagnosis(4) o MMR - give booster dose in patients off-therapy for 6 months o varicella vaccine  in patients in continuous remission for ≥ 1 year with lymphocyte count > 700/mcL and platelet count > 100,000/mcL, give booster dose  if patient still being treated in an endemic period, stop drug administration 1 week before and 1 week after vaccination o diphtheria, tetanus, inactivated poliovirus, Hib, pneumococcal, meningococcal vaccines - give booster dose in patients off-therapy for 3 months o inactivated influenza - give booster dose regardless of chemotherapy o hepatitis A - give booster dose if epidemic risk, regardless of chemotherapy o hepatitis B - give 2 booster doses at least 3 months apart if epidemic risk, regardless of chemotherapy


o

pertussis - not known if booster needed

Hematopoetic stem cell transplant (HSCT) recipients:  

immunosuppression may occur from pretransplant conditioning and graft-versushost disease(4) suggested reimmunization schedule for HSCT recipients(4) o HLA-identical sibling, syngeneic, or autologous HSCT  inactivated influenza vaccine yearly, starting 6 months after HSCT and continue for as long as patient considered immunocompromised  DTaP, IPV, Hib-conjugate, meningococcal - give 3 doses at 1-2 month intervals, starting 12 months after HSCT  hepatitis B - give 3 doses at 0, 1, and 6 months, starting 12 months after HSCT  PCV7 - give 2 doses at 1-2 month intervals, starting 12-15 months after HSCT  MMR - give first dose 18 months after HSCT and second dose 6 months later  23-valent pneumococcal conjugate vaccine at 24 months after HSCT o any other allogeneic HSCT  DTaP, IPV, Hib-conjugate, meningococcal - give 3 doses at 1-2 month intervals, starting 18 months after HSCT  hepatitis B - give 3 doses at 0, 1, and 6 months, starting 18 months after HSCT  PCV7 - give 2 doses at 1-2 month intervals, starting 18-21 months after HSCT  MMR - give first dose 24 months after HSCT and second dose 6 months later  23-valent pneumococcal conjugate vaccine at 30 months after HSCT

Children with HIV infection:  

 

give inactivated vaccines according to routine schedule(4) in children with mild clinical disease and CD4 counts > 15%(4) o live vaccines appear safe o give MMR at age 12 months and second dose as early as 28 days after first dose o consider monovalent varicella vaccine if CD4 count > 200 (or > 15%) in 2 doses, 3 months apart in severely immunocompromised children, do not give measles vaccine (4) antiretroviral therapy reported to reduce antibody protection to MMR and varicella vaccines in previously immunized children with HIV-1 infection (level 3 [lacking direct] evidence) o based on case series o 59 children with HIV-1 infection preimmunized with MMR and varicella vaccines before starting highly active antiretroviral therapy (HAART) were evaluated


o

24 children (43%) had specific antibodies against all 3 MMR components at baseline o among children who were seropositive at baseline  14 of 35 (40%) lost antibodies against measles  11 of 29 (38%) lost antibodies against mumps  5 of 45 (11%) lost antibodies against rubella  7 of 34 (21%) lost antibodies against varicella o Reference - Pediatrics 2006 Aug;118(2):e315 consider repeating childhood immunizations for children with HIV infection after successful treatment with combination antiretroviral therapy, reimmunization improved seroconversion rates in retrospective study of 19 children (Pediatrics 2003 Jun;111(6):e641 ) review of efficacy of HiB conjugate vaccines in children with HIV infection can be found in Vaccine 2010 Feb 17;28(7):1677

Children on systemic corticosteroids:  

immunosupression related to systemic steroids, underlying disease, other treatments, and frequency and route of steroid therapy(4) in children receiving high-dose prednisone (> 2 mg/kg or > 20 mg/day)(4) o if treatment > 14 days, delay giving live-virus vaccines until at least 1 month after discontinuation of steroid therapy o if treatment < 14 days, consider giving live-virus vaccines immediately after discontinuation of steroid therapy, or delaying for 2 weeks

Children with asplenia and hyposplenia:  

follow routine schedule for immunizations(4) considerations for pneumococcal and meningococcal vaccines (4) o pneumococcal conjugate and/or polysaccharide vaccine indicated for all children with asplenia at the recommended age  polysaccharide vaccine (PPSV23)  should only be given to children > 2 years old with functional asplenia, at least 8 weeks after previous conjugate vaccine dose  give booster dose 5 years after first dose of PPSV23  consider reimmunization in children with asplenia who received conjugate and/or polysaccharide vaccine before age 24 months (choice of vaccine used for reimmunization depends on patient's age and which vaccine was given previously)  single dose of PCV13 or PPSV23 acceptable for children > 5 years old not previously immunized o tetravalent conjugate meningococcal vaccine indicated for all children with asplenia from age 9 months through adolescence  give booster at 5 years if ≥ 7 years old when previously vaccinated  give booster at 3 years if aged 9 months to 6 years when previously vaccinated


 continue to revaccinate at 5-year intervals if at increased risk vaccination schedule should be complete at least 2 weeks before elective splenectomy(4)

Children with rheumatologic and inflammatory bowel diseases: 

children with rheumatologic disease have increased risk of infection due to use of immunosuppressant drugs and aberrant immunity(4) o follow routine schedule for immunizations o pneumococcal and influenza vaccines strongly recommended considerations for patients with juvenile idiopathic arthritis or inflammatory bowel disease o consider giving vaccines early (for example, adolescent dTap) o if varicella history or serology negative, give varicella vaccine 4-6 weeks before starting immunosuppressive agents, including biologic therapies o check hepatitis B serology to assure protective levels o Reference - Expert Rev Vaccines 2011 Feb;10(2):175

Internationally adopted children:  

no clear consensus about optimal strategy to ensure complete immunization of all international adoptees(4) strategies from American Academy of Pediatrics, Infectious Disease Society of America, and Advisory Committee on Immunization Practices include (4) o accept all appropriate preadoption records of immunization o measure serum antibodies against vaccine-preventable pathogens for which reliable testing is available and if present accept all corresponding preadoption immunization records o measure serum antibodies against vaccine-preventable pathogens for which reliable testing is available and if positive consider child to have received 1 immunization in series o accept no preadoption records of immunization and immunize all adoptees with age-appropriate vaccinations

Vaccination Techniques 

subcutaneous injections(3) o 23-25 gauge needle o needle length 5/8 inch (16 mm) o injection site  age 1-12 months - fatty tissue over anterolateral thigh muscle  > 12 months old - fatty tissue over anterolateral thigh muscle or fatty tissue over triceps o administer at 45 degree angle to skin intramuscular injections(3) o 22-25 gauge needle


Injection Site and Needle Length for Intramuscular Injections: Age Needle Length Injection Site ≤ 28 days old 5/8 inch (16 mm)* Anterolateral thigh muscle 1-12 months 1 inch (25 mm) Anterolateral thigh muscle 1-1 1/4 inch (25-32 mm) Anterolateral thigh muscle or deltoid 1-2 years muscle of arm 5/8-1 inch (16-25 mm)* 5/8-1 inch (16-25 mm)* Deltoid muscle of arm or anterolateral 3-18 years 1-1 1/4 inch (25-32 thigh muscle mm) * 5/8 inch needle may be used for patients weighing < 130 lbs (60 kg) for intramuscular injection in deltoid muscle only if skin is stretched tight, subcutaneous tissue is not bunched, and injection is made at a 90-degree angle.

o administer at 90 degree angle to skin injection method or site o World Health Organization technique appears to be optimal method for anterolateral thigh intramuscular injection in children (grade B recommendation [inconsistent or limited evidence]) based on 1 randomized trial showing reduced irritability (level 1 [likely reliable] evidence)  375 children receiving vaccines at age 2-18 months were randomized to anterolateral thigh intramuscular injection using Australian vs. WHO vs. United States technique by solo practitioner  Australian technique is needle inserted at junction of upper and middle thirds of vastus lateralis with needle angled 45-60 degrees from skin and pointing towards knee; using 23 gauge, 25 mm long needle  WHO technique is needle inserted into anterolateral thigh at 90 degrees to long axis of femur with skin compressed between index finger and thumb; using 25 gauge, 16 mm long needled  United States technique is needled inserted in upper lateral quadrant at 45 degrees to long axis of femur and posteriorly at 45 degrees to table top with infant supine, thigh muscle bunched at injection site; using 23 gauge, 25 mm long needle  InfanrixHepB (diphtheria, tetanus, acellular pertussis, hepatitis B) given at ages 2, 4 and 6 months, Infanrix (diphtheria, tetanus, acellular pertussis) given at age 18 months, Pedvax (Haemophilus influenzae type b conjugate vaccine) given at age 2 and 4 months, oral polio vaccine given at ages 2, 4 and 6 months


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361 (96%) children assessed by blinded observer (practice nurse) at 24 hours after vaccination, 14 dropouts did not have adverse effects based on telephone follow-up  WHO technique associated with significantly lower rates of irritability and possibly bruising  irritability reported in 30% following WHO technique vs. 45.5% following Australian technique vs. 49.2% following United States technique (p = 0.0039, NNT 6-7)  no significant differences in rates of perceived fever (3.3% to 7.5%), persistent crying/screaming (8.3% to 12.5%), drowsiness (4.2% to 5%) or vomiting/poor feeding (8.3% to 10.7%)  bruising with acellular pertussis vaccine reported in 0.8% with WHO technique vs. 2.5% with Australian technique vs. 6.7% with United States technique (NNT 17 comparing WHO vs. United States technique)  no significant differences in bruising with Pedvax  Reference - Med J Aust 2005 Jul 18;183(2):60 DTap vaccine in arm associated with increased risk of medically attended local site reactions in children aged 12-35 months (level 2 [midlevel] evidence)  based on retrospective cohort study  1.4 million children aged 1-6 years received 6 million vaccine injections and were assessed for medically attended local reactions  analyses included intramuscular vaccines commonly administered alone (inactivated influenza, hepatitis A, and diphtheria-tetanusacellular pertussis [DTaP])  DTaP vaccine  rate of local reactions higher  compared to thigh, arm injection associated with higher risk of medically attended local reactions in children aged 12-35 months (relative risk 1.88, 95% CI 1.34-2.65)  inactivated influenza and hepatitis A vaccines  medically attended local reactions relatively uncommon  no significant difference in risk of local reaction comparing arm vs. thigh injections  Reference - Pediatrics 2013 Feb;131(2):283 intramuscular and subcutaneous injection associated with comparable immunogenicity and tolerability for M-M-RvaxPro and VARIVAX vaccines (level 2 [mid-level] evidence)  based on randomized trial without blinding  752 patients aged 12-18 months were randomized to measles, mumps and rubella vaccine (M-M-RvaxPro) administered intramuscularly (IM) with varicella vaccine (VARIVAX) by same route at separate injection sites vs. M-M-RvaxPro and VARIVAX administered subcutaneously (SC) and followed for 42 days


antibody response rates at 42 days post vaccination for children initially seronegative to measles, mumps, rubella or varicella similar in both groups  adverse events 0-4 days similar in both groups  Reference - BMC Med 2009 Apr 14;7:16 needle length and gauge o 25 mm (1 inch) needle reduces local reaction rate compared with 16 mm (5/8 inch) needle in infants  based on 2 randomized trials and 1 prospective cohort study  long needles have less reactogenicity than short needles with comparable immunogenicity in infants receiving intramuscular injection to anterolateral thigh  696 healthy term infants receiving vaccines at ages 2, 3 and 4 months were randomized to wide, long (23 gauge, 25 mm) vs. narrow, short (25 gauge, 16 mm) vs. narrow, long (25 gauge, 25 mm) needles and assessed at 6 hours,1, 2 and 3 days  combined DPT/HiB (ACT-HiB DTP) given intramuscularly in right anterolateral thigh  meningococcal C vaccine (Meningitec or Menjugate) given intramuscularly in left anterolateral thigh  86 infants (12%) dropped out, of whom 11 dropped out due to large local reaction (10 in narrow, short group)  rates of local reactions  decreased over time following vaccine  reduced with narrow, long needles compared to narrow, short needles (significant for days 1-3 after all 3 doses, NNH 6 for first dose and 8 for second and third doses)  reduced with narrow, long needles compared to wide, long needles (significant only on day 1 after third dose)  reaction rates to meningococcal vaccine were lower and not statistically significant  no significant differences in immunogenicity measured 28-42 days after third vaccine dose for needle any needle size  Reference - BMJ 2006 Sep 16;333(7568):571 , editorial can be found in BMJ 2006 Sep 16;333(7568):563, commentary can be found in Am Fam Physician 2007 Jan 1;75(1):109 and in Evid Based Med 2007 Apr;12(2):41  23 gauge, 25 mm (1 inch) needle associated with less local reactions than 25 gauge, 16 mm (5/8 inch) hub needle  119 infants 4 months old randomized to DPT/HiB immunization in anterolateral thigh using 23 gauge 25 mm blue hub vs. 25 gauge 16 mm orange hub needles with local reactions recorded by parents for 3 days


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any local reaction with 23 gauge, 25 mm needles 62% vs. 84% with 25 gauge, 16 mm needles (p = 0.009, NNH 5)  redness and swelling were each significantly reduced with 25 mm needle at 6 hours, 1, 2 and 3 days (NNT 3-5)  Reference - BMJ 2000 Oct 14;321(7266):931, commentary can be found in BMJ 2001 Feb 10;322(7282):364, commentary can be found in BMJ 2001 Feb 24;322(7284):492, commentary including that study used DTP vaccine which has been replaced with less reactogenic DTaP in many countries can be found in ACP J Club 2001 Jul-Aug;135(1):29, editorial suggesting that different patients may require different needle sizes to ensure intramuscular injections (although most of discussion relates to adults) (BMJ 2000 Nov 18;321(7271):1237 )  Dynamed commentary -- unclear if injections were subcutaneous or intramuscular which could affect the reactions  25 mm (1 inch) length needle associated with fewer local reactions than 16 mm needle in arm vaccinations for fifth diphtheria-tetanus-acellular pertussis vaccination (level 2 [midlevel] evidence)  based on prospective cohort study  1,315 children aged 4-6 years receiving diphtheria-tetanusacellular pertussis (DTaP) vaccine with either 25 mm length needle or 16 mm needle were assessed for adverse events for 7 days post-vaccination  11% vaccinated in thigh (65% with 25 mm, 35% with 16 mm)  89% vaccinated in arm (67.5% with 25 mm, 32.5% with 16 mm)  comparing vaccination in arm with 25 mm needle vs. 16 mm needle  ≥ 5 cm redness at local site in 38% vs. 47% (p = 0.003, NNH 11)  redness persisting on day 2 in 52% vs. 63% (p < 0.001, NNH 9)  swelling in 55% vs. 67% (p < 0.001, NNH 8)  thigh vaccination showed nonsignificant reduction for ≥ 10 cm redness at local site for 25 mm needles  Reference - Pediatrics 2008 Mar;121(3):e646 body weight might predict optimal needle length for intramuscular injection in adolescents (level 3 [lacking direct] evidence)  based on cohort study without clinical outcomes  141 children aged 11-15 years had ultrasound of deltoid muscle and underlying bone during flattening or bunching of site  optimal needle length defined as  ≥ skin-to-muscle depth plus 5 mm (1/5 inch)


 < skin-to-bone depth optimal needle length by ultrasound significantly correlated with  weight  body mass index  arm circumference  correlation between optimal needle length and weight was  16 mm (5/8 inch) in children < 60 kg (132 lbs)  25 mm (1 inch) in children 60-70 kg (132-154 lbs)  Reference - Pediatrics 2009 Aug;124(2):667 Centers for Disease Control and Prevention, American Academy of Family Physicians and American Academy of Pediatrics recommend observing patients for adverse reactions for 15-20 minutes after immunization (grade C recommendation [lacking direct evidence]) (Arch Pediatr Adolesc Med 2005 Nov;159(11):1083) aspiration prior to intramuscular injection may increase pain (level 2 [midlevel] evidence) o based on randomized trial o 113 infants ages 4-6 months receiving primary intramuscular DPTaP-HiB vaccination were randomized to aspiration vs. no aspiration before injection o comparing aspiration vs. no aspiration  crying in 82.5% vs. 42.9% (p < 0.001, NNH 2)  median time required for vaccination 8.8 vs. 0.9 seconds (p < 0.001)  median pain score on visual analog scale (0-10) by pediatrician 2.8 vs. 1.4 (p < 0.001) o Reference - Arch Dis Child 2007 Dec;92(12):1105 , commentary can be found in Arch Dis Child 2008 May;93(5):449 Priorix vaccine may be less painful than M-M-R II vaccine (level 2 [mid-level] evidence) o based on small randomized trial o 49 infants aged 12 months receiving first MMR vaccine randomized to Priorix vs. M-M-R II o pain response quantified at baseline and within 15 seconds of vaccination by visual analog scale (VAS) of 0-100 done by parent and pediatrician, and Modified Behavioral Pain Scale of 0-10 by coder blinded to vaccine allocation o comparing pain scores after immunization with Priorix vs M-M-R II  parent VAS 22 vs. 53 (p = 0.007)  pediatrician VAS 15 vs. 58 (p = 0.001)  Modified Behavioral Pain Scale 6 vs. 8 (p = 0.02) o Reference - Arch Pediatr Adolesc Med 2004 Apr;158(4):323, editorial can be found in Arch Pediatr Adolesc Med 2004 Apr;158(4):311 methods to reduce immunization pain o breastfeeding reduces crying during immunization injections (level 1 [likely reliable] evidence)  based on randomized trial  66 healthy infants having second, third or fourth-month immunization with intramuscular diphtheria, tetanus and pertussis 


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randomized to breastfeeding before, during and after injection vs. no breastfeeding  mean crying time was 36 seconds with breastfeeding vs. 76 seconds with control (p = 0.001)  heart rate and oxygen saturation levels similar in both groups  Reference - Appl Nurs Res 2007 Feb;20(1):10 administering DPTaP-HiB before PCV may reduce immunization pain in infants (level 2 [mid-level] evidence)  based on randomized trial with allocation concealment not stated  120 infants aged 2-6 months having routine DPTaP-HiB and PCV immunizations were randomized to DPTaP first vs. PCV first and assessed for pain response  administering DPTaP first associated with  reduced pain scores reported by blinded investigator assessing via videotape (p = 0.037)  reduced pain reported by parent (p = 0.003)  Reference - Arch Pediatr Adolesc Med 2009 May;163(5):469 analgesics  acetaminophen may reduce post-vaccination fussiness and fever in infants (level 2 [mid-level] evidence)  based on randomized trial with allocation concealment not stated  374 infants aged 6 weeks to 9 months having routine vaccinations (2-6 per infant) randomized to post-vaccine acetaminophen 10-15 mg/kg orally vs. placebo  comparing acetaminophen vs. placebo  unusually high infant fussiness in 10% vs. 24% (p = 0.001, NNT 8)  fever ≥ 38 degrees C (100.4 degrees F) within 32 hours postvaccination in  14% vs. 22% overall (p = 0.053)  13% vs. 25% in prespecified subgroup analysis of infants ≥ 24 weeks old (p = 0.03, NNT 9)  no significant difference between groups in parent time lost from work, parent sleep, or infant sleep  Reference - PLoS One 2011;6(6):e20102 PDF oral sweeteners plus human contact  combination of skin-to-skin contact and oral dextrose associated with reduced pain during immunization in neonates (level 2 [mid-level] evidence)  based on randomized trial with incomplete blinding  640 term neonates randomized to intramuscular hepatitis B injection with 1 of  sterile water 1 mL orally 2 minutes before injection, infant in crib with no contact from 2 minutes before until 2 minutes after injection (no analgesia)


25% dextrose 1 mL orally 2 minutes before injection, no contact until 2 minutes after injection  skin-to-skin contact from 2 minutes before until 2 minutes after injection  combination of dextrose 1 mL orally 2 minutes before injection and skin-to-skin contact with mother from 2 minutes before until 2 minutes after injection  investigators not blinded to skin-to-skin contact during outcome assessment  pain reduction at injection  associated with combination dextrose and skin-to-skin contact (p < 0.001)  no significant differences between dextrose alone, skin contact alone or no analgesia  pain reduction after injection associated with  any intervention compared to no analgesia (p < 0.001)  combination therapy compared to dextrose alone or skin contact alone (p < 0.001)  skin-to-skin contact alone compared to dextrose alone (p = 0.045)  Reference - Pediatrics 2009 Dec;124(6):e1101, commentary can be found in Pediatrics 2010 Mar;125(3):e709 "5 S's" physical intervention after immunization in young infants may reduce pain compared with oral sucrose or water (level 2 [mid-level] evidence)  based on randomized trial with incomplete blinding  230 infants aged 2 months (170 infants) and 4 months (60 infants) randomized during well-child visit involving routine immunization to 1 of 4 interventions  2 mL water 2 minutes prior to immunization then subsequent comfort by parent or guardian (control)  2 mL 24% oral sucrose 2 minutes prior to immunization then subsequent comfort by parent or guardian (sucrose)  2 mL water 2 minutes prior to immunization then subsequent physical intervention by pediatric resident (swaddling, side-stomach position, shushing, swinging, and sucking [5S's])  2 mL 24% oral sucrose prior to immunization then subsequent physical intervention with 5S's by pediatric resident (5S's and sucrose)  pain score based on quality of cry, facial grimace and body movement, and assessed every 15 seconds for 2 minutes, then every 30 seconds for 5 minutes postvaccination  5S's (without sucrose) associated with decreased pain score vs. control or sucrose (p < 0.05 for both)  no significance differences in pain


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with 5S's alone compared to 5S's and sucrose with any intervention in subgroup analysis of 4month-old infants  Reference - Pediatrics 2012 May;129(5):815  combination of oral sucrose, oral tactile stimulation and being held by parents reduces crying duration in infants receiving 2month-old immunizations (level 2 [mid-level] evidence)  based on randomized trial with incomplete blinding  116 infants receiving 4 injections (DTaP, IPV, HiB/HBV, and Prevnar) randomized to sucrose and oral tactile stimulation (with pacifier or bottle) plus being held by their parents during immunization vs. no interventions  median first cry duration 19 seconds vs. 58 seconds (p = 0.002)  Reference - Arch Pediatr Adolesc Med 2003 Nov;157(11):1115 oral sweetener  25% oral glucose reduces pain and crying time in healthy infants having 2-month immunizations (level 1 [likely reliable] evidence)  based on randomized trial  120 healthy term infants (median age 2.2 months) having routine 2-month immunizations were randomized to glucose 25% solution 2 mL orally vs. sterile water control immediately before receiving immunizations by 2 consecutive intramuscular injections  pain measured on Modified Behavioural Pain Scale (0-10 scale of 3 observable behaviors of facial expression, crying, and body movements with higher score indicating greater pain)  comparing glucose vs. control  median pain score during immunization 8 vs. 9 (p = 0.005)  median pain score for 10 seconds immediately following second injection 4 vs. 6 (p < 0.001)  mean time crying of 38 seconds vs. 77.9 seconds (p < 0.001)  Reference - Int J Nurs Stud 2012 Mar;49(3):249  sweet-tasting solutions may reduce duration of crying time and pain in healthy infants having needle-related procedures (level 2 [mid-level] evidence)  based on Cochrane review limited by clinical heterogeneity  systematic review of 14 randomized trials evaluating sweettasting solutions to reduce needle-related procedural pain in 1,551 healthy infants aged 1-12 months  treatment type, strength, volume, method and timing of administration varied considerably between studies precluding meta-analysis for most comparisons


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all included trials evaluated infants receiving routine immunizations, trials involving circumcision, lumbar puncture or suprapubic bladder aspiration were excluded  compared to placebo, sweet-tasting solutions associated with reduced  duration of total crying for  30%-75% concentration solutions (-7.7 seconds, 95% CI -11.4 to -3.9 seconds) in analysis of 4 trials with 523 infants  12%-25% concentration solutions (-34.7 seconds, 95% CI -41.9 to -27.5 seconds) in analysis of 3 trials with 267 infants  both analyses had significant heterogeneity  score on validated pain scale in 6 of 7 trials  no significant difference in total crying time or pain score comparing lidocaine-prilocain cream vs. 12% sucrose in 1 trial with 27 infants  no clinically significant adverse events reported  Reference - Cochrane Database Syst Rev 2012 Dec 12;(12):CD008411  sweet tasting oral solutions may reduce pain in infants (level 2 [mid-level] evidence)  based on systematic review without evaluation of trial quality  systematic review of 125 studies evaluating effects of oral sweet solution for pain control in infants  sweet solution more effective than placebo or no treatment in 103 of 111 studies (93%) with this comparison  Reference - Pediatrics 2010 Nov;126(5):894  administration of oral sucrose solution may be associated with quicker return to near normal state and modest reduction of pain (level 2 [mid-level] evidence)  based on randomized trial with small sample size  pain response measured with University of Wisconsin Children's Hospital Pain Scale  Reference - Pediatrics 2008 Feb;121(2):e327, commentary can be found in Pediatrics 2008 Jun;121(6):1294  review of sucrose for procedural pain management in infants can be found in Pediatrics 2012 Nov;130(5):918 topical anesthetics  vapocoolant spray and EMLA cream may be equally effective in reducing immunization pain in study of 62 children given DTaP (Pediatrics 1997 Dec;100(6):e5 )  EMLA cream reduced pain in infants aged 6 months but not in infants aged 2-4 months in randomized placebo-controlled trial of 165 infants who had patched applied 1-3 hours before vaccination; EMLA did not affect antibody titers at 7 months of age; cost, inconvenience and limited benefit make EMLA inappropriate for


widespread use before vaccinations (Pediatr Infect Dis J 2002 May;21(5):399 in J Watch Online 2002 Jun 14)  amethocaine 4% gel (Ametop) applied 30 minutes before MMR vaccine may reduce pain in randomized placebo-controlled trial of 120 infants (Pediatrics 2004 Dec;114(6):e720 ); amethocaine gel (Ametop) available in Australia, Canada, New Zealand and United Kingdom (Pediatric Notes 2005 Feb 3;29(5):17)  combination EMLA cream 1 hour prior and 1 mL of glucose 300 mg/mL (16.65 mmol/L) instilled on tongue 2 minutes before injection reduced pain compared to double placebo in randomized trial of 90 infants age 3 months given DPT (Pain 2003 Jul;104(12):381 in JAMA 2003 Sep 24;290(12):1557) o behavioral interventions  distraction and possibly other cognitive-behavioral interventions may reduce pain and distress in children and adolescents (level 2 [mid-level] evidence)  based on Cochrane review of mostly lower-quality evidence  Reference - Cochrane Database Syst Rev 2006 Oct 18;(4):CD005179  combination of visual distraction, focusing task and verbal suggestion appears to reduce discomfort associated with immunizations in children (level 2 [mid-level] evidence)  based on small randomized trial  41 children aged 4-6 years receiving 3 prekindergarten immunizations randomized to distraction intervention vs. routine administration  intervention included  verbal suggestions of decreased sensation  plastic multipronged arm gripper  vibrating instrument moving along contralateral arm  topical ethyl chloride spray  intervention associated with reduced pain and discomfort by  patient self-report (p < 0.0013)  parent report (p < 0.0002)  clinical observation score (p < 0.0001)  Reference - Pediatrics 2009 Aug;124(2):e203 o review of pain reduction during pediatric immunizations can be found in Pediatrics 2007 May;119(5):e1184 effect of antipyretics and analgesics on vaccine reactions o paracetamol (acetaminophen) at time of vaccination associated with reduced fever but also reduced vaccine response in infants (level 3 [lacking direct] evidence)  based on 2 randomized trials without clinical outcomes  459 healthy infants 9-16 weeks old randomized to prophylactic paracetamol (acetaminophen) every 6-8 hours as suppository vs. no prophylactic paracetamol after each vaccination (primary and booster vaccines implemented as separate consecutive trials)


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paracetamol at primary vaccination was 80 mg for infants weighing 4.5 to < 7 kg (9 lb 14 oz- < 15 lb 7 oz), and 125 mg for infants ≥ 7 kg (15 lb 7 oz) (in 3 doses within first 24 hours)  paracetamol at booster vaccination was 125 mg (3 doses within first 24 hours for infants 7 kg to < 9 kg [15 lb 7 oz to 19 lb 13 oz] and 4 doses within 24 hours for infants ≥ 9 kg [19 lbs 13 oz])  primary vaccination with 10-valent pneumococcal nontypeable H. influenzae protein D-conjugate vaccine (PHiDCV) co-administered with hexavalent diphtheria-tetanus-3component acellular pertussis-hepatitis B-inactivated poliovirus types 1, 2, and 3-H influenzae type b (DTPa-HBVIPV/ HiB) and oral human rotavirus vaccines  booster dose of PHiD-CV plus DTPa-HBV-IPV/HiB administered at age 12-15 months  comparing paracetamol vs. no paracetamol  fever > 39.5 degrees C (103.1 degrees F) in 0.4% vs. 1.3% (not significant)  fever ≥ 38 degrees C (100.4 degrees F) after primary vaccination in 42% vs. 66% (p < 0.05, NNT 5)  fever ≥ 38 degrees C (100.4 degrees F) after booster in 36% vs. 58% (p < 0.05, NNT 5)  antibody geometric mean concentrations significantly lower with prophylactic paracetamol after primary vaccination for all 10 pneumococcal vaccine serotypes, protein D, antipolyribosyl-ribitol phosphate, antidiphtheria, antitetanus, and antipertactin  after boosting, lower antibody geometric mean concentrations persisted for antitetanus, protein D, and all pneumococcal serotypes (other than 19F)  swelling and redness uncommon in both groups, but reduced with paracetamol  Reference - Lancet 2009 Oct 17;374(9698):1339, editorial can be found in Lancet 2009 Oct 17;374(9698):1305 prophylactic acetaminophen or ibuprofen do not prevent local reactions following fifth DTaP vaccination (level 1 [likely reliable] evidence)  based on randomized trial  372 children aged 4-6 years randomized to 1 of 3 interventions 2 hours before to 30 minutes after DTaP vaccine, followed by 2 doses at 6-12 hour intervals  acetaminophen 15 mg/kg (maximum dose 450 mg)  ibuprofen 10 mg/kg (maximum dose 300 mg)  placebo  no significant difference in local reactions among groups  Reference - Pediatrics 2006 Mar;117(3):620

breastfeeding after immunization associated with decreased fever in infants


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based on prospective cohort study 460 infants scheduled for first or second dose of hexavalent combination vaccine monitored for degree of breastfeeding and fever for 3 days postvaccination fever reported in 172 infants (p < 0.01 for trend)  25% of exclusively breastfed infants  31% of partially breastfed infants  53% of infants with no breastfeeding Reference - Pediatrics 2010 Jun;125(6):e1448

Contraindications and Adverse Effects Contraindications:    

contraindications to vaccination are uncommon all vaccines have contraindication of history of severe allergic reaction to previous vaccine or vaccine constituent live vaccines (varicella, MMR, herpes zoster) are contraindicated in pregnant women and severely immunocompromised patients Reference - J Fam Pract 2005 Jul;54(7):621, MMWR Morb Mortal Wkly Rep 2007 Oct 19;55(41):Q1

Adverse effects: 

childhood immunizations not associated with increased risk of atopic diseases o pertussis vaccine may not affect incidence of childhood or adolescent asthma (level 2 [mid-level] evidence)  based on systematic review of observational studies  systematic review of 7 studies evaluating incidence of asthma in 186,663 patients receiving whole-cell pertussis vaccine  no significant association between pertussis vaccine and incidence of asthma during childhood and adolescence  Reference - Pediatrics 2007 Nov;120(5):e1269 o infant vaccinations do not appear to cause allergic disease  based on systematic review  systematic review of studies correlating vaccination with diphtheria, pertussis, tetanus (DPT), measles, mumps, rubella (MMR), and/or Bacillus Calmette-Guérin (BCG) vaccine and development of allergic disease  no evidence of increased risk of developing allergic disease  Reference - Vaccine 2004 Sep 3;22(25-26):3375, commentary can be found in Vaccine 2005 Feb 10;23(12):1427, Vaccine 2005 Jun 10;23(30):3875 o delay in DPT immunization associated with reduced risk of childhood asthma (level 2 [mid-level] evidence)  based on retrospective cohort study


11,531 children from birth to 7 years old receiving at least 4 doses of DPT evaluated for association between timing of immunizations and development of asthma  reduced risk of asthma in children with delays in all 3 doses (odds ratio 0.39, 95% CI 0.18-0.86)  Reference - J Allergy Clin Immunol 2008 Mar;121(3):626 , commentary can be found in J Allergy Clin Immunol 2008 Sep;122(3):656 o standard vaccination schedule does not appear to affect risk of eczema or recurrent wheeze (level 2 [mid-level] evidence)  based on prospective birth cohort study  2,764 families with infants were followed for 1 year comparing receipt of standard schedule of immunizations to incidence of eczema or recurrent wheeze  at 6 months old 77% had been completely vaccinated, 15% incompletely vaccinated, and 7% never vaccinated  no differences in 1-year rates of eczema or recurrent wheeze among groups  Reference - Pediatrics 2007 Feb;119(2):e367 childhood immunizations not associated with increased risk of neuropsychological deficits o thimerosal exposure from vaccinations associated with few significant differences in neuropsychological outcome in later childhood (level 2 [mid-level] evidence)  based on cohort study  1,403 children who received high vs. low dose thimerosal during routine vaccinations tested for 24 neuropsychological outcomes 10 years after vaccination  high dose defined as cumulative ethylmercury intake 137.5 mcg  low dose defined as cumulative ethylmercury intake 62.5 mcg  in girls only, high dose associated with small but statistically significant decrease in mean scores of  finger-tapping with dominant hand (p < 0.05)  object naming from line drawings (p < 0.05)  no other significant differences in neuropsychological performance associated with level of exposure  Reference - Pediatrics 2009 Feb;123(2):475 o early thimerosal exposure NOT associated with neuropsychological deficits at age 7-10 years (level 2 [mid-level] evidence)  based on cohort study  1,047 children aged 7-10 years tested for 42 neuropsychological outcomes  exposure to mercury (from thimerosal) during prenatal period, neonatal period, and first 7 months of life not associated with consistent effects


few significant differences were mixed (some positive, some negative)  Reference - N Engl J Med 2007 Sep 27;357(13):1281, editorials can be found in N Engl J Med 2007 Sep 27;357(13):1275, N Engl J Med 2007 Sep 27;357(13):1278, commentary can be found in N Engl J Med 2008 Jan 3;358(1):93 o full schedule vaccines in first year of life not associated with neuropsychological deficits at 7-10 years  based on cohort study  1,047 children with thimerosal vaccine in first year of life assessed for neuropsychological outcomes at age 7-10 years  491 children met full immunization schedule in first year, 235 met all immunizations but not on time, 311 did not receive all vaccines  full on-schedule immunizations associated with significantly better performance on speed naming test and intelligence performance IQ scale  children with untimely immunization had no significantly better outcomes  Reference - Pediatrics 2010 Jun;125(6):1134 childhood immunizations not associated with increased risk of other infections o recent immunization not associated with increased risk of serious bacterial infection in febrile infants (level 2 [mid-level] evidence)  based on retrospective cohort study  1,978 infants aged 6-12 weeks presenting to pediatric emergency department with fever ≥ 38 degrees C (100.4 degrees F)  213 infants had received immunization ≤ 72 hours preceding emergency department visit  prevalence of serious bacterial infection 2.8% in recently immunized infants vs. 7% in non-immunized infants (relative risk 0.41, 95% CI 0.19-0.9)  all serious bacterial infections in recently immunized infants were urinary tract infections  Reference - Acad Emerg Med 2009 Dec;16(12):1284 o vaccination not associated with increase in risk of hospitalization for non-targeted infectious diseases (level 2 [mid-level] evidence)  based on prospective cohort study in Denmark  805,206 children aged 1 month to 4 years were evaluated for type and number of vaccine doses received and hospitalization with infectious diseases  84,317 hospitalizations for non-targeted infectious disease identified during 2,900,463 person-years of follow-up  no adverse associations between an increasing number of vaccinations and infectious diseases  Reference - JAMA 2005 Aug 10;294(6):699, commentary can be found in Am Fam Physician 2005 Dec 1;72(11):2322 no evidence of increased risk of encephalopathy after measles or pertussis vaccination


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based on case-control study 452 children ≤ 6 years old hospitalized with encephalopathy or related conditions evaluated for vaccination with DTP or MMR 90 days before disease onset and compared to up to 3 matched controls o no significant difference in recent vaccination between groups o Reference - Pediatr Infect Dis J 2006 Sep;25(9):768 immune thrombocytopenic purpura (ITP) o MMR, hepatitis A, varicella, and DaPT associated with increased incidence of ITP (level 2 [mid-level] evidence)  based on retrospective cohort study  1,800,000 children aged 6 weeks to 17 years who received 15,000,000 vaccine doses from 2000 to 2009  197 confirmed cases of ITP  incident rate ratio of acute onset of ITP comparing children during immunization exposure (1-42 days) vs. unexposed periods  MMR vaccine at age 12-19 months (incidence rate ratio [IRR] 5.48, 95% CI 1.61-18.64) based on 6 vaccine-exposed cases  hepatitis A vaccine at age 7-17 years (IRR 23.14, 95% CI 3.59-149.3) based on 2 vaccine-exposed cases  varicella vaccine at age 11-17 years (IRR 12.14, 95% CI 1.1133.96) based on 1 vaccine-exposed case  DaPT vaccine at age 11-17 years (IRR 20.29, 95% CI 3.12131.83) based on 2 vaccine-exposed cases  most ITP was acute and mild with no serious long-term sequelae  Reference - Pediatrics 2012 Feb;129(2):248 o MMR vaccine given in second year of life may be associated with increased risk of ITP  based on retrospective cohort study  records of 1,036,689 children aged 1-18 receiving 1,107,814 measles-mumps-rubella vaccinations from1991 to 2000 were assessed  259 confirmed patients with immune thrombocytopenia purpura  incident rate ratio of acute onset of immune thrombocytopenic purpura comparing children during MMR-exposed vs. MMRunexposed periods  3.94 (95% CI 2.01-7.69) for age 12-23 months  7.10 (95% CI 2.03-25.03) for age 12-15 months  14.59 (95% CI 1.84-114.43) for boys age 12-15 months  3.22 (95% CI 0.59-17.64) for girls age 12-15 months  Reference - Pediatrics 2008 Mar;121(3):e687 , editorial can be found in Pediatrics 2008 Mar;121(3):625 fever, diarrhea and rash appear common after first MMR vaccine but not after second dose (level 2 [mid-level] evidence) o based on prospective cohort study o 1,800 children had rates of fever, diarrhea, and rash recorded during 2 weeks before and 2 weeks after MMR


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first MMR in 535 toddlers aged 12-24 months second MMR in 633 kindergarteners aged 4-6 years second MMR in 632 middle schoolers aged 10-12 years effect on fever, diarrhea and rash  estimated net 18% of toddlers had MMR vaccine-associated events (NNH 6)  median onset 5-10 days postvaccination  duration 2-5 days  no increases for kindergarteners middle schoolers Reference - Pediatrics 2006 Oct;118(4):1422

apnea o

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DTaP at age 2 months in neonatal intensive care unit may not be associated with increased risk of apnea or bradycardia in infants born preterm (level 2 [mid-level] evidence)  based on randomized trial with high dropout rate  242 preterm infants in neonatal intensive care unit (NICU) aged 5660 days were randomized to receive DTaP vs. no DTaP and assessed for apnea and bradycardia for 2 pretreatment days and 2 posttreatment days  79.6% included in analysis  no significant difference between groups in frequency or severity of apnea or bradycardia  Reference - Pediatrics 2008 May;121(5):e1085, commentary can be found in J Pediatr 2008 Nov;153(5):726 preimmunization apnea, Score for Neonatal Acute Physiology> 10, weight < 2,000 g, and age < 67 days may be associated with postimmunization apnea in infants in NICU  based on retrospective cohort study  497 infants (mean corrected gestational age 36.8 weeks) with minimum hospital stay of 53 days receiving ≥ 1 vaccine analyzed for risk factors of post-vaccine apnea  risk factors included  preimmunization apnea (strongest predictor for postimmunization apnea)  Score for Neonatal Acute Physiology (SNAP-II) > 10  weight < 2,000 g  age < 67 days  Reference - Pediatrics 2008 Mar;121(3):463 DTP-IPV-HiB vaccine in very preterm infants associated with increased rate of apnea, bradycardia and desaturations in subsequent 72 hours  based on cohort study  124 very preterm infants (≤ 32 weeks gestational age) immunized with DTP-IPV-HiB vaccine were compared to 124 gestational agematched unimmunized infants  resurgence of or increased rate of apnea, bradycardia, and desaturations 72 hours post-immunization 45.1% in immunized


infants vs. 29% in unimmunized infants (adjusted odds ratio 2.41, 95% CI 1.29-4.51)  no significant difference in increased risk of cardiorespiratory events between whole cell or acellular pertussis vaccine  Reference - BMC Pediatr 2006 Jun 19;6:20 case report of post-vaccination acute myopericarditis in adolescent can be found in Pediatrics 2007 Jun;119(6):e1400

Quality Improvement Compliance: 

11.5% of parents reported to refuse ≥ 1 immunization for their child or children o based on cross-sectional study o nationally representative sample of 2,521 parents of children ≤ 17 years old were surveyed about attitudes regarding vaccines in 2009 o 1,552 parents (62%) responded to survey o among 11.5% refused at least 1 vaccine overall  56.4% refused HPV vaccine  32.3% refused varicella vaccine  31.8% refused meningococcal conjugate vaccine  17.7% refused MMR vaccine o common reasons for refusal included  risk for adverse effects  children at low risk for disease  read or heard about problems with vaccine  not enough research  would rather have child get disease  vaccine not on market long enough  vaccine not effective o Reference - Pediatrics 2010 Apr;125(4):654 patient reminder/recall systems in primary care settings may be effective at improving immunization rates (level 2 [mid-level] evidence) o based on Cochrane review of trials with methodologic limitations o systematic review of 44 randomized trials and 3 controlled before-and-after trials o methodologic limitations included  allocation concealment not stated  no blinding of outcome assessors  reliability of primary outcome not documented o reminders effective for childhood vaccinations, childhood influenza vaccinations, and adult pneumococcus, tetanus, hepatitis B and influenza vaccinations o reminders not effective in 1 new study of adolescent immunizations in urban setting


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all types of reminders were effective, telephone reminders most effective but also most expensive Reference - Cochrane Database Syst Rev 2008 Oct 8;(4):CD003941, commentary on earlier version can be found in ACP J Club 2003 JulAug;139(1):18

reminder postcards followed by increasing intensity of case management for delayed or delinquent preventive care increases immunization rates and receipt of recommended well-child care by age 15 months (level 1 [likely reliable] evidence) o based on randomized trial o 811 neonates born in urban hospital randomized to 3-step intervention vs. control and were followed through age 15 months o intervention included  language appropriate reminder postcard for every well-child visit  telephone reminder, postcard, telephone recall for missed immunization or well-child visit  intensive case management and home visitation for delinquent immunizations or well-child care o comparing intervention vs. control at age 15 months  immunizations up to date in 44% vs. 33% (p < 0.01, NNT 9)  time without immunizations up to date 109 vs. 192 days (p < 0.01)  ≥ 5 well-child visits completed in 65% vs. 47% (p < 0.01, NNT 6) o monthly cost per child for intervention $23.30 o Reference - Pediatrics 2009 Aug;124(2):455

lay health workers may be useful in increasing proportion of children with up to date immunization schedules (level 3 [lacking direct] evidence) o based on Cochrane review with post hoc analysis without clinical outcomes o systematic review included 8 randomized trials comparing lay health worker interventions to promote immunization uptake with usual care o in post hoc analysis limited to pediatric trials, strategies involving lay health workers associated with increased immunization uptake in children (risk ratio 1.22, 95% CI 1.1-1.37), but results limited by significant heterogeneity (p = 0.07) o Reference - Cochrane Database Syst Rev 2010 Mar 17;(3):CD004015 patient-held vaccination records associated with increased immunization rates in young children (level 2 [mid-level] evidence) o based on retrospective cohort study o nationally representative survey of > 5 million children aged 19-35 months during 2004-2006 in United States o vaccinations up to date in 83.9% with vs. 78.6% without patient-held records (p < 0.001) o greater benefit for children with multiple providers, low maternal education, and ≥ 4 children in household o Reference - Pediatrics 2010 Mar;125(3):e467


Physician Quality Reporting System Quality Measures: 

240. Childhood Immunization Status o The percentage of children two years of age who had four diphtheria tetanus and acellular pertussis (DTaP), three polio (IPV), one measles mumps rubella (MMR), three H influenza type B (HiB), three hepatitis B (Hep B), one chicken pox (VZV), four pneumococcal conjugate (PCV), two hepatitis A (Hep A), two or three rotavirus (RV), and two influenza (flu) vaccines by their second birthday

see Physician Quality Reporting System Quality Measures for additional information

Guidelines and Resources Guidelines: Pediatric: 

general immunization or vaccination schedules o Advisory Committee on Immunization Practices (ACIP) recommended immunization schedule for persons aged 0 through 18 years can be found in MMWR Surveill Summ. 2013 Feb 1;62(1):2-8 PDF or at National Guideline Clearinghouse 2013 Apr 1:39538, or at CDC 2013 Jan 29, previous version can be found in MMWR Morb Mortal Wkly Rep 2012 Feb 10;61(5):1 or in Pediatrics 2012 Feb;129(2):385 o American College of Preventive Medicine practice policy statement on childhood immunizations can be found in Am J Prev Med 2003 Aug;25(2):169 o National Vaccine Advisory Committee standards on child and adolescent immunization practices can be found in Pediatrics 2003 Oct;112(4):958 , correction can be found in Pediatrics 2004 Jan;113(1):184 o American Academy of Pediatrics (AAP)  AAP clinical report on reaffirmation: responding to parents who refuse immunization for their children can be found in Pediatrics 2013 May;131(5):e1696  AAP recommendation on childhood and adolescent immunization schedule in United States can be found in Pediatrics 2013 Feb;131(2):397  AAP recommendations on immunization of premature and low birth weight infants can be found in Pediatrics 2003 Jul;112(1):193  AAP recommendations on immunizations for Native American (American Indian/Alaskan Native) children include (in addition to general immunization guidelines) use of PRP-OMP Haemophilus conjugate vaccine for first dose of HiB series, hepatitis A vaccine at age 2 years, and single dose of pneumococcal 23-valent polysaccharide vaccine at age 2 years in areas with increased risk of


invasive pneumococcal disease (Pediatrics 1999 Sep;104(3 Pt 1):564 )  AAP policy statement on increasing immunization coverage can be found in Pediatrics 2010 Jun;125(6):1295 o Public Health Agency of Canada immunization guide can be found at Public Health Agency of Canada o Spanish Association of Pediatrics (Asociacion Espanola de Pediatría [AEP]) 2012 recommendations on pediatric vaccination schedule can be found in An Pediatr (Barc) 2012 Jan;76(1):43.e1 o Spanish Society of Paediatric Infectious Diseases/Spanish Paediatrics Association (Sociedad Española de Enfermedades Infecciosas Pediátricas/Asociacion Espanola de Pediatría [SEIP/AEP]) consensus document on vaccination in immunocompromised children can be found in An Pediatr (Barc) 2011 Dec;75(6):413.e1 [Spanish] o French (Groupe Avancees Vaccinales) update in vaccinations can be found in Med Mal Infect 2009 Apr;39(4):212 [French] o expert consensus update on vaccination guideline for allergic children can be found in Expert Rev Vaccines 2009 Nov;8(11):1541 specific vaccinations o Paediatric European Network for Treatment of AIDS Vaccines Group (PENTA), PENTA Steering Committee/Children's HIV Association (CHIVA) guidance on vaccination of HIV-infected children in Europe can be found in HIV Med 2012 Jul;13(6):333-6; e1 o Cincinnati Children's Hospital Medical Center (CCHMC) Best evidence statement (BESt) on improving pneumococcal and influenza vaccination rates in children with sickle cell disease can be found at National Guideline Clearinghouse 2011 Oct 3:33273 o Advisory Committee on Immunization Practices (ACIP) of CDC recommendations for prevention of hepatitis A through active or passive immunization can be found in MMWR Recomm Rep 2006 May 19;55(RR7):1 , summary can be found in Am Fam Physician 2006 Jun 15;73(12):2233, summary of previous version can be found in Am Fam Physician 2000 Apr 1;61(7):2246 o American Academy of Pediatrics (AAP) policy statement on recommendations for influenza immunization of children can be found in Pediatrics 2008 Nov;122(5):1135 or at National Guideline Clearinghouse 2009 May 18:13435, correction can be found in Pediatrics 2009 Jan;123(1):197 o American Academy of Pediatrics (AAP) meningococcal conjugate vaccines policy update: booster dose recommendations can be found in Pediatrics 2011 Dec;128(6):1213 o American Cancer Society guideline on HPV vaccine use to prevent cervical cancer and its precursors can be found in CA Cancer J Clin 2007 JanFeb;57(1):7, commentary can be found in Am Fam Physician 2008 Mar 15;77(6):852 o German evidenced-based guideline for prophylactic vaccination against HPV-associated neoplasia can be found in Vaccine 2009 Jul 23;27(34):4551


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British recommendations for prevention of secondary Haemophilius influenzae type b (HiB) disease can be found in J Infect 2009 Jan;58(1):3 Pediatric Infectious Diseases Society position statement regarding personal belief exemption from immunization mandates can be found at PIDS 2011 Mar PDF National Association of School Nurses (NASN) position statement on immunizations can be found in NASN Sch Nurse 2011 Mar;26(2):121 European League Against Rheumatism (EULAR) recommendation on vaccination in paediatric patients with rheumatic diseases can be found in Ann Rheum Dis 2011 Oct;70(10):1704

Other: 

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World Health Organization (WHO) Strategic Advisory Group of Experts (SAGE) recommendations on immunization can be found at WHO 2012 May 25 PDF, endorsed by American Academy of Pediatrics (AAP) Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) general recommendations on immunizations can be found in MMWR Recomm Rep 2011 Jan 28;60(2):1 or at National Guideline Clearinghouse 2011 Jun 13:25633, correction can be found in MMWR Morb Mortal Wkly Rep 2011 Jul 29;60(29):993 CDC guidelines for maintaining vaccine cold chain can be found in MMWR Morb Mortal Wkly Rep 2003 Oct 24;52(42):1023 CDC provider resources for vaccine conversations with parents (including information on vaccination refusal) can be found at CDC Institute for Clinical Systems Improvement (ICSI) guideline on immunizations can be found at ICSI 2013 Jan PDF, previous version can be found at ICSI 2012 Mar PDF or at National Guideline Clearinghouse 2012 Aug 6:36813 American College of Obstetricians and Gynecologists (ACOG) o ACOG Committee Opinion 558 on integrating immunizations into practice can be found in Obstet Gynecol 2013 Apr;121(4):897 o ACOG Committee Opinion 534 on well-woman visit can be found in Obstet Gynecol 2012 Aug;120(2 Pt 1):421, commentary can be found in ACOG News Release 2012 Jul 23 Indonesian Society of Medical Gerontology national consensus guideline on geriatric immunization can be found in Acta Med Indones 2012 Jan;44(1):78 PDF Surgical Infection Society guidelines on vaccination after traumatic injury can be found in Surg Infect (Larchmt) 2006 Jun;7(3):275 Infectious Diseases Society of America (IDSA) clinical practice guideline on immunization programs for infants, children, adolescents, and adults can be found in Clin Infect Dis 2009 Sep 15;49(6):817 or at National Guideline Clearinghouse 2010 June 7:15442 American College Health Association (ACHA) recommendations for institutional prematriculation immunizations can be found in J Am Coll Health 2011 Apr;59(5):450 American Academy of Pediatrics statement on


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increasing immunization coverage can be found in Pediatrics 2010 Jun;125(6):1295 immunization information systems can be found in Pediatrics 2006 Sep;118(3):1293 full text, reaffirmed 2011 Oct responding to parental refusals of immunization of children can be found in Pediatrics 2005 May;115(5):1428, reaffirmed 2013 April

American Academy of Pediatrics (AAP) HPV vaccine recommendations can be found at Pediatrics 2012 Mar;129(3):602

Brighton Collaboration Methods Working Group guideline on collection, analysis and presentation of vaccine safety in surveillance systems can be found in Vaccine 2009 Apr 6;27(16):2289 Joint Task Force on practice parameters for allergy and immunology on adverse reactions to vaccines can be found in Ann Allergy Asthma Immunol 2009 Oct;103(4 Suppl 2):S1

British Committee for Standards in Haematology (BCSH) guideline on prevention and treatment of infection in patients with absent or dysfunctional spleen can be found in Br J Haematol 2011 Nov;155(3):308

Working Party on Infection Prevention in Hyposplenia and Asplenia (De Werkgroep voor Infectiepreventie bij Hyposplenia en Asplenia) guideline on prevention of severe infections in patients with hyposplenism or asplenia can be found in Ned Tijdschr Geneeskd 2012;156(44):A4857 [Dutch]

expert consensus on immunization of patients with chronic disease can be found in Rev Med Suisse 2010 Apr 21;6(245):798 [French]

Argentinian expert guideline on vaccines in primary immunodeficiencies patients can be found in Arch Argent Pediatr 2010 Oct;108(5):454 [Spanish]

American Diabetes Association (ADA) position statement on standards of medical care in diabetes can be found in Diabetes Care 2013 Jan;36 Suppl 1:S11 , executive summary can be found in Diabetes Care 2013 Jan;36 Suppl 1:S4

Review articles:    

see also Immunization Action Coalition News Releases review of vaccination in children can be found in Acta Paediatr 2010 Sep;99(9):1287 review of update on childhood and adolescent vaccines can be found in Mayo Clin Proc 2009 May;84(5):457 review of update on immunizations in children and adolescents can be found in Am Fam Physician 2008 Jun 1;77(11):1561


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review of randomized trials evaluating nonspecific effects of vaccines on mortality in children in low-income countries can be found in Pediatr Infect Dis J 2010 May;29(5):457 review of immunization of premature and low birth-weight infants cane be found in Paediatr Drugs 2007;9(1):17 review of immunizations for patients with metabolic disorders can be found in Pediatrics 2006 Aug;118(2):e460, editorial can be found in Pediatrics 2006 Aug;118(2):810 review of booster vaccinations can be found in Pediatrics 2009 Dec;124(6):1633 review of vaccine administration and efficient office practice can be found in Fam Pract Manag 2007 Mar;14(3):48 review of vaccine adverse events can be found in Am Fam Physician 2002 Dec 1;66(11):2113 review of vaccine safety can be found in JAMA 2002 Dec 25;288(24):3155 critique of alternative vaccination schedules and decision of parents to refuse some or all of standard vaccinations can be found in Pediatrics 2009 Jan;123(1):e164 review of vaccine refusal, mandatory immunization, and risks of vaccinepreventable diseases can be found in N Engl J Med 2009 May 7;360(19):1981, commentary can be found in N Engl J Med 2009 Aug 13;361(7):723 review of health maintenance in school-aged children: history, physical examination, screening, and immunizations can be found in Am Fam Physician 2011 Mar 15;83(6):683 review of health maintenance in school-aged children: counseling recommendations can be found in Am Fam Physician 2011 Mar 15;83(6):689 review of infant protection by maternal vaccination can be found in Clin Microbiol Infect 2012 Oct;18 Suppl 5:85 review of sucrose for procedural pain management in infants can be found in Pediatrics 2012 Nov;130(5):918

MEDLINE search: 

to search MEDLINE for (Immunizations in infants and children) with targeted search (Clinical Queries), click therapy, diagnosis or prognosis


Immunizations in children and adolescents