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Childhood Vaccines DTaP, Polio, HiB, Hep B, Prevnar Continuity Clinic Lecture July 9, 2009 Objectives: Brief review of diseases Individual and combination vaccines Vaccine Schedules Side Effects and Contraindications Diphtheria Greek diphthera (leather hide) Recognized by Hippocrates in 5th century BCE Epidemics described in 6th century C. diphtheriae described by Klebs in 1883 Toxoid developed in 1920s Corynebacterium diphtheriae Aerobic gram-positive bacillus Toxin production occurs only when C. diphtheriae infected by virus (phage) carrying tox gene If isolated, must be distinguished from normal diphtheroid Diphtheria Clinical Features Incubation period 2-5 days (range, 1-10 days) May involve any mucous membrane Classified based on site of infection anterior nasal pharyngeal and tonsillar laryngeal cutaneous ocular genital Pharyngeal and Tonsillar Diphtheria Insidious onset of exudative pharyngitis Exudate spreads within 2-3 days and may form adherent membrane Membrane may cause respiratory obstruction Fever usually not high but patient appears toxic Diphtheria Complications Most attributable to toxin Severity generally related to extent of local disease Most common complications are myocarditis and neuritis Death occurs in 5%-10% for respiratory disease Diphtheria Antitoxin Produced in horses First used in the U.S. in 1891 Used only for treatment of diphtheria Neutralizes only unbound toxin Diphtheria Epidemiology Reservoir Human carriers Usually asymptomatic Transmission Temporal pattern Winter and spring Communicability Up to several weeks without antibiotics Respiratory Skin and fomites rarely Cases Diphtheria - United States, 19402007 20000 18000 16000 14000 12000 10000 8000 6000 4000 2000 0 1940 1950 1960 1970 Year 1980 1990 2000 Diphtheria - United States, 19802007 6 5 Cases 4 3 2 1 0 1980 1985 1990 1995 Year 2000 2005 Diphtheria – United States, 1980-2004 Age Distribution of Reported Cases 25 Cases 20 15 10 5 0 <5 N=53 5-14 15-24 25-39 Age group (yrs) 40-64 65+ Routine DTaP Primary Vaccination Schedule Dose Primary 1 Primary 2 Primary 3 Primary 4 Age Interval 2 months --4 months 4 wks 6 months 4 wks 15-18 months 6 mos Routine DTaP Schedule for Children Younger Than 7 Years of Age Booster Doses 4 through 6 years of age, before entering school 11 or 12 years of age if 5 years since last dose (Tdap) Every 10 years thereafter (Td) Diphtheria and Tetanus Toxoids Adverse Reactions Local reactions (erythema, induration) Exaggerated local reactions (Arthustype) Fever and systemic symptoms not common Severe systemic reactions rare Diphtheria and Tetanus Toxoids Contraindications and Precautions Severe allergic reaction to vaccine component or following a prior dose Moderate or severe acute illness Tetanus First described by Hippocrates Etiology discovered in 1884 by Carle and Rattone Passive immunization used for treatment and prophylaxis during World War I Tetanus toxoid first widely used during World War II Clostridium tetani Anaerobic gram-positive, sporeforming bacteria Spores found in soil, animal feces; may persist for months to years Multiple toxins produced with growth of bacteria Tetanospasmin estimated human lethal dose = 2.5 ng/kg Tetanus Pathogenesis Anaerobic conditions allow germination of spores and production of toxins Toxin binds in central nervous system Interferes with neurotransmitter release to block inhibitor impulses Leads to unopposed muscle contraction and spasm Tetanus Clinical Features Incubation period; 8 days (range, 3-21 days) Three clinical forms: local (not common), cephalic (rare), generalized (most common) Generalized tetanus: descending symptoms of trismus (lockjaw), difficulty swallowing, muscle rigidity, spasms Spasms continue for 3-4 weeks Complete recovery may take months Neonatal Tetanus Generalized tetanus in newborn infant Infant born without protective passive immunity Estimated more than 250,000 deaths worldwide in 2000-2003* *www.who.int/immunization_monitoring/diseases/neonatal_tetanus/en/index.html Tetanus Complications Laryngospasm Fractures Hypertension Nosocomial infections Pulmonary embolism Aspiration pneumonia Death Tetanus Epidemiology Reservoir Soil and intestine of animals and humans Transmission Contaminated wounds Tissue injury Temporal pattern Peak in summer or wet season Communicability Not contagious Tetanus—United States, 1947-2007 700 600 Cases 500 400 300 200 100 0 1950 1960 *2005 provisional total 1970 Year 1980 1990 2000 Cases Tetanus—United States, 1980-2007 100 90 80 70 60 50 40 30 20 10 0 1980 1985 *2005 provisional total 1990 1995 Year 2000 Tetanus Toxoid Formalin-inactivated tetanus toxin Schedule Three or four doses + booster Booster every 10 years Efficacy Approximately 100% Duration Approximately 10 years Should be administered with diphtheria toxoid as DTaP, DT, Td, or Tdap Pertussis Highly contagious respiratory infection caused by Bordetella pertussis Outbreaks first described in 16th century Bordetella pertussis isolated in 1906 Estimated 294,000 deaths worldwide in 2002 Bordetella pertussis Fastidious gram-negative bacteria Antigenic and biologically active components: pertussis toxin (PT) filamentous hemagglutinin (FHA) agglutinogens adenylate cyclase pertactin tracheal cytotoxin Pertussis Pathogenesis Primarily a toxin-mediated disease Bacteria attach to cilia of respiratory epithelial cells Inflammation occurs which interferes with clearance of pulmonary secretions Pertussis Clinical Features Incubation period 5-10 days (range 4-21 days) Insidious onset, similar to minor upper respiratory infection with nonspecific cough Fever usually minimal throughout course of illness Pertussis Clinical Features Catarrhal stage 1-2 weeks Paroxysmal cough stage 1-6 weeks Convalescence Weeks to months Pertussis Among Adolescents and Adults Disease often milder than in infants and children Infection may be asymptomatic, or may present as classic pertussis Persons with mild disease may transmit the infection Older persons often source of infection for children Pertussis Deaths in the United States, 2004-2006 Age at onset 2004 <3 mos >3 mos Total 2005 24 3 27 32 7 39 13 3 16 69 13 82 (84%) (16%) 2006 Total CDC, unpublished data, 2007 Pertussis Complications by Age* Pneumonia Hospitalization 70 60 Percent 50 40 30 20 10 0 <6 m 6-11 m 1-4 y 5-9 y 10-19 y Age group *Cases reported to CDC 1997-2000 (N=28,187) 20+ y Pertussis—United States, 1940-2007 250000 Cases 200000 150000 100000 50000 0 1940 1950 1960 1970 Year 1980 1990 2000 Pertussis—United States, 1980-2007 30000 25000 Cases 20000 15000 10000 5000 0 1980 1985 1990 1995 Year 2000 2005 Reported Pertussis by Age Group, 1990-2007 <11 11-18 >18 30000 Cases 25000 20000 15000 10000 5000 0 1990 1995 2000 Year 2005 Whole-Cell Pertussis Vaccine Developed in mid-1930s and combined as DTP in mid-1940s 70%-90% efficacy after 3 doses Protection for 5-10 years Local adverse reactions common Pertussis-containing Vaccines DTaP (pediatric) approved for children 6 weeks through 6 years (to age 7 years) Tdap (adolescent and adult) approved for persons 10 through 64 years (Boostrix) and 11 through 64 years (Adacel) DTaP Fourth Dose Recommended at 15-18 months* May be given at 12 months of age if: child is 12 months of age, and 6 months since DTaP 3rd dose, and unlikely to return at 15-18 months *15-20 months for Daptacel School Entry (Fifth) Dose Fifth dose recommended when 4th dose given before age 4 years All DTaP vaccines are licensed for 5th dose after DTaP series Interchangeability of Different Brands of DTaP Vaccine Whenever feasible, the same DTaP vaccine should be used for all doses of the series Limited data suggest that “mix and match” DTaP schedules do not adversely affect safety and immunogenicity If vaccine used for earlier doses is not known or not available, any brand may be used to complete the series Pediarix DTaP – Hep B – IPV combination Minimum age 6 weeks Approved for 3 doses at 2, 4 and 6 months Not approved for booster doses Licensed for children 6 weeks to 7 years of age Pediarix May be used interchangeably with other pertussis-containing vaccines if necessary Can be given at 2, 4, and 6 months in infants who received a birth dose of hepatitis B vaccine (total of 4 doses) May be used in infants whose mothers are HBsAg positive or ACIP recommendation status *off-label unknown* www.cdc.gov/vaccines/programs/vfc/downloads/resolutions/1003hepb.pdf Pentacel Vaccine Contains lyophilized Hib (ActHIB) vaccine that is reconstituted with a liquid DTaP-IPV solution Approved for doses 1 through 4 among children 6 weeks through 4 years of age The DTaP-IPV solution should not be used separately (i.e., only use to reconstitute the Hib component) DTaP Adverse Reactions Local reactions 20%-40% (pain, redness, swelling) Temp of 101oF 3%-5% or higher More severe adverse reactions not common Local reactions more common following 4th and 5th doses Adverse Reactions Following the 4th and 5th DTaP Dose Local adverse reactions and fever increased with 4th and 5th doses of DTaP Reports of swelling of entire limb Extensive swelling after 4th dose NOT a contraindication to 5th dose Adverse Reactions Reported Following 1st and 4th Doses of Infanrix Infanrix1 40 Infanrix4 35 35 Percent 30 26 26 25 20 15 10 5 4 6 2 0 Swelling Pain Symptom or sign Source: Infanrix package insert, 2003 Temp >101.4F DTaP Contraindications Severe allergic reaction to vaccine component or following a prior dose Encephalopathy not due to another identifiable cause occurring within 7 days after vaccination DTaP Precautions* Moderate or severe acute illness Temperature >105°F (40.5°C) or higher within 48 hours with no other identifiable cause Collapse or shock-like state (hypotonic hyporesponsive episode) within 48 hours Persistent, inconsolable crying lasting >3 hours, occurring within 48 hours Convulsions with or without fever occurring within 3 days *may consider use in outbreaks Haemophilus influenzae type b Severe bacterial infection, particularly among infants During late 19th century believed to cause influenza Immunology and microbiology clarified in 1930s Haemophilus influenzae Aerobic gram-negative bacteria Polysaccharide capsule Six different serotypes (a-f) of polysaccharide capsule 95% of invasive disease caused by type b Haemophilus influenzae type b Pathogenesis Organism colonizes nasopharynx In some persons organism invades bloodstream and cause infection at distant site Antecedent upper respiratory tract infection may be a contributing factor Haemophilus influenzae type b Clinical Features* Epiglottitis 17% Meningitis 50% Pneumonia 15% Osteomyelitis 2% Arthritis 8% Cellulitis 6% Bacteremia 2% *prevaccination era Haemophilus influenzae type b Epidemiology Reservoir carriers Human Asymptomatic Transmission Respiratory droplets Temporal pattern Peaks in Sept-Dec and March-May Communicability Generally limited but higher in some circumstances Incidence*of Invasive Hib Disease, 1990-2007 25 Incidence 20 15 10 5 0 1990 1992 1994 1996 1998 Year 2000 2002 *Rate per 100,000 child *Rate per 100,000 children <5 years of age 2004 2005 Incidence Haemophilus influenzae type b, 1986 Incidence* by Age Group 200 180 160 140 120 100 80 60 40 20 0 0-1 12-13 24-25 36-37 Age group (mos) *Rate per 100,000 population, prevaccine era 48-49 60 Haemophilus influenzae type b—United States, 2002-2006 Incidence has fallen more than 99% since prevaccine era 123 confirmed Hib cases reported (average of 25 cases per year) Most recent cases in unvaccinated or incompletely vaccinated children Haemophilus influenzae type b Conjugate Vaccines Two conjugate vaccines licensed for use in infants as young as 6 weeks of age Use different carrier proteins 3 doses of any combination confers protection Conjugate Hib Vaccines* PRP-T ActHIB, TriHIBit, Pentacel PRP-OMP PedvaxHIB, Comvax *HbOC (HibTiter) no longer available in the United States Haemophilus influenzae type b Vaccine Routine Schedule Vaccine 2 mo 4 mo PRP-T x x PRP-OMP x x 6 mo 12-18 mo x x x Haemophilus influenzae type b Vaccine Recommended interval 8 weeks for primary series doses Minimum interval 4 weeks for primary series doses Vaccination at younger than 6 weeks of age may induce immunologic tolerance to Hib antigen Minimum age 6 weeks Haemophilus influenzae type b Vaccine Interchangeability Both conjugate Hib vaccines (except TriHIBit) are interchangeable for primary series and booster dose 3 dose primary series if more than one brand of vaccine used Haemophilus influenzae type b Vaccine Delayed Vaccination Schedule Unvaccinated children 7 months of age or older may not need entire 3 or 4 dose series Number of doses child requires depends on current age All children 15-59 months of age need at least 1 dose TriHIBit ActHIB reconstituted with Tripedia Not approved for the primary series at 2, 4, or 6 months of age Approved for the fourth dose of the DTaP and Hib series only Primary series Hib doses given as TriHIBit should be disregarded TriHIBit • • May be used as the booster dose of the Hib series at 12 months of age or older following any Hib vaccine series* Should not be used if child has receive no prior Hib doses *booster dose should follow prior dose by at least 2 months COMVAX Hepatitis B-Hib combination Use when either antigen is indicated Cannot use before 6 weeks of age May be used in infants whose mothers are HBsAg positive or status is unknown Comvax Minimum Intervals Package insert implies 8 to 11month interval between doses 2 and 3 This applies only if dose 2 given at 4 months of age Minimum interval if not on schedule is TWO months (minimum age 12 months) Haemophilus influenzae type b Vaccine Adverse Reactions Swelling, redness, or pain in 5%30% of recipients Systemic reactions infrequent Serious adverse reactions rare Haemophilus influenzae type b Vaccine Contraindications and Precautions Severe allergic reaction to vaccine component or following a prior dose Moderate or severe acute illness Age less than 6 weeks Poliomyelitis First described by Michael Underwood in 1789 First outbreak described in U.S. in 1843 21,000 paralytic cases reported in the U. S. in 1952 Global eradication in near future Poliovirus Enterovirus (RNA) Three serotypes: 1, 2, 3 Minimal heterotypic immunity between serotypes Rapidly inactivated by heat, formaldehyde, chlorine, ultraviolet light Most poliovirus infections are asymptomatic Poliomyelitis Pathogenesis Entry into mouth Replication in pharynx, GI tract, local lymphatics Hematologic spread to lymphatics and central nervous system Viral spread along nerve fibers Destruction of motor neurons Outcomes of Poliovirus Infection Asymptomatic Aseptic menigitis 0 20 Minor non-CNS illness Paralytic 40 60 Percent 80 100 Poliovirus Epidemiology Reservoir Transmission Communicability onset Human Fecal-oral Oral-oral possible 7-10 days before Virus present in stool 3-6 weeks Poliomyelitis—United States, 1950-2007 25000 Inactivated vaccine Cases 20000 15000 10000 Live oral vaccine Last indigenous case 5000 0 1950 1960 1970 1980 1990 2000 Poliomyelitis—United States, 1980-2007 14 VAPP 12 Imported Cases 10 8 6 4 2 * 0 1980 1985 1990 1995 2000 *Vaccine-acquired paralytic polio (VAPP) in a U.S. resident acquired outside the U.S. 2005 Poliovirus Vaccine 1955 Inactivated vaccine 1961 Types 1 and 2 monovalent OPV 1962 Type 3 monovalent OPV 1963 Trivalent OPV 1987 Enhanced-potency IPV (IPV) Inactivated Polio Vaccine (IPV) Contains 3 serotypes of vaccine virus Grown on monkey kidney (Vero) cells Inactivated with formaldehyde Contains 2-phenoxyethanol, neomycin, streptomycin, polymyxin B Oral Polio Vaccine (OPV) Contains 3 serotypes of vaccine virus Grown on monkey kidney (Vero) cells Contains neomycin and streptomycin Shed in stool for up to 6 weeks following vaccination Inactivated Polio Vaccine Highly effective in producing immunity to poliovirus >90% immune after 2 doses >99% immune after 3 doses Duration of immunity not known with certainty Oral Polio Vaccine Highly effective in producing immunity to poliovirus 50% immune after 1 dose >95% immune after 3 doses Immunity probably lifelong Polio Vaccination Recommendations, 1996-1999 Increased use of IPV (sequential IPV- OPV schedule) recommended in 1996 Intended to reduce the risk of vaccine- associated paralytic polio (VAPP) Continued risk of VAPP for contacts of OPV recipients Polio Vaccination Recommendations Exclusive use of IPV recommended in 2000 OPV no longer routinely available in the United States Indigenous VAPP eliminated Polio Vaccination Schedule Age Vaccine 2 months IPV 4 months IPV 6-18 months IPV 4-6 years* IPV Minimum Interval --4 wks 4 wks 4 wks *the fourth dose of IPV may be given as early as 18 weeks of age Schedules that Include Both IPV and OPV Only IPV is available in the United States Schedule begun with OPV should be completed with IPV Any combination of 4 doses of IPV and OPV by 5 years constitutes a complete series Combination Vaccines That Contain IPV Pediarix Kinrix DTaP, Hepatitis B and IPV DTaP and IPV Pentacel DTaP, Hib and IPV KINRIX Contains DTaP (Infanrix) and IPV Approved ONLY for the 5th dose of DTaP and 4th dose of IPV in children 4 through 6 years of age* Do NOT use for earlier doses in the DTaP or IPV series Use of KINRIX for any dose other than DTaP5 and IPV4 is off-label, and should be considered a medication error *whose previous doses have been with Infanrix and/or Pediarix for the first 3 doses and Infanrix for the 4th dose Polio Vaccine Adverse Reactions Rare local reactions (IPV) No serious reactions to IPV have been documented Paralytic poliomyelitis (OPV) Vaccine-Associated Paralytic Polio (VAPP) 1980-1998 Healthy recipients of OPV Healthy contacts of OPV recipients Community acquired Immunodeficient 41% 31% 5% 24% Polio Vaccine Contraindications and Precautions Severe allergic reaction to a vaccine component or following a prior dose of vaccine Moderate or severe acute illness Polio Eradication Last case in United States in 1979 Western Hemisphere certified polio free in 1994 Last isolate of type 2 poliovirus in India in October 1999 Global eradication goal Hepatitis B Epidemic jaundice described by Hippocrates in 5th century BCE Jaundice reported among recipients of human serum and yellow fever vaccines in 1930s and 1940s Serologic tests developed in 1970s Hepatitis B Virus Hepadnaviridae family (DNA) Numerous antigenic components Humans are only known host May retain infectivity for more than 7 days at room temperature Hepatitis B Virus Infection More than 350 million chronically infected worldwide Established cause of chronic hepatitis and cirrhosis Human carcinogen—cause of up to 80% of hepatocellular carcinomas More than 600,000 deaths worldwide in 2002 Hepatitis B Clinical Features Incubation period 60-150 days (average 90 days) Nonspecific prodrome of malaise, fever, headache, myalgia Illness not specific for hepatitis B At least 50% of infections asymptomatic Hepatitis B Complications Fulminant hepatitis Hospitalization Cirrhosis Hepatocellular carcinoma Death Risk of Chronic HBV Carriage by Age of Infection 100 Carrier risk (%) 90 80 70 60 50 40 30 20 10 0 Birth 1-6 mo 7-12 mo Age of infection 1-4 yrs 5+ yrs Hepatitis B Perinatal Transmission If mother positive for HBsAg and HBeAg 70%-90% of infants infected 90% of infected infants become chronically infected If positive for HBsAg only 5%-20% of infants infected 90% of infected infants become chronically infected Hepatitis B—United States, 1978-2007 Decline among men who have sex with men 30000 Decline among IV drug users 25000 Cases 20000 15000 10000 Hepatitis B vaccine licensed 5000 0 1978 1980 1985 1990 Year 1995 2000 2005 HBV Disease Burden in the United States Prevaccine era estimated 300,000 persons infected annually, including 24,000 infants and children 2005 estimated 51,000 infections Hepatitis B Vaccine Formulations Recombivax HB (Merck) - 5 mcg/0.5 mL (pediatric) - 10 mcg/1 mL (adult) - 40 mcg/1 mL (dialysis) Engerix-B (GSK) - 10 mcg/0.5 mL (pediatric) - 20 mcg/1 mL (adult) Protection by Age Group and Dose* Dose Infants** Teens and Adults*** 1 16%-40% 20%-30% 2 80%-95% 75%-80% 3 98%-100% 90%-95% *dka * Anti-HBs antibody titer of 10 mIU/mL or higher ** Preterm infants less than 2 kg have been shown to respond to vaccination less often *** Factors that may lower vaccine response rates are age older than 40 years, male gender, smoking, obesity, and immune deficiency Hepatitis B Routine Schedule Dose 1 Birth Dose 2 one month of age Dose 3 six months of age Interval: dose 1-2 is 4 weeks Interval: dose 2-3 is 8 weeks Third Dose of Hepatitis B Vaccine Minimum of 8 weeks after second dose, and At least 16 weeks after first dose, and For infants, at least 24 weeks of age COMVAX Hepatitis B-Hib combination Use when either antigen is indicated Cannot use at younger than 6 weeks of age May be used in infants whose mother is HBsAg positive or status is unknown Combination Vaccine Rule The minimum intervals between doses of a combination vaccine are dictated by the single antigen with the longest minimum intervals For Pediarix the minimum intervals are determined by the hepatitis B component Hepatitis B Vaccine Adverse Reactions Pain at injection site Mild systemic complaints (fatigue, headache) Temperature ≤99.9°F (37.7°C) Severe Rare systemic reactions Infants and Adults Children 13%-29% 3%-9% 11%-17% 0%-20% 1% 0.4%-6% rare rare Hepatitis B Vaccine Contraindications and Precautions Severe allergic reaction to a vaccine component or following a prior dose Moderate or severe acute illness Pneumococcal Disease S. pneumoniae first isolated by Pasteur in 1881 Confused with other causes of pneumonia until discovery of Gram stain in 1884 More than 80 serotypes described by 1940 First U.S. vaccine in 1977 Streptococcus pneumoniae Gram-positive bacteria 90 known serotypes Polysaccharide capsule important virulence factor Type-specific antibody is protective Pneumococcal Disease Second most common cause of vaccine-preventable death in the U.S. (after influenza) Major clinical syndromes include pneumonia, bacteremia, and meningitis Pneumococcal Disease in Children Bacteremia without known site of infection most common clinical presentation S. pneumoniae leading cause of bacterial meningitis among children younger than 5 years of age Highest rate of meningitis among children younger than 1 year of age Common cause of acute otitis media Burden of Pneumococcal Disease in Children* Syndrome Cases Bacteremia 13,000 Meningitis 700 Death Otitis media 200 5,000,000 *Prior to routine use of pneumococcal conjugate vaccine Invasive Pneumococcal Disease Incidence by Age Group, 1998 and 2002 1998 2002 250 Rate * 200 150 100 50 0 <1 1 2-4 5-17 18-34 35-49 50-64 Age Group (Yrs) * Rate per 100,000 population Source: Active Bacterial Core Surveillance/EIP Network 65+ Direct Benefit of Vaccination: Invasive Pneumococcal Disease (IPD) Among Children Younger Than 5 Years of Age Rate/100,000 children younger than 5 years Before vaccine 2006 100 24 All IPD Vaccine serotypes 80 0.5 Source: Active Bacterial Core Surveillance/EIP Network Direct Effect of Vaccination: Invasive Pneumococcal Disease Among Children <5 Years of Age, 1998/992006 Overall PCV7 type Cases per 100,000 120 100 80 60 40 PCV7 introduction 20 0 1998 1999 2000 2001 2002 2003 2004 2005 2006 Pneumococcal Vaccines 1977 14-valent polysaccharide vaccine licensed 1983 23-valent polysaccharide vaccine licensed (PPV23) 2000 7-valent polysaccharide conjugate vaccinelicensed (PCV7) Pneumococcal Conjugate Vaccine Pneumococcal polysaccharide conjugated to nontoxic diphtheria toxin (7 serotypes) Vaccine serotypes account for 86% of bacteremia and 83% of meningitis among children younger than 6 years of age Pneumococcal Polysaccharide Vaccine Not effective in children younger than 2 years 60%-70% against invasive disease Less effective in preventing pneumococcal pneumonia Pneumococcal Conjugate Vaccine Highly immunogenic in infants and young children, including those with high-risk medical conditions 97% effective against invasive disease caused by vaccine serotypes 73% effective against pneumonia 7% reduction in all episodes of acute otitis media Pneumococcal Conjugate Vaccine Recommendations All children 24 months of age Unvaccinated children 24-59 months with a high-risk medical condition MMWR 2000;49(RR-9):1-35 Pneumococcal Conjugate Vaccine Recommendations Doses at 2, 4, 6, months of age, booster dose at 12-15 months of age First dose as early as 6 weeks Minimum interval of 4 weeks between first 3 doses At least 8 weeks between dose 3 and dose 4 Unvaccinated children 7 months of age or older require fewer doses MMWR 2000;49(RR-9):1-35 Pneumococcal Vaccines Adverse Reactions Local reactions 30%-50% 10%-20% Fever, myalgia polysaccharide conjugate polysaccharide conjugate Severe adverse reactions <1% 15%-24% rare Pneumococcal Vaccines Contraindications and Precautions Severe allergic reaction to vaccine component or following prior dose of vaccine Moderate or severe acute illness