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Pediatrics_Nelson. Vaccines Birth 1 mo 2 mos 4 mos 6 mos 9 mos 12 mos 15 mos 18 mos 19–23 mos 2-3 yrs 4-6 yrs 7-10 yrs 11-12 yrs 13–15 yrs 16–18 yrs Hepatitis B (HepB) Rotavirus (RV) RV-1 (2-dose series); RV-5 (3-dose series) Diphtheria, tetanus, & acellular pertussis (DTaP: <7 yrs) Tetanus, diphtheria, & acellular pertussis (Tdap: >7 yrs) type b (Hib) Pneumococcal conjugate (PCV13) Pneumococcal polysaccharide (PPSV23) Inactivated Poliovirus (IPV) (<18years) (IIV; LAIV) 2 doses for some : see footnote 8 Measles, mumps, rubella (MMR) Varicella (VAR) Hepatitis A (HepA) Human papillomavirus (HPV2: females only; HPV4: males and females) Meningococcal (Hib-MenCY > 6 weeks; MCV4-D > 9 mos; MCV4-CRM > 2 yrs.) booster 1 dosesee footnote 13 (3-dose series) 2dose series, see footnote 11 2 dose1 dose 2 dose1 dose Annual vaccination (IIV or LAIV) Annual vaccination (IIV only) 4 dose3 dose2 dose1 dose 4 dose3 dose2 dose1 dose 3 or 4 dose, see footnote 5 See footnote 52 dose1 dose (Tdap) 5 dose4 dose3 dose2 dose1


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Pediatrics_Nelson. vaccination (IIV or LAIV) Annual vaccination (IIV only) 4 dose3 dose2 dose1 dose 4 dose3 dose2 dose1 dose 3 or 4 dose, see footnote 5 See footnote 52 dose1 dose (Tdap) 5 dose4 dose3 dose2 dose1 dose See footnote 22 dose1 dose 3 dose2 dose1 dose


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Pediatrics_Nelson. Range of recommended ages during which ages for all children Range of recommended Range of recommended ages Range of recommended ages for Not routinely recommended high-risk groups catch-up is encouraged and for certain for catch-up immunization certain high-risk groups


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Pediatrics_Nelson. This schedule includes recommendations in effect as of January 1, 2013. Any dose not administered at the recommended age should be administered at a subsequent visit, when indicated and feasible. The use of a combination vaccine generally is preferred over separate injections of its equivalent component vaccines. Vaccination providers should consult the relevant Advisory Committee on Immunization Practices (ACIP) statement for detailed recommendations, available online at http://www.cdc.gov/vaccines/pubs/acip-list.htm. Clinically significant adverse events that follow vaccination should be reported to the Vaccine Adverse Event Reporting System (VAERS) online ( http://www.vaers.hhs.gov ) or by telephone (800-822-7967). Suspected cases of vaccine-preventable diseases should be reported to the state or local health department. Additional information, including precautions and contraindications for vaccination, is available from CDC online (http://www.cdc.gov/vaccines ) or by telephone


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Pediatrics_Nelson. the state or local health department. Additional information, including precautions and contraindications for vaccination, is available from CDC online (http://www.cdc.gov/vaccines ) or by telephone (800-CDC-INFO [800-232-4636]).


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Pediatrics_Nelson. This schedule is approved by the Advisory Committee on Immunization Practices (http://www.cdc.gov/vaccines/acip/index.html), the American Academy of Pediatrics (http://www. aap.org), the American Academy of Family Physicians ( http://www.aafp.org), and the American College of Obstetricians and Gynecologists ( http://www.acog.org). Figure 94-1 Recommended immunization schedules for persons ages 0 through 18 years—United States, 2013. (Approved by the Advisory Committee on Immunization Practices; American Academy of Pediatrics; American Academy of Family Physicians; and American College of Obstetricians and Gynecologists). (Courtesy of the U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, http://www.cdc.gov/vaccines/schedules/hcp/child-adolescent.html For further guidance on the use of the vaccines mentioned below, see: http://www.cdc.gov/vaccines/pubs/acip-list.htm.


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Pediatrics_Nelson. 1. Hepatitis B (HepB) vaccine. (Minimum age: birth) Routine vaccination: At birth  Administer monovalent HepB vaccine to all newborns before hospital discharge.  For infants born to hepatitis B surface antigen (HBsAg)–positive mothers, administer HepB vaccine and 0.5 mL of hepatitis B immune globulin (HBIG) within 12 hours of birth. These infants should be tested for HBsAg and antibody to HBsAg (anti-HBs) 1 to 2 months after completion of the HepB series, at age 9 through 18 months (preferably at the next well-child visit).  If mother’s HBsAg status is unknown, within 12 hours of birth administer HepB vaccine to all infants regardless of birth weight. For infants weighing <2,000 grams, administer HBIG in addition to HepB within 12 hours of birth. Determine mother’s HBsAg status as soon as possible and, if she is HBsAg-positive, also administer HBIG for infants weighing 2,000 grams (no later than age 1 week). Doses following the birth dose  The second dose should be


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Pediatrics_Nelson. status as soon as possible and, if she is HBsAg-positive, also administer HBIG for infants weighing 2,000 grams (no later than age 1 week). Doses following the birth dose  The second dose should be administered at age 1 or 2 months. Monovalent HepB vaccine should be used for doses administered before age 6 weeks.  Infants who did not receive a birth dose should receive 3 doses of a HepB-containing vaccine on a schedule of 0, 1 to 2 months, and 6 months starting as soon as feasible. See Figure 2.  The minimum interval between dose 1 and dose 2 is 4 weeks and between dose 2 and 3 is 8 weeks. The final (third or fourth) dose in the HepB vaccine series should be administered no earlier than age 24 weeks, and at least 16 weeks after the first dose.  Administration of a total of 4 doses of HepB vaccine is recommended when a combination vaccine containing HepB is administered after the birth dose. Catch-up vaccination:  Unvaccinated persons should complete a 3-dose series.  A


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Pediatrics_Nelson. of HepB vaccine is recommended when a combination vaccine containing HepB is administered after the birth dose. Catch-up vaccination:  Unvaccinated persons should complete a 3-dose series.  A 2-dose series (doses separated by at least 4 months) of adult formulation Recombivax HB is licensed for use in children aged 11 through 15 years.  For other catch-up issues, see Figure 2.


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Pediatrics_Nelson. 2. Rotavirus (RV) vaccines. (Minimum age: 6 weeks for both RV-1 [Rotarix] and RV-5 [RotaTeq]). Routine vaccination:  Administer a series of RV vaccine to all infants as follows: 1. If RV-1 is used, administer a 2-dose series at 2 and 4 months of age. 2. If RV-5 is used, administer a 3-dose series at ages 2, 4, and 6 months. 3. If any dose in series was RV-5 or vaccine product is unknown for any dose in the series, a total of 3 doses of RV vaccine should be administered. Catch-up vaccination:  The maximum age for the first dose in the series is 14 weeks, 6 days.  Vaccination should not be initiated for infants aged 15 weeks 0 days or older.  The maximum age for the final dose in the series is 8 months, 0 days.  If RV-1(Rotarix) is administered for the first and second doses, a third dose is not indicated.  For other catch-up issues, see Figure 2.


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Pediatrics_Nelson. 3. Diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine. (Minimum age: 6 weeks) Routine vaccination:  Administer a 5-dose series of DTaP vaccine at ages 2, 4, 6, 15–18 months, and 4 through 6 years. The fourth dose may be administered as early as age 12 months, provided at least 6 months have elapsed since the third dose. Catch-up vaccination:  The fifth (booster) dose of DTaP vaccine is not necessary if the fourth dose was administered at age 4 years or older.  For other catch-up issues, see Figure 2.


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Pediatrics_Nelson. 4. Tetanus and diphtheria toxoids and acellular pertussis (Tdap) vaccine. (Minimum age: 10 years for Boostrix, 11 years for Adacel). Routine vaccination:  Administer 1 dose of Tdap vaccine to all adolescents aged 11 through 12 years.  Tdap can be administered regardless of the interval since the last tetanus and diphtheria toxoid-containing vaccine.  Administer one dose of Tdap vaccine to pregnant adolescents during each pregnancy (preferred during 27 through 36 weeks gestation) regardless of number of years from prior Td or Tdap vaccination. Catch-up vaccination:  Persons aged 7 through 10 years who are not fully immunized with the childhood DTaP vaccine series, should receive Tdap vaccine as the first dose in the catch-up series; if additional doses are needed, use Td vaccine. For these children, an adolescent Tdap vaccine should not be given.  Persons aged 11 through 18 years who have not received Tdap vaccine should receive a dose followed by tetanus and diphtheria


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Pediatrics_Nelson. For these children, an adolescent Tdap vaccine should not be given.  Persons aged 11 through 18 years who have not received Tdap vaccine should receive a dose followed by tetanus and diphtheria toxoids (Td) booster doses every 10 years thereafter.  An inadvertent dose of DTaP vaccine administered to children aged 7 through 10 years can count as part of the catch-up series. This dose can count as the adolescent Tdap dose, or the child can later receive a Tdap booster dose at age 11–12 years.  For other catch-up issues, see Figure 2.


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Pediatrics_Nelson. 5. Haemophilus influenzae type b (Hib) conjugate vaccine. (Minimum age: 6 weeks) Routine vaccination:  Administer a Hib vaccine primary series and a booster dose to all infants. The primary series doses should be administered at 2, 4, and 6 months of age; however, if PRP-OMP (PedvaxHib or Comvax) is administered at 2 and 4 months of age, a dose at age 6 months is not indicated. One booster dose should be administered at age 12 through15 months.  Hiberix (PRP-T) should only be used for the booster (final) dose in children aged 12 months through 4 years, who have received at least 1 dose of Hib. Catch-up vaccination:  If dose 1 was administered at ages 12-14 months, administer booster (as final dose) at least 8 weeks after dose 1.  If the first 2 doses were PRP-OMP (PedvaxHIB or Comvax), and were administered at age 11 months or younger, the third (and final) dose should be administered at age 12 through 15 months and at least 8 weeks after the second dose.  If the first


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Pediatrics_Nelson. Comvax), and were administered at age 11 months or younger, the third (and final) dose should be administered at age 12 through 15 months and at least 8 weeks after the second dose.  If the first dose was administered at age 7 through 11 months, administer the second dose at least 4 weeks later and a final dose at age 12 through 15 months, regardless of Hib vaccine (PRP-T or PRP-OMP) used for first dose.  For unvaccinated children aged 15 months or older, administer only 1 dose.  For other catch-up issues, see Figure 2. Vaccination of persons with high-risk conditions:  Hib vaccine is not routinely recommended for patients older than 5 years of age. However one dose of Hib vaccine should be administered to unvaccinated or partially vaccinated persons aged 5 years or older who have leukemia, malignant neoplasms, anatomic or functional asplenia (including sickle cell disease), human immunodeficiency virus (HIV) infection, or other immunocompromising conditions.


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Pediatrics_Nelson. 6a. Pneumococcal conjugate vaccine (PCV). (Minimum age: 6 weeks) Routine vaccination:  Administer a series of PCV13 vaccine at ages 2, 4, 6 months with a booster at age 12 through 15 months.  For children aged 14 through 59 months who have received an age-appropriate series of 7-valent PCV (PCV7), administer a single supplemental dose of 13-valent PCV (PCV13). Catch-up vaccination:  Administer 1 dose of PCV13 to all healthy children aged 24 through 59 months who are not completely vaccinated for their age.  For other catch-up issues, see Figure 2. Vaccination of persons with high-risk conditions:  For children aged 24 through 71 months with certain underlying medical conditions (see footnote 6c), administer 1 dose of PCV13 if 3 doses of PCV were received previously, or administer 2 doses of PCV13 at least 8 weeks apart if fewer than 3 doses of PCV were received previously.  A single dose of PCV13 may be administered to previously unvaccinated children aged 6 through 18


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Pediatrics_Nelson. 2 doses of PCV13 at least 8 weeks apart if fewer than 3 doses of PCV were received previously.  A single dose of PCV13 may be administered to previously unvaccinated children aged 6 through 18 years who have anatomic or functional asplenia (including sickle cell disease), HIV infection or an immunocompromising condition, cochlear implant or cerebrospinal fluid leak. See MMWR 2010;59 (No. RR-11), available at http://www.cdc.gov/mmwr/pdf/rr/rr5911.pdf.  Administer PPSV23 at least 8 weeks after the last dose of PCV to children aged 2 years or older with certain underlying medical conditions (see footnotes 6b and 6c).


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Pediatrics_Nelson. 6b. Pneumococcal polysaccharide vaccine (PPSV23). (Minimum age: 2 years) Vaccination of persons with high-risk conditions:  Administer PPSV23 at least 8 weeks after the last dose of PCV to children aged 2 years or older with certain underlying medical conditions (see footnote 6c). A single revaccination with PPSV should be administered after 5 years to children with anatomic or functional asplenia (including sickle cell disease) or an immunocompromising condition.


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Pediatrics_Nelson. 6c. Medical conditions for which PPSV23 is indicated in children aged 2 years and older and for which use of PCV13 is indicated in children aged 24 through 71 months:  Immunocompetent children with chronic heart disease (particularly cyanotic congenital heart disease and cardiac failure); chronic lung disease (including asthma if treated with high-dose oral corticosteroid therapy), diabetes mellitus; cerebrospinal fluid leaks; or cochlear implant.  Children with anatomic or functional asplenia (including sickle cell disease and other hemoglobinopathies, congenital or acquired asplenia, or splenic dysfunction);  Children with immunocompromising conditions: HIV infection, chronic renal failure and nephrotic syndrome, diseases associated with treatment with immunosuppressive drugs or radiation therapy, including malignant neoplasms, leukemias, lymphomas and Hodgkin disease; or solid organ transplantation, congenital immunodeficiency.


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Pediatrics_Nelson. 7. Inactivated poliovirus vaccine (IPV). (Minimum age: 6 weeks) Routine vaccination:  Administer a series of IPV at ages 2, 4, 6–18 months, with a booster at age 4–6 years. The final dose in the series should be administered on or after the fourth birthday and at least 6 months after the previous dose. Catch-up vaccination:  In the first 6 months of life, minimum age and minimum intervals are only recommended if the person is at risk for imminent exposure to circulating poliovirus (i.e., travel to a polio-endemic region or during an outbreak).  If 4 or more doses are administered before age 4 years, an additional dose should be administered at age 4 through 6 years.  A fourth dose is not necessary if the third dose was administered at age 4 years or older and at least 6 months after the previous dose.  If both OPV and IPV were administered as part of a series, a total of 4 doses should be administered, regardless of the child’s current age.  IPV is not routinely recommended for


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Pediatrics_Nelson. previous dose.  If both OPV and IPV were administered as part of a series, a total of 4 doses should be administered, regardless of the child’s current age.  IPV is not routinely recommended for U.S. residents aged 18 years or older.  For other catch-up issues, see Figure 2.


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Pediatrics_Nelson. 8. Influenza vaccines. (Minimum age: 6 months for inactivated influenza vaccine [IIV]; 2 years for live, attenuated influenza vaccine [LAIV]) Routine vaccination:  Administer influenza vaccine annually to all children beginning at age 6 months. For most healthy, nonpregnant persons aged 2 through 49 years, either LAIV or IIV may be used. However, LAIV should NOT be administered to some persons, including 1) those with asthma, 2) children 2 through 4 years who had wheezing in the past 12 months, or 3) those who have any other underlying medical conditions that predispose them to influenza complications. For all other contraindications to use of LAIV see MMWR 2010; 59 (No. RR-8), available at http://www.cdc.gov/mmwr/pdf/rr/rr5908.pdf.  Administer 1 dose to persons aged 9 years and older.


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Pediatrics_Nelson.  Administer 1 dose to persons aged 9 years and older. For children aged 6 months through 8 years:  For the 2012–13 season, administer 2 doses (separated by at least 4 weeks) to children who are receiving influenza vaccine for the first time. For additional guidance, follow dosing guidelines in the 2012 ACIP influenza vaccine recommendations, MMWR 2012; 61: 613–618, available at http://www.cdc.gov/mmwr/pdf/wk/mm6132.pdf.  For the 2013–14 season, follow dosing guidelines in the 2013 ACIP influenza vaccine recommendations.


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Pediatrics_Nelson. 9. Measles, mumps, and rubella (MMR) vaccine. (Minimum age: 12 months for routine vaccination) Routine vaccination:  Administer the first dose of MMR vaccine at age 12 through 15 months, and the second dose at age 4 through 6 years. The second dose may be administered before age 4 years, provided at least 4 weeks have elapsed since the first dose.  Administer 1 dose of MMR vaccine to infants aged 6 through 11 months before departure from the United States for international travel. These children should be revaccinated with 2 doses of MMR vaccine, the first at age 12 through 15 months (12 months if the child remains in an area where disease risk is high), and the second dose at least 4 weeks later.  Administer 2 doses of MMR vaccine to children aged 12 months and older, before departure from the United States for international travel. The first dose should be administered on or after age 12 months and the second dose at least 4 weeks later. Catch-up vaccination:  Ensure that all


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Pediatrics_Nelson. from the United States for international travel. The first dose should be administered on or after age 12 months and the second dose at least 4 weeks later. Catch-up vaccination:  Ensure that all school-aged children and adolescents have had 2 doses of MMR vaccine; the minimum interval between the 2 doses is 4 weeks.


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Pediatrics_Nelson. 10. Varicella (VAR) vaccine. (Minimum age: 12 months) Routine vaccination:  Administer the first dose of VAR vaccine at age 12 through 15 months, and the second dose at age 4 through 6 years. The second dose may be administered before age 4 years, provided at least 3 months have elapsed since the first dose. If the second dose was administered at least 4 weeks after the first dose, it can be accepted as valid. Figure 94-1, cont’d Catch-up vaccination:  Ensure that all persons aged 7 through 18 years without evidence of immunity (see MMWR 2007;56 [No. RR-4], available at http://www.cdc.gov/mmwr/pdf/rr/rr5604.pdf) have 2 doses of varicella vaccine. For children aged 7 through 12 years the recommended minimum interval between doses is 3 months (if the second dose was administered at least 4 weeks after the first dose, it can be accepted as valid); for persons aged 13 years and older, the minimum interval between doses is 4 weeks.


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Pediatrics_Nelson. 11. Hepatitis A vaccine (HepA). (Minimum age: 12 months) Routine vaccination:  Initiate the 2-dose HepA vaccine series for children aged 12 through 23 months; separate the 2 doses by 6 to 18 months.  Children who have received 1 dose of HepA vaccine before age 24 months, should receive a second dose 6 to 18 months after the first dose.  For any person aged 2 years and older who has not already received the HepA vaccine series, 2 doses of HepA vaccine separated by 6 to 18 months may be administered if immunity against hepatitis A virus infection is desired. Catch-up vaccination:  The minimum interval between the two doses is 6 months. Special populations:  Administer 2 doses of Hep A vaccine at least 6 months apart to previously unvaccinated persons who live in areas where vaccination programs target older children, or who are at increased risk for infection.


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Pediatrics_Nelson. 12. Human papillomavirus (HPV) vaccines. (HPV4 [Gardasil] and HPV2 [Cervarix]). (Minimum age: 9 years) Routine vaccination:  Administer a 3-dose series of HPV vaccine on a schedule of 0, 1-2, and 6 months to all adolescents aged 11-12 years. Either HPV4 or HPV2 may be used for females, and only HPV4 may be used for males.  The vaccine series can be started beginning at age 9 years.  Administer the second dose 1 to 2 months after the first dose and the third dose 6 months after the first dose (at least 24 weeks after the first dose). Catch-up vaccination:  Administer the vaccine series to females (either HPV2 or HPV4) and males (HPV4) at age 13 through 18 years if not previously vaccinated.  Use recommended routine dosing intervals (see above) for vaccine series catch-up.


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Pediatrics_Nelson. 13. Meningococcal conjugate vaccines (MCV). (Minimum age: 6 weeks for Hib-MenCY, 9 months for Menactra [MCV4-D], 2 years for Menveo [MCV4-CRM]). Routine vaccination:  Administer MCV4 vaccine at age 11–12 years, with a booster dose at age 16 years.  Adolescents aged 11 through 18 years with human immunodeficiency virus (HIV) infection should receive a 2-dose primary series of MCV4, with at least 8 weeks between doses. See MMWR 2011; 60:1018–1019 available at: http://www.cdc.gov/mmwr/pdf/wk/mm6030.pdf.  For children aged 2 months through 10 years with high-risk conditions, see below. Catch-up vaccination:  Administer MCV4 vaccine at age 13 through 18 years if not previously vaccinated.  If the first dose is administered at age 13 through 15 years, a booster dose should be administered at age 16 through 18 years with a minimum interval of at least 8 weeks between doses.  If the first dose is administered at age 16 years or older, a booster dose is not needed.  For other catch-up


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Pediatrics_Nelson. at age 16 through 18 years with a minimum interval of at least 8 weeks between doses.  If the first dose is administered at age 16 years or older, a booster dose is not needed.  For other catch-up issues, see Figure 2. Vaccination of persons with high-risk conditions:  For children younger than 19 months of age with anatomic or functional asplenia (including sickle cell disease), administer an infant series of Hib-MenCY at 2, 4, 6, and 12-15 months.  For children aged 2 through 18 months with persistent complement component deficiency, administer either an infant series of Hib-MenCY at 2, 4, 6, and 12 through 15 months or a 2-dose primary series of MCV4-D starting at 9 months, with at least 8 weeks between doses. For children aged 19 through 23 months with persistent complement component deficiency who have not received a complete series of Hib-MenCY or MCV4-D, administer 2 primary doses of MCV4-D at least 8 weeks apart.  For children aged 24 months and older with persistent


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Pediatrics_Nelson. deficiency who have not received a complete series of Hib-MenCY or MCV4-D, administer 2 primary doses of MCV4-D at least 8 weeks apart.  For children aged 24 months and older with persistent complement component deficiency or anatomic or functional asplenia (including sickle cell disease), who have not received a complete series of Hib-MenCY or MCV4-D, administer 2 primary doses of either MCV4-D or MCV4-CRM. If MCV4-D (Menactra) is administered to a child with asplenia (including sickle cell disease), do not administer MCV4-D until 2 years of age and at least 4 weeks after the completion of all PCV13 doses. See MMWR 2011;60:1391–2, available at http://www.cdc.gov/mmwr/pdf/wk/mm6040.pdf.  For children aged 9 months and older who are residents of or travelers to countries in the African meningitis belt or to the Hajj, administer an age appropriate formulation and series of MCV4 for protection against serogroups A and W-135. Prior receipt of Hib-MenCY is not sufficient for children


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Pediatrics_Nelson. meningitis belt or to the Hajj, administer an age appropriate formulation and series of MCV4 for protection against serogroups A and W-135. Prior receipt of Hib-MenCY is not sufficient for children traveling to the meningitis belt or the Hajj. See MMWR 2011;60:1391–2, available at http://www.cdc.gov/mmwr/pdf/wk/mm6040.pdf.  For children who are present during outbreaks caused by a vaccine serogroup, administer or complete an age and formulation-appropriate series of Hib-MenCY or MCV4.  For booster doses among persons with high-risk conditions refer to http://www.cdc.gov/vaccines/pubs/acip-list.htm#mening.


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Pediatrics_Nelson. Additional information  For contraindications and precautions to use of a vaccine and for additional information regarding that vaccine, vaccination providers should consult the relevant ACIP statement available online at http://www.cdc.gov/vaccines/pubs/acip-list.htm.  For the purposes of calculating intervals between doses, 4 weeks = 28 days. Intervals of 4 months or greater are determined by calendar months.  Information on travel vaccine requirements and recommendations is available at http://wwwnc.cdc.gov/travel/page/vaccinations.htm.  For vaccination of persons with primary and secondary immunodeficiencies, see Table 13, “Vaccination of persons with primary and secondary immunodeficiencies,” in General Recommendations on Immunization (ACIP), available at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6002a1.htm; and American Academy of Pediatrics. Immunization in Special Clinical Circumstances. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS eds. Red book: 2012 report of the


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Pediatrics_Nelson. and American Academy of Pediatrics. Immunization in Special Clinical Circumstances. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS eds. Red book: 2012 report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics.


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Pediatrics_Nelson. The figure below provides catch-up schedules and minimum intervals between doses for children whose vaccinations have been delayed. A vaccine series does not need to be restarted, regardless of the time that has elapsed between doses. Use the section appropriate for the child’s age. Always use this table in conjunction with Figure 94-1 and the footnotes that follow.


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Pediatrics_Nelson. Figure 94-2 Catch-up immunization schedule for persons ages 4 months through 18 years who start late or who are more than 1 month behind—United States, 2013. This figure provides catch-up schedules and minimum intervals between doses for children whose vaccinations have been delayed. A vaccine series does not need to be restarted, regardless of the time that has elapsed between doses. Use the section appropriate for the child’s age. Always use this table in conjunction with the Recommended Immunization Schedule for 2013 and the footnotes that follow. (Approved by the Advisory Committee on Immunization Practices; American Academy of Pediatrics; American Academy of Family Physicians; and American College of Obstetricians and Gynecologists.) (Courtesy of the U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, http://www.cdc.gov/vaccines/schedules/hcp/child-adolescent.html


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Pediatrics_Nelson. For further guidance on the use of the vaccines mentioned below, see: http://www.cdc.gov/vaccines/pubs/acip-list.htm.


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Pediatrics_Nelson. 1. Hepatitis B (HepB) vaccine. (Minimum age: birth) Routine vaccination: At birth  Administer monovalent HepB vaccine to all newborns before hospital discharge.  For infants born to hepatitis B surface antigen (HBsAg)–positive mothers, administer HepB vaccine and 0.5 mL of hepatitis B immune globulin (HBIG) within 12 hours of birth. These infants should be tested for HBsAg and antibody to HBsAg (anti-HBs) 1 to 2 months after completion of the HepB series, at age 9 through 18 months (preferably at the next well-child visit).  If mother’s HBsAg status is unknown, within 12 hours of birth administer HepB vaccine to all infants regardless of birth weight. For infants weighing <2,000 grams, administer HBIG in addition to HepB within 12 hours of birth. Determine mother’s HBsAg status as soon as possible and, if she is HBsAg-positive, also administer HBIG for infants weighing 2,000 grams (no later than age 1 week). Doses following the birth dose  The second dose should be


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Pediatrics_Nelson. status as soon as possible and, if she is HBsAg-positive, also administer HBIG for infants weighing 2,000 grams (no later than age 1 week). Doses following the birth dose  The second dose should be administered at age 1 or 2 months. Monovalent HepB vaccine should be used for doses administered before age 6 weeks.  Infants who did not receive a birth dose should receive 3 doses of a HepB-containing vaccine on a schedule of 0, 1 to 2 months, and 6 months starting as soon as feasible. See Figure 2.  The minimum interval between dose 1 and dose 2 is 4 weeks and between dose 2 and 3 is 8 weeks. The final (third or fourth) dose in the HepB vaccine series should be administered no earlier than age 24 weeks, and at least 16 weeks after the first dose.  Administration of a total of 4 doses of HepB vaccine is recommended when a combination vaccine containing HepB is administered after the birth dose. Catch-up vaccination:  Unvaccinated persons should complete a 3-dose series.  A


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Pediatrics_Nelson. of HepB vaccine is recommended when a combination vaccine containing HepB is administered after the birth dose. Catch-up vaccination:  Unvaccinated persons should complete a 3-dose series.  A 2-dose series (doses separated by at least 4 months) of adult formulation Recombivax HB is licensed for use in children aged 11 through 15 years.  For other catch-up issues, see Figure 2.


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Pediatrics_Nelson. 2. Rotavirus (RV) vaccines. (Minimum age: 6 weeks for both RV-1 [Rotarix] and RV-5 [RotaTeq]). Routine vaccination:  Administer a series of RV vaccine to all infants as follows: 1. If RV-1 is used, administer a 2-dose series at 2 and 4 months of age. 2. If RV-5 is used, administer a 3-dose series at ages 2, 4, and 6 months. 3. If any dose in series was RV-5 or vaccine product is unknown for any dose in the series, a total of 3 doses of RV vaccine should be administered. Catch-up vaccination:  The maximum age for the first dose in the series is 14 weeks, 6 days.  Vaccination should not be initiated for infants aged 15 weeks 0 days or older.  The maximum age for the final dose in the series is 8 months, 0 days.  If RV-1(Rotarix) is administered for the first and second doses, a third dose is not indicated.  For other catch-up issues, see Figure 2.


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Pediatrics_Nelson. 3. Diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine. (Minimum age: 6 weeks) Routine vaccination:  Administer a 5-dose series of DTaP vaccine at ages 2, 4, 6, 15–18 months, and 4 through 6 years. The fourth dose may be administered as early as age 12 months, provided at least 6 months have elapsed since the third dose. Catch-up vaccination:  The fifth (booster) dose of DTaP vaccine is not necessary if the fourth dose was administered at age 4 years or older.  For other catch-up issues, see Figure 2.


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Pediatrics_Nelson. 4. Tetanus and diphtheria toxoids and acellular pertussis (Tdap) vaccine. (Minimum age: 10 years for Boostrix, 11 years for Adacel). Routine vaccination:  Administer 1 dose of Tdap vaccine to all adolescents aged 11 through 12 years.  Tdap can be administered regardless of the interval since the last tetanus and diphtheria toxoid-containing vaccine.  Administer one dose of Tdap vaccine to pregnant adolescents during each pregnancy (preferred during 27 through 36 weeks gestation) regardless of number of years from prior Td or Tdap vaccination. Catch-up vaccination:  Persons aged 7 through 10 years who are not fully immunized with the childhood DTaP vaccine series, should receive Tdap vaccine as the first dose in the catch-up series; if additional doses are needed, use Td vaccine. For these children, an adolescent Tdap vaccine should not be given.  Persons aged 11 through 18 years who have not received Tdap vaccine should receive a dose followed by tetanus and diphtheria


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Pediatrics_Nelson. For these children, an adolescent Tdap vaccine should not be given.  Persons aged 11 through 18 years who have not received Tdap vaccine should receive a dose followed by tetanus and diphtheria toxoids (Td) booster doses every 10 years thereafter.  An inadvertent dose of DTaP vaccine administered to children aged 7 through 10 years can count as part of the catch-up series. This dose can count as the adolescent Tdap dose, or the child can later receive a Tdap booster dose at age 11–12 years.  For other catch-up issues, see Figure 2.


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Pediatrics_Nelson. 5. Haemophilus influenzae type b (Hib) conjugate vaccine. (Minimum age: 6 weeks) Routine vaccination:  Administer a Hib vaccine primary series and a booster dose to all infants. The primary series doses should be administered at 2, 4, and 6 months of age; however, if PRP-OMP (PedvaxHib or Comvax) is administered at 2 and 4 months of age, a dose at age 6 months is not indicated. One booster dose should be administered at age 12 through15 months.  Hiberix (PRP-T) should only be used for the booster (final) dose in children aged 12 months through 4 years, who have received at least 1 dose of Hib. Catch-up vaccination:  If dose 1 was administered at ages 12-14 months, administer booster (as final dose) at least 8 weeks after dose 1.  If the first 2 doses were PRP-OMP (PedvaxHIB or Comvax), and were administered at age 11 months or younger, the third (and final) dose should be administered at age 12 through 15 months and at least 8 weeks after the second dose.  If the first


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Pediatrics_Nelson. Comvax), and were administered at age 11 months or younger, the third (and final) dose should be administered at age 12 through 15 months and at least 8 weeks after the second dose.  If the first dose was administered at age 7 through 11 months, administer the second dose at least 4 weeks later and a final dose at age 12 through 15 months, regardless of Hib vaccine (PRP-T or PRP-OMP) used for first dose.  For unvaccinated children aged 15 months or older, administer only 1 dose.  For other catch-up issues, see Figure 2. Vaccination of persons with high-risk conditions:  Hib vaccine is not routinely recommended for patients older than 5 years of age. However one dose of Hib vaccine should be administered to unvaccinated or partially vaccinated persons aged 5 years or older who have leukemia, malignant neoplasms, anatomic or functional asplenia (including sickle cell disease), human immunodeficiency virus (HIV) infection, or other immunocompromising conditions.


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Pediatrics_Nelson. 6a. Pneumococcal conjugate vaccine (PCV). (Minimum age: 6 weeks) Routine vaccination:  Administer a series of PCV13 vaccine at ages 2, 4, 6 months with a booster at age 12 through 15 months.  For children aged 14 through 59 months who have received an age-appropriate series of 7-valent PCV (PCV7), administer a single supplemental dose of 13-valent PCV (PCV13). Catch-up vaccination:  Administer 1 dose of PCV13 to all healthy children aged 24 through 59 months who are not completely vaccinated for their age.  For other catch-up issues, see Figure 2. Vaccination of persons with high-risk conditions:  For children aged 24 through 71 months with certain underlying medical conditions (see footnote 6c), administer 1 dose of PCV13 if 3 doses of PCV were received previously, or administer 2 doses of PCV13 at least 8 weeks apart if fewer than 3 doses of PCV were received previously.  A single dose of PCV13 may be administered to previously unvaccinated children aged 6 through 18


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Pediatrics_Nelson. 2 doses of PCV13 at least 8 weeks apart if fewer than 3 doses of PCV were received previously.  A single dose of PCV13 may be administered to previously unvaccinated children aged 6 through 18 years who have anatomic or functional asplenia (including sickle cell disease), HIV infection or an immunocompromising condition, cochlear implant or cerebrospinal fluid leak. See MMWR 2010;59 (No. RR-11), available at http://www.cdc.gov/mmwr/pdf/rr/rr5911.pdf.  Administer PPSV23 at least 8 weeks after the last dose of PCV to children aged 2 years or older with certain underlying medical conditions (see footnotes 6b and 6c).


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Pediatrics_Nelson. 6b. Pneumococcal polysaccharide vaccine (PPSV23). (Minimum age: 2 years) Vaccination of persons with high-risk conditions:  Administer PPSV23 at least 8 weeks after the last dose of PCV to children aged 2 years or older with certain underlying medical conditions (see footnote 6c). A single revaccination with PPSV should be administered after 5 years to children with anatomic or functional asplenia (including sickle cell disease) or an immunocompromising condition.


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Pediatrics_Nelson. 6c. Medical conditions for which PPSV23 is indicated in children aged 2 years and older and for which use of PCV13 is indicated in children aged 24 through 71 months:  Immunocompetent children with chronic heart disease (particularly cyanotic congenital heart disease and cardiac failure); chronic lung disease (including asthma if treated with high-dose oral corticosteroid therapy), diabetes mellitus; cerebrospinal fluid leaks; or cochlear implant.  Children with anatomic or functional asplenia (including sickle cell disease and other hemoglobinopathies, congenital or acquired asplenia, or splenic dysfunction);  Children with immunocompromising conditions: HIV infection, chronic renal failure and nephrotic syndrome, diseases associated with treatment with immunosuppressive drugs or radiation therapy, including malignant neoplasms, leukemias, lymphomas and Hodgkin disease; or solid organ transplantation, congenital immunodeficiency.


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Pediatrics_Nelson. 7. Inactivated poliovirus vaccine (IPV). (Minimum age: 6 weeks) Routine vaccination:  Administer a series of IPV at ages 2, 4, 6–18 months, with a booster at age 4–6 years. The final dose in the series should be administered on or after the fourth birthday and at least 6 months after the previous dose. Catch-up vaccination:  In the first 6 months of life, minimum age and minimum intervals are only recommended if the person is at risk for imminent exposure to circulating poliovirus (i.e., travel to a polio-endemic region or during an outbreak).  If 4 or more doses are administered before age 4 years, an additional dose should be administered at age 4 through 6 years.  A fourth dose is not necessary if the third dose was administered at age 4 years or older and at least 6 months after the previous dose.  If both OPV and IPV were administered as part of a series, a total of 4 doses should be administered, regardless of the child’s current age.  IPV is not routinely recommended for


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Pediatrics_Nelson. previous dose.  If both OPV and IPV were administered as part of a series, a total of 4 doses should be administered, regardless of the child’s current age.  IPV is not routinely recommended for U.S. residents aged 18 years or older.  For other catch-up issues, see Figure 2.


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Pediatrics_Nelson. 8. Influenza vaccines. (Minimum age: 6 months for inactivated influenza vaccine [IIV]; 2 years for live, attenuated influenza vaccine [LAIV]) Routine vaccination:  Administer influenza vaccine annually to all children beginning at age 6 months. For most healthy, nonpregnant persons aged 2 through 49 years, either LAIV or IIV may be used. However, LAIV should NOT be administered to some persons, including 1) those with asthma, 2) children 2 through 4 years who had wheezing in the past 12 months, or 3) those who have any other underlying medical conditions that predispose them to influenza complications. For all other contraindications to use of LAIV see MMWR 2010; 59 (No. RR-8), available at http://www.cdc.gov/mmwr/pdf/rr/rr5908.pdf.  Administer 1 dose to persons aged 9 years and older.


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Pediatrics_Nelson.  Administer 1 dose to persons aged 9 years and older. For children aged 6 months through 8 years:  For the 2012–13 season, administer 2 doses (separated by at least 4 weeks) to children who are receiving influenza vaccine for the first time. For additional guidance, follow dosing guidelines in the 2012 ACIP influenza vaccine recommendations, MMWR 2012; 61: 613–618, available at http://www.cdc.gov/mmwr/pdf/wk/mm6132.pdf.  For the 2013–14 season, follow dosing guidelines in the 2013 ACIP influenza vaccine recommendations.


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Pediatrics_Nelson. 9. Measles, mumps, and rubella (MMR) vaccine. (Minimum age: 12 months for routine vaccination) Routine vaccination:  Administer the first dose of MMR vaccine at age 12 through 15 months, and the second dose at age 4 through 6 years. The second dose may be administered before age 4 years, provided at least 4 weeks have elapsed since the first dose.  Administer 1 dose of MMR vaccine to infants aged 6 through 11 months before departure from the United States for international travel. These children should be revaccinated with 2 doses of MMR vaccine, the first at age 12 through 15 months (12 months if the child remains in an area where disease risk is high), and the second dose at least 4 weeks later.  Administer 2 doses of MMR vaccine to children aged 12 months and older, before departure from the United States for international travel. The first dose should be administered on or after age 12 months and the second dose at least 4 weeks later. Catch-up vaccination:  Ensure that all


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Pediatrics_Nelson. from the United States for international travel. The first dose should be administered on or after age 12 months and the second dose at least 4 weeks later. Catch-up vaccination:  Ensure that all school-aged children and adolescents have had 2 doses of MMR vaccine; the minimum interval between the 2 doses is 4 weeks.


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Pediatrics_Nelson. 10. Varicella (VAR) vaccine. (Minimum age: 12 months) Routine vaccination:  Administer the first dose of VAR vaccine at age 12 through 15 months, and the second dose at age 4 through 6 years. The second dose may be administered before age 4 years, provided at least 3 months have elapsed since the first dose. If the second dose was administered at least 4 weeks after the first dose, it can be accepted as valid. Figure 94-2, cont’d Catch-up vaccination:  Ensure that all persons aged 7 through 18 years without evidence of immunity (see MMWR 2007;56 [No. RR-4], available at http://www.cdc.gov/mmwr/pdf/rr/rr5604.pdf) have 2 doses of varicella vaccine. For children aged 7 through 12 years the recommended minimum interval between doses is 3 months (if the second dose was administered at least 4 weeks after the first dose, it can be accepted as valid); for persons aged 13 years and older, the minimum interval between doses is 4 weeks.


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Pediatrics_Nelson. 11. Hepatitis A vaccine (HepA). (Minimum age: 12 months) Routine vaccination:  Initiate the 2-dose HepA vaccine series for children aged 12 through 23 months; separate the 2 doses by 6 to 18 months.  Children who have received 1 dose of HepA vaccine before age 24 months, should receive a second dose 6 to 18 months after the first dose.  For any person aged 2 years and older who has not already received the HepA vaccine series, 2 doses of HepA vaccine separated by 6 to 18 months may be administered if immunity against hepatitis A virus infection is desired. Catch-up vaccination:  The minimum interval between the two doses is 6 months. Special populations:  Administer 2 doses of Hep A vaccine at least 6 months apart to previously unvaccinated persons who live in areas where vaccination programs target older children, or who are at increased risk for infection.


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Pediatrics_Nelson. 12. Human papillomavirus (HPV) vaccines. (HPV4 [Gardasil] and HPV2 [Cervarix]). (Minimum age: 9 years) Routine vaccination:  Administer a 3-dose series of HPV vaccine on a schedule of 0, 1-2, and 6 months to all adolescents aged 11-12 years. Either HPV4 or HPV2 may be used for females, and only HPV4 may be used for males.  The vaccine series can be started beginning at age 9 years.  Administer the second dose 1 to 2 months after the first dose and the third dose 6 months after the first dose (at least 24 weeks after the first dose). Catch-up vaccination:  Administer the vaccine series to females (either HPV2 or HPV4) and males (HPV4) at age 13 through 18 years if not previously vaccinated.  Use recommended routine dosing intervals (see above) for vaccine series catch-up.


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Pediatrics_Nelson. 13. Meningococcal conjugate vaccines (MCV). (Minimum age: 6 weeks for Hib-MenCY, 9 months for Menactra [MCV4-D], 2 years for Menveo [MCV4-CRM]). Routine vaccination:  Administer MCV4 vaccine at age 11–12 years, with a booster dose at age 16 years.  Adolescents aged 11 through 18 years with human immunodeficiency virus (HIV) infection should receive a 2-dose primary series of MCV4, with at least 8 weeks between doses. See MMWR 2011; 60:1018–1019 available at: http://www.cdc.gov/mmwr/pdf/wk/mm6030.pdf.  For children aged 2 months through 10 years with high-risk conditions, see below. Catch-up vaccination:  Administer MCV4 vaccine at age 13 through 18 years if not previously vaccinated.  If the first dose is administered at age 13 through 15 years, a booster dose should be administered at age 16 through 18 years with a minimum interval of at least 8 weeks between doses.  If the first dose is administered at age 16 years or older, a booster dose is not needed.  For other catch-up


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Pediatrics_Nelson. at age 16 through 18 years with a minimum interval of at least 8 weeks between doses.  If the first dose is administered at age 16 years or older, a booster dose is not needed.  For other catch-up issues, see Figure 2. Vaccination of persons with high-risk conditions:  For children younger than 19 months of age with anatomic or functional asplenia (including sickle cell disease), administer an infant series of Hib-MenCY at 2, 4, 6, and 12-15 months.  For children aged 2 through 18 months with persistent complement component deficiency, administer either an infant series of Hib-MenCY at 2, 4, 6, and 12 through 15 months or a 2-dose primary series of MCV4-D starting at 9 months, with at least 8 weeks between doses. For children aged 19 through 23 months with persistent complement component deficiency who have not received a complete series of Hib-MenCY or MCV4-D, administer 2 primary doses of MCV4-D at least 8 weeks apart.  For children aged 24 months and older with persistent


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Pediatrics_Nelson. deficiency who have not received a complete series of Hib-MenCY or MCV4-D, administer 2 primary doses of MCV4-D at least 8 weeks apart.  For children aged 24 months and older with persistent complement component deficiency or anatomic or functional asplenia (including sickle cell disease), who have not received a complete series of Hib-MenCY or MCV4-D, administer 2 primary doses of either MCV4-D or MCV4-CRM. If MCV4-D (Menactra) is administered to a child with asplenia (including sickle cell disease), do not administer MCV4-D until 2 years of age and at least 4 weeks after the completion of all PCV13 doses. See MMWR 2011;60:1391–2, available at http://www.cdc.gov/mmwr/pdf/wk/mm6040.pdf.  For children aged 9 months and older who are residents of or travelers to countries in the African meningitis belt or to the Hajj, administer an age appropriate formulation and series of MCV4 for protection against serogroups A and W-135. Prior receipt of Hib-MenCY is not sufficient for children


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Pediatrics_Nelson. meningitis belt or to the Hajj, administer an age appropriate formulation and series of MCV4 for protection against serogroups A and W-135. Prior receipt of Hib-MenCY is not sufficient for children traveling to the meningitis belt or the Hajj. See MMWR 2011;60:1391–2, available at http://www.cdc.gov/mmwr/pdf/wk/mm6040.pdf.  For children who are present during outbreaks caused by a vaccine serogroup, administer or complete an age and formulation-appropriate series of Hib-MenCY or MCV4.  For booster doses among persons with high-risk conditions refer to http://www.cdc.gov/vaccines/pubs/acip-list.htm#mening.


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Pediatrics_Nelson. Additional information  For contraindications and precautions to use of a vaccine and for additional information regarding that vaccine, vaccination providers should consult the relevant ACIP statement available online at http://www.cdc.gov/vaccines/pubs/acip-list.htm.  For the purposes of calculating intervals between doses, 4 weeks = 28 days. Intervals of 4 months or greater are determined by calendar months.  Information on travel vaccine requirements and recommendations is available at http://wwwnc.cdc.gov/travel/page/vaccinations.htm.  For vaccination of persons with primary and secondary immunodeficiencies, see Table 13, “Vaccination of persons with primary and secondary immunodeficiencies,” in General Recommendations on Immunization (ACIP), available at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6002a1.htm; and American Academy of Pediatrics. Immunization in Special Clinical Circumstances. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS eds. Red book: 2012 report of the


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Pediatrics_Nelson. and American Academy of Pediatrics. Immunization in Special Clinical Circumstances. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS eds. Red book: 2012 report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics.


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Pediatrics_Nelson. Table 94-1 Guide to Tetanus Prophylaxis in Routine Wound Management CLEAN MINOR WOUNDS ALL OTHER WOUNDS* Previous Tetanus Immunization (Doses) DTap, Tdap, or Td† TIG†,‡ DTap, Tdap, or Td TIG‡ ≥3 doses Yes if ≥10 yr since the last tetanus No Yes if ≥5 yr since the last tetanus No toxoid-containing vaccine dose Modified from American Academy of Pediatrics. Pickering LK, editor: Red Book: 2012 report of the committee on infectious diseases, ed 29, Elk Grove Village, IL, 2012, American Academy of Pediatrics. Tdap, tetanus and diphtheria toxoids, adsorbed (for adolescents >11 yr of age and adults); Td, Tetanus-diphtheria toxoid; TIG, tetanus immunoglobulin. *Such as, but not limited to, wounds contaminated with dirt, feces, soil, or saliva; puncture wounds; avulsions; and wounds resulting from missiles, crushing, burns, and frostbite.


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Pediatrics_Nelson. †Tdap is preferred for adolescents who have never received Tdap. Td is preferred to tetanus toxoid for adolescents who received Tdap previously or when Tdap is not available. ‡Immune globulin intravenous should be used if TIG is not available. contact with the index patient, or medical personnel without direct exposure to the patient’s oral secretions. Rifampin twice daily for 2 days, ceftriaxone once, and ciprofloxacin once (>18 years of age) are the recommended regimens. Azithromycin may be used in the case of resistant organisms. All postexposure wound treatment begins with immediate, thorough cleansing using soap and water, removal of foreign bodies, and debridement of devitalized tissue. Tetanus prophylaxis after wounds and injuries includes vaccination of persons with incomplete immunization and tetanus immunoglobulin for contaminated wounds (soil, feces, saliva), puncture wounds, avulsions, and wounds resulting from missiles, crushing, burns, and frostbite (Table 94-1).


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Pediatrics_Nelson. Rabies immune globulin (RIG) and rabies vaccine are extremely effective for prophylaxis after exposure to rabies but are of no known benefit after symptoms appear. Because rabies is one of the deadliest infections, recognition of potential exposure and prophylaxis are crucial. Any healthy-appearing domestic animal responsible for an apparently unprovoked bite should be observed for 10 days for signs of rabies, without immediate treatment of the victim. Prophylaxis should be administered if the animal is rabid or suspected to be rabid, or if the animal develops signs of rabies while under observation. A captured wild animal should be euthanized (by animal control officials) without a period of observation and its brain examined for evidence of rabies. If the biting animal is not captured, particularly if it is a wild animal of a species known to harbor the virus in the region, rabies should be presumed and prophylaxis administered to the victim. Skunks, raccoons, foxes, woodchucks,


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Pediatrics_Nelson. particularly if it is a wild animal of a species known to harbor the virus in the region, rabies should be presumed and prophylaxis administered to the victim. Skunks, raccoons, foxes, woodchucks, most other carnivores, and bats are regarded as rabid unless proved negative by testing. Prophylaxis also should be provided following exposure to a bat for persons who might be unaware or unable to relate that a bite or direct contact has occurred, such as a mentally disabled person, a sleeping child, or an unattended infant.


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Pediatrics_Nelson. All rabies postexposure management begins with immediate thorough cleansing of the bite using soap and water and, if available, irrigation with a virucidal agent such as povidone-iodine. RIG at a dose of 20 U/kg should be administered, with the full dose of RIG infiltrated subcutaneously into the area around the wound, if possible. Any remaining RIG that cannot be infiltrated into the wound should be administered as an intramuscular injection. Inactivated rabies vaccine should be administered simultaneously as soon as possible, with additional vaccine doses at 3, 7, and 14 days. The selection of anti-infective therapy depends on a number of factors: the site of infection and clinical syndrome, host immunity, probable causative agents, the pathogen’s susceptibility to antimicrobial agents and the local epidemiology of resistance, the pharmacokinetics of the selected agents, and their pharmacodynamics in specific patient populations.


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Pediatrics_Nelson. Empirical or presumptive anti-infective therapy is based on a clinical diagnosis combined with published evidence and experience of the probable causative pathogens. Definitive therapy relies on microbiologic diagnosis by isolation or other direct evidence of a pathogen. Microbiologic diagnosis permits characterization of the pathogen’s anti-infective drug susceptibilities and delivery of the appropriate anti-infective agent to the site of infection in concentrations sufficient to kill or alter the pathogen and facilitate an effective immune response. Antiviral therapy must include consideration of the intracellular nature of viral replication and, to avoid toxicity to host cells, must be targeted to viral-specific proteins, such as the thymidine kinase of herpesviruses or the reverse transcriptase of human immunodeficiency virus.


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Pediatrics_Nelson. Empirical antimicrobial therapy is best initiated after obtaining appropriate cultures of fluids or tissues. In high-risk circumstances, such as neonatal sepsis or bacteremia in immunocompromised persons, empirical therapy includes broad-spectrum antimicrobials (see Chapters 96 and 120). Empirical antimicrobial therapy may be tailored to specific pathogens based on the clinical diagnosis (e.g., streptococcal pharyngitis) or defined risks (e.g., close exposure to tuberculosis). Definitive therapy can additionally minimize drug toxicity, development of resistant microorganisms, and cost.


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Pediatrics_Nelson. Antimicrobial agents are an adjunct to the normal host immune response. Infections associated with foreign bodies, such as an intravascular catheter, are difficult to eradicate with antimicrobials alone because of organism-produced biofilms that impair phagocytosis. Similarly it is difficult for phagocytic cells to eradicate bacteria amid vegetations of fibrin and platelets on infected heart valves. Prolonged, bactericidal therapy is required with these infections, and outcomes are not always satisfactory. Foreign body devices may have to be removed if sterilization does not occur promptly. Infections in closed spaces with limited perfusion (such as abscesses or chronic osteomyelitis with poorly perfused bone) are difficult to cure without surgical drainage, debridement of the infected tissue, and reestablishment of a good vascular supply.


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Pediatrics_Nelson. Optimal antimicrobial therapy requires an understanding of both the pharmacokinetics (e.g., bioavailability and tissue penetration) of the administered drugs and their pharmacodynamics (e.g., metabolism and excretion by the body) in specific patient populations. The bioavailability of orally administered antibiotics varies, depending on the acid stability of the drug; degree of gastric acidity; and whether it is taken with food, antacids, H2 blockers, or other medications. An ileus or profuse diarrhea may alter intestinal transit time and result in unpredictable absorption. The site and nature of the infection may affect the choice of antimicrobials. Aminoglycosides, active against aerobic organisms only, have significantly reduced activity in abscesses with low pH and oxygen tension. Infections of the central nervous system or the eye necessitate treatment with antimicrobials that penetrate and achieve therapeutic levels in these sites.


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Pediatrics_Nelson. Limited renal function (as in premature infants or those with renal failure) requires increasing dosing intervals to allow time for excretion of certain drugs. The larger volume of distribution of certain hydrophilic antimicrobials and increased renal clearance (e.g., in cystic fibrosis) requires higher doses to achieve therapeutic levels. Weight-based dosage regimens may result in overdoses in obese children due to significantly smaller volumes of distribution for hydrophilic drugs. Determining serum drug levels for antibiotics with narrow safety margins (e.g., aminoglycosides and vancomycin) minimizes adverse effects of treatment.


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Pediatrics_Nelson. Drug-drug interactions must be considered when multiple antimicrobial agents are used to treat infection. Use of two or more antimicrobial agents may be justified before organism identification or for the benefit of two drugs with different mechanisms of action. Several antimicrobials are administered routinely in combination (e.g., trimethoprim-sulfamethoxazole, amoxicillin-clavulanate) because of synergism(significantly greater bacterial killing or spectrum of activity than when either is used alone). The use of a bacteriostatic drug, such as a tetracycline, along with a β-lactam agent, effective against growing organisms only, may result in antibiotic antagonism, or less bacterial killing in the presence of both drugs than if either is used alone. Available @ StudentConsult.com Fever without a Source Fever of Unknown Origin


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Pediatrics_Nelson. Available @ StudentConsult.com Fever without a Source Fever of Unknown Origin Core body temperature is normally maintained within 1° C to 1.5° C in a range of 37° C to 38° C. Normal body temperature is generally considered to be 37° C (98.6° F; range, 97° F to 99.6° F). There is a normal diurnal variation, with maximum temperature in the late afternoon. Rectal temperatures higher than 38° C (>100.4° F) generally are considered abnormal, especially if associated with symptoms.


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Pediatrics_Nelson. Normal body temperature is maintained by a complex regulatory system in the anterior hypothalamus. Development of fever begins with release of endogenous pyrogens into the circulation as the result of infection, inflammatory processes, or malignancy. Microbes and microbial toxins act as exogenous pyrogens by stimulating release of endogenous pyrogens, including cytokines such as interleukin-1, interleukin-6, tumor necrosis factor, and interferons. These cytokines reach the anterior hypothalamus, liberating arachidonic acid, which is metabolized to prostaglandin E2. Elevation of the hypothalamic thermostat occurs via a complex interaction of complement and prostaglandin-E2 production. Antipyretics (acetaminophen, ibuprofen, aspirin) inhibit hypothalamic cyclooxygenase, decreasing production of prostaglandin E2. Aspirin is associated with Reye syndrome in children and is not recommended as an antipyretic. The response to antipyretics does not distinguish bacterial from viral infections.


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Pediatrics_Nelson. The pattern of fever in children may vary, depending on ageand the nature of the illness. Neonates may not have a febrileresponse and may be hypothermic, despite significant infection,whereas older infants and children younger than 5 years of agemay have an exaggerated febrile response with temperatures ofup to 105° F (40.6° C) in response to either a serious bacterialinfection or an otherwise benign viral infection. Fever to this degree is unusual in older children and adolescents and suggests a serious process. The fever pattern does not reliably distinguish fever caused by infectious microorganisms from that resulting from malignancy, autoimmune diseases, or drugs.


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Pediatrics_Nelson. Children with fever without a focus present a diagnostic challenge that includes identifying bacteremia and sepsis. Bacteremia, the presence of bacteria in the bloodstream, may be primary or secondary to a focal infection. Sepsis is the systemic response to infection that is manifested by hyperthermia or hypothermia, tachycardia, tachypnea, and shock (see Chapter 40). Children with septicemia and signs of central nervous system dysfunction (irritability, lethargy), cardiovascular impairment (cyanosis, poor perfusion), and disseminated intravascular coagulation (petechiae, ecchymosis) are readily recognized as toxic appearing or septic. Most febrile illnesses in children may be categorized as follows: Fever of short duration accompanied by localizing signs and symptoms, in which a diagnosis can often be established by clinical history and physical examination


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Pediatrics_Nelson. Fever of short duration accompanied by localizing signs and symptoms, in which a diagnosis can often be established by clinical history and physical examination Fever without localizing signs (fever without a focus), frequently occurring in children younger than 3 years of age, in which a history and physical examination fail to establish a cause Fever of unknown origin (FUO), defined as fever for >14 days without an identified etiology despite history, physical examination, and routine laboratory tests or after 1 week of hospitalization and evaluation


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Pediatrics_Nelson. Fever or temperature instability in infants younger than3 months of age is associated with a higher risk of serious bacterial infections than in older infants. These youngerinfants usually exhibit only fever and poor feeding, without localizing signs of infection. Most febrile illnesses inthis age group are caused by common viral pathogens, butserious bacterial infections include bacteremia (caused by group B streptococcus [GBS], Escherichia coli, and Listeria monocytogenes in neonates; and Streptococcus pneumoniae, Haemophilus influenzae, nontyphoidal Salmonella, and Neisseria meningitidis in 1to 3-month-old infants), urinary tract infection (UTI) (E. coli), pneumonia (S. pneumoniae, GBS, or Staphylococcus aureus), meningitis (S. pneumoniae, H. influenzae type b, GBS, N. meningitidis, herpes simplex virus [HSV], enteroviruses), bacterial diarrhea (Salmonella, Shigella, E. coli), and osteomyelitis or septic arthritis (S. aureus or GBS).


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Pediatrics_Nelson. Differentiation between viral and bacterial infections in young infants is difficult. Febrile infants <3 months of age who appear ill, especially if follow-up is uncertain, and all febrile infants <4 weeks of age should be admitted to the hospital for empirical antibiotics pending culture results. After blood, urine, and cerebrospinal fluid cultures are obtained, broad-spectrum parenteral antibiotics (typically ampicillin with cefotaxime or gentamicin) are administered. The choice of antibiotics depends on the pathogens suggested by localizing findings. The possibility of neonatal HSV should also be considered in febrile children <4 weeks old, and empirical acyclovir begun in those in whom neonatal HSV is a concern. Well-appearing febrile infants ≥4 weeks of age without an identifiable focus and with certainty of follow-up are at a low risk of developing a serious bacterial infection (0.8% develop bacteremia, and 2% develop a serious localized bacterial infection). Specific criteria


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Pediatrics_Nelson. and with certainty of follow-up are at a low risk of developing a serious bacterial infection (0.8% develop bacteremia, and 2% develop a serious localized bacterial infection). Specific criteria identifying these low-risk infants include age older than 1 month, well-appearing without a focus of infection, no history of prematurity or prior antimicrobial therapy, a white blood cell (WBC) count of 5000 to 15,000/μL, and urine with less than 10 WBCs/high-power field. Fecal leukocyte testing and chest radiograph can be considered in infants with diarrhea or respiratory signs. Low-risk infants may be followed as outpatients without empirical antibiotic treatment, or, alternatively, may be treated with intramuscular ceftriaxone. Regardless of antibiotic treatment, close follow-up for at least 72 hours, including re-evaluation in 24 hours or immediately with any clinical change, is essential.


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Pediatrics_Nelson. A common problem is the evaluation of a febrile but well-appearing child younger than 3 years of age without localizing signs of infection. Although most of these children have self-limited viral infections, some have occult bacteremia (bacteremia without identifiable focus) or UTIs, and a few have severe and potentially life-threatening illnesses. It is difficult, even for experienced clinicians, to differentiate patients with bacteremia from those with benign illnesses.


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Pediatrics_Nelson. Observational assessment is a key part of the evaluation. Descriptions of normal appearance and alertness include child looking at the observer and looking around the room, with eyes that are shiny or bright. Descriptions that indicate severe impairment include glassy eyes and stares vacantly into space. Observations such as sitting, moving arms and legs on table or lap, and sits without support reflect normal motor ability, whereas no movement in mother’s arms and lies limply on tableindicate severe impairment. Normal behaviors, such as vocalizing spontaneously, playing with objects, reaching for objects, smiling, and crying with noxious stimuli, reflect playfulness; abnormal behaviors reflect irritability. Normally, crying children are consolable and stop crying when held by the parent, whereas severe impairment is indicated by continual cry despite being held and comforted.


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Pediatrics_Nelson. Children between 2 months and 3 years of age are atincreased risk for infection with organisms with polysaccharide capsules, including S. pneumoniae, H. influenzae, N. meningitidis, and nontyphoidal Salmonella. Effective phagocytosisof these organisms requires opsonic antibody. Transplacentalmaternal IgG initially provides immunity to these organisms,but as the IgG gradually dissipates, risk of infection increases.In the United States, use of conjugate H. influenzae type b and S. pneumoniae vaccines has dramatically reduced the incidence of these infections. Determining the child’s immunization status is essential to evaluate risk of these infections. An approach to evaluation of these children is outlined inFigure 96-1.


Pediatrics_Nelson

Pediatrics_Nelson. Most episodes of fever in children younger than 3 years of age have a demonstrable source of infection elicited by history, physical examination, or a simple laboratory test. In this age group, the most commonly identified serious bacterial infection is a UTI. A blood culture to evaluate for occult bacteremia, and urinalysis and urine culture to evaluate for a UTI, should be considered for all children younger than 3 years of age with fever without localizing signs. Stool culture should be obtained in those with diarrhea marked by blood or mucous. Ill-appearing children should be admitted to the hospital and treated with empirical antibiotics. Approximately 0.2% of well-appearing febrile children 3 to 36 months of age vaccinated against S. pneumoniae and


Pediatrics_Nelson

Pediatrics_Nelson. Approximately 0.2% of well-appearing febrile children 3 to 36 months of age vaccinated against S. pneumoniae and H. influenzae and without localizing signs have occult bacteremia. Risk factors for occult bacteremia include temperature of 102.2° F (39° C) or greater, WBC count of 15,000/mm3 or more, and elevated absolute neutrophil count, band count, erythrocyte sedimentation rate, or C-reactive protein. No combination of demographic factors (socioeconomic status, race, gender, and age), clinical parameters, or laboratory tests in these children reliably predicts occult bacteremia. Occult bacteremia in otherwise healthy children is usually transient and self-limited but may progress to serious localizing infections. Well-appearing children usually are followed as Assess H and P for “low risk” status Age? <1 mo >1 mo Low risk Not low risk CBC with differential, blood culture, urine culture All parameters normal? No Yes


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Pediatrics_Nelson. Assess H and P for “low risk” status Age? <1 mo >1 mo Low risk Not low risk CBC with differential, blood culture, urine culture All parameters normal? No Yes All parameters normal? NoYes outpatients without empirical antibiotic treatment or, alternatively, treated with intramuscular ceftriaxone. Regardless of antibiotic treatment, close follow-up for at least 72 hours, including re-evaluation in 24 hours or immediately with any clinical change, is essential. Children with a positive blood culture require immediate re-evaluation, repeat blood culture, consideration for lumbar puncture, and empirical antibiotic treatment.


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Pediatrics_Nelson. Children with sickle cell disease have impaired splenic function and properdin-dependent opsonization that places them at increased risk for bacteremia, especially during the first 5 years of life. Children with sickle cell disease and fever who appear seriously ill, have a temperature of 104° F (40° C) or greater, or WBC count less than 5000/mm3 or greater than 30,000/mm3 should be hospitalized and treated empirically with antibiotics. Other children with sickle cell disease and fever should have blood culture, empirical treatment with ceftriaxone, and close outpatient follow-up. Osteomyelitis resulting from Salmonella or S. aureus is more common in children with sickle cell disease; blood culture is not always positive in the presence of osteomyelitis. Available @ StudentConsult.com Fever of Unknown Origin


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Pediatrics_Nelson. Available @ StudentConsult.com Fever of Unknown Origin FUO is defined as temperature greater than 100.4° F (38° C) lasting for >14 days without an obvious cause despite a complete history, physical examination, and routine screening laboratory evaluation. It is important to distinguish persistent fever from recurrent or periodic fevers, which usually represent serial acute illnesses. The initial evaluation of FUO requires a thorough history and physical examination supplemented with a few screening laboratory tests (Fig. 96-2). Additional laboratory and imaging tests are guided by abnormalities on initial evaluation. Figure 96-1 Approach to a child younger than 36 months of age with fever without localizing signs. The specific management varies, depending on the age and clinical status of the child.


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Pediatrics_Nelson. Figure 96-1 Approach to a child younger than 36 months of age with fever without localizing signs. The specific management varies, depending on the age and clinical status of the child. Important historical elements include the impact the fever has on the child’s health and activity; weight loss; the use of drugs, medications, or immunosuppressive therapy; history of unusual, severe, or chronic infection suggesting immunodeficiency (see Chapter 72); immunizations; exposure to unprocessed or raw foods; history of pica and exposure to soil-borne or waterborne organisms; exposure to industrial or hob-by-related chemicals; blood transfusions; domestic or foreign travel; exposure to animals; exposure to ticks or mosquitoes; ethnic background; recent surgical procedures or dental work; tattooing and body piercing; and sexual activity.


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Pediatrics_Nelson. The etiology of most occult infections causing FUO is an unusual presentation of a common disease. Sinusitis, endocarditis, intra-abdominal abscesses (perinephric, intrahepatic, subdiaphragmatic), and central nervous system lesions (tuberculoma, cysticercosis, abscess, toxoplasmosis) may be relatively asymptomatic. Infections are the most common cause of FUO in children, followed by inflammatory diseases, malignancy, and other etiologies (Table 96-1). Inflammatory diseases account for approximately 20% of episodes. Malignancies are a less common cause of FUO in children than in adults, accounting for about 10% of all episodes. Approximately 15% of children with FUO have no diagnosis. Fever eventually resolves in many of these cases, usually without sequelae, although some may develop definable signs of rheumatic disease over time. Common infections causing FUO in patients with known or newly diagnosed immunodeficiencyinclude viral hepatitis, Epstein-Barr virus, cytomegalovirus,


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Pediatrics_Nelson. definable signs of rheumatic disease over time. Common infections causing FUO in patients with known or newly diagnosed immunodeficiencyinclude viral hepatitis, Epstein-Barr virus, cytomegalovirus, Bartonella henselae, ehrlichiosis, Salmonella, and tuberculosis.


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Pediatrics_Nelson. Factitious fever or fever produced or feigned intentionally by the patient (Munchausen syndrome) or the parent of a child (Munchausen syndrome by proxy) is an importantconsideration, particularly if family members are familiar with health care practices (see Chapter 22). Fever should be recorded in the hospital by a reliable individual who remains with the patient when the temperature is taken. Continuous observation over a long period and repetitive evaluation are essential. Screening tests for FUO include complete blood count with WBC and differential count, platelet count, erythrocyte Admit, obtain appropriate tests Begin appropriate therapy Additional tests (special cultures, PCR, serology, biopsy) and imaging studies (CT, MRI, radionuclide scans)


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Pediatrics_Nelson. Admit, obtain appropriate tests Begin appropriate therapy Additional tests (special cultures, PCR, serology, biopsy) and imaging studies (CT, MRI, radionuclide scans) Figure 96-2 Approach to the evaluation of fever of unknown origin (FUO) in children. Screening laboratory tests include a complete blood count and differential white blood cell count, platelet count, erythrocyte sedimentation rate, hepatic transaminase levels, urinalysis, bacterial cultures of urine and blood, chest radio-graph, and evaluation for rheumatic disease with antinuclear antibody, rheumatoid factor, and serum complement (C3, C4, CH50). PCR, polymerase chain reaction. Abscesses: abdominal, brain, dental, hepatic, pelvic, perinephric, rectal, subphrenic, splenic, periappendiceal, psoas Cholangitis Infective endocarditis Mastoiditis Osteomyelitis Pneumonia Pyelonephritis Sinusitis


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Pediatrics_Nelson. Mycoplasma pneumoniae Relapsing fever (Borrelia recurrentis, other Borrelia) Salmonellosis Spirillum minus (rat-bite fever) Streptobacillus moniliformis (rat-bite fever) Causes of Fever of Unknown Origin in Children—cont’d Juvenile idiopathic arthritis (systemic onset, Still disease) Inflammatory bowel disease (Crohnʼs disease, ulcerative colitis) Kawasaki disease Polyarteritis nodosa Rheumatic fever Castleman disease Chronic active hepatitis Cyclic neutropenia Deafness, urticaria, amyloidosis syndrome Periodic fever syndromes Poisoning Postoperative (pericardiotomy, craniectomy) Modified from Nield LS, Kamat D: Fever without a focus. In Kliegman RM, Stanton BF, St. Geme III JW, et al: Nelson Textbook of Pediatrics, ed 19, Philadelphia, 2011, Saunders.


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Pediatrics_Nelson. Modified from Nield LS, Kamat D: Fever without a focus. In Kliegman RM, Stanton BF, St. Geme III JW, et al: Nelson Textbook of Pediatrics, ed 19, Philadelphia, 2011, Saunders. sedimentation rate, C-reactive protein, hepatic transaminase and B. henselae antibody. Consultation with infectious dis-levels, urinalysis, cultures of urine and blood, chest radio-ease, immunology, rheumatic disease, or oncology specialists graph, and evaluation for rheumatic disease with antinuclear should be considered. Further tests may include lumbar puncantibody, rheumatoid factor, and serum complement (C3, C4, ture for cerebrospinal fluid analysis and culture; computed CH50). Additional tests for FUO may include throat culture, tomography or magnetic resonance imaging of the chest, stool culture, tuberculin skin test or interferon-gamma release abdomen, and head; radionuclide scans; and bone marrow assay, HIV antibody, Epstein-Barr virus antibody profile, biopsy for cytology and culture.


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Pediatrics_Nelson. Available @ StudentConsult.com Rashes are a common manifestation of many infections; this chapter describes five common childhood viral exanthems characterized by fever and rash. Rash distribution and appearance provide important clues to the differential diagnosis, including other infectious agents (Table 97-1).


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Pediatrics_Nelson. Measles (rubeola) is highly contagious and is caused by a single-stranded RNA paramyxovirus with one antigenic type. Humans are the only natural host. Measles virus infects the upper respiratory tract and regional lymph nodes and is spread systemically during a brief, low-titer primary viremia. A secondary viremia occurs within 5 to 7 days as virus-infected monocytes spread the virus to the respiratory tract, skin, and other organs. Virus is present in respiratory secretions, blood, and the urine of infected individuals. Measles virus is transmitted by droplets or the airborne route and is highly contagious. Infected persons are contagious from 1 to 2 days before onset of symptoms—from about 5 days before to 4 days after the appearance of rash—and immunocompromised persons can have prolonged excretion of contagious virus.


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Pediatrics_Nelson. Measles remains endemic in regions of the world where measles vaccination is not available and is responsible for about 1 million deaths annually. Since 2000 there typically have been fewer than 100 cases reported annually in the United States, although outbreaks resulting from imported virus after international travel occur. Infections of nonimmigrant children during outbreaks may occur among those too young to be vaccinated or in communities with low immunization rates. Most young infants are protected by transplacental maternal antibody until the end of their first year. Measles infection is divided into four phases: incubation, prodromal (catarrhal), exanthematous (rash), and recovery. The incubation period is 8 to 12 days from exposure to symptom onset and a mean of 14 days (range, 7 to 21) from exposure to rash onset. The manifestations of the 3-day prodromal period Viruses Adenovirus Measles Rubella Roseola (HHV-6 or HHV-7) Erythema infectiosum (fifth disease, parvovirus


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Pediatrics_Nelson. Viruses Adenovirus Measles Rubella Roseola (HHV-6 or HHV-7) Erythema infectiosum (fifth disease, parvovirus Meningococcal infection (early) Salmonella typhi (typhoid fever, “rose spots”) Lyme disease (erythema migrans) Rickettsiae Rocky Mountain spotted fever (early) Typhus (scrub, endemic) Ehrlichiosis Bacteria Scarlet fever (group A streptococcus) Staphylococcal scalded skin syndrome Toxic shock syndrome (Staphylococcus aureus, Bacteria M. pneumoniae Group A streptococcus Other Drug reaction Serum sickness Vesicular, Bullous, Pustular Bacteria Sepsis (meningococcal, gonococcal, pneumococcal, Haemophilus influenzae type b) Fungi Necrotic eschar (Aspergillus, Mucor) HBV, Hepatitis B virus; HHV, human herpesvirus.


Pediatrics_Nelson

Pediatrics_Nelson. Fungi Necrotic eschar (Aspergillus, Mucor) HBV, Hepatitis B virus; HHV, human herpesvirus. are cough, coryza, conjunctivitis, and the pathognomonic Koplik spots (gray-white, sand grain-sized dots on the buccal mucosa opposite the lower molars) that last 12 to 24 hours. The conjunctiva may reveal a characteristic transverse line of inflammation along the eyelid margin (Stimson line). The classic symptoms of cough, coryza, and conjunctivitis occur during the secondary viremia of the exanthematous phase, which often is accompanied by high fever (40° C to 40.5° C [104° F to 105° F]). The macular rash begins on the head (often above the hairline) and spreads over most of the body in a cephalad to caudal pattern over 24 hours. Areas of the rash often are confluent. The rash fades in the same pattern, and illness severity is related to the extent of the rash. It may be petechial or hemorrhagic (black measles). As the rash fades, it undergoes brownish discoloration and desquamation.


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Pediatrics_Nelson. Cervical lymphadenitis, splenomegaly, and mesenteric lymphadenopathy with abdominal pain may be noted with the rash. Otitis media, pneumonia, and diarrhea are more common in infants. Liver involvement is more common in adults. The term modified measles describes mild cases of measles occurring in persons with partial protection against measles. Modified measles occurs in persons vaccinated before 12 months of age or with coadministration of immune serum globulin, in infants with disease modified by transplacental antibody, or in persons receiving immunoglobulin.


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Pediatrics_Nelson. Routine laboratory findings are nonspecific and do not aid in diagnosis. Leukopenia is characteristic. In patients with acute encephalitis, the cerebrospinal fluid reveals an increased protein, a lymphocytic pleocytosis, and normal glucose levels. Measles virus culture is not generally available, though identification of measles RNA via reverse transcriptase-polymerase chain reaction (PCR) may be available through state public health departments or the Centers for Disease Control and Prevention (CDC). Serologic testing for IgM antibodies that appear within 1 to 2 days of the rash and persist for 1 to 2 months in unimmunized persons confirms the clinical diagnosis, though IgM antibodies may be present only transiently in immunized people. Suspected cases should be reported immediately to the local or state health department.


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Pediatrics_Nelson. The constellation of fever, rash, cough, and conjunctivitis isdiagnostic for measles. Koplik spots are pathognomonic butare not always present at the time the rash is most pronounced.Confirmation is by diagnostic antibody increases in acute andconvalescent sera. The rash must be differentiated from rubella, roseola, enteroviral or adenoviral infection, infectious mononucleosis, toxoplasmosis, meningococcemia, scarlet fever, rickettsial disease, Kawasaki disease, serum sickness, and drug rash. Routine supportive care includes maintaining adequate hydration and antipyretics. High-dose vitamin A supplementation has been shown to improve the outcome of infants with measles in developing countries. The World Health Organization recommends routine administration of vitamin A for 2 days to all children with acute measles.


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Pediatrics_Nelson. Otitis media is the most common complication of measles infection. Interstitial (measles) pneumonia can occur, or pneumonia may result from secondary bacterial infection with Streptococcus pneumoniae, Staphylococcus aureus, or group A streptococcus. Persons with impaired cell-mediated immunity may develop giant cell (Hecht) pneumonia, which is usually fatal. Myocarditis and mesenteric lymphadenitis are infrequent complications.


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Pediatrics_Nelson. Encephalomyelitis occurs in 1 to 2 per 1000 cases and usually occurs 2 to 5 days after the onset of the rash. Early encephalitis probably is caused by direct viral infection of brain tissue, whereas later onset encephalitis is a demyelinating and probably an immunopathologic phenomenon. Subacute sclerosing panencephalitis is a late neurologic complication of slow measles infection that is characterized by progressive behavioral and intellectual deterioration and eventual death. It occurs in approximately 1 in every 1 million cases of measles, an average of 8 to 10 years after measles. There is no effective treatment.


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Pediatrics_Nelson. Deaths most frequently result from bronchopneumonia orencephalitis, with much higher risk in persons with malignancy,severe malnutrition, age under 5 years, or immunocompromise (such as HIV infection). Late deaths in adolescents andadults usually result from subacute sclerosing panencephalitis. Other forms of measles encephalitis in immunocompetentpersons are associated with a mortality rate of approximately15%, with 20% to 30% of survivors having serious neurologicsequelae.


Pediatrics_Nelson

Pediatrics_Nelson. Live measles vaccine prevents infection and is recommended as measles, mumps, and rubella (MMR) for children at 12 to 15 months and 4 to 6 years of age. The MMRV (MMR combined with varicella vaccine) is an alternative vaccine for children 12 months to 12 years of age, provided there are no contraindications, but is associated with a higher rate of febrile seizures following administration. The second dose of MMR is not a booster dose but significantly reduces the primary vaccine failure rate, from <5% to <1%. Contraindications to measles vaccine include immunocompromised states or an immunosuppressive course of corticosteroids (>2 mg/kg/day for >14 days); pregnancy; or recent administration of immunoglobulin (3 to 11 months, depending on dose). MMR vaccination is recommended for all HIV-infected persons without evidence of severe immunosuppression (low age-specific total CD4 T-lymphocyte count or a low CD4 T-lymphocyte count as a percentage of total lymphocytes), children with cancer


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Pediatrics_Nelson. persons without evidence of severe immunosuppression (low age-specific total CD4 T-lymphocyte count or a low CD4 T-lymphocyte count as a percentage of total lymphocytes), children with cancer in remission who have not received chemotherapy in the previous 3 months, and children who have not received immunosuppressive corticosteroids in the previous month. Susceptible household contacts with a chronic disease or who are immunocompromised should receive postexposure prophylaxiswith measles vaccine within 72 hours of measles exposure or immunoglobulin within 6 days of exposure.


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Pediatrics_Nelson. Rubella, also known as German measles or 3-day measles,is caused by a single-stranded RNA virus with a glycolipid envelope and is a member of the togavirus family. Humans are the only natural host. Rubella virus invades the respiratory epithelium and disseminates via a primary viremia. Afterreplication in the reticuloendothelial system, a secondaryviremia ensues, and the virus can be isolated from peripheral blood monocytes, cerebrospinal fluid, and urine. Rubellavirus is most contagious through direct or droplet contactwith nasopharyngeal secretions from 2 days before until5 to 7 days after rash onset, although virus may be present innasopharyngeal secretions from 7 days before until 14 days after the rash.


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Pediatrics_Nelson. Infection in utero results in significant morbidity from congenital rubella syndrome (CRS) with associated ophthalmologic, cardiac, and neurologic manifestations (see Chapter 66).Maternal infection during the first trimester results in fetalinfection with generalized vasculitis in more than 90% of cases.Infants with congenital rubella may shed the virus in nasopharyngeal secretions and urine for longer than 12 months afterbirth and may transmit the virus to susceptible contacts. In unvaccinated populations, rubella usually occurs in the spring, with epidemics occurring in cycles of every 6 to 9 years. Approximately 25% to 50% of cases are subclinical. Fewer than 20 cases of rubella now occur annually in the United States. Outbreaks of rubella occasionally occur in nonvaccinated groups from internationally imported cases. Transplacental antibody is protective during the first 6 months of life. Available @ StudentConsult.com


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Pediatrics_Nelson. Available @ StudentConsult.com The incubation period for postnatal rubella is typically 16 to18 days (range, 14 to 21 days). The mild catarrhal symptomsof the prodromal phase of rubella may go unnoticed. The characteristic signs of rubella are retroauricular, posterior cervical,and posterior occipital lymphadenopathy accompanied by anerythematous, maculopapular, discrete rash. The rash beginson the face and spreads to the body, lasting for 3 days and lessprominent than that of measles. Rose-colored spots on the softpalate, known as Forchheimer spots, develop in 20% of patientsand may appear before the rash. Other manifestations of rubellainclude mild pharyngitis, conjunctivitis, anorexia, headache,malaise, and low-grade fever. Polyarthritis, usually of the hands,may occur, especially among adult females, but usually resolveswithout sequelae. Paresthesias and tendinitis may occur.


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Pediatrics_Nelson. Routine laboratory findings are nonspecific and generally do not aid in diagnosis. The white blood cell count usually is normal or low, and thrombocytopenia rarely occurs. Diagnosis is confirmed by serologic testing for IgM antibodies (typically positive 5 days after symptom onset) or by a fourfold or greater increase in specific IgG antibodies in paired acute and convalescent sera. CRS cases can have detectable IgM until 3 months of age, and stable or rising IgG titers over the first 7 to 11 months of age. False-positive IgM results can occur. Cases of suspected congenital rubella syndrome and postnatal rubella infection should be reported to the local and state health department. The rash must be differentiated from measles, roseola, enteroviral or adenoviral infection, infectious mononucleosis, toxoplasmosis, scarlet fever, rickettsial disease, Kawasaki disease, serum sickness, and drug rash.


Pediatrics_Nelson

Pediatrics_Nelson. There is no specific therapy for rubella. Routine supportive care includes maintaining adequate hydration and antipyretics. Other than congenital rubella syndrome (see Chapter 66) arising from rubella infection during pregnancy, complications are rare. Deaths rarely occur with rubella encephalitis. Live rubella vaccine prevents infection and is recommended as MMR for children at 12 to 15 months and at 4 to 6 yearsof age. After vaccination, rubella virus is shed from the nasopharynx for several weeks, but it is not communicable. In children, rubella vaccine rarely is associated with adverse effects,but in postpubertal females, it causes arthralgias in 25% ofvaccinated individuals and acute arthritis-like symptoms in10% of vaccinated individuals. These symptoms typicallydevelop 1 to 3 weeks after vaccination and last 1 to 3 days.


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Pediatrics_Nelson. Contraindications to rubella vaccine include immunocompromised states or an immunosuppressive course of corticosteroids (>2 mg/kg/day for >14 days); pregnancy; or recent administration of immunoglobulin (3 to 11 months, depending on dose). Vaccine virus has been recovered from fetal tissues, although no cases of CRS have been identified among infants born to women inadvertently vaccinated against rubella during pregnancy. Nevertheless women are cautioned to avoid pregnancy after receipt of rubella-containing vaccine for 28 days. All pregnant women should have prenatal serologic testing to determine their immune status to rubella, and susceptible mothers should be vaccinated after delivery and before hospital discharge. Susceptible, nonpregnant persons exposed to rubella should receive rubella vaccination. Immunoglobulin is not recommended for postexposure prophylaxis of susceptible, pregnant women exposed to rubella.


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Pediatrics_Nelson. Roseola infantum (exanthem subitum, sixth disease) is caused primarily by human herpesvirus type 6 (HHV-6), and by HHV-7 in 10% to 30% of cases. HHV-6 and HHV-7 are large, enveloped double-stranded DNA viruses that are members of the herpesvirus family. They infect mature mononuclear cells and cause a relatively prolonged (3 to 5 day) viremia during primary infection. They can be detected in the saliva of healthy adults, which suggests, as with other herpes-viruses, the development of lifelong latent infection and intermittent viral shedding.


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Pediatrics_Nelson. Transplacental antibody protects most infants until 6 months ofage. The incidence of infection increases as maternally derivedantibody levels decline. By 12 months of age, approximately60% to 90% of children have antibodies to HHV-6, and essentially all children are seropositive by 2 to 3 years of age. Thevirus is likely acquired from asymptomatic adults who periodically shed these viruses. HHV-6 is a major cause of acute febrileillnesses in infants and may be responsible for 20% of visits tothe emergency department for children 6 to 18 months of age.


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Pediatrics_Nelson. Roseola is characterized by high fever (often >40° C) with an abrupt onset that lasts 3 to 5 days. A maculopapular, rose-colored rash erupts coincidentally with defervescence, although it may be present earlier. The rash usually lasts 1 to 3 days but may fade rapidly and is not present in all infants with HHV-6 infection. Upper respiratory symptoms, nasal congestion, erythematous tympanic membranes, and cough may occur. Gastrointestinal symptoms are described. Most children with roseola are irritable and appear toxic. Roseola is associated with approximately one third of febrile seizures. Roseola caused by HHV-6 and HHV-7 is clinically indistinguishable, although HHV-6-associated roseola typically occurs in younger infants. Reactivation of HHV-6 following bone marrow transplantation may result in bone marrow suppression, hepatitis, rash, and encephalitis.


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Pediatrics_Nelson. Routine laboratory findings are nonspecific and do not aid in diagnosis. Encephalitis with roseola is characterized by pleocytosis (30 to 200 cells/mm3) with mononuclear cell predominance, elevated protein concentration, and normal glucose concentration. Serologic testing showing a fourfold rise in acute and convalescent sera or documentation of HHV-6 DNA by PCR in the cerebrospinal fluid is diagnostic. The pattern of high fever for 3 to 5 days without significant physical findings followed by onset of rash with defervescence of fever is characteristic. Many febrile illnesses may be easily confused with roseola during the preeruptive stage. Serious infections must be excluded, although most children are alert, behave normally, and continue with their usual daily activities. There is no specific therapy for roseola. Routine supportive care includes maintaining adequate hydration and antipyretics. In immunocompromised hosts, use of ganciclovir or foscarnet can be considered.


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Pediatrics_Nelson. The prognosis for roseola is excellent. A few deaths have been attributed to HHV-6, usually in cases complicated by encephalitis or virus-associated hemophagocytosis syndrome. There are no guidelines for prevention of roseola. Erythema infectiosum (fifth disease) is caused by the human parvovirus B19, a single-stranded DNA virus producing a benign viral exanthem in healthy children. The viral affinity for red blood cell progenitor cells makes it an important cause of aplastic crisis in patients with hemolytic anemias, including sickle cell disease, spherocytosis, and thalassemia. Parvovirus B19 also causes fetal anemia and hydrops fetalis after primary infection during pregnancy. The cell receptor for parvovirus B19 is the erythrocyte P antigen, a glycolipid present on erythroid cells. The virus replicates in actively dividing erythroid stem cells, leading to cell death that results in erythroid aplasia and anemia.


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Pediatrics_Nelson. Erythema infectiosum is common. Parvovirus B19 seroprevalence is only 2% to 9% in children younger than 5 years of age but increases to 15% to 35% in children 5 to 18 years and 30% to 60% in adults. Community epidemics usually occur in the spring. The virus is transmitted by respiratory secretions and by blood product transfusions.


Pediatrics_Nelson

Pediatrics_Nelson. The incubation period is typically 4 to 14 days and rarely maylast 21 days. Parvovirus B19 infections usually begin with a mild,nonspecific illness characterized by fever, malaise, myalgias, andheadache. In some cases, the characteristic rash appears 7 to 10days later. Erythema infectiosum is manifested by rash, low-grade or no fever, and occasionally pharyngitis and mild conjunctivitis. The rash appears in three stages. The initial stage istypically a “slapped cheek” rash with circumoral pallor. An erythematous symmetric, maculopapular, truncal rash appears 1 to4 days later, then fades as central clearing takes place, giving adistinctive lacy, reticulated rash that lasts 2 to 40 days (mean, 11days). This rash may be pruritic, does not desquamate, and mayrecur with exercise, bathing, rubbing, or stress. Adolescents andadults may experience myalgia, significant arthralgias or arthritis, headache, pharyngitis, coryza, and gastrointestinal upset.