118. American Academy of Pediatrics. Screening for elevated blood lead levels. American Academy of Pediatrics Committee on Environmental Health. Pediatrics 1998;101:1072–8. 119. Daniel K, Sedlis M, Polk L, et al. Childhood lead poisoning, New York City, 1988. MMWR 1990;39:1–7. Health Maintenance Visits: a Critical Review 37 CHAPTER 3 Immunization Ronald Gold, MD, MPH, FRCPC  Immunization prevents disease and saves lives. It is also one of the few health interventions that saves more money than it costs. Successful implementation of childhood immunization programs requires that both the health professionals involved in administering vaccines and parents be knowledgeable about the risks of the diseases and the benefits as well as the risks of the vaccines. In particular, it is extremely important that the true precautions and con- traindications are understood. The only absolute contraindications to immunization are as follows: 1,2 • Anaphylaxis to a previous dose of vaccine • Anaphylaxis to a constituent of a vaccine (eg, severe allergic reaction to influenza and yellow fever vaccines after eating eggs or allergy to neomycin in the case of inactivated polio vaccine[IPV] or mumps-measles-rubella [MMR] vaccine) • Pregnancy, in the case of MMR • Immunodeficiency, in the case of MMR Precautions which may indicate deferral of immunization include the following: • Recent administration of immunoglobulin, in the case of MMR (see 1,3 for details) • Moderate or severe acute illness with or without fever Conditions which are not contraindications to immunization are as follows: 1,2 • Local reaction to previous dose of vaccine • Mild acute illness with or without fever • Convalescent phase of an acute minor illness • Current antimicrobial therapy • Recent exposure to infection • Prematurity • Personal or family history of allergy • Family history of convulsions, sudden infant death syndrome (SIDS) • Convulsion, hypotonic–hypo-responsive (HHR) episode, or high fever (≥40.5°C) within 48 hours or persistent inconsolable crying lasting ≥3 h after prior dose of diph- theria-pertussis-tetanus (DPT) vaccine • Pregnancy, in the case of hepatitis B and influenza vaccines • Diagnosis of multiple sclerosis, any other autoimmune disorder, or muscular dystrophy Viral respiratory and gastrointestinal infections are very common in children less than 2 years of age. Studies have demonstrated that there is no increase in adverse events and no diminution of the immune responses if vaccination is performed while a child has a minor illness. Deferral of vaccination because of minor illness is all too common but should be avoided because children whose vaccinations are delayed have an increased probability of not being fully immunized. IMMUNIZATION SCHEDULES The Canadian schedule for routine immunization of children is given in Table 3–1. 1 The combined diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influen- zae type b vaccine is now used in all Canadian provinces and territories. Differences exist between jurisdictions regarding at what age the second dose of MMR and at which grade school–based hepatitis B vaccination should be administered. Information on schedules for children whose immunization did not begin in early infancy can be found in the Canadian Immunization Guide. The routine immunization schedules differ between the United States and Canada because (1) the combined vaccine is not yet available, (2)a sequential killed–live polio vaccine schedule is recommended, and (3) both hepatitis B and varicella vaccines are recommended for infants in the United States (Table 3–2). 4,5 DIPHTHERIA Epidemiology Since 1983, less than five cases of diphtheria have been reported annually in Canada, almost all of which were in adults who had been either partially immunized or not immunized at all. Diphtheria is still a severe disease—the case fatality rate is 5 to 10 percent. Diphtheria Toxoid Diphtheria toxoid (D) is available in Canada and the United States, either separately or com- bined with one or more vaccines, including tetanus toxoid (T), acellular pertussis vaccine (aP), and (IPV). The combination recommended for routine immunization in Canada is D, T, aP, and IPV, DTaP-IPV, which is used to dissolve lyophilized Haemophilus influenzae type b vaccine (tetanus toxoid conjugate polyribose-phosphate, [PRP-T]). The resulting combi- nation, DTaP-IPV/PRP-T, is administered as a single injection. The recommended vaccine in the United States is DTaP since combinations with IPV and/or Haemophilus b (Hib) vac- cine are not yet licensed. 4 For children over 7 years old and adults, a reduced amount of diphtheria toxoid is used (2 Lf units per dose rather than 12 to 25 Lf units) to minimize local reactions in persons who 40 Evidence-Based Pediatrics Table 3–1 Routine Immunization of Infants and Children in Canada Age DTaP IPV Hib MMR Td HB 2 mo X X X X or 4 mo X X X 6 mo X X X 12 mo X 18 mo X X X X or 4–6 y X X X 9–12 y X 14–16 y X DTaP = diphtheria, tetanus, acellular pertussis vaccine, usually combined with IPV and PRP-T. DTaP should be used for all doses, including completion of the series in those started with whole-cell pertussis vaccine; IPV = inac- tivated polio vaccine; Hib = Haemophilus influenzae type b conjugate vaccine: tetanus toxoid conjugate (PRP-T) used with combined DTaP-IPV in Canada; MMR = measles mumps rubella vaccine, first dose on or after first birthday, second dose either at 18 mo or at 4 to 6 y, depending on province; Td = adult tetanus, diphtheria vac- cine with reduced dose of diphtheria toxoid for those ≥7 years of age; HB = hepatitis B vaccine: 3 doses at 0, 1, and 6 months either in infancy or in preadolescence, depending on province. Immunization 41 Table 3–2 Routine Immunization of Infants and Children in the United States * Birth 1 mo 2 mo 4 mo 6 mo 12 mo 15 mo 18 mo 4–6 y 11–12 y 14–16 y Hepatitis 1 Hep B Hep B Hep B Hep B Diphtheria, Tetanus, Pertussis 2 DTaP DTaP DTaP DTaP DTaP Td H. influenzae type b 3 Hib Hib Hib Polio 4 IPV IPV Polio Measles, Mumps, Rubella 5 MMR Vari ce lla 6 * modified from 4,5 Vaccines are listed under recommended ages. Bars indicate the range of ages recommended for immunization. Shaded bars indicate vaccines to be given if previously recommended doses were missed or given earlier than minimum age. 1. Infants born to HbsAg–negative mothers should receive the 2nd dose of HBV vaccine at least 1 month after 1st dose. The 3rd dose should be given at least 4 months after the 1st dose and at least 2 months after the 2nd dose but not before 6 months of age. 2. DTaP (diphtheria and tetanus toxoids and acellular pertussis vaccine) is preferred vaccine for all doses, including completion of series in those that began with whole-cell DTP. The 4th dose of DTaP can be given as early as 12 months, provided 6 months have elapsed since the 3rd dose and if the child is unlikely to return at 15 to 18 months. Td is recommended at 11 to 12 months of age if at least 5 years have elapsed since the last dose of DTP, DTaP, or DT. Subsequent doses of Td should be given every 10 years. 3. Three Hib conjugate vaccines are licensed for infant use. Consult package insert for appropriate schedule. 4. Both inactivated (IPV) and oral (OPV) polio vaccines are licensed. The first two doses should be IPV to minimize the risk of vaccine-associated paralytic polio. The 3rd and 4th doses can be either IPV (for all IPV schedule) or OPV (for sequential IPV–OPV schedule). OPV is no longer recommended for the first two doses. 5. The 2nd dose of MMR is recommended at 4 to 6 years of age but may be given at any visit provided at least 4 weeks have elapsed since the administration of the 1st dose. The 1st dose should be given at or after 12 months of age. 6. Varicella vaccine is recommended at any visit on or after the first birthday for susceptible children, that is, those who lack a reliable history of chickenpox. Susceptible persons 13 years of age or older should receive two doses, given at least 4 weeks apart. VarVar MMRMMR Polio Hib have previously been vaccinated. 6–8 The adult formulation is usually combined with Td or with Td and IPV (Td-IPV). Adverse Events The most common reaction caused by diphtheria toxoid is redness, swelling, pain, and ten- derness at the site of the injection. The pain may cause babies to cry and be irritable. Local reactions are much more common in children and adults receiving boosters of the diphthe- ria toxoid than in infants receiving the first three doses. Efficacy Diphtheria toxoid prevents disease in most children and adults who are fully immunized. Those who do get diphtheria in spite of being fully vaccinated have a milder illness with fewer complications. Evidence for the efficacy of diphtheria toxoid includes • trials in school children in Toronto, which demonstrated a 75 percent reduction in the incidence of diphtheria in vaccinated compared to unvaccinated children; 9 • the virtual disappearance of diphtheria cases in all countries in which immunization of infants and children is routine; 10–13 • milder disease and fewer complications in fully immunized persons. 14 Indirect evidence supporting the effectiveness of diphtheria toxoid is provided by the current experience in Russia, Ukraine, and other states of the former Soviet Union. 13 A marked decrease in the number of children being vaccinated was followed by epidemics of diphtheria; over 100,000 cases of diphtheria and more than 1,200 deaths occurred in Russia and Ukraine since 1990. 13 Recommendations There is good evidence to support the recommendation of routine immunization of all chil- dren with diphtheria toxoid, including one well-designed controlled trial without random- ization, dramatic declines in disease incidence in all countries within a short period of introduction of mass immunization, and resurgence of epidemics when vaccination coverage declines (Table 3–3). The optimal schedule of boosters for adults remains to be determined. TETANUS Epidemiology The frequency of tetanus has declined in all countries with successful immunization pro- grams. Since 1985, there have been fewer than five cases per year in Canada. Most cases of tetanus now occur in persons over 60 years who have never been vaccinated. 42 Evidence-Based Pediatrics Table 3–3 Summary of Quality of Evidence Supporting Use of DTaP-PV and Hib Vaccines Immunizing Agent Quality of Evidence Recommendation Diphtheria toxoid II–1, II–3 A Tetanus toxoid I, II–3 A Acellular pertussis vaccine I, II–2 A Inactivated polio vaccine I, II–3 A Hib vaccine I, II–3 A Tetanus Toxoid Tetanus toxoid is supplied in Canada and the United States either by itself or combined with one or more other vaccines, including diphtheria toxoid, pertussis vaccine, and IPV. (See sec- tion above on “Diphtheria Toxoid” for description of combinations available in Canada.) Adverse Events Redness, swelling, pain, and tenderness at the site of injection are the most common reac- tions occurring after administration of tetanus toxoid. 15 The likelihood of local reactions increases with the number of doses given. 16 Severe local reactions after boosters occur in less than 2 percent of adults, primarily in those who have too many boosters, that is more than once every 10 years. 17 Other reactions following tetanus vaccination include swollen lymph glands (especially those near the site of injection), fever, headache, and muscle aches. Allergic reactions (usually hives) do occur but are rare. 18 As tetanus toxoid is usually given in combination with other vaccines, the exact factor causing a reaction may not be easy to identify. Severe allergic reactions are much less common in infants and young children than in adults. 19 Adverse neurologic events have been reported following administration of tetanus tox- oid. The frequency of neurologic reactions is estimated to be less than one per million doses of vaccine, making it impossible to determine whether the association is coincidental or causal. 20 Efficacy Routine immunization of U.S. soldiers during World War II resulted in a 30-fold reduction in the incidence of tetanus occurring after war wounds, compared with World War I. 21 Pro- grams to prevent tetanus of newborns in the developing countries confirm that tetanus tox- oid is extremely effective; in a double-blind controlled trial, no disease was seen in infants born to mothers who had received at least two doses of tetanus toxoid compared with a rate of 78 per 1,000 live births in control infants. 22 Tetanus is extremely rare in all countries with effective programs for vaccination of children. 23 Recommendations There is good evidence to support the recommendation of routine immunization of all chil- dren with tetanus toxoid including the reduced incidence of tetanus in U.S. military per- sonnel in World War II compared with World War I; 21 the dramatic declines in incidence in all countries within a short period of introduction of mass immunization; 23 and random- ized, double-blind controlled trials confirming the efficacy of tetanus toxoid in preventing neonatal tetanus in the developing countries (see Table 3–3). 22 The optimal schedule of boosters for adults remains to be determined. PERTUSSIS Epidemiology Introduction of routine immunization with DPT in the 1940s resulted in a 90 percent decrease in reported cases of pertussis, from an average of 17,463 cases reported annually in the immediate prevaccine era to 4,900 cases per year for 1986 through 1995. 24 The actual number of cases is 10 to 15 times greater than the reported number because of incomplete reporting of the disease by physicians. 25 The introduction of routine DPT vaccination was also followed by a significant change in the age distribution of pertussis. In the prevaccine era, the peak incidence of pertussis occurred in children 1 to 5 years of age and less than 15 percent of reported cases occurred Immunization 43 in infants. 26 With routine vaccination, the peak incidence switched from young children to infants less than 1 year of age, among whom approximately 50 percent of reported cases occurred. Concurrently, there has been a significant increase in the proportion of cases occurring in adolescents and young adults. 27 Approximately 85 percent of Canadian children have received 4 doses of DPT by 2 years of age and >90 percent have received 5 doses by 6 years of age. 24 However, disease continues to occur, along with epidemics every 3 to 5 years. 24,25 The lack of change in the interval between epidemics is strong evidence that routine vaccination, as presently practiced with a primary series of DPT at 2, 4, and 6 months followed by boosters at 18 months and at 4 to 6 years, has failed to interrupt the transmission of Bordetella pertussis in the population. 26 Acellular Pertussis Vaccine The new acellular pertussis vaccines consist of purified proteins extracted from the bacteria. The acellular vaccines differ in both the number and concentration of the following proteins purified from B. pertussis: pertussis toxoid (PT), filamentous hemagglutinin (FHA), pertactin (PRN, formerly designated 69 kD protein), and fimbriae (FIM) 2 and 3 (Table 3–4). The Canadian acellular pertussis vaccine contains PT, FHA, PRN, and both FIM 2 and FIM 3. It has completely replaced the use of whole-cell pertussis vaccine throughout Canada. The rou- tine immunization schedule did not change with the replacement of whole-cell by acellular pertussis vaccine (see Table 3–1). The Canadian vaccine has not yet been licensed in the United States, where four acellular pertussis vaccines from other manufacturers are avail- able. 4 Adverse Events The frequency of adverse effects after whole-cell and acellular pertussis vaccines are sum- marized in Table 3–5. These results were obtained from Canadian studies comparing whole- cell pertussis (DPT–IPV/PRP–T) with acellular pertussis combination vaccines (DTaP-IPV/PRP-T), given at 2, 4, and 6 months of age. 28 Both local and systemic adverse events were two to four times less common after acellular vaccine. The severity of reactions was also significantly less with acellular vaccine. Similar results have been obtained with all acellular pertussis vaccines. 29,30 Severe allergic reactions such as anaphylaxis have been described after immunization with whole-cell pertussis vaccine. With both whole-cell and acellular pertussis vaccines that 44 Evidence-Based Pediatrics Table 3–4 Components of B. pertussis Involved in Pathogenesis of Disease and Immunity Role of pertussis proteins in Pertussis proteins Attachment to mucosa Immunity Pertussis toxin ++ ++ ++ Filamentous hemagglutinin ++ 0 ± Pertactin ++ ? ++ Fimbriae 2 and 3 ++ 0 ++ Adenylate cyclase 0 ++ ? Tracheal cytotoxin 0 ± ? ++ = important ; ± = possibly important; 0 = not important; ? = importance unknown are currently available, the occurrence of anaphylaxis has been so rare that it is not possible to calculate the risk. Naturally, any child who has an allergic reaction of any kind after per- tussis or any other vaccine should not receive the same vaccine again until the cause of the reaction has been identified by appropriate evaluation. Other severe reactions that may occur after both whole-cell and acellular pertussis vac- cines include prolonged crying, “collapse” reaction (also known as hypotonic–hypo-respon- sive episode), and convulsions. All these events are less frequent after immunization with acellular than with whole-cell pertussis vaccine. 31 About 1 in 100 infants have nonstop, incon- solable crying or screaming lasting more than 3 hours after administration of whole-cell vac- cine, but this reduction is much less frequent after acellular pertussis vaccines. There is no evidence that prolonged crying is caused by a neurologic reaction, and recovery is complete. Hypotonic–hypo-responsive episodes occur most often after the first dose of DPT and almost never after the fourth or fifth dose. 32 They occur about once in every 1,750 DPT injec- tions. Symptoms begin within 12 hours of the injection and may last up to 1 day. The infant becomes pale, floppy, and less responsive than normal. The cause of HHE is unknown. Infants with HHE recover completely and can receive additional doses of pertussis vaccine without risk of recurrence of HHE. 33,34 Any vaccine which can induce fever can precipitate febrile convulsions in susceptible children. The incidence of convulsions after whole-cell pertussis vaccination is between 1 in 1,700 vaccinations and 1 in 10,000 vaccinations. 35,36 Convulsions are more common after the third and fourth doses than after the first two doses. Febrile convulsions do not cause per- manent brain damage and do not increase the risk of epilepsy or any other disorder of the brain. 37 Immunization is not associated with an increased incidence of afebrile convul- sions. 38 Immunization 45 Table 3–5 Incidence of Adverse Events after Whole-Cell or Acellular Pertussis Combined Pentavalent Vaccines in Canadian Infants Incidence of Adverse Events (%) Adverse Event DPT-IPV/PRP-T * DTaP-IPV/PRP-T * Local redness 33.3 10.7 Local swelling 31.1 10.0 Local tenderness 59.5 24.4 Fever — 38.0˚C 61.8 17.7 Fever — 39.0˚C 9.8 0.7 Fussiness 80.5 44.7 Crying 69.8 33.3 Drowziness 65.5 32.9 Anorexia 44.2 21.3 Vomiting 11.6 6.2 Diarrhea 11.9 8.2 * DPT-IPV/PRP-T, DtaP-IPV/PRP-T: whole-cell and acellular pertussis combined pentavalent vaccines (Pasteur Mérieux Connaught, Canada) Febrile seizures, prolonged crying, and HHE have been observed following the admin- istration of acellular pertussis vaccine. 31,39,40 The rates of such reactions appear to be lower with acellular than with whole-cell pertussis vaccine. 31 However, since none of the reactions that occurred after whole-cell vaccine are known to cause permanent brain damage, it is unlikely that damage will occur after administration of the acellular vaccine. Many other conditions have been blamed on the pertussis vaccine. Such allegations are based on anecdotes rather than scientific studies. There are no valid scientific studies which demonstrate a causal link between pertussis vaccine and encephalopathy, brain damage, autism, infantile spasms, epilepsy, mental retardation, learning disorders, hyperactivity, SIDS, asthma, or atopic diseases. 1,41,42 The only contraindication to administration of pertussis vaccine is an anaphylactic reac- tion to a previous dose. Efficacy Routine vaccination of infants and young children has resulted in a marked decline in the frequency of pertussis in every country with effective childhood vaccination programs. Con- versely, discontinuation or declines in vaccine coverage have resulted in large epidemics in Japan, Sweden, the United Kingdom, and the newly independent states of the former Soviet Union. 43 When vaccine coverage rose again in Japan and England, the incidence of pertus- sis declined. 44 Randomized, placebo-contolled studies in Sweden showed that the Canadian acellular vaccine protected 85 percent of infants against pertussis. 39,40 Similar results were obtained with other acellular pertussis vaccines. 45 Products containing multiple pertussis antigens are more effective than those with PT alone or PT plus FHA against pertussis. The Canadian vaccine is also very effective against mild disease. 39,40 The results from recent efficacy trials have confirmed that there are antibody cor- relates of protection; vaccinated children with high antibody levels against PT, PRN, and FIM had a much lower secondary attack rate after household exposure to pertussis than did vacci- nated children with low titers. The titer of antibody to FHA did not correlate with protection. 46,47 Another very important finding of the recent studies is the demonstration that re-infec- tion with pertussis is a common event because of waning immunity, which occurs not only in vaccinated individuals but also in those with prior pertussis infection. 27 Such re-infection may be asymptomatic, being detectable only by demonstrating a rise in antibodies to per- tussis antigens but may also result in illness with cough. 48,49 Because adverse reactions are so much less common with acellular than with whole-cell vaccine, it is possible to give boosters to adolescents and adults. It has become increasingly recognized that pertussis is very common in adolescents and young adults. In fact, the great- est rise in incidence of disease during the 1990s in North America occurred in persons 10 to 29 years of age. Approximately 15 to 25 percent of young adults presenting with cough of more than 7 days duration have pertussis. 50–52 A single booster of either Td or Td-IPV combined with acellular pertussis vaccine has been shown to be safe and highly immunogenic in those between 10 and 60 years of age. 53,54 Such boosters may prolong the duration of protection against pertussis, thereby resulting in reduced transmission of B. pertussis in the population. If routine boosters do reduce the inci- dence of pertussis in adolescents and adults, infants under 6 months of age who have not yet completed the primary series would greatly benefit because of reduced risk of exposure to infection from siblings and parents. Recommendations There is good evidence to support the recommendation of routine immunization of all chil- dren with acellular pertussis vaccine, including two well-designed randomized, placebo-con- 46 Evidence-Based Pediatrics trolled trials 39,55 and one randomized controlled trial without placebo; 40 several case-control trials; epidemiologic evidence of dramatic declines in disease incidence in all countries within a short period of introduction of mass immunization and resurgence of epidemics when vaccination coverage declines (see Table 3–3). The optimal schedule of boosters for adolescents and adults remains to be determined. POLIOMYELITIS Epidemiology Within 12 years after the introduction of IPV in 1955, the incidence of paralytic polio decreased by almost 99 percent in Canada, United States, and all other countries with suc- cessful polio vaccine programs using either IPV or oral polio vaccine (OPV). The global cam- paign to eradicate polio has been remarkably successful. 56 Indigenous transmission of wild polioviruses has been interrupted throughout the entire western hemisphere and the region was certified as polio free in 1994. Today, the remaining major foci of transmission of wild polioviruses are in Africa. 57 Because of the speed and extent of travel in all parts of the world, we must continue to immunize children until polioviruses have been eliminated worldwide. Polio Vaccine In Canada, an IPV–only schedule is used. 1 The change from OPV to IPV was based on the efficacy on an IPV–only schedule, the eradication of wild polio from the western hemisphere and declining risk of importation of wild polio viruses because of the success of the World Health Organization (WHO) polio eradication program in most parts of the world, and the desire to avoid the risk of vaccine-associated paralytic polio (VAPP) due to OPV. Inactivated polio vaccine contains types 1, 2, and 3 wild-type polio viruses which have been killed with formalin. The viruses in IPV are grown in either human MRC-5 cells or Vero cells. In Canada, IPV is supplied either by itself or in combination with the following vaccines: DTP-IPV, DTaP-IPV, DT-IPV, or Td-IPV. Both DPT/IPV and DTaP-IPV can be used to dis- solve the lyophilized Hib vaccine so that all five vaccines can be administered as a single injec- tion. In the United States, either IPV-only or sequential IPV-OPV schedules are recom- mended by the American Academy of Pediatrics. 5 Oral polio vaccine consists of attenuated strains of live type 1, 2, and 3 polio viruses grown on monkey kidney cell cultures. Adverse Events Associated with IPV Other than minor pain and redness at the injection site, side effects with IPV are extremely rare. Current methods of production and testing before release of each batch of IPV ensure that there is no live polio virus in the vaccine. In 1960, some batches of rhesus monkey kidney cells used to grow polio virus were dis- covered to be infected with a monkey virus called simian virus 40 (SV40). Live SV40 was sub- sequently found in some batches of both IPV and OPV, which had been used in many parts of the world. Vaccine production methods were altered in order to ensure that SV40 was not present in cells used to grow polio viruses. All polio vaccines, both IPV and OPV, used since 1963 have been free of SV40. Simian virus 40 is a papovavirus, a group of viruses known to cause cancer in several species of animals. No differences in death rates from all causes or in cancer deaths have been detected among groups who had received vaccine containing SV40 compared with those given vaccine free of SV40. 58 A workshop on SV40 at the National Institutes of Health (NIH) concluded that there is no evidence of harm to humans as a result of exposure to SV40 in polio vaccines. 59 Immunization 47 [...]... 1996;14: 126 5-7 2 9 McKinnon N, Ross M, Defries R Reduction of diphtheria in 36,000 Toronto school children as a result of an immunization campaign Canad J Publ Hlth 1931 ;22 :21 7 23 10 Munford R, Ory H, Brooks G, et al Diphtheria deaths in the United States, 195 9-1 970 JAMA 1974 ;22 9:1890–3 11 Griffith A The role of immunization in the control of diphtheria Develop Biol Standard 1979; 43: 3-1 3 12 Dixon J... Dept 1947;7:371–85 22 Newell KW, Duenas Lehman A, LeBlanc DR, et al The use of tetanus toxoid for the prevention of tetanus neonatorum Final report of a double-blind controlled field trial Bull World Hlth Org 1966;35:863–71 58 Evidence- Based Pediatrics 23 Izurieta HS, Sutter RW, Strebel PM, et al Tetanus surveillance–United States, 199 5-1 997 Morb Mortal Wkly Rep 1998;47 (SS2): 1-1 3 24 Laboratory Center... strategies JAMA 1996 ;27 5 :22 4–9 100 Peltola H, Heinonen O, Valle M, et al The elimination of indigenous measles, mumps, and rubella from Finland by a 12 year two-dose vaccination program N Eng J Med 1994; 331:1397–4 02  62 Evidence- Based Pediatrics 101 Cheek J, Baron R, Atlas H, et al Mumps outbreak in a highly vaccinated school population Arch Pediatr Adolesc Med 1995; 149:774–8 1 02 Plotkin SA Rubella... Department of Health, Education and Welfare; 19 62 61 Strebel P, Sutter R, Cochi S, et al Epidemiology of poliomyelitis in the United States one decade after the last reported case of indigenous wild virus—associated disease Clin Infect Dis 19 92; 14:568–79 60 Evidence- Based Pediatrics 62 Sutter RW, Prevost DR Vaccine-associated paralytic poliomyelitis among immunodeficient persons Infect Med 1994;11: 426 ,... are not readily applicable to primary-care pediatrics There is insufficient evidence to include, or to exclude, exercise programs in the routine treatment of obese children.8 3-8 6 There is fair evidence to recommend against very-low-caloric diets for preadolescents.85,87 There is insufficient evidence to recommend for or against exercise programs or intensive family -based programs for most obese children... Recommendation Hepatitis B vaccine I, II 2, II–3 A 56 Evidence- Based Pediatrics Table 3–8 Summary of Quality of Evidence Supporting Use of Varicella Vaccine Immunizing Agent Varicella vaccine Quality of Evidence Recommendation I A parents and/or sick leave benefits incurred by them, the costs of doctor visits, and the management of the complications of chickenpox. 124 , 125 Varicella Vaccine A live attenuated... 1980;303:833–41 121 Francis DP, Hadler SC, Thompson SE, et al Prevention of hepatitis B with vaccine Report of the Centers for Disease Control multi-center efficacy trial among homosexual men Ann Int Med 19 82; 97:3 62 6 Immunization 63 122 Beasley RP, Hwang LY, Lee GC, et al Prevention of perinatally transmitted hepatitis B virus with hepatitis B immune globulin and hepatitis B vaccine Lancet 1983 ;2: 1099–1 02 123 Mahoney... Can Comm Dis Rep 1998 ;25 :41 2 82 Bloch AB, Orenstein WA, Ewing WM, et al Measles outbreak in a pediatric practice: airborne transmission in an office setting Pediatrics 1985;75:676–83 83 Hope-Simpson RE Infectiousness of communicable diseases in the household Lancet 19 52; 2: 549–54 84 Committee on Infectious Diseases 1997 Red Book, 24 th ed Elk Grove Village, IL: American Academy of Pediatrics; 1997.p.347... without evidence of prior infection is recommended REFERENCES 1 National Advisory Committee on Immunization Canadian Immunization Guide, 4th ed Ottawa: Health Canada; 1998.p .21 5 2 Committee on Infectious Diseases 1997 Red Book, 24 th ed Elk Grove Village, IL: American Academy of Pediatrics; 1997.p .26 –35 3 Committee on Infectious Diseases 1997 Red Book, 24 th ed Elk Grove Village, IL: American Academy of Pediatrics; ... report of the Institute of Medicine JAMA 19 92; 267:3 92 6 105 Tingle A, Mitchell L, Grace M, et al Randomized double-blind placebo-controlled study of adverse effects of rubella immunization in seronegative women Lancet 1997;349: 127 7–81 106 Preblud SR, Serdula MK, Frank JA, et al Rubella vaccination in the United States: A 10-year review Epidemiol Rev 1980 ;2: 171–94 107 Centers for Disease Control and . 59.5 24 .4 Fever — 38.0˚C 61.8 17.7 Fever — 39.0˚C 9.8 0.7 Fussiness 80.5 44.7 Crying 69.8 33.3 Drowziness 65.5 32. 9 Anorexia 44 .2 21.3 Vomiting 11.6 6 .2 Diarrhea 11.9 8 .2 * DPT-IPV/PRP-T, DtaP-IPV/PRP-T:. good evidence to support the recommendation of routine immunization of all chil- dren with acellular pertussis vaccine, including two well-designed randomized, placebo-con- 46 Evidence- Based Pediatrics trolled. good evidence to support the recommendation of routine immunization of all chil- dren with hepatitis B vaccine, including randomized, placebo-controlled trials, 120 – 122 epi- demiologic evidence