Recommendations for Using Pneumococcal Vaccine in Children

Transcription

1 / AMERICAN ACADEMY OF PEDIATRICS Committee on Infectious Diseases Recommendations for Using Pneumococcal Vaccine in Children A 23-valent pneumococcal polysaccharide vaccine licensed in the United States in 1983 replaces the 14-valent polysaccharide vaccine licensed in This statement contains new data about pneumococcal vaccine and its effectiveness that have become available since 1977 and new recommendations regarding its use in children. PNEUMOCOCCAL DISEASE Streptococcus pneumoniae (pneumococcus) is the most common cause of acute otitis media, and it is a frequent cause of bacterial pneumonia, bacterial meningitis, and sinusitis in children. Pneumococ- cus is the most common cause of bacteremia in infants and children aged 1 to 24 months; some of these children with fever and bacteremia have no evidence of a primary focus of infection. Mortality from pneumococcal disease is highest in patients who have bacteremia or meningitis and in patients with certain underlying medical conditions. Patients at increased risk of developing severe pneumococcal disease, because of impaired immunologic response to pneumococcus, are those with sickle cell anemia, Hodgkin disease, congenital or acquired immunodeficiency, nephrotic syndrome, and splenic dysfunction, and those who have had splenectomy or organ transplantation. Certain other patients also may be at greater risk of suffer- ing severe pneumococcal infections, such as some. patients with diabetes mellitus, congestive heart failure, chronic pulmonary disease, and renal failure. Patients with CSF leakage complicating skull fracture or neurosurgical procedure may have recurrent pneumococcal meningitis. To date, 83 pneumococcal types have been identified by the serologic properties of their capsular polysaccharides. Certain of these polysaccharides share physicochemical and antigenic properties. Ten serotypes account for the majority of pneumococcal infections in children and adults. Certain serotypes are more prevalent in adults, and others are more prevalent in children. Serotypes in Danish groups 1, 3, 4, 6, 7, 9, 14, 18, 19, and 23 cause the majority of childhood pneumococcal infections. PNEUMOCOCCAL VACCINES POLYSACCHARIDE The new pneumococcal vaccine is composed of purified, capsular polysaccharide antigens of 23 types of S pneumoniae (Danish types 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, ba, ha, 12F, 14, 15B, 17F, 18C, 19A, 19F, 2, 22F, 23F, and 33F). Each polysaccharide is extracted separately and combined into the final product. Each.5-mL dose of the new vaccine contains 25 zg of each polysaccharide antigen (575 sg total polysaccharide) contrasted with 5 tg each in the old 14-valent vaccine. Worldwide surveillance of pneumococcal disease has shown that the 14-valent vaccine included only 71% ofthe types causingbacteremia and meningitis in adults, 97% of the types causing bacteremia and meningitis in children,2 and 65% of the types causing acute otitis media in children.#{176} The new, more comprehensive 23-valent vaccine (Pneumovax 23- Merck; Pnu-Immune 23-Lederle) includes the capsular antigens representing 88% of the types causing adult bacteremia and meningitis, nearly 1% of the types causing childhood bacteremia and meningitis,2 and 85% of the types causing acute otitis media.3 AGE-SPECIFIC RESPONSE TO PNEUMOCOCCAL POLYSACCHARIDE VACCINES PEDIATRICS (ISSN 31 45). Copyright 1985 by the American Academy of Pediatrics. Most healthy adults show at least a twofold increase in type-specific antibody in serum within 3 Downloaded from PEDIATRICS by guest on November Vol , No June

2 weeks after vaccination. In a study of 53 adults, 35 Lg of polysaccharide antigen, the amount in the new 23-valent vaccine, was comparable in immunogenicity to a 5-rg dose, the amount in the old 14-valent vaccine.4 Although estimates of protective titers of antibody for these serotypes are available, determination of antibody levels in vaccinated persons is a research activity and is not generally indicated nor is it generally available. Children younger than 5 years of age show little antibody response to some polysaccharide antigens in pneumococcal vaccine, especially those from pneumococcal types 6A, 14, 19F, and 23F, which are most likely to cause infection in children.5 In one study, vaccination of healthy infants at 6 months of age stimulated a significant increase in serum antibody against only one of eight vaccine antigens, and vaccinated 12-month-old infants showed an antibody increase against only four types.6 Antibody stimulated by vaccination did not persist, and serum antibody levels for vaccinated and unvaccinated children were similar at age 2 years. A greater number of vaccine antigens stimulated significant antibody in children aged 2 to 6 years, and levels of antibody were better maintained in older children.7 However, type 6A, which is one of the most prevalent types causing disease in children, did not stimulate a protective antibody response at all ages through 6 years. EFFECTIVENESS OF PNEUMOCOCCAL POLYSACCHARIDE VACCINES Most of the evidence for the protective effect of pneumococcal vaccine is derived from studies of adults. The effectiveness of pneumococcal vaccines in preventing pneumonia was clearly demonstrated iii two randomized controlled trials in South Africa and the highlands of Papua, New Guinea, in healthy young adults who experience a high incidence of pneumococcal disease.8 9 These studies confirmed earlier results using an old vaccine formulation.1#{176} Two randomized, controlled trials of pneumococcal vaccine in the elderly have been conducted in the United States; in neither was there a difference in the occurrence of respiratory morbidity and mortality between those vaccinated with pneumococcal vaccine and those given a placebo. 1 However, data from the first study suggested some vaccine protection against bacteremic pneumococcal disease, but the incidence of pneumococcal disease was too low to enable a valid assessment of vaccine effectiveness. Three double-blind, placebo-controlled studies have been conducted to measure the effectiveness of the older 14-valent vaccine in preventing acute respiratory infection in 6-month to 5-year-old children. A vaccine study of861 children was conducted in the highlands of Papua, New Guinea, where morbidity and mortality of acute lower respiratory tract infection is prevalent. Pneumococcus appears to be the most important respiratory pathogen in this population. The incidence of acute lower respiratory tract infection was 37% lower in vaccinated children who were at least 17 months of age at the time of vaccination, but was not different in vaccinated and unvaccinated children younger than 17 months. 2 In Lund, Sweden, where 45 children enrolled in day care were studied, the incidence of acute respiratory tract infection was 27% lower in vaccinated children who were older than 2 years at vaccination, but was not different in vaccinated and unvaccinated younger children. 3 In contrast, a large study of 1,24 children in Adelaide, Australia, showed no consistent benefit for younger or older vaccine recipients. 4 The decreased incidence of respiratory illness in vaccinated older children in New Guinea and in Sweden, but not in Adelaide, may be explained by the higher prevalence of respiratory infection due to Pneumococcus in the former two populations, by differences in bacteriologic sampling and culture techniques, and, perhaps, by differences in serotype distribution. It is not possible to conclude from these studies that pneumococcal vaccine would have an appreciable impact on the incidence of respiratory infection in healthy children in the United States. Eight vaccine trials have been conducted to examine the usefulness of polyvalent pneumococcal vaccine in preventing otitis media #{176}The overall incidence of acute otitis media in children younger than 2 years of age, who were vaccinated with the older 8-valent and 14-valent vaccines, was not lower than in unvaccinated children; however, vaccinated children experienced fewer episodes of pneumococcal otitis media caused by the few serotypes in the vaccines against which serum antibody was produced. Therefore, a more immunogenic vaccine might reduce the total incidence of acute otitis media in young children. Three studies 4 7 2#{176} have evaluated the effectiveness of pneumococcal vaccine in preventing recurrent otitis media in older children; one of these studies2#{176} demonstrated a small but significant reduction (2%) in total episodes of otitis media and a 58% reduction in vaccine-type pneumococcal otitis media. Another study 7 reported only a 12% reduction in episodes of otitis and a 36% reduction in vaccine-type pneumococcal otitis media in older children. The third study showed no significant benefit for the vaccine. 4 Because recurring otitis media in older children may include more chronic middle ear pathology than does acute otitis media in young children, recurring otitis media may be Downloaded from by guest on November 15, PNEUMOCOCCAL VACCINE

3 more difficult to prevent simply by immunization. A small, nonrandomized study of children and young adults (ages 2 to 25 years) who had sickle cell disease or elective splenectomy has been con- ducted; the vaccinated group experienced significantly less bacteremic disease than the nonvaccinated patients.2 The effectiveness of pneumococcal vaccine in preventing infection in children and young adults with other chronic conditions has been inferred from studies of serologic response after vaccine administration. In healthy asplenic children, pneumococcal vaccination stimulates a normal antibody response, measured by radioimmunoassay or mdirect hemagglutination,212#{176} but not by enyzmelinked immunoabsorbent assay.2#{176} It was suggested, moreover, that a qualitative difference in the type of antibodies produced in asplenic patients may account for serious pneumococcal disease reported after vaccine administration in some of these cases. One study reported that asplenic children produced pneumococcal antibody with reduced opsonic activity after vaccination.25 In other instances, antibody decline, which may be as much as 5% per year for some serotypes in vaccinated asplenic patients, could have accounted for vaccine failure Finally, some of the cases were caused by serotypes not included in the older pneumococcal vaccines. The timing of vaccine administration relative to O splenectomy appears not to be critical, although clinical studies have not been designed and conducted which directly address this concern. Giebink et al25 reported that the antibody responses of ten children vaccinated within 4 weeks after splenectomy were equal to the responses of five children vaccinated 4 to 6 years after splenectomy. Addiego et a12#{176} noted that the antibody responses of untreated patients with Hodgkin disease who were vaccinated two to three days before splenectomy were similar to those of patients vaccinated three to five days after splenectomy. Moreover, a pneumococcal vaccine study in rats showed that the antibody response was similar for groups of rats vaccinated 3 weeks before splenectomy, at the time of splenectomy, and 6 weeks after splenectomy.3#{176} However, a few studies26 3 indicate that the antibody response to vaccine is impaired after splenectomy; these studies suggest that whenever possible, pneumococcal vaccine should be adminstered before splenectomy. Untreated patients with Hodgkin disease, regardless of the stage, have normal concentrations of pneumococcal antibody in serum, and, if vaccinated more than 1 days before initiating therapy, these patients mount a normal antibody response.32 An- tibody levels decrease after initiating treatment, and decreases are greater with more intense treatment; however, all groups of patients vaccinated before treatment appear to have higher levels of pneumococcal antibody than comparably treated nonvaccinated patients.32 In a small number of patients, the time of vaccination relative to splenectomy appeared to have no effect on the levels of antibody.32 If patients are vaccinated after initiating treatment, the magnitude of the antibody response after vaccination is lowest in intensively treated patients and improves as the number of days between treatment and vaccination is increased. Improvement in the response is relatively rapid during the first 24 months after treatment ends, but antibody responses of maximally treated patients may be significantly lower than normal for as long as eight years after treatment.32 Children with steroid-responsive nephrotic syndrome who are not receiving corticosteroid treatment have serum pneumococcal antibody levels before vaccination that are similar to levels in healthy children, and these children have a normal antibody increase after vaccination.33 During corticosteroid treatment, children with steroid-responsive nephrotic syndrome have slightly lower antibody levels for a few pneumococcal serotypes.33 In one study, five children with steroid-resistant nephrotic syndrome, who were not receiving steroid therapy, had significantly depressed antibody levels, and although vaccination stimulated an antibody increase, only low antibody concentrations were attained.33 ADVERSE REACTIONS TO PNEUMOCOCCAL POLYSACCHARIDE VACCINES Pneumococcal vaccines are well tolerated, although information about adverse reactions is based largely on experience with the old 14-valent vaccine. The adverse reactivity observed in clinical studies has not been serious and has been of short duration. Local soreness and/or induration at the injection site has been reported in 29% to 44% of 826 vaccinated children in two large clinical trials, and fever greater than 37.7#{176}C(99.9#{176}F) has been reported in 3% to 19% ofvaccinated children Fever is usually confined to the 24-hour period following vaccination. Although rare, fever greater than 38.9#{176}C (12#{176}F) and marked local swelling have been reported. Reactions of greater severity, duration, or extent are unusual. Rarely, anaphylactoid reactions have been reported. REPEAT VACCINATION Because of the more frequent occurrence of adverse reactions in adults and children given a second dose of the old 14-valent vaccine,7 35 routine readministration of pneumococcal vaccine is not Downloaded from by guest on November 15, 218 AMERICAN ACADEMY OF PEDIATRICS 1155

4 recommended at this time. In healthy children, mild-to-moderate local reactions occurred six times more frequently after revaccination than after mitial vaccination, and one of 52 revaccinated children experienced a febrile and severe local reaction.7 Reactions are thought to result from combination of circulating antibody with antigen at the injection site.35 In high-risk children, such as those with asplenia or sickle cell disease, revaccination may be justified despite the possibility of more frequent and severe reactions because the morbidity and mortality of overwhelming pneumococcal sepsis in these children is high. Clinical studies in a small number of patients with sickle cell disease have not indicated a significant increase in the frequency or severity of reaction after one revaccination,m and one center routinely revaccinates children with sickle cell anemia 3 to 5 years after the initial vaccination.37 The optimum interval between vaccine administrations is not known. Additional research is urgently needed to determine the duration of protection after vaccination, the need for and timing of revaccination, the need for vaccinating persons with other high-risk and chronic conditions, and methods for improving vaccine immunogenicity in young infants. RECOMMENDATIONS 1. Children aged 2 years and older, who are at increased risk of acquiring pneumococcal infection or who are at increased risk of serious disease should they become infected, should be vaccinated with.5 ml ofthe 23-valent pneumococcal vaccine; the vaccine is administered subcutaneously or intramuscularly. Included in this high-risk category are children with (1) sickle cell disease, (2) functional or anatomic asplenia, (3) nephrotic syndrome, and (4) children about to undergo cytoreduction therapy for Hodgkin disease. For children with Hodgkin disease, the vaccine should be given at least ten days and preferably more than 14 days before beginning treatment to increase the likelihood of obtaining a protective antibody response.32 Vaccination should be avoided during chemotherapy because antibody responses are poor, and vaccination is not likely to be effective in preventing pneumococcal infection; one study suggested waiting 3 or 4 months after discontinuing therapy before administering vaccine.32 In elective splenectomy for nonmalignant conditions, the time of vaccine administration relative to splenectomy appears not to be critical, 3#{176} although the results of two studies suggest that whenever possible the vaccine should be given before splenectomy In addition to administering pneumococcal vaccine to children with functional or anatomic asplenia, it is essential that parents and patients understand the risk of fulminant pneumococcal disease, and that vaccination does not guarantee protection. Prompt medical attention is required for febrile illnesses. Immediate, expectant antimicrobial treatment should be given for suspected bacteremia, the initial signs and symptoms of which may be quite subtle. Antimicrobial agents selected for expectant treatment should be effective against Streptococcus pneumoniae, Neisseria meningitidis and fl-lactamase producing Haemophilus influenzae type b; in sickle cell disease, infection may also be due to Mycopkzsma pneumoniae, Escherichia coli, or Salrnonellae. Many experts recommend that these children should also receive continuous antimicrobial prophylaxis although there are no data in humans to prove that antimicrobial prophylaxis is effective. Antimicrobial prophylaxis may be particularly useful for children not likely to respond to vaccine, such as children less than 2 years of age or children receiving intensive chemotherapy or cytoreduction therapy. 3. Recommendations cannot be made at this time for using pneumococcal vaccine to prevent infection in other high-risk and chronic conditions because of insufficient data to measure the degree of risk, and because vaccine trials to test efficacy have not been conducted in these populations. 4. Passive immunoprophylaxis with intramuscular or intravenous immunoglobulin preparations is recommended for preventing pneumococcal infection in patients with immunoglobulin deficiencies. 5. Vaccination is not recommended for preventing upper or lower respiratory tract infection in healthy children living in the United States. 6. Vaccination is not recommended for preventing otitis media during the first 2 years of life; there are inadequate data to evaluate the effectiveness of pneumococcal vaccine in preventing otitis media in children more than 2 years of age. 7. Routine repeat administration of pneumococcal vaccine is not currently recommended because the duration of protection from primary vaccination has not been determined and revaccinated persons may experience severe reaction. However, revaccination may be justified in certain children at high risk of overwhelming pneumococcal sepsis, such as those with asplenia and sickle cell disease, despite the possibility of more frequent and severe adverse reactions to vaccine. The optimum interval between vaccinations is not known. Patients with Hodgkin disease, who received vaccine during chemotherapy, should be revaccinated 3 or PNEUMOCOCCAL Downloaded VACCINE from by guest on November 15, 218

5 months after chemotherapy has been completed. 8. Persons who have received the 14-valent pneumococcal vaccine should not be revaccinated with the 23-valent vaccine simply to broaden protection inasmuch as the modest increase in protection does not warrant the possible increased risk of adverse reactions. 9. Vaccination should generally be deferred during pregnancy, as the effect of the vaccine on the fetus is unknown. The risk of severe pneumococcal disease in the pregnant woman must be weighed against the potential hazard of the vaccine. 1. Studies with the old 14-valent vaccine mdicate that pneumococcal vaccine and whole-virus influenza vaccine can be given concurrently without diminishing the antibody response to either vaccine or increasing the rate of adverse effects.m Although there are no data, there is no reason to believe that concurrent administration ofpneumococcal vaccine with either diphtheria-tetanus-pertussis (DTP) or polio vaccines will increase the severity of reactions or diminish the antibody responses. COMMITFEE ON INFECTIOUS DISEASES, Philip A. Brunell, MD, Chairman James W. Bass, MD Robert S. Daum, MD William B. Gamble, Jr, MD G. Scott Giebink, MD Caroline Breese Hall, MD George H. McCracken, Jr, MD Georges Peter, MD Stanley A. Plotkin, MD Harry T. Wright, Jr, MD O Liaison Representatives Alan R. Hinman, MD William S. Jordan, Jr, MD Paul Parkman, MD David Scheifele, MD AAP Section Liaison John A. Anderson, MD REFERENCES 1. Robbins JB, Austrian R, Lee C-J, et a!: Considerations for formulating the second-generation pneumococcal capsular polysaccharide vaccine with emphasis on the cr58-reactive types within groups. J Infect Dis 1983;148: Klein JO: The epidemiology of pneumococcal disease in infants and children. Rev Infect Dis 1981;3:S246-S Austrian R, Howie VM, Ploussard JH: The bacteriology of pneumococcal otitis media. John Hopkins Med J 1977;141: Pankey G, Schiffman G: The immunogenicity and reactogenicity of a 22-valent pneumococcal vaccine. Clin Res 1982;2:376A 5. Douglas RM, Paton JC, Duncan SJ, et al: Antibody response to pneumococcal vaccination in children younger than five years of age. J Infect Dis 1983;148: Sell SH, Wright PF, Vaughn WK, et al: Clinical studies of pneumococcal vaccines in infants: I. Reactogenicity and immunogenicity of two polyvalent polysaccharide vaccines. Rev Infect Dis 1981;3:S97-S17 7. Lawrence EM, Edwards KM, Schiffman G, et al: Pneumococcal vaccine in normal children: Primary and secondary vaccination. Am J Dis Child 1983;137: Austrian R, Douglas RM, Schiffman G, et al: Prevention of pneumococcal pneumonia by vaccination. Trans Assoc Am Physicians 1976;89: Riley ID, Andrews M, Howard R, et a!: Immunization with a polyvalent pneumococcal vaccine: Reduction of adult respiratory mortality in a New Guinea highlands community. Lancet 1977;1: MacLeod CM, Hodges RG, Heidelberger M, et a!: Prevention of pneumococcal pneumonia by immunization with specific capsular polysaccharides. J Exp Med 1945;82: Austrian R: Surveillance of Pneumococcoi Infection for Field Trials of Polyvalent Pneurnococcal Vaccine, Report DAP- VDP National Institutes of Health, Riley ID, Everingham FA, Smith DE, et a!: Immunisation with a polyvalent pneumococcal vaccine: Effect on respiratory mortality in children living in the New Guinea highlands. Arch Dis Child 1981;56: Rosen C, Christensen P, Hovelius B, et al: Effect of pneumococcal vaccination on upper respiratory tract infection in children: Design of a follow-up study. Scand J Infect Dis 1983;39(suppl): Douglas RM, Miles HB: Vaccination against Streptococcus pneumoniae in childhoo& Lack of demonstrable benefit in young Australian children. J Infect Dis 1984;149: Howie VM, Ploussard JH, Sloyer JL: Immunization against recurrent otitis media. Ann Otol Rhinol Laryngol 1976;85(Suppl 24): Teele DW, Klein JO, and The Greater Boston Collaborative Otitis Media Study Group: Use ofpneumococcal vaccine for prevention of recurrent acute otitis media in infants in Boston. Rev Infect Dis 1981;3:S113-S M#{228}kel#{228} PH, Leinonen M, Pukander J, et a!: A study of the pneumococcal vaccine in prevention of clinically acute attacks of recurrent otitis media. Rev Infect Dis 1981;3:S Sloyer JL Jr, Ploussard JH, Howie VM: Efficacy of pneumococcal polysaccharide vaccine in preventing acute otitis media in infanth in Huntsville, Alabama. Rev Infect Dis 1981;3:S119-S Wright PF, Sell SH, Vaughn WK, et a!: Clinical studies of pneumococcal vaccines in infants: II Efficacy and effect on nasopharyngeal carriage. Rev Infect Dis 1981;3:(suppl): S18-S Rosen C, Christensen P, Henricksen J, et al: Beneficial effect of pneumococcal vaccination on otitis media in chilthen over two years old. mt J Pediatr Otorhinolaryrigol 1984;7: Ammann AJ, Addiego J, Wara DW, et a!: Polyvalent pneumococcal polysaccharide immunization of patients with sickle cell anemia and patients with splenectomy. N Engi J Med 1977;297: Overturf G, Rigau-Perez J, Honig G, et a!: Pneumococcal polysaccharide immunization of children with sickle cell disease: II. Serologic response and pneumococcal disease following immunization. Am J Pediatr Hernatol Oncol 1982;4: Sullivan JL, Ochs, HD, Schiffman G, et a!: Immune response after splenectomy. Lancet 1978;1: Buchanan GR, Schiffman G: Antibody responses to polyvalent pneumococcal vaccine in infants with sickle cell anemia. J Pediatr 198;96: Giebink GS, Foker JE, Kim Y, et a!: Serum antibody and opsonic response to pneumococcal capsular polysaccharide vaccination in normal and splenectomized children. J Infect Dis 198;141: Hosea SW, Burch CG, Brown EJ, et a!: Impaired immune Downloaded from AMERICAN by guest ACADEMY on November 15, OF 218PEDIATRICS 1157

6 response of splenectomized patients to polyvalent pneumococcal vaccine. Lancet 1981;1: Giebink GS, Le CT, Cosi F, et al: Serum antibody responses of high-risk children and adults to vaccination with capsular polysaccharides of Streptococcus pneumoniae. Rev Infect Dis 1981;3:S168-S Giebink GS, Le CT, Schiffman G: Decline ofserum antibody in splenectomized children after vaccination with pneumococcal capsular polysaccharides. J Pediatr 1984;15: Addiego JE Jr, Amman AJ, Schiffman G, et al: Response to pneumococcal polysaccharide vaccine in patients with Untreated Hodgkin s disease: Children s Cancer Study Group report. Lancet 198;2: Barringer M, Meredith W, Sterchi M, et al: Effect of anesthesia and splenectomy on antibody response to pneumococcal polysaccharide immunization. Am Surg 1982;48: Pedersen FK, Henricksen J, Schiffman G: Antibody response to vaccination with pneumococcal capsular polysaccharides in splenectomized children. Acta Paediat Scand 1982;71: Siber GR, Weitzman SA, Aisenberg AC: Antibody response of patients with Hodgkin s disease to protein and polysaccharide antigens. Rev Infect Dis 1981;3:S144-S Spika JS, Halsey NA, Fish AJ, et al: Serum antibody response to pneumococcal vaccine in children with nephrotic syndrome. Pediatrics 1982;69: Weibel RE, Vella PP, McLean AA, et al: Studies in human subjects ofpolyvalent pneumococcal vaccines. Proc Soc Exp Biol Med 1977;156: Borgono JM, McLean AA, Vella PP, et a!: Vaccination and revaccination with polyvalent pneumococcal polysaccharide vaccines in adults and infants. Proc Soc Exp Biol Med 1978;157: Rigau-Perez JG, Overturf GD, Chan LS, et al: Reactions to booster pneumococcal vaccination in patients with sickle cell disease. Pediatr Infect Dis 1983;2: Weintrub PS, Schiffman G, Addiego JE Jr, et al: Long-term follow-up and booster immunization with polyvalent pneumococcal polysaccharide in patients with sickle cell anemia. J Pediatr 1984;15: DeStafano F, Goodman RA, Noble GR, et al: Simultaneous administration of influenza and pneumococcal vaccines. JAMA 1982;247: MALABSORPTION OF KNOWLEDGE Scientists, including those who speak most eloquently to the public, are continually saying We must known more. This is true, of course, but the muted conviction that this in itself will save us is false. Knowledge does not automatically order itself in human terms, and if this is true of science generally, it is all the more true of the sciences of human behavior. More startling, and contrary to the workaday beliefs of most scientists, knowledge does not even always accumulate, in the simplest, additive sense. A few years ago a colleague of mine came back from a conference on information retrieval where one of the speakers argued (using, of course, calculation) that for some of the knowledge unearthed by scientists of the past, it would be cheaper to rediscover it than to retrieve it. Imagine, if you will, the wave of uneasy movement that might have rippled through the graves of dead scientists at that argument: For some, the work to which they devoted their lives was not merely wrongheaded-this they were prepared for-it was, even when right, never absorbed in the body of human knowledge. Submitted by Student From Konner M: The Tangled Wing. New York, Holt, Rinehart and Winston, PNEUMOCOCCALDownloaded VACCINE from by guest on November 15, 218

7 Recommendations for Using Pneumococcal Vaccine in Children Pediatrics 1985;75;1153 Updated Information & Services Permissions & Licensing Reprints including high resolution figures, can be found at: Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: Information about ordering reprints can be found online: Downloaded from by guest on November 15, 218

8 Recommendations for Using Pneumococcal Vaccine in Children Pediatrics 1985;75;1153 The online version of this article, along with updated information and services, is located on the World Wide Web at: Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 67. Copyright 1985 by the American Academy of Pediatrics. All rights reserved. Print ISSN: Downloaded from by guest on November 15, 218