CURRENT VACCINE

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opmental catch-up, and deficit, following adoption after severe global early privation.J Child Psychol Psychiatry.1998;39:465– 476

39. Law CM, Shiell AW. Is blood pressure inversely related to birth weight? The strength of evidence from a systematic review of the literature.

J Hypertension.1996;14:935–941

40. Rich-Edwards JW, Stamfer MJ, Manson JE, et al. Birth weight and risk of cardiovascular disease in a cohort of women followed-up since 1976.

Br Med J.1997;315:396 – 400

41. Martyn CN, Barker DJP, Osmond C. Mothers’ pelvic size, fetal growth, and coronary heart disease in men in the UK. Lancet. 1996;348: 1264 –1268

42. Katzman R. Education and the prevalence of dementia and Alzheimer’s disease.Neurology.1993;43:13–20

43. Jacobi A. The President’s address: the relation of pediatrics to general medicine.Trans Am Pediatr Soc.1893;1:6 –17

Pneumococcal Vaccine: An Update

ABBREVIATION. HIV, human immunodeficiency virus.

S

treptococcus pneumoniae is the most common cause of invasive bacterial infection in children. In addition, the organism causes 30% to 50% of cases of acute otitis media; 24 million visits to pedi-atricians per year in the United States are referable to this diagnosis.1_{It is also responsible for a significant}

amount of morbidity and mortality in children and adults in the United States and in other countries. A majority of cases of invasive disease caused by S pneumoniae occur in children ,2 years of age and adults 65 years of age and older.1 _{The current}

23-valent pneumococcal vaccine has been shown to be ineffective in children ,2 years old.2 _{In addition,}

resistance ofS pneumoniaeto penicillin, cephalospo-rins, and other antibiotics has become a serious prob-lem.3 _{These factors prompted investigations that}

have culminated in the development of conjugated polysaccharide-protein vaccines. These new vaccines are similar in design to the already licensed Hae-mophilus influenzae,type b conjugate vaccine. Wide-spread deployment of the conjugateH influenzae vac-cine in 1987 has been followed by a major decrease in morbidity and mortality ofH influenzaeinfection.4

In this commentary, we will review briefly pneu-mococcal infection and discuss the roles of current and future vaccines in the prevention of pneumococ-cal disease.

Nasopharyngeal colonization with S pneumoniae

occurs in a majority of children and is most common in children ,4 years of age.2 _{Colonization may be}

followed by acute otitis media and other upper res-piratory infections, as well as by pneumonia. Severe infection, including bacteremia and meningitis, also may occur with significant attendant morbidity and mortality.1_{Children 6 to 24 months of age are at the}

highest risk for pneumococcal infection because pas-sively acquired maternal antibodies are no longer

present. The currently available pneumococcal vac-cine has been ineffective in producing a significant antibody response in children,2 years of age; how-ever, a new conjugate vaccine may be effective in this population.4

CURRENT VACCINE

To date, at least 90 serotypes ofS pneumoniaehave been identified. The current pneumococcal vaccine, licensed in 1983, contains purified, capsular polysac-charide antigen of 23 serotypes ofS pneumoniae(1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F). These serotypes are responsible for 85% to 90% of adult infections and virtually 100% of invasive disease in children. The current vaccine replaced a 14-valent vaccine li-censed in the United States in 1977.4

The current 23-valent vaccine had efficacy rates of 61% and 75% in two studies of immunocompetent adults in the prevention of bacteremia and meningi-tis caused by the S pneumoniae serotypes that were incorporated into the vaccine that was used.5,6_Butler

and associates5_{also reported a 57% efficacy rate in all}

persons.5 years of age.

Although the current polysaccharide vaccine has been effective in reducing severe disease in the adult population,5 _{it cannot impact significantly on the}

frequency of disease in children ,2 years of age because it does not elicit a significant antibody re-sponse in these children.4 _{The current vaccine also}

has not been shown to be effective in protection against acute otitis media caused by S pneumoniae.2

Current recommendations of the Committee on In-fectious Diseases of the American Academy of Pedi-atrics do not include routine use of the vaccine in children unless they suffer from a specific medical condition that puts them at a higher risk than normal children for severe pneumococcal infection.

CURRENT INDICATIONS

According to the 1997 Red Book,2 _pneumococcal

vaccine is indicated in children 2 years of age and older with:

• sickle cell disease

• functional or anatomic asplenia

• nephrotic syndrome or chronic renal failure • immunodeficiency for various reasons, including

organ transplant and prolonged use of systemic steroids

• cerebrospinal fluid leaks and

• human immunodeficiency virus (HIV) infection

In patients with HIV, antibody response may vary with the patient’s immune status.2

Pneumococcal vaccine also is indicated in children with chronic cardiovascular disease, chronic pulmo-nary disease (cystic fibrosis or emphysema, but not asthma), or chronic liver disease (cirrhosis). The American Academy of Pediatrics also recommends vaccination of children .2 years of age who live in special environmental or social situations where the risk of invasive pneumococcal infection or its com-Received for publication Jan 5, 1999; accepted Jan 5, 1999.

Reprint requests to (R.D.F.) Texas Children’s Hospital, MC 1-3420, 6621 Fannin St, Houston, TX 77030.

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plications is high (eg, certain American Indian pop-ulations and Alaskan natives).

ADVERSE REACTIONS

Because it has been used clinically since 1977, pneumococcal vaccine generally is considered to be safe. Mild local reactions, including erythema or pain at the injection site, occur in approximately half of immunization recipients and usually resolve in,48 hours. Reports of fever, myalgia, and severe local-ized reactions are rare and reports of systemic reac-tion or anaphylaxis are exceedingly rare.1

CONTRAINDICATIONS

Immunization during pregnancy should be de-ferred because effects of pneumococcal vaccine in the fetus are unknown.1 _{Although one study}

docu-mented a transient increase in viral load after immu-nization of patients affected with HIV,7 _{there have}

been no other reports of this occurrence. According to the Advisory Committee on Immunization Prac-tices of the Centers for Disease Control, patients with HIV still should be immunized.

NEED FOR CONJUGATE VACCINE

Several factors have made the development of new preventive strategies in the battle against pneumo-coccal infection a prominent issue. Resistance of S pneumoniaeto multiple antibiotics has increased rap-idly in the United States and even more raprap-idly in other parts of the world.3_Children,_{2 years of age,}

who have the highest rate of invasive pneumococcal infection, do not develop an effective antibody re-sponse to the current polysaccharide vaccine. These factors have made the development of a new and more efficacious vaccine important in the United States as well as in developing countries where mor-bidity and mortality from invasive pneumococcal disease are higher than in the United States.

INFORMATION ON HEPTAVALENT CONJUGATE VACCINE

Recently, pneumococcal vaccine preparations that couple capsular polysaccharide antigen to carrier proteins from a nontoxic variant of diphtheria toxin (CRM197) or a meningococcal outer membrane

pro-tein complex have been made available for clinical trials.8 –12_{Although this concept proved effective for}

prevention of H influenzae, type b infection, its po-tential applicability to the prevent of disease caused byS pneumoniaeis more problematic because of the higher number of serotypes ofS pneumoniaethat may cause disease. Each antigen must be coupled and the vaccine preparation titrated to include enough anti-gen to induce an effective immune response but with a minimum of adverse reactions to the vaccine prep-aration.8_{A pentavalent vaccine preparation}

(contain-ing capsular, polysaccharide antigen of 5 serotypes) has been proven to be immunogenic and safe.10

Most recently, a heptavalent preparation (includ-ing serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) was deployed in two large prospective efficacy trials in northern California11 _{and Finland. Preliminary data}

from these trials revealed a serotype-specific

anti-body response in patients. To date, the vaccine has been 90% effective in preventing pneumococcal bac-teremia and meningitis in approximately 19 000 chil-dren who received the vaccine in California (S. L. Kaplan, personal conversation)13 _{Final results from}

this study may be expected in the near future. Re-ports from this and from other studies of new con-jugate vaccines should provide information regard-ing the potential impact of conjugate vaccine on invasive disease and on the frequency of otitis media caused byS pneumoniae.14

IMPLICATIONS OF A NEW VACCINE Implementation of routine immunization with the new conjugate pneumococcal vaccine could lead to a significant reduction in morbidity fromS pneumoniae

bacteremia and meningitis as well as from pneumo-nia, otitis media, and other respiratory tract infec-tions. If conjugate vaccine use eliminates nasopha-ryngeal carriage ofS pneumoniae, (as one early study has shown) then decreased person-to-person trans-mission will ensue and the incidence of disease cause byS pneumoniaewill decrease markedly.12

The epidemiology of pneumococcal infection will require intensive study after the introduction of a new vaccine to determine which serotypes are caus-ing infection. Several investigators have suggested that increased antibody response to the seven cur-rently predominant serotypes could lead to the emer-gence of pneumococcal serotypes in the community that currently are less common.8,11

R. Paul Wadwa, MD

Department of Pediatrics

Ohio State University College of Medicine and Public Health

Columbus, OH 43210

Ralph D. Feigin, MD

Department of Pediatrics Baylor College of Medicine Houston, TX 77030

REFERENCES

1. Centers for Disease Control and Prevention. Prevention of pneumococ-cal disease: recommendations of the Advisory Committee on Immuni-zation Practices (ACIP).MMWR.1997;46(RR-8):1–24

2. American Academy of Pediatrics. Pneumococcal infections. In: Peter G, ed.1997 Red Book: Report of the Committee on Infectious Diseases.24th ed. Elk Grove Village, IL: American Academy of Pediatrics; 1997:410 – 418 3. Kaplan SL. The emerging antibiotic resistance ofStreptococcus

pneu-moniae. Semin Pediatr Infect Dis.1996;7:245–249

4. Dennehy PH, Jost EE, Peter G. Active immunizing agents. In: Feigin RD, Cherry JD, eds.Textbook of Pediatric Infectious Diseases.4th ed. Philadel-phia, PA: WB Saunders; 1998:2731–2769

5. Butler JC, Breiman RF, Campbell JF, Lipman HB, Broome CV, Facklam RR. Pneumococcal polysaccharide vaccine efficacy: an evaluation of current recommendations.JAMA.1993;270:1826 –1831

6. Shapiro ED, Berg AT, Austrian R, et al. The protective efficacy of polyvalent pneumococcal polysaccharide vaccine.N Engl J Med.1991; 325:1453–1460

7. Brichacek B, Swindells S, Janoff EN, Pirruccello S, Stevenson M. In-creased plasma human immunodeficiency virus type 1 burden follow-ing antigenic challenge with pneumococcal vaccine.J Infect Dis.1996; 174:1191–1199

8. Black S, Shinefield H. Issues and challenges: pneumococcal vaccination in pediatrics.Pediatr Ann.1997;26:355–360

9. Ahman H, Kayhty H, Lehtonen H, Leroy O, Froeschle J, Eskola J.

Streptococcus pneumoniae capsular polysaccharide-diphtheria toxoid conjugate vaccine is immunogenic in early infancy and able to induce

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immunologic memory.Pediatr Infect Dis J.1998;17:211–216

10. Ahman H, Kayhty H, Tamminen P, Vuorela A, Malinoski F, Eskola J. Pentavalent pneumococcal oligosaccharide conjugate vaccine PncCRM is well-tolerated and able to induce an antibody response in infants.

Pediatr Infect Dis J.1996;15:135–139

11. Rennels MB, Edwars KM, Keyserling HL, et al. Safety and immunoge-nicity of heptavalent pneumococcal vaccine conjugated to CRM197in

United States infants.Pediatrics.1998;101:604 – 611

12. Dagan R, Melamed R, Muallem M, et al. Reduction of nasopharyngeal carriage of pneumococci during the second year of life by a heptavalent conjugate pneumococcal vaccine.J Infect Dis.1996;174:1271–1278 13. Internet information (http://www.unisci.com/stories/0928984.htm) 14. Daum RS. Pneumococcal vaccines for children: an update.Pediatr Infect

Dis J.1998;17:823– 824

THE LURE OF TECHNOLOGY

. . . Based on the pronouncements of ‘‘authorities’’ and flawed studies using historical controls, electronic fetal monitoring took obstetrics by storm in the 1970s. After two decades and numerous randomized, controlled trials, we have belatedly learned that this technology hurts women by increasing operative delivery rates and that it provides no lasting benefit to their children. The US Preventive Services Task Force gave routine electronic fetal monitoring a ‘‘D’’ rating, meaning fair evidence indicates we should abandon its use in low-risk women. Nevertheless, more than three fourths of all births in the United States use this technology. While this battle has clearly been lost, we may be able to hold the line against other ineffective—yet heavily promoted—technologies such as home uterine activity monitoring . . . Four randomized, controlled trials of antepartum nonstress cardio-tocography, all published in the British literature (and thus unknown to most US physicians), showed that use of this test triples the risk of perinatal mortality in high-risk pregnancies. Despite compelling evidence, these worthless procedures continue to overgraze on the medical commons.

REFERENCES

Grimes DA.Contemporary OB/GYN. January 1999:41-54

Thacker SB, Stroup DF, Peterson HB. Efficacy and safety of intrapartum electronic fetal monitoring: an update.Obstet Gynecol.1995;86:613-620

US Preventive Services Task Force.Guide to Clinical Preventive Services. 2nd ed. Baltimore, MD: Williams & Wilkins; 1995

Grimes DA. Technology follies. The uncritical acceptance of medical innovation.JAMA.1993;:269:3030-3033 Enkin M, Kierse MJNC, Renfrew M, et al.A Guide to Effective Care in Pregnancy and Childbirth.2nd ed. Oxford, England: Oxford University Press; 1995

Hiatt HH. Protecting the medical commons: who is responsible?N Engl J Med.1975;293:235-241

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