Chapter 128. Pneumococcal Infections (Part 10) Prevention Capsular Polysaccharide Vaccine The pneumococcal capsular polysaccharide vaccine administered to adults since the early 1980s contains 25 µg per dose of capsular polysaccharide from each of the 23 most prevalent serotypes of S. pneumoniae. Vaccination stimulates antibody to most serotypes in most recipients. One case-control study showed a protection rate of 85% lasting ≥5 years in adults <55 years old (Table 128-7). The level and duration of protection decreased with advancing age. Other studies have suggested an overall protection rate in the adult population of 50–70%. In high- risk subgroups (e.g., debilitated elderly persons and individuals with severe chronic lung disease), vaccine has not been shown conclusively to be effective. Persons who most need the vaccine because of poor IgG responses (e.g., those with lymphoma or AIDS) are likely not to respond at all. Nevertheless, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention has broadened its recommendations for pneumococcal vaccination to include all persons >2 years of age who are at substantially increased risk of developing pneumococcal infection and/or having a serious complication of such an infection. Perhaps most in need of vaccination are persons with anatomic or functional asplenia, who are at risk for overwhelming, life- threatening infections. Others who might fall within these recommendations are persons who (1) are over the age of 65; (2) have a CSF leak, diabetes mellitus, alcoholism, cirrhosis, chronic renal insufficiency, chronic pulmonary disease, or advanced cardiovascular disease; (3) have an immunocompromising condition associated with increased risk of pneumococcal disease (e.g., multiple myeloma, lymphoma, Hodgkin's disease, HIV infection, organ transplantation, or chronic glucocorticoid use); (4) are genetically at increased risk (e.g., Native Americans and Native Alaskans); or (5) live in environments where outbreaks are particularly likely to occur (e.g., nursing homes). Table 128- 7 Protective Efficacy of Polyvalent Pneumococcal Polysaccharide Vaccine a Years since Last Vaccination Age, Years No. of Subject Pairs <3 3–5 >5 <55 125 93 89 85 55–64 149 88 82 75 65–74 213 80 71 58 75–84 188 67 53 32 ≥85 133 46 22 –13 a Results of a case- control study involving all cases of invasive pneumococcal disease in Connecticut during 7 years (1984– 1990). Vaccinated subjects were matched with controls, and the rate of invasive pne umococcal disease was related to age and time since vaccination. The data, showing protective efficacy, suggest that, within 5 years of vaccination, protection rates decline with age— i.e., from ~90% in persons <65 years of age to <50% in persons ≥85 years old. Protection also declines with increasing time from vaccination to infection, and this decline is more prominent in older patients. Source: Data adapted from ED Shapiro et al: N Engl J Med 325:1453, 1991; with permission. Recommendations regarding revaccination seem somewhat inconsistent. A single revaccination is advocated for persons over the age of 65 if >5 years have elapsed since the first vaccination. Since antibody levels decline and there is no anamnestic response, it seems more reasonable simply to recommend revaccination at 5-year intervals, especially in persons over the age of 65, who tend to have almost no adverse reaction to vaccination, and in splenectomized patients, who are most in need. Protein-Conjugate Pneumococcal Vaccine Pneumococcal polysaccharide vaccine is not useful in children <2 years of age, whose immune system does not respond well to polysaccharide antigens. Conjugating the polysaccharide to a protein yields an immunogen that is effective in infants and young children. Initial studies of a protein-conjugate pneumococcal vaccine consisting of capsular material from the seven serotypes most likely to cause disease in children (Prevnar) showed a 98% reduction in rates of bacteremia and meningitis and a 67% reduction in rates of otitis media due to vaccine serotypes. Since it was marketed in 2000, widespread use of this vaccine has caused a dramatic decline in the incidence of invasive pneumococcal disease among infants and children (Fig. 128-4). Colonization rates have also greatly decreased. In an Alaskan village, rates of carriage of vaccine strains decreased in children from 55% to 10% and in adults from 15% to 5%. Studies of protein conjugate vaccines that contain antigen from more than seven common infecting serotypes are nearing completion, with favorable results. Figure 128-4 The rate of invasive pneumococcal disease per 100,000 population (vertical axis) is presented for each year since 2000 (bars ) for different age groups (horizontal axis). Invasive pneumococcal di sease is more common at the extremes of age. The incidence in all age groups has fallen steadily during the past 5 years. The observed reductions reflect direct effects and indirect ("herd") effects of widespread use of the 7-valent pneumococcal protein-co njugate vaccine (PCV7; see text). (Adapted from Centers for Disease Control and Prevention, MMWR 54:893, 2005.) The incidence of invasive pneumococcal disease has also declined among unvaccinated children and among adults, to whom this vaccine is not even offered (Fig. 128-4). This decrease illustrates the "herd effect"— i.e., the impact of widespread vaccination on unvaccinated members of the population— and is probably attributable to the effects of the conjugate vaccine on nasopharyngeal carriage of vaccin e serotypes. Another effect of the widespread use of this vaccine is the decreasing proportion of all pneumococcal disease that is due to antibiotic- resistant isolates, a trend that reflects the targeting of antibiotic- resistant strains by the vaccine. An unwanted effect of vaccination has been an increase in infections caused by serotypes that are not included in the vaccine (replacement serotypes ), which, in fact, are increasingly expressing antibiotic resistance. Still, as noted above, the overall incide nce of pneumococcal disease in all segments of the population has steadily declined. For further information, the reader is referred to the American Academy of Pediatrics Red Book Online (http://aapredbook.aappublications.org). Further Readings American Academy of Pediatrics and American Academy of Family Physicians Clinical Practice Guideline: Diagnosis and management of acute otitis media. Pediatrics 113:1451, 2004 Centers for Disease Control and Prevention: Direct and indirect effects of routine vaccination of children with 7- valent conjugate vaccine on incidence of invasive pneumococcal disease—United States 1998-2003. MMWR 54:893, 2005 Fedson DS, Musher DM: Pneumococcal vaccine, in Vaccines, 4th ed, SA Plotkin, EA Mortimer Jr (eds). Philadelphia, Saunders, 2003 Karlowsky JA et al: Factors associated with relative rates of antimicrobial resistance among Streptococcus pneumoniae in the United States: Results from the TRUST Surveillance Program (1998- 2002). Clin Infect Dis 36:963, 2003 [PMID: 12684907] Lexau CA et al: Changing epidemiology of invasive pneumococcal disease among older adults in the era of pediatric pneumococcal conjugate vaccine. JAMA 294:2043, 2005 [PMID: 16249418] Mandell LA et al: Update of practice guidelines for the management of community- acquired pneumonia in immunocompetent adults. Clin Infect Dis 37:1405, 2003 [PMID: 14614663] Musher DM: Pneumococcal vaccine— direct and indirect ("herd") effects (editorial). N Engl J Med 354:1522, 2006 [PMID: 16598050] ———: Streptococcus pneumoniae, in Principles and Practice of Infectious Diseases, 6th ed, GL Mandell et al (eds). New York, Churchill Livingstone, 2004 ——— e t al: A fresh look at the definition of susceptibility of Streptococcus pneumoniae to beta- lactam antibiotics. Arch Intern Med 161:2538, 2001 Tuomanen EI et al (eds): The Pneumococcus . Washington, DC, ASM Press, 2004 Bibliography Gwaltney JM et al: Acute community- acquired bacterial sinusitis: The value of antimicrobial treatment and the natural history. Clin Infect Dis 38:227, 2004 [PMID: 14699455] Heffron R: Pneumonia: With Special Reference to Pneumococcus Lobar Pneumonia. A Commonwealth Fund Book, © 1939. Reprinted by Harvard University Press, Cambridge, MA, 1979 Musher DM et al: Diagnostic value of microscopic examination of Gram- stained sputum and sputum culture in patients with bacteremic pneumococcal pneumonia. Clin Infect Dis 39:165, 2004 [PMID: 15307023] ——— et al: Bacteremic and nonbacteremic pneumococcal pneumonia: A prospective study. Medicine 79:210, 2000 Rahav G et al: Invasive pneumococcal infections: A comparison between adults and children. Medicine 76:295, 1997 [PMID: 9279335] Scheld WM et al: Pathophysiology of bacterial meningitis: Mechanism(s ) of neuronal injury. J Infect Dis 186(Suppl 2):S225, 2002 Shapiro ED et al: The protective efficacy of polyvalent pneumococcal polysaccharide vaccine. N Engl J Med 325:1453, 1991 [PMID: 1944423] Sinus and Allergy Health Partnership: Antimicrobial trea tment guidelines for acute bacterial rhinosinusitis. Otolaryngol Head Neck Surg 130(Suppl):1, 2004 Watanakunakorn Cet al: Adult bacteremic pneumococcal pneumonia in a community teaching hospital, 1992– 1996. A detailed analysis of 108 cases. Arch Intern Med 157:1965, 1997 [PMID: 9308508] Thornsberry C et al: Regional trends in antimicrobial resistance among clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae , and Moraxella catarrhalis in the United States: Results from the TRUST Surveil lance Program, 1999–2000. Clin Infect Dis 34(Suppl 1):S4, 2002 Whitney CG et al: Decline in invasive pneumococcal disease after the introduction of protein- polysaccharide conjugate vaccine. N Engl J Med 348:1737, 2003 [PMID: 12724479] . Chapter 128. Pneumococcal Infections (Part 10) Prevention Capsular Polysaccharide Vaccine The pneumococcal capsular polysaccharide vaccine administered. broadened its recommendations for pneumococcal vaccination to include all persons >2 years of age who are at substantially increased risk of developing pneumococcal infection and/or having. where outbreaks are particularly likely to occur (e.g., nursing homes). Table 128- 7 Protective Efficacy of Polyvalent Pneumococcal Polysaccharide Vaccine a Years since Last Vaccination