Impact of universal infant immunization with pneumococcal (Streptococcus pneumoniae) conjugate vaccines in the United States
- Elaine I Tuomanen, MD
Elaine I Tuomanen, MD
- Chair, Infectious Diseases
- St Jude Children's Research Hospital
Streptococcus pneumoniae (pneumococcus) is a leading cause of serious illness among children worldwide . Before universal infant immunization with pneumococcal conjugate vaccine in the United States, S. pneumoniae caused approximately 17,000 cases of invasive disease each year among children younger than five years of age, including 700 cases of meningitis and 200 deaths . It was the most frequent cause of bacteremia, bacterial pneumonia, bacterial meningitis, sinusitis, and acute otitis media .
The 7-valent pneumococcal conjugate vaccine (PCV7) was added to the schedule of recommended vaccines for children younger than two years of age in the United States in 2000 [1,2]. PCV7 contains serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F conjugated to a mutant of diphtheria toxoid (table 1). The routine use of PCV7 resulted in a decreased incidence of invasive pneumococcal disease in children. However, there were increasing data to suggest that universal infant immunization with PCV7 changed the serotype patterns of invasive disease, nasopharyngeal (NP) colonization, and antibiotic resistance patterns. In 2010, a 13-valent pneumococcal conjugate vaccine replaced PCV7 in the routine childhood immunization schedule .
The impact of universal infant immunization with PCV7 and PCV13 on invasive serotypes, nasopharyngeal flora, and antibiotic resistance in children in the United States will be reviewed here. The impact in adults is discussed separately. (See "Invasive pneumococcal (Streptococcus pneumoniae) infections and bacteremia", section on 'Impact of childhood vaccination'.)
Pneumococcal conjugate and polysaccharide vaccines also are discussed separately. (See "Pneumococcal (Streptococcus pneumoniae) conjugate vaccines in children" and "Pneumococcal (Streptococcus pneumoniae) polysaccharide vaccines in children" and "Pneumococcal vaccination in adults".)
Surveillance after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) to the standard childhood immunization schedule has shown that pneumococcal conjugate vaccines are effective in preventing invasive pneumococcal disease (IPD) and providing herd immunity (figure 1). In 2003, it was estimated that 29,599 cases of vaccine serotype IPD were prevented through routine immunization. Approximately two-thirds of these cases were prevented through herd immunity . The greatest decline has been noted in pneumococcal bacteremia without a focus.
- Advisory Committee on Immunization Practices. Preventing pneumococcal disease among infants and young children. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2000; 49:1.
- American Academy of Pediatrics. Committee on Infectious Diseases. Policy statement: recommendations for the prevention of pneumococcal infections, including the use of pneumococcal conjugate vaccine (Prevnar), pneumococcal polysaccharide vaccine, and antibiotic prophylaxis. Pediatrics 2000; 106:362.
- Centers for Disease Control and Prevention (CDC). Licensure of a 13-valent pneumococcal conjugate vaccine (PCV13) and recommendations for use among children - Advisory Committee on Immunization Practices (ACIP), 2010. MMWR Morb Mortal Wkly Rep 2010; 59:258.
- Centers for Disease Control and Prevention (CDC). Direct and indirect effects of routine vaccination of children with 7-valent pneumococcal conjugate vaccine on incidence of invasive pneumococcal disease--United States, 1998-2003. MMWR Morb Mortal Wkly Rep 2005; 54:893.
- Kaplan SL, Mason EO Jr, Wald ER, et al. Decrease of invasive pneumococcal infections in children among 8 children's hospitals in the United States after the introduction of the 7-valent pneumococcal conjugate vaccine. Pediatrics 2004; 113:443.
- Byington CL, Samore MH, Stoddard GJ, et al. Temporal trends of invasive disease due to Streptococcus pneumoniae among children in the intermountain west: emergence of nonvaccine serogroups. Clin Infect Dis 2005; 41:21.
- Singleton RJ, Hennessy TW, Bulkow LR, et al. Invasive pneumococcal disease caused by nonvaccine serotypes among alaska native children with high levels of 7-valent pneumococcal conjugate vaccine coverage. JAMA 2007; 297:1784.
- Pelton SI, Huot H, Finkelstein JA, et al. Emergence of 19A as virulent and multidrug resistant Pneumococcus in Massachusetts following universal immunization of infants with pneumococcal conjugate vaccine. Pediatr Infect Dis J 2007; 26:468.
- Hicks LA, Harrison LH, Flannery B, et al. Incidence of pneumococcal disease due to non-pneumococcal conjugate vaccine (PCV7) serotypes in the United States during the era of widespread PCV7 vaccination, 1998-2004. J Infect Dis 2007; 196:1346.
- Schutze GE, Tucker NC, Mason EO Jr. Impact of the conjugate pneumococcal vaccine in arkansas. Pediatr Infect Dis J 2004; 23:1125.
- Centers for Disease Control and Prevention (CDC). Invasive pneumococcal disease in children 5 years after conjugate vaccine introduction--eight states, 1998-2005. MMWR Morb Mortal Wkly Rep 2008; 57:144.
- Jacobs MR, Good CE, Bajaksouzian S, Windau AR. Emergence of Streptococcus pneumoniae serotypes 19A, 6C, and 22F and serogroup 15 in Cleveland, Ohio, in relation to introduction of the protein-conjugated pneumococcal vaccine. Clin Infect Dis 2008; 47:1388.
- Hsu HE, Shutt KA, Moore MR, et al. Effect of pneumococcal conjugate vaccine on pneumococcal meningitis. N Engl J Med 2009; 360:244.
- Park IH, Moore MR, Treanor JJ, et al. Differential effects of pneumococcal vaccines against serotypes 6A and 6C. J Infect Dis 2008; 198:1818.
- Carvalho Mda G, Pimenta FC, Gertz RE Jr, et al. PCR-based quantitation and clonal diversity of the current prevalent invasive serogroup 6 pneumococcal serotype, 6C, in the United States in 1999 and 2006 to 2007. J Clin Microbiol 2009; 47:554.
- Pilishvili T, Lexau C, Farley MM, et al. Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine. J Infect Dis 2010; 201:32.
- Byington CL, Hulten KG, Ampofo K, et al. Molecular epidemiology of pediatric pneumococcal empyema from 2001 to 2007 in Utah. J Clin Microbiol 2010; 48:520.
- Hsu KK, Shea KM, Stevenson AE, et al. Changing serotypes causing childhood invasive pneumococcal disease: Massachusetts, 2001-2007. Pediatr Infect Dis J 2010; 29:289.
- Techasaensiri C, Messina AF, Katz K, et al. Epidemiology and evolution of invasive pneumococcal disease caused by multidrug resistant serotypes of 19A in the 8 years after implementation of pneumococcal conjugate vaccine immunization in Dallas, Texas. Pediatr Infect Dis J 2010; 29:294.
- Weinberger DM, Malley R, Lipsitch M. Serotype replacement in disease after pneumococcal vaccination. Lancet 2011; 378:1962.
- Green MC, Mason EO, Kaplan SL, et al. Increase in prevalence of Streptococcus pneumoniae serotype 6C at Eight Children's Hospitals in the United States from 1993 to 2009. J Clin Microbiol 2011; 49:2097.
- Yildirim I, Stevenson A, Hsu KK, Pelton SI. Evolving picture of invasive pneumococcal disease in massachusetts children: a comparison of disease in 2007-2009 with earlier periods. Pediatr Infect Dis J 2012; 31:1016.
- Moore MR, Link-Gelles R, Schaffner W, et al. Effect of use of 13-valent pneumococcal conjugate vaccine in children on invasive pneumococcal disease in children and adults in the USA: analysis of multisite, population-based surveillance. Lancet Infect Dis 2015; 15:301.
- Kaplan SL, Barson WJ, Lin PL, et al. Early trends for invasive pneumococcal infections in children after the introduction of the 13-valent pneumococcal conjugate vaccine. Pediatr Infect Dis J 2013; 32:203.
- Iroh Tam PY, Madoff LC, Coombes B, Pelton SI. Invasive pneumococcal disease after implementation of 13-valent conjugate vaccine. Pediatrics 2014; 134:210.
- Black S. Changing epidemiology of invasive pneumococcal disease: a complicated story. Clin Infect Dis 2008; 47:485.
- Fenoll A, Aguilar L, Granizo JJ, et al. Has the licensing of respiratory quinolones for adults and the 7-valent pneumococcal conjugate vaccine (PCV-7) for children had herd effects with respect to antimicrobial non-susceptibility in invasive Streptococcus pneumoniae? J Antimicrob Chemother 2008; 62:1430.
- Moore MR. Rethinking replacement and resistance. J Infect Dis 2009; 199:771.
- Pai R, Moore MR, Pilishvili T, et al. Postvaccine genetic structure of Streptococcus pneumoniae serotype 19A from children in the United States. J Infect Dis 2005; 192:1988.
- Centers for Disease Control and Prevention (CDC). Emergence of antimicrobial-resistant serotype 19A Streptococcus pneumoniae--Massachusetts, 2001-2006. MMWR Morb Mortal Wkly Rep 2007; 56:1077.
- Kaplan SL, Barson WJ, Lin PL, et al. Serotype 19A Is the most common serotype causing invasive pneumococcal infections in children. Pediatrics 2010; 125:429.
- Pichichero ME, Casey JR. Emergence of a multiresistant serotype 19A pneumococcal strain not included in the 7-valent conjugate vaccine as an otopathogen in children. JAMA 2007; 298:1772.
- Ongkasuwan J, Valdez TA, Hulten KG, et al. Pneumococcal mastoiditis in children and the emergence of multidrug-resistant serotype 19A isolates. Pediatrics 2008; 122:34.
- Xu Q, Pichichero ME, Casey JR, Zeng M. Novel type of Streptococcus pneumoniae causing multidrug-resistant acute otitis media in children. Emerg Infect Dis 2009; 15:547.
- McNeil JC, Hulten KG, Mason EO Jr, Kaplan SL. Serotype 19A is the most common Streptococcus pneumoniae isolate in children with chronic sinusitis. Pediatr Infect Dis J 2009; 28:766.
- Whitney CG. Impact of conjugate pneumococcal vaccines. Pediatr Infect Dis J 2005; 24:729.
- Huang SS, Platt R, Rifas-Shiman SL, et al. Post-PCV7 changes in colonizing pneumococcal serotypes in 16 Massachusetts communities, 2001 and 2004. Pediatrics 2005; 116:e408.
- Millar EV, O'Brien KL, Watt JP, et al. Effect of community-wide conjugate pneumococcal vaccine use in infancy on nasopharyngeal carriage through 3 years of age: a cross-sectional study in a high-risk population. Clin Infect Dis 2006; 43:8.
- Park SY, Moore MR, Bruden DL, et al. Impact of conjugate vaccine on transmission of antimicrobial-resistant Streptococcus pneumoniae among Alaskan children. Pediatr Infect Dis J 2008; 27:335.
- Huang SS, Hinrichsen VL, Stevenson AE, et al. Continued impact of pneumococcal conjugate vaccine on carriage in young children. Pediatrics 2009; 124:e1.
- Gounder PP, Bruce MG, Bruden DJ, et al. Effect of the 13-valent pneumococcal conjugate vaccine on nasopharyngeal colonization by Streptococcus pneumoniae--Alaska, 2008-2012. J Infect Dis 2014; 209:1251.
- Lee GM, Kleinman K, Pelton SI, et al. Impact of 13-Valent Pneumococcal Conjugate Vaccination on Streptococcus pneumoniae Carriage in Young Children in Massachusetts. J Pediatric Infect Dis Soc 2014; 3:23.
- Dunais B, Bruno P, Touboul P, et al. Impact of the 13-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae among children attending group daycare in southeastern France. Pediatr Infect Dis J 2015; 34:286.
- Desai AP, Sharma D, Crispell EK, et al. Decline in Pneumococcal Nasopharyngeal Carriage of Vaccine Serotypes After the Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Children in Atlanta, Georgia. Pediatr Infect Dis J 2015; 34:1168.
- 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.
- Mbelle N, Huebner RE, Wasas AD, et al. Immunogenicity and impact on nasopharyngeal carriage of a nonavalent pneumococcal conjugate vaccine. J Infect Dis 1999; 180:1171.
- Dagan R, Givon-Lavi N, Zamir O, Fraser D. Effect of a nonavalent conjugate vaccine on carriage of antibiotic-resistant Streptococcus pneumoniae in day-care centers. Pediatr Infect Dis J 2003; 22:532.
- Pelton SI, Loughlin AM, Marchant CD. Seven valent pneumococcal conjugate vaccine immunization in two Boston communities: changes in serotypes and antimicrobial susceptibility among Streptococcus pneumoniae isolates. Pediatr Infect Dis J 2004; 23:1015.
- Ghaffar F, Barton T, Lozano J, et al. Effect of the 7-valent pneumococcal conjugate vaccine on nasopharyngeal colonization by Streptococcus pneumoniae in the first 2 years of life. Clin Infect Dis 2004; 39:930.
- Hanage WP, Huang SS, Lipsitch M, et al. Diversity and antibiotic resistance among nonvaccine serotypes of Streptococcus pneumoniae carriage isolates in the post-heptavalent conjugate vaccine era. J Infect Dis 2007; 195:347.
- O'Brien KL, Millar EV, Zell ER, et al. Effect of pneumococcal conjugate vaccine on nasopharyngeal colonization among immunized and unimmunized children in a community-randomized trial. J Infect Dis 2007; 196:1211.
- Nahm MH, Lin J, Finkelstein JA, Pelton SI. Increase in the prevalence of the newly discovered pneumococcal serotype 6C in the nasopharynx after introduction of pneumococcal conjugate vaccine. J Infect Dis 2009; 199:320.
- van Gils EJ, Veenhoven RH, Hak E, et al. Effect of reduced-dose schedules with 7-valent pneumococcal conjugate vaccine on nasopharyngeal pneumococcal carriage in children: a randomized controlled trial. JAMA 2009; 302:159.
- Wroe PC, Lee GM, Finkelstein JA, et al. Pneumococcal carriage and antibiotic resistance in young children before 13-valent conjugate vaccine. Pediatr Infect Dis J 2012; 31:249.
- van Gils EJ, Veenhoven RH, Hak E, et al. Pneumococcal conjugate vaccination and nasopharyngeal acquisition of pneumococcal serotype 19A strains. JAMA 2010; 304:1099.
- Long SS. Capsules, clones, and curious events: pneumococcus under fire from polysaccharide conjugate vaccine. Clin Infect Dis 2005; 41:30.
- Carter R, Wolf J, van Opijnen T, et al. Genomic analyses of pneumococci from children with sickle cell disease expose host-specific bacterial adaptations and deficits in current interventions. Cell Host Microbe 2014; 15:587.
- Regev-Yochay G, Dagan R, Raz M, et al. Association between carriage of Streptococcus pneumoniae and Staphylococcus aureus in Children. JAMA 2004; 292:716.
- Bogaert D, van Belkum A, Sluijter M, et al. Colonisation by Streptococcus pneumoniae and Staphylococcus aureus in healthy children. Lancet 2004; 363:1871.
- Loughlin AM, Hsu K, Silverio AL, et al. Direct and indirect effects of PCV13 on nasopharyngeal carriage of PCV13 unique pneumococcal serotypes in Massachusetts' children. Pediatr Infect Dis J 2014; 33:504.
- Millar EV, Watt JP, Bronsdon MA, et al. Indirect effect of 7-valent pneumococcal conjugate vaccine on pneumococcal colonization among unvaccinated household members. Clin Infect Dis 2008; 47:989.
- Hammitt LL, Bruden DL, Butler JC, et al. Indirect effect of conjugate vaccine on adult carriage of Streptococcus pneumoniae: an explanation of trends in invasive pneumococcal disease. J Infect Dis 2006; 193:1487.
- Hampton LM, Farley MM, Schaffner W, et al. Prevention of antibiotic-nonsusceptible Streptococcus pneumoniae with conjugate vaccines. J Infect Dis 2012; 205:401.
- Tomczyk S, Lynfield R, Schaffner W, et al. Prevention of Antibiotic-Nonsusceptible Invasive Pneumococcal Disease With the 13-Valent Pneumococcal Conjugate Vaccine. Clin Infect Dis 2016; 62:1119.
- Moore MR, Link-Gelles R, Schaffner W, et al. Effectiveness of 13-valent pneumococcal conjugate vaccine for prevention of invasive pneumococcal disease in children in the USA: a matched case-control study. Lancet Respir Med 2016; 4:399.
- Olarte L, Barson WJ, Barson RM, et al. Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Pneumococcal Meningitis in US Children. Clin Infect Dis 2015; 61:767.
- Richter SS, Diekema DJ, Heilmann KP, et al. Changes in pneumococcal serotypes and antimicrobial resistance after introduction of the 13-valent conjugate vaccine in the United States. Antimicrob Agents Chemother 2014; 58:6484.
- Klugman KP. Vaccination: a novel approach to reduce antibiotic resistance. Clin Infect Dis 2004; 39:649.
- Gertz RE Jr, Li Z, Pimenta FC, et al. Increased penicillin nonsusceptibility of nonvaccine-serotype invasive pneumococci other than serotypes 19A and 6A in post-7-valent conjugate vaccine era. J Infect Dis 2010; 201:770.
- Gounder PP, Brewster M, Bruce MG, et al. Impact of the Pneumococcal Conjugate Vaccine and Antibiotic Use on Nasopharyngeal Colonization by Antibiotic Nonsusceptible Streptococcus pneumoniae, Alaska, 2000[FIGURE DASH]2010. Pediatr Infect Dis J 2015; 34:1223.
- Garbutt J, Rosenbloom I, Wu J, Storch GA. Empiric first-line antibiotic treatment of acute otitis in the era of the heptavalent pneumococcal conjugate vaccine. Pediatrics 2006; 117:e1087.
- Greenberg D, Givon-Lavi N, Sharf AZ, et al. The association between antibiotic use in the community and nasopharyngeal carriage of antibiotic-resistant Streptococcus pneumoniae in Bedouin children. Pediatr Infect Dis J 2008; 27:776.
- Nesin M, Ramirez M, Tomasz A. Capsular transformation of a multidrug-resistant Streptococcus pneumoniae in vivo. J Infect Dis 1998; 177:707.
- Caimano MJ, Hardy GG, Yother J. Capsule genetics in Streptococcus pneumoniae and a possible role for transposition in the generation of the type 3 locus. Microb Drug Resist 1998; 4:11.
- Lee CJ, Banks SD, Li JP. Virulence, immunity, and vaccine related to Streptococcus pneumoniae. Crit Rev Microbiol 1991; 18:89.