Ahead of Print -Changes in Capsule and Drug Resistance of Pneumococci after Introduction of PCV7, Japan, 2010–2013 - Volume 20, Number 7—July 2014 - Emerging Infectious Disease journal - CDC

full-text ►

Ahead of Print -Changes in Capsule and Drug Resistance of Pneumococci after Introduction of PCV7, Japan, 2010–2013 - Volume 20, Number 7—July 2014 - Emerging Infectious Disease journal - CDC

Volume 20, Number 7—July 2014

Research

Changes in Capsule and Drug Resistance of Pneumococci after Introduction of PCV7, Japan, 2010–2013

Article Contents

• Methods
• Results
• Discussion
• Acknowledgment
• References
• Figure 1
• Figure 2
• Figure 3
• Figure 4
• Table 1
• Table 2
• Table 3
• Suggested Citation

Naoko Chiba, Miyuki Morozumi, Michi Shouji, Takeaki Wajima, Satoshi Iwata, Kimiko Ubukata , and the Invasive Pneumococcal Diseases Surveillance Study Group

Author affiliations: Keio University School of Medicine, Tokyo, Japan (N. Chiba, M. Morozumi, S. Iwata, K. Ubukata); Kitasato University, Tokyo (N. Chiba, M. Morozumi, K. Ubukata); National Cancer Center Hospital, Tokyo (M. Shouji); Tokyo University of Pharmacy and Life Sciences, Tokyo (T. Wajima)

Suggested citation for this article

Abstract

We aimed to clarify changes in serotypes and genotypes mediating β-lactam and macrolide resistance in Streptococcus pneumoniae isolates from Japanese children who had invasive pneumococcal disease (IPD) after the 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into Japan; 341 participating general hospitals conducted IPD surveillance during April 2010–March 2013. A total of 300 pneumococcal isolates were collected in 2010, 146 in 2011, and 156 in 2012. The proportion of vaccine serotypes in infectious isolates decreased from 73.3% to 54.8% to 14.7% during the 3 years. Among vaccine serotype strains, genotypic penicillin-resistant S. pneumoniae strains also declined each year. Among nonvaccine serotype strains, 19A, 15A, 15B, 15C, and 24 increased in 2012. Increases were noted especially in genotypic penicillin-resistant S. pneumoniae isolates of serotypes 15A and 35B, as well as macrolide resistance mediated by the erm(B) gene in 15A, 15B, 15C, and 24.

Invasive pneumococcal disease (IPD), such as meningitis, sepsis, and empyema, substantially contributes to illness and death in children (1,2). After increasing numbers of cases caused by penicillin (PEN)–resistant Streptococcus pneumoniae (PRSP) emerged and rapidly spread worldwide during the 1990s (3,4), the need for a vaccine effective in infants became clear. In the United States, a 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2000 and made available for routine use in all children 2–23 months of age and in children 24–59 months of age at risk for pneumococcal infection (5). Subsequent surveillance studies demonstrated a marked decrease in prevalence of pneumococcal infection caused by vaccine serotypes, including PRSP (6–8). In particular, PCV7 appears to have decreased incidence of meningitis caused by vaccine serotypes (9), and cases caused by non-PCV7 serotype strains, such as PRSP with serotype 19A, have increased in the United States (8,10,11). Such changes suggest that nonvaccine serotypes are replacing vaccine serotypes in some countries (12–14).

A next-generation 13-valent pneumococcal conjugate vaccine (PCV13) was licensed for use in the United States in 2010 (15). PCV13 has been approved in 128 countries, and children in 83 countries have undergone routine PCV13 vaccination. Recently, Richter et al. reported that an increase of type 19A was halted by introduction of PCV13, whereas serotype 35B increased; coverage provided by PCV13 was effective in only 41.4% of children <5 years of age in 2010 and 2011 (16). Furthermore, Kaplan et al. reported a slight increase in serotype 33F (17).

In Japan, PRSP has increased rapidly as a cause of respiratory tract infections, acute otitis media, and IPD in children since the late 1990s (18,19). PCV7 received final approval in October 2009 and has been used clinically in infants on a voluntary basis since February 2010. Since November 2010, PCV7 use has been encouraged for children <5 years of age throughout Japan by an official program, the Provisional Special Fund for the Urgent Promotion of Vaccination. As a result, estimated rates of PCV7 vaccination for such children were <10% in 2010, 50%–60% in 2011, and 80%–90% in 2012.

PCV7 was incorporated into the routine vaccination schedule for children in Japan beginning in April 2013; before then, however, its coverage rate against IPD had decreased rapidly from 71.8% in 2006 to 51.6% in 2011 (20). Most recently, PCV13 was approved by the government in June 2013, later replacing PCV7 as a routine vaccination in December 2013. The purpose of our study was to clarify changes during April 2010–March 2013 of serotypes and genotypes mediating β-lactam and macrolide resistance in S. pneumoniae isolates from children <18 years of age who had IPD before and after PCV7 introduction.

Dr Chiba is a microbiologist at Keio University School of Medicine. Her research interests include molecular epidemiology, particularly pathogens causing respiratory infection.

Acknowledgment

Our study was funded in part by a grant under the category, “Research on Emerging and Re-emerging Infectious Diseases” (H22-013), from the Japanese Ministry of Health, Labour and Welfare to K.U.

References

1. World Health Organization. Pneumococcal conjugate vaccine for childhood immunization: WHO position paper. [PubMed]. Wkly Epidemiol Rec. 2007;82:93–104.PubMed
2. O'Brien KL, Wolfson LJ, Watt JP, Henkle E, Deloria-Knoll M, McCall N, ; Hib and Pneumococcal Global Burden of Disease Study Team. Burden of disease caused byStreptococcus pneumoniae in children younger than 5 years: global estimates. [PubMed].Lancet. 2009;374:893–902. DOIPubMed
3. Appelbaum PC. Antimicrobial resistance in Streptococcus pneumoniae: an overview. Clin Infect Dis. 1992;15:77–83. PubMed DOI
4. Whitney CG, Farley MM, Hadler J, Harrison LH, Lexau C, Reingold A, ; Active Bacterial Core Surveillance Program of the Emerging Infections Program Network. Increasing prevalence of multidrug-resistant Streptococcus pneumoniae in the United States.[PubMed]. N Engl J Med. 2000;343:1917–24. DOIPubMed
5. Advisory Committee on Immunization Practices. Preventing pneumococcal disease among infants and young children: recommendations of the Advisory Committee on Immunization Practices (ACIP). [PubMed]. MMWR Recomm Rep. 2000;49(RR-9):1–35.PubMed
6. Whitney CG, Farley MM, Hadler J, Harrison LH, Bennett NM, Lynfield R, Active Bacterial Core Surveillance of the Emerging Infections Program Network. Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. [PubMed]. N Engl J Med. 2003;348:1737–46. DOIPubMed
7. Centers for Disease Control and Prevention. 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. [PubMed]. MMWR Morb Mortal Wkly Rep. 2005;54:893–7.PubMed
8. Kyaw MH, Lynfield R, Schaffner W, Craig AS, Hadler J, Reingold A, Active Bacterial Core Surveillance of the Emerging Infections Program Network. Effect of introduction of the pneumococcal conjugate vaccine on drug-resistant Streptococcus pneumoniae. [PubMed].N Engl J Med. 2006;354:1455–63. DOIPubMed
9. Hsu HE, Shutt KA, Moore MR, Beall BW, Bennett NM, Craig AS, Effect of pneumococcal conjugate vaccine on pneumococcal meningitis. [PubMed]. N Engl J Med.2009;360:244–56. DOIPubMed
10. Moore MR, Gertz RE Jr, Woodbury RL, Barkocy-Gallagher GA, Schaffner W, Lexau C,Population snapshot of emergent Streptococcus pneumoniae serotype 19A in the United States, 2005. [PubMed]. J Infect Dis. 2008;197:1016–27. DOIPubMed
11. Hampton LM, Farley MM, Schaffner W, Thomas A, Reingold A, Harrison LH, Prevention of antibiotic-nonsusceptible Streptococcus pneumoniae with conjugate vaccines. [PubMed]. J Infect Dis. 2012;205:401–11. DOIPubMed
12. Miller E, Andrews NJ, Waight PA, Slack MP, George RC. Herd immunity and serotype replacement 4 years after seven-valent pneumococcal conjugate vaccination in England and Wales: an observational cohort study. [PubMed]. Lancet Infect Dis. 2011;11:760–8. DOIPubMed
13. World Health Organization. Changing epidemiology of pneumococcal serotypes after introduction of conjugate vaccine: July 2010 report. [PubMed]. Wkly Epidemiol Rec.2010;85:434–6.PubMed
14. Weinberger DM, Malley R, Lipsitch M. Serotype replacement in disease after pneumococcal vaccination. [PubMed]. Lancet. 2011;378:1962–73. DOIPubMed
15. Centers for Disease Control and Prevention. Licensure of a 13-valent pneumococcal conjugate vaccine (PCV13) and recommendations for use among children. Advisory Committee on Immunization Practices (ACIP). [PubMed]. MMWR Morb Mortal Wkly Rep.2010;59:258–61.PubMed
16. Richter SS, Heilmann KP, Dohrn CL, Riahi F, Diekema DJ, Doern GV. Pneumococcal serotypes before and after introduction of conjugate vaccines, United States, 1999–2011. [PubMed]. Emerg Infect Dis. 2013;19:1074–83. DOIPubMed
17. Kaplan SL, Barson WJ, Lin PL, Romero JR, Bradley JS, Tan TQ, Early trends for invasive pneumococcal infections in children after the introduction of the 13-valent pneumococcal conjugate vaccine. [PubMed]. Pediatr Infect Dis J. 2013;32:203–7. DOIPubMed
18. Ubukata K, Asahi Y, Okuzumi K, Konno M. Incidence of penicillin-resistant Streptococcus pneumoniae in Japan, 1993–1995. J Infect Chemother. 1996;1:177–84. DOI
19. Ubukata K, Chiba N, Hasegawa K, Kobayashi R, Iwata S, Sunakawa K. Antibiotic susceptibility in relation to penicillin-binding protein genes and serotype distribution ofStreptococcus pneumoniae strains responsible for meningitis in Japan, 1999 to 2002.[PubMed]. Antimicrob Agents Chemother. 2004;48:1488–94. DOIPubMed
20. Chiba N, Morozumi M, Shouji M, Wajima T, Iwata S, Sunakawa K, ; Invasive Pneumococcal Diseases Surveillance Study Group. Rapid decrease of 7-valent conjugate vaccine coverage for invasive pneumococcal diseases in pediatric patients in Japan.[PubMed]. Microb Drug Resist. 2013;19:308–15. DOIPubMed
21. Chiba N, Morozumi M, Ubukata K. Application of the real-time PCR method for genotypic identification of β-lactam resistance in isolates from invasive pneumococcal diseases.[PubMed]. Microb Drug Resist. 2012;18:149–56. DOIPubMed
22. Chiba N, Kobayashi R, Hasegawa K, Morozumi M, Nakayama E, Tajima T, ; Acute Respiratory Diseases Study Group. Antibiotic susceptibility according to genotype of penicillin-binding protein and macrolide resistance genes, and serotype of Streptococcus pneumoniae isolates from community-acquired pneumonia in children. [PubMed]. J Antimicrob Chemother. 2005;56:756–60. DOIPubMed
23. Sakai F, Chiba N, Ono A, Yamagata Murayama S, Ubukata K, Sunakawa K, Molecular epidemiologic characteristics of Streptococcus pneumoniae isolates from children with meningitis in Japan from 2007 through 2009. [PubMed]. J Infect Chemother.2011;17:334–40. DOIPubMed
24. Isaacman DJ, McIntosh ED, Reinert RR. Burden of invasive pneumococcal disease and serotype distribution among Streptococcus pneumoniae isolates in young children in Europe: impact of the 7-valent pneumococcal conjugate vaccine and considerations for future conjugate vaccines. [PubMed]. Int J Infect Dis. 2010;14:e197–209. DOIPubMed
25. Hanquet G, Kissling E, Fenoll A, George R, Lepoutre A, Lernout T, Pneumococcal serotypes in children in 4 European countries. [PubMed]. Emerg Infect Dis.2010;16:1428–39. DOIPubMed
26. McIntosh ED, Reinert RR. Global prevailing and emerging pediatric pneumococcal serotypes. [PubMed]. Expert Rev Vaccines. 2011;10:109–29. DOIPubMed
27. Gertz RE Jr, Li Z, Pimenta FC, Jackson D, Juni BA, Lynfield R, ; Active Bacterial Core Surveillance Team. Increased penicillin nonsusceptibility of nonvaccine-serotype invasive pneumococci other than serotypes 19A and 6A in post–7-valent conjugate vaccine era.[PubMed]. J Infect Dis. 2010;201:770–5. DOIPubMed
28. Okada T, Morozumi M, Tajima T, Hasegawa M, Sakata H, Ohnari S, Rapid effectiveness of minocycline or doxycycline against macrolide-resistant Mycoplasma pneumoniae infection in a 2011 outbreak among Japanese children. [PubMed]. Clin Infect Dis.2012;55:1642–9. DOIPubMed
29. Wajima T, Morozumi M, Chiba N, Shouji M, Iwata S, Sakata H, Associations of macrolide and fluoroquinolone resistance with molecular typing in Streptococcus pyogenes from invasive infections, 2010–2012. [PubMed]. Int J Antimicrob Agents. 2013;42:447–9. DOIPubMed
30. Brueggemann AB, Pai R, Crook DW, Beall B. Vaccine escape recombinants emerge after pneumococcal vaccination in the United States. [PubMed]. PLoS Pathog. 2007;3:e168. DOIPubMed

Figures

• Figure 1. Distribution of general hospitals participating in surveillance for invasive pneumococcal disease, Japan, April 2010–March 2013Numbers in light gray circles show the number of the hospitals in each prefectureNumbers in...
• Figure 2. Changes in serotype number and penicillin resistance according to genotype, Japan, April 2010–March 2013gPSSP, genotypic penicillin-susceptible Streptococcus pneumoniae; gPISP, genotypic penicillin-intermediate resistant Spneumoniae; gPRSP, penicillin-resistantSpneumoniaeThe parentheses express abnormal...
• Figure 3. Proportional yearly changes in macrolide resistance according to resistance geneserm(B) and mef(A) identified by real-time PCR, Japan, April 2010–March 2013The percentage of each resistance gene was calculated from...
• Figure 4. Changes in serotype number and macrolide resistance of Streptococcus pneumoniaestrains according to genotype, Japan, April 2010–March 2013MLS, macrolide-susceptible strains not possessing any resistance gene; MLR-mef(A), macrolide-resistant strain possessing...

Tables

• Table 1. Vaccine and nonvaccine serotypes of Streptococcus pneumoniae in children after introduction of PCV7, Japan, April 2010–March 2013
• Table 2. Year-to-year changes in prevalence of vaccine and nonvaccine serotypes ofStreptococcus pneumoniae in children after introduction of PCV7, Japan, April 2010–March 2013
• Table 3. Pneumococcal vaccination history and age for 156 children with invasive pneumococcal disease, Japan, 2012

Suggested citation for this article: Chiba N, Morozumi M, Shouji M, Wajima T, Iwata S, Ubukata K et al. Changes in capsule and drug resistance of pneumococci after introduction of PCV7, Japan, 2010–2013. Emerg Infect Dis [Internet]. 2014 Jul [date cited].http://dx.doi.org/10.3201/eid2007.131485

DOI: 10.3201/eid2007.131485