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Re: Global serotype distribution among Streptococcus pneumoniae isolates causing otitis media in children: Potential implications for pneumococcal conjugate vaccines
Vaccine 27 (2009) 4739–4740
Contents lists available at ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Letter to the Editor a r t i c l e
i n f o
Keywords: Streptococcus pneumoniae Acute otitis media Serotype
a b s t r a c t Acute otitis media (AOM) is one of the most commonly diagnosed childhood infections. Analysis of global serotype distribution among Streptococcus pneumonia isolates causing otitis media in children may improve coverage of future pneumococcal conjugate vaccines. Serotypes like 3 or 19A should not only be included in future vaccine formulations but they should preferably protect against these serotypes. To construct future AOM vaccine with higher vaccine efficacy also other pathogens causing AOM need to be taken into consideration. © 2009 Elsevier Ltd. All rights reserved.
Re: Global serotype distribution among Streptococcus pneumoniae isolates causing otitis media in children: Potential implications for pneumococcal conjugate vaccines Antibiotic prescription for acute otitis media is one of the major factors driving antibiotic resistance. There are ongoing discussions how to optimize therapeutic management and the development of appropriate vaccines against AOM is an important challenge. Broadening serotype coverage can significantly increase vaccine efficacy and limit the space for possible non-vaccine serotype replacement. Authors Rodgers et al. selected in their paper “Global serotype distribution among Streptococcus pneumoniae isolates causing otitis media in children: potential implications for pneumococcal conjugate vaccines” a more or less quantitative descriptive approach [1]. The last sentence of this paper may be misleading for the readers as it states that serotypes 3, 6A and 19A should be included in future vaccine formulations instead of stating that vaccines should protect against these serotypes. If we speculate on PCV7 efficacy against covered serotypes in FinOM trial we have only 7% overall efficacy, in spite of fact the clinical impact might be slightly higher in different epidemiological settings, assuming 57% efficacy against vaccine specific serotypes. Adding a few new serotypes will in this case lead to theoretical increase in net efficacy by only single percents and it is based on another crucial assumption, the added serotypes should work. Based on our experience with the candidate 11-valent pneumococcal PD-conjugate vaccine, containing serotype 3, no efficacy could be demonstrated against otitis due to this serotype (negative point estimate of efficacy) [2]. Additionally serotype 3 seems to induce an atypical immunological response, that results in postbooster antibody concentrations that are lower compared to those measured after primary vaccination, and also lower compared to measured after a first dose of serotype 3 conjugate or even plain serotype 3 polysaccharide vaccine in the second year of life. Such immune profile was also observed with the experimental 13-valent CRM-conjugate vaccine [3–5]. Serotype 6A should be not only included in vaccines but these vaccines should be efficacious against 6A. We can however speculate if this is the crucial serotype for inclusion in new vaccines. Both already registered vaccines demonstrated cross-protection against this serotype and in spite of fact 0264-410X/$ – see front matter © 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2009.05.098
the crossprotection is only partial serotype 6A disappeared, based on recent US data, and the only remaining serotype representing serogroup 6 is 6C. Serotype 19A no doubt is very important one and it is major replacing serotype with invasive and resistance developing potential however the incidence is variable from one country to another. Demonstrating limited added value for AOM vaccine serotype coverage for serotypes 1, 5, 7F is probably a true observation due to the low contribution of these serotypes to otitis media, however stating that adding serotypes 3, 6A and 19A to a vaccines is needed in future vaccine formulations may not be fully correct. Factors like cross-protection for 6A, lack of efficacy for serotype 3 and limited occurrence of serotype 19A in many countries can significantly lower expected benefit. Future vaccine against AOM should demonstrate their efficacy against AOM. Indirect proof of efficiency based on example of decreased number of visits for AOM is definitely supportive, however it cannot replace data from controlled randomized double-blind trials. Risk of confounding factors and various biases is too high to provide real scientific evidence. Other factors such as time coincidence may play an important role, like various other measurements (new antibiotics prescription guidelines, reimbursement schemes, public health programmes, etc.). Conclusion: It is necessary not only to add more pneumococcal serotypes to the vaccine, but to add serotypes eliciting appropriate response and also protect. Besides this, to increase efficacy against bacterial AOM, future vaccines should cover other major pathogens such as non-typeable H. influenzae and maybe also M. catarrhalis irrespective of the mechanism of action (active carrier protein, combined vaccines with other bacterial pathogen(s)). References [1] Rodgers GL, Arguedas A, Cohen R, Dagan R. Global serotype distribution among Streptococcus pneumoniae isolates causing otitis media in children: potential implications for pneumococcal conjugate vaccines. Vaccine 2009;27:3802– 10. [2] Poolman J, Kriz P, Feron Ch, Di-Paolo E, Henckaerts I, Miseur A, et al. Pneumococcal serotype 3 otitis media, limited effect of polysaccharide conjugate immunisation and strain characteristics. Vaccine 2009;27:3213–22.
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Letter to the Editor / Vaccine 27 (2009) 4739–4740
[3] Prymula R, Peeters P, Chrobok V, Kriz P, Novakova E, Kaliskova E, et al. Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typeable Haemophilus influenzae: a randomized double-blind efficacy study. Lancet 2006;367: 740–8. [4] Bryant KA, Block SL, Scott DA. Safety and immunogenicity of a 13-valent pneumococcal conjugate vaccine. In: 25th annual meeting of the European Society for Paediatric Infectious Diseases (ESPID), Abstract book. 2007. p. 32 [Abstract no. 53]. [5] Bryant KA, Block SL, Scott DA. Safety and immunogenicity of a 4th dose of 13valent pneumococcal conjugate vaccine in healthy toddlers. In: 26th annual meeting of the European Society for Paediatric Infectious Diseases (ESPID), Abstract book. 2008. p. 309 [Abstract no. 600].
Roman Prymula ∗ Faculty of Military Health Sciences, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic ∗ Tel.:
+420 973 253 001; fax: +420 495 513 018. E-mail address: [email protected] 28 May 2009 Available online 21 June 2009
Contents lists available at ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Letter to the Editor a r t i c l e
i n f o
Keywords: Streptococcus pneumoniae Acute otitis media Serotype
a b s t r a c t Acute otitis media (AOM) is one of the most commonly diagnosed childhood infections. Analysis of global serotype distribution among Streptococcus pneumonia isolates causing otitis media in children may improve coverage of future pneumococcal conjugate vaccines. Serotypes like 3 or 19A should not only be included in future vaccine formulations but they should preferably protect against these serotypes. To construct future AOM vaccine with higher vaccine efficacy also other pathogens causing AOM need to be taken into consideration. © 2009 Elsevier Ltd. All rights reserved.
Re: Global serotype distribution among Streptococcus pneumoniae isolates causing otitis media in children: Potential implications for pneumococcal conjugate vaccines Antibiotic prescription for acute otitis media is one of the major factors driving antibiotic resistance. There are ongoing discussions how to optimize therapeutic management and the development of appropriate vaccines against AOM is an important challenge. Broadening serotype coverage can significantly increase vaccine efficacy and limit the space for possible non-vaccine serotype replacement. Authors Rodgers et al. selected in their paper “Global serotype distribution among Streptococcus pneumoniae isolates causing otitis media in children: potential implications for pneumococcal conjugate vaccines” a more or less quantitative descriptive approach [1]. The last sentence of this paper may be misleading for the readers as it states that serotypes 3, 6A and 19A should be included in future vaccine formulations instead of stating that vaccines should protect against these serotypes. If we speculate on PCV7 efficacy against covered serotypes in FinOM trial we have only 7% overall efficacy, in spite of fact the clinical impact might be slightly higher in different epidemiological settings, assuming 57% efficacy against vaccine specific serotypes. Adding a few new serotypes will in this case lead to theoretical increase in net efficacy by only single percents and it is based on another crucial assumption, the added serotypes should work. Based on our experience with the candidate 11-valent pneumococcal PD-conjugate vaccine, containing serotype 3, no efficacy could be demonstrated against otitis due to this serotype (negative point estimate of efficacy) [2]. Additionally serotype 3 seems to induce an atypical immunological response, that results in postbooster antibody concentrations that are lower compared to those measured after primary vaccination, and also lower compared to measured after a first dose of serotype 3 conjugate or even plain serotype 3 polysaccharide vaccine in the second year of life. Such immune profile was also observed with the experimental 13-valent CRM-conjugate vaccine [3–5]. Serotype 6A should be not only included in vaccines but these vaccines should be efficacious against 6A. We can however speculate if this is the crucial serotype for inclusion in new vaccines. Both already registered vaccines demonstrated cross-protection against this serotype and in spite of fact 0264-410X/$ – see front matter © 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2009.05.098
the crossprotection is only partial serotype 6A disappeared, based on recent US data, and the only remaining serotype representing serogroup 6 is 6C. Serotype 19A no doubt is very important one and it is major replacing serotype with invasive and resistance developing potential however the incidence is variable from one country to another. Demonstrating limited added value for AOM vaccine serotype coverage for serotypes 1, 5, 7F is probably a true observation due to the low contribution of these serotypes to otitis media, however stating that adding serotypes 3, 6A and 19A to a vaccines is needed in future vaccine formulations may not be fully correct. Factors like cross-protection for 6A, lack of efficacy for serotype 3 and limited occurrence of serotype 19A in many countries can significantly lower expected benefit. Future vaccine against AOM should demonstrate their efficacy against AOM. Indirect proof of efficiency based on example of decreased number of visits for AOM is definitely supportive, however it cannot replace data from controlled randomized double-blind trials. Risk of confounding factors and various biases is too high to provide real scientific evidence. Other factors such as time coincidence may play an important role, like various other measurements (new antibiotics prescription guidelines, reimbursement schemes, public health programmes, etc.). Conclusion: It is necessary not only to add more pneumococcal serotypes to the vaccine, but to add serotypes eliciting appropriate response and also protect. Besides this, to increase efficacy against bacterial AOM, future vaccines should cover other major pathogens such as non-typeable H. influenzae and maybe also M. catarrhalis irrespective of the mechanism of action (active carrier protein, combined vaccines with other bacterial pathogen(s)). References [1] Rodgers GL, Arguedas A, Cohen R, Dagan R. Global serotype distribution among Streptococcus pneumoniae isolates causing otitis media in children: potential implications for pneumococcal conjugate vaccines. Vaccine 2009;27:3802– 10. [2] Poolman J, Kriz P, Feron Ch, Di-Paolo E, Henckaerts I, Miseur A, et al. Pneumococcal serotype 3 otitis media, limited effect of polysaccharide conjugate immunisation and strain characteristics. Vaccine 2009;27:3213–22.
4740
Letter to the Editor / Vaccine 27 (2009) 4739–4740
[3] Prymula R, Peeters P, Chrobok V, Kriz P, Novakova E, Kaliskova E, et al. Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typeable Haemophilus influenzae: a randomized double-blind efficacy study. Lancet 2006;367: 740–8. [4] Bryant KA, Block SL, Scott DA. Safety and immunogenicity of a 13-valent pneumococcal conjugate vaccine. In: 25th annual meeting of the European Society for Paediatric Infectious Diseases (ESPID), Abstract book. 2007. p. 32 [Abstract no. 53]. [5] Bryant KA, Block SL, Scott DA. Safety and immunogenicity of a 4th dose of 13valent pneumococcal conjugate vaccine in healthy toddlers. In: 26th annual meeting of the European Society for Paediatric Infectious Diseases (ESPID), Abstract book. 2008. p. 309 [Abstract no. 600].
Roman Prymula ∗ Faculty of Military Health Sciences, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic ∗ Tel.:
+420 973 253 001; fax: +420 495 513 018. E-mail address: [email protected] 28 May 2009 Available online 21 June 2009