Efficacy of a Pneumococcal Conjugate Vaccine against Acute Otitis Media

Eskola, Juhani; Kilpi, Terhi; Palmu, Arto A.; Jokinen, Jukka; Haapakoski, Jaason; Herva, Elja; Takala, Aino K.; Käyhty, Helena; Karma, Pekka; Kohberger, Robert; Siber, George R.; Ph, Mäkelä

doi:10.1056/nejm200102083440602

Cited by 1,332 publications

(914 citation statements)

References 38 publications

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“…The pneumococcal 165 serotypes detected were the common ones known to cause AOM infections among 166 children [1]. PCV7 and PCV10 would have covered 75% of the serotypes detected, and 167 PCV13 would have covered 86%.…”

Section: Prevalence Of Pilus-encoding Islets and Clonality Of Pneumocmentioning

confidence: 98%

“…However, our finding of a PI-1 169 association with both 6A and 6B is of special interest. Although the Finnish clinical 170 AOM trial with PCV7 gives reason to expect cross-protection within serogroup 6 [1], the 171 serotypes 6A and 19A, both included only in the PCV13, are of worldwide concern. They 172 cause both invasive and non-invasive disease and have been claimed as replacement 173 serotypes with increasing resistance to antimicrobials [2,13,14].…”

Section: Prevalence Of Pilus-encoding Islets and Clonality Of Pneumocmentioning

confidence: 99%

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Prevalence of pilus-encoding islets and clonality of pneumococcal isolates from children with acute otitis media

Vainio

Kaijalainen

Hakanen

et al. 2011

Eur J Clin Microbiol Infect Dis

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To cite this version:A. Vainio, T. Kaijalainen, A. J. Hakanen, A. Virolainen. Prevalence of pilus-encoding islets and clonality of pneumococcal isolates from children with acute otitis media. We characterized prevalence of pilus islets 1 (PI-1) and 2 (PI-2) and clonality of 25 Streptococcus pneumoniae isolates taken from children with acute otitis media (AOM) to 26 study the association between pilus existence and AOM disease potential prior to 27 pneumococcal conjugate vaccine and increased antimicrobial resistance. 28The study material consisted of 75 pneumococcal isolates cultured from middle ear fluid 29 and/or nasopharyngeal aspirate of 56 children with AOM in Finland during 1990Finland during -1992 Isolates were studied for antimicrobial susceptibility and were serotyped, genotyped by 31 multilocus sequence typing (MLST), and tested for the presence of pneumococcal PI-1 32 and PI-2 genes. 33All isolates were susceptible to penicillin, 14 different serotypes were found, and 20% of 34 the isolates were positive for PI-1 genes. PI-2 genes were not found. MLST showed high 35 heterogeneity: 52 AOM isolates belonged to 18 known Clonal Complexes (CC). PI-1 was 36 associated with serotypes 6A, 6B, and 9V, and genotype CC490. 37In the time prior to PCV7 and increased antimicrobial resistance, pneumococcal AOM 38 isolates carried PI-1 genes in rather low prevalence. PI-2 genes were not detected. PI-1 39 was related with serotype rather than genotype. The importance of PI-1 in AOM 40 infections and its association with the spread of antimicrobial resistance requires further 41 research. 42 6

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Section: Prevalence Of Pilus-encoding Islets and Clonality Of Pneumocmentioning

confidence: 98%

Section: Prevalence Of Pilus-encoding Islets and Clonality Of Pneumocmentioning

confidence: 99%

Prevalence of pilus-encoding islets and clonality of pneumococcal isolates from children with acute otitis media

Vainio

Kaijalainen

Hakanen

et al. 2011

Eur J Clin Microbiol Infect Dis

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“…The observed reduction in vaccine serotypes has also been associated with an increase in carriage of non-vaccine serotypes in vaccinated children in carriage studies [13] and in vaccine trials for PCV against otitis media [14]. This phenomenon of serotype replacement has also been explored by mathematical modelling [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

A longitudinal household study of Streptococcus pneumoniae nasopharyngeal carriage in a UK setting

Hussain¹,

Melegaro

Pebody³

et al. 2005

Epidemiol. Infect.

172

163

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SUMMARYA 10-month longitudinal household study of pre-school children and their families was undertaken with monthly visits collecting epidemiological data and nasopharyngeal swabs in Hertfordshire, England from 2001 to 2002. Pneumococcal culture was with standard methods. In total, 121 families (489 individuals) took part. Mean prevalence of carriage ranged from 52 % for age groups 0-2 years, 45 % for 3-4 years, 21 % for 5-17 years and 8 % for o18 years. Carriage occurred more than once in 86 % of children aged 0-2 years compared to 36 % of those aged o18 years. The most prevalent serotypes in the 0-2 years age group were 6B followed by 19F, 23F, 6A and 14. Young children were responsible for the majority of introductions of new serotypes into a household. Erythromycin resistance (alone or in combination) occurred in 10% of samples and penicillin non-susceptibility in 3 . 7%. Overall the recently licensed 7-valent conjugate vaccine (PCV) would protect against 64 % of serotypes with no intra-serogroup cross protection and 82% with such protection. Nasopharyngeal carriage of S. pneumoniae is common in a UK setting in the pre-conjugate vaccine era. PCV would protect against a large proportion of carriage isolates. However, the impact of vaccination on non-vaccine serotypes will need to be monitored.

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“…However, conjugation of PS to protein carriers allows T cell help through recruitment of carrier-specific T cells [10][11][12][13][14] and makes the PPS immunogenic in early infancy (reviewed in [15]). Protective immunity against both invasive disease [16,17] and otitis media [18] has been demonstrated after vaccination of infants with pneumococcal conjugate vaccines. In addition, pneumococcal conjugate vaccines induce PS-specific memory B cells [19][20][21], similar to what has been observed after immunization with protein antigens.…”

Section: Introductionmentioning

confidence: 99%

Early life T cell responses to pneumococcal conjugates increase with age and determine the polysaccharide‐specific antibody response and protective efficacy

et al. 2006

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Immunization with a tetanus-protein (TT) pneumococcal polysaccharide (PPS) conjugate vaccine (Pnc1-TT) induces protective immunity against lethal pneumococcal infections in neonatal and infant mice, but anti-PPS IgG response and protective efficacy is lower than in adult mice. Here, we show that reduced antibody (Ab) response and protection against infections is directly related to impaired T cell response to the carrier. Whereas spleen cells from adult mice immunized with Pnc1-TT responded with proliferation and IFN-gamma secretion to in vitro stimulation with TT, spleen cells from neonatal and infant mice did not. However, significant, but age dependent, Th2-cytokine responses were observed in mice immunized with Pnc1-TT. Impaired IFN-gamma production upon TT-stimulation in vitro was also reflected in reduced IFN-gamma/IL-5 ratio. The IL--5 response correlated with IgG anti-PPS titers, and the lack of PPS Ab in the majority of neonatal mice was clearly associated with absence of carrier-specific IL-5 production. These results show that immunization with Pnc1-TT induces carrier-specific T cell responses that increase with age and determine the levels of PPS-specific Ab elicited. Whereas a weak and Th2-biased response was observed in neonatal mice, infant mice showed a mixed Th1-Th2 response as observed in adults

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Efficacy of a Pneumococcal Conjugate Vaccine against Acute Otitis Media

Abstract: The heptavalent pneumococcal polysaccharide-CRM197 conjugate vaccine is safe and efficacious in the prevention of acute otitis media caused by the serotypes included in the vaccine.

Cited by 1,332 publications

References 38 publications

Prevalence of pilus-encoding islets and clonality of pneumococcal isolates from children with acute otitis media

Prevalence of pilus-encoding islets and clonality of pneumococcal isolates from children with acute otitis media

A longitudinal household study of Streptococcus pneumoniae nasopharyngeal carriage in a UK setting

Early life T cell responses to pneumococcal conjugates increase with age and determine the polysaccharide‐specific antibody response and protective efficacy

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