New Patterns in the Otopathogens Causing Acute Otitis Media Six to Eight Years After Introduction of Pneumococcal Conjugate Vaccine
To describe NP and AOM otopathogens during the time frame 2007 to 2009, 6 to 8 years after the introduction of 7-valent pneumococcal conjugate (PCV7) in the United States and to compare nasopharyngeal (NP) colonization and acute otitis media (AOM) microbiology in children 6 to 36 months of age having first and second AOM episodes with children who are otitis prone.
Prospectively, the microbiology of NP colonization and AOM episodes was determined in 120 children with absent or infrequent AOM episodes. NP samples were collected at 7 routine visits between 6 and 30 months of age and at the time of AOM. For first and subsequent AOM episodes, middle ear fluid (MEF) was obtained by tympanocentesis. Eighty otitis prone children were comparatively studied. All 200 children received age-appropriate doses of PCV7.
We found PCV7 serotypes were virtually absent: (0.9% isolated from both NP and MEF) in both study groups. However, non-PCV7 serotypes replaced PCV serotypes such that the frequency of isolation of S. pneumoniae (Spn) was nearly equal to that of non-typeable Haemophilus influenzae (NTHi). M. catarrhalis (Mcat) was less common and Staphylococcus aureus infrequent in the NP and MEF from the 2 groups. The proportion of Spn, NTHi and Mcat causing AOM was similar in children with first and second AOM episodes compared to otitis prone children. However, oxacillin-resistant Spn isolated from the NP and MEF was 19% for the absent/infrequent and 58% for the otitis prone groups, P < 0.0001. Beta-lactamase producing NTHi occurred more frequently in the otitis prone group, P = 0.04.
Six to 8 years after widespread use of PCV7, Spn strains expressing vaccine-type serotypes have virtually disappeared from the NP and MEF of vaccinated children. NP colonization and AOM has changed to non-PCV7 strains of Spn. NTHi continues to be a major AOM pathogen. The otopathogens in first and second AOM and in otitis prone children are very similar although Spn and NTHi are more often antibiotic resistant in the otitis prone.
Available from: Astrid Bosch
- "Vaccination with PCV7 resulted in increased levels of H. influenzae in previous randomized controlled trials after PCV7 vaccinations [40,41] and follow-up surveillance studies [16,17,42]. This coincided with increased involvement of (mainly nontypeable ) H. influenzae in otitis media in a RCT on PCV7 and AOM  and after the widespread implementation of PCV7  . Here we show that carriage of H. influenzae remained on a level albeit stable on the long term compared with pre-PCV7 vaccination data, also in PCV10 vaccinated children even though in PCV10 eight of the ten serotypes are conjugated to Protein D, a conserved outer membrane protein of non-typeable H. influenzae. "
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ABSTRACT: After introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in the infant national immunization program (NIP) in the Netherlands in 2006, Streptococcus pneumoniae strains of the non-vaccine serotype 19A emerged and became the dominant serotype in carriage in children and their parents. Similar patterns were observed in other European countries and the United States. Increases in carriage rates of Staphylococcus aureus and non-typeable (NT) Haemophilus influenzae were also observed. After switching of PCV7 to 10-valent vaccine (PCV10) in 2011, a new carriage surveillance study was performed in the winter of 2012/2013. Nasopharyngeal carriage of S. pneumoniae, H. influenzae, S. aureus, and Moraxella catarrhalis was determined by conventional culture in 330 PCV10-vaccinated 11-month-old children, 330 PCV7-vaccinated 24-month-old children, and their parents. Carriage prevalence was compared with similar carriage studies conducted in 2005, 2009, and 2010/2011. Although serotype 19A remained the most frequently carried pneumococcal serotype in children, prevalence of 19A significantly declined in PCV7-vaccinated 24-month-old children (14% to 8%, p = 0.01), but less in PCV10-vaccinated 11-month-old children (12% to 9%, p = 0.31). Carriage of H. influenzae remained stable at an elevated level (65% in 11-month-olds and 69% in 24-month-olds), while the carriage of S. aureus returned to pre-PCV7 levels in 11-month-old children (14% in 2010/2011 to 7% in 2012/2013), but not in 24-month-olds (remained at 7%). Our results might indicate a new balance between replacing non-vaccine pneumococcal serotypes and other potential pathogenic bacteria in nasopharyngeal carriage. Carriage studies are valuable tools in assessing vaccine effects on pathogens circulating in the population, for evaluation of PCV impact, and in predicting changes in respiratory and invasive disease.
- "Conversely, disease due to non-typeable H. influenzae (NTHi) involves, after establishment on respiratory mucosa, contiguous spread within the respiratory tract and, occasionally, to sterile sites[3,4]. Otitis media is the most commonly diagnosed bacterial infection in children and an increasing role for NTHi has been recently described[3,5,6]. The introduction of conjugate vaccines against H. influenzae type b (Hib)has led to a drastic reduction in invasive Hib disease in industrialized countries. "
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Haemophilus influenzae is an important pathogen able to cause a wide spectrum of diseases in children. Colonization of the upper respiratory tract is a risk factor for developing disease. This study aimed to investigate the oropharyngeal carriage rate of H. influenzae in young children in two Italian cities, 15 years after H. influenzae type b (Hib) vaccination was introduced. Antibiotic resistant traits and genotypes of the colonizing H. influenzae isolates were investigated.
Oropharyngeal swabs were obtained from 717 healthy children aged <6 years (June 2012-July 2013). Potential risk factors for H. influenzae colonization were investigated. H. influenzae isolates from carriage were characterized by PCR capsular typing, ampicillin susceptibility testing, resistance-associated gene sequencing and multilocus sequence typing (MLST). For comparison purposes, 38 non-typeable H. influenzae (NTHi) isolates from invasive disease were genotyped by MLST.
The overall H. influenzae carriage rate was 14.1% (101/717). Age, study site, presence of young siblings, and complete Hib vaccination status were independently associated with colonization. Of 101 isolates, 98 were NTHi, 2 were type e and 1 was type f. The overall ampicillin resistance rate was 15.8% (16/101). Resistance was mediated by TEM-1 β-lactamase production in half of isolates (n=8) or modifications in penicillin-binding protein (PBP) 3 in the other half (n=8). Several substitutions were discovered in PBP3 including the Asn526Lys change. Seventy-six different STs were identified among 98 NTHi isolates from carriage, with only 4 STs (ST12, ST57, ST238, ST1238) encompassing ≥3 isolates. Comparison of carriage and disease isolates found that several STs were shared between the two sources, although none of the major disease-associated STs were observed in carriage isolates.
NTHi is the predominant serotype in carriage. The importance of monitoring both NTHi colonization rate and circulating genotypes should be emphasized in the era of the Hib conjugate vaccines.
Available from: Shamez Ladhani
- "Analysis of national Hospital Episode Statistics (HES) data also revealed 20% reduction in hospitalizations for pneumonia and empyema in England following PCV7 introduction . The reduction in PCV7-type pneumococcal infections, however, was associated with an increase in non-vaccine serotypes in carriage and, consequently, in invasive disease, led to replacement of PCV7 in national immunization schedules with a 13-valent vaccine (PCV13) that provided protection against six additional serotypes (1, 3, 5, 6A, 7F and 19A)  .In the UK, PCV13 replaced PCV7 in April 2010 without a catch-up for older children. In other developed countries in Europe and North America, the success of PCV7 in reducing community acquired-pneumonia and OM has been demonstrated in a number of clinical trials and observational studies         . "
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ABSTRACT: Studies have demonstrated a reduction for otitis media (OM) following the introduction of seven-valent pneumococcal conjugate vaccine (PCV7), but this has not been evaluated in the United Kingdom (UK). Moreover, there are limited data on any additional impact of PCV13 introduction in 2010.
We conducted an observational cohort study to investigate the trends in OM incidence and associated antibiotic prescriptions in children aged <10 year-olds during 2002-2012 using a national primary care database. Three time-periods were defined to estimate monthly incidence: pre-PCV7 (January 2002-August 2006), post-PCV7 (September 2007-March 2010), and post-PCV13 (April 2011-December 2012).
Overall annual OM incidence declined by 51.3% from 135.8 episodes/1000 person-years in 2002 to 66.1 episodes/1000 person-years in 2012; antibiotic prescription rates for OM declined by 72.9% from 57.9 prescriptions/1000 person-years to 15.7 prescriptions/1000 person-years, respectively. PCV7 introduction was associated with significant decline in OM rates across all age-groups (21.8%; 95% CI, 20.2-23.4), including <2 year-olds (19.8%; 95% CI, 16.0-23.5%); 2-4 year-olds (23.0%; 95% CI, 20.4-25.4%) and 5-9 year-olds (20.2%; 95% CI, 17.6-22.7%). There was an additional significant reduction in OM (18.5%; 95% CI, 16.7-20.2%) and associated antibiotic prescribing (12.2%; 95% CI, 8.6-15.6%) after the introduction of PCV13 across all age-groups.
The introduction of PCV7 was associated with a 22% significant reductions in OM in children aged <10 year-olds with an additional 19% reductions after PCV13 introduction. These declines are equivalent to 592,000 and 15,700 fewer consultations and OM-related hospitalizations, respectively, in England and Wales every year. Although the continuing decline in OM rates in our study suggests that further reduction may continue to occur, it is important to monitor long-term trends in all pneumococcal diseases, including OM and pneumonia, because of increasing replacement of non-vaccine pneumococcal serotypes in carriage and disease.
Copyright © 2015. Published by Elsevier Ltd.
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