PCV7- and PCV10-Vaccinated Otitis-Prone Children in New Zealand Have Similar Pneumococcal and Haemophilus influenzae Densities in Their Nasopharynx and Middle Ear (original) (raw)

Predominance of nontypeable Haemophilus influenzae in children with otitis media following introduction of a 3+0 pneumococcal conjugate vaccine schedule

Vaccine, 2011

In Australia the 7-valent pneumococcal conjugate vaccine (PCV7) is administered at 2, 4 and 6 months of age, with no booster dose. Information on bacterial carriage and the aetiology of recurrent acute otitis media (rAOM) after introduction of PCV7 using the 3 + 0 schedule is required to evaluate the potential impact of second generation pneumococcal vaccines. We found that 2-4 years after introduction of PCV7 in the National Immunisation Program, nontypeable Haemophilus influenzae (NTHi) was the predominant pathogen isolated from the nasopharynx and middle ear of children with a history of rAOM. Compared with healthy controls (n = 81), NTHi and Streptococcus pneumoniae carriage rates were significantly higher in children with a history of rAOM (n = 186) (19% vs. 56% p < 0.0001 and 26% vs. 41%, p = 0.02, respectively). Carriage of PCV7 pneumococcal serotypes was rare, whereas PCV7-related and non-PCV7 serotypes were isolated of 38% of cases and 24% of controls. Serotype 19A was the most common serotype isolated from the nasopharynx and middle ear and accounted for 36% (14/39) of total pneumococcal isolates with reduced susceptibility to cotrimoxazole. Of the 119 children carrying NTHi, 17% of isolates were ␤-lactamase positive. The scarcity of PCV7 serotypes in children with and without a history of rAOM indicates that the 3 + 0 PCV7 schedule is preventing carriage and rAOM from PCV7 serotypes. Introduction of new vaccines in Australia with increased pneumococcal serotype and pathogen coverage, including 19A and NTHi, should decrease the circulation of antibiotic-resistant bacteria and reduce the burden of rAOM.

Modeling the decline in pneumococcal acute otitis media following the introduction of pneumococcal conjugate vaccines in the US

Vaccine, 2011

We hypothesized that following the introduction of PCV7, the exchange of vaccine serotypes (VST) for non-vaccine serotypes (NVST) in the nasopharynx has resulted in fewer episodes of pneumococcal acute otitis media (AOM) due to the reduced capacity for common NVST strains to cause disease. We modeled the change in the proportion of children colonized with S. pneumoniae who would develop pneumococcal AOM that would occur due to serotype replacement, and projected the future impact of PCV13. Our model is based on observed changes in the nasopharyngeal pneumococcal serotype distribution from the preto post-PCV7 era, and an estimated capacity of each serotype to produce pneumococcal AOM given colonization; the latter was derived by dividing serotype-specific disease prevalence by serotype-specific carriage prevalence in the same population. Our results indicate a 12% (95% CI 0.5-26) decline in the number of AOM episodes attributable to S. pneumoniae in children less than 3 years of age between 2000 and 2007 due to the combined effects of PCV7 vaccine efficacy and vaccine-induced serotype replacement, and predicts that PCV13 will further decrease pneumococcal AOM an additional 27% (95% CI 13-40) from 2007 to 2013. Evaluation of changes in VST disease revealed a 91% (95% CI 83-97) decrease in PCV7-VST AOM from 2000 to 2007, and predicted an additional 65% (95% CI 57-74) decrease in PCV13-VST AOM from 2007 to 2013. Our model indicates that following vaccination, nasopharyngeal replacement of VST by NVST has led to a decrease in the amount of pneumococcal AOM despite a consistent rate of S. pneumoniae colonization, and that pneumococcal AOM may continue to decrease as pneumococcal serotypes with greater capacity to cause disease are replaced by less locally invasive serotypes.

Nasopharyngeal flora in children with acute otitis media before and after implementation of 7 valent pneumococcal conjugate vaccine in France

BMC Infectious Diseases, 2012

Background: Several studies have investigated the impact of 7-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal (Sp) and staphylococcal (Sa) nasopharyngeal (NP) carriage. Few have investigated the impact on Haemophilus influenzae (Hi) and Moraxella catarrhalis (Mc) carriage. We aimed to compare the NP carriage rates in young children with acute otitis media (AOM) before and after PCV7 implementation in France. Methods: Prior to PCV7 implementation, we performed 4 successive randomized trials with NP samples. These studies compared several antibiotic regimens for treating AOM in young children (6 to 30 months). After PCV7 implementation, to assess the impact of the vaccination program on NP flora, young children with AOM were enrolled in a prospective surveillance study. In each study, we obtained an NP sample to analyze the carriage rates of Sp, Hi, Mc and Sa and the factors influencing the carriage. Standardized history and physical examination findings were recorded; the methods used for NP swabs (sampling and cultures) were the same in all studies. Results: We enrolled 4,405 children (mean age 13.9 months, median 12.8). Among the 2,598 children enrolled after PCV7 implementation, 98.3% were vaccinated with PCV7. In comparing the pre-and post-PCV7 periods, we found a slight but non-significant decrease in carriage rates of pneumococcus (AOR = 0.85 [0.69;1.05]), H. influenzae (AOR = 0.89 [0.73;1.09]) and S. aureus (AOR = 0.92 [0.70;1.19]). By contrast, the carriage rate of M. catarrhalis increased slightly but not significantly between the 2 periods (AOR = 1.08 [0.95;1.2]). Among Sp carriers, the proportion of PCV7 vaccine types decreased from 66.6% to 10.7% (P < 0.001), penicillin intermediate-resistant strains increased from 30.3% to 43.4% (P < 0.001), and penicillin-resistant strains decreased greatly from 22.8% to 3.8% (P < 0.001). The proportion of Hi ß-lactamase-producing strains decreased from 38.6% to 17.1% (P < 0.001). Conclusion: The carriage rates of otopathogen species (Sp, Hi, Mc) and Sa did not significantly change in children with AOM after PCV7 implementation in France. However, we observed significant changes in carriage rates of PCV7 vaccine serotypes and penicillin non-susceptible Sp.

What is behind the ear drum? The microbiology of otitis media and the nasopharyngeal flora in children in the era of pneumococcal vaccination

Journal of Paediatrics and Child Health, 2014

This study aims to describe the microbiology of middle ear fluid (MEF) in a cohort of children vaccinated with Streptococcus pneumoniae conjugate vaccine (PCV7) having ventilation tube insertion. Nasopharyngeal (NP) carriage of otopathogens in these children is compared with children without history of otitis media. Methods: Between May and November 2011, MEF and NP samples from 325 children aged <3 years were collected in three major centres in New Zealand at the time of ventilation tube insertion. An age-matched non-otitis-prone comparison group of 137 children had NP samples taken. A questionnaire was completed by both groups. Results: Immunisation coverage with at least one dose of PCV7 was 97%. Haemophilus influenzae was cultured in 19.4% of MEF and was polymerase chain reaction (PCR) positive in 43.4%. S. pneumoniae and Moraxella catarrhalis were cultured in <10% of MEF samples but were PCR positive for 23.1% and 38.7%, respectively. H. influenzae was the most common organism isolated from NP samples (60%) in the grommet group, while M. catarrhalis (56%) was the most common in the non-otitis prone group. S. pneumoniae was more commonly found in the nasopharynx of children with ear disease (41% vs. 29%). 19F was the most prominent S. pneumoniae serotype in NP samples of both groups, but no serotype dominated in MEF. Ninety-five per cent of H. influenzae isolates were confirmed to be non-typeable H. influenzae. Conclusion: In this cohort of children with established ear disease requiring surgical intervention, non-typeable H. influenzae is the dominant pathogen in both the nasopharynx and MEF.

A 13-year survey of pneumococcal nasopharyngeal carriage in children with acute otitis media following PCV7 and PCV13 implementation

Vaccine, 2015

This nasopharyngeal (NP) carriage surveillance study was requested by the European Agency for the Evaluation of Medicinal Products as a post-licensing commitment to determine whether the use of the pneumococcal conjugate vaccines (PCVs) including 7 then 13 valents (introduced in 2001 and 2010, respectively) caused a shift in the distribution of Streptococcus pneumoniae serotypes in children with acute otitis media and modified the resistance of this bacterial species to antibiotics. Between 2001 and 2014, 121 pediatricians obtained nasopharyngeal swabs from children with acute otitis media aged 6-24 months. The swabs were analyzed by the French National Reference Centre for Pneumococci. Demographics, medical history and physical examination findings were recorded. Over the 13 years, among the 7991 enrolled patients, the proportion of PCV-vaccinated children (≥1 dose) increased (54.3-99.7%, p<0.001). Overall, pneumococcal carriage was reduced from 71.2% to 56.2% from 2001 to 2014 ...

The impact of the widespread introduction of pneumococcal conjugate vaccines on pneumococcal and non-pneumococcal otitis media

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2016

The pneumococcal conjugated vaccines (PCVs) impact on complex otitis media (including recurrent, non-responsive, spontaneously draining and chronic OM with effusion) was greater than that against simple, acute-OM in previous studies. Since complex OM is often a polymicrobial disease, we speculated that reduction of complex OM by PCVs will be associated in addition with reduction of non-pneumococcal OM. In a prospective, population-based, active surveillance, all OM episodes submitted for middle ear fluid (MEF) culture in children <3 years, during 2004-2015 were included. Three sub-periods were defined: pre-PCV, PCV7, and PCV13 periods. Incidence rate ratios (IRRs) comparing the three periods were calculated for pneumococcal, non-typeable Haemophilus influenzae (NTHi), Moraxella catarrhalis, Streptococcus pyogenes and culture-negative OM. Overall, 7,475 episodes were included. Of all NTHi cases in the pre-PCV period, 34% were mixed with Streptococcus pneumoniae IRRs (95% confid...

Serotype distribution of pneumococci isolated from pediatric patients with acute otitis media and invasive infections, and potential coverage of pneumococcal conjugated vaccines

Revista Argentina de microbiología

A 16-month prospective, descriptive study was conducted on pneumococcal serotype distribution isolated from children with acute otitis media (AOM) and invasive infections (INV). Eighty-nine children with pneumococcal INV and 324 with a first episode of AOM were included. Bacterial pathogens (N = 326) were isolated from the middle-ear fluid of 250 patients. A total of 30 pneumococcal serotypes were identified. Prevalent serotypes were 14, 19A, 9V, 3, 19F, 6A, 23F, and 18C in AOM and 14, 1, 19A, 5, 12F, 6B, and 18C in INV. Potential coverage with PCV10 vaccine would be 46.5 % and 60.7 % for pneumococci involved in AOM and INV, respectively; it would be 71.7 % and 73 % with PCV13. PCV10, conjugated with a Haemophilus protein, would have an immunologic coverage of 39.9 % for AOM vs. 18.5 % with PCV13. However, differences in the prevention of INV were crucial for the decision to include the 13-valent vaccine in the national calendar for children less than two years old in Argentina.

Higher levels of mucosal antibody to pneumococcal vaccine candidate proteins are associated with reduced acute otitis media caused by Streptococcus pneumoniae in young children

Mucosal immunology, 2015

Mucosal immunity has a crucial role in controlling human respiratory tract infections. This study characterizes the naturally acquired mucosal antibody levels to three Streptococcus pneumoniae (Spn) protein antigens, pneumococcal histidine triad protein D (PhtD), pneumococcal choline binding protein A (PcpA), and pneumolysin (Ply), and assesses the association of the mucosal antibody levels with occurrence of acute otitis media (AOM) caused by Spn. Both nasopharyngeal (NP) immunoglobulin G (IgG) and IgA levels to all three proteins slightly decreased in children from 6 to 9 months of age and then gradually increased through 24 months of age. Spn NP colonization was associated with higher mucosal antibody levels to all three proteins. However, children with Spn AOM had 5-8-fold lower IgG and 3-6-fold lower IgA levels to the three proteins than children without AOM but asymptomatically colonized with Spn. Antigen-specific antibody levels in the middle ear fluid (MEF) were correlated w...