Abstract

Otitis media (OM) is a major reason for antibiotic consumption and surgery in children. Nasopharyngeal carriage of otopathogens, Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi), is a prerequisite for development of OM, and increased nasopharyngeal otopathogen density correlates with disease onset. Vaccines can reduce or eliminate otopathogen carriage, as demonstrated for pneumococcal serotypes included in pneumococcal conjugate vaccines (PCV). The 10-valent PCV (PCV10) includes an NTHi carrier protein, and in 2011 superseded 7-valent PCV on the New Zealand Immunisation Program. Data are conflicting on whether PCV10 provides protection against NTHi carriage or disease. Assessing this in otitis-prone cohorts is important for OM prevention. We compared otopathogen density in the nasopharynx and middle ear of New Zealand PCV7-vaccinated and PCV10-vaccinated otitis-prone and non-otitis-prone children to determine PCV10 impact on NTHi and S. pneumoniae carriage. We applied qPCR to specimens collected from 217 PCV7-vaccinated children (147 otitis-prone and 70 non-otitis-prone) and 240 PCV10-vaccinated children (178 otitis-prone and 62 non-otitis-prone). After correcting for age and day-care attendance, no difference was observed between NTHi density in the nasopharynx of PCV7-vaccinated versus PCV10-vaccinated otitis-prone (p = 0.563) or non-otitis-prone (p = 0.513) children. In contrast, pneumococcal nasopharyngeal density was higher in PCV10-vaccinated otitis-prone children than PCV7-vaccinated otitis-prone children (p = 0.003). There was no difference in otopathogen density in middle ear effusion from PCV7-vaccinated versus PCV10-vaccinated otitis-prone children (NTHi p = 0.918; S. pneumoniae p = 0.415). When pneumococcal carriage was assessed by vaccine serotypes (VT) and non-vaccine serotypes (NVT), there was no difference in VT density (p = 0.546) or NVT density (p = 0.315) between all PCV7-vaccinated versus all PCV10-vaccinated children. In summary, PCV10 did not reduce NTHi density in the nasopharynx or middle ear, and was associated with increased pneumococcal nasopharyngeal density in otitis-prone children in New Zealand. Development of therapies that prevent or reduce otopathogen colonisation density in the nasopharynx are warranted to reduce the burden of OM.

Highlights

  • Otitis media (OM) is the most common paediatric infection for which medical care is sought, and the most common indication for prescription of antibiotics in children [1,2]

  • All children included in this study were fully vaccinated with either PCV7 or PCV10 according to the National

  • Day-care attendance was more common in the otitis-prone cases compared to the non-otitis-prone controls in both the PCV7-vaccinated (63% versus 40%; p = 0.002) and

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Summary

Introduction

Otitis media (OM) is the most common paediatric infection for which medical care is sought, and the most common indication for prescription of antibiotics in children [1,2]. OM is one of the most common reasons for children to undergo surgery for ventilation tube insertion (VTI), with recurrent acute OM (rAOM) or persistent otitis media with effusion (OME) being the usual indications. Nasopharyngeal colonization with otopathogens is considered to be a prerequisite to development of disease [6,7,8,9,10,11]. Vaccines that target these pathogens have the potential to reduce nasopharyngeal carriage and transmission, leading to a reduction in the prevalence of OM and in turn to a reduction in antibiotic prescriptions and children undergoing VTI surgery. Introduction of pneumococcal conjugate vaccines (PCV) has reduced the incidence of OM from the serotypes included in the vaccine [12,13,14], but has had a limited impact on the overall prevalence of OM due to replacement disease from non-vaccine serotypes and other otopathogens [15,16]

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