Date Published: February 1, 2017
Publisher: Public Library of Science
Author(s): Robert Cilveti, Montserrat Olmo, Josefa Pérez-Jove, Juan-José Picazo, Josep-Lluis Arimany, Emiliano Mora, Tomás M. Pérez-Porcuna, Ignacio Aguilar, Aurora Alonso, Francesc Molina, María del Amo, Cristina Mendez, Eliane N. Miyaji.
The Epidemiology of otitis media with spontaneous perforation of the tympanic membrane and associated nasopharyngeal carriage of bacterial otopathogens was analysed in a county in Catalonia (Spain) with pneumococcal conjugate vaccines (PCVs) not included in the immunization programme at study time. A prospective, multicentre study was performed in 10 primary care centres and 2 hospitals (June 2011-June 2014), including all otherwise healthy children ≥2 months ≤8 years with otitis media presenting spontaneous tympanic perforation within 48h. Up to 521 otitis episodes in 487 children were included, showing by culture/PCR in middle ear fluid (MEF): Haemophilus influenzae [24.2%], both Streptococcus pneumoniae and H. influenzae [24.0%], S. pneumoniae [15.9%], Streptococcus pyogenes [13.6%], and Staphylococcus aureus [6.7%]. Culture-negative/PCR-positive otitis accounted for 31.3% (S. pneumoniae), 30.2% (H. influenzae) and 89.6% (mixed S. pneumoniae/H. influenzae infections). Overall, incidence decreased over the 3-year study period, with significant decreases in otitis by S. pneumoniae and by H. influenzae, but no decreases for mixed S. pneumoniae/H. influenzae infections. Concordance between species in nasopharynx and MEF was found in 58.3% of cases, with maximal rates for S. pyogenes (71.8%), and with identical pneumococcal serotype in 40.5% of cases. Most patients (66.6%) had past episodes. PCV13 serotypes were significantly more frequent in first episodes, in otitis by S. pneumoniae as single agent, and among MEF than nasopharyngeal isolates. All non-PCV13 serotypes separately accounted for <5% in MEF. Up to 73.9% children had received ≥1 dose of PCV, with lower carriage of PCV13 serotypes than among non-vaccinated children. Pooling pneumococcal isolates from MEF and nasopharynx, 30% were multidrug resistant, primarily belonging to serotypes 19A [29.8%], 24A [14.3%], 19F [8.3%] and 15A [6.0%]. Our results suggest that increasing PCV13 vaccination would further reduce transmission of PCV13 serotypes with special benefits for youngest children (with none or uncompleted vaccine schedules), preventing first otitis episodes and subsequent recurrences.
Otitis media remains a major public health problem in early childhood worldwide, with the highest incidence between 6 and 24 months of age. By their third birthday, 80% of children will have experienced at least one episode (about half ≥3 episodes)  and 40% of children will have 6 or more recurrences by the age of 7 years .
This study, a large multicentre prospective study on OM and nasopharyngeal carriage in a Spanish region without PCVs included in the regional immunization programme, showed a significant decrease in the overall IR of OM over the study period, with significant reductions in IRs of OM by S. pneumoniae and by H. influenzae, but not in IRs of mixed OM by S. pneumoniae + H. influenzae, which represented a high proportion of OM. H. influenzae was the most frequent otopathogen, involved as single or mixed agent (with S. pneumoniae) in almost half cases of OM. It has been suggested that the decline of PCV13 serotypes after vaccine implementation may result in an increased relative predominance of H. influenzae as otopathogen [16,24]. Since in Catalonia, the Spanish region where our study was performed, a marked 72% reduction in vaccine-type otitis has been reported , the predominance of H. influenzae was not surprising. In addition, other factors associated in the literature with high H. influenzae involvement such as recurrences [26,27], day care attendance, PCV vaccination  or H. influenzae colonization at onset of infection  were also present in a high number of children in our series. In the multivariate model, OM by H. influenzae was associated with recurrences and nasopharyngeal colonization.
This study, a large multicentre prospective study on OM and nasopharyngeal carriage in a Spanish region without PCVs in the regional immunization programme, showed >50% MEF-nasopharyngeal concordance of otopathogen isolation, differences in aetiology between first episodes (associated with S. pneumoniae infection) and recurrent episodes (associated with H. influenzae involvement), and association of PCV13 serotypes with first episodes. Our results suggest that increasing PCV13 vaccination would further reduce transmission of pneumococcal vaccine serotypes with special benefits for youngest children (with none or uncompleted vaccine schedules), preventing first episodes of OM and subsequent recurrent episodes.