Recent Advances in Otitis Media
Department of Pediatrics, Boston University School of Medicine, Boston, MA, USA. The Pediatric Infectious Disease Journal
(Impact Factor: 2.72).
10/2009; 28(10 Suppl):S133-7. DOI: 10.1097/INF.0b013e3181b6d81a
Otitis media (OM) is a pervasive illness in infants and children, and many children suffer multiple episodes during the first years of life. High rates of acute otitis media (AOM) are reported in developed and emerging countries. Early onset is common in both settings. Recurrent OM is associated with several factors, including early onset of disease, having a sibling with a history of AOM and absence of breast-feeding. Early onset disease has been hypothesized to result from Eustachian tube dysfunction, immunologic naivete and immaturity, and viral upper respiratory tract infection. Nasopharyngeal colonization with bacterial otopathogens increases the likelihood of AOM and the disease is most frequent in children with viral respiratory tract infection colonized with multiple otopathogens (Streptococcus pneumoniae, nontypeable Haemophilus influenzae [NTHi], Moraxella catarrhalis), potentially as a result of inflammation resulting from competition among the bacterial species within the nasopharynx. Epidemiologic observations and studies of pathogenesis suggest that successful strategies for reducing the burden of disease will be best accomplished by targeting multiple viral and/or bacterial pathogens and preventing early onset disease. Guidelines (2004) for the treatment of AOM in children establish a clear hierarchy among the various antibacterials for the treatment of this disease. Failure to achieve early bacterial eradication during antibiotic therapy for AOM increases the clinical failure rates in AOM in young children. Most recurrent AOM episodes occurring within 1 month after successful completion of antibiotic therapy are due to new otopathogens. Failure to eradicate middle ear and/or nasopharyngeal pathogens is associated with higher rates of clinical recurrent AOM, even when the patients show clinical improvement or cure at the end of therapy for the initial episode. Optimal strategy for the prevention of AOM recurrences requires sterilization of the middle ear and eradication of nasopharyngeal carriage of otopathogens during antimicrobial therapy.
Available from: Atsushi Matsubara
- "As a topical treatment for EOM, it is also important to remove middle ear effusion enriched with eosinophils and their inflammatory mediators as soon as possible. Heparin is used for easy removal of gelatinous middle ear effusion and its inhibitory effects on eosinophilic chemotaxis and neutralizing effects on eosinophil granule cationic proteins . A recent report indicates that long-term anti-IgE therapy could be effective for EOM . "
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As the periods of intratympanic injection of ovalbumin (OVA) to the middle ear became longer, marked eosinophil infiltration in the perilymphatic space was observed. Moreover severe morphological damage of the organ of Corti was observed in the 28-day antigen-stimulation side. These results indicate that eosinophilic inflammation occurred in the inner ear and caused profound hearing loss.
The purpose of the present study was to elucidate the inner ear damage in a new animal model of eosinophilic otitis media (EOM) which we recently constructed.
We constructed the animal model of EOM by intraperitoneal and intratympanic injection of OVA. Infiltrating cells and the inner ear damage were examined by histological study.
In the inner ear, a few eosinophils were seen in the scala tympani of the organ of Corti and the dilation of capillaries of the stria vascularis was observed in the 7-day stimulation side. In the 14-day antigen stimulation side, some eosinophils and macrophages were seen in not only the scala tympani but also the scala vestibule. In the 28-day antigen-stimulation side, severe morphological damage of the organ of Corti and many eosinophils, red blood cells, and plasma cells infiltrating the perilymph were observed.
Acta oto-laryngologica 12/2013; 134(3). DOI:10.3109/00016489.2013.859395 · 1.10 Impact Factor
Available from: Claudio Donati
- "Disease-causing pneumococci represent a phenotypically and genotypically diverse population of strains that cause bacteraemia, meningitis, pneumonia, sinusitis, and acute otitis media in children –. Effective epidemiological surveillance, along with the characterization and the classification of the circulating strains, are important tools to understand the evolution and the population dynamics that support the success of specific pneumococcal lineages –. "
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ABSTRACT: Multi-Locus Sequence Typing (MLST) of Streptococcus pneumoniae is based on the sequence of seven housekeeping gene fragments. The analysis of MLST allelic profiles by eBURST allows the grouping of genetically related strains into Clonal Complexes (CCs) including those genotypes with a common descent from a predicted ancestor. However, the increasing use of MLST to characterize S. pneumoniae strains has led to the identification of a large number of new Sequence Types (STs) causing the merger of formerly distinct lineages into larger CCs. An example of this is the CC156, displaying a high level of complexity and including strains with allelic profiles differing in all seven of the MLST loci, capsular type and the presence of the Pilus Islet-1 (PI-1). Detailed analysis of the CC156 indicates that the identification of new STs, such as ST4945, induced the merging of formerly distinct clonal complexes. In order to discriminate the strain diversity within CC156, a recently developed typing schema, 96-MLST, was used to analyse 66 strains representative of 41 different STs. Analysis of allelic profiles by hierarchical clustering and a minimum spanning tree identified ten genetically distinct evolutionary lineages. Similar results were obtained by phylogenetic analysis on the concatenated sequences with different methods. The identified lineages are homogenous in capsular type and PI-1 presence. ST4945 strains were unequivocally assigned to one of the lineages. In conclusion, the identification of new STs through an exhaustive analysis of pneumococcal strains from various laboratories has highlighted that potentially unrelated subgroups can be grouped into a single CC by eBURST. The analysis of additional loci, such as those included in the 96-MLST schema, will be necessary to accurately discriminate the clonal evolution of the pneumococcal population.
PLoS ONE 04/2013; 8(4):e61003. DOI:10.1371/journal.pone.0061003 · 3.23 Impact Factor
Available from: Sara Filippini
- "Streptococcus pneumoniae (S. pneumoniae) is a Gram-positive commensal of the nasopharyngeal tract of both children and healthy adults. However, S. pneumoniae is also a leading cause of morbidity and mortality worldwide, being responsible for non-invasive and invasive diseases such as acute otitis media, pneumonia, sepsis and meningitis    . "
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ABSTRACT: RrgB321, a fusion protein of the three Streptococcus pneumoniae pilus-1 backbone RrgB variants, is protective in vivo against pilus islet 1 (PI-1) positive pneumococci. In addition, antibodies to RrgB321 mediate a complement-dependent opsonophagocytosis of PI-1 positive strains at levels comparable to those obtained with antisera against glycoconjugate vaccines. In the pneumococcus, pilus-1 displays a biphasic expression pattern, with different proportions of two bacterial phenotypes, one expressing and one not expressing the pilus-1. These two populations can be stably separated in vitro giving rise to the enriched high (H) and low (L) pilus expressing populations. In this work we demonstrate that: (i) the opsonophagocytic killing mediated in vitro by RrgB321 antisera is strictly dependent on the pilus expression ratio of the strain used; (ii) during the opsonophagocytosis assay pilus-expressing pneumococci are selectively killed, and (iii) no switch towards the pilus non-expressing phenotype can be observed. Furthermore, in sepsis and pneumonia models, mice immunized with RrgB321 are significantly protected against challenge with either the H or the L pilus-expressing population of strains representative of the three RrgB variants. This suggests that the pilus-1 expression is not down-regulated, and also that the expression of the pilus-1 could be up-regulated in vivo. In conclusion, these data provide evidence that RrgB321 is protective against PI-1 positive strains regardless of their pilus expression level, and support the rationale for the inclusion of this fusion protein into a multi-component protein-based pneumococcal vaccine.
Vaccine 12/2011; 30(7):1349-56. DOI:10.1016/j.vaccine.2011.12.080 · 3.62 Impact Factor
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