scholarly journals Therapeutic Transcutaneous Immunization with a Band-Aid Vaccine Resolves Experimental Otitis Media

2015 ◽  
Vol 22 (8) ◽  
pp. 867-874 ◽  
Author(s):  
Laura A. Novotny ◽  
John D. Clements ◽  
Lauren O. Bakaletz
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Respiratory Tract ◽  
Otitis Media ◽  
Middle Ear ◽  
Lymphoid Tissue ◽  
Content Type ◽  
Middle Ear Fluid ◽  
Transcutaneous Immunization

ABSTRACTTranscutaneous immunization (TCI) is a noninvasive strategy to induce protective immune responses. We describe TCI with a band-aid vaccine placed on the postauricular skin to exploit the unique organization of the stratum corneum and to promote the development of immune responses to resolve active experimental otitis media due to nontypeableHaemophilus influenzae(NTHI). This therapeutic immunization strategy induced significantly earlier resolution of middle ear fluid and rapid eradication of both planktonic and mucosal biofilm-resident NTHI within 7 days after receipt of the first immunizing band-aid vaccine. Efficacy was ascribed to the homing of immunogen-bearing cutaneous dendritic cells to the nasal-associated lymphoid tissue, induction of polyfunctional CD4+T cells, and the presence of immunogen-specific IgM and IgG within the middle ear. TCI using band-aid vaccines could expand the use of traditional parenteral preventative vaccines to include treatment of active otitis media, in addition to other diseases of the respiratory tract due to NTHI.

scholarly journals Niche- and Gender-Dependent Immune Reactions in Relation to the Microbiota Profile in Pediatric Patients with Otitis Media with Effusion

2020 ◽  
Vol 88 (10) ◽  
Author(s):  
Frida Enoksson ◽  
Alicia Ruiz Rodriguez ◽  
Chikondi Peno ◽  
Carlos Balcazar Lopez ◽  
Fredrik Tjernström ◽  
...  
Keyword(s):  
Immune Responses ◽  
Otitis Media ◽  
Middle Ear ◽  
Inflammatory Mediators ◽  
Otitis Media With Effusion ◽  
Bacterial Species ◽  
Microbial Community Composition ◽  
Low Grade ◽  
Content Type ◽  
Anti Inflammatory

ABSTRACT Otitis media with effusion (OME) is a common inflammatory disease that primarily affects children. OME is defined as a chronic low-grade inflammation of the middle ear (ME), without any signs of infection and with effusion persisting in the ME for more than 3 months. The precise pathogenesis is, however, not fully understood. Here, we comprehensively characterized and compared the host immune responses (inflammatory cells and mediators) and the overall microbial community composition (microbiota) present in matched middle ear effusion (MEE) samples, external ear canal (EEC) lavages, and nasopharynx (NPH) samples from children with OME. Female patients had significantly increased percentages of T lymphocytes and higher levels of a wide array of inflammatory mediators in their MEE compared to that of male patients, which were unrelated to microbiota composition. The relative abundances of identified microorganisms were strongly associated with their niche of origin. Furthermore, specific inflammatory mediators were highly correlated with certain bacterial species. Interestingly, some organisms displayed a niche-driven inflammation pattern in which presence of Haemophilus spp. and Corynebacterium propinquum in MEE was accompanied by proinflammatory mediators, whereas their presence in NPH was accompanied by anti-inflammatory mediators. For Turicella and Alloiococcus, we found exactly the opposite results, i.e., an anti-inflammatory profile when present in MEE, whereas their presence in the the NPH was accompanied by a proinflammatory profile. Together, our results indicate that immune responses in children with OME are highly niche- and microbiota-driven, but gender-based differences were also observed, providing novel insight into potential pathogenic mechanisms behind OME.

scholarly journals Efficacy of Solithromycin (CEM-101) for Experimental Otitis Media Caused by Nontypeable Haemophilus influenzae and Streptococcus pneumoniae

2016 ◽  
Vol 60 (9) ◽  
pp. 5533-5538 ◽  
Author(s):  
M. Figueira ◽  
P. Fernandes ◽  
S. I. Pelton
Keyword(s):  
Streptococcus Pneumoniae ◽  
Haemophilus Influenzae ◽  
Otitis Media ◽  
Middle Ear ◽  
Fourth Generation ◽  
Minimal Bactericidal Concentration ◽  
Nontypeable Haemophilus Influenzae ◽  
Time Curve ◽  
Content Type ◽  
Middle Ear Fluid

ABSTRACTSolithromycin (CEM-101) is a “fourth-generation” macrolide, as it has three binding site and is acid stable. The three binding sites confer activity against bacteria resistant to the older macrolides and ketolides, including multidrug-resistantStreptococcus pneumoniaeand nontypeableHaemophilus influenzae(NTHi). The objective of this study was to evaluate solithromycin pharmacokinetics (PK), middle ear fluid (MEF) concentrations, and microbiologic efficacy in a chinchilla model of experimental otitis media (EOM) due to strains ofS. pneumoniaeor NTHi. Plasma PK (maximum concentration of drug in serum [Cmax] and area under the concentration-time curve from 0 to 24 h [AUC0–24]) and middle ear fluid (MEF) concentrations were determined. Isolates with specified antimicrobial susceptibility patterns were inoculated directly into the middle ear (ME). Plasma and MEF were collected for PK and MEF cultures performed to determine efficacy. Solithromycin administered at 150 mg/kg of body weight/day resulted inCmaxand AUC0–24values of 2.2 μg/ml and 27.4 μg · h/ml in plasma and 1.7 μg/ml and 28.2 μg · h/ml in extracellular MEF on day 1. By day 3,Cmaxand AUC0–24values had increased to 4.5 μg/ml and 54 μg · h/ml in plasma and 4.8 μg/ml and 98.6 μg · h/ml in extracellular MEF. For NTHi EOM, three isolates with MIC/minimal bactericidal concentration (MBC) ratios of 0.5/1 μg/ml (isolate BCH1), 2/2 μg/ml (isolate BMC1247C), and 4/4 μg/ml (isolate BMC1213C) were selected. The MEF of >85% of animals infected with BCH1 and BMC1247C was sterilized. For NTHi BMC1213, >85% of MEF cultures remained positive. ForS. pneumoniaeEOM, 3 isolates with MIC/MBC ratios of 0.06/0.125 μg/ml (S. pneumoniae331), 0.125/1 μg/ml (S. pneumoniaeCP-645 [MLSBphenotype]), and 0.5/2 μg/ml (CP-712 [mefAsubclassmefAresistance]) were selected. Solithromycin sterilized MEF in 100% of animals infected withS. pneumoniae331 andS. pneumoniaeCP-645. ME infection persisted in 60% of animals infected with CP-712. In a model of EOM, solithromycin sterilized MEF in >85% of animals challenged with NTHi with an MIC of ≤2 μg/ml and 100% of ME infected withS. pneumoniaewith an MIC of ≤0.125 μg/ml.

scholarly journals Microbial Communities of the Upper Respiratory Tract and Otitis Media in Children

mBio ◽  
2011 ◽  
Vol 2 (1) ◽  
Author(s):  
Alison S. Laufer ◽  
Joshua P. Metlay ◽  
Janneane F. Gent ◽  
Kristopher P. Fennie ◽  
Yong Kong ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Respiratory Tract ◽  
Microbial Communities ◽  
Otitis Media ◽  
Middle Ear ◽  
Upper Respiratory Tract ◽  
Content Type ◽  
Increased Risk ◽  
Causal Pathway ◽  
Upper Respiratory

ABSTRACTStreptococcus pneumoniaeasymptomatically colonizes the upper respiratory tract of children and is a frequent cause of otitis media. Patterns of microbial colonization likely influenceS. pneumoniaecolonization and otitis media susceptibility. This study compared microbial communities in children with and without otitis media. Nasal swabs and clinical and demographic data were collected in a cross-sectional study of Philadelphia, PA, children (6 to 78 months) (n= 108) during the 2008-2009 winter respiratory virus season. Swabs were cultured forS. pneumoniae. DNA was extracted from the swabs; 16S rRNA gene hypervariable regions (V1 and V2) were PCR amplified and sequenced by Roche/454 Life Sciences pyrosequencing. Microbial communities were described using the Shannon diversity and evenness indices. Principal component analysis (PCA) was used to group microbial community taxa into four factors representing correlated taxa. Of 108 children, 47 (44%) were colonized byS. pneumoniae, and 25 (23%) were diagnosed with otitis media. Microbial communities withS. pneumoniaewere significantly less diverse and less even. Two PCA factors were associated with a decreased risk of pneumococcal colonization and otitis media, as follows: one factor included potentially protective flora (CorynebacteriumandDolosigranulum), and the other factor includedPropionibacterium,Lactococcus, andStaphylococcus. The remaining two PCA factors were associated with an increased risk of otitis media. One factor includedHaemophilus, and the final factor includedActinomyces,Rothia,Neisseria, andVeillonella. Generally, these taxa are not considered otitis media pathogens but may be important in the causal pathway. Increased understanding of upper respiratory tract microbial communities will contribute to the development of otitis media treatment and prevention strategies.IMPORTANCEOtitis media (middle ear infection) is the most common reason for pediatric sick visits in the United States.Streptococcus pneumoniaeis a leading otitis media pathogen.S. pneumoniaemust colonize the upper respiratory tract and compete with a complex community of nonpathogenic bacteria before infecting the middle ear. We compared microbial communities in the upper respiratory tract of children who had otitis media and those who did not. Members of the normal flora, i.e.,CorynebacteriumandDolosigranulum, were protective forS. pneumoniaecolonization and otitis media. As expected, the generaHaemophiluswas associated with otitis media. Surprisingly,Actinomyces,Rothia,Neisseria, andVeillonellawere associated with an increased risk of otitis media. These bacteria are not otitis media pathogens but may be associated with antibiotic use or involved in the causal pathway to disease. Increased understanding of upper respiratory tract microbial communities will lead to new ways to prevent middle ear infections, including probiotics.

Mucosal Immune System: Implications in Otitis Media with Effusion

1980 ◽  
Vol 89 (3_suppl) ◽  
pp. 326-332 ◽  
Author(s):  
J. M. Bernstein ◽  
Pearay L. Ogra
Keyword(s):  
Immune System ◽  
Gastrointestinal Tract ◽  
Respiratory Tract ◽  
Otitis Media ◽  
Middle Ear ◽  
Lymphoid Tissue ◽  
Otitis Media With Effusion ◽  
Mucosal Immune System ◽  
Lymphoid Cells ◽  
Upper Respiratory Tract

The ontogeny of the mucosal immune system as it relates to the development of lymphoid tissue in the respiratory tract and the gastrointestinal tract has been studied quite extensively over the past few years. It is apparent now that the bronchus-associated lymphoid tissue and gut-associated lymphoid tissue are the major sources of immunocompetent precursor B lymphocytes. After the induction of antigens in the respiratory tract or the gastrointestinal tract, precursor lymphoid cells in these sites are preferentially activated to undergo significant proliferation. Such antigen-sensitized cells eventually migrate to other mucosa sites, such as mammary glands, genital tract, conjuctiva, etc. Recent evidence has suggested that the immunocompetent tissue observed in the middle ear cleft during otitis media with effusion may function as an extension of the mucosal immune system in the upper respiratory tract. The implications of these observations relative to middle ear disease are discussed.

scholarly journals Toll-Like Receptors: Expression and Roles in Otitis Media

2021 ◽  
Vol 22 (15) ◽  
pp. 7868
Author(s):  
Su Young Jung ◽  
Dokyoung Kim ◽  
Dong Choon Park ◽  
Sung Soo Kim ◽  
Tong In Oh ◽  
...  
Keyword(s):  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Otitis Media ◽  
Middle Ear ◽  
Upper Respiratory Tract Infection ◽  
Upper Respiratory Tract ◽  
Toll Like Receptors ◽  
Upper Respiratory

Otitis media is mainly caused by upper respiratory tract infection and eustachian tube dysfunction. If external upper respiratory tract infection is not detected early in the middle ear, or an appropriate immune response does not occur, otitis media can become a chronic state or complications may occur. Therefore, given the important role of Toll-like receptors (TLRs) in the early response to external antigens, we surveyed the role of TLRs in otitis media. To summarize the role of TLR in otitis media, we reviewed articles on the expression of TLRs in acute otitis media (AOM), otitis media with effusion (OME), chronic otitis media (COM) with cholesteatoma, and COM without cholesteatoma. Many studies showed that TLRs 1–10 are expressed in AOM, OME, COM with cholesteatoma, and COM without cholesteatoma. TLR expression in the normal middle ear mucosa is absent or weak, but is increased in inflammatory fluid of AOM, effusion of OME, and granulation tissue and cholesteatoma of COM. In addition, TLRs show increased or decreased expression depending on the presence or absence of bacteria, recurrence of disease, tissue type, and repeated surgery. In conclusion, expression of TLRs is associated with otitis media. Inappropriate TLR expression, or delayed or absent induction, are associated with the occurrence, recurrence, chronicization, and complications of otitis media. Therefore, TLRs are very important in otitis media and closely related to its etiology.

Air Conduction Thresholds and Secretory Otitis Media: A Conventional and Extra-High Frequency Audiometric Comparison

1989 ◽  
Vol 98 (10) ◽  
pp. 767-771 ◽  
Author(s):  
Iain W. S. Mair ◽  
Oddbjørn Fjermedal ◽  
Einar Laukli
Keyword(s):  
Otitis Media ◽  
Middle Ear ◽  
High Frequency ◽  
Pure Tone ◽  
Low Frequency ◽  
Secretory Otitis Media ◽  
Middle Ear Fluid ◽  
Ventilation Tubes ◽  
Air Conduction

A comparison has been made of air conduction threshold changes up to 1 year after myringotomy, aspiration of middle ear fluid, and insertion of ventilation tubes in ten patients with bilateral and 12 with unilateral secretory otitis media (SOM). Pure tone air conduction thresholds have been analyzed in three frequency groups: Low frequency (LF; 0.25, 0.5, and 1 kHz), high frequency (HF; 2,4, and 8 kHz), and extra-high frequency (EHF; 10, 12, 14, and 16 kHz). In the LF and HF ranges, significant improvement came during the first 24 hours after intubation, while in the EHF range, threshold lowering occurred gradually over the following 2 months. Possible explanations for these findings are discussed.

scholarly journals Acute Mastoiditis in the Pneumococcal Conjugate Vaccine Era

2014 ◽  
Vol 21 (8) ◽  
pp. 1189-1191 ◽  
Author(s):  
Sharon Ovnat Tamir ◽  
Yehudah Roth ◽  
Ilan Dalal ◽  
Abraham Goldfarb ◽  
Tal Marom
Keyword(s):  
Streptococcus Pneumoniae ◽  
Middle Ear ◽  
Pneumococcal Conjugate Vaccine ◽  
Inverse Relationship ◽  
Acute Otitis Media ◽  
Acute Mastoiditis ◽  
Conjugate Vaccines ◽  
Content Type ◽  
Bacterial Cultures ◽  
Middle Ear Fluid

ABSTRACTFollowing the introduction of the 7- and 13-valent pneumococcal conjugate vaccines, we observed an inverse relationship between the increasing rate of immunized children and the proportion of middle ear fluid cultures collected during acute mastoiditis episodes that tested positive forStreptococcus pneumoniaeamong a subset of children 0 to 6 years old who had initially presented with severe acute otitis media and had bacterial cultures collected during tympanocentesis or from spontaneous otorrhea.

scholarly journals Influenza-Induced Inflammation Drives Pneumococcal Otitis Media

2013 ◽  
Vol 81 (3) ◽  
pp. 645-652 ◽  
Author(s):  
Kirsty R. Short ◽  
Patrick C. Reading ◽  
Lorena E. Brown ◽  
John Pedersen ◽  
Brad Gilbertson ◽  
...  
Keyword(s):  
Otitis Media ◽  
Middle Ear ◽  
Influenza A ◽  
Pneumococcal Disease ◽  
Influenza Viruses ◽  
Dependent Manner ◽  
Proinflammatory Response ◽  
Content Type ◽  
Infant Mouse ◽  
Human Middle Ear

ABSTRACTInfluenza A virus (IAV) predisposes individuals to secondary infections with the bacteriumStreptococcus pneumoniae(the pneumococcus). Infections may manifest as pneumonia, sepsis, meningitis, or otitis media (OM). It remains controversial as to whether secondary pneumococcal disease is due to the induction of an aberrant immune response or IAV-induced immunosuppression. Moreover, as the majority of studies have been performed in the context of pneumococcal pneumonia, it remains unclear how far these findings can be extrapolated to other pneumococcal disease phenotypes such as OM. Here, we used an infant mouse model, human middle ear epithelial cells, and a series of reverse-engineered influenza viruses to investigate how IAV promotes bacterial OM. Our data suggest that the influenza virus HA facilitates disease by inducing a proinflammatory response in the middle ear cavity in a replication-dependent manner. Importantly, our findings suggest that it is the inflammatory response to IAV infection that mediates pneumococcal replication. This study thus provides the first evidence that inflammation drives pneumococcal replication in the middle ear cavity, which may have important implications for the treatment of pneumococcal OM.

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