Pathogenesis Of Acute Otitis Media Research Articles

Chronic Suppurative Otitis Media: A Comprehensive Review of Epidemiology, Pathogenesis, Microbiology, and Complications.

Otitis media is a significant contributor to healthcare visits and the prescription of drugs. Its associated complications and consequences pose the primary factors for preventable hearing impairment, especially in developing nations. Chronic suppurative otitis media (CSOM) is prevalent among children globally as one of the commonest chronic infectious diseases during childhood. The subsequent complications and sequelae play a central role in causing avoidable hearing loss, particularly within developing countries. In addition to impaired hearing, this condition can lead to severe health complications, such as issues involving the intracranial region. Despite the involvement of microbial, immunological, and genetic factors as well as Eustachian tube characteristics, in the development of CSOM, there remains a need for further elucidation regarding its pathogenesis. Based on its microorganisms, the treatment of choice will be affected to prevent further complications in the child. The primary approach to treating acute otitis media (AOM) involves effectively addressing ear pain and fever symptoms, while antibiotics are only administered in cases where children experience severe, long-lasting, or frequent infections. Despite the extensive investigation on AOM pathogenesis, research is scarce regarding CSOM. Given that antibiotic resistance and drug-induced ear damage are growing problems and surgery-related complications, it is imperative to devise effective therapeutic interventions against CSOM arises. Therefore, comprehending the host's immune function concerning CSOM and identifying how bacteria sidestep these potent responses becomes crucial. Acquiring insight into molecular mechanisms associated with CSOM will enable scientists to formulate innovative treatment approaches to combat this disease, thereby averting hearing loss consequences. The management consists of watchful waiting, primarily for children with chronic effusions and hearing loss.

Modern aspects of immune protection of the middle ear in the pathogenesis of acute otitis media and its complications

The relevance of the study is due to the need for an extended search for information on the current state of the problem of acute otitis media in adults based on the experience of Ukrainian and foreign authors. The aim of our research: To analyze the world experience on the etiology, pathogenesis and diagnosis of acute otitis media in adults. Materials and methods: 125 modern literature sources of electronic databases PubMed, EMBASE, MED-LINE, U.S. National Library of Medicine Clinical Trials, Research Gate and Cochrane Library. Introduction: The problem of otitis media as a component of the problem of inflammatory diseases of the upper respiratory tract remains relevant in modern medicine, based on its incidence and prevalence in the structure of otolaryngological diseases. Despite the achievements of modern medical science, these indicators remain consistently substantial, which determines the relevance of further research to improve diagnosis and treatment. Results: By conducting a bibliographic method of research it was found that most scientific articles are devoted to the problem of acute otitis media in children, while the problem of acute otitis media in adults is not sufficiently studied. Clinical and experimental studies have established that the function of immune protection of the middle ear is present at almost all physiological levels from epithelial cells to intracellular nuclear factor. This function is realized through the messengers of the cytokine network. Among the pool of cytokines, IL-1, IL-6 and TNF-α are important for the pathogenesis of acute otitis media. One of the features of the immune defense is a clear succession of stages of inflammation with its own features at each stage. It is shown that each of the links of immune defense (including cytokines) is able to detect (in case of discrepancy in strength and time) a negative effect with the maintenance or intensification of inflammation. The data of experimental analysis of pathomorphological changes in the middle ear depending on the duration of the disease are presented. It is also shown that the issue of complicated course (in particular mastoiditis) is still relevant. The role of acute otitis media in the deveopment of intracranial complications (meningitis) has been established. The significance of comorbidity for the pathogenesis of acute otitis media and the role of diabetes mellitus in the structure of comorbidity was proved. The main factors of reducing the effectiveness of diagnosis and treatment of acute otitis media are convincingly outlined: the multifactorial nature of the etiology, the peculiarities of immune protection and the tendency of otopathogens to evade the host's immune response, the importance of comorbid pathology in adult pat ients with ENT diseases. A certain number of literature sources are devoted to the features of the course of acute otitis media in diabetes mellitus. The shortcoming identified by the results of the analysis of literature sources: the lack of research on the peculiarities of the clinic and diagnosis of acute otitis media in adults, especially in the setting of comorbid pathology, primarily type 2 diabetes mellitus, indicates the relevance of further research on this problem.

Influence of glucose metabolism disorders and manifestations of dyslipidemia on the cytokine profile and peculiarities of correlation pleiades in patients with acute otitis media

The relevance of the study is due to the lack of data to determine the pathogenetic significance of cytokine profile specifics and correlation pleiades in patients with acute otitis media (AOM) on the background of disorders of glucose metabolism and dyslipidemia manifestations. The aim of our research: to determine the peculiarities of cytokine profile of peripheral blood in the amount of IL-4, IL-6 and TNF-α and to investigate the correlation pleiades in patients with AOM on the basis of glucose metabolism disorders with regard to the processes of glucose formation, dyslipidemia, and bone tissue metabolism. Materials and methods: We examined 73 patients with AOM aged 18 to 79 (29 males and 44 females), who were randomized into 4 groups.1 and 2 groups (comparison) (17 patients with acute AOM and 15 patients with AOM with paranasal sinus pathology in groups accordingly) and groups 3 and 4 (main groups) (20 patients with AOM with type 2 diabetes and 21 patients with AOM with glucose metabolism disorders accordingly). Apart from the clinical examination, all patients were tested for glucosylated hemoglobin (HbAlc), IL-4, IL-6, TNF-α and low-density lipoproteins (LDL). The pathogenetic significance of the observed changes was assessed by determining the correlations of the indices given, taking into account the previously established metabolism of bone tissue in the amount of parathormone, osteocalcin, and calcium. Results of the study and discussion: In patients with acute otitis media with impaired glucose metabolism there was a significant (p˂0.001) increase in the pool of proinflammatory cytokines IL-6 (10.26±0.46 pkg/ml and 10.94±0.5 pkg/ml in groups 3 and 4 accordingly) and TNF-α (11.05±0.5 pkg/ml and 9.7±0.5 pkg/ml accordingly in groups 3 and 4).The increase in the level of TNF-α was 1.9 times greater in patients with type 2 diabetes and 1.7 times greater in patients with transient disorders of glucose metabolism, in relat ion to the increase in the amount of IL-6 (1.1 to 1.3 times in groups 3 and 4, respectively).The amount of antiinflammatory cytokine IL-4 was within the reference norms for the methodology used, but was consistent ly lower in patients with glucose metabolism disorders (7.27±0.2 pkg/ml and 7.79±0.2 pkg/ml in groups 3 and 4 respectively, p˂0,001).We also found a significant (p˂0,001) increase in low density lipoproteins as a manifestation of dyslipidemia in patients with AOM against the background of impaired glucose metabolism 1.8 times in group 3 patients (4,6±0,25 mmol/l) and 1.7 times in group 4 patients (4,27±0,2 mmol/l). Influence of carbohydrate metabolism disorders on formation of cytokine profile and significance of dyslipidemia in pathogenesis of AOM is confirmed by the determined authenticity of variations in glucose content, HbAlc and these indices in patients in the main groups (groups 3 and 4) and the comparison groups (groups 1 and 2) due to the absence of differences in the data between groups 1 and 2 and 3 and 4 (p˃0,05). The study of the correlat ion pleiades of the indices with the markers of bone tissue metabolism revealed the inimitability of their presence, number and strength in patients in groups 1-2 due to the lack of correlation with indicators of glucose and HbAlc, IL-6, LDL and parathormone, which may indicate that in these patients only the mucous membrane of the middle ear is involved in the process. In patients with AOM with type 2 diabetes mellitus, multiple interactions of moderate strength, both direct (glucose – TNF-α, IL-6; HbAlc – LDL, TNF-α, IL-6; parathormone – IL-6, LDL; LDL – TNF-α) and inverse (calcium – TNF-α, LDL; IL-6 – calcium, IL-4), with the effect on bone tissue metabolism were found. In patients of group 4, the presence and strength of the interrelationships were similar to the above on the background of type 2 diabetes with a decrease in their number and a strong direct correlation of HbAlc – parathormone, IL-6; parathormone – IL-6, LDL; LDL – IL-6. Conclusions: Blood cytokine profile in patients with acute otitis media with impaired glucose metabolism is characterized by a significant increase in the pool of proinflammatory cytokines ІL-6 and TNF-α, a decrease in the level of anti-inflammatory cytokine ІL-4 in dyslipidemia by indicators of a significant increase in LDL. Multiple interrelationships of the studied indicators in patients with AOM on the background of type 2 diabetes characterize the complex proinflammatory background with an impact on the indicators of bone tissue metabolism. Similar interrelations on the background of transient disorders of glucose metabolism indicate their importance in the pathogenesis of a particular AOM, which is also confirmed by the validity of differences in the indicators and observed correlations in patients of groups 1-2 and 3-4. Taking into account the presence and peculiarities of the influence of any disorders of carbohydrate metabolism, including transient ones, is valuable for increasing the efficiency of diagnosis and treatment of AOM in adults.

Age-Dependent Dissimilarity of the Nasopharyngeal and Middle Ear Microbiota in Children With Acute Otitis Media.

Acute bacterial otitis media is usually caused by otopathogens ascending to the middle ear from the nasopharynx (NP). However, it is unknown if the nasopharyngeal microbiota of children with acute otitis media (AOM) can serve as an age-dependent or independent proxy for the microbial communities of the middle ear fluid (MEF) as there is a lack of 16S rRNA amplicon sequencing studies simultaneously analyzing the microbial communities of the two sites. Within this study, we performed 16S rRNA next generation sequencing on a total of 286 nasopharyngeal swabs (NPSs) collected between 2004 and 2013 within a Swiss national AOM surveillance program from children (0–6 years) with AOM. In addition, 42/286 children had spontaneous tympanic membrane perforation and, therefore, those MEF could also be analyzed. We found that alpha [Richness, Shannon diversity index (SDI) and Evenness] and beta diversity measurements of the nasopharyngeal bacterial microbiota showed a clear dependency of the increasing age of the children. In more detail, bacterial richness and personalized profiles (measured by beta dispersion) were higher and more frequent in older children, respectively. Dissimilarity values based on the binary distance matrix of the microbiota patterns of the NP and the MEF also correlated with increasing age. In general, positive (PPV) and negative predictive values (NPV) of the most abundant operational taxonomic units (OTUs) in the NP were moderately and well predictive for their presence in the MEF, respectively. This data is crucial to better understand polymicrobial infections and therefore AOM pathogenesis.

Biofilm production by Haemophilus influenzae and Streptococcus pneumoniae isolated from the nasopharynx of children with acute otitis media

BackgroundBiofilm production by Haemophilus influenzae and Streptococcus pneumoniae has been implicated in the pathogenesis of otitis media, mainly in chronic and recurrent cases. We studied the “in vitro” biofilm production by these 2 species isolated alone or together from the nasopharynx of children with acute otitis media.MethodsThe studied strains were from 3 pneumococcal conjugate vaccine (PCV) periods: pre-PCV7, post-PCV7/pre-PCV13 and post-PCV13. A modified microtiter plate assay with crystal violet stain was used to study the biofilm production of 182 H. influenzae and 191 S. pneumoniae strains.ResultsOverall, 117/181 (64.6%) H. influenzae and 128/191 (66.8%) S. pneumoniae strains produced biofilm. The proportion of biofilm-producing H. influenzae strains was greater with than without the isolation of S. pneumoniae in the same sample (75.5% vs 52.3%, p = 0.001). Conversely, the proportion of biofilm-producing S. pneumoniae strains was not affected by the presence or not of H. influenzae (66.3% vs 67.4%). S. pneumoniae serotypes 6B, 15B/C, 19A, 35F and 35B were the better biofilm producers (80%). Serotypes 11A, 14, 15A, 19F and 19A were more associated with H. influenzae biofilm-producing strains. Overall, 89/94 (94.6%) of cases with combined isolation showed biofilm production by S. pneumoniae or H. influenzae.ConclusionThis study emphasizes the high proportion of biofilm production by H. influenzae and S. pneumoniae strains isolated from the nasopharynx of children with acute otitis media, which reinforces the results of studies suggesting the importance of biofilm in the pathogenesis of acute otitis media.

Human enterovirus and rhinovirus infections are associated with otitis media in a prospective birth cohort study

BackgroundHuman enteroviruses (HEVs) and rhinoviruses (HRVs) have been linked to acute otitis media (AOM). ObjectivesThe present study evaluates the aforementioned association in a birth cohort setting. Study designThe cohort included 286 healthy infants (191 boys) followed from birth up to the age of 2 years in the Type 1 Diabetes Prediction and Prevention study in Finland. Stool samples were collected monthly and analyzed for the presence of HRV and HEV RNA using RT-PCR. Clinical symptoms were recorded by a questionnaire every 3–6 months. ResultsAltogether 610 AOM episodes were reported during the follow-up. 9.8% of the stool samples were positive for HRV and 6.8% for HEV. HRV positivity peaked at the age of 3–6 months declining gradually after this age, whereas HEV positivity peaked later, at the age of 12–24 months. The risk of AOM was increased in children who were HEV positive at least once at the age of 6–12 months (OR 2.2 [95%CI 1.1–4.2], P=0.023) or who were HRV positive at least once at the age of 18–24 months (OR 2.3 [95%CI 1.0–5.2], P=0.042). Having an older sibling, short breast-feeding and maternal smoking during pregnancy were also significantly associated with AOM. ConclusionsHRV and HEV infections are frequent during the first months of life. The observed trend for increased risk of AOM in HRV and HEV positive children is in line with the results from hospital series suggesting that these viruses may play an independent role in the pathogenesis of AOM.

Acute Otitis Media and Other Complications of Viral Respiratory Infection.

Viral upper and lower respiratory tract infections (URI, LRI) are common in infants. We determined the prevalence of viral URI and its complications, including acute otitis media (AOM) and LRI, and assessed the effect of bacterial-viral interactions, and genetic and environmental risks on AOM development. Healthy infants were enrolled from near birth and followed to the first episode of AOM up to 12 months of age. Nasopharyngeal specimens were collected at monthly intervals (months 1-6, 9) and during viral URI episodes for bacterial culture and viral polymerase chain reaction studies. Subjects were followed closely for AOM development. A total of 367 infants were followed for 286 child-years; 887 URI (305 infants) and 180 AOM episodes (143 infants) were documented. Prevalence of URI, LRI, and AOM in the first year was 3.2, 0.25, and 0.67 per child-year, respectively. Cumulative AOM incidence by ages 3, 6, and 12 months was 6%, 23%, and 46%. Infants with and without AOM had 4.7 and 2.3 URI episodes per child-year, respectively (P < .002). Pathogenic bacterial colonization rates by month were significantly higher in infants with AOM (P < .005). Breastfeeding reduced both URI and AOM risks (P < .05). Significant bacterial-viral interactions occurred with Moraxella catarrhalis and a variety of respiratory viruses and altered URI and AOM risks. Almost half of infants experienced AOM by age 1. Important AOM risk factors included frequent viral URI, pathogenic bacterial colonization, and lack of breastfeeding. Bacterial-viral interactions may play a significant role in AOM pathogenesis and deserve further investigation.

Current concepts in the pathogenesis and treatment of chronic suppurative otitis media.

Otitis media (OM) is an inflammation of the middle ear associated with infection. Despite appropriate therapy, acute OM (AOM) can progress to chronic suppurative OM (CSOM) associated with ear drum perforation and purulent discharge. The effusion prevents the middle ear ossicles from properly relaying sound vibrations from the ear drum to the oval window of the inner ear, causing conductive hearing loss. In addition, the inflammatory mediators generated during CSOM can penetrate into the inner ear through the round window. This can cause the loss of hair cells in the cochlea, leading to sensorineural hearing loss. Pseudomonas aeruginosa and Staphylococcus aureus are the most predominant pathogens that cause CSOM. Although the pathogenesis of AOM is well studied, very limited research is available in relation to CSOM. With the emergence of antibiotic resistance as well as the ototoxicity of antibiotics and the potential risks of surgery, there is an urgent need to develop effective therapeutic strategies against CSOM. This warrants understanding the role of host immunity in CSOM and how the bacteria evade these potent immune responses. Understanding the molecular mechanisms leading to CSOM will help in designing novel treatment modalities against the disease and hence preventing the hearing loss.

Bacterial and Respiratory Viral Interactions in the Etiology of Acute Otitis Media in HIV-infected and HIV-uninfected South African Children.

Bacteria and respiratory viruses are implicated in the pathogenesis of acute otitis media (AOM); however, data from low-middle income countries are sparse. We investigated the etiology of AOM in HIV-infected (HIV+), HIV-uninfected (HIV-) and HIV-exposed clinically asymptomatic for HIV-infection (HEU) South African children. Children ≥3 months to <5 years of age with AOM were enrolled between May 2009 and April 2010 (NCT01031082). Middle ear fluid samples were cultured for bacteria; antibacterial susceptibility was done and serotyping undertaken for Streptococcus pneumoniae and Haemophilus influenzae. Nasopharyngeal aspirates were analyzed for respiratory viruses using immunofluorescence assay and polymerase chain reaction. Of 260 AOM episodes (HIV+:15; HIV-:182; HEU:63), bacteria were found in 54.6%, including Haemophilus influenzae (30.8%), 98.8% of which were nontypeable, and Streptococcus pneumoniae (20.4%), Staphylococcus aureus (15.8%), Moraxella catarrhalis (5.0%) and Streptococcus pyogenes (1.5%). Nonsusceptibility of Streptococcus pneumoniae to penicillin was 64.2%. Respiratory viruses were detected in 74.2% of cases. Human rhinovirus was most frequently detected (37.7%), followed by adenovirus (14.2%) and human bocavirus (11.5%) overall and irrespective of HIV status. Respiratory viruses were identified concurrently with S. pneumoniae, H. influenzae, M. catarrhalis (76.9-78.8%) and Staphylococcus aureus (63.4%) cultured from middle ear fluid, as well as in 72.0% of episodes negative for any bacteria. The study suggests that respiratory viruses and pathogenic bacteria play an important role in the development of AOM in children. A similar spectrum of pathogens was observed independently of HIV status. Vaccines targeting both nontypeable Haemophilus influenzae and S. pneumoniae may have a broad impact on AOM in South Africa.

Polymorphisms in IL-6, IL-10, TNF-α, IFN-γ and TGF-β1 Genes and Susceptibility to Acute Otitis Media in Early Infancy

Genetic susceptibility has a major role in the pathogenesis of acute otitis media (AOM). In the present study, we investigated the variability of 5 cytokine genotypes as related to susceptibility and outcome of AOM in early infancy. Single nucleotide polymorphisms in IL-6 (-174 G→C), IL-10 (-592 C→A, -819 C→T and -1082 G→A), TNF-α (-308 G→A), IFN-γ (+874 A→T) and TGF-β1 (codon 10 C→T; codon 25 G→C) genes were investigated and related to clinical course and outcome in 96 infants younger than 9 months with AOM. Compared with wild genotypes, IL-10 (-592, -819 and -1082) and TGF-β1 (codon 10) genotypes carrying the alternative allele were related to more AOM episodes (P < 0.0001, P < 0.0001, P < 0.0001 and P = 0.002, respectively) and the need for tympanostomy tubes. Furthermore, IL-10 (-1082) and TGF-β1 (codon 10) genotypes carrying the alternative allele were related to later onset of first AOM episode than wild-type genotypes (P = 0.007 and P = 0.039, respectively). No relationship was found about AOM complications. Our findings suggest that IL-10 and TGF-β1 genotypes are related to the age of AOM onset, multiple AOM episodes and insertion of tympanostomy tubes, pointing to the involvement of anti-inflammatory cytokines in AOM during infancy.

Role of Human Bocavirus in Upper Respiratory Tract Infections and Acute Otitis Media.

BackgroundHuman bocavirus (HBoV) is a newly described parvovirus. HBoV1 has been associated with respiratory infections, including acute otitis media (AOM), but the knowledge on the significance of HBoV1 in upper respiratory tract infections (URI) and AOM in relation to other respiratory viruses is limited. The objective of this study was to compare the rate of detection of HBoV1 to that of other respiratory viruses in specimens from children with URI, with and without AOM complication.MethodsNasopharyngeal secretions (NPS) were collected during URI from healthy children (6–35 months) followed prospectively for 1 year; specimens have been previously analyzed for broad spectrum of respiratory viruses. Archived NPS were analyzed for HBoV1 using a high-throughput, quantitative polymerase chain reaction method.ResultsSeven hundred and seven NPS samples collected during URI episodes from 201 children were studied for HBoV1. A total of 94 (47%) children tested positive for HBoV1 DNA during 172 (24%) URI episodes; HBoV1 was present as the only virus in 44 (6%) URI episodes. Overall, 37% of URI episodes were complicated by AOM. Of URI associated with single virus (n = 303), the rate of AOM complicating URI associated with HBoV1 only was 52% (23 of 44); this was a higher AOM rate, compared to that of other respiratory viruses.ConclusionsAmong URI associated with single respiratory virus, HBoV1-URI was commonly associated with AOM complication. The important role of HBoV1 on AOM pathogenesis needs to be studied further.

Acute Bacterial Sinusitis in Children

On the basis of strong research evidence, the pathogenesis of sinusitis involves 3 key factors: sinusostia obstruction, ciliary dysfunction, and thickening of sinus secretions. On the basis of studies of the microbiology of otitis media, H influenzae is playing an increasingly important role in the etiology of sinusitis, exceeding that of S pneumoniae in some areas, and b-lactamase production by H influenzae is increasing in respiratory isolates in the United States. On the basis of some research evidence and consensus,the presentation of acute bacterial sinusitis conforms to 1 of 3 predicable patterns; persistent, severe, and worsening symptoms. On the basis of some research evidence and consensus,the diagnosis of sinusitis should be made by applying strict clinical criteria. This approach will select children with upper respiratory infection symptoms who are most likely to benefit from an antibiotic. On the basis of some research evidence and consensus,imaging is not indicated routinely in the diagnosis of sinusitis. Computed tomography or magnetic resonance imaging provides useful information when complications of sinusitis are suspected. On the basis of some research evidence and consensus,amoxicillin-clavulanate should be considered asa first-line agent for the treatment of sinusitis.

New Paradigms in the Pathogenesis of Otitis Media in Children

Acute otitis media (AOM) is a multifactorial disease with a significant socioeconomic impact. The pathogenesis of AOM is attributed to a variety of well-established internal and extrinsic factors. Recent evidence strongly points to bacterial biofilm formation as an important contributor to this disease entity. The nasopharynx is a likely reservoir for infection with subsequent seeding of pathogens to the middle ear via planktonic shedding. Various modalities have been used to directly detect biofilm formation in the middle ear mucosa of children with AOM. Further insights into this disease may lead to new strategies for prevention and treatment.

Bacterial and viral interactions within the nasopharynx contribute to the risk of acute otitis media

SummaryObjectivesTo understand relationships between microbes in pathogenesis of acute otitis media during respiratory tract infections, we compared nasopharyngeal bacteria and respiratory viruses in symptomatic children with and without AOM.MethodsWe enrolled children (6–35 months) with acute symptoms suggestive of AOM and analyzed their nasopharyngeal samples for bacteria by culture and for 15 respiratory viruses by PCR. Non-AOM group had no abnormal otoscopic signs or only middle ear effusion, while AOM group showed middle ear effusion and acute inflammatory signs in pneumatic otoscopy along with acute symptoms.ResultsOf 505 children, the non-AOM group included 187 and the AOM group 318. One or more bacterial AOM pathogen (Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis) was detected in 78% and 96% of the non-AOM and AOM group, respectively (P < .001). Colonization with S. pneumoniae and H. influenzae, each alone, increased risk of AOM (odds ratio (OR) 2.92; 95% confidence interval (CI), .91–9.38, and 5.13; 1.36–19.50, respectively) and co-colonization with M. catarrhalis further increased risk (OR 4.36; 1.46–12.97, and 9.00; 2.05–39.49, respectively). Respiratory viruses were detected in 90% and 87% of the non-AOM and AOM group, respectively. RSV was significantly associated with risk of AOM without colonization by bacterial AOM pathogens (OR 6.50; 1.21–34.85).ConclusionsCo-colonization by M. catarrhalis seems to increase risk of AOM and RSV may contribute to AOM pathogenesis even without nasopharyngeal bacterial colonization.

Suture restriction of the temporal bone as a risk factor for acute otitis media in children: cohort study.

BackgroundEustachian tube (ET) dysfunction plays an important role in the pathogenesis of acute otitis media (AOM). Unfortunately, there is a lack of knowledge about the exact role of the ET’s bony support, the temporal bone, on occurrence of AOM. This study investigates whether severe suture restriction of the temporal bone is a risk factor for development of AOM in young children.MethodsUsing a prospective cohort design, 64 children aged 6 to 18 months without prior history of AOM were followed during the cold season (September 2009 to April 2010). Temporal bone status (categorized as with or without severe suture restriction) was evaluated using palpation and a cranial bone mobility test. Information about potential baseline confounders and risk factors for AOM (gender, age, birth weight, gestational age, use of pacifier, daycare attendance, presence of siblings, low socioeconomic status, breastfeeding ≥ 6 months, parental smoking and history of upper respiratory tract infection) were also collected. Occurrence of AOM diagnosed by physicians blinded to temporal bone status was the main outcome. Data were analyzed using hierarchical linear and nonlinear (multilevel) models.ResultsSevere suture restriction of the temporal bone was identified in 23 children (35.9%). At least one AOM episode was diagnosed in 14 (48.3%) of the ears associated with temporal bones previously identified as having severe suture restriction and in 28 (28.3%) of those without severe suture restriction. Higher risk for AOM was explained by severe suture restriction of the temporal bone (adjusted relative risk (RR), 2.26, 95% CI 1.43 to 2.91, p<.01), pacifier use (RR, 2.59, 95% CI 1.51 to 3.22, p<.01) and younger age (RR, 0.22, 95% CI 0.10 to 0.52, p=.001).ConclusionsThe study results indicate that severe suture restriction of the temporal bone is a risk factor for AOM in young children. Subsequent intervention studies are needed to determine if this mechanical risk factor can be modified in young children.

Nasopharyngeal Microbiota in Infants With Acute Otitis Media

Background. Interspecies interactions of the nasopharyngeal microbiota are likely to be involved in the pathogenesis of acute otitis media (AOM). Capturing the breadth of microbial interactions requires a detailed description of the microbiota during health and AOM. Methods. The nasopharyngeal microbiota of 163 infants with (n = 153) or without (n = 10) AOM was characterized using nasopharyngeal swabs and multiplexed pyrosequencing of 16S rRNA. Nasopharyngeal swab specimens were collected during 4 winter seasons from 2004 through 2010 for infants with AOM and during 2010 for controls. Results. Fifty-eight bacterial families were identified, of which Moraxellaceae, Streptococcaceae, and Pasteurellaceae were the most frequent. Commensal families were less prevalent in infants with AOM than in controls. In infants with AOM, prior exposure to antimicrobials and administration of the heptavalent conjugated pneumococcal polysaccharide vaccine (PCV7) were also associated with reduced prevalence of distinct commensal families (Streptococcaceae and Corynebacteriaceae). In addition, antimicrobial exposure increased the prevalence of Enterobacteriaceae and the abundance of Pasteurellaceae. Other factors, such as age, sex, day care, and a history of recurrent AOM, did not influence the microbiota. Conclusions. Infants’ nasopharyngeal microbiota undergoes significant changes during AOM and after exposure to antimicrobials and PCV7, which is mainly attributable to reduced prevalence of commensal bacterial families.

Systemic Cytokine Response Profiles Associated With Respiratory Virus-Induced Acute Otitis Media

Acute otitis media (AOM) results from a complex interplay between the infectious agents and host immune responses. Cytokines play a major role in the pathogenesis of AOM, but there are few studies on the systemic cytokine response during AOM. Sera were collected from 145 children (median age = 13.5 months) at the time of diagnosis of AOM. Concentrations of 17 cytokines (IL-1beta, -2, -4, -5, -6, -7, -8, -10, -12, -13, -17, granulocyte-colony stimulating factor (G-CSF), granulocyte-monocyte-colony stimulating factor, interferon-gamma, MCP-1, MIP-1beta, TNF-alpha) were determined and correlated with viral etiology and clinical outcome. The statistical analysis was conducted using bioinformatics software. Cluster patterns of concentrations of cytokines were examined by unsupervised hierarchical clustering algorithms. Four major cluster groups were identified, one of the groups was significantly enriched for cases of respiratory syncytial virus (RSV)-induced AOM as compared with other viruses. Specifically, RSV-induced AOM had significantly higher concentrations of G-CSF, MCP-1, IL-10, IL-6, interferon-gamma, and IL-8 (P < 0.05). Using a decision tree classifier, higher G-CSF concentrations produced 87.6% accuracy to predict RSV-induced AOM. Overall, higher IL-13 concentrations produced 84.2% accuracy to predict early clinical failure of antibiotic treatment. Children with AOM have a unique pattern of systemic cytokine response that relates to virus etiology and clinical outcome. Based on G-CSF and IL-13 measurements, it is possible to accurately classify RSV-induced AOM and early treatment failure, respectively; these observations will need to be validated in an independent population.

Detection of respiratory viruses in nasopharyngeal secretions and middle ear fluid from children with acute otitis media

Conclusions. Our results suggest that various respiratory viruses contribute to the pathogenesis of acute otitis media (AOM). Objective. AOM is one of the most common complications of viral upper respiratory tract infections in children. Recently, the importance of respiratory viruses has been stressed as causative agents of AOM. Subjects and methods. A total of 1092 children ≤10 years old (average age 1.38 years) diagnosed as having AOM between 2002 and 2004 were studied. Bacterial and viral cultures of both nasopharyngeal secretions (NPS) and middle ear fluid (MEF) were performed for all 1092 children. Body temperature, changes of the tympanic membrane, and the number of days from the onset of illness were analyzed. Results. Respiratory viruses were detected in 360 of 1092 NPS specimens, including 157 isolates of respiratory syncytial virus and 88 of influenza virus. Among 1092 MEF specimens, 102 were virus-positive, including 43 for respiratory syncytial virus and 29 for influenza virus. In 75 children, respiratory viruses were only detected in MEF. The viral detection rate was higher in children with fever at an early stage of their illness. The tympanic membrane changes associated with viral infection tended to be less severe, while changes were more severe in cases with bacterial infection, especially co-infection with bacteria and viruses.

Middle Ear Effusion Interleukin-6 and Interleukin-8 levels could Differentiate between Bacterial and Non-Bacterial Acute Otitis Media and Help to Identify the Type of Infecting Bacteria

This study aimed to investigate the middle ear effusion (MEE) levels of interleukin-6 (IL-6) and IL-8 inchildren with acute otitis media (AOM) and their relation to its etiology and type of infecting bacteria as a trial to define a faster diagnostic modality than traditional culture and sensitivity testso as to early initiate therapy. The study included 70 children; 44 males and 26 females, with a mean age of 19.3±8 months; 50 patients had unilateral and 20 bilateral AOM (n=90 ears). The diagnosis of AOM was based on presence of fever, irritabilityor earache and signs of inflammation of thetympanic membrane. The presence of MEE was documented by tympanocentesisand MEE sampleswere obtained for culture to define the offending pathogen, cytological examination to grade it according to number of polymophonuclear leucocytes (PNL) and ELISA estimation of the levels of IL-6 and IL-8. Sensitivity and specificity of MEE IL-6 and IL-8 levels for differentiation between bacterial and non-bacterial cases and identification of infecting bacteria were evaluated using the receiver operating characteristic (ROC) curve analysis judged by the area under the curve (AUC). Bacteriological examination identified the infective pathogen in 61 samples (67.7%) and no bacterial infection in 29 samples (32.3%). Combined infection with Haemophilus influenzae (H. inf.) and Streptococcus pneumoniae (S. pn.) was detected in 12 samples. However, single pathogen infection was detected in 49 samples; H. inf in 35 samples, S. pn in 11 samples, Moraxella catarrhalis in 2 samples and S. pyogenes in one sample. Effusion was serous in 52, mucoid in 28 and purulent in 10 effusions. Nine samples weregrade I, 35 were grade II, 29 samples were grade III and 17 samples were grade IV. There was a significant (p 0.05) elevated compared to levels estimated in samples with mixed infection. ROC curve analysis revealed that estimation of MEE levels of both IL-6 and IL-8 are specific for the presence of bacterial AOM with AUC=0.832 & 0.897, respectively. Elevated MEE level of IL-6 could differentiate between H. inf. and S. pn. infection with high specificity with AUC=0.758, while IL-8 was more sensitive indictor of H. inf. infection with AUC=0.363. It may be concluded that AOM is associated with elevated MEE levels ofIL-6 and IL-8 which may suggest a role imposed by these cytokines in pathogenesis of AOM. The elevated levels of both cytokines could differentiate bacterial from non-bacterial cases with high specificity. Elevated MEE level of IL-6 may be specific for S. pn infection, while elevated IL-8 levels may be a sensitive for H. inf. infection

Prospects for Prevention of Otitis Media

Understanding the pathogenesis of acute otitis media provides insight into strategies for immunoprophylaxis. This article evaluates the interactions between pathogen and host defense, and identifies potential bacterial and viral vaccine targets. Discussed in detail are the attributes for a candidate antigen necessary to achieve a greater reduction in the burden of middle ear disease. These include: (1) the need to target a broad spectrum of otopathogens; (2) antigens need to be shared across all (or most) isolates within a bacterial species; (3) antigens need to be surface exposed during middle ear infection; and (4) preferred antigens have an essential function such that nonexpressing bacterial mutants have reduced virulence. A vaccine candidate (Pnc-PD) that encompasses these "attributes" is discussed from the perspective of how it may provide additional protection from middle ear disease if further studies confirm initial data on efficacy.