Prevention Of Otitis Media Research Articles

Clinical and economic burden of otitis media in children under 5 years of age in the United States: A retrospective study

ABSTRACT Reductions in all-cause otitis media (OM) following widespread pneumococcal conjugate vaccine use have plateaued. Granular burden of disease data are needed to guide evaluation and implementation of new measures targeting OM prevention. We conducted a retrospective study to assess the incidence and treatment costs of OM, tympanostomy tube placement (TTP), and hearing loss in children aged <5 years in the United States (US). OM episodes and TTP between 2016 and 2017 were identified in IBM MarketScan Commercial Claims and Encounters, Medicare Supplemental and Coordination of Benefits, and Multi-Medicaid databases using diagnosis codes (ICD-10). The incidence rate per 100,000 person-years (IR) of OM in <5-year-olds was 62,726 in Commercial/Medicare databases and 55,874 in Medicaid. IRs peaked at 9–<12 months (115,552 and 110,960, respectively). Approximately 5% and 4% of OM episodes in the respective databases had TTP (IR 3233 and 2404). Around 2% of children with OM had hearing loss (IR 1468 and 1109, respectively), of whom 41% had TTP. We estimated that there were 11.1 million OM episodes in 2020 costing USD 4.8 billion. 243,618 children were estimated to have OM with hearing loss at a direct total cost of USD 637 million, or 13% of the overall cost. The clinical and economic burden attributable to OM in the US was high in children aged <5 years during the study period. Novel approaches are needed to improve and broaden vaccine-induced protection against OM and its complications. The study results could guide policymakers considering age-specific interventions to reduce the OM burden.

Otitis media at 6-monthly assessments of Australian First Nations children between ages 12–36 months: Findings from two randomised controlled trials of combined pneumococcal conjugate vaccines

ObjectivesIn remote communities of northern Australia, First Nations children with hearing loss are disproportionately at risk of poor school readiness and performance compared to their peers with no hearing loss. The aim of this trial is to prevent early childhood persisting otitis media (OM), associated hearing loss and developmental delay. To achieve this, we designed a mixed pneumococcal conjugate vaccine (PCV) schedule that could maximise immunogenicity and thereby prevent bacterial otitis media (OM) and a trajectory of educational and social disadvantage. MethodsIn two sequential parallel, open-label, randomised controlled trials, eligible infants were first allocated 1:1:1 to standard or mixed PCV primary schedules at age 28–38 days, then at age 12 months to a booster dose (1:1) of 13-valent PCV, PCV13 (Prevenar13®, +P), or 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugated vaccine, PHiD-CV10 (Synflorix®, +S). Here we report findings of standardised ear assessments conducted six-monthly from age 12–36 months, by booster dose. ResultsFrom March 2013 to September 2018, 261 children were allocated to booster + P (n = 131) or + S (n = 130). There were no significant differences in prevalence of any OM diagnosis by booster dose or when stratified by primary schedule. We found high, almost identical prevalence of OM in both boost groups at each age (for example 88% of 129 and 91% of 128 children seen, respectively, at primary endpoint age 18 months, difference −3% [95% Confidence Interval −11, 5]). At each age prevalence of bilateral OM was 52%–78%, and tympanic membrane perforation was 10%–18%. ConclusionDespite optimal pneumococcal immunisation, the high prevalence of OM persists throughout early childhood. Novel approaches to OM prevention are needed, along with improved early identification strategies and evaluation of expanded valency PCVs.

Interferon Gamma Response in Human Saliva Following Exposure to the Oral Probiotic Streptococcus salivarius BLIS K12.

Streptococcus salivarius BLIS K12 is a probiotic strain developed for application to the oral cavity. The strain was originally characterised for its in vitro antibacterial activity against the prominent oral pathogen Streptococcus pyogenes. More recent research has expanded its applications to include reducing halitosis, preventing otitis media and protecting against virus infections of the respiratory tract. A potential mechanism for this anti-viral activity could be the stimulation of salivary interferon gamma (IFN-γ) production in the oral cavity. The aim of this study was to investigate whether the ingestion of and oral cavity colonisation by S. salivarius BLIS K12 is associated with enhancement of IFN-γ levels in saliva. Application of ELISA demonstrated that consumption of S. salivarius BLIS K12 effected an increase in salivary IFN-γ, and this response was more consistent with use of viable cells than following ingestion of heat-killed S. salivarius BLIS K12. Interestingly, those subjects who more successfully colonised with S. salivarius BLIS K12 did not experience a relatively larger increase in their IFN-γ levels, indicating that the observed IFN-γ response occurs independently of colonisation efficacy. In summary, the consumption of S. salivarius BLIS K12 increases salivary levels of IFN-γ, an effect that may contribute to protection of the host against certain virus infections.

The Impact of the COVID-19 Pandemic on Otitis Media.

Otitis media is one of the most common diseases in children, with 80% of children experiencing it by the age of three years. Therefore, the resulting social burden is enormous. In addition, many countries still suffer from complications due to otitis media. Meanwhile, COVID-19 has affected many diseases, with otitis media being one of the most strongly affected. This review aims to find out how COVID-19 has affected otitis media and its significance. A series of measures brought about by COVID-19, including emphasis on personal hygiene and social distancing, had many unexpected positive effects on otitis media. These can be broadly classified into four categories: first, the incidence of otitis media was drastically reduced. Second, antibiotic prescriptions for otitis media decreased. Third, the incidence of complications of otitis media was reduced. Fourth, the number of patients visiting the emergency room due to otitis media decreased. The quarantine measures put in place due to COVID-19 suppressed the onset and exacerbation of otitis media. This has great implications for the treatment and prevention of otitis media.

Do probiotics prevent otitis media in children prone to recurrent infections?

Do probiotics prevent otitis media in children prone to recurrent infections?

For healthy children under the age of three years, what are the effects of zinc supplements for preventing otitis media?

For healthy children under the age of three years, what are the effects of zinc supplements for preventing otitis media?

Can the PHiD-PC10 pneumococcal conjugate vaccine given in early infancy help prevent otitis media in children?

Can the PHiD-PC10 pneumococcal conjugate vaccine given in early infancy help prevent otitis media in children?

In vitro Inhibition of Clinical Isolates of Otitis Media Pathogens by the Probiotic Streptococcus salivarius BLIS K12.

Otitis media is a common childhood infection, frequently requiring antibiotics. With high rates of antibiotic prescribing and increasing antibiotic resistance, new strategies in otitis media prevention and treatment are needed. The aim of this study was to assess the in vitro inhibitory activity Streptococcus salivarius BLIS K12 against otitis media pathogens. Efficacy of the bacteriocin activity of S. salivarius BLIS K12 against the otitis media isolates was assessed using the deferred antagonism test. Overall, 48% of pathogenic isolates exhibited some growth inhibition by S. salivarius BLIS K12. S. salivarius BLIS K12 can inhibit the in vitro growth of the most common pathogens.

A collaborative approach towards prevention of otitis media in Aboriginal children

ABSTRACT Otitis media is very common in Aboriginal children in Western Australia and chronic ear disease causes major problems in speech and language development and education. Up until recently, most programmes dealing with the problem of OM have focused on clinical interventions rather than prevention. The Enhanced Prevention Working Group was established as part of the WA Child Ear Health Strategy (2017–2021). The Group has worked collaboratively to develop a set of recommendations for prevention of OM in Aboriginal children. These recommendations were informed by WA-based health promotion interventions initiated by Aboriginal Health Practitioners at a community level. This paper provides a historical perspective of the current situation and discusses each of the recommendations from Aboriginal Health Practitioners working within their community.

Role of Endoplasmic Reticulum Stress in Otitis Media.

Endoplasmic reticulum (ER) stress occurs in many inflammatory responses. Here, we investigated the role of ER stress and its associated apoptosis in otitis media (OM) to elucidate the mechanisms of OM and the signaling crosstalk between ER stress and other cell damage pathways, including inflammatory cytokines and apoptosis. We examined the expression of inflammatory cytokine- and ER stress-related genes by qRT-PCR, Western blotting, and immunohistochemistry (IHC) in the middle ear of C57BL/6J mice after challenge with peptidoglycan polysaccharide (PGPS), an agent inducing OM. We also evaluated the effect of the suppression of ER stress with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor. The study revealed the upregulation of ER stress- and apoptosis-related gene expression after the PGPS treatment, specifically ATF6, CHOP, BIP, caspase-12, and caspase-3. TUDCA treatment of PGPS-treated mice decreased OM; reduced the expression of CHOP, BIP, and caspase 3; and significantly decreased the proinflammatory gene expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). These results suggest that PGPS triggers ER stress and downstream proinflammatory gene expression in OM and that inhibition of ER stress alleviates OM. We propose that ER stress plays a critical role in inflammation and cell death, leading to the development of OM and points to ER stress inhibition as a potential therapeutic approach for the prevention of OM.

Panel 8: Vaccines and immunology

ObjectiveTo review and highlight significant advances made towards vaccine development and understanding of the immunology of otitis media (OM) since the 19th International Symposium on Recent Advances in Otitis Media (ISOM) in 2015, as well as identify future research directions and knowledge gaps. Data sourcesPubMed database, National Library of Medicine. Review methodsKey topics were assigned to each panel member for detailed review. Draft reviews were collated, circulated, and thoroughly discussed when the panel met at the 20th ISOM in June 2019. The final manuscript was prepared with input from all panel members. ConclusionsSince 2015 there have been a number of studies assessing the impact of licensed pneumococcal vaccines on OM. While these studies have confirmed that these vaccines are effective in preventing carriage and/or disease caused by vaccine serotypes, OM caused by non-vaccine serotype pneumococci and other otopathogens remains a significant health care burden globally. Development of multi-species vaccines is challenging but essential to reducing the global burden of OM. Influenza vaccination has been shown to prevent acute OM, and with novel vaccines against nontypeable Haemophilus influenzae (NTHi), Moraxella catarrhalis and Respiratory Syncytial Virus (RSV) in clinical trials, the potential to significantly prevent OM is within reach. Research into alternative vaccine delivery strategies has demonstrated the power of maternal and mucosal vaccination for OM prevention. Future OM vaccine trials must include molecular diagnostics of middle ear effusion, for detection of viruses and bacteria that are persisting in biofilms and to enable accurate assessment of vaccine impact on OM etiology. Understanding population differences in natural and vaccine-induced immune responses to otopathogens is also important for development of the most effective OM vaccines. Improved understanding of the interaction between otopathogens will also advance development of effective therapies and encourage the assessment of the indirect benefits of vaccination. Implications for practiceWhile NTHi and M. catarrhalis are the predominant otopathogens, funding opportunities to drive vaccine development for these species are limited due to a focus on prevention of childhood mortality rather than morbidity. Delivery of a comprehensive report on the high financial and social costs of OM, including the potential for OM vaccines to reduce antibiotic use and subsequent development of antimicrobial resistance (AMR), would likely assist in engaging stakeholders to recognize the value of prevention of OM and increase support for efforts on OM vaccine development. Vaccine trials with OM prevention as a clinical end-point are challenging, however a focus on developing assays that measure functional correlates of protection would facilitate OM vaccine development.

Can the PHiD-PC10 pneumococcal conjugate vaccine in early infancy help prevent otitis media in children?

Can the PHiD-PC10 pneumococcal conjugate vaccine in early infancy help prevent otitis media in children?

PCV7- and PCV10-Vaccinated Otitis-Prone Children in New Zealand Have Similar Pneumococcal and Haemophilus influenzae Densities in Their Nasopharynx and Middle Ear.

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.

Otitis media causes and management

Otitis media is a major cause of health care visits across the world, and its complications are significant causes of preventable hearing loss, predominantly in the developing world. They are a group of inflammatory and complex infective conditions that affect the middle ear. They have several different subtypes, and affects primarily children from 3 to 7 years of age. When not treated properly, they can lead to many complications including permanent hearing loss. In this article we will discuss updates on recent scientific developments in the field of otitis media clinical management and research. We conducted this review using a comprehensive search of MEDLINE, PubMed and EMBASE from January 1979 to March 2017. The following search terms were used: otitis media, middle ear infections, pediatric infections, causes of otitis media, treatment otitis media, and prevention of otitis media. Otitis media is one of the most common pathologies in the pediatric age group making it one the most common reasons of doctor visits. Fortunately, the management is simple and promising, but if neglected, can lead to several complications including permanent hearing loss. Newer studies are focusing on preventive measures such as pneumococcal vaccine, and in avoiding creation of resistant species of the common bacteria that cause the pathology.

Mapping Protective Regions on a Three-Dimensional Model of the Moraxella catarrhalis Vaccine Antigen Oligopeptide Permease A.

A vaccine against Moraxella catarrhalis would reduce tremendous morbidity, mortality, and financial burden by preventing otitis media in children and exacerbations of chronic obstructive pulmonary disease (COPD) in adults. Oligopeptide permease A (OppA) is a candidate vaccine antigen that is (i) a nutritional virulence factor expressed on the bacterial cell surface during infection, (ii) widely conserved among strains, (iii) highly immunogenic, and (iv) a protective antigen based on its capacity to induce protective responses in immunized animals. In the present study, we show that the antibodies to OppA following vaccination mediate accelerated clearance in animals after pulmonary challenge. To identify regions of OppA that bind protective antibodies, truncated constructs of OppA were engineered and studied to map regions of OppA with surface-accessible epitopes that bind high-avidity antibodies following vaccination. Protective epitopes were located in the N and C termini of the protein. Immunization of mice with constructs corresponding to these regions (T5 and T8) induced protective responses. Studies of overlapping peptide libraries of constructs T5 and T8 with OppA immune serum identified two discrete regions on each construct. These potentially protective regions were mapped on a three-dimensional computational model of OppA, where regions with solvent-accessible amino acids were identified as three potentially protective epitopes. In all, these studies revealed two regions with three specific epitopes in OppA that induce potentially protective antibody responses following vaccination. Detection of antibodies to these regions could serve to guide vaccine formulation and as a diagnostic tool for monitoring development of protective responses during clinical trials.

Knowledge, Attitude and Practices towards Otitis Media in Saudi Arabia Community

Background: otitis media (OM) and its complications resulted in high prevalence of hearing loss and increasing the rates of health care visits with special regard to the developing countries. Aim of the work: this study aimed toevaluate the knowledge, attitude and practice (KAP) toward otitis media among adult teachers in Kingdom of Saudi Arabia (KSA). Patients and Methods: this isa cross sectional questionnaire based study and it was conducted among a random sample of teachers in KSA from March to June 2017. All the teachers were inter viewed in their schools during the break period and answered the questionnaire that was comprised of four objects including the socio-demographics of subjects, knowledge, attitude and practice pattern of participants toward otitis media. Results: the overall knowledge about the risk factors, disease prevention and serous type was improper. Also, a poor level of attitude and practice pattern was found among most of the subjects. The overall KAP of the teachers was poor among 58.8%, while 41.2% showed adequate KAP about Otitis media. The good KAP showed a significant association with higher economic level, while other variables showed no association with KAP including age, gender and cigarette smoking. Conclusion: the suboptimal knowledge about otitis media would result in poor attitude and practice pattern which increased the prevalence and complications of otitis media. The economic level was associated with OM, thus it was considered a vital factor in prevention of otitis media.

Panel 5: Immunology.

Objective To perform a state-of-the-art review of the literature from January 2012 through May 2015 on studies that advanced our knowledge of the innate and adaptive immunology related to otitis media. This review also proposes future directions for research in this area. Data Sources PubMed database of the National Library of Medicine. Review Methods Three subpanels comprising experts in the field focused on sections relevant to cytokines, innate immunity, and adaptive immunity. The review focused on animal, cell line, and human studies and was critical in relation to the recommendations from the previous publication and for determination of the proposed goals and priorities. The panel met at the 18th International Symposium on Recent Advances in Otitis Media in June 2015 to consolidate its prior search results and discuss, plan, and refine the review. The panel approved the final draft. Conclusion From 2012 to 2014, tremendous progresses in immunology of otitis media were established-especially in the areas of innate immunity associated with the pathogenesis of otitis media. Implications for Practice The advances of the past 4 years formed the basis for a series of short- and long-term research goals in an effort to guide the field. Accomplishing these goals will provide opportunities for the development of novel interventions, including new ways to better treat and prevent otitis media, especially for recurrent otitis media.

Preliminary results of a novel quorum sensing inhibitor against pneumococcal infection and biofilm formation with special interest to otitis media and cochlear implantation

The purpose of the study is to assess the effect of a novel quorum sensing inhibitor (QSI), coded as 'yd 47', against otitis media and biofilm formation on Cochlear implants (CIs). Small pieces cut from cochlear implant were implanted under the skin in the retroauricular area on both sides of four guinea pigs. The implant pieces in the study and control sides were implanted in Streptococcus pneumoniae strain solution and saline, respectively. The right and left middle ears were also instilled with a solution containing pneumococci and saline, respectively. The animals were only given an intraperitoneal 'yd 47' twice daily for three months to be assessed later with electron microscopy. Clinical examination with palpation, inspection and otoscopy did not reveal any sign of implant infection or otitis media. In the study and control implant materials, soft tissues around the implant and tympanic membranes, there was no biofilm formation by pneumococci. Contamination by various cells and some rod-shaped bacteria (not diplococcic) were seen in some of the materials. In conclusion, the novel QSI seems promising in the prevention of otitis media and biofilm formation on CIs by pneumococci.

Panel 6: Vaccines

To update progress on the effectiveness of vaccine for prevention of acute otitis media (AOM) and identification of promising candidate antigens against Streptococcus pneumoniae, nontypeable Haemophilus influenzae, and Moraxella catarrhalis. Literature searches were performed in OvidSP and PubMed restricted to articles published between June 2007 and September 2011. Search terms included otitis media, vaccines, vaccine antigens, and each of the otitis pathogens and candidate antigens identified in the ninth conference report. The current report provides further evidence for the effectiveness of pneumococcal conjugate vaccines (PCVs) in the prevention of otitis media. Observational studies demonstrate a greater decline in AOM episodes than reported in clinical efficacy trials. Unmet challenges include extending protection to additional serotypes and additional pathogens, the need to prevent early episodes, the development of correlates of protection for protein antigens, and the need to define where an otitis media vaccine strategy fits with priorities for child health. Acute otitis media continues to be a burden on children and families, especially those who suffer from frequent recurrences. The 7-valent PCV (PCV7) has reduced the burden of disease as well as shifted the pneumococcal serotypes and the distribution of otopathogens currently reported in children with AOM. Antibiotic resistance remains an ongoing challenge. Multiple candidate antigens have demonstrated the necessary requirements of conservation, surface exposure, immunogenicity, and protection in animal models. Further research on the role of each antigen in pathogenesis, in the development of correlates of protection in animal models, and in new adjuvants to elicit responses in the youngest infants is likely to be productive and permit more antigens to move into human clinical trials.

Panel 5: Microbiology and Immunology Panel

The objective is to perform a comprehensive review of the literature from January 2007 through June 2011 on the virology, bacteriology, and immunology related to otitis media. PubMed database of the National Library of Medicine. Three subpanels with co-chairs comprising experts in the virology, bacteriology, and immunology of otitis media were formed. Each of the panels reviewed the literature in their respective fields and wrote draft reviews. The reviews were shared with all panel members, and a second draft was created. The entire panel met at the 10th International Symposium on Recent Advances in Otitis Media in June 2011 and discussed the review and refined the content further. A final draft was created, circulated, and approved by the panel. Excellent progress has been made in the past 4 years in advancing an understanding of the microbiology and immunology of otitis media. Advances include laboratory-based basic studies, cell-based assays, work in animal models, and clinical studies. The advances of the past 4 years formed the basis of a series of short-term and long-term research goals in an effort to guide the field. Accomplishing these goals will provide opportunities for the development of novel interventions, including new ways to better treat and prevent otitis media.