Prevention of early episodes of otitis media by pneumococcal vaccines might reduce progression to complex disease

Dagan, Ron; Pelton, Stephen I.; Bakaletz, Lauren O.; Cohen, Robert

doi:10.1016/s1473-3099(15)00549-6

Cited by 116 publications

(94 citation statements)

References 133 publications

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“…Nonetheless, this procedure is the least invasive method to ensure that all animals enter the study colonized with NTHI. In the clinical setting, however, complete eradication of NTHI from the nasopharynx is not necessarily a desired outcome as it could provide the opportunity for replacement by a more pathogenic organism, as is of concern following licensure and broad use of current pneumococcal capsular conjugate vaccines (13,42). Therefore, reduction of the nasopharyngeal NTHI burden to a colonizing level that is tolerated by the host immune system is more desirable.…”

Section: Discussionmentioning

confidence: 99%

“…Immunization to prevent the onset of OM is the preferred goal, with a tremendous associated potential to diminish dependence on the aforementioned therapeutic strategies and their associated risks, such as development of antibiotic resistance, for which treatment of OM is considered a major driving force worldwide (12). Importantly, immunization against the first incidence of OM is projected to limit subsequent episodes and their associated sequelae (13).…”

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confidence: 99%

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Transcutaneous Immunization with a Band-Aid Prevents Experimental Otitis Media in a Polymicrobial Model

Novotny

Clements

Goodman

2017

Clin Vaccine Immunol

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Otitis media (OM) is a common pediatric disease, and nontypeable Haemophilus influenzae (NTHI) is the predominant pathogen in chronic OM, recurrent OM, and OM associated with treatment failure. OM is also a polymicrobial disease, wherein an upper respiratory tract viral infection predisposes to ascension of NTHI from the nasopharynx, the site of colonization, to the normally sterile middle ear, resulting in disease. Using a clinically relevant viral-bacterial coinfection model of NTHIinduced OM, we performed transcutaneous immunization (TCI) via a band-aid delivery system to administer each of three promising NTHI vaccine candidates derived from bacterial adhesive proteins and biofilm mediators: recombinant soluble PilA (rsPilA), chimV4, and integration host factor. Each immunogen was admixed with the adjuvant LT(R192G/L211A), a double mutant of Escherichia coli heat-labile enterotoxin, and assessed for relative ability to prevent the onset of experimental OM. For each cohort, the presence of circulating immunogen-specific antibody-secreting cells and serum antibody was confirmed prior to intranasal NTHI challenge. After bacterial challenge, blinded video otoscopy and tympanometry revealed a significant reduction in the proportion of animals with signs of OM compared to levels in animals receiving adjuvant only, with an overall vaccine efficacy of 64 to 77%. These data are the first to demonstrate the efficacy afforded by TCI with a band-aid vaccine delivery system in a clinically relevant polymicrobial model of OM. The simplicity of TCI with a band-aid and the significant efficacy observed here hold great promise for reducing the global burden of OM in the pediatric population.KEYWORDS IHF, biofilms, chimV4, nontypeable Haemophilus influenzae, rsPilA T ranscutaneous immunization (TCI) is a noninvasive strategy to induce an immune response by engagement of the numerous antigen-presenting cells within the dermis and epidermis (1, 2). This regime results in both systemic and mucosal immune responses, important outcomes as the mucosae serve as critical defensive barriers to antigenic insult and bacterial disease (3, 4). TCI is needle free, which is expected to aid in patient compliance, to limit risks associated with both administration and waste, and to reduce costs related to formulation and delivery (5). Thus, TCI promises to facilitate greater vaccine distribution.Otitis media (OM) is a disease of the uppermost respiratory tract mucosa and is one of the most common bacterial diseases of childhood due to a multifactorial combination of anatomical, immunological, and environmental factors (6). OM is also a polymicrobial disease caused by one or more of several bacterial species that typically reside within the human nasopharynx. The ability of nontypeable Haemophilus influenzae (NTHI), Streptococcus pneumoniae, and Moraxella catarrhalis to ascend from the nasopharynx through the Eustachian tube and gain access to the normally sterile middle ear space is facilitated by perturbation of the physical and inn...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Transcutaneous Immunization with a Band-Aid Prevents Experimental Otitis Media in a Polymicrobial Model

Novotny

Clements

Goodman

2017

Clin Vaccine Immunol

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“…Collectively, Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi) cause most OM cases [3]. Coinfections with these 2 pathogens are associated with more-severe disease than either pathogen typically causes alone; in comparison to single-species infections, mixed pneumococci-NTHi OM is more likely to present bilaterally, incur treatment failure, and recur or become chronic [4,5]. However, limited understanding of the biological mediators of pneumococci-NTHi interaction currently hampers the clinical management and prevention of coinfections.…”

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confidence: 99%

Density, Serotype Diversity, and Fitness ofStreptococcus pneumoniaein Upper Respiratory Tract Cocolonization With NontypeableHaemophilus influenzae

et al. 2016

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Background. Coinfections by Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi) are frequently implicated in complex otitis media. Whereas upper respiratory tract carriage precedes disease for both pathogens, interactions between species in cocolonized hosts are poorly understood. We compared colonization densities and the diversity and fitness of pneumococcal serotypes in single-species and mixed-species colonization.Methods. We analyzed nasopharyngeal pneumococcal carriage and nasopharyngeal and oropharyngeal NTHi carriage in 13 541 samples collected over 6909 study visits from 769 children 2-30 months old in a 7-valent pneumococcal conjugate vaccine dosing trial. We measured density associations between the species and compared pneumococcal serotype diversity during and in the absence of NTHi colonization. We used logistic regression to quantify associations between NTHi colonization and previously published pneumococcal serotype factors related to fitness.Results. Densities of the 2 species were positively associated when they co-occur in the nasopharynx. NTHi colonization was associated with reduced pneumococcal serotype diversity among children 2-18 months old and was more prevalent among children carrying pneumococcal serotypes with greater capsular thickness, neutrophil resistance, and metabolic efficiency.Conclusions. Pneumococcal-NTHi cocolonization is associated with an elevated density of both species and with reduced diversity and increased fitness of pneumococcal serotypes. NTHi colonization may create a selective environment favoring pneumococci with immune-evasive phenotypes.

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“…First episode of bacterial infection with invasive strains (like invasive strains of Streptococcus pneumonia) can lead to mucosal changes which make the ear more susceptible to acquire the disease by less virulent strains [21]. In cases of simultaneous infection with pathogenic viruses and bacteria, antibiotic responsiveness appears to be inferior to that of children with only bacterial infection, and microbiologic failure can occur despite clear in vitro sensitivity to the antibiotic used.…”

Section: Streptococcus Pneumoniae Haemophilus Influenzae Andmentioning

confidence: 99%

“…PCV7 has been shown to decrease OM rates and tympanostomy tube placement for recurrent diseases [13]; in fact, this vaccine is more effective if given during infancy [6]. It can prevent the early episodes of the disease and prevent the mucosal changes, by this it makes the ear less susceptible to infection by other S pneumoniae serotypes not covered by PCV [21]. Some studies found live attenuated influenza vaccine (LAIV) has decreased the incidence of AOM by 12.4% if given between 6-71 months of age [7], but others found influenza vaccine is not effective in preventing AOM [6].…”

Section: Prevention Of Aommentioning

confidence: 99%

Acute Otitis Media- An Update

Shawabkeh¹,

Haidar²,

Larem³

et al. 2017

JOENTR

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Objective: To review the literature about Acute otitis media (AOM).Introduction: AOM is a common condition with an incidence of 10.8/ 100 people per year; it is more common in pediatric age group and tends to occur more in male patients. It is considered the main cause of prescribing antibiotics in pediatrics. Physicians tend to over diagnose this disease leading to an unnecessary antibiotics prescription which exposes the child to an unwanted side effects mainly diarrhea. USA spends $2-3.5 billion per year for the treatment of AOM. Taking these points in our mind, it is important to know how to accurately diagnose this condition and how to treat it and what is the pathophysiology that underlies that disease, all of which are discussed in details in this review article.Methodology: a comprehensive review of the literature about AOM.Results: AOM is a result of different host, environmental, microbiological and genetic factors. It is highly related to upper respiratory infection and the disease is thought to be viral in origin with bacterial superinfection happens later on. Respiratory syncytial virus (RSV) has the best link with AOM. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are still the most important pathogens. It is a symptomatic disease; Ear pain is the most important symptom, and bulging of the tympanic membrane is the most important sign that can lead to diagnosis. The American Academy of Pediatrics has put certain guidelines for the treatment of AOM. Prevetive measures play an important role in decreasing of its incidence. Conclusion:AOM has an impact on the child, family, and the community as a whole, in term of health and costs.

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Prevention of early episodes of otitis media by pneumococcal vaccines might reduce progression to complex disease

Cited by 116 publications

References 133 publications

Transcutaneous Immunization with a Band-Aid Prevents Experimental Otitis Media in a Polymicrobial Model

Transcutaneous Immunization with a Band-Aid Prevents Experimental Otitis Media in a Polymicrobial Model

Density, Serotype Diversity, and Fitness ofStreptococcus pneumoniaein Upper Respiratory Tract Cocolonization With NontypeableHaemophilus influenzae

Acute Otitis Media- An Update

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