Viral-Bacterial Interactions and Risk of Acute Otitis Media Complicating Upper Respiratory Tract Infection

Pettigrew, Melinda M.; Gent, Janneane F.; Pyles, Richard B.; Miller, Aaron L.; Nokso-Koivisto, Johanna; Chonmaitree, Tasnee

doi:10.1128/jcm.01186-11

Cited by 137 publications

(140 citation statements)

References 37 publications

(68 reference statements)

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“…Preceding or concurrent viral upper respiratory tract infection is typical in AOM (10), and interactions of viruses and bacteria in the nasopharynx may play an important role in the pathogenesis of AOM (10)(11)(12). In the era of increasing antimicrobial resistance, precise information concerning MEF pathogens may be beneficial for empirical antibiotic therapy, and therefore PCR technique applied to samples from this primarily sterile site may help to achieve more-accurate bacterial etiologic diagnosis of AOM.…”

Section: B Acterial Culture Of Middle Ear Fluid (Mef) Has Been the Stmentioning

confidence: 99%

Moraxella catarrhalis Might Be More Common than Expected in Acute Otitis Media in Young Finnish Children

et al. 2016

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f According to studies based on bacterial cultures of middle ear fluids, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis have been the most common pathogens in acute otitis media. However, bacterial culture can be affected by reduced viability or suboptimal growth of bacteria. PCR detects bacterial DNA from samples with greater sensitivity than culture. In the present study, we analyzed the middle ear pathogens with both conventional culture and semiquantitative real-time PCR in 90 middle ear fluid samples obtained from children aged 5 to 42 months during acute otitis media episodes. Samples were tested for the presence of S. pneumoniae, H. influenzae, M. catarrhalis, Alloiococcus otitidis, Staphylococcus aureus, and Pseudomonas aeruginosa. One or more bacterial pathogens were detected in 42 (47%) samples with culture and in 69 (77%) samples with PCR. According to PCR analysis, M. catarrhalis results were positive in 42 (47%) samples, H. influenzae in 30 (33%), S. pneumoniae in 27 (30%), A. otitidis in 6 (6.7%), S. aureus in 5 (5.6%), and P. aeruginosa in 1 (1.1%). Multibacterial etiology was seen in 34 (38%) samples, and M. catarrhalis was detected in most (85%) of those cases. Fifteen signals for M. catarrhalis were strong, suggesting a highly probable etiological role of the pathogen. In conclusion, even though M. catarrhalis is often a part of mixed flora in acute otitis media, a considerable proportion of cases may be primarily attributable to this pathogen. B acterial culture of middle ear fluid (MEF) has been the standard for etiologic diagnosis of acute otitis media (AOM).Streptococcus pneumoniae is considered the most common bacterial pathogen, followed by Haemophilus influenzae and Moraxella catarrhalis (1-3). About 44% to 75% of MEF samples are positive for bacterial pathogens in conventional culture (2, 4). However, the proportions of culture-positive MEF samples decrease in patients with recurrent AOM (5) and in patients with treatment failure (6). Host defense mechanisms and previous antibiotic treatments may directly contribute to diminished survival of the pathogens in clinical samples and diminish the likelihood of detection of bacteria by culture. In addition, the presence of bacterial biofilms has been correlated with negative bacterial cultures (7) and some of the bacterial pathogens, e.g., Alloiococcus otitidis, grow poorly in conventional cultures (8).Virus infections have also been considered causative agents in AOM (2, 9). Preceding or concurrent viral upper respiratory tract infection is typical in AOM (10), and interactions of viruses and bacteria in the nasopharynx may play an important role in the pathogenesis of AOM (10-12). In the era of increasing antimicrobial resistance, precise information concerning MEF pathogens may be beneficial for empirical antibiotic therapy, and therefore PCR technique applied to samples from this primarily sterile site may help to achieve more-accurate bacterial etiologic diagnosis of AOM.Previous studies of AOM in Finnish pop...

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Section: B Acterial Culture Of Middle Ear Fluid (Mef) Has Been the Stmentioning

confidence: 99%

Moraxella catarrhalis Might Be More Common than Expected in Acute Otitis Media in Young Finnish Children

et al. 2016

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“…4, we explored protection in an in vivo model that mimics the clinical progression of pneumococcal disease onset. Epidemiological evidence suggests that pneumococcal disease is strongly associated with a concomitant infection with upper respiratory tract viruses, such as influenza A virus (IAV) (40,41). Mice were infected intranasally with IAV 48 h after colonization with S. pneumoniae, a protocol designed to mediate the release of virulent pneumococci from colonizing biofilms for subsequent dissemination to the lungs and blood.…”

Section: Directed Response and Extended Coverage Provided By Combinedmentioning

confidence: 99%

Directed vaccination against pneumococcal disease

Hill

Beitelshees

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Immunization strategies against commensal bacterial pathogens have long focused on eradicating asymptomatic carriage as well as disease, resulting in changes in the colonizing microflora with unknown future consequences. Additionally, current vaccines are not easily adaptable to sequence diversity and immune evasion. Here, we present a “smart” vaccine that leverages our current understanding of disease transition from bacterial carriage to infection with the pneumococcus serving as a model organism. Using conserved surface proteins highly expressed during virulent transition, the vaccine mounts an immune response specifically against disease-causing bacterial populations without affecting carriage. Aided by a delivery technology capable of multivalent surface display, which can be adapted easily to a changing clinical picture, results include complete protection against the development of pneumonia and sepsis during animal challenge experiments with multiple, highly variable, and clinically relevant pneumococcal isolates. The approach thus offers a unique and dynamic treatment option readily adaptable to other commensal pathogens.

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“…Other studies have revealed that PspA, when employed as an immunogen in mouse models, protects against primary pneumococcal infection (20-23) and against pneumococcal challenge subsequent to a viral infection (24,25). The vast majority of these investigations, however, examined the protection offered by PspA immunization against invasive disease caused by challenge with planktonic, broth-grown pneumococci, which do not represent either the biofilm community of S. pneumoniae normally found residing in the nasopharynx prior to contact with IAV or the bacteria released from biofilms in response to virus infection (4). Thus, the capacity of PspA, when used as an immunogen, to protect against invasive disease produced by pneumococci that are residing in a commensal nasopharyngeal biofilm subsequent to infection with IAV and its protective role against pneumonia and otitis media have not been adequately evaluated.…”

mentioning

confidence: 99%

“…One of the most important of these biological pairings is the interaction between influenza A virus (IAV) and Streptococcus pneumoniae (the pneumococcus) (2). In children, the most frequent complication following IAV infections is acute otitis media, of which S. pneumoniae is one of the most common etiologic agents (3)(4)(5). S. pneumoniae is also the most frequently identified pathogen in hospitalized children and adults who present with primary or secondary community-acquired pneumonia (6).…”

mentioning

confidence: 99%

Novel Strategy To Protect against Influenza Virus-Induced Pneumococcal Disease without Interfering with Commensal Colonization

Greene

Marks

et al. 2016

Infect Immun

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dStreptococcus pneumoniae commonly inhabits the nasopharynx as a member of the commensal biofilm. Infection with respiratory viruses, such as influenza A virus, induces commensal S. pneumoniae to disseminate beyond the nasopharynx and to elicit severe infections of the middle ears, lungs, and blood that are associated with high rates of morbidity and mortality. Current preventive strategies, including the polysaccharide conjugate vaccines, aim to eliminate asymptomatic carriage with vaccinetype pneumococci. However, this has resulted in serotype replacement with, so far, less fit pneumococcal strains, which has changed the nasopharyngeal flora, opening the niche for entry of other virulent pathogens (e.g., Streptococcus pyogenes, Staphylococcus aureus, and potentially Haemophilus influenzae). The long-term effects of these changes are unknown. Here, we present an attractive, alternative preventive approach where we subvert virus-induced pneumococcal disease without interfering with commensal colonization, thus specifically targeting disease-causing organisms. In that regard, pneumococcal surface protein A (PspA), a major surface protein of pneumococci, is a promising vaccine target. Intradermal (i.d.) immunization of mice with recombinant PspA in combination with LT-IIb(T13I), a novel i.d. adjuvant of the type II heat-labile enterotoxin family, elicited strong systemic PspA-specific IgG responses without inducing mucosal anti-PspA IgA responses. This response protected mice from otitis media, pneumonia, and septicemia and averted the cytokine storm associated with septic infection but had no effect on asymptomatic colonization. Our results firmly demonstrated that this immunization strategy against virally induced pneumococcal disease can be conferred without disturbing the desirable preexisting commensal colonization of the nasopharynx.

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Viral-Bacterial Interactions and Risk of Acute Otitis Media Complicating Upper Respiratory Tract Infection

Cited by 137 publications

References 37 publications

Moraxella catarrhalis Might Be More Common than Expected in Acute Otitis Media in Young Finnish Children

Moraxella catarrhalis Might Be More Common than Expected in Acute Otitis Media in Young Finnish Children

Directed vaccination against pneumococcal disease

Novel Strategy To Protect against Influenza Virus-Induced Pneumococcal Disease without Interfering with Commensal Colonization

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