Identification of Respiratory Virus Antigens in Middle Ear Fluids of Children with Acute Otitis Media

Sarkkinen, Hannu; Ruuskanen, Olli; Meurman, Olli; Puhakka, H; Virolainen, Erkki; Eskola, J.

doi:10.1093/infdis/151.3.444

Cited by 89 publications

(33 citation statements)

References 14 publications

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“…In one study, RSV antigens were found in the middle ear fluid of 15% of children with AOM, and in 7% RSV was the sole pathogen found. 16 Studies in both hospitalized patients 17 and in a day-care setting 18 have suggested that the incidence of AOM is higher in RSV infection than it is in infection with other respiratory viruses (especially parainfluenza 1 through 3 and rhinovirus). Our outpatient data do not reveal striking relative differences among viruses in viral-associated AOM.…”

Section: Discussionmentioning

confidence: 99%

Twenty Years of Outpatient Respiratory Syncytial Virus Infection: A Framework for Vaccine Efficacy Trials

et al. 1997

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ABSTRACT. Background. Respiratory syncytial virus (RSV) is the most important viral respiratory pathogen of infancy and childhood. Much has been written about inpatients with severe disease. Inpatients, however, represent only a minority of RSV-infected children. We studied the characteristics of symptomatic outpatient RSV infection in healthy children to gain a better understanding of RSV disease and to provide a background for the testing of intervention strategies in children without high-risk conditions.Methods. A total of 1113 children were followed during 20 consecutive RSV seasons. Signs and symptoms of respiratory infection were monitored. Cultures were obtained for febrile upper respiratory infection, acute otitis media, and lower respiratory infection (LRI). Rates of febrile upper respiratory infection, acute otitis media, LRI, and hospitalization were calculated. Given those rates, numbers of children needed to demonstrate efficacy of a vaccine product were calculated.Results. Mild disease from RSV infection lacked some of the classic features of RSV infection seen in hospitalized children. Involvement of the lower respiratory tract was, however, noted to be much higher in RSV infection than it was in infection with other viral respiratory pathogens. LRI was, therefore, considered the best candidate endpoint for vaccine trials. A product with 60% efficacy could be proven, with a power of 0.8, to be efficacious with as few as 1500 infants.Conclusions. RSV infection is common and often involves the lower respiratory tract, even in outpatients. Our 20-year study of RSV infection provides a basis for calculation of sample sizes to be used in trials of vaccine candidates. Pediatrics 1997;99(2). URL: http://www. pediatrics.org/cgi/content/full/99/2/e7; respiratory syncytial virus, outpatient, epidemiology, vaccine, bronchiolitis.ABBREVIATIONS. RSV, respiratory syncytial virus; URI, upper respiratory infection; LRI, lower respiratory infection; AOM, acute otitis media.Respiratory syncytial virus (RSV) is widely recognized as the most important viral respiratory pathogen of infancy and childhood.1 It causes distinct winter epidemics in a predictable fashion each year 2 and leads to frequent hospitalizations for bronchiolitis and pneumonia. Newborns and young infants are particularly prone to developing more severe lower respiratory tract disease. 3More than 50% of infants acquire the infection during their first RSV season, 4 and it is thought that most primary RSV infections are symptomatic.4 By the time they have lived through two RSV seasons, more than 90% of children demonstrate serologic evidence of infection. 4 Accordingly, the development of a vaccine for RSV has received a high priority.5 Many vaccine products are currently undergoing animal studies and early clinical trials. A thorough understanding of the clinical syndrome of RSV infection, including attack rates and symptom frequency in an otherwise healthy outpatient population, will be critical to the design of such trials.Although many studies o...

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Section: Discussionmentioning

confidence: 99%

Twenty Years of Outpatient Respiratory Syncytial Virus Infection: A Framework for Vaccine Efficacy Trials

et al. 1997

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“…Paramyxoviruses, which include Sendai virus, Newcastle disease virus (NDV), respiratory syncytial virus, measles virus, and mumps virus, cause disease in many species (10,29,46,55,65). Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus and emerging pathogen of this family.…”

mentioning

confidence: 99%

“…Editing in NiV produces a V protein and a W protein from the P gene (3,12,24,50,57). NiV V and W proteins have been shown to interact with signal transducer and activator of transcription 1 (STAT1) through the N-terminal domain shared with P, sequestering STATs in high-molecular-weight complexes (16,54,55). While NiV W and V proteins share identical N termini, the unique C terminus of NiV W contains a nuclear localization signal that compartmentalizes the effects of its interferon antagonism (56).…”

mentioning

confidence: 99%

Novel Nipah Virus Immune-Antagonism Strategy Revealed by Experimental and Computational Study

Seto

Qiao

Guenzel

et al. 2010

J Virol

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Nipah virus is an emerging pathogen that causes severe disease in humans. It expresses several antagonist proteins that subvert the immune response and that may contribute to its pathogenicity. Studies of its biology are difficult due to its high pathogenicity and requirement for biosafety level 4 containment. We integrated experimental and computational methods to elucidate the effects of Nipah virus immune antagonists. Individual Nipah virus immune antagonists (phosphoprotein and V and W proteins) were expressed from recombinant Newcastle disease viruses, and the responses of infected human monocyte-derived dendritic cells were determined. We developed an ordinary differential equation model of the infectious process that that produced results with a high degree of correlation with these experimental results. In order to simulate the effects of wild-type virus, the model was extended to incorporate published experimental data on the time trajectories of immune-antagonist production. These data showed that the RNA-editing mechanism utilized by the wild-type Nipah virus to produce immune antagonists leads to a delay in the production of the most effective immune antagonists, V and W. Model simulations indicated that this delay caused a disconnection between attenuation of the antiviral response and suppression of inflammation. While the antiviral cytokines were efficiently suppressed at early time points, some early inflammatory cytokine production occurred, which would be expected to increase vascular permeability and promote virus spread and pathogenesis. These results suggest that Nipah virus has evolved a unique immune-antagonist strategy that benefits from controlled expression of multiple antagonist proteins with various potencies.

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“…44,45 Among the various mechanisms by which UAI may predispose patients to RAOM and COME, are inflammation and harm to the mucocilliary movement of the epithelium that lines the auditive tube, which has been experimentally 46 and clinically demonstrated. 47 …”

Section: Upper Airway Infectionsmentioning

confidence: 99%

Fatores de risco para otite média aguda recorrente: onde podemos intervir? - uma revisão sistemática da literatura

Neto

Hemb²,

Silva³

2006

J. Pediatr. (Rio J.)

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Objective: Review evidence about modifiable risk factors for recurrent acute otitis media.Source of data: MEDLINE with no language restriction, from January 1966 to July 2005, using descriptors acute otitis media/risk factors. Two hundred and fifty-seven articles were obtained. These included randomized clinical trials, cohorts, case-control and cross-sectional studies that contained analyses of modifiable risk factors for the development of recurrent acute otitis media as the main objective and with samples of individuals up to the age of 18 years. Except when relevant, the following were excluded: non-systematic reviews, reports of cases, series of cases, and medical society guidelines. Summary of data:Nine risk factors linked to the host and eight linked to the environment were identified. Of the first group, allergy, craniofacial abnormalities, gastroesophageal reflux and the presence of adenoids were classified as modifiable. In the second category, upper airway infections, day care center attendance, presence of siblings/family size, passive smoking, breastfeeding and use of pacifiers were included. Afterwards, the risk factors were classified in accordance with levels of evidence. Conclusions:The risk factors established for recurrent acute otitis media and capable of being modified were the use of pacifiers and care in daycare centers. The probable risk factors were privation of mothers milk, presence of siblings, craniofacial abnormalities, passive smoking and presence of adenoids. No modifiable factor was classified as unlikely. Among those that need further study are allergy, gastroesophageal reflux and passive smoking during gestation. J Pediatr (Rio J)

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Identification of Respiratory Virus Antigens in Middle Ear Fluids of Children with Acute Otitis Media

Cited by 89 publications

References 14 publications

Twenty Years of Outpatient Respiratory Syncytial Virus Infection: A Framework for Vaccine Efficacy Trials

Twenty Years of Outpatient Respiratory Syncytial Virus Infection: A Framework for Vaccine Efficacy Trials

Novel Nipah Virus Immune-Antagonism Strategy Revealed by Experimental and Computational Study

Fatores de risco para otite média aguda recorrente: onde podemos intervir? - uma revisão sistemática da literatura

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