Tasnee Chonmaitree

Prevalence of Various Respiratory Viruses in the Middle Ear during Acute Otitis Media

BACKGROUND Vaccines against respiratory viruses may be able to reduce the frequency of acute otitis media. Although the role of respiratory viruses in the pathogenesis of acute otitis media is well established, the relative importance of various viruses is unknown. METHODS We determined the prevalence of various respiratory viruses in the middle-ear fluid in 456 children (age, two months to seven years) with acute otitis media. At enrollment and after two to five days of antibiotic therapy, specimens of middle-ear fluid and nasal-wash specimens were obtained for viral and bacterial cultures and the detection of viral antigens. The viral cause of the infections was also assessed by serologic studies of serum samples obtained during the acute illness and convalescence. RESULTS A specific viral cause of the respiratory tract infections was identified in 186 of the 456 children (41 percent). Respiratory syncytial virus was the most common virus identified in middle-ear fluid: it was detected in the middle-ear fluid of 48 of the 65 children (74 percent) infected by this virus (P< or =0.04 for the comparison with any other virus). Parainfluenza viruses (15 of 29 children [52 percent]) and influenzaviruses (10 of 24 children [42 percent]) were detected in the middle-ear fluid significantly more often than enteroviruses (3 of 27 children [11 percent]) or adenoviruses (1 of 23 children [4 percent]) (P< or =0.01 for all comparisons). CONCLUSION Respiratory syncytial virus is the principal virus invading the middle ear during acute otitis media. An effective vaccine against upper respiratory tract infections caused by respiratory syncytial virus may reduce the incidence of acute otitis media in children.

Viral upper respiratory tract infection and otitis media complication in young children.

Abstract Background. The common cold or upper respiratory infection (URI) is highly prevalent among young children and often results in otitis media (OM). The incidence and characteristics of OM complicating URI due to specific viruses have not been well studied. Methods. We performed a prospective, longitudinal cohort study of 294 healthy children (age range, 6 months to 3 years). Each child was observed for 1 year to assess the occurrence of URI, acute OM (AOM), and OM with effusion (OME) complicating URI due to specific viruses. Results. We documented 1295 URI episodes (5.06 episodes per child-year) and 440 AOM episodes (1.72 episodes per child-year). Virus studies were performed for 864 URI episodes; 63% were virus positive. Rhinovirus and adenovirus were most frequently detected during URI. The overall incidence of OM that complicated URI was 61%, including a 37% incidence of AOM and a 24% incidence of OME. Young age was the most important predictor of AOM that complicated URI. AOM occurred in approximately one-half of children with URI due to adenovirus, respiratory syncytial virus, or coronavirus and in approximately one-third of those with URI due to influenza virus, parainfluenza virus, enterovirus, or rhinovirus. Conclusions. More than 60% of episodes of symptomatic URI among young children were complicated by AOM and/or OME. Young age and specific virus types were predictors of URI complicated by AOM. For young children, the strategy to prevent OM should involve prevention of viral URI. The strategy may be more effective if the priority is given to development of means to prevent URI associated with adenovirus and respiratory syncytial virus.

Importance of Respiratory Viruses in Acute Otitis Media

SUMMARY Acute otitis media is usually considered a simple bacterial infection that is treated with antibiotics. However, ample evidence derived from studies ranging from animal experiments to extensive clinical trials supports a crucial role for respiratory viruses in the etiology and pathogenesis of acute otitis media. Viral infection of the upper respiratory mucosa initiates the whole cascade of events that finally leads to the development of acute otitis media as a complication. The pathogenesis of acute otitis media involves a complex interplay between viruses, bacteria, and the host’s inflammatory response. In a substantial number of children, viruses can be found in the middle-ear fluid either alone or together with bacteria, and recent studies indicate that at least some viruses actively invade the middle ear. Viruses appear to enhance the inflammatory process in the middle ear, and they may significantly impair the resolution of otitis media. Prevention of the predisposing viral infection by vaccination against the major viruses would probably be the most effective way to prevent acute otitis media. Alternatively, early treatment of the viral infection with specific antiviral agents would also be effective in reducing the occurrence of acute otitis media.

Effect of viral respiratory tract infection on outcome of acute otitis media

We prospectively studied 271 infants and children (2 months to 7 years of age) with acute otitis media (AOM) for viral and bacterial causes, outcome at the end of therapy, and frequency of recurrence within 1 month. Comprehensive virologic methods, including viral antigen detection, cell culture, and serologic studies, were used to diagnose viral infection of the respiratory tract, middle ear, or both. Evidence of viral infection was found in 46% (124/271) of patients with AOM. Sixty-six patients (24%) had virus or viral antigen in the middle ear fluid; 50 of these patients (76%) also had bacteria in middle ear fluid, and 16 (24%) had virus alone. More patients with AOM and combined bacterial and viral infection (51%) had persistent otitis (3 to 12 days after institution of antibiotic treatment), compared with those with only bacterial otitis (35%; p = 0.05) or patients with only viral infection (19%; p less than 0.01). Of patients with only viral infection, 4 of 10 with virus in middle ear fluid had persistent otitis, compared with none of 11 patients who had virus only in nasal wash specimens or whose viral infection was diagnosed only by serologic studies. Our data suggest that viruses interact with bacteria and that concurrent viral infection can significantly worsen the clinical course of bacterial AOM. The presence of virus in middle ear fluid may contribute to the pathogenesis and outcome of bacterial AOM. The mechanism of these interactions deserve further investigation.

Nonsevere acute otitis media: a clinical trial comparing outcomes of watchful waiting versus immediate antibiotic treatment.

Objective. The widespread use of antibiotics for treatment of acute otitis media (AOM) has resulted in the emergence of multidrug-resistant pathogens that are difficult to treat. However, it has been shown that most children with nonsevere AOM recover without ABX. The objective of this study was to evaluate the safety, efficacy, acceptability, and costs of a non-ABX intervention for children with nonsevere AOM. Methodology. Children 6 months to 12 years old with AOM were screened by using a novel AOM-severity screening index. Parents of children with nonsevere AOM received an educational intervention, and their children were randomized to receive either immediate antibiotics (ABX; amoxicillin plus symptom medication) or watchful waiting (WW; symptom medication only). The investigators, but not the parents, were blinded to enrollment status. Primary outcomes included parent satisfaction with AOM care, resolution of symptoms, AOM failure/recurrence, and nasopharyngeal carriage of Streptococcus pneumoniae strains resistant to ABX. Secondary outcomes included medication-related adverse events, serious adverse events, unanticipated AOM-related office and emergency department visits and telephone calls, the childs absence from day care or school resulting from AOM, the parents absence from school or work because of their childs AOM, and costs of treatment. Subjects were defined as failing (days 0–12) or recurring (days 13–30) if they experienced a higher AOM-severity score on reexamination. Results. A total of 223 subjects were recruited: 73% were nonwhite, 57% were <2 years old, 47% attended day care, 82% had experienced prior AOM, and 83% had not been fully immunized with heptavalent pneumococcal vaccine. One hundred twelve were randomized to ABX, and 111 were randomized to WW. Ninety-four percent of the subjects were followed to the 30-day end point. Parent satisfaction with AOM care was not different between the 2 treatment groups at either day 12 or 30. Compared with WW, symptom scores on days 1 to 10 resolved faster in subjects treated with immediate ABX. At day 12, among the immediate-ABX group, 69% of tympanic membranes and 25% of tympanograms were normal, compared with 51% of normal tympanic membranes and 10% of normal tympanograms in the WW group. Parents of children in the ABX group gave their children fewer doses of pain medication than did parents of children in the WW group. Subjects in the ABX group experienced 16% fewer failures than subjects in the WW group. Of the children in the WW group, 66% completed the study without needing ABX. Immediate ABX resulted in eradication of S pneumoniae carriage in the majority of children, but S pneumoniae strains cultured from children in the ABX group at day 12 were more likely to be multidrug-resistant than strains from children in the WW group. More ABX-related adverse events were noted in the ABX group, compared with the WW group. No serious AOM-related adverse events were observed in either group. Office and emergency department visits, phone calls, and days of work/school missed were not different between groups. Prescriptions for ABX were reduced by 73% in the WW group compared with the ABX group. Costs of ABX averaged

Microbial interactions during upper respiratory tract infections.

47.41 per subject in the ABX group and

Administration of oral acyclovir suppressive therapy after neonatal herpes simplex virus disease limited to the skin, eyes and mouth: Results of a phase I/II trial

11.43 in the WW group. Conclusions. Sixty-six percent of subjects in the WW group completed the study without ABX. Parent satisfaction was the same between groups regardless of treatment. Compared with WW, immediate ABX treatment was associated with decreased numbers of treatment failures and improved symptom control but increased ABX-related adverse events and a higher percent carriage of multidrug-resistant S pneumoniae strains in the nasopharynx at the day-12 visit. Key factors in implementing a WW strategy were (a) a method to classify AOM severity; (b) parent education; (c) management of AOM symptoms; (d) access to follow-up care; and (e) use of an effective ABX regimen, when needed. When these caveats are observed, WW may be an acceptable alternative to immediate ABX for some children with nonsevere AOM.

Trends in Otitis Media–Related Health Care Use in the United States, 2001-2011

Competitive interactions between bacteria differ by number and species present; thus, vaccination and treatment strategies may alter nasopharyngeal flora and disease susceptibility.

Incidence of Acute Otitis Media and Sinusitis Complicating Upper Respiratory Tract Infection: The Effect of Age

BACKGROUND Neonatal herpes simplex virus (HSV) infections limited to the skin, eyes and mouth (SEM) can result in neurologic impairment. A direct correlation exists between the development of neurologic deficits and the frequency of cutaneous HSV recurrences. Thus, the National Institutes of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted a Phase I/II trial of oral acyclovir therapy for the suppression of cutaneous recurrences after SEM disease in 26 neonates. METHODS Infants < or = 1 month of age with virologically confirmed HSV-2 SEM disease were eligible for enrollment. Suppressive oral acyclovir therapy (300 mg/m2/dose given either twice daily or three times per day) was administered for 6 months. RESULTS Twelve (46%) of the 26 infants developed neutropenia (< 1000 cells/mm3) while receiving acyclovir. Thirteen (81%) of the 16 infants who received drug 3 times per day experienced no recurrences of skin lesions while receiving therapy. In comparison, a previous Collaborative Antiviral Study Group study found that only 54% of infants have no cutaneous recurrences in the 6 months after resolution of neonatal HSV disease if oral acyclovir suppressive therapy is not initiated. In one infant, HSV DNA was detected in the cerebrospinal fluid during a cutaneous recurrence, and an acyclovir-resistant HSV mutant was isolated from another patient during the course of the study. CONCLUSIONS Administration of oral acyclovir can prevent cutaneous recurrences of HSV after neonatal SEM disease. The effect of such therapy on neurologic outcome must be assessed in a larger, Phase III study. As such, additional investigation is necessary before routine use of suppressive therapy in this population can be recommended.

Comparison of the FilmArray Respiratory Panel and Prodesse Real-Time PCR Assays for Detection of Respiratory Pathogens

IMPORTANCE Otitis media (OM) is a leading cause of pediatric health care visits and the most frequent reason children consume antibiotics or undergo surgery. During recent years, several interventions have been introduced aiming to decrease OM burden. OBJECTIVE To study the trend in OM-related health care use in the United States during the pneumococcal conjugate vaccine (PCV) era (2001-2011). DESIGN, SETTING, AND PARTICIPANTS An analysis of an insurance claims database of a large, nationwide managed health care plan was conducted. Enrolled children aged 6 years or younger with OM visits were identified. MAIN OUTCOMES AND MEASURES Annual OM visit rates, OM-related complications, and surgical interventions were analyzed. RESULTS Overall, 7.82 million unique children (5.51 million child-years) contributed 6.21 million primary OM visits; 52% were boys and 48% were younger than 2 years. There was a downward trend in OM visit rates from 2004 to 2011, with a significant drop that coincided with the advent of the 13-valent vaccine (PCV-13) in 2010. The observed OM visit rates in 2010 (1.00/child-year) and 2011 (0.81/child-year) were lower than the projected rates based on the 2005-2009 trend had there been no intervention (P < .001). Recurrent OM (≥3 OM visits within 6-month look-back) rates decreased at 0.003/child-year (95% CI, 0.002-0.004/child-year) in 2001-2009 and at 0.018/child-year (95% CI, 0.008-0.028/child-year) in 2010-2011. In the PCV-13 premarket years, there was a stable rate ratio (RR) between OM visit rates in children younger than 2 years and in those aged 2 to 6 years (RR, 1.38; 95% CI, 1.38-1.39); the RR decreased significantly (P < .001) during the transition year 2010 (RR 1.32; 95% CI, 1.31-1.33) and the postmarket year 2011 (RR 1.01; 95% CI, 1.00-1.02). Tympanic membrane perforation/otorrhea rates gradually increased (from 3721 per 100,000 OM child-years in 2001 to 4542 per 100,000 OM child-years in 2011; P < .001); the increase was significant only in the older children group. Mastoiditis rates substantially decreased (from 61 per 100,000 child-years in 2008 to 37 per 100,000 child-years in 2011; P < .001). Ventilating tube insertion rate decreased by 19% from 2010 to 2011 (P = .03). CONCLUSIONS AND RELEVANCE There was an overall downward trend in OM-related health care use from 2001 to 2011. The significant reduction in OM visit rates in 2010-2011 in children younger than 2 years coincided with the advent of PCV-13. Although tympanic membrane perforation/otorrhea rates steadily increased during that period, mastoiditis and ventilating tube insertion rates decreased in the last years of the study.