Effect of inhaled corticosteroids on episodes of wheezing associated with viral infection in school age children: randomised double blind placebo controlled trial.

OBJECTIVES: To determine the effect of regular prophylactic inhaled corticosteroids on wheezing episodes associated with viral infection in school age children. DESIGN: Randomised, double blind, placebo controlled trial. SETTING: Community based study in Southampton. SUBJECTS: 104 children aged 7 to 9 years who had had wheezing in association with symptoms of upper and lower respiratory tract infection in the preceding 12 months. INTERVENTIONS: After a run in period of 2-6 weeks children were randomly allocated twice daily inhaled beclomethasone dipropionate 200 micrograms or placebo through a Diskhaler for 6 months with a wash out period of 2 months. Children were assessed monthly. MAIN OUTCOME MEASURES: Forced expiratory volume in 1 second (FEV1); bronchial responsiveness to methacholine (PD20); percentage of days with symptoms of upper and lower respiratory tract infection with frequency, severity, and duration of episodes of upper and lower respiratory symptoms and of reduced peak expiratory flow rate. RESULTS: During the treatment period there was a significant increase in mean FEV1 (1.63 v 1.53 1; adjusted difference 0.09 1 (95% confidence interval 0.04 to 0.14); P = 0.001) and methacholine PD20 12.8 v 7.2 mumol/l; adjusted ratio of means 1.7 (1.2 to 2.4); P = 0.007) in children receiving beclomethasone dipropionate compared with placebo. There were, however, no significant differences in the percentage of days with symptoms or in the frequency, severity, or duration of episodes of upper or lower respiratory symptoms or of reduced peak expiratory flow rate during the treatment period between the two groups. CONCLUSIONS: Although lung function is improved with regular beclomethasone dipropionate 400 micrograms/day, this treatment offers no clinically significant benefit in school age children with wheezing episodes associated with viral infection.     

Randomized trial of a fixed combination (KanJang) of herbal extracts containing Adhatoda vasica, Echinacea purpurea and Eleutherococcus senticosus in patients with upper respiratory tract infections.

The clinical efficacy of KanJang oral solution, a fixed combination of standardised extracts of Echinacea purpurea, Adhatoda vasica and Eleutherococcus senticosus, was compared with the combined extracts of Echinacea purpurea and Eleutherococcus senticosus alone (Echinacea mixture) in a controlled, double blind, randomized trial, and with Bromhexine (a standard treatment) in a controlled, open, randomized clinical trial on patients with non-complicated acute respiratory tract infections. Many of the parameters evaluated, such as severity of coughing, frequency of coughing, efficacy of mucus discharge in the respiratory tract, nasal congestion and a general feeling of sickness, showed significantly greater improvement in patients treated with KanJang compared with those receiving the standard treatment. However, no significant differences in the improvement of these symptoms (except in a reduced frequency of coughing) were observed between patients treated with the Echinacea mixture and those receiving the standard treatment. The only explanation is that the lack of extract of A. vasica in the Echinacea mixture reduces its efficacy compared with the complete KanJang oral solution even though direct double-blind comparison yielded no significant differences between these two groups of patients. The recovery time of patients being treated with KanJang or Echinacea mixture was 2 days shorter than that of patients receiving the standard treatment. None of the patients completing the study reported adverse reactions to the medication taken. The significance of the results obtained in this study is discussed with respect to the efficacy of KanJang in the treatment of acute respiratory infection and to the concept that multi-drug therapy offers higher efficacy compared with mono-drug treatment of such infections.     

Effectiveness of adenotonsillectomy in children with mild symptoms of throat infections or adenotonsillar hypertrophy: open,randomised controlled trial

Objective To assess the effectiveness of adenotonsillectomy in children with mild symptoms of throat infections or adenotonsillar hypertrophy.Design Open, randomised controlled trial.Setting 21 general hospitals and three academic centres in the Netherlands.Participants 300 children aged 2-8 years requiring adenotonsillectomy.Intervention Adenotonsillectomy compared with watchful waiting.Main outcome measures Episodes of fever, throat infections, upper respiratory tract infections, and health related quality of life.Results During the median follow up period of 22 months, children in the adenotonsillectomy group had 2.97 episodes of fever per person year compared with 3.18 in the watchful waiting group (difference -0.21, 95% confidence interval -0.54 to 0.12), 0.56 throat infections per person year compared with 0.77 (-0.21, -0.36 to -0.06), and 5.47 upper respiratory tract infections per person year compared with 6.00 (-0.53, -0.97 to -0.08). No clinically relevant differences were found for health related quality of life. Adenotonsillectomy was more effective in children with a history of three to six throat infections than in those with none to two. 12 children had complications related to surgery.Conclusion Adenotonsillectomy has no major clinical benefits over watchful waiting in children with mild symptoms of throat infections or adenotonsillar hypertrophy.     

Echinaforce and other Echinacea fresh plant preparations in the treatment of the common cold. A randomized, placebo controlled, double-blind clinical trial.

The aim of this randomized, double-blind, placebo controlled study was to investigate the efficacy and safety of different doses and preparations of Echinacea purpurea in the treatment of common cold. 246 of 559 recruited healthy, adult volunteers caught a common cold and took 3 times daily 2 tablets of either Echinaforce (Echinacea purpurea-preparation from 95% herba and 5% radix), Echinacea purpurea concentrate (same preparation at 7 times higher concentration), special Echinacea purpurea radix preparation (totally different from that of Echinaforce) or placebo until they felt healthy again but not longer than 7 days. The primary endpoint was the relative reduction of the complaint index defined by 12 symptoms during common cold according to the doctor's record. Echinaforce and its concentrated preparation were significantly more effective than the special Echinacea extract or placebo. All treatments were well tolerated. Among the Echinacea groups the frequency of adverse events was not significantly higher than in the placebo group. Therefore, Echinacea concentrate as well as Echinaforce represent a low-risk and effective alternative to the standard symptomatic medicines in the acute treatment of common cold.     

A standardized polyphenol mixture extracted from poplar-type propolis for remission of symptoms of uncomplicated upper respiratory tract infection (URTI): A monocentric,randomized, double-blind,placebo-controlled clinical trial

BackgroundThe most common symptoms of mild upper respiratory tract infections (URTIs) are sore throat, muffled dysphonia, and swelling and redness of the throat, which result from the inflammation process following acute bacterial or viral infection.Hypothesis/purposeAs propolis is a natural resinous substance traditionally used to maintain oral cavity and upper respiratory tract health due to its antimicrobial and anti-inflammatory properties, the aim of this study is to evaluate the efficacy of an oral spray based on poplar-type propolis extract with a known and standardized polyphenol content, on the remission of the symptoms associated with mild uncomplicated URTIs.Study designA monocentric, randomized, double-blind, placebo-controlled clinical trial was performed.MethodsThis study was conducted in 122 healthy adults who had perceived mild upper respiratory tract infections. Participants, randomly assigned to receive either propolis oral spray (N = 58) or placebo (N = 64), underwent four visits (baseline = t0, after 3 days = t1 and after 5 days = t2 and after a follow-up of 15 days = t3) in an outpatient setting. Propolis oral spray total polyphenol content was 15 mg/ml. The dosage was 2-4 sprays three times/day (corresponding to 12-24 mg of polyphenols/day), for five days. The duration of the study was 8 weeks.ResultsAfter 3 days of treatment, 83% of subjects treated with propolis oral spray had remission of symptoms, while 72% of subjects in the placebo group had at least one remaining symptom. After five days, all subjects had recovered from all symptoms. This means that resolution from mild uncomplicated URTIs took place two days earlier, instead of taking place in five days as recorded in the control group. There was no relationship between the ingestion of propolis oral spray or placebo and adverse reactions.ConclusionPropolis oral spray can be used to improve both bacterial and viral uncomplicated URTI symptoms in a smaller number of days without the use of pharmacological treatment, leading to a prompt symptom resolution.     

Effect of homoeopathic medicines on daily burden of symptoms in children with recurrent upper respiratory tract infections.

OBJECTIVE--To investigate the intrinsic effects of individually prescribed homoeopathic medicines. DESIGN--Randomised double blind placebo controlled study. SETTING--Paediatric outpatient department of university hospital. PATIENTS--175 children with frequently recurring upper respiratory tract infections. Of the 170 children evaluable, 86 were randomised to homoeopathic medicines (47 boys, 39 girls; median age at start 4.2 years; median number of episodes in past year 4) and 84 to placebo (43 boys, 41 girls; median age at start 3.6 years; median number of episodes in past year 4). MAIN OUTCOME MEASURES--Mean score for daily symptoms, number of antibiotic courses, and number of adenoidectomies and tonsillectomies over one year of follow up. RESULTS--The mean daily symptom score was 2.61 in the placebo group and 2.21 in the treatment group (difference 0.41; 95% confidence interval -0.02 to 0.83). In both groups the use of antibiotics was greatly reduced compared with that in the year before entering the trial (from 73 to 33 in the treatment group and from 69 to 43 in the placebo group). The proportion of children in the treatment group having adenoidectomies was lower in the treatment group (16%, 8/50) than in the placebo group (21%, 9/42). The proportion having tonsillectomies was the same in both groups (5%). CONCLUSION--Individually prescribed homoeopathic medicines seem to add little to careful counselling of children with recurrent upper respiratory tract infection in reducing the daily burden of symptoms, use of antibiotics, and need for adenoidectomy and tonsillectomy.     

Antitussive effect of a fixed combination of Justicia adhatoda,Echinacea purpurea and Eleutherococcus senticosus extracts in patients with acute upper respiratory tract infection: A comparative,randomized, double-blind,placebo-controlled study

BackgroundKan Jang® oral solution (KJ) is a fixed combination of aqueous ethanolic extracts of Justicia adhatoda L. leaf, Echinacea purpurea (L.) Moench root, and Eleutherococcus senticosus (Rupr. & Maxim.) Harms root. It is approved in Scandinavia as an herbal medicinal product for respiratory tract infection treatment.PurposeThe present clinical trial aimed to compare the antitussive effect of KJ with placebo (PL) and bromhexine (BH) among patients of 18–65 years old with non-complicated upper respiratory infections (URI; i.e., common cold).Study designWe performed a parallel-group, randomized, double-blinded, placebo-controlled trial in in 177 patients with acute URI over a 5 day period.MethodsWe investigated the antitussive effects of a KJ (30 ml/day; 762 mg genuine extracts with standardized contents of 0.2 mg/ml vasicine, 0.8 mg/ml chicoric acid, and 0.03 mg/ml eleutherosides B and E), bromhexine hydrochloride (24 mg/30 ml/day) and PL on cough and blood markers. The primary outcome was cough relief, which was assessed as the change of cough frequency from baseline (cough index). Secondary outcomes were safety with regards to reported adverse events (AEs) and hematological data.ResultsBoth KJ and BH relieved cough more effectively than placebo. On the third and fourth days of treatment, we observed faster improvement in the group receiving KJ compared to in the groups receiving BH (100%) or PL (100%), indicating a slightly shorter recovery time in the KJ group. KJ showed a good tolerability and safety profile.ConclusionKJ exerted significant antitussive effects in URI. The present data further support the therapeutic use of KJ in upper respiratory tract infections.     

Management and outcome of winter upper respiratory tract infections in children aged 0-9 years.

Age-specific incidences for upper respiratory tract infections in children from a new-town population during 1975-7 were studied, and 965 consecutive upper respiratory tract infections in children aged under 10 during two winters were analysed in detail. Significantly different management plans made by seven doctors did not correlate with the clinical outcome as judged by complications, recall rates, and demand for treatment for similar episodes in the future. Two hundred and thirty-two children (24%) returned for another consultation for the same episode of upper respiratory tract infection. The main reason for these repeat consultations seemed to be that parental expectations about the natural history of the illness were not fulfilled. More realistic parental expectations might be set and safer clinical standards maintained if doctors warned parents about symptoms such as cough and occasional diarrhoea or vomiting that are commonly associated with upper respiratory tract infections in children.     

Community study of role of viral infections in exacerbations of asthma in 9-11 year old children.

OBJECTIVE--To study the association between upper and lower respiratory viral infections and acute exacerbations of asthma in schoolchildren in the community. DESIGN--Community based 13 month longitudinal study using diary card respiratory symptom and peak expiratory flow monitoring to allow early sampling for viruses. SUBJECTS--108 Children aged 9-11 years who had reported wheeze or cough, or both, in a questionnaire. SETTING--Southampton and surrounding community. MAIN OUTCOME MEASURES--Upper and lower respiratory viral infections detected by polymerase chain reaction or conventional methods, reported exacerbations of asthma, computer identified episodes of respiratory tract symptoms or peak flow reductions. RESULTS--Viruses were detected in 80% of reported episodes of reduced peak expiratory flow, 80% of reported episodes of wheeze, and in 85% of reported episodes of upper respiratory symptoms, cough, wheeze, and a fall in peak expiratory flow. The median duration of reported falls in peak expiratory flow was 14 days, and the median maximum fall in peak expiratory flow was 81 l/min. The most commonly identified virus type was rhinovirus. CONCLUSIONS--This study supports the hypothesis that upper respiratory viral infections are associated with 80-85% of asthma exacerbations in school age children.     

Impact of massive dose of vitamin A given to preschool children with acute diarrhoea on subsequent respiratory and diarrhoeal morbidity.

OBJECTIVE--To assess the impact of vitamin A supplementation on morbidity from acute respiratory tract infections and diarrhoea. DESIGN--Double blind randomised placebo controlled field trial. SETTING--An urban slum area in New Delhi, India. SUBJECTS--900 children aged 12-60 months attending a local health facility for acute diarrhoea of less than seven days'' duration randomly allocated to receive vitamin A 200,000 IU or placebo. MAIN OUTCOME MEASURES--Incidence and prevalence of acute lower respiratory tract infections and diarrhoea during the 90 days after termination of the enrolment diarrhoeal episode measured by twice weekly household surveillance. RESULTS--The incidence (relative risk 1.07; 95% confidence interval 0.92 to 1.26) and average number of days spent with acute lower respiratory tract infections were similar in the vitamin A supplementation and placebo groups. Among children aged 23 months or less there was a significant reduction in the incidence of measles (relative risk 0.06; 95% confidence interval 0.01 to 0.48). The incidence of diarrhoea was also similar (relative risk 0.95; 0.86 to 1.05) in the two groups. There was a 36% reduction in the mean daily prevalence of diarrhoea associated with fever in the vitamin A supplemented children older than 23 months. CONCLUSIONS--Results were consistent with a lack of impact on acute lower respiratory tract related mortality after vitamin A supplementation noted in other trials and a possible reduction in the severity of diarrhoea.     

Results of ciprofloxacin therapy in urinary and respiratory tract infections

Ciprofloxacin was administered to 218 patients with various urinary and respiratory tracts infections, including 142 patients with urinary tract infections and 76 patients with respiratory tract infections. Bacteriological tests and routine laboratory tests were performed thrice (before, during and after therapy) in all patients. Ciprofloxacin was administered orally in daily dose of 500 mg for 10 days. Daily dose was increased to 1000 mg in 23 patients with severe respiratory tract infections. Satisfactory results (recovery or regression of the symptoms of exacerbated chronic disease) were achieved in 185 patients (84.9%) and no effect in 10 patients (4.6%). Significant improvement or transient improvement were noted in 23 patients (10.5%).     

A double blind, placebo-controlled study of Andrographis paniculata fixed combination Kan Jang in the treatment of acute upper respiratory tract infections including sinusitis.

A double blind, placebo-controlled, parallel-group clinical study was carried out to evaluate the effect of an Andrographis paniculata (N.) extract SHA-10 fixed combination, Kan Jang, in the treatment of acute upper respiratory tract infections, including sinusitis. Ninety-five individuals in the treatment group and 90 individuals in the placebo group completed the study according to the protocol. The medication was taken for 5 days. Temperature, headache, muscle aches, throat symptoms, cough, nasal symptoms, general malaise and eye symptoms were taken as outcome measures with given scores. The total score analysis showed a highly significant improvement in the verum group versus the placebo. This result applied to the group as a whole and to the sinusitis subgroups. The individual symptoms of headache and nasal and throat symptoms together with general malaise showed the most significant improvement while cough and eye symptoms did not differ significantly between the groups. Temperature was moderately reduced in the verum group. It can be concluded that Kan Jang has a positive effect in the treatment of acute upper respiratory tract infections and also relieves the inflammatory symptoms of sinusitis. The study drug was well tolerated.     

High viral load of human bocavirus correlates with duration of wheezing in children with severe lower respiratory tract infection

Background

Human bocavirus (HBoV) is a newly discovered parvovirus and increasing evidences are available to support its role as an etiologic agent in lower respiratory tract infection (LRTI). The objective of this study is to assess the impact of HBoV viral load on clinical characteristics in children who were HBoV positive and suffered severe LRTI.

Methods

Lower respiratory tract aspirates from 186 hospitalized children with severe LRTI were obtained by bronchoscopy. HBoVs were detected by real-time PCR and other 10 infectious agents were examined using PCR and/or direct fluorescent assay.

Results

Thirty-one patients (24.6%) were tested positive for HBoV in the respiratory tract aspirates. Fifteen samples had a high viral load (>10⁴ copies/mL) and the other sixteen samples had a low viral load (<10⁴ copies/mL). The duration of presented wheezing and hospitalization was longer in children with high viral load of HBoV than that in children with low viral load. The days of wheezing showed a correlation with viral load of HBoV.

Conclusion

We confirmed that HBoV was frequently detected in patients with severe LRTI. Wheezing was one of the most common symptoms presented by patients with positive HBoV. A high HBoV viral load could be an etiologic agent for LRTI, which led to more severe lower respiratory tract symptom, longer duration of wheezing and hospitalization.     

Respiratory infections in the first year of life in children at risk of developing atopy.

Ninety-two infants, each of whom had one parent with asthma or hay fever, were followed up from birth to age of 1 year and 72 to the age of three years. During the first year of life respiratory symptoms, eczema, and respiratory viral infections were all reported. Within the first year 24 babies developed eczema; 28 had a wheal of 1 mm in diameter or more on prick skin testing with cutaneous allergens. Forty-three children had one or both of these characteristics and formed an atopic subgroup; by the same criteria, 49 children were non-atopic. The number of respiratory infections in the two groups was not significantly different; similar viruses were isolated from both groups. These viruses were associated with both upper and lower respiratory tract infections. Wheezing was a clinical feature in 12 children during lower respiratory tract infections. Of these babies six were atopic in the first year of life. Of the six non-atopic babies, one had eczema in the second year and five children developed raised total serum IgE values within the 3 years.     

The reactogenicity and safety of a multicomponent vaccine (VP-4) in the prevention of acute respiratory diseases in preschoolers

The reactogenicity and safety of poly-component vaccine (VP-4), prepared from the antigens of opportunistic bacteria, in the prophylaxis of acute respiratory diseases (ARD) in children aged 2.6-6 years. The vaccine was administered intranasally in 3 administrations and orally in 6-8 administrations at intervals of 3-4 days for a period of 24 +/- 4 days. The prophylaxis of ARD with the use of VP-4 was carried out in 168 children in 4 children's preschool institutions. The control group was made up of 120 children, attending the same institutions. The study revealed that VP-4 had low reactogenicity and induced short-time systemic and local reactions (common cold, cough). The administration of VP-4 at a period of the epidemic rise on influenza and ARD morbidity did not lead to an increase in the frequency and duration of ARD in the vaccinees, as well as to the exacerbation of chronic infection and the allergization of the body.     

Safety, efficacy and effectiveness of cold-adapted, live, attenuated, trivalent, intranasal influenza vaccine in adults and children.

Studies in children and adults revealed cold-adapted, live, attenuated, trivalent, intranasal influenza vaccine (CAIV-T) to be well accepted, well tolerated and highly protective against culture-confirmed influenza, and to provide significant health benefits. A 2 year, multicentre, double-blind, placebo-controlled efficacy field trial of CAIV-T in children aged 15-71 months with annual re-immunization revealed the vaccine to be highly protective against culture-confirmed influenza. Vaccine induced serum and secretory antibodies in vaccinated children. Overall, during 2 years of study, vaccine was 92% protective against culture-confirmed influenza. During the second year of study the vaccine was 86% protective against influenza A/Sydney/5/97-like virus, a significantly drifted strain not well matched to the vaccine. Antibody studies on children given CAIV-T revealed that high titres of cross-reacting antibodies to influenza A/Sydney/5/97 were induced with vaccination by live attenuated influenza A/Wuhan/359/95-like vaccine. Effectiveness measures revealed significant reductions in febrile illness (21% reduction in year 1, 19% reduction in year 2), febrile otitis media (33% reduction in year 1, 16% reduction in year 2) and associated antibiotic use among vaccinated children compared with placebo recipients. In adults, vaccination with CAIV-T resulted in protection during experimental challenge with virulent wild-type viruses. An effectiveness trial in adults demonstrated significant benefits of CAIV-T vaccine (28% reduction in days of missed work for febrile upper respiratory illness days with associated 45% reduction in days taking antibiotics). General use of CAIV-T has the potential to significantly reduce the impact of influenza in children and adults.     

Metabolic acidosis and fatal myocardial failure after propofol infusion in children: five case reports.

OBJECTIVE--To examine the possible contribution of sedation with propofol in the deaths of children who were intubated and required intensive care. DESIGN--Case note review. SETTING--Three intensive care units. SUBJECTS--Five children with upper respiratory tract infections aged between 4 weeks and 6 years. RESULTS--Four patients had laryngotracheo-bronchitis and one had bronchiolitis. All were sedated with propofol. The clinical course in all five cases was remarkably similar: an increasing metabolic acidosis was associated with brady-arrhythmia and progressive myocardial failure, which did not respond to resuscitative measures. All children developed lipaemic serum after starting propofol. These features are not usually associated with respiratory tract infections. No evidence was found of viral myocarditis, which was considered as a possible cause of death. CONCLUSION--Although the exact cause of death in these children could not be defined, propofol may have been a contributing factor.     

Twice-daily antibiotics in the treatment of acute otitis media: trimethoprim-sulfamethoxazole versus amoxicillin-clavulanate.

Twice-daily trimethoprim-sulfamethoxazole has been shown to be effective in the treatment of acute otitis media except that caused by group A beta-streptococci. Amoxicillin-clavulanate potassium is effective in vitro against all bacterial pathogens causing acute otitis media and has been reported to be effective when given twice daily for urinary tract infections, acute otitis media and respiratory tract infections. To determine whether the in-vitro efficacy of amoxicillin-clavulanate carries over clinically, we conducted a prospective randomized double-blind trial in 219 children presenting at a pediatric walk-in clinic. Diagnosis and follow-up assessments were made by means of examination of the tympanic membrane and acoustic otoscopy. Of the 219 children 202 (101 in either group) were assessed by a specially trained nurse at a follow-up visit 12 to 16 (mean 14) days after treatment was begun. Cure was defined as absence of symptoms and normal results of both visual inspection of the tympanic membrane and acoustic reflectometry; improvement was defined as absence of symptoms and either normal appearance of the tympanic membrane or normal results of acoustic reflectometry; treatment failure was defined as abnormal appearance of the tympanic membrane along with an acoustic reflectometry reading of 5 units or more. There were no differences in age (mean 60 months), sex or proportion of subjects with unilateral versus bilateral disease between the two groups. The combined rate of cure an improvement was significantly higher with trimethoprim-sulfamethoxazole (93%) than with amoxicillin-clavulanate (82%) (p = 0.03). The rate of compliance (more than 80% of the drug taken) did not differ significantly between the two groups. Gastrointestinal side effects were more common with amoxicillin-clavulanate (p less than 0.0001). Our results suggest that for acute otitis media twice-daily trimethoprim-sulfamethoxazole is more effective clinically and produces fewer side effects than twice-daily amoxicillin-clavulanate.     

Safety and Immunogenicity of a Live Attenuated RSV Vaccine in Healthy RSV-Seronegative Children 5 to 24 Months of Age

Despite substantial morbidity associated with respiratory syncytial virus (RSV) infection, there is no licensed vaccine. MEDI-559 is a live attenuated intranasal vaccine candidate being developed for prevention of lower respiratory illness due to RSV in young children. This randomized, placebo-controlled study evaluated safety of MEDI-559 in healthy, RSV-seronegative children. MEDI-559 or placebo was administered on 3 occasions, 2 months apart. Primary safety was based on solicited symptoms (SSs) and adverse events (AEs) collected for 28 days after each dose. Nasal wash samples were collected 3 times after each dose (days 7-10, 12-18, 28-34) and at sick visits. Serum was collected for measuring antibody immune responses to RSV prior to first vaccination and 28 days post final dose. Long-term safety was monitored for 365 days from first dose. SSs were mild and frequent (MEDI-559 84%; placebo 91%); most common SSs were runny/stuffy nose, cough, and irritability/fussiness. AEs occurred in 67% MEDI-559 and 57% placebo recipients: most common AE was upper respiratory tract infection (MEDI-559 35%; placebo 23%). Higher incidence of medically attended lower respiratory illness within 28 days after dosing occurred in the MEDI-559 arm compared to placebo (none associated with vaccine virus shedding). There was no evidence of enhanced RSV disease. Vaccine virus was detected only in MEDI-559 recipients; shedding occurred in 56%subjects, primarily post dose 1. A functional immune response was observed in 59% and 9% MEDI-559 and placebo recipients, respectively, by an RSV microneutralization assay. Vaccine take, assessed by proportion that shed vaccine-type virus or had a seroresponse against RSV, was seen in 95% MEDI-559 subjects. MEDI-559 is therefore biologically active and immunogenic in this seronegative pediatric population. Although the frequency of SSs and AEs was not considered clinically significant, the increase in medically attended lower respiratory illnesses in the vaccine group warrants expanded safety studies.

Trial Registration

ClinicalTrials.gov NCT00767416     

Upper respiratory tract microbial communities, acute otitis media pathogens, and antibiotic use in healthy and sick children

The composition of the upper respiratory tract microbial community may influence the risk for colonization by the acute otitis media (AOM) pathogens Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. We used culture-independent methods to describe upper respiratory tract microbial communities in healthy children and children with upper respiratory tract infection with and without concurrent AOM. Nasal swabs and data were collected in a cross-sectional study of 240 children between 6 months and 3 years of age. Swabs were cultured for S. pneumoniae, and real-time PCR was used to identify S. pneumoniae, H. influenzae, and M. catarrhalis. The V1-V2 16S rRNA gene regions were sequenced using 454 pyrosequencing. Microbial communities were described using a taxon-based approach. Colonization by S. pneumoniae, H. influenzae, and M. catarrhalis was associated with lower levels of diversity in upper respiratory tract flora. We identified commensal taxa that were negatively associated with colonization by each AOM bacterial pathogen and with AOM. The balance of these relationships differed according to the colonizing AOM pathogen and history of antibiotic use. Children with antibiotic use in the past 6 months and a greater abundance of taxa, including Lactococcus and Propionibacterium, were less likely to have AOM than healthy children (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.25 to 0.85). Children with no antibiotic use in the past 6 months, a low abundance of Streptococcus and Haemophilus, and a high abundance of Corynebacterium and Dolosigranulum were less likely to have AOM (OR, 0.51; 95% CI, 0.31 to 0.83). An increased understanding of polymicrobial interactions will facilitate the development of effective AOM prevention strategies.