***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Objective To evaluate the effects of influenza vaccination with or without heptavalent pneumococcal conjugate vaccination on  respiratory tract infections ( RTIs ) in children . Study design This was a r and omized , double-blind , placebo-controlled trial comprising 579 children age 18 to 72 months with a previous history of physician-diagnosed RTI , recruited between 2003 and 2005 . The children were assigned to 2 doses of parenteral inactivated trivalent subunit influenza plus heptavalent pneumococcal conjugate vaccination ( TIV+PCV7 ) , influenza plus placebo vaccination ( TIV+plac ) , or control hepatitis B virus vaccination plus placebo ( HBV+plac ) . Main outcome measures were febrile RTI and related polymerase chain reaction (PCR)-confirmed influenza , primary care visits , antibiotic prescriptions , and acute otitis media ( AOM ) episodes . Results During influenza seasons , febrile RTI were reduced by 24 % ( 95 % confidence interval [ CI ] = 1 % to 42 % ) in the TIV+PCV7 group and by 13 % ( 95 % CI = -12 % to 32 % ) in the TIV+plac group compared with the control group . The occurrence of PCR-confirmed influenza was reduced by 52 % ( 95 % CI = 7 % to 75 % ) in the TIV+PCV7 group and by 51 % ( 95 % CI = 3 % to 75 % ) in the TIV+plac group . Episodes of AOM were reduced by 57 % ( 95 % CI = 6 % to 80 % ) in the TIV+PCV7 group and by 71 % ( 95 % CI = 30 % to 88 % ) in the TIV+plac group . Outside of the influenza seasons , no significant effects of vaccinations were demonstrated on the studied outcomes . Conclusions During influenza seasons , influenza vaccination with or without pneumococcal conjugate vaccination substantially reduced cases of confirmed influenza and AOM episodes BACKGROUND Pneumococcal conjugate vaccine prevents recurrent acute otitis media ( AOM ) in infants immunised at 2 , 4 , 6 , and 12 - 15 months of age . We aim ed to find out whether this vaccine also prevents AOM in older children who have had previous episodes of AOM . METHODS In this double-blind , r and omised study , we enrolled 383 patients aged 1 - 7 years who had had two or more episodes of AOM in the year before entry . R and omisation was stratified in four groups according to age ( 12 - 24 months vs 25 - 84 months ) and the number of previous AOM episodes ( two or three episodes vs four or more episodes ) . Children received either 7-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine , or hepatitis A or B vaccines . They were followed up for 18 months for recurrence of AOM . We also cultured sample s of middle-ear fluid and nasopharyngeal swabs to assess association of pneumococcal serotypes with AOM after vaccination . FINDINGS We noted no reduction of AOM episodes in the pneumococcal vaccine group compared with controls ( intention-to-treat analysis : rate ratio 1.25 , 95 % CI 0.99 - 1.57 ) . Although nasopharyngeal carriage of pneumococci of serotypes included in the conjugate-vaccine was greatly reduced after pneumococcal vaccinations , immediate and complete replacement by non-vaccine pneumococcal serotypes took place . INTERPRETATION These data do not lend support to the use of pneumococcal conjugate vaccine to prevent otitis media in previously unvaccinated toddlers and children with a history of recurrent AOM A group-r and omized , double-masked , phase III trial of a Streptococcus pneumoniae conjugate vaccine is being conducted in American Indian population s in the southwestern United States . Approximately 9000 infants will be enrolled in the primary efficacy cohort with vaccine allocation determined by community of residence . The trial is design ed to continue until 48 cases of invasive pneumococcal disease due to vaccine serotypes have accumulated . Thirty-eight geographically and socially distinct areas were r and omized within blocks formed by population size and geographic location . This design affords the opportunity to capture the effects of herd immunity ( indirect effects ) by estimating the impact of the vaccine intervention on nonimmunized infants . Group-r and omized trials have challenging design and analysis features , many of which are discussed here in the context of the first such trial design ed to lead to licensure of a drug or biologic in the United States Objective : We sought to determine whether  recurrent acute otitis media ( rAOM )  occurring within 30 days of amoxicillin/clavulanate treatment was caused by bacterial relapse or new pathogens . Methods : Pneumococcal conjugate vaccinated children , age 6–36 months , enrolled in a prospect i ve , longitudinal study experiencing rAOM < 1 month after completing amoxicillin/clavulanate therapy  were studied . AOM episodes occurred between June 2006 and November 2012 . Multilocus sequence typing was used to genotype isolates . Results : Sixty-six children were in the study cohort ; 63 otopathogens were recovered from middle ear fluid after tympanocentesis . Nontypeable Haemophilus influenzae ( NTHi ) accounted for 47 % of initial AOMs versus 15 % by Streptococcus pneumoniae ( Spn ) , P < 0.0001 . NTHi accounted for 42 % of rAOM versus 24 % by Spn ( P value = 0.04 ) . NTHi was the main otopathogen that caused true bacteriologic relapses ( 77 % ) . & bgr;-lactamase – producing NTHi and penicillin nonsusceptible Spn were not more common in rAOM than initial AOM infections . Among 21 paired ( initial and rAOM events ) NTHi isolates genotyped , 13 ( 61.9 % ) were the same organism ; 1 of 9 ( 11.1 % ) of paired Spn isolates was the same ( P value = 0.017 ) . rAOM occurring within a week of stopping amoxicillin/clavulanate was a different pathogen in 21 % of cases , 8–14 days later in 33 % , 15–21 days in 41 % and 22–30 days in 57 % ( P = 0.04 ) . Conclusions : In amoxicillin/clavulanate-treated children , NTHi was the main otopathogen that caused true bacteriologic relapses . New pathogens causing rAOM versus persistence of the initial pathogen significantly increased week to week . Neither relapses nor new infections were caused more frequently by & bgr;-lactamase producing NTHi or penicillin nonsusceptible Spn Pneumococcal vaccines may be effective in preventing or decreasing the burden of disease related to otitis media . In study reported here , we investigated the effectiveness of pneumococcal vaccination on otitis media with effusion ( OME ) in children ( n = 383 children aged 1–7 years ) with a history of recurrent otitis media within the framework of a r and omized double blind placebo controlled trial . Children were r and omized to be immunized with either a 7-valent pneumococcal conjugate vaccine followed by the 23-valent pneumococcal polysaccharide vaccine , or by hepatitis A or B vaccines . The proportion of children diagnosed with OME at the scheduled follow-up visits – 7 , 14 , 20 and 26 months after r and omization – was then calculated . OME was diagnosed according to an algorithm combining tympanometry and otoscopy . The percentage of children diagnosed with OME was similar in the pneumococcal vaccination group and control group at both baseline and the follow-up visits at 7 , 14 , 20 and 26 months – 52.9 versus 52.7 , 44.9 versus 44.2 , 34.9 versus 31.5 , 40.8 versus 32.2 and 31.4 versus 26.1 , respectively ( corresponding to p-values of 0.96 , 0.89 , 0.51 , 0.13 and 0.36 , respectively ) . We conclude that the combined pneumococcal conjugate and the polysaccharide vaccination have no beneficial effect on OME in children aged 1 year or older with a history of recurrent otitis media . Therefore , these vaccinations are not indicated in the prevention of OME in these children Background High rates of potentially pathogenic bacteria and respiratory viruses can be detected in the upper respiratory tract of healthy children . Investigating presence of and associations between these pathogens in healthy individuals is still a rather unexplored field of research , but may have implication s for interpreting findings during disease . Methodology /Principal Findings We selected 986 nasopharyngeal sample s from 433 6- to 24-month-old healthy children that had participated in a r and omized controlled trial . We determined the presence of 20 common respiratory viruses using real-time PCR . Streptococcus pneumoniae , Haemophilus influenzae , Moraxella catarrhalis and Staphylococcus aureus were identified by conventional culture methods . Information on risk factors was obtained by question naires . We performed multivariate logistic regression analyses followed by partial correlation analysis to identify the overall pattern of associations . S. pneumoniae colonization was positively associated with the presence of H. influenzae ( adjusted odds ratio 1.60 , 95 % confidence interval 1.18–2.16 ) , M. catarrhalis ( 1.78 , 1.29–2.47 ) , human rhinoviruses ( 1.63 , 1.19–2.22 ) and enteroviruses ( 1.97 , 1.26–3.10 ) , and negatively associated with S. aureus presence ( 0.59 , 0.35–0.98 ) . H. influenzae was positively associated with human rhinoviruses ( 1.63 , 1.22–2.18 ) and respiratory syncytial viruses ( 2.78 , 1.06–7.28 ) . M. catarrhalis colonization was positively associated with coronaviruses ( 1.99 , 1.01–3.93 ) and adenoviruses ( 3.69 , 1.29–10.56 ) , and negatively with S. aureus carriage ( 0.42 , 0.25–0.69 ) . We observed a strong positive association between S. aureus and influenza viruses ( 4.87 , 1.59–14.89 ) . In addition , human rhinoviruses and enteroviruses were positively correlated ( 2.40 , 1.66–3.47 ) , as were enteroviruses and human bocavirus , WU polyomavirus , parainfluenza viruses , and human parechovirus . A negative association was observed between human rhinoviruses and coronaviruses . Conclusions / Significance Our data revealed high viral and bacterial prevalence rates and distinct bacterial-bacterial , viral-bacterial and viral-viral associations in healthy children , hinting towards the complexity and potential dynamics of microbial communities in the upper respiratory tract . This warrants careful consideration when associating microbial presence with specific respiratory diseases Context . The heptavalent pneumococcal conjugate vaccine ( PCV ) is recommended for infants to protect against invasive disease , but its impact on otitis might also have public health importance . Objective . To examine the impact of PCV on the incidence of otitis media , frequent otitis media and tympanostomy tube procedures and to assess whether the effectiveness of the vaccine wanes after age 24 months and varies by race , sex or season . Design , setting and patients .. From 1995 to 1998 , 37 868 children at Kaiser Permanente in Northern California were r and omized to receive PCV or a control vaccine in a double blind trial and were followed through April 1999 . Interventions . Children received a primary series at 2 , 4 and 6 months of age and a booster at 12 to 15 months . Main outcome measures . Visits for otitis , frequent visits for otitis and tympanostomy tube procedures . Otitis was ascertained from diagnosis checklists routinely marked by physicians . Results . Control children averaged 1.8 otitis visits per year . Children given PCV had fewer otitis visits than control children in every age group , sex , race and season examined . Intention-to-treat analysis permitted rejection of the null hypothesis that PCV is ineffective against otitis media ( P < 0.0001 ) . In children who completed the primary series per protocol , PCV reduced otitis visits by 7.8 % [ 95 % confidence interval ( CI ) , 5.4 to 10.2 % ] and antibiotic prescriptions by 5.7 % ( CI 4.2 to 7.2 % ) . Frequent otitis was reduced by amounts that increased with otitis frequency , from a 10 % reduction in the risk of 3 visits to a 26 % reduction in the risk of 10 visits within a 6-month period . Tube placements 
    Output:
    
CRM197-PCV7 followed by 23-valent pneumococcal polysaccharide vaccination administered after infancy in older children with a history of AOM showed no beneficial effect on first occurrence and later AOM episodes .
In a study in older children with a previously diagnosed respiratory tract infection , performed during the influenza season , a trivalent influenza vaccine combined with placebo ( TIV/placebo ) led to fewer all-cause AOM episodes than vaccination with TIV and PCV7 ( TIV/PCV7 ) when compared to hepatitis B vaccination and placebo ( HBV/placebo ) ( RRR 71 % , 95 % CI 30 % to 88 % versus RRR 57 % , 95 % CI 6 % to 80 % , respectively ) indicating that CRM197-PCV7 after infancy may even have negative effects on AOM .
AUTHORS ' CONCLUSIONS Based on current evidence of the effects of PCVs for preventing AOM , the licensed 7-valent CRM197-PCV7 has modest beneficial effects in healthy infants with a low baseline risk of AOM .
Administering PCV7 in high-risk infants , after early infancy and in older children with a history of AOM , appears to have no benefit in preventing further episodes .