Influenza In Young Children Research Articles

Severe A(H1N1)pdm09 influenza acute encephalopathy outbreak in children in Tuscany, Italy, December 2023 to January 2024.

A severe outbreak of influenza A(H1N1pdm09) infection in seven children (median age: 52 months) occurred between December 2023 and January 2024 in Tuscany, Italy. Clinical presentation ranged from milder encephalopathy to acute necrotizing encephalopathy (ANE) with coma and multiorgan failure; one child died. This report raises awareness for clinicians to identify and treat early acute encephalopathy caused by H1N1 influenza and serves as a reminder of severe presentations of influenza in young children and the importance of vaccination.

Effects of scheduled school breaks on the circulation of influenza in children, school-aged population, and adults in China: A spatio-temporal analysis

ObjectivesTo investigate the effect of scheduled school break on the circulation of influenza in young children, school-aged population, and adults. MethodsIn a spatial-temporal analysis using influenza activity, school break dates, and meteorological covariates across mainland China during 2015-2018, we estimated age-specific, province-specific, and overall relative risk (RR) and effectiveness of school break on influenza. ResultsWe included data in 24, 25, and 17 provinces for individuals aged 0-4 years, 5-19 years and 20+ years. We estimated a RR meta-estimate of 0.34 (95% confidence interval 0.29-0.40) and an effectiveness of 66% for school break in those aged 5-19 years. School break showed a lagged and smaller mitigation effect in those aged 0-4 years (RR meta-estimate: 0.73, 0.68-0.79) and 20+ years (RR meta-estimate: 0.89, 0.78-1.01) versus those aged 5-19 years. ConclusionThe results show heterogeneous effects of school break between population subgroups, a pattern likely to hold for other respiratory infectious diseases. Our study highlights the importance of anticipating age-specific effects of implementing school closure interventions and provides evidence for rational use of school closure interventions in future epidemics.

Societal costs of influenza in young children substantial in China

Societal costs of influenza in young children substantial in China

How lethal is SARS-CoV-2 pneumonia when compared with respiratory syncytial virus and influenza in young children?

SARS-CoV-2 is known to cause milder disease in children when compared with adults, but the extent of this is unclear. The aim of this article is to estimate the case fatality rate (CFR) for SARS-CoV-2 infection and SARS-CoV-2 pneumonia in young children aged <5 years, and compare this with estimated CFRs for respiratory syncytial virus (RSV) and influenza. This article reviews published case series of SARS-CoV-2 infection in the paediatric population and epidemiological data on COVID-19 published on official government websites internationally andin Australia. The CFR of SARS-CoV-2 pneumonia inchildren aged <5 years is estimated tobe0.15-1.35%, which is lower than theestimated CFR of RSV pneumonia of0.3-2.1%, but higher than the estimated CFR of influenza pneumonia of 0.14-0.45%. SARS-CoV-2 infection is likely to be less lethal than RSV in children aged <5 years, but more lethal than influenza.

The impact of influenza infection on young children, their family and the health care system.

BackgroundInfluenza is a major cause of respiratory illness in young children. Assessing the impact of infection on children and the community is required to guide immunisation policies.ObjectivesTo describe the impact of laboratory‐proven influenza in young children and to compare its impact with that of other respiratory viruses on the child, their family and the health care system.MethodsPreschool children presenting for care or admission to a tertiary paediatric hospital during the 2008‐2014 influenza seasons were tested for respiratory virus by polymerase chain reaction and culture. Parental surveys were used to determine the impact of infection on illness duration, medication use, absenteeism and health service utilisation. Multivariate regression analyses were used to assess the impact of influenza and to evaluate the association between influenza status and outcomes.ResultsAmong 1191 children assessed, 238 had influenza. Among children with influenza, 87.8% were administered antipyretics and 40.9% antibiotics. 28.6% had secondary complications. 65.4% of children missed school/day care, and 53.4% of parents missed work. When influenza and other viruses were compared, significant differences were noted including duration of illness (influenza: 9.54 days, other viruses: 8.50 days; P = 0.005) and duration of absenteeism for both the child (23.1 vs 17.3 hours; P = 0.015) and their parents (28.5 vs 22.7 hours; P = 0.012).ConclusionsInfluenza infection in young children has a significant impact on medication use, absenteeism and the use of health care service. Significant differences are identified when compared with other ILI. These data demonstrate that influenza prevention strategies including immunisation are likely to have wide and significant impacts.

AS03- and MF59-Adjuvanted Influenza Vaccines in Children.

Influenza is a major cause of respiratory disease leading to hospitalization in young children. However, seasonal trivalent influenza vaccines (TIVs) have been shown to be ineffective and poorly immunogenic in this population. The development of live-attenuated influenza vaccines and adjuvanted vaccines are important advances in the prevention of influenza in young children. The oil-in-water emulsions MF59 and adjuvant systems 03 (AS03) have been used as adjuvants in both seasonal adjuvanted trivalent influenza vaccines (ATIVs) and pandemic monovalent influenza vaccines. Compared with non-adjuvanted vaccine responses, these vaccines induce a more robust and persistent antibody response for both homologous and heterologous influenza strains in infants and young children. Evidence of a significant improvement in vaccine efficacy with these adjuvanted vaccines resulted in the use of the monovalent (A/H1N1) AS03-adjuvanted vaccine in children in the 2009 influenza pandemic and the licensure of the seasonal MF59 ATIV for children aged 6 months to 2 years in Canada. The mechanism of action of MF59 and AS03 remains unclear. Adjuvants such as MF59 induce proinflammatory cytokines and chemokines, including CXCL10, but independently of type-1 interferon. This proinflammatory response is associated with improved recruitment, activation and maturation of antigen presenting cells at the injection site. In young children MF59 ATIV produced more homogenous and robust transcriptional responses, more similar to adult-like patterns, than did TIV. Early gene signatures characteristic of the innate immune response, which correlated with antibody titers were also identified. Differences were detected when comparing child and adult responses including opposite trends in gene set enrichment at day 3 postvaccination and, unlike adult data, a lack of correlation between magnitude of plasmablast response at day 7 and antibody titers at day 28 in children. These insights show the utility of novel approaches in understanding new adjuvants and their importance for developing improved influenza vaccines for children.

Risk factors for admission to hospital with laboratory-confirmed influenza in young children: birth cohort study.

We determined risk factors for influenza hospital admission in children aged <2 years to guide the design of paediatric vaccination programmes.We linked all singleton live births in Scotland from 2007 to 2015 to hospital administrative data and influenza laboratory reports. Cox proportional hazard models were used to identify birth and family risk factors for influenza admissions.There were 1115 influenza admissions among 424 048 children. 85.1% of admitted children were born at term and were not in a high-risk group. Presence of an older sibling was strongly associated with increased risk of influenza admission, particularly for children aged <6 months: hazard ratio for second- versus first-born child was 2.02 (95% CI 1.52-2.69). Maternal age <30 years and birth during autumn (age <6 months) or spring (age 6-23 months) were also associated with admission risk.Targeting vaccination programmes to high-risk children will not prevent the vast majority of influenza admissions. Parents of children aged <2 years should be advised that vaccination of older siblings will protect younger children against influenza infection. As evidence of the impact of the universal influenza vaccine programme emerges, there may be a need to reconsider universal influenza vaccination in children aged 6 months to 2 years in the UK.

Pharmacokinetics of oseltamivir in infants under the age of 1 year.

BackgroundOseltamivir is the only antiviral treatment recommended for influenza in young children over the age of 1 year. There is scant data on oseltamivir pharmacokinetics (PK) in infants <1 year. We set out to perform PK measurements in infants who received oseltamivir.MethodsThis study was a prospective, uncontrolled, open label evaluation of the pharmacokinetics of oseltamivir metabolism, safety of oseltamivir, viral clearance in infants <12 months diagnosed with influenza by nasopharyngeal influenza nucleic acid antigen test (NAAT). Blood levels of the prodrug oseltamivir and its active carboxylate were measured prior to a dose of oseltamivir and at 4 time points afterwards, to calculate Cmax (ng/mL), Tmax (h), AUC0−t (ng h/mL) and time for AUC (h).ResultsFour children with influenza A received oral oseltamivir, 2.35–3 mg/kg/dose. This dose range produced a target oseltamivir carboxylate plasma concentration in excess of the proposed 12-h target AUC of 3800 ng h/mL, selected from earlier studies to avert resistance. One patient developed GIT adverse event: dry retching.ConclusionOseltamivir was well tolerated at a dose of 2.35–3 mg/kg/dose twice a day in infants under the age of 1 year. In general agreement with earlier data, these doses produced a target oseltamivir carboxylate plasma exposure in excess of the proposed 12-h target exposure of AUC equal to 3800 ng h/mL in two patients. The limited plasma concentration data in the remaining two patients were not inconsistent with the target exposure being reached.

Influenza-associated outpatient visits among children less than 5 years of age in eastern China, 2011-2014.

BackgroundThe disease burden of influenza in China has not been well described, especially among young children. The aim of this study was to estimate the incidence of outpatient visits associated with influenza in young children in Suzhou, a city of more than 11 million residents in Jiangsu Province in eastern China.MethodsInfluenza-like illness (ILI) was defined as the presence of fever (axillary temperature ≥38 °C) and cough or sore throat. We collected throat swabs for children less than 5 years of age with ILI who visited Suzhou University Affiliated Children’s Hospital (SCH) outpatient clinic or emergency room between April 2011 and March 2014. Suzhou CDC, a national influenza surveillance network laboratory, tested for influenza viruses by real-time reverse transcription-polymerase chain reaction assay (rRT-PCR). Influenza-associated ILI was defined as ILI with laboratory-confirmed influenza by rRT-PCR. To calculate the incidence of influenza-associated outpatient visits, we conducted community-based healthcare utilization surveys to determine the proportion of hospital catchment area residents who sought care at SCH.ResultsThe estimated incidence of influenza-associated ILI outpatient visits among children aged <5 years in the catchment area of Suzhou was, per 100 population, 17.4 (95 % CI 11.0–25.3) during April 2011-March 2012, 14.6 (95 % CI 5.2–26.2) during April 2012-March 2013 and 21.4 (95 % CI: 10.9–33.5) during April 2013-March 2014. The age-specific outpatient visit rates of influenza-associated ILI were 4.9, 21.1 and 21.2 per 100 children aged 0- <6 months, 6- <24 months and 24- <60 months, respectively.ConclusionInfluenza virus infection causes a substantial burden of outpatient visits among young children in Suzhou, China. Targeted influenza prevention and control strategies for young children in Suzhou are needed to reduce influenza-associated outpatient visits in this age group.

How to better inform the decision making about universal influenza vaccination in children

The disease burden of seasonal influenza in young children is substantial. And yet only the USA, Canada, Finland and one state in Australia currently have a routine influenza vaccine policy in place for young children. Few countries seem keen to follow their lead. This paper reviews the evidence required to inform a policy of universal paediatric vaccination; key features include protective effect, economic impacts and the safety of influenza vaccination in this age group. We found that i. there is insufficient data on the protective effect of vaccinating infants aged 6–23 months, ii. there are very few economic evaluations and most of the current published economic evaluations involve modelling and were performed using data from a variety of sources which are not setting specific, and iii. safety data have not been specifically addressed by an in-depth separate systematic review. To better inform relevant policy making, we suggest that interdisciplinary research, (combining epidemiology and health economics at least), is required to fully examine the protective effect, economic impacts and safety of influenza vaccination in children aged 6–59 months. We also suggest that the safety data on influenza vaccination in this age group should be assessed specifically by an in-depth separate systematic review, using published and grey literature.

Influenza vaccine in pregnancy: policy and research strategies

Influenza vaccination in pregnancy reduces maternal illness, improves fetal outcomes, prevents influenza in the infant up to 6 months of age, and potentially improves long-term adult outcomes for the infant (table 1). These effects on four life stages are not widely known by policy makers, and we provide a summary with recommendations for policy and needed research. Table 1Effects of influenza infection and immunisation in pregnancy Influenza infection effect Antenatal vaccine effect Nature of evidence Pregnancy 1 Rasmussen SA Jamieson DJ Uyeki TM Effects of influenza on pregnant women and infants. Am J Obstet Gynecol. 2012; 207: 3-8 Summary Full Text Full Text PDF PubMed Scopus (237) Google Scholar Hospitalisation Increased 200–500% Decreased 40–50% Retrospective cohorts Fetus–newborn (table 2) Preterm birth Increased Decreased 10–20% Retrospective cohorts Fetal growth restriction Increased Decreased 10–20% Retrospective cohorts, RCT Infant (0–6 months) 2 Poehling KA Edwards KM Griffin MR et al. The burden of influenza in young children, 2004–09. Paediatrics. 2013; 131: 207-216 Crossref PubMed Scopus (135) Google Scholar , 3 Zaman K Roy E Arifeen SE et al. Effectiveness of maternal influenza immunization in mothers and infants. N Engl J Med. 2008; 359: 1555-1564 Crossref PubMed Scopus (971) Google Scholar Hospitalisation/burden of influenza infection About 1/100 Decreased 40–63% Retrospective cohorts, RCT Adult 4 Moster D Lie RT Markestad T Long-term medical and social consequences of preterm birth. N Engl J Med. 2008; 359: 262-273 Crossref PubMed Scopus (946) Google Scholar , 5 Gluckman PD Hanson MA Cooper C Thornburg KL Effect of in utero and early-life conditions on adult health and disease. N Engl J Med. 2008; 359: 61-73 Crossref PubMed Scopus (2583) Google Scholar Long-term outcomes of fetal effects .. Retrospective studies needed RCT=randomised controlled trial. Open table in a new tab RCT=randomised controlled trial.

Rates of respiratory virus-associated hospitalization in children aged

SummaryObjectivesThough respiratory viruses are thought to cause substantial morbidity globally in children aged <5 years, the incidence of severe respiratory virus infections in children is unknown in India where 20% of the world's children live.MethodsDuring August 2009–July 2011, prospective population-based surveillance was conducted for hospitalizations of children aged <5 years in a rural community in Haryana State. Clinical data and respiratory specimens were collected. Swabs were tested by RT-PCR for influenza and parainfluenza viruses, respiratory syncytial virus (RSV), human metapneumovirus, coronaviruses, and adenovirus. Average annual hospitalization incidence was calculated using census data and adjusted for hospitalizations reported to occur at non-study hospitals according to a comunity healthcare utilization survey.ResultsOf 245 hospitalized children, respiratory viruses were detected among 98 (40%), of whom 92 (94%) had fever or respiratory symptoms. RSV accounted for the highest virus-associated hospitalization incidence (34.6/10,000, 95% CI 26.3–44.7) and 20% of hospitalizations. There were 11.8/10,000 (95% CI 7.9–18.4) influenza-associated hospitalizations (7% of hospitalizations). RSV and influenza virus detection peaked in winter (November–February) and rainy seasons (July), respectively.ConclusionRespiratory viruses were associated with a substantial proportion of hospitalizations among young children in a rural Indian community. Public health research and prevention in India should consider targeting RSV and influenza in young children.

The Burden of Influenza in Young Children, 2004–2009

To characterize the health care burden of influenza from 2004 through 2009, years when influenza vaccine recommendations were expanded to all children aged ≥6 months. Population-based surveillance for laboratory-confirmed influenza was performed among children aged <5 years presenting with fever and/or acute respiratory illness to inpatient and outpatient settings during 5 influenza seasons in 3 US counties. Enrolled children had nasal/throat swabs tested for influenza by reverse transcriptase-polymerase chain reaction and their medical records reviewed. Rates of influenza hospitalizations per 1000 population and proportions of outpatients (emergency department and clinic) with influenza were computed. The study population comprised 2970, 2698, and 2920 children from inpatient, emergency department, and clinic settings, respectively. The single-season influenza hospitalization rates were 0.4 to 1.0 per 1000 children aged <5 years and highest for infants <6 months. The proportion of outpatient children with influenza ranged from 10% to 25% annually. Among children hospitalized with influenza, 58% had physician-ordered influenza testing, 35% had discharge diagnoses of influenza, and 2% received antiviral medication. Among outpatients with influenza, 7% were tested for influenza, 7% were diagnosed with influenza, and <1% had antiviral treatment. Throughout the 5 study seasons, <45% of influenza-negative children ≥6 months were fully vaccinated against influenza. Despite expanded vaccination recommendations, many children are insufficiently vaccinated, and substantial influenza burden remains. Antiviral use was low. Future studies need to evaluate trends in use of vaccine and antiviral agents and their impact on disease burden and identify strategies to prevent influenza in young infants.

Accuracy of rapid influenza diagnostic test and immunofluorescence assay compared to real time RT-PCR in children with influenza A(H1N1)pdm09 infection

The influenza burden among children is underestimated. The aim of our study was to estimate the accuracy of the rapid influenza detection test (RIDT) BD Directigen™ EZ Flu A+B® and direct immunofluorescence assay (DFA) used among children with influenza-like illness (ILI) consulted in the ambulatory care clinic. A total of 150 patients were enrolled in the study. Inclusion criteria were: age less than 59 months, presentation of ILI according to the CDC (Centers for Disease Control and Prevention) definition (fever >37.8°C, cough and/or sore throat in the absence of another known cause of illness), duration of symptoms shorter than 96 hours. Two nasal swabs and one pharyngeal swab were obtained from patients and tested by RIDT, DFA and real time RT-PCR as the reference method. For influenza A (H1N1)pdm09 virus sensitivity of RIDT was 62.2% (95% CI 46.5-76.2%), specificity 97.1% (95% CI 91.8-99.4%), PPV 90.3% (95% CI 74.3-98%), NPV 85.7% (95% CI 78.1-91.5%), for DFA sensitivity was 60% (95% CI 51.9-63.2%), specificity 96% (95% CI 88.7-98.8%), PPV 93.1% (95% CI 80.5-98%), NPV 72.7% (95% CI 67.2-74.9%). Analysis of logistic regression revealed that the chance of receiving a true positive result of RIDT was twice as high when the test was conducted during the first 48 hours of symptoms (OR 0.40 vs OR 0.22). The accuracy of RIDT is comparable with DFA and both methods are very specific but moderately sensitive in diagnosis of influenza in young children. Both methods may be recommended for screening for influenza among children.

Clinical Predictors of Influenza in Young Children: The Limitations of "Influenza-Like Illness".

BackgroundInfluenza-like illness (ILI) definitions have been infrequently studied in young children. Despite this, clinical definitions of ILI play an important role in influenza surveillance. This study aims to identify clinical predictors of influenza infection in children ≤5 years old from which age-specific ILI definitions are then constructed.MethodsChildren aged 6–59 months with a history of fever and acute respiratory symptoms were recruited in the Western Australia Influenza Vaccine Effectiveness (WAIVE) Study. Clinical data and per-nasal specimens were obtained from all children. Logistic regression identified significant predictors of influenza infection. Different ILI definitions were compared for diagnostic accuracy.ResultsChildren were recruited from 2 winter influenza seasons (2008–2009; n = 944). Of 919 eligible children, 179 (19.5%) had laboratory-confirmed influenza infection. Predictors of infection included increasing age, lack of influenza vaccination, lower birth weight, fever, cough, and absence of wheeze. An ILI definition comprising fever ≥38°C, cough, and no wheeze had 58% sensitivity (95% confidence interval [CI], 50–66), 60% specificity (95% CI, 56–64), 26% positive predictive value (95% CI, 21–31), and 86% negative predictive value (95% CI, 82–89). The addition of other symptoms or higher fever thresholds to ILI definition had little impact. The Centers for Disease Control and Prevention definition of ILI (presence of fever [≥37.8°C] and cough and/or sore throat) was sensitive (92%; 95% CI, 86–95), yet lacked specificity (10%; 95% CI, 8–13) in this population.ConclusionsInfluenza-like illness is a poor predictor of laboratory-confirmed influenza infection in young children but can be improved using age-specific data. Incorporating age-specific ILI definitions and/or diagnostic testing into influenza surveillance systems will improve the accuracy of epidemiological data.

Indirect, out-of-pocket and medical costs from influenza-related illness in young children

BackgroundStudies have documented direct medical costs of influenza-related illness in young children, however little is known about the out-of-pocket and indirect costs (e.g., missed work time) incurred by caregivers of children with medically attended influenza. ObjectiveTo determine the indirect, out-of-pocket (OOP), and direct medical costs of laboratory-confirmed medically attended influenza illness among young children. MethodsUsing a population-based surveillance network, we evaluated a representative group of children aged <5 years with laboratory-confirmed, medically attended influenza during the 2003–2004 season. Children hospitalized or seen in emergency department (ED) or outpatient settings in surveillance counties with laboratory-confirmed influenza were identified and data were collected from medical records, accounting databases, and follow-up interviews with caregivers. Outcome measures included work time missed, OOP expenses (e.g., over-the-counter medicines, travel expenses), and direct medical costs. Costs were estimated (in 2009 US Dollars) and comparisons were made among children with and without high risk conditions for influenza-related complications. ResultsData were obtained from 67 inpatients, 121 ED patients and 92 outpatients with laboratory-confirmed influenza. Caregivers of hospitalized children missed an average of 73 work hours (estimated cost $1456); caregivers of children seen in the ED and outpatient clinics missed 19 ($383) and 11 work hours ($222), respectively. Average OOP expenses were $178, $125 and $52 for inpatients, ED-patients and outpatients, respectively. OOP and indirect costs were similar between those with and without high risk conditions (p>0.10). Medical costs totaled $3990 for inpatients and $730 for ED-patients. ConclusionsOut-of-pocket and indirect costs of laboratory-confirmed and medically attended influenza in young children are substantial and support the benefits of vaccination.

Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis

The global burden of disease attributable to seasonal influenza virus in children is unknown. We aimed to estimate the global incidence of and mortality from lower respiratory infections associated with influenza in children younger than 5 years. We estimated the incidence of influenza episodes, influenza-associated acute lower respiratory infections (ALRI), and influenza-associated severe ALRI in children younger than 5 years, stratified by age, with data from a systematic review of studies published between Jan 1, 1995, and Oct 31, 2010, and 16 unpublished population-based studies. We applied these incidence estimates to global population estimates for 2008 to calculate estimates for that year. We estimated possible bounds for influenza-associated ALRI mortality by combining incidence estimates with case fatality ratios from hospital-based reports and identifying studies with population-based data for influenza seasonality and monthly ALRI mortality. We identified 43 suitable studies, with data for around 8 million children. We estimated that, in 2008, 90 million (95% CI 49-162 million) new cases of influenza (data from nine studies), 20 million (13-32 million) cases of influenza-associated ALRI (13% of all cases of paediatric ALRI; data from six studies), and 1 million (1-2 million) cases of influenza-associated severe ALRI (7% of cases of all severe paediatric ALRI; data from 39 studies) occurred worldwide in children younger than 5 years. We estimated there were 28,000-111,500 deaths in children younger than 5 years attributable to influenza-associated ALRI in 2008, with 99% of these deaths occurring in developing countries. Incidence and mortality varied substantially from year to year in any one setting. Influenza is a common pathogen identified in children with ALRI and results in a substantial burden on health services worldwide. Sufficient data to precisely estimate the role of influenza in childhood mortality from ALRI are not available. WHO; Bill & Melinda Gates Foundation.

Assessment of the burden of influenza in children

Memories of the 2009 influenza pandemic are fading fast. Globally, seasonal influenza A H1N1 has been almost wholly displaced by the pandemic strain of H1N1 (H1N1 2009pdm), with no identifications of seasonal H1N1 since early 2011. Several different types and subtypes of influenza (H1N1, H3N2, and B) co-circulate in various proportions in different countries. 1 WHOInfluenza A (H1N1) 2009 virus: current situation and post-pandemic recommendations. Wkly Epidemiol Rec. 2011; 86: 61-72 PubMed Google Scholar As noted for decades, discrete seasonal epidemics occur in temperate climates with more continuous circulation in tropical regions. The present situation therefore represents baseline interpandemic influenza. Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysisInfluenza is a common pathogen identified in children with ALRI and results in a substantial burden on health services worldwide. Sufficient data to precisely estimate the role of influenza in childhood mortality from ALRI are not available. Full-Text PDF

Vaccine effectiveness for laboratory-confirmed influenza in children 6–59 months of age, 2005–2007

To estimate the effectiveness of influenza vaccine against medical care visits for laboratory-confirmed influenza in young children we conducted a matched case-control study in children with acute respiratory illness or fever from 2005-2007. Influenza vaccine effectiveness (VE) was calculated using cases with laboratory-confirmed influenza and controls who tested negative for influenza. The effectiveness of influenza vaccine in fully vaccinated children 6-59 months of age was 56% (95% CI: 25%-74%); a significant VE was not found for partial vaccination.

The Efficacy of Live Attenuated Influenza Vaccine Against Influenza-associated Acute Otitis Media in Children

Acute otitis media (AOM) is a frequent complication of influenza in young children. Influenza vaccination is known to protect against AOM by preventing influenza illness. We sought to determine the efficacy of the live attenuated influenza vaccine (LAIV) against influenza-associated AOM compared with placebo and trivalent inactivated influenza vaccine (TIV). LAIV is approved for eligible children aged ≥ 2 years in the United States and in several other countries. AOM incidence data from 6 randomized, double-blind, placebo-controlled trials and 2 randomized, double-blind, TIV-controlled trials in children 6 to 83 months of age were pooled and analyzed. A total of 290 cases of AOM were identified in 24,046 study subjects. LAIV efficacy against influenza-associated AOM was 85.0% (95% confidence interval [CI], 78.3%-89.8%) compared with placebo and 54.0% (95% CI, 27.0%-71.7%) compared with TIV. Efficacy trended higher in those ≥ 24 months of age compared with those aged 6 to 23 months. In placebo-controlled trials, among children who acquired influenza despite vaccination, AOM was diagnosed in 10.3% of LAIV recipients and 16.8% of placebo recipients, representing a 38.2% (95% CI, 11.0%-58.2%) relative reduction in the development of AOM. In TIV-controlled studies, among subjects with breakthrough influenza illness, the proportions of LAIV and TIV recipients who developed AOM were similar. Children receiving LAIV had a high level of protection against influenza-associated AOM when compared with placebo or TIV. This was most evident in children older than 2 years, for whom LAIV is indicated. LAIV recipients who contracted breakthrough influenza illness despite vaccination developed AOM at a significantly lower rate than did unvaccinated children who developed influenza.