Influenza Illness In Children Research Articles

Accuracy of Influenza ICD-10 Diagnosis Codes in Identifying Influenza Illness in Children

Studies of influenza in children commonly rely on coded diagnoses, yet the ability of International Classification of Diseases, Ninth Revision codes to identify influenza in the emergency department (ED) and hospital is highly variable. The accuracy of newer International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes to identify influenza in children is unknown. To determine the accuracy of ICD-10 influenza discharge diagnosis codes in the pediatric ED and inpatient settings. Children younger than 18 years presenting to the ED or inpatient settings with fever and/or respiratory symptoms at 7 US pediatric medical centers affiliated with the Centers for Disease Control and Prevention-sponsored New Vaccine Surveillance Network from December 1, 2016, to March 31, 2020, were included in this cohort study. Nasal and/or throat swabs were collected for research molecular testing for influenza, regardless of clinical testing. Data, including ICD-10 discharge diagnoses and clinical testing for influenza, were obtained through medical record review. Data analysis was performed in August 2023. The accuracy of ICD-10-coded discharge diagnoses was characterized using molecular clinical or research laboratory test results as reference. Measures included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Estimates were stratified by setting (ED vs inpatient) and age (0-1, 2-4, and 5-17 years). A total of 16 867 children in the ED (median [IQR] age, 2.0 [0.0-4.0] years; 9304 boys [55.2%]) and 17 060 inpatients (median [IQR] age, 1.0 [0.0-4.0] years; 9798 boys [57.4%]) were included. In the ED, ICD-10 influenza diagnoses were highly specific (98.0%; 95% CI, 97.8%-98.3%), with high PPV (88.6%; 95% CI, 88.0%-89.2%) and high NPV (85.9%; 95% CI, 85.3%-86.6%), but sensitivity was lower (48.6%; 95% CI, 47.6%-49.5%). Among inpatients, specificity was 98.2% (95% CI, 98.0%-98.5%), PPV was 82.8% (95% CI, 82.1%-83.5%), sensitivity was 70.7% (95% CI, 69.8%-71.5%), and NPV was 96.5% (95% CI, 96.2%-96.9%). Accuracy of ICD-10 diagnoses varied by patient age, influenza season definition, time between disease onset and testing, and clinical setting. In this large cohort study, influenza ICD-10 discharge diagnoses were highly specific but moderately sensitive in identifying laboratory-confirmed influenza; the accuracy of influenza diagnoses varied by clinical and epidemiological factors. In the ED and inpatient settings, an ICD-10 diagnosis likely represents a true-positive influenza case.

Vaccine Effectiveness Against Pediatric Influenza-A-Associated Urgent Care, Emergency Department, and Hospital Encounters During the 2022-2023 Season: VISION Network.

During the 2022-2023 influenza season, the United States experienced the highest influenza-associated pediatric hospitalization rate since 2010-2011. Influenza A/H3N2 infections were predominant. We analyzed acute respiratory illness (ARI)-associated emergency department or urgent care (ED/UC) encounters or hospitalizations at 3 health systems among children and adolescents aged 6 months-17 years who had influenza molecular testing during October 2022-March 2023. We estimated influenza A vaccine effectiveness (VE) using a test-negative approach. The odds of vaccination among influenza-A-positive cases and influenza-negative controls were compared after adjusting for confounders and applying inverse-propensity-to-be-vaccinated weights. We developed overall and age-stratified VE models. Overall, 13 547 of 44 787 (30.2%) eligible ED/UC encounters and 263 of 1862 (14.1%) hospitalizations were influenza-A-positive cases. Among ED/UC patients, 15.2% of influenza-positive versus 27.1% of influenza-negative patients were vaccinated; VE was 48% (95% confidence interval [CI], 44-52%) overall, 53% (95% CI, 47-58%) among children aged 6 months-4 years, and 38% (95% CI, 30-45%) among those aged 9-17 years. Among hospitalizations, 17.5% of influenza-positive versus 33.4% of influenza-negative patients were vaccinated; VE was 40% (95% CI, 6-61%) overall, 56% (95% CI, 23-75%) among children ages 6 months-4 years, and 46% (95% CI, 2-70%) among those 5-17 years. During the 2022-2023 influenza season, vaccination reduced the risk of influenza-associated ED/UC encounters and hospitalizations by almost half (overall VE, 40-48%). Influenza vaccination is a critical tool to prevent moderate-to-severe influenza illness in children and adolescents.

Vaccine Effectiveness Against Life-Threatening Influenza Illness in US Children.

Predominance of 2 antigenically drifted influenza viruses during the 2019-2020 season offered an opportunity to assess vaccine effectiveness against life-threatening pediatric influenza disease from vaccine-mismatched viruses in the United States. We enrolled children aged <18 years admitted to the intensive care unit with acute respiratory infection across 17 hospitals. Respiratory specimens were tested using reverse-transcription polymerase chain reaction for influenza viruses and sequenced. Using a test-negative design, we estimated vaccine effectiveness comparing odds of vaccination in test-positive case patients vs test-negative controls, stratifying by age, virus type, and severity. Life-threating influenza included death or invasive mechanical ventilation, vasopressors, cardiopulmonary resuscitation, dialysis, or extracorporeal membrane oxygenation. We enrolled 159 critically ill influenza case-patients (70% ≤8 years; 51% A/H1N1pdm09 and 25% B-Victoria viruses) and 132 controls (69% were aged ≤8 years). Among 56 sequenced A/H1N1pdm09 viruses, 29 (52%) were vaccine-mismatched (A/H1N1pdm09/5A+156K) and 23 (41%) were vaccine-matched (A/H1N1pdm09/5A+187A,189E). Among sequenced B-lineage viruses, majority (30 of 31) were vaccine-mismatched. Effectiveness against critical influenza was 63% (95% confidence interval [CI], 38% to 78%) and similar by age. Effectiveness was 75% (95% CI, 49% to 88%) against life-threatening influenza vs 57% (95% CI, 24% to 76%) against non-life-threating influenza. Effectiveness was 78% (95% CI, 41% to 92%) against matched A(H1N1)pdm09 viruses, 47% (95% CI, -21% to 77%) against mismatched A(H1N1)pdm09 viruses, and 75% (95% CI, 37% to 90%) against mismatched B-Victoria viruses. During a season when vaccine-mismatched influenza viruses predominated, vaccination was associated with a reduced risk of critical and life-threatening influenza illness in children.

Association Between Hemagglutination Inhibition Antibody Titers and Protection Against Reverse-Transcription Polymerase Chain Reaction-Confirmed Influenza Illness in Children 6-35 Months of Age: Statistical Evaluation of a Correlate of Protection.

BackgroundData from a randomized controlled efficacy trial of an inactivated quadrivalent influenza vaccine in children 6–35 months of age were used to determine whether hemagglutination inhibition (HI) antibody titer against A/H1N1 and A/H3N2 is a statistical correlate of protection (CoP) for the risk of reverse-transcription polymerase chain reaction (RT-PCR)–confirmed influenza associated with the corresponding strain.MethodsThe Prentice criteria were used to statistically validate strain-specific HI antibody titer as a CoP. The probability of protection was identified using the Dunning model corresponding to a prespecified probability of protection at an individual level. The group-level protective threshold was identified using the Siber approach, leading to unbiased predicted vaccine efficacy (VE). A case-cohort subsample was used for this exploratory analysis.ResultsPrentice criteria confirmed that HI titer is a statistical CoP for RT-PCR–confirmed influenza. The Dunning model predicted a probability of protection of 49.7% against A/H1N1 influenza and 54.7% against A/H3N2 influenza at an HI antibody titer of 1:40 for the corresponding strain. Higher titers of 1:320 were associated with >80% probability of protection. The Siber method predicted VE of 61.0% at a threshold of 1:80 for A/H1N1 and 46.6% at 1:113 for A/H3N2.ConclusionsThe study validated HI antibody titer as a statistical CoP, by demonstrating that HI titer is correlated with clinical protection against RT-PCR–confirmed influenza associated with the corresponding influenza strain and is predictive of VE in children 6–35 months of age.Clinical Trials RegistrationNCT01439360.

2731. Does Last Season’s Influenza Vaccination Affect Current Season’s Vaccine Effectiveness in Young Children?

BackgroundWe evaluated influenza VE over two consecutive years vs. the current season against influenza illness during two H3N2-predominant seasons in children receiving care at emergency/urgent care (ED/UC) facilities in metropolitan Colorado.MethodsWe conducted a test-negative case–control analysis of 1478 children aged 6 months to 8 years enrolled at Children’s Hospital Colorado ED/UC with influenza like illness during the 2016–2017 and 2017–2018 influenza seasons. The primary outcome was PCR-confirmed influenza and vaccination status was confirmed using electronic medical record and parental interviews. Vaccination status was defined as completely vaccinated (all doses of influenza vaccine according to child’s age); partially or not vaccinated children were defined as unvaccinated. Multivariable logistic regression models adjusted for high-risk medical condition, age, race and insurance status were used to calculate odds ratios (OR) and 95% confidence intervals. Vaccine effectiveness was calculated as (1 − OR) × 100.ResultsOf the 1224 (82.8%) children enrolled in the study with known vaccination status for both seasons, 361 (29%) tested positive for influenza. Overall, VE against influenza was 49% (95% CI, 33–61%) after adjusting for other covariates in the model. VE did not differ significantly between those vaccinated in both seasons and those vaccinated in only the current season (VE 69%, 95% CI 41–115) (Table 1).ConclusionOur estimates of influenza VE for two predominantly H3N2-influenza seasons in Colorado are comparable to the CDC -VE for children 6 months to 8 years. VE against ED or UC-attended influenza illness in children did not vary significantly by prior seasons’ vaccination status. Disclosures All authors: No reported disclosures.

The use of antiviral drugs for influenza: Guidance for practitioners.

This practice point summarizes the use of antiviral drugs to manage influenza illness in children and youth. Recommendations are based on previously published Canadian recommendations for clinicians on the use of antiviral drugs to prevent and treat influenza. Detailed information on the selective use of chemoprophylaxis can be found in the original document, which also highlights the importance of secondary bacterial infections (i.e., Streptococcus pneumoniae, methicillin-sensitive Staphylococcus aureus and methicillin-resistant S aureus) in cases of severe influenza illness. This document serves as a reference for all clinicians while providing general principles and a user-friendly flow diagram to assist decision-making.

Post-licensure surveillance of quadrivalent live attenuated influenza vaccine United States, Vaccine Adverse Event Reporting System (VAERS), July 2013–June 2014

BackgroundQuadrivalent live attenuated influenza vaccine (LAIV4) was approved in 2012 for healthy persons aged 2–49 years. Beginning with the 2013–2014 influenza season, LAIV4 replaced trivalent live attenuated influenza vaccine (LAIV3). MethodsWe analyzed LAIV4 reports to VAERS, a national spontaneous reporting system. LAIV4 reports in 2013–2014 were compared to LAIV3 reports from the previous three influenza seasons. Medical records were reviewed for non-manufacturer serious reports (i.e., death, hospitalization, prolonged hospitalization, life-threatening illness, permanent disability) and reports of selected conditions of interest. We conducted Empirical Bayesian data mining to identify disproportional reporting for LAIV4. ResultsIn 2013–2014, 12.7 million doses of LAIV4 were distributed and VAERS received 779 reports in individuals aged 2–49 years; 95% were non-serious. Expired drug administered (42%), fever (13%) and cough (8%) were most commonly reported in children aged 2–17 years when LAIV4 was administered alone, while headache (18%), expired drug administered (15%) and exposure during pregnancy (12%) were most common in adults aged 18–49 years. We identified one death report in a child who died from complications of cerebellar vascular tumors. Among non-death serious reports, neurologic conditions were common in children and adults. In children, seizures (3) and Guillain-Barré syndrome (2) were the most common serious neurologic outcomes. We identified three serious reports of asthma/wheezing following LAIV4 in children. Data mining detected disproportional reporting for vaccine administration errors and for influenza illness in children. ConclusionsOur analysis of VAERS reports for LAIV4 did not identify any concerning patterns. The data mining finding for reports of influenza illness is consistent with low LAIV4 vaccine effectiveness observed for influenza A disease in children in 2013–2014. Reports of LAIV4 administration to persons in whom the vaccine is not recommended (e.g., pregnant women) indicate the need for education, training and screening regarding indications.

1132Seasonal Incidence of Medically Attended RSV and Influenza Illness in Children 6-59 Months Old

1132Seasonal Incidence of Medically Attended RSV and Influenza Illness in Children 6-59 Months Old

Efficacy of live attenuated influenza vaccine against influenza illness in children as a function of illness severity

A recent study of inactivated influenza vaccine (IIV) in children aged 3–8 years demonstrated higher efficacy against moderate/severe influenza. A meta-analysis of all previous published randomized clinical trials of live attenuated influenza vaccine (LAIV) that collected information on illness severity in children aged 24–71 months was conducted. Moderate/severe influenza was defined as fever >39°C, acute otitis media, or lower respiratory tract illness; other cases were classified as milder influenza. LAIV efficacy versus placebo was 95.4% [95% confidence interval: 88.5, 98.1] (year 1) and 88.5% [77.4, 94.9] (year 2) against moderate/severe influenza and 91.4% [77.9, 96.7] (year 1) and 84.2% [56.7, 94.3] (year 2) against milder influenza. The relative efficacy of LAIV versus IIV was 52.2% [31.6, 66.6] for moderate/severe influenza and 45.0% [28.6, 57.5] for milder influenza. Efficacy against all influenza illnesses, regardless of severity, is critical to prevent influenza illness and transmission in the community.

Effectiveness of Influenza Vaccine Against Life-threatening RT-PCR-confirmed Influenza Illness in US Children, 2010–2012

No studies have examined the effectiveness of influenza vaccine against intensive care unit (ICU) admission associated with influenza virus infection among children. In 2010-2011 and 2011-2012, children aged 6 months to 17 years admitted to 21 US pediatric intensive care units (PICUs) with acute severe respiratory illness and testing positive for influenza were enrolled as cases; children who tested negative were PICU controls. Community controls were children without an influenza-related hospitalization, matched to cases by comorbidities and geographic region. Vaccine effectiveness was estimated with logistic regression models. We analyzed data from 44 cases, 172 PICU controls, and 93 community controls. Eighteen percent of cases, 31% of PICU controls, and 51% of community controls were fully vaccinated. Compared to unvaccinated children, children who were fully vaccinated were 74% (95% CI, 19% to 91%) or 82% (95% CI, 23% to 96%) less likely to be admitted to a PICU for influenza compared to PICU controls or community controls, respectively. Receipt of 1 dose of vaccine among children for whom 2 doses were recommended was not protective. During the 2010-2011 and 2011-2012 US influenza seasons, influenza vaccination was associated with a three-quarters reduction in the risk of life-threatening influenza illness in children.

The use of antiviral drugs for influenza: Guidance for practitioners, 2012/2013; Paediatric summary

This practice point summarizes the use of antiviral drugs to manage influenza illness in children and youth for the 2012/2013 season. It excerpts a recently published, full-length update of Canadian recommendations for clinicians on the use of antiviral drugs for the prevention and treatment of influenza, with a focus on paediatric antiviral therapy. Detailed information on the selective use of chemoprophylaxis can be found in the source document, which also highlights the importance of secondary bacterial infections (Streptococcus pneumoniae, methicillin-sensitive Staphylococcus aureus and methicillin-resistant S aureus) in cases of severe influenza illness.

Burden of paediatric influenza in Western Europe: a systematic review

BackgroundInfluenza illness in children causes significant clinical and economic burden. Although some European countries have adopted influenza immunisation policies for healthy children, the debate about paediatric influenza vaccination in most countries of the European Union is ongoing. Our aim was to summarise influenza burden (in terms of health outcomes and economic burden) in children in Western Europe via a systematic literature review.MethodsWe conducted a systematic literature search of PubMed, EMBASE, and the Cochrane Library (1970-April 2011) and extracted data on influenza burden in children (defined as aged ≤ 18 years) from 50 publications (13 reporting laboratory-confirmed influenza; 37 reporting influenza-like illness).ResultsChildren with laboratory-confirmed influenza experienced hospitalisations (0.3%-20%), medical visits (1.7-2.8 visits per case), antibiotic prescriptions (7%-55%), and antipyretic or other medications for symptomatic relief (76%-99%); young children and those with severe illness had the highest rates of health care use. Influenza in children also led to absenteeism from day care, school, or work for the children, their siblings, and their parents. Average (mean or median) length of absence from school or day care associated with confirmed influenza ranged from 2.8 to 12.0 days for the children, from 1.3 to 6.0 days for their siblings, and from 1.3 to 6.3 days for their parents. Influenza negatively affected health-related quality of life in children with asthma, including symptoms and activities; this negative effect was smaller in vaccinated children than in non-vaccinated children.ConclusionsInfluenza burden in children is substantial and has a significant direct impact on the ill children and an indirect impact on their siblings and parents. The identified evidence regarding the burden of influenza may help inform both influenza antiviral use in children and paediatric immunisation policies in European countries.

Safety, Efficacy, and Effectiveness of Cold-Adapted Influenza Vaccine-Trivalent Against Community-Acquired, Culture-Confirmed Influenza in Young Children Attending Day Care

The goal was to evaluate the safety, tolerability, and efficacy of an investigational, refrigerator-stable formulation of live attenuated influenza vaccine (cold-adapted influenza vaccine-trivalent) against culture-confirmed influenza, acute otitis media, and effectiveness outcomes in young children in day care over 2 consecutive influenza seasons. Children 6 to <36 months of age who were attending day care were assigned randomly in year 1 to receive 2 doses of vaccine or placebo intranasally, 35 +/- 7 days apart. In year 2, subjects received 1 dose of the same treatment as in year 1. A total of 1616 subjects (vaccine: 951 subjects; placebo: 665 subjects) in year 1 and 1090 subjects (vaccine: 640 subjects; placebo: 450 subjects) in year 2 were able to be evaluated for efficacy. The mean age at first vaccination was 23.4 +/- 7.9 months. In year 1, the overall efficacy of the vaccine against influenza subtypes similar to the vaccine was 85.4%; efficacy was 91.8% against A/H1N1 and 72.6% against B. In year 2, the overall efficacy was 88.7%; efficacy was 90.0% against H1N1, 90.3% against A/H3N2, and 81.7% against B. Efficacy against all episodes of acute otitis media associated with culture-confirmed influenza was 90.6% in year 1 and 97.0% in year 2. Runny nose or nasal discharge after dose 1 in year 1 was the only reactogenicity event that was significantly more frequent with cold-adapted influenza vaccine-trivalent (82.3%) than placebo (75.4%). Cold-adapted influenza vaccine-trivalent was well tolerated and effective in preventing culture-confirmed influenza illness in children as young as 6 months of age who attended day care.

Surveillance for Influenza Admissions Among Children Hospitalized in Canadian Immunization Monitoring Program Active Centers, 2003–2004

Influenza is a common childhood infection that may result in hospitalization. Our objectives were to (1) determine characteristics of children hospitalized for influenza and disease manifestations and (2) obtain baseline data before implementation of new recommendations for routine immunization of young children and their caretakers against influenza. All of the children hospitalized with laboratory-confirmed influenza at 9 Canadian tertiary care hospitals during the 2003-2004 influenza season were identified from virology laboratory reports, and their charts were reviewed. There were 505 children admitted because of influenza. Fifty-seven percent were < 2 years old. Previously healthy children accounted for 58% of all of the cases. Pulmonary and neurologic disorders were the most common underlying chronic conditions. Fever and cough were the most frequent manifestations. Seizures occurred in 9% of cases. Serious complications included myocarditis (2), encephalopathy (6), and meningitis (1). There were 3 influenza-related deaths. Mean duration of hospitalization was 5.3 days. Twelve percent of children required ICU admission, and 6% required mechanical ventilation. Antibiotic therapy was administered in 77% of cases, and 7% received anti-influenza drugs. Information on influenza vaccination was available for 84 of 154 children identified as vaccine candidates. Twenty two had received vaccine, but only 7 children had been fully immunized > 14 days before the onset of illness. Healthy young children and children with chronic conditions are at risk for serious illness with influenza. Ongoing surveillance is needed to evaluate the impact of changing immunization recommendations on the burden of influenza illness in children.

The Burden of Influenza Illness in Children with Asthma and Other Chronic Medical Conditions

Purpose of the Study. To measure the burden of influenza among children with asthma and other medical conditions, many of whom do not receive influenza vaccination. Study Population. Study participants included black and white children aged <15 years who were enrolled in the Tennessee Medicaid program from 1973–1993. Three high-risk patient categories were established including asthma, other lung disease, and other chronic disease. The second data set included ongoing prospective virus surveillance system at Vanderbilt University, which permits precise definition of the …

Influenza vaccine in children with asthma: Why no progress?

In an average year, 20% to 30% of chil- dren will be infected with influenza; this attack rate may be substantially higher during epidemic years and among certain populations, such as children in day care. Although most regard influenza as a self-limited ill- ness in children, it may cause substan- tial morbidity in children with and fluenza-associated excess hospitaliza- tion rates of 3 per 1000 high-risk chil- dren younger than 4 years. 2 For the vast majority of these children, the high-risk condition was asthma. Simi- larly, we conducted a study of children with asthma enrolled in Tennessee Medicaid and demonstrated excess hospitalization rates of 5.6 per 1000 children with asthma aged 1 to 3 years. 3 The hospitalization rates in both of these studies are comparable to rates in adult high-risk populations for whom influenza vaccine is recom- mended. In addition, in the Tennessee Medicaid study, an estimated 10% to 20% of children with asthma younger than 15 years had an additional outpa- tient visit during an average influenza season, and approximately 14% of such children received an additional antibiotic prescription. 3

The burden of influenza illness in children with asthma and other chronic medical conditions

Objective: Although influenza immunization is recommended for children with high-risk medical conditions, the majority of such children do not receive influenza vaccine. This study was designed to measure the burden of influenza among children with asthma and other chronic medical conditions. Study design: We performed a retrospective cohort study of children younger than 15 years with medically treated asthma or other chronic medical conditions enrolled in the Tennessee Medicaid program from 1973 to 1993. We determined rates of hospitalization for acute cardiopulmonary disease, outpatient visits, and antibiotic courses throughout the year. Annual differences between event rates when influenza virus was circulating and event rates during winter months when there was no influenza in the community were used to calculate influenza-attributable morbidity. Results: Influenza accounted for an average of 19, 8, and 2 excess hospitalizations for cardiopulmonary disease yearly per 1000 high-risk children aged <1 year, 1 to <3 years, and 3 to <15 years, respectively. For every 1000 children, an estimated 120 to 200 outpatient visits and 65 to 140 antibiotic courses were attributable to influenza annually. Conclusions: Children younger than 15 years with asthma and other chronic medical conditions experience substantial morbidity requiring inpatient and outpatient care during influenza season. More effective targeting of this population for annual influenza immunization is warranted. (J Pediatr 2000;137:856-64)

Effect of passive maternal antibody on influenza illness in children: a prospective study of influenza A in mother-infant pairs.

To determine the effect of passive antibody on the incidence of influenza in infants, infants born to mothers with serum antibody to influenza A (immune) and those born to mothers without evidence for this serum antibody (non-immune) were followed during the influenza H1N1 epidemic of 1979. Immune mothers had higher H1-specific antibody titers before the epidemic (P less than 0.001), were less frequently culture positive, showed fewer titer rises (P less than 0.001) and were less symptomatic than were nonimmune mothers. Infants of immune mothers had higher H1-specific passive antibody titers that correlated with their mother's antibody titers. Although infants of both groups showed no difference in incidence of influenza infection, infants of immune mothers had influenza symptoms that were delayed in onset (P = 0.02) and were of shorter mean duration compared with infants of nonimmune mothers. These findings suggest that passive maternal antibody delays the onset and decreases the severity of influenza disease in young infants.