Acute viral respiratory infections are a major health burden in children worldwide. In recent years, rapid and sensitive multiplex nucleic acid amplification tests (NAATs) have replaced conventional ...methods for routine virus detection in the clinical laboratory.
We compared BioFire® FilmArray® Respiratory Panel (FilmArray V1.7), Luminex NxTag® Respiratory Pathogen Panel (NxTag RPP) and Applied Biosystems TaqMan Array Card (TAC) for the detection of eight viruses in pediatric respiratory specimens. Results from the three platforms were analyzed with a single-plex real-time RT-PCR (rRT-PCR) assay for each virus.
Of the 170/210 single-plex virus-positive samples, FilmArray detected a virus in 166 (97.6%), TAC in 163 (95.8%) and NxTag RPP in 160 (94.1%) samples. The Positive Percent Agreement (PPA) of FilmArray, NxTag RPP and TAC was highest for influenza B (100%, 100% and 95.2% respectively) and lowest for seasonal coronaviruses on both FilmArray (90.2%) and NxTag RPP (81.8%), and for parainfluenza viruses 1- 4 on TAC (84%). The Negative Percent Agreement (NPA) was lowest for rhinovirus/enterovirus (92.9%, 96.7% and 97.3%) on FilmArray, NxTag RPP and TAC respectively. NPA for all three platforms was highest (100%) for both parainfluenza viruses 1- 4 and influenza A and B, and 100% for human metapneumovirus with TAC as well.
All three multiplex platforms displayed high overall agreement (>90%) and high NPA (>90%), while PPA was pathogen dependent and varied among platforms; high PPA (>90%) was observed for FilmArray for all eight viruses, TAC for six viruses and NxTag RPP for 4 viruses.
To assess medical costs of hospitalizations and emergency department (ED) care associated with respiratory syncytial virus (RSV) disease in children enrolled in the New Vaccine Surveillance Network.
...We used accounting and prospective surveillance data from 6 pediatric health systems to assess direct medical costs from laboratory-confirmed RSV-associated hospitalizations (n = 2007) and ED visits (n = 1267) from 2016 through 2019 among children aged <5 years. We grouped costs into categories relevant to clinical care and administrative billing practices. We examined RSV-associated medical costs by care setting using descriptive and bivariate analyses. We assessed associations between known RSV risk factors and hospitalization costs and length of stay using χ2 tests of association.
The median cost was $7100 (IQR $4006-$13 355) per hospitalized child and $503 (IQR $387-$930) per ED visit. Eighty percent (n = 2628) of our final sample were children aged younger than 2 years. Fewer weeks’ gestational age was associated with greater median costs in hospitalized children (P < .001, ≥37 weeks of gestational age: $6840 $3905-$12 450; 29-36 weeks of gestational age: $7721 $4362-$15 274; <29 weeks of gestational age: $9131 $4518-$19 924). Infants born full term accounted for 70% of the total expenditures in our sample. Almost three quarters of the health care dollars spent originated in children younger than 12 months of age, the primary age group targeted by recommended RSV prophylactics.
Reducing the cost burden for RSV-associated medical care in young children will require prevention of RSV in all young children, not just high-risk infants. Newly available maternal vaccine and immunoprophylaxis products could substantially reduce RSV-associated medical costs.
Parents of children with autism spectrum disorder (ASD) may be at greater risk for developing antivaccine beliefs that lead to vaccine delays and/or refusals for their children. We investigated ...current parental vaccine hesitancy, parents’ beliefs about causes of children’s developmental delays, and children’s vaccination histories among parents of children with ASD or non-ASD developmental delays. Data were analyzed from 89/511 parents (17.4%) who completed the Parent Attitudes About Childhood Vaccines questionnaire and the Revised Illness Perception Questionnaire; 46.1% had childhood vaccination records available. Overall, 21/89 (23.6%, 95% confidence interval CI: 15.0-34.0) of parents were vaccine hesitant (ASD n = 19/21 90.5%, non-ASD n = 2/21 9.5%). Parents of children with ASD were significantly more likely to agree with “toxins in vaccines” as a cause of their child’s developmental delays (28.4% vs 5.0%, P = .034). The odds of being vaccine hesitant were 11.9 times (95% CI 2.9-48.0) greater among parents who agreed versus disagreed that toxins in vaccines caused their children’s developmental delays. Rates of prior vaccine receipt did not differ between hesitant and nonhesitant groups.
Background. We assessed vaccine effectiveness (VE) for RotaTeq (RV5; 3 doses) and Rotarix (RV1; 2 doses) at reducing rotavirus acute gastroenteritis (AGE) inpatient and emergency department (ED) ...visits in US children. Methods. We enrolled children <5 years of age hospitalized or visiting the ED with AGE symptoms from November 2009–June 2010 and from November 2010–June 2011 at 7 medical institutions. Fecal specimens were tested for rotavirus by enzyme immunoassay and genotyped. Vaccination among laboratory-confirmed rotavirus cases was compared with rotavirus-negative AGE controls. Regression models calculated VE estimates for each vaccine, age, ethnicity, genotype, and clinical setting. Results. RV5-specific analyses included 359 rotavirus cases and 1811 rotavirus-negative AGE controls. RV1-specific analyses included 60 rotavirus cases and 155 rotavirus-negative AGE controls. RV5 and RV1 were 84% (95% confidence interval CI, 78%–88%) and 70% (95% CI, 39%–86%) effective, respectively, against rotavirus-associated ED visits and hospitalizations combined. By clinical setting, RV5 VE against ED and inpatient rotavirus-associated visits was 81% (95% CI, 70%–84%) and 86% (95% CI, 74%–91%), respectively. RV1 was 78% (95% CI, 46%–91%) effective against ED rotavirus disease; study power was insufficient to evaluate inpatient RV1 VE. No waning of immunity was evident during the first 4 years of life for RV5, nor during the first 2 years of life for RV1. RV5 provided genotype-specific protection against each of the predominant strains (G1P8, G2P4, G3P8, G12P8, while RV1 VE was statistically significant for the most common genotype, G3P8. Conclusions. Both RV5 and RV1 significantly protected against medically attended rotavirus gastroenteritis in this real-world assessment.
Influenza virus infection during pregnancy is associated with severe maternal disease and may be associated with adverse birth outcomes. Inactivated influenza vaccine during pregnancy is safe and ...effective and can protect young infants, but recent evidence, particularly after the 2009 novel influenza A (H1N1) pandemic, is limited.
To evaluate the effectiveness of influenza vaccination during pregnancy against laboratory-confirmed influenza-associated hospitalizations and emergency department (ED) visits in infants younger than 6 months.
This was a prospective, test-negative case-control study using data from the New Vaccine Surveillance Network from the 2016 to 2017 through 2019 to 2020 influenza seasons. Infants younger than 6 months with an ED visit or hospitalization for acute respiratory illness were included from 7 pediatric medical institutions in US cities. Control infants with an influenza-negative molecular test were included for comparison. Data were analyzed from June 2022 to September 2023.
Maternal influenza vaccination during pregnancy.
We estimated maternal vaccine effectiveness against hospitalizations or ED visits in infants younger than 6 months, those younger than 3 months, and by trimester of vaccination. Maternal vaccination status was determined using immunization information systems, medical records, or self-report. Vaccine effectiveness was estimated by comparing the odds of maternal influenza vaccination 14 days or more before delivery in infants with influenza vs those without.
Of 3764 infants (223 with influenza and 3541 control infants), 2007 (53%) were born to mothers who were vaccinated during pregnancy. Overall vaccine effectiveness in infants was 34% (95% CI, 12 to 50), 39% (95% CI, 12 to 58) against influenza-associated hospitalizations, and 19% (95% CI, -24 to 48) against ED visits. Among infants younger than 3 months, effectiveness was 53% (95% CI, 30 to 68). Effectiveness was 52% (95% CI, 30 to 68) among infants with mothers who were vaccinated during the third trimester and 17% (95% CI, -15 to 40) among those with mothers who were vaccinated during the first or second trimesters.
Maternal vaccination was associated with reduced odds of influenza-associated hospitalizations and ED visits in infants younger than 6 months. Effectiveness was greatest among infants younger than 3 months, for those born to mothers vaccinated during the third trimester, and against influenza-associated hospitalizations.
Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complication that has disproportionately affected ...racial/ethnic minority children. We conducted a pilot study to investigate risk factors for MIS-C aiming to understand MIS-C disparities.
This case-control study included MIS-C cases and SARS-CoV-2-positive outpatient controls less than 18 years old frequency-matched 4:1 to cases by age group and site. Patients hospitalized with MIS-C were admitted between March 16 and October 2, 2020, across 17 pediatric hospitals. We evaluated race, ethnicity, social vulnerability index (SVI), insurance status, weight-for-age and underlying medical conditions as risk factors using mixed effects multivariable logistic regression.
We compared 241 MIS-C cases with 817 outpatient SARS-CoV-2-positive at-risk controls. Cases and controls had similar sex, age and U.S. census region distribution. MIS-C patients were more frequently previously healthy, non-Hispanic Black, residing in higher SVI areas, and in the 95th percentile or higher for weight-for-age. In the multivariable analysis, the likelihood of MIS-C was higher among non-Hispanic Black children adjusted odds ratio (aOR): 2.07; 95% CI: 1.23-3.48. Additionally, SVI in the 2nd and 3rd tertiles (aOR: 1.88; 95% CI: 1.18-2.97 and aOR: 2.03; 95% CI: 1.19-3.47, respectively) were independent factors along with being previously healthy (aOR: 1.64; 95% CI: 1.18-2.28).
In this study, non-Hispanic Black children were more likely to develop MIS-C after adjustment for sociodemographic factors, underlying medical conditions, and weight-for-age. Investigation of the potential contribution of immunologic, environmental, and other factors is warranted.
Adult studies have demonstrated within-season declines in influenza vaccine effectiveness (VE); data in children are limited.
We conducted a prospective, test-negative study of children 6 months ...through 17 years hospitalized with acute respiratory illness at 7 pediatric medical centers during the 2015-2016 through 2019-2020 influenza seasons. Case-patients were children with an influenza-positive molecular test matched by illness onset to influenza-negative control-patients. We estimated VE 100% × (1 - odds ratio) by comparing the odds of receipt of ≥1 dose of influenza vaccine ≥14 days before illness onset among influenza-positive children to influenza-negative children. Changes in VE over time between vaccination date and illness onset date were estimated using multivariable logistic regression.
Of 8430 children, 4653 (55%) received ≥1 dose of influenza vaccine. On average, 48% were vaccinated through October and 85% through December each season. Influenza vaccine receipt was lower in case-patients than control-patients (39% vs 57%, P < .001); overall VE against hospitalization was 53% (95% confidence interval CI: 46, 60%). Pooling data across 5 seasons, the odds of influenza-associated hospitalization increased 4.2% (-3.2%, 12.2%) per month since vaccination, with an average VE decrease of 1.9% per month (n = 4000, P = .275). Odds of hospitalization increased 2.9% (95% CI: -5.4%, 11.8%) and 9.6% (95% CI: -7.0%, 29.1%) per month in children ≤8 years (n = 3084) and 9-17 years (n = 916), respectively. These findings were not statistically significant.
We observed minimal, not statistically significant within-season declines in VE. Vaccination following current Advisory Committee on Immunization Practices (ACIP) guidelines for timing of vaccine receipt remains the best strategy for preventing influenza-associated hospitalizations in children.
Respiratory syncytial virus (RSV) is the leading cause of hospitalization in US infants. Accurate estimates of severe RSV disease inform policy decisions for RSV prevention.
We conducted prospective ...surveillance for children <5 years old with acute respiratory illness from 2016 to 2020 at 7 pediatric hospitals. We interviewed parents, reviewed medical records, and tested midturbinate nasal ± throat swabs by reverse transcription polymerase chain reaction for RSV and other respiratory viruses. We describe characteristics of children hospitalized with RSV, risk factors for ICU admission, and estimate RSV-associated hospitalization rates.
Among 13 524 acute respiratory illness inpatients <5 years old, 4243 (31.4%) were RSV-positive; 2751 (64.8%) of RSV-positive children had no underlying condition or history of prematurity. The average annual RSV-associated hospitalization rate was 4.0 (95% confidence interval CI: 3.8-4.1) per 1000 children <5 years, was highest among children 0 to 2 months old (23.8 95% CI: 22.5-25.2 per 1000) and decreased with increasing age. Higher RSV-associated hospitalization rates were found in premature versus term children (rate ratio = 1.95 95% CI: 1.76-2.11). Risk factors for ICU admission among RSV-positive inpatients included: age 0 to 2 and 3 to 5 months (adjusted odds ratio aOR = 1.97 95% CI: 1.54-2.52 and aOR = 1.56 95% CI: 1.18-2.06, respectively, compared with 24-59 months), prematurity (aOR = 1.32 95% CI: 1.08-1.60) and comorbid conditions (aOR = 1.35 95% CI: 1.10-1.66).
Younger infants and premature children experienced the highest rates of RSV-associated hospitalization and had increased risk of ICU admission. RSV prevention products are needed to reduce RSV-associated morbidity in young infants.
Background
Respiratory viral infections are common in febrile infants ≤90 days. However, the detection of viruses other than enterovirus in the blood and cerebrospinal fluid (CSF) of young infants is ...not well defined. We sought to quantify the occurrence of respiratory viruses in the blood and CSF of febrile infants ≤90 days.
Methods
We conducted a nested cohort study examining plasma and CSF samples from febrile infants 15–90 days via rtPCR. The samples were tested for respiratory viruses (respiratory syncytial virus, influenza, enterovirus, parechovirus, adenovirus, bocavirus). Clinical and laboratory data were also collected to determine the presence of serious bacterial infections (SBI).
Results
Twenty‐four percent (30 of 126) of infants had plasma/CSF specimens positive for a respiratory virus. Enterovirus and parechovirus were the most commonly detected respiratory viruses. Viral positivity was highest in plasma samples at 25% (27 of 107) compared with CSF samples at 15% (nine of 62). SBIs (specifically urinary tract infections) were less common in infants with a sample positive for a respiratory virus compared to those without a virus detected (3% vs. 26%, p = 0.008).
Conclusions
Our findings support the use of molecular diagnostics to include the identification of parechovirus in addition to enterovirus in febrile infants ≤90 days. Additionally, these data support the utilization of blood specimens to diagnose enterovirus and parechovirus infections in febrile infants ≤90 days.
This study aims to evaluate the cost-benefit of vaccination services, mostly partial series administration, provided by a mobile clinic program (MCP) in Houston for children of transient and ...low-income families. The study included 469 patients who visited the mobile clinics on regular service days in 2 study periods in 2014 and 836 patients who attended vaccination events in the summer of 2014. The benefit of partial series vaccination was estimated based on vaccine efficacy/effectiveness data. Our conservative cost-benefit estimates show that, compared with office-based settings, every dollar spent on vaccination by the MCP would result in $0.9 societal cost averted as an incremental benefit in regular service days and $3.7 during vaccination-only events. To further improve the cost-benefit of vaccination services in the MCP, decision-makers and stakeholders may consider improving work efficiency during regular service days or hosting more vaccination events.
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