Reflections on The Advisory Committee on Immunization Practices during the COVID-19 Pandemic.

Pediatricians and primary care providers serve an important role in building trust with families and communities. To support the critical role of front-line providers, this perspective seeks to reflect on the work of the Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices to support COVID-19 pandemic response efforts. Although ACIP recommends vaccines for all age groups, this perspective focuses on the pediatric lens and is tailored to Academic Pediatrics. ACIP adapted from in-person meetings 3 times yearly to virtual meetings on an emergency basis to ensure a thorough review and presentation of all the components of Evidence to Recommendation framework, including explicit consideration of equity in the decision-making process. The need for diverse enrollment in clinical trials was highlighted as critical for supporting recommendations and enhancing trust. Near real-time vaccine safety surveillance was implemented at scale and emphasized the importance of collaboration between federal partners engaged in vaccine safety in the U.S. and extended to other countries with similar safety surveillance systems to enable early recognition and response to safety concerns. A key equity opportunity for future pandemics is to shorten the time between vaccine was available for adults and young children.

A pilot randomized controlled trial of text messages to improve well-child visit attendance after no-show.

OBJECTIVE: Evaluate the effectiveness of text messages to systematically engage parents/guardians ("caregivers") to reschedule a well-child visit (WCV) that was missed ("no-show") and attend that rescheduled WCV visits. METHODS: Patients <18 years in one of five pediatrics or family medicine clinics, in one health system in the Southeast U.S., were eligible. Patients without a rescheduled WCV after a no-show were randomized into intervention (text messages) or care-as-usual comparison, stratified by language (English/Spanish). Enrollment occurred May-July 2022. Up to three text messages were sent to caregivers one week apart via REDCap and Twilio, advising how to reschedule the missed appointment by phone or health portal. Primary outcomes were (1) rescheduling a WCV within 6 weeks of no-show and (2) completing a rescheduled WCV within 6 weeks. Risk differences (RD) and odds ratios (OR) were used to evaluate the effect of text messages. RESULTS: 720 patients were randomized and analyzed (texts: 361, comparison: 359). The proportion rescheduling WCV after text versus usual care was English: 18.85% vs. 15.02%, respectively, and Spanish: 5.94% vs. 8.14%, with overall RD +1.98% (95% CI: -1.85, 5.81) and OR 1.21 (95% CI: 0.79, 1.84; p-value 0.38). Completed WCV rates in text or usual care were English: 13.08% vs. 6.59%, and Spanish: 5.81% vs. 5.94% with texts associated with RD +2.83% (95% CI: 1.66, 4.00) and OR 1.86 (95% CI: 1.09, 3.19). CONCLUSION: Text message follow-up after a no-show WCV may positively impact attendance at WCVs rescheduled in the subsequent 6 weeks. TRIAL REGISTRATION: ClinicalTrials.gov NCT05086237.

Use of the Pfizer Pentavalent Meningococcal Vaccine Among Persons Aged ≥10 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2023.

Meningococcal disease is a life-threatening invasive infection caused by Neisseria meningitidis. Two quadrivalent (serogroups A, C, W, and Y) meningococcal conjugate vaccines (MenACWY) (MenACWY-CRM [Menveo, GSK] and MenACWY-TT [MenQuadfi, Sanofi Pasteur]) and two serogroup B meningococcal vaccines (MenB) (MenB-4C [Bexsero, GSK] and MenB-FHbp [Trumenba, Pfizer Inc.]), are licensed and available in the United States and have been recommended by CDC's Advisory Committee on Immunization Practices (ACIP). On October 20, 2023, the Food and Drug Administration approved the use of a pentavalent meningococcal vaccine (MenACWY-TT/MenB-FHbp [Penbraya, Pfizer Inc.]) for prevention of invasive disease caused by N. meningitidis serogroups A, B, C, W, and Y among persons aged 10-25 years. On October 25, 2023, ACIP recommended that MenACWY-TT/MenB-FHbp may be used when both MenACWY and MenB are indicated at the same visit for the following groups: 1) healthy persons aged 16-23 years (routine schedule) when shared clinical decision-making favors administration of MenB vaccine, and 2) persons aged ≥10 years who are at increased risk for meningococcal disease (e.g., because of persistent complement deficiencies, complement inhibitor use, or functional or anatomic asplenia). Different manufacturers' serogroup B-containing vaccines are not interchangeable; therefore, when MenACWY-TT/MenB-FHbp is used, subsequent doses of MenB should be from the same manufacturer (Pfizer Inc.). This report summarizes evidence considered for these recommendations and provides clinical guidance for the use of MenACWY-TT/MenB-FHbp.

Tick-Borne Encephalitis Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023.

Tick-borne encephalitis (TBE) virus is focally endemic in parts of Europe and Asia. The virus is primarily transmitted to humans by the bites of infected: Ixodes species ticks but can also be acquired less frequently by alimentary transmission. Other rare modes of transmission include through breastfeeding, blood transfusion, solid organ transplantation, and slaughtering of viremic animals. TBE virus can cause acute neurologic disease, which usually results in hospitalization, often permanent neurologic or cognitive sequelae, and sometimes death. TBE virus infection is a risk for certain travelers and for laboratory workers who work with the virus. In August 2021, the Food and Drug Administration approved Ticovac TBE vaccine for use among persons aged ≥1 year. This report summarizes the epidemiology of and risks for infection with TBE virus, provides information on the immunogenicity and safety of TBE vaccine, and summarizes the recommendations of the Advisory Committee on Immunization Practices (ACIP) for use of TBE vaccine among U.S. travelers and laboratory workers.

The Present and Future of the Adult Pneumococcal Vaccine Program in the United States.

Adult Pneumococcal Vaccine Program in the United StatesStreptococcus pneumoniae (pneumococcus) is a common cause of bacterial respiratory infections leading to substantial morbidity and mortality. Here, Kobayashi et al. discuss the recently updated U.S. guidelines for adult pneumococcal vaccination.

Use of 15-Valent Pneumococcal Conjugate Vaccine Among U.S. Children: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2022.

The 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13, Wyeth Pharmaceuticals, Inc, a subsidiary of Pfizer, Inc]) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Merck Sharp & Dohme LLC]) have been recommended for U.S. children, and the recommendations vary by age group and risk group (1,2). In 2021, 15-valent pneumococcal conjugate vaccine (PCV15 [Vaxneuvance, Merck Sharp & Dohme LLC]) was licensed for use in adults aged ≥18 years (3). On June 17, 2022, the Food and Drug Administration (FDA) approved an expanded usage for PCV15 to include persons aged 6 weeks-17 years, based on studies that compared antibody responses to PCV15 with those to PCV13 (4). PCV15 contains serotypes 22F and 33F (in addition to the PCV13 serotypes) conjugated to CRM197 (genetically detoxified diphtheria toxin). On June 22, 2022, CDC's Advisory Committee on Immunization Practices (ACIP) recommended use of PCV15 as an option for pneumococcal conjugate vaccination of persons aged <19 years according to currently recommended PCV13 dosing and schedules (1,2). ACIP employed the Evidence to Recommendation (EtR) Framework,* using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE)† approach to guide its deliberations regarding use of these vaccines. Risk-based recommendations on use of PPSV23 for persons aged 2-18 years with certain underlying medical conditions§ that increase the risk for pneumococcal disease have not changed.

Associations Between Weight and Lower Respiratory Tract Disease Outcomes in Hospitalized Children.

OBJECTIVE: To identify associations between weight status and clinical outcomes in children with lower respiratory tract infection (LRTI) or asthma requiring hospitalization. METHODS: We performed a retrospective cohort study of 2 to 17 year old children hospitalized for LRTI and/or asthma from 2009 to 2019 using electronic health record data from the PEDSnet clinical research network. Children <2 years, those with medical complexity, and those without a calculable BMI were excluded. Children were classified as having underweight, normal weight, overweight, or class 1, 2, or 3 obesity based on Body Mass Index percentile for age and sex. Primary outcomes were need for positive pressure respiratory support and ICU admission. Subgroup analyses were performed for children with a primary diagnosis of asthma. Outcomes were modeled with mixed-effects multivariable logistic regression incorporating age, sex, and payer as fixed effects. RESULTS: We identified 65 132 hospitalizations; 6.7% with underweight, 57.8% normal weight, 14.6% overweight, 13.2% class 1 obesity, 5.0% class 2 obesity, and 2.8% class 3 obesity. Overweight and obesity were associated with positive pressure respiratory support (class 3 obesity versus normal weight odds ratio [OR] 1.62 [1.38-1.89]) and ICU admission (class 3 obesity versus normal weight OR 1.26 [1.12-1.42]), with significant associations for all categories of overweight and obesity. Underweight was also associated with positive pressure respiratory support (OR 1.39 [1.24-1.56]) and ICU admission (1.40 [1.30-1.52]). CONCLUSIONS: Both underweight and overweight or obesity are associated with increased severity of LRTI or asthma in hospitalized children.

Dengue: A Growing Problem With New Interventions.

Dengue is the disease caused by 1 of 4 distinct, but closely related dengue viruses (DENV-1-4) that are transmitted by Aedes spp. mosquito vectors. It is the most common arboviral disease worldwide, with the greatest burden in tropical and sub-tropical regions. In the absence of effective prevention and control measures, dengue is projected to increase in both disease burden and geographic range. Given its increasing importance as an etiology of fever in the returning traveler or the possibility of local transmission in regions in the United States with competent vectors, as well as the risk for large outbreaks in endemic US territories and associated states, clinicians should understand its clinical presentation and be familiar with appropriate testing, triage, and management of patients with dengue. Control and prevention efforts reached a milestone in June 2021 when the Advisory Committee on Immunization Practices (ACIP) recommended Dengvaxia for routine use in children aged 9 to 16 years living in endemic areas with laboratory confirmation of previous dengue virus infection. Dengvaxia is the first vaccine against dengue to be recommended for use in the United States and one of the first to require laboratory testing of potential recipients to be eligible for vaccination. In this review, we outline dengue pathogenesis, epidemiology, and key clinical features for front-line clinicians evaluating patients presenting with dengue. We also provide a summary of Dengvaxia efficacy, safety, and considerations for use as well as an overview of other potential new tools to control and prevent the growing threat of dengue .

Use of 15-Valent Pneumococcal Conjugate Vaccine and 20-Valent Pneumococcal Conjugate Vaccine Among U.S. Adults: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2022.

In 2021, 20-valent pneumococcal conjugate vaccine (PCV) (PCV20) (Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.) and 15-valent PCV (PCV15) (Merck Sharp & Dohme Corp.) were licensed by the Food and Drug Administration for adults aged ≥18 years, based on studies that compared antibody responses to PCV20 and PCV15 with those to 13-valent PCV (PCV13) (Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.). Antibody responses to two additional serotypes included in PCV15 were compared to corresponding responses after PCV13 vaccination, and antibody responses to seven additional serotypes included in PCV20 were compared with those to the 23-valent pneumococcal polysaccharide vaccine (PPSV23) (Merck Sharp & Dohme Corp.). On October 20, 2021, the Advisory Committee on Immunization Practices (ACIP) recommended use of either PCV20 alone or PCV15 in series with PPSV23 for all adults aged ≥65 years, and for adults aged 19-64 years with certain underlying medical conditions or other risk factors* who have not previously received a PCV or whose previous vaccination history is unknown. ACIP employed the Evidence to Recommendation (EtR) framework,† using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE)§ approach to guide its deliberations regarding use of these vaccines. Before this, PCV13 and PPSV23 were recommended for use for U.S. adults and the recommendations varied by age and risk groups. This was simplified in the new recommendations.

Weight Status and Risk of Inpatient Admission for Children With Lower Respiratory Tract Disease.

OBJECTIVES: To identify associations between weight category and hospital admission for lower respiratory tract disease (LRTD), defined as asthma, community-acquired pneumonia, viral pneumonia, or bronchiolitis, among children evaluated in pediatric emergency departments (PEDs). METHODS: We performed a retrospective cohort study of children 2 to <18 years of age evaluated in the PED at 6 children's hospitals within the PEDSnet clinical research network from 2009 to 2019. BMI percentile of children was classified as underweight, healthy weight, overweight, and class 1, 2, or 3 obesity. Children with complex chronic conditions were excluded. Mixed-effects multivariable logistic regression was used to assess associations between BMI categories and hospitalization or 7- and 30-day PED revisits, adjusted for covariates (age, sex, race and ethnicity, and payer). RESULTS: Among 107 446 children with 218 180 PED evaluations for LRTD, 4.5% had underweight, 56.4% had healthy normal weight, 16.1% had overweight, 14.6% had class 1 obesity, 5.5% had class 2 obesity, and 3.0% had class 3 obesity. Underweight was associated with increased risk of hospital admission compared with normal weight (odds ratio [OR] 1.76; 95% confidence interval [CI] 1.69-1.84). Overweight (OR 0.87; 95% CI 0.85-0.90), class 1 obesity (OR 0.88; 95% CI 0.85-0.91), and class 2 obesity (OR 0.91; 95% CI 0.87-0.96) had negative associations with hospital admission. Class 1 and class 2, but not class 3, obesity had small positive associations with 7- and 30-day PED revisits. CONCLUSIONS: We found an inverse relationship between patient weight category and risk for hospital admission in children evaluated in the PED for LRTD.

Dengue Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021.

Dengue is a vectorborne infectious disease caused by dengue viruses (DENVs), which are predominantly transmitted by Aedes aegypti and Aedes albopictus mosquitos. Dengue is caused by four closely related viruses (DENV-1-4), and a person can be infected with each serotype for a total of four infections during their lifetime. Areas where dengue is endemic in the United States and its territories and freely associated states include Puerto Rico, American Samoa, the U.S. Virgin Islands, the Federated States of Micronesia, the Republic of Marshall Islands, and the Republic of Palau. This report summarizes the recommendations of the Advisory Committee on Immunization Practices (ACIP) for use of the Dengvaxia vaccine in the United States. The vaccine is a live-attenuated, chimeric tetravalent dengue vaccine built on a yellow fever 17D backbone. Dengvaxia is safe and effective in reducing dengue-related hospitalizations and severe dengue among persons who have had dengue infection in the past. Previous natural infection is important because Dengvaxia is associated with an increased risk for severe dengue in those who experience their first natural infection (i.e., primary infection) after vaccination. Dengvaxia was licensed by the Food and Drug Administration for use among children and adolescents aged 9-16 years (referred to in this report as children). ACIP recommends vaccination with Dengvaxia for children aged 9-16 having evidence of a previous dengue infection and living in areas where dengue is endemic. Evidence of previous dengue infection, such as detection of anti-DENV immunoglobulin G with a highly specific serodiagnostic test, will be required for eligible children before vaccination.

Advisory Committee on Immunization Practices Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger - United States, 2020.

At its October 2019 meeting, the Advisory Committee on Immunization Practices (ACIP)* approved the 2020 Recommended Child and Adolescent Immunization Schedule for Ages 18 Years or Younger. The 2020 child and adolescent immunization schedule summarizes ACIP recommendations, including several changes from the 2019 immunization schedule† on the cover page, three tables, and notes found on the CDC immunization schedule website (https://www.cdc.gov/vaccines/schedules/index.html). Health care providers are advised to use the tables and the notes together. This immunization schedule is recommended by ACIP (https://www.cdc.gov/vaccines/acip/index.html) and approved by the CDC Director, the American Academy of Pediatrics, the American Academy of Family Physicians, the American College of Obstetricians and Gynecologists, and, for the first time, the American College of Nurse-Midwives.

Suboptimal uptake of human papillomavirus (HPV) vaccine in survivors of childhood and adolescent and young adult (AYA) cancer.

PURPOSE: To estimate the population-based incidence of HPV vaccination after childhood cancer. METHODS: Pediatric and young adult cancer survivors identified in the institutional Comprehensive Cancer Center registry were linked to the North Carolina Immunization Registry (NCIR). Initiation and completion of any HPV vaccine was evaluated in survivors born between 1984 and 2002 with an NCIR record by December 2014. Descriptive statistics and Kaplan-Meier estimates of cumulative incidence were stratified by sex and age at eligibility for vaccine. Cox proportional hazards were conducted and stratified by sex. RESULTS: Among 879 (n = 428 female; n = 451 male) study-eligible cancer survivors without prior HPV vaccination (n = 501 < 18 years, n = 378 ≥ 18 years at the time of eligibility), the cumulative incidence of HPV vaccine initiation following cancer therapy was 48.1% among females at 8.2 years and 29.2% among males at 5.0 years after vaccine eligibility among those < 18 years, and 6.2% among females at 8.1 years and 2.0% among males at 4.2 years after vaccine eligibility among those ≥ 18 years. Among those who initiated vaccination, 53% of females and 43% of males completed a 3-dose series. Younger age at cancer diagnosis (≤ 10 and 11-14 years vs. ≥ 15 years) and shorter interval from diagnosis to vaccine eligibility were more likely to initiate vaccination in models adjusted for age at eligibility, race/ethnicity, cancer type, relapse, and transplant. CONCLUSIONS: Despite the benefit of a cancer prevention strategy, cancer survivors are sub-optimally vaccinated against HPV. IMPLICATIONS FOR CANCER SURVIVORS: Immunization registries can help oncologists and primary care providers identify gaps in vaccination and target HPV vaccine delivery in survivors.

Is weight associated with severity of acute respiratory illness?

BACKGROUND/OBJECTIVES: Obesity was an independent risk factor for severe disease in hospitalized adults during the 2009 pandemic H1N1 influenza season. Few studies have investigated the association between weight and severity of acute respiratory illnesses in children or in adults seeking care in the emergency department (ED) during other winter respiratory seasons. SUBJECTS/METHODS: We prospectively and systematically enrolled patients ≥2 years of age who presented to the ED or inpatient setting in a single geographic region with fever/acute respiratory illness over four consecutive winter respiratory seasons (2010-2014). We collected demography, height and weight, and high risk co-morbid conditions. Multivariable logistic regression was used for prediction of hospital admission (primary outcome), length of stay and supplemental oxygen requirement among those hospitalized, and antibiotic prescription (secondary outcomes). RESULTS: We enrolled 3560 patients (N = 749 children, 2811 adults), 1405 (39%) with normal weight, 860 (24%) with overweight, and 1295 (36%) with obesity. Following multivariable logistic regression, very young or very old age (p < 0.001) and high-risk conditions (p < 0.001) predicted hospitalization. Risk of hospitalization was decreased for adults with overweight [aOR 0.8 (95% CI 0.6-1.0)], class 1 obesity [aOR 0.7 (95% CI 0.5-1.0)], and class 2 obesity [aOR 0.6 (95% CI 0.4-0.8)] compared to normal-weight. Class 3 obesity was associated with supplemental oxygen requirement in adults [aOR 1.6 (95% CI 1.1-2.5)]. No association was seen in children. CONCLUSION: Overweight and obesity were not associated with increased risk of hospitalization during winter respiratory seasons in children or adults.

Association of Prior Vaccination With Influenza Vaccine Effectiveness in Children Receiving Live Attenuated or Inactivated Vaccine.

Importance: Some studies have reported negative effects of prior-season influenza vaccination. Prior-season influenza vaccination effects on vaccine effectiveness (VE) in children are not well understood. Objective: To assess the association of prior-season influenza vaccination with subsequent VE in children aged 2 to 17 years. Design, Setting, and Participants: This multiseason, test-negative case-control study was conducted in outpatient clinics at 4 US sites among children aged 2 to 17 years with a medically attended febrile acute respiratory illness. Participants were recruited during the 2013-2014, 2014-2015, and 2015-2016 seasons when influenza circulated locally. Cases were children with influenza confirmed by reverse-transcription polymerase chain reaction. Test-negative control individuals were children with negative test results for influenza. Exposures: Vaccination history, including influenza vaccine type received in the enrollment season (live attenuated influenza vaccine [LAIV], inactivated influenza vaccine [IIV], or no vaccine) and season before enrollment (LAIV, IIV, or no vaccine), determined from medical records and immunization registries. Main Outcomes and Measures: LAIV and IIV effectiveness by influenza type and subtype (influenza A[H1N1]pdm09, influenza A[H3N2], or influenza B), estimated as 100 × (1 - odds ratio) in a logistic regression model with adjustment for potential confounders. Prior season vaccination associations were assessed with an interaction term. Results: Of 3369 children (1749 [52%] male; median age, 6.6 years [range, 2-17 years]) included in the analysis, 772 (23%) had a positive test result for influenza and 1674 (50%) were vaccinated in the enrollment season. Among LAIV recipients, VE against influenza A(H3N2) was higher among children vaccinated in both the enrollment and 1 prior season (50.3% [95% CI, 17.0% to 70.2%]) than among those without 1 prior season vaccination (-82.4% [95% CI, -267.5% to 9.5%], interaction P < .001). The effectiveness of LAIV against influenza A(H1N1)pdm09 was not associated with prior season vaccination among those with prior season vaccination (47.5% [95% CI, 11.4% to 68.9%]) and among those without prior season vaccination (7.8% [95% CI, -101.9% to 57.9%]) (interaction P = .37). Prior season vaccination was not associated with effectiveness of IIV against influenza A(H3N2) (38.7% [95% CI, 6.8% to 59.6%] among those with prior-season vaccination and 23.2% [95% CI, -38.3% to 57.4%] among those without prior-season vaccination, interaction P = .16) or with effectiveness of IIV against influenza A[H1N1]pdm09 (72.4% [95% CI, 56.0% to 82.7%] among those with prior season vaccination and 67.5% [95% CI, 32.1% to 84.4%] among those without prior season vaccination, interaction P = .93). Residual protection from prior season vaccination only (no vaccination in the enrollment season) was observed for influenza B (LAIV: 60.0% [95% CI, 36.8% to 74.7%]; IIV: 60.0% [36.9% to 74.6%]). Similar results were observed in analyses that included repeated vaccination in 2 and 3 prior seasons. Conclusions and Relevance: Influenza VE varied by influenza type and subtype and vaccine type, but prior-season vaccination was not associated with reduced VE. These findings support current recommendations for annual influenza vaccination of children.