COVID-19 Vaccine Safety Technical (VaST) Work Group: Enhancing vaccine safety monitoring during the pandemic.

During the COVID-19 pandemic, candidate COVID-19 vaccines were being developed for potential use in the United States on an unprecedented, accelerated schedule. It was anticipated that once available, under U.S. Food and Drug Administration (FDA) Emergency Use Authorization (EUA) or FDA approval, COVID-19 vaccines would be broadly used and potentially administered to millions of individuals in a short period of time. Intensive monitoring in the post-EUA/licensure period would be necessary for timely detection and assessment of potential safety concerns. To address this, the Centers for Disease Control and Prevention (CDC) convened an Advisory Committee on Immunization Practices (ACIP) work group focused solely on COVID-19 vaccine safety, consisting of independent vaccine safety experts and representatives from federal agencies - the ACIP COVID-19 Vaccine Safety Technical Work Group (VaST). This report provides an overview of the organization and activities of VaST, summarizes data reviewed as part of the comprehensive effort to monitor vaccine safety during the COVID-19 pandemic, and highlights selected actions taken by CDC, ACIP, and FDA in response to accumulating post-authorization safety data. VaST convened regular meetings over the course of 29 months, from November 2020 through April 2023; through March 2023 FDA issued EUAs for six COVID-19 vaccines from four different manufacturers and subsequently licensed two of these COVID-19 vaccines. The independent vaccine safety experts collaborated with federal agencies to ensure timely assessment of vaccine safety data during this time. VaST worked closely with the ACIP COVID-19 Vaccines Work Group; that work group used safety data and VaST's assessments for benefit-risk assessments and guidance for COVID-19 vaccination policy. Safety topics reviewed by VaST included those identified in safety monitoring systems and other topics of scientific or public interest. VaST provided guidance to CDC's COVID-19 vaccine safety monitoring efforts, provided a forum for review of data from several U.S. government vaccine safety systems, and assured that a diverse group of scientists and clinicians, external to the federal government, promptly reviewed vaccine safety data. In the event of a future pandemic or other biological public health emergency, the VaST model could be used to strengthen vaccine safety monitoring, enhance public confidence, and increase transparency through incorporation of independent, non-government safety experts into the monitoring process, and through strong collaboration among federal and other partners.

Training Residents and Medical Students to Overcome Parents' Vaccine Hesitancy.

Strong provider recommendations increase vaccine confidence. Medical students and pediatric residents, as future physicians, will play an important role in the messaging about vaccines to their parents and patients. The importance of inclusion of vaccine education and communication skills in the medical school curriculum and residency training programs must be recognized to ensure provider confidence in discussions with vaccine-hesitant parents and patients.

Case report of atypical Lemierre's Syndrome associated with Fusobacterium nucleatum infection without internal or external jugular venous thrombophlebitis.

Fusobacterium nucleatum is an anaerobe that is commensal to the human oral cavity. It is usually a component of periodontal plaque that is emerging as a pathogen and quickly attracting attention of the medical and research communities. It has been even discovered in bronchoalveolar lavage of some patients with lung cancer. Lemierre's syndrome (LS) is characterized as septic thrombophlebitis of the internal jugular vein, which usually begins with oropharyngeal infection that worsens and leads to inflammation of the wall of the jugular vein. This is the hallmark of the disease. However, in this case, there was no thrombophlebitis of the internal jugular vein. There is one other case presentation where it was diagnosed without the internal jugular vein involvement. Most sequelae involve infected thrombus of the vein, soft tissue inflammation, persistent bacteremia, and septic emboli, often leading to metastatic infections. Interestingly enough, in the age of SARS-COV-2, LS has also been mistaken for multisystem inflammatory syndrome in children (MIS-C). We present a previously healthy 20-year-old female college student who was transferred from her local hospital to Bristol-Myers Squibb Children's Hospital (BMSCH) at Robert Wood Johnson University Hospital for suspected LS with loculated pleural effusions and necrotizing pneumonia with lung abscess secondary to Fusobacterium nucleatum, systemic and emphysematous osteomyelitis possibly secondary to septic emboli, thrombocytopenia, and palatine tonsil and thyroid abscesses.

Pediatric COVID-19 and Appendicitis: A Gut Reaction to SARS-CoV-2?

BACKGROUND: We describe the temporal pattern of COVID-19 admissions to a tertiary care children's hospital in central New Jersey during the SARS-CoV-2 surge, covering the time period from March 29 to July 26, 2020. METHODS: Medical charts were reviewed for the date of admission, past medical history, and demographic variables, presenting signs and symptoms, admitting laboratory values, diagnostic imaging, diagnosis, treatment modalities, and outcomes including length of stay and disease severity. RESULTS: Patients with symptomatic SARS-CoV-2 infection tended to present with pneumonia early during the study period, which coincided with the early surge in New Jersey cases. Approximately 2 weeks after the peak in reported SARS-CoV-2 cases in New Jersey, we began to see fewer pneumonia cases and an increase in admissions for Multi-Inflammatory Syndrome in Children and cases of acute appendicitis in association with a diagnosis of SARS-CoV-2 infection. CONCLUSIONS: We present a novel association of acute appendicitis in children infected with SARS-CoV-2 and postulate that it may represent a postinfectious hyperinflammatory complication of SARS-CoV-2 infection occurring 2 weeks after the early manifestation of acute pneumonia disease in children.

Pediatric Hospital Medicine: A Proposed New Subspecialty.

Over the past 20 years, hospitalists have emerged as a distinct group of pediatric practitioners. In August of 2014, the American Board of Pediatrics (ABP) received a petition to consider recommending that pediatric hospital medicine (PHM) be recognized as a distinct new subspecialty. PHM as a formal subspecialty raises important considerations related to: (1) quality, cost, and access to pediatric health care; (2) current pediatric residency training; (3) the evolving body of knowledge in pediatrics; and (4) the impact on both primary care generalists and existing subspecialists. After a comprehensive and iterative review process, the ABP recommended that the American Board of Medical Specialties approve PHM as a new subspecialty. This article describes the broad array of challenges and certain unique opportunities that were considered by the ABP in supporting PHM as a new pediatric subspecialty.

Treatment Response in Association with Adherence Patterns to Highly Active Antiretroviral Therapy in Pediatric Patients with Perinatally Acquired HIV Infection.

BACKGROUND: Assessment of longitudinal adherence patterns on virologic and immunologic responses to HAART in perinatally acquired HIV patients has not been studied. METHODS: Perinatally infected pediatric HIV patients with adherence documented at least twice and corresponding viral load and T-cell (%) data measured during 2008-2009 were studied. Multiple adherence measures were utilized to identify patients with persistent adherence, nonadherence, or alteration of adherence. Virologic and immunologic outcomes were assessed. RESULTS: Persistent adherence, nonadherence, and alteration of adherence to HAART were recorded in 41.9%, 8.1%, and 50.0% of 62 studied patients. Persistent adherence was associated with higher likelihood for persistent virologic suppression and lower risk for persistent virologic failure. CONCLUSION: Alteration of adherence to HAART is a significant predictor of persistent virologic failure and high viremia in perinatally infected HIV patients. Implementation of longitudinal adherence assessments may target patients with nonsustained adherence patterns and help decrease the risk for virologic failure and disease progression.

Disparity in hospital utilization of rapid HIV-1 testing for women in labor with undocumented HIV status.

OBJECTIVES: The implementation of rapid HIV-1 testing for women in labor with undocumented HIV status is an essential tool for the prevention of perinatal HIV transmission. Unfortunately, practices of rapid HIV testing for women with unknown HIV status in labor have not been studied. We evaluated the utilization of rapid HIV testing prior to and after implementation of CDC recommendations as well as factors that may affect the utilization rate. DESIGN STUDY: participants were randomly selected from all deliveries (n = 2,359) six months prior to (n = 422) and after (n = 403) hospital implementation of the rapid HIV testing protocol. We reviewed prenatal and labor/delivery records to identify HIV testing history during pregnancy and HIV status at admission; we studied Rapid HIV testing utilization in respect to the implementation of the CDC recommendation; and we analyzed maternal sociodemographic and perinatal factors in association with rapid HIV testing utilization. RESULTS: Unknown HIV status at admission was recorded for 22.0% of women who gave birth prior to, and 18.1% after, implementation of the hospital policy due to either no offering or no acceptance of HIV testing during the pregnancy. Among those eligible for rapid HIV testing, 7.6% were tested prior to, and 9.6% were tested after, implementation of the new policy. As compared with tested women, women not tested were more likely to be white, married, and to have received prenatal primary care from a private physician. CONCLUSIONS: We found that low utilization of rapid HIV-1 testing for women in labor with undocumented HIV status is mostly associated with the sociodemographic inequality of the population of women served. Continuous education of health care providers and a systematic review of rapid HIV testing utilization in the hospital setting are needed in order to achieve successful implementation of the current CDC recommendations.

Protease inhibitor associated mutations compromise the efficacy of therapy in human immunodeficiency virus-1 (HIV-1) infected pediatric patients: a cross-sectional study.

BACKGROUND: Although the introduction of combined therapy with reverse transcriptase and protease inhibitors has resulted in considerable decrease in HIV related mortality; it has also induced the development of multiple drug-resistant HIV-1 variants. The few studies on HIV-1 mutagenesis in HIV infected children have not evaluated the impact of HIV-1 mutations on the clinical, virological and immunological presentation of HIV disease that is fundamental to optimizing the treatment regimens for these patients. RESULTS: A cross sectional study was conducted to evaluate the impact of treatment regimens and resistance mutation patterns on the clinical, virological, and immunological presentation of HIV disease in 41 children (25 male and 16 female) at the Robert Wood Johnson Pediatric AIDS Program in New Brunswick, New Jersey. The study participants were symptomatic and had preceding treatment history with combined ARV regimens including protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Fifteen (36.6%) children were treated with NRTI+NNRTI+ PI, 6 (14.6%) with NRTI+NNRTIs, 13 (31.7%) with NRTI+PIs, and the remaining 7 (17.1%) received NRTIs only. Combined ARV regimens did not significantly influence the incidence of NRTI and NNRTI associated mutations. The duration of ARV therapy and the child's age had no significant impact on the ARV related mutations. The clinico-immunological presentation of the HIV disease was not associated with ARV treatment regimens or number of resistance mutations. However, primary mutations in the protease (PR) gene increased the likelihood of plasma viral load (PVL) > or = 10,000 copies/mL irrespective of the child's age, duration of ARV therapy, presence of NRTI and NNRTI mutation. Viremia > or = 10,000 copies/mL was recorded in almost all the children with primary mutations in the PR region (n = 12/13, 92.3%) as compared with only 50.0% (n = 14/28) of HIV infected children without (PR-), P < 0.008. However, CD-4 T cells were not affected by the mutations in the PR gene of the HIV-1 isolates. CONCLUSION: Primary PR resistance mutations significantly increase the likelihood for high viral replication in pediatric patients with moderate/severe HIV-1 infection, which may affect the long-term clinical prognosis of the HIV infected children.

Rates of Neisseria meningitidis increasing in young adults.

The burden of meningococcal disease has remained unchanged in the United States for the past 4 decades. The currently available meningococcal vaccine is safe and effective, however, due to immunogenic limitations inherent to polysaccharide vaccines, it has been available only for high-risk populations older than 2. Incorporation of a more immunogenic and effective conjugated vaccine into the routine immunization schedule offers an opportunity to substantially affect the incidence of meningococcal disease. The routine use of a meningococcal conjugate vaccine in the United States will save lives and prevent significant morbidity in children and young adults.

Strengthening the supply of routinely recommended vaccines in the United States: recommendations from the National Vaccine Advisory Committee.

Between late 2000 and the spring of 2003, the United States experienced shortages of vaccines against 8 of 11 preventable diseases in children. In response, the Department of Health and Human Services requested that the National Vaccine Advisory Committee (NVAC) make recommendations on strengthening the supply of routinely recommended vaccines. The NVAC appointed a Working Group to identify potential causes of vaccine supply shortages, develop strategies to alleviate or prevent shortages, and enlist stakeholders to consider the applicability and feasibility of these strategies. The NVAC concluded that supply disruptions are likely to continue to occur. Strategies to be implemented in the immediate future include expansion of vaccine stockpiles, increased support for regulatory agencies, maintenance and strengthening of liability protections, improved communication among stakeholders, increased availability of public information, and a campaign to emphasize the benefits of vaccination. Strategies requiring further study include evaluation of appropriate financial incentives to manufacturers and streamlining the regulatory process without compromising safety or efficacy.

Standards for adult immunization practices.

Since the Standards for Adult Immunization Practices were first published in 1990, healthcare researchers and providers have learned important lessons on how to better achieve and maintain high vaccination rates in adults. The success rate of childhood immunization far exceeds the success rate of adult immunization. Thus, information and practices that will produce higher success rates for adult vaccination are crucial, resulting in overall societal cost savings and substantial reductions in hospitalizations and deaths. The Standards, which were developed to encourage the best immunization practices, represent the collective efforts of more than 100 people from more than 60 organizations. The revised Standards are more comprehensive than the 1990 Standards and focus on the accessibility and availability of vaccines, proper assessment of patient vaccination status, opportunities for patient education, correct procedures for administering vaccines, implementation of strategies to improve vaccination rates, and partnerships with the community to reach target patient populations. The revised Standards are recommended for use by all healthcare professionals and all public and private sector organizations that provide immunizations for adults. All who are involved in adult immunization should strive to follow the Standards in order to create the same level of success achieved by childhood vaccination programs and to meet the Healthy People 2010 goals.