Development of Next-Generation COVID-19 Vaccines: BARDA Supported Phase 2b Study Designs.

In response to the COVID-19 pandemic, vaccines were quickly and successfully developed and deployed, saving millions of lives globally. While first generation vaccines are safe and effective in preventing disease caused by SARSCoV-2, next-generation vaccines have the potential to improve efficacy and safety. Vaccines delivered by a mucosal route may elicit greater protective immunity at respiratory surfaces thereby reducing transmission. Inclusion of viral antigens in addition to the spike protein may enhance protection against emerging variants of concern. Next-generation vaccine platforms with a new mechanism of action may necessitate efficacy trials to fulfill regulatory requirements. The Biomedical Advanced Research and Development Authority (BARDA) will be supporting Phase 2b clinical trials of candidate next-generation vaccines. The primary endpoint will be improved efficacy in terms of symptomatic disease relative to a currently approved COVID-19 vaccine. In this paper, we discuss the planned endpoints and potential challenges to this complex program.

Utilization of chronic lung disease treatment before the respiratory syncytial virus season as palivizumab prophylaxis qualifier in the American Academy of Pediatrics Guidelines.

Guidelines from the American Academy of Pediatrics recommend palivizumab immunoprophylaxis for children with CLD in their second year of life if they continue to need treatment within 6 months before the RSV season. The utilization patterns of treatment (chronic corticosteroid therapy, diuretic therapy, or supplemental oxygen) are not well understood. We examined variations in CLD treatment for ten consecutive 20-day segments preceding RSV season onset. Among infants and children with CLD (n = 19,026), 35.2% received one or more medical treatments for CLD any time within 200 days before entering the second RSV season: 8.6%, 3.2%, and 29.7% received supplemental oxygen, diuretics, and corticosteroids, respectively. Utilization decreased as infants' age increased with corticosteroids surpassing oxygen and diuretics. To avoid the capture of intermittent use of corticosteroids for acute infections, we found requiring a minimum of 45 days cumulative exposure was reasonable to determine chronic use. What is Known: • Guidelines from the American Academy of Pediatrics recommend palivizumab immunoprophylaxis for children with CLD in their second year of life if they continue to need treatment within 6 months before the RSV season. • The utilization patterns of treatment (chronic corticosteroid therapy, diuretic therapy, or supplemental oxygen) are not well understood. A definition of chronic corticosteroid therapy in this setting is not available. What is New: • Among infants and children with CLD of prematurity, 35.2% received one or more medical treatments for CLD any time within 200 days before entering the second RSV season: 8.6%, 3.2%, and 29.7% received oxygen, diuretics, and corticosteroids, respectively. Utilization decreased as infants' age increased with corticosteroids surpassing oxygen and diuretics. • A minimum of 45 days cumulative corticosteroid use within the past 90 days would accurately capture chronic use to fulfill criteria for immunoprophylaxis while limiting the inclusion of intermittent use of corticosteroids for acute infections.

The Facts About Vaccine Safety.

The Vaccine Compensation System evaluates true and false associations between vaccination and adverse events. The data from the system enable the calculation of the risk of serious adverse events per million doses given of each vaccine.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA): 2020 Guideline on Diagnosis and Management of Babesiosis.

The purpose of this guideline is to provide evidence-based guidance for the most effective strategies for the diagnosis and management of babesiosis. The diagnosis and treatment of co-infection with babesiosis and Lyme disease will be addressed in a separate Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR) guideline [1]. Recommendations for the diagnosis and treatment of human granulocytic anaplasmosis can be found in the recent rickettsial disease guideline developed by the Centers for Disease Control and Prevention [2]. The target audience for the babesiosis guideline includes primary care physicians and specialists caring for this condition, such as infectious diseases specialists, emergency physicians, intensivists, internists, pediatricians, hematologists, and transfusion medicine specialists.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA): 2020 Guideline on Diagnosis and Management of Babesiosis.

The purpose of this guideline is to provide evidence-based guidance for the most effective strategies for the diagnosis and management of babesiosis. The diagnosis and treatment of co-infection with babesiosis and Lyme disease will be addressed in a separate Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR) guideline [1]. Recommendations for the diagnosis and treatment of human granulocytic anaplasmosis can be found in the recent rickettsial disease guideline developed by the Centers for Disease Control and Prevention [2]. The target audience for the babesiosis guideline includes primary care physicians and specialists caring for this condition, such as infectious diseases specialists, emergency physicians, intensivists, internists, pediatricians, hematologists, and transfusion medicine specialists.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Usability of encounter data for Medicaid comprehensive managed care vs traditional Medicaid fee-for-service claims among pregnant women.

BACKGROUND: The completeness of medical encounters capture among Medicaid enrollees in comprehensive managed care (CMC) has been shown to vary across states and years. CMC penetration has grown, and CMC encounter capture specific to pregnancy care is understudied. OBJECTIVES: To compare the completeness of encounter data for pregnant beneficiaries in CMC versus traditional fee-for-service (FFS) in Texas and Florida between 2007 and 2010. METHODS: Using Medicaid Analytic eXtract (MAX) data linked to Florida and Texas birth certificate records, for each state and study year, we compared proportions using seven themes: (a) delivery; (b) prenatal visits; (c) dispensed prescriptions during pregnancy; (d) gestational diabetes and blood glucose testing; (e) antidiabetics and diagnosis of diabetes mellitus; (f) antibiotics for urinary tract infection and outpatient encounter; and (g) bacterial vaginosis and dispensing for metronidazole or clindamycin. We considered CMC data to be acceptable if proportions were no less than 10% below the corresponding (2007 to 2010) FFS control values. RESULTS: Pregnancy-related characteristics of FFS vs CMC denominators were comparable. Proportions for the seven measures among FFS controls ranged from 26% to 98%. In Texas, CMC encounter data met the thresholds for all measures between 2007 and 2010. Florida had usable CMC encounter data starting from 2009 with incomplete medical and pharmacy records in 2007 and 2008. CONCLUSIONS: The quality of CMC encounter data in MAX files for pregnant women varied in Florida and Texas and improved over time. Use of pregnancy-specific measures can aid researchers in selecting states and years with acceptable encounter data quality.

Identifying Gaps in Respiratory Syncytial Virus Disease Epidemiology in the United States Prior to the Introduction of Vaccines.

Respiratory syncytial virus (RSV) causes lower respiratory tract illness frequently. No effective antivirals or vaccines for RSV are approved for use in the United States; however, there are at least 50 vaccines and monoclonal antibody products in development, with those targeting older adults and pregnant women (to protect young infants) in phase 2 and 3 clinical trials. Unanswered questions regarding RSV epidemiology need to be identified and addressed prior to RSV vaccine introduction to guide the measurement of impact and future recommendations. The Centers for Disease Control and Prevention (CDC) convened a technical consultation to gather input from external subject matter experts on their individual perspectives regarding evidence gaps in current RSV epidemiology in the United States, potential studies and surveillance platforms needed to fill these gaps, and prioritizing efforts. Participants articulated their individual views, and CDC staff synthesized individuals' input into this report.

Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP).

Meningococcal disease describes the spectrum of infections caused by Neisseria meningiditis, including meningitdis, bacteremia, and bacteremic pneumonia. Two quadrivalent meningococcal polysaccharide-protein conjugate vaccines that provide protection against meningococcal serogroups A, C, W, and Y (MenACWY-D [Menactra, manufactured by Sanofi Pasteur, Inc., Swiftwater, Pennsylvania] and MenACWY-CRM [Menveo, manufactured by Novartis Vaccines, Cambridge, Massachusetts]) are licensed in the United States for use among persons aged 2 through 55 years. MenACWY-D also is licensed for use among infants and toddlers aged 9 through 23 months. Quadrivalent meningococcal polysaccharide vaccine (MPSV4 [Menommune, manufactured by sanofi pasteur, Inc., Swiftwater, Pennsylvania]) is the only vaccine licensed for use among persons aged ≥56 years. A bivalent meningococcal polysaccharide protein conjugate vaccine that provides protection against meningococcal serogroups C and Y along with Haemophilus influenzae type b (Hib) (Hib-MenCY-TT [MenHibrix, manufactured by GlaxoSmithKline Biologicals, Rixensart, Belgium]) is licensed for use in children aged 6 weeks through 18 months. This report compiles and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) regarding prevention and control of meningococcal disease in the United States, specifically the changes in the recommendations published since 2005 (CDC. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2005;54 [No. RR-7]). As a comprehensive summary of previously published recommendations, this report does not contain any new recommendations; it is intended for use by clinicians as a resource. ACIP recommends routine vaccination with a quadrivalent meningococcal conjugate vaccine (MenACWY) for adolescents aged 11 or 12 years, with a booster dose at age 16 years. ACIP also recommends routine vaccination for persons at increased risk for meningococcal disease (i.e., persons who have persistent complement component deficiencies, persons who have anatomic or functional asplenia, microbiologists who routinely are exposed to isolates of N. meningitidis, military recruits, and persons who travel to or reside in areas in which meningococcal disease is hyperendemic or epidemic). Guidelines for antimicrobial chemoprophylaxis and for evaluation and management of suspected outbreaks of meningococcal disease also are provided.