Cytomegalovirus Infection Drives Avidity Selection of Natural Killer Cells.

The process of affinity maturation, whereby T and B cells bearing antigen receptors with optimal affinity to the relevant antigen undergo preferential expansion, is a key feature of adaptive immunity. Natural killer (NK) cells are innate lymphocytes capable of "adaptive" responses after cytomegalovirus (CMV) infection. However, whether NK cells are similarly selected on the basis of their avidity for cognate ligand is unknown. Here, we showed that NK cells with the highest avidity for the mouse CMV glycoprotein m157 were preferentially selected to expand and comprise the memory NK cell pool, whereas low-avidity NK cells possessed greater capacity for interferon-γ (IFN-γ) production. Moreover, we provide evidence for avidity selection occurring in human NK cells during human CMV infection. These results delineate how heterogeneity in NK cell avidity diversifies NK cell effector function during antiviral immunity, and how avidity selection might serve to produce the most potent memory NK cells.

The Impact of Climate Change on Asthma and Allergic-Immunologic Disease.

PURPOSE OF REVIEW: This review discusses climate change-related impacts on asthma and allergic-immunologic disease, relevant US public health efforts, and healthcare professional resources. RECENT FINDINGS: Climate change can impact people with asthma and allergic-immunologic disease through various pathways, including increased exposure to asthma triggers (e.g., aeroallergens, ground-level ozone). Climate change-related disasters (e.g., wildfires, floods) disrupting healthcare access can complicate management of any allergic-immunologic disease. Climate change disproportionately affects some communities, which can exacerbate disparities in climate-sensitive diseases like asthma. Public health efforts include implementing a national strategic framework to help communities track, prevent, and respond to climate change-related health threats. Healthcare professionals can use resources or tools to help patients with asthma and allergic-immunologic disease prevent climate change-related health impacts. Climate change can affect people with asthma and allergic-immunologic disease and exacerbate health disparities. Resources and tools are available to help prevent climate change-related health impacts at the community and individual level.

Association between thromboembolic events and COVID-19 infection within 30 days: a case-control study among a large sample of adult hospitalized patients in the United States, March 2020-June 2021.

The association between thromboembolic events (TE) and COVID-19 infection is not completely understood at the population level in the United States. We examined their association using a large US healthcare database. We analyzed data from the Premier Healthcare Database Special COVID-19 Release and conducted a case-control study. The study population consisted of men and non-pregnant women aged ≥ 18 years with (cases) or without (controls) an inpatient ICD-10-CM diagnosis of TE between 3/1/2020 and 6/30/2021. Using multivariable logistic regression, we assessed the association between TE occurrence and COVID-19 diagnosis, adjusting for demographic factors and comorbidities. Among 227,343 cases, 15.2% had a concurrent or prior COVID-19 diagnosis within 30 days of their index TE. Multivariable regression analysis showed a statistically significant association between a COVID-19 diagnosis and TE among cases when compared to controls (adjusted odds ratio [aOR] 1.75, 95% CI 1.72-1.78). The association was more substantial if a COVID-19 diagnosis occurred 1-30 days prior to index hospitalization (aOR 3.00, 95% CI 2.88-3.13) compared to the same encounter as the index hospitalization. Our findings suggest an increased risk of TE among persons within 30 days of being diagnosed COVID-19, highlighting the need for careful consideration of the thrombotic risk among COVID-19 patients, particularly during the first month following diagnosis.

Mental Health Conditions and Severe COVID-19 Outcomes after Hospitalization, United States.

Among 664,956 hospitalized COVID-19 patients during March 2020-July 2021 in the United States, select mental health conditions (i.e., anxiety, depression, bipolar, schizophrenia) were associated with increased risk for same-hospital readmission and longer length of stay. Anxiety was also associated with increased risk for intensive care unit admission, invasive mechanical ventilation, and death.

Post-COVID-19 Symptoms and Conditions Among Children and Adolescents - United States, March 1, 2020-January 31, 2022.

Post-COVID-19 (post-COVID) symptoms and conditions* are new, recurring, or ongoing health problems that occur 4 or more weeks after infection with SARS-CoV-2 (the virus that causes COVID-19). Previous studies have characterized and estimated the incidence of post-COVID conditions among adults (1,2), but data among children and adolescents are limited (3-8). Using a large medical claims database, CDC assessed nine potential post-COVID signs and symptoms (symptoms) and 15 potential post-COVID conditions among 781,419 U.S. children and adolescents aged 0-17 years with laboratory-confirmed COVID-19 (patients with COVID-19) compared with 2,344,257 U.S. children and adolescents without recognized COVID-19 (patients without COVID-19) during March 1, 2020-January 31, 2022. The analysis identified several symptoms and conditions with elevated adjusted hazard ratios among patients with COVID-19 (compared with those without). The highest hazard ratios were recorded for acute pulmonary embolism (adjusted hazard ratio [aHR] = 2.01), myocarditis and cardiomyopathy (1.99), venous thromboembolic event (1.87), acute and unspecified renal failure (1.32), and type 1 diabetes (1.23), all of which were rare or uncommon in this study population. Conversely, symptoms and conditions that were most common in this study population had lower aHRs (near or below 1.0). Patients with COVID-19 were less likely than were patients without to experience respiratory signs and symptoms, symptoms of mental conditions, muscle disorders, neurological conditions, anxiety and fear-related disorders, mood disorders, and sleeping disorders. COVID-19 prevention strategies, including vaccination for all eligible children and adolescents, are critical to prevent SARS-CoV-2 infection and subsequent illness, including post-COVID symptoms and conditions (9).

Mortality Risk Among Patients Hospitalized Primarily for COVID-19 During the Omicron and Delta Variant Pandemic Periods - United States, April 2020-June 2022.

The risk for COVID-19-associated mortality increases with age, disability, and underlying medical conditions (1). Early in the emergence of the Omicron variant of SARS-CoV-2, the virus that causes COVID-19, mortality among hospitalized COVID-19 patients was lower than that during previous pandemic peaks (2-5), and some health authorities reported that a substantial proportion of COVID-19 hospitalizations were not primarily for COVID-19-related illness,* which might account for the lower mortality among hospitalized patients. Using a large hospital administrative database, CDC assessed in-hospital mortality risk overall and by demographic and clinical characteristics during the Delta (July-October 2021), early Omicron (January-March 2022), and later Omicron (April-June 2022) variant periods† among patients hospitalized primarily for COVID-19. Model-estimated adjusted mortality risk differences (aMRDs) (measures of absolute risk) and adjusted mortality risk ratios (aMRRs) (measures of relative risk) for in-hospital death were calculated comparing the early and later Omicron periods with the Delta period. Crude mortality risk (cMR) (deaths per 100 patients hospitalized primarily for COVID-19) was lower during the early Omicron (13.1) and later Omicron (4.9) periods than during the Delta (15.1) period (p<0.001). Adjusted mortality risk was lower during the Omicron periods than during the Delta period for patients aged ≥18 years, males and females, all racial and ethnic groups, persons with and without disabilities, and those with one or more underlying medical conditions, as indicated by significant aMRDs and aMRRs (p<0.05). During the later Omicron period, 81.9% of in-hospital deaths occurred among adults aged ≥65 years and 73.4% occurred among persons with three or more underlying medical conditions. Vaccination, early treatment, and appropriate nonpharmaceutical interventions remain important public health priorities for preventing COVID-19 deaths, especially among persons most at risk.

Interim Recommendation of the Advisory Committee on Immunization Practices for Use of the Novavax COVID-19 Vaccine in Persons Aged ≥18 years - United States, July 2022.

The NVX-CoV2373 (Novavax) COVID-19 vaccine is a recombinant spike (rS) protein nanoparticle vaccine with Matrix-M adjuvant to protect against infection with SARS-CoV-2, the virus that causes COVID-19. On July 13, 2022, the Food and Drug Administration (FDA) issued Emergency Use Authorization (EUA) for the Novavax vaccine for primary COVID-19 immunization of unvaccinated adults aged ≥18 years, administered as 2 doses (5 µg rS and 50 µg Matrix-M adjuvant in each dose) 3 weeks apart (1). On July 19, 2022, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for use of the Novavax vaccine in persons aged ≥18 years for the prevention of COVID-19.* In the per-protocol† efficacy analysis, vaccine efficacy (VE) against reverse transcription-polymerase chain reaction (RT-PCR)-confirmed symptomatic COVID-19 was 89.6% (95% CI = 82.4%-93.8%). The Alpha variant (B.1.1.7) of SARS-CoV-2 was the predominant circulating variant during the period of case accrual for VE assessments. Cases of myocarditis or pericarditis were reported in temporal association with vaccination, suggesting a possible causal relationship. The ACIP recommendation for the use of the Novavax COVID-19 vaccine is interim and will be updated as additional information becomes available. The adjuvanted, protein subunit-based Novavax COVID-19 vaccine provides an additional option for unvaccinated adults, increasing flexibility for the public and for vaccine providers. Vaccination is important for protection against COVID-19.

The shifting prevalence of asthma and allergic disease in US children.

BACKGROUND: Asthma is a chronic lung disease that affected 5 million children. Allergy is a common comorbidity of asthma. Having both conditions is associated with unfavorable health outcomes and impaired quality of life. OBJECTIVE: Purpose of this study was to assess allergy and its association with asthma by select characteristics among children to determine differences by populations. METHODS: National Health Interview Survey data (2007-2018) were used to assess asthma and allergy status, trends, and the association between allergy and asthma by select characteristics among US children (aged 0-17 years). RESULTS: Prevalence of asthma decreased among all children (slope [-] P < .001) and among those with allergy (slope [-] P = .002). More children had respiratory allergy (14.7%), followed by skin allergy (12.7%) and food allergy (6.4%). Prevalence of respiratory allergy significantly decreased among White non-Hispanic children (slope [-] P = .002), food allergy increased among White non-Hispanic (slope [+] P < .001) and Hispanic children (slope [+] P = .003), and skin allergy increased among Hispanic children (slope [+] P = .04). Depending on number and type, children with allergy were 2 to 8 times (skin allergy only and having all 3 allergies, respectively) more likely to have current asthma than were children without allergy. Among children with current asthma, having any allergy was significantly associated with missed school days (adjusted prevalence ratio, 1.33 [1.03-1.72]; P = .02) and taking preventive medication daily (adjusted prevalence ratio, 1.89 [1.32-2.71]; P < .001). CONCLUSION: Trends in allergies across years differed by race and ethnicity. Strength of association between asthma and allergy differed by type and number of allergies, being highest among children having all 3 types of allergies. Having both asthma and allergy was associated with unfavorable asthma outcomes.

Clinical outcomes among hospitalized US adults with asthma or chronic obstructive pulmonary disease, with or without COVID-19.

OBJECTIVE: This study assesses the risk of severe clinical outcomes during hospitalizations of adults with asthma and/or COPD plus COVID-19 and compares those risks with those during hospitalizations of adults with asthma and/or COPD without COVID-19. METHODS: We used data from 877 U.S. hospitals from the Premier Healthcare Database during March 2020-March 2021. Hospitalizations (n = 311,215) among patients aged ≥18 years with an ICD-10-CM diagnosis involving asthma or COPD were classified into three groups: adults with asthma (but not COPD), adults with COPD (but not asthma), and adults with both asthma and COPD. We used multivariable Poisson regression to assess associations of severe clinical outcomes [intensive care unit (ICU) admission, use of invasive mechanical ventilation (IMV), and death] and COVID-19 status. RESULTS: The percentage of hospitalizations among patients with asthma and COVID-19 resulting in ICU admission, IMV, and death were 46.9%, 14.0%, and 8.0%, respectively. These risks were higher than those among patients with asthma without COVID-19 (adjusted risk ratio [aRR], 1.17 [95% confidence interval (CI), 1.14-1.21], 1.61 [95% CI, 1.50-1.73], and 5.56 [95% CI, 4.89-6.32]), respectively. Risks of ICU admission, IMV, and death were also high among patients with COPD and COVID-19 and exceeded the corresponding risks among patients with COPD without COVID-19. CONCLUSION: Hospitalizations among patients with asthma and/or COPD with COVID-19 had a more severe clinical course than hospitalizations for asthma and/or COPD exacerbations without COVID-19.Supplemental data for this article is available online at at www.tandfonline.com/ijas .

Personalized Cancer Vaccines: Clinical Landscape, Challenges, and Opportunities.

Tremendous innovation is underway among a rapidly expanding repertoire of promising personalized immune-based treatments. Therapeutic cancer vaccines (TCVs) are attractive systemic immunotherapies that activate and expand antigen-specific CD8+ and CD4+ T cells to enhance anti-tumor immunity. Our review highlights key issues impacting TCVs in clinical practice and reports on progress in development. We review the mechanism of action, immune-monitoring, dosing strategies, combinations, obstacles, and regulation of cancer vaccines. Most trials of personalized TCVs are ongoing and represent diverse platforms with predominantly early investigations of mRNA, DNA, or peptide-based targeting strategies against neoantigens in solid tumors, with many in combination immunotherapies. Multiple delivery systems, routes of administration, and dosing strategies are used. Intravenous or intramuscular administration is common, including delivery by lipid nanoparticles. Absorption and biodistribution impact antigen uptake, expression, and presentation, affecting the strength, speed, and duration of immune response. The emerging trials illustrate the complexity of developing this class of innovative immunotherapies. Methodical testing of the multiple potential factors influencing immune responses, as well as refined quantitative methodologies to facilitate optimal dosing strategies, could help resolve uncertainty of therapeutic approaches. To increase the likelihood of success in bringing these medicines to patients, several unique development challenges must be overcome.

Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis.

OBJECTIVES: To determine s.c. tocilizumab (s.c.-TCZ) dosing regimens for systemic JIA (sJIA) and polyarticular JIA (pJIA). METHODS: In two 52-week phase 1 b trials, s.c.-TCZ (162 mg/dose) was administered to sJIA patients every week or every 2 weeks (every 10 days before interim analysis) and to pJIA patients every 2 weeks or every 3 weeks with body weight ≥30 kg or <30 kg, respectively. Primary end points were pharmacokinetics, pharmacodynamics and safety; efficacy was exploratory. Comparisons were made to data from phase 3 trials with i.v. tocilizumab (i.v.-TCZ) in sJIA and pJIA. RESULTS: Study participants were 51 sJIA patients and 52 pJIA patients aged 1-17 years who received s.c.-TCZ. Steady-state minimum TCZ concentration (Ctrough) >5th percentile of that achieved with i.v.-TCZ was achieved by 49 (96%) sJIA and 52 (100%) pJIA patients. In both populations, pharmacodynamic markers of disease were similar between body weight groups. Improvements in Juvenile Arthritis DAS-71 were comparable between s.c.-TCZ and i.v.-TCZ. By week 52, 53% of sJIA patients and 31% of pJIA patients achieved clinical remission on treatment. Safety was consistent with that of i.v.-TCZ except for injection site reactions, reported by 41.2% and 28.8% of sJIA and pJIA patients, respectively. Infections were reported in 78.4% and 69.2% of patients, respectively. Two sJIA patients died; both deaths were considered to be related to TCZ. CONCLUSION: s.c.-TCZ provides exposure and risk/benefit profiles similar to those of i.v.-TCZ. S.c. administration provides an alternative administration route that is more convenient for patients and caregivers and that has potential for in-home use. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01904292 and NCT01904279.

Association Between COVID-19 and Myocarditis Using Hospital-Based Administrative Data - United States, March 2020-January 2021.

Viral infections are a common cause of myocarditis, an inflammation of the heart muscle (myocardium) that can result in hospitalization, heart failure, and sudden death (1). Emerging data suggest an association between COVID-19 and myocarditis (2-5). CDC assessed this association using a large, U.S. hospital-based administrative database of health care encounters from >900 hospitals. Myocarditis inpatient encounters were 42.3% higher in 2020 than in 2019. During March 2020-January 2021, the period that coincided with the COVID-19 pandemic, the risk for myocarditis was 0.146% among patients diagnosed with COVID-19 during an inpatient or hospital-based outpatient encounter and 0.009% among patients who were not diagnosed with COVID-19. After adjusting for patient and hospital characteristics, patients with COVID-19 during March 2020-January 2021 had, on average, 15.7 times the risk for myocarditis compared with those without COVID-19 (95% confidence interval [CI] = 14.1-17.2); by age, risk ratios ranged from approximately 7.0 for patients aged 16-39 years to >30.0 for patients aged <16 years or ≥75 years. Overall, myocarditis was uncommon among persons with and without COVID-19; however, COVID-19 was significantly associated with an increased risk for myocarditis, with risk varying by age group. These findings underscore the importance of implementing evidence-based COVID-19 prevention strategies, including vaccination, to reduce the public health impact of COVID-19 and its associated complications.

Trends in COVID-19 Cases, Emergency Department Visits, and Hospital Admissions Among Children and Adolescents Aged 0-17 Years - United States, August 2020-August 2021.

Although COVID-19 generally results in milder disease in children and adolescents than in adults, severe illness from COVID-19 can occur in children and adolescents and might require hospitalization and intensive care unit (ICU) support (1-3). It is not known whether the B.1.617.2 (Delta) variant,* which has been the predominant variant of SARS-CoV-2 (the virus that causes COVID-19) in the United States since late June 2021,† causes different clinical outcomes in children and adolescents compared with variants that circulated earlier. To assess trends among children and adolescents, CDC analyzed new COVID-19 cases, emergency department (ED) visits with a COVID-19 diagnosis code, and hospital admissions of patients with confirmed COVID-19 among persons aged 0-17 years during August 1, 2020-August 27, 2021. Since July 2021, after Delta had become the predominant circulating variant, the rate of new COVID-19 cases and COVID-19-related ED visits increased for persons aged 0-4, 5-11, and 12-17 years, and hospital admissions of patients with confirmed COVID-19 increased for persons aged 0-17 years. Among persons aged 0-17 years during the most recent 2-week period (August 14-27, 2021), COVID-19-related ED visits and hospital admissions in the states with the lowest vaccination coverage were 3.4 and 3.7 times that in the states with the highest vaccination coverage, respectively. At selected hospitals, the proportion of COVID-19 patients aged 0-17 years who were admitted to an ICU ranged from 10% to 25% during August 2020-June 2021 and was 20% and 18% during July and August 2021, respectively. Broad, community-wide vaccination of all eligible persons is a critical component of mitigation strategies to protect pediatric populations from SARS-CoV-2 infection and severe COVID-19 illness.

Medicaid expansion, health insurance coverage, and cost barriers to care among low-income adults with asthma: the Adult Asthma Call-Back Survey.

OBJECTIVE: To examine Medicaid expansion (ME) effects on health insurance coverage (HIC) and cost barriers to medical care among people with asthma. METHOD: We analyzed 2012-2013 and 2015-2016 data from low-income adults with current asthma aged 18-64 years in the Behavioral Risk Factor Surveillance System Asthma Call-Back Survey (state-level telephone survey). We calculated weighted percentages and 95% confidence intervals from ME and non-ME jurisdictions (according to 2014 ME status). Outcomes were HIC and cost barriers to buying asthma medication (MED), seeing a health care provider for asthma (HCP), or any asthma care (AAC). Using SUDAAN, we performed survey-weighted difference-in-differences analyses, adjusting for demographics. Subgroup analyses were stratified by demographics. RESULTS: Our study population included 6445 participants from 25 states plus Puerto Rico. In 2015-2016 compared to 2012-2013, HIC was more common in ME jurisdictions (P < 0.001) but unchanged in non-ME jurisdictions. Adjusted difference-in-differences analyses showed ME was associated with a statistically significant 13.36 percentage-point increase in HIC (standard error = 0.053). Cost barriers to MED, HCP, and AAC did not change significantly for either group in descriptive and difference-in-differences analyses. In subgroup analyses, we noted variation in outcomes by demographics and 2014 ME status. CONCLUSIONS: We found ME significantly affected HIC among low-income adults with asthma, but not cost barriers to asthma-related health care. Strategies to reduce cost barriers to asthma care could further improve health care access among low-income adults with asthma in ME jurisdictions.

Daycare attendance and asthma control, Asthma Call-back Survey 2012-2014.

OBJECTIVE: To examine the association between daycare attendance and asthma control among children aged 0 to 4 years with asthma. METHODS: We analyzed 2012-2014 data from the Behavioral Risk Factor Surveillance System Asthma Call-back Survey on 388 children with asthma aged 0 to 4 years with information on daycare attendance in the past 12 months. We calculated weighted prevalence ratios to assess the association between daycare attendance and asthma control (categorized based on day-time and nighttime asthma symptoms, activity limitation, and short-acting beta agonist use). Adjusted models controlled for parent or guardian education, household income, race, sex, cost barriers to asthma care, long-term control medication use, and the number of other children in the child's household. RESULTS: In this sample of children with asthma, representative of 520,400 children in 26 U.S. states, 34% attended daycare in the past 12 months. Only 32% of children who attended daycare in the past 12 months reported having an asthma action plan on file at the daycare they most recently attended. Presence of the asthma triggers of pets, mold, and smoking in a child's daycare were reported to be uncommon. Prevalence of uncontrolled asthma was 44% in children who attended daycare in the past 12 months and 68% in children who did not. The adjusted prevalence ratio between daycare attendance and uncontrolled asthma was 0.96 (95% confidence interval 0.73, 1.25). CONCLUSIONS: When adjusting for covariates, we observed no evidence of an association between daycare attendance in early life and uncontrolled asthma.

Return on investment of self-management education and home visits for children with asthma.

OBJECTIVE: Priorities of the Centers for Disease Control and Prevention's 6|18 Initiative include outpatient asthma self-management education (ASME) and home-based asthma visits (home visit) as interventions for children with poorly-controlled asthma. ASME and home visit intervention programs are currently not widely available. This project was to assess the economic sustainability of these programs for state asthma control programs reimbursed by Medicaid. METHODS: We used a simulation model based on parameters from the literature and Medicaid claims, controlling for regression to the mean. We modeled scenarios under various selection criteria based on healthcare utilization and age to forecast the return on investment (ROI) using data from New York. The resulting tool is available in Excel or Python. RESULTS: Our model projected health improvement and cost savings for all simulated interventions. Compared against home visits alone, the simulated ASME alone intervention had a higher ROI for all healthcare utilization and age scenarios. Savings were primarily highest in simulated program participants who had two or more asthma-related emergency department visits or one inpatient visit compared to those participants who had one or more asthma-related emergency department visits. Segmenting the selection criteria by age did not significantly change the results. CONCLUSIONS: This model forecasts reduced healthcare costs and improved health outcomes as a result of ASME and home visits for children with high urgent healthcare utilization (more than two emergency department visits or one inpatient hospitalization) for asthma. Utilizing specific selection criteria, state based asthma control programs can improve health and reduce healthcare costs.

Medicaid Coverage of Guidelines-Based Asthma Care Across 50 States, the District of Columbia, and Puerto Rico, 2016-2017.

Asthma affects more than 24 million Americans, including 6.2 million children. Although asthma cannot be cured, it can be effectively managed with care based on nationally recognized guidelines. Ensuring the availability and accessibility of guidelines-recommended treatments and services can help patients receive the most appropriate care. In this article, we describe the American Lung Association's Asthma Guidelines-Based Care Coverage Project (the Project) to determine the extent of asthma care coverage and associated barriers in state Medicaid programs - information that has been previously unavailable. The Project tracked coverage for 7 areas of guidelines-based asthma care and 9 barriers related to accessing care in Medicaid programs for all 50 states, the District of Columbia, and Puerto Rico. Results from the Project show a lack of consistent and comprehensive coverage across states, as well as coverage-related challenges to accessing asthma care within states.

Workgroup Report by the Joint Task Force Involving American Academy of Allergy, Asthma & Immunology (AAAAI); Food Allergy, Anaphylaxis, Dermatology and Drug Allergy (FADDA) (Adverse Reactions to Foods Committee and Adverse Reactions to Drugs, Biologicals, and Latex Committee); and the Centers for Disease Control and Prevention Botulism Clinical Treatment Guidelines Workgroup-Allergic Reactions to Botulinum Antitoxin: A Systematic Review.

Background: Naturally occurring botulism is rare, but a large number of cases could result from unintentional or intentional contamination of a commercial food. Despeciated, equine-derived, heptavalent botulinum antitoxin (HBAT) is licensed in the United States. Timely treatment reduces morbidity and mortality, but concerns that botulinum antitoxin can induce anaphylaxis exist. We sought to quantify the allergy risk of botulinum antitoxin treatment and the usefulness of skin testing to assess this risk. Methods: We conducted a systematic review of (1) allergic reactions to botulinum antitoxin and (2) the predictive value of skin testing (ST) before botulinum antitoxin administration. We searched 5 scientific literature databases, reviewed articles' references, and obtained data from the HBAT manufacturer and from the Centers for Disease Control and Prevention. Anaphylaxis incidence was determined for HBAT and previously employed botulinum antitoxins. We calculated the positive predictive value (PPV) and negative predictive value (NPV) of ST for anaphylaxis related to HBAT and other botulinum antitoxins. Results: Seven articles were included. Anaphylaxis incidence was 1.64% (5/305 patients) for HBAT and 1.16% (8/687 patients) for all other botulinum antitoxins (relative risk, 1.41 [95% confidence interval, .47-4.27]; P = .5). Observed values for both PPV and NPV for HBAT-ST (33 patients) were 100%. Observed PPVs and NPVs of ST for other botulinum antitoxins (302 patients) were 0-56% and 50%-100%, respectively. There were no reports of fatal anaphylaxis. Conclusions: Considering the <2 % rate of anaphylaxis, fatal outcomes, modest predictive value of ST, resource requirements for ST, and the benefits of early treatment, data do not support delaying HBAT administration to perform ST in a mass botulinum toxin exposure. Anaphylactic reactions may occur among 1%-2% of botulinum antitoxin recipients and will require epinephrine and antihistamine treatment and, possibly, intensive care.