Background rates for severe cutaneous reactions in the US: Contextual support for safety assessment of COVID-19 vaccines and novel biologics.

The global COVID-19 public health crisis has resulted in extraordinary collaboration to expeditiously develop vaccines and therapeutics. The safety of these biologics is closely monitored by the US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC). Novel products may have limited safety data, and although serious medical outcomes associated with vaccination are rare, knowledge of background incidence rates of medical conditions in the US population puts reported adverse events (AEs) in perspective for further study. Although relatively minor vaccination skin reactions are common, rare instances of severe delayed hypersensitivity reactions such as erythema multiforme (EM), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome may occur. To aid in the assessment of these events, we performed a literature search in PubMed and Web of Science on the background incidence of EM, SJS, SJS/TEN, and TEN in the US population and on published reports of these conditions occurring post-vaccination. The US background annual incidence rates per million individuals of all ages ranged from 5.3 to 63.0 for SJS, from 0.4 to 5.0 for TEN, and from 0.8 to 1.6 for SJS/TEN. Since these conditions may overlap, some studies reported rates for EM/SJS/TEN combined, however we did not find studies with exclusive EM incidence rates. The published literature, including studies of reports submitted to the FDA/CDC Vaccine Adverse Event Reporting System (VAERS), describes post-vaccination EM, SJS, SJS/TEN and/or TEN as rare occurrences. The vaccines most frequently associated with these conditions were measles, mumps, and rubella; diphtheria, tetanus, and pertussis; and varicella. The majority of VAERS reports of EM, SJS, SJS/TEN, or TEN occurred in children within 30 days of vaccination. This review summarizes background rates of these disorders in the general population and published AEs among vaccine recipients, to support safety surveillance of COVID-19 vaccines and other biologics.

U.S. Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines.

The Coronavirus Disease 2019 (COVID-19) pandemic has had a devastating impact on global health, and has resulted in an unprecedented, international collaborative effort to develop vaccines to control the outbreak, protect human lives, and avoid further social and economic disruption. Mass vaccination campaigns are underway in multiple countries and are expected worldwide once more vaccine becomes available. Some early candidate vaccines use novel platforms, such as mRNA encapsulated in lipid nanoparticles, and relatively new platforms, such as replication-deficient viral vectors. While these new vaccine platforms hold promise, limited safety data in humans are available. Serious health outcomes linked to vaccinations are rare, and some outcomes may occur incidentally in the vaccinated population. Knowledge of background incidence rates of these medical conditions is a critical component of vaccine safety monitoring to aid in the assessment of adverse events temporally associated with vaccination and to put these events into context with what would be expected due to chance alone. A list of 22 potential adverse events of special interest (AESI), including neurologic, autoimmune, and cardiovascular disorders, was compiled by subject matter experts at the U.S. Food and Drug Administration and the Centers for Disease Control and Prevention. The most recently available U.S. background rates for these medical conditions, overall and by age, sex, and race/ethnicity (when available), were sourced from reported statistics (data published by medical panels/ associations or federal government reports), and literature reviews in PubMed. This review provides estimates of background incidence rates for medical conditions that may be monitored or studied as AESI during safety surveillance and research for COVID-19 vaccines and other new vaccines.

Characterizing occupational heat-related mortality in the United States, 2000-2010: an analysis using the Census of Fatal Occupational Injuries database.

BACKGROUND: Occupational heat-related mortality is not well studied and risk factors remain largely unknown. This paper describes the epidemiological characteristics of heat-related deaths among workers in the US 2000-2010. METHODS: Fatality data were obtained at the Bureau of Labor Statistics from the confidential on-site Census of Fatal Occupational Injuries database. Fatality rates and risk ratios with 95% confidence intervals were calculated by year, sex, age group, ethnicity, race, state, and industry. RESULTS: Between 2000 and 2010, 359 occupational heat-related deaths were identified in the U.S., for a yearly average fatality rate of 0.22 per 1 million workers. Highest rates were found among Hispanics, men, the agriculture and construction industries, the state of Mississippi, and very small establishments. CONCLUSIONS: This study provides the first comprehensive national profile of heat-related deaths in the U.S. workplace. Prevention efforts should be directed at small businesses and at industries and individuals with the highest risk.

The epidemiology of occupational heat exposure in the United States: a review of the literature and assessment of research needs in a changing climate.

In recent years, the United States has experienced record-breaking summer heat. Climate change models forecast increasing US temperatures and more frequent heat wave events in the coming years. Exposure to environmental heat is a significant, but overlooked, workplace hazard that has not been well-characterized or studied. The working population is diverse; job function, age, fitness level, and risk factors to heat-related illnesses vary. Yet few studies have examined or characterized the incidence of occupational heat-related morbidity and mortality. There are no federal regulatory standards to protect workers from environmental heat exposure. With climate change as a driver for adaptation and prevention of heat disorders, crafting policy to characterize and prevent occupational heat stress for both indoor and outdoor workers is increasingly sensible, practical, and imperative.

Transfusion-transmitted babesiosis in the United States: summary of a workshop.

Infections of humans with intraerythrocytic parasites of the genus Babesia can be locally prevalent in diverse regions of the United States. Transfusion of blood and blood products collected from donors infected with Babesia may result in a serious illness that can be fatal. In September 2008, the Food and Drug Administration organized a public workshop to discuss the various aspects of transfusion-transmitted babesiosis in the United States including the possible strategies to identify and defer blood donors who may have been infected with Babesia. Discussions were also held on the biology, pathogenesis, and epidemiology of Babesia species. In this article, we summarize the scientific presentations and panel discussions that took place during the workshop.

Babesia infection through blood transfusions: reports received by the US Food and Drug Administration, 1997-2007.

BACKGROUND: Human babesiosis is an illness with clinical manifestations that range from asymptomatic to fatal. Although babesiosis is not nationally notifiable, the US incidence appears to be increasing. Babesia infection is a transfusion-transmissable disease. An estimated 70 cases were reported during 1979-2007; most of these cases were reported during the past decade. METHODS: We queried the 3 following US Food and Drug Administration safety surveillance systems to assess trends in babesiosis reporting since 1997: fatality reports for blood donors and transfusion recipients, the Adverse Event Reporting System (which includes MedWatch), and the Biological Product Deviations Reporting system.We analyzed fatality reports for time frames, clinical presentations, and patient and donor demographic characteristics. RESULTS: Eight of 9 deaths due to transfusion-transmitted babesiosis that were reported since 1997 occurred within the past 3 years (2005-2007). Four implicated donors and 5 patients lived in areas where Babesia infection is not endemic. Increasing numbers of Biological Product Deviations Reports were submitted to the US Food and Drug Administration over the past decade; the Adverse Event Reporting System received no reports. CONCLUSIONS: After nearly a decade with no reported death due to transfusion-transmitted babesiosis, the US Food and Drug Administration received 8 reports from November 2005 onward. The increased numbers of deaths reported and Biological Product Deviations Reports suggest an increasing incidence of transfusion-transmitted babesiosis. Physicians should consider babesiosis in the differential diagnosis in immunocompromised, febrile patients with a history of recent transfusion, even in areas where Babesia infection is not endemic. Accurate and timely reporting of babesiosis-related donor and transfusion events assists the US Food and Drug Administration in developing appropriate public health-control measures.

Animals as early detectors of bioevents: veterinary tools and a framework for animal-human integrated zoonotic disease surveillance.

The threat of bioterrorism and emerging infectious diseases has prompted various public health agencies to recommend enhanced surveillance activities to supplement existing surveillance plans. The majority of emerging infectious diseases and bioterrorist agents are zoonotic. Animals are more sensitive to certain biological agents, and their use as clinical sentinels, as a means of early detection, is warranted. This article provides design methods for a local integrated zoonotic surveillance plan and materials developed for veterinarians to assist in the early detection of bioevents. Zoonotic surveillance in the U.S. is currently too limited and compartmentalized for broader public health objectives. To rapidly detect and respond to bioevents, collaboration and cooperation among various agencies at the federal, state, and local levels must be enhanced and maintained. Co-analysis of animal and human diseases may facilitate the response to infectious disease events and limit morbidity and mortality in both animal and human populations.