Pediatric Medical Countermeasures: Antidotes and Cytokines for Radiological and Nuclear Incidents and Terrorism.

The war in Ukraine raises concerns for potential hazards of radiological and nuclear incidents. Children are particularly vulnerable in these incidents and may need pharmaceutical countermeasures, including antidotes and cytokines. Searches found no published study comparing pediatric indications and dosing among standard references detailing pediatric medications for these incidents. This study addresses this gap by collecting, tabulating, and disseminating this information to healthcare professionals caring for children. Expert consensus chose the following references to compare their pediatric indications and dosing of medical countermeasures for radiation exposure and internal contamination with radioactive materials: Advanced Hazmat Life Support (AHLS) for Radiological Incidents and Terrorism, DailyMed, Internal Contamination Clinical Reference, Medical Aspects of Radiation Incidents, and Medical Management of Radiological Casualties, as well as Micromedex, POISINDEX, and Radiation Emergency Medical Management (REMM). This is the first study comparing pediatric indications and dosing for medical countermeasures among commonly used references for radiological and nuclear incidents.

Marburg virus disease: A summary for clinicians.

OBJECTIVES: This article summarizes the countermeasures for Marburg virus disease, focusing on pathogenesis, clinical features and diagnostics. There is an emphasis on therapies and vaccines that have demonstrated, through their evaluation in nonhuman primates (NHPs) and/or in humans, potential for use in an emergency situation. METHODS: A standardized literature review was conducted on vaccines and treatments for Marburg virus disease, with a focus on human and nonhuman primate data published in the last five years. More detail on the methods that were used is summarized in a companion methods paper. RESULTS: The study identified six treatments and four vaccine platforms that have demonstrated, through their efficacy in NHPs, potential benefit for treating or preventing infection in humans. CONCLUSION: Succinct summaries of Marburg countermeasures are provided to give the busy clinician a head start in reviewing the literature if faced with a patient with Marburg virus disease. Links to other authoritative sources of information are also provided.

Advanced Preparation Makes Research in Emergencies and Isolation Care Possible: The Case of Novel Coronavirus Disease (COVID-19).

The optimal time to initiate research on emergencies is before they occur. However, timely initiation of high-quality research may launch during an emergency under the right conditions. These include an appropriate context, clarity in scientific aims, preexisting resources, strong operational and research structures that are facile, and good governance. Here, Nebraskan rapid research efforts early during the 2020 coronavirus disease pandemic, while participating in the first use of U.S. federal quarantine in 50 years, are described from these aspects, as the global experience with this severe emerging infection grew apace. The experience has lessons in purpose, structure, function, and performance of research in any emergency, when facing any threat.

Review of Literature for Air Medical Evacuation High-Level Containment Transport.

INTRODUCTION: Aeromedical evacuation (AE) is a challenging process, further complicated when a patient has a highly hazardous communicable disease (HHCD). We conducted a review of the literature to evaluate the processes and procedures utilized for safe AE high-level containment transport (AE-HLCT) of patients with HHCDs. METHODS: A literature search was performed in PubMed/MEDLINE (from 1966 through January 2019). Authors screened abstracts for inclusion criteria and full articles were reviewed if the abstract was deemed to contain information related to the aim. RESULTS: Our search criteria yielded 14 publications and were separated based upon publication dates, with the natural break point being the beginning of the 2013-2016 Ebola virus disease epidemic. Best practices and recommendations from identified articles are subdivided into pre-flight preparations, inflight operations, and post-flight procedures. CONCLUSIONS: Limited peer-reviewed literature exists on AE-HLCT, including important aspects related to healthcare worker fatigue, alertness, shift scheduling, and clinical care performance. This hinders the sharing of best practices to inform evacuations and equip teams for future outbreaks. Despite the successful use of different aircraft and technologies, the unique nature of the mission opens the opportunity for greater coordination and development of consensus standards for AE-HLCT operations.

A Methodology for Determining Which Diseases Warrant Care in a High-Level Containment Care Unit.

Although the concept of high-level containment care (HLCC or 'biocontainment'), dates back to 1969, the 2014-2016 outbreak of Ebola virus disease (EVD) brought with it a renewed emphasis on the use of specialized HLCC units in the care of patients with EVD. Employment of these units in the United States and Western Europe resulted in a significant decrease in mortality compared to traditional management in field settings. Moreover, this employment appeared to significantly lessen the risk of nosocomial transmission of disease; no secondary cases occurred among healthcare workers in these units. While many now accept the wisdom of utilizing HLCC units and principles in the management of EVD (and, presumably, of other transmissible and highly hazardous viral hemorrhagic fevers, such as those caused by Marburg and Lassa viruses), no consensus exists regarding additional diseases that might warrant HLCC. We propose here a construct designed to make such determinations for existing and newly discovered diseases. The construct examines infectivity (as measured by the infectious dose needed to infect 50% of a given population (ID50)), communicability (as measured by the reproductive number (R0)), and hazard (as measured by morbidity and mortality). Diseases fulfilling all three criteria (i.e., those that are highly infectious, communicable, and highly hazardous) are considered candidates for HLCC management if they also meet a fourth criterion, namely that they lack effective and available licensed countermeasures.

Ebola Virus Disease: Clinical Challenges, Recognition, and Management.

The 2014 to 2016 Ebola outbreak response resulted in many lessons learned about biocontainment patient care, leading to enhanced domestic capabilities for highly infectious and hazardous communicable diseases. However, additional opportunities for improvement remain. The article identifies and describes key considerations and challenges for laboratory analysis, clinical management, transportation, and personnel management during the care of patients infected with Ebola or other special pathogens. Dedication to maintaining preparedness enables biocontainment patient care teams to perform at the highest levels of safety and confidence.

Salmonella enterica Serotype Panama: An exceptionally virulent cause of illness in children?

Salmonella enterica serotype Panama accounts for <1% of all reported cases of Salmonellosis. Previous reports suggest that it may be unusually virulent in children. We report the case of a family, five of six of whom developed a diarrheal illness due to this organism following exposure during a trip to Costa Rica. Included among these patients were three children, all of whom developed clinical shock requiring aggressive fluid resuscitation, and all of whom ultimately recovered. DNA fingerprinting, using pulsed-field gel electrophoresis, demonstrated that all three children were infected with an identical strain of Salmonella. Moreover, this strain was unique among strains recovered in Nebraska. Clinicians should be aware of the propensity of Salmonella enterica serotype Panama to cause especially severe disease in children; laboratory personnel should be aware of the unique need for thiourea buffering when attempting to perform pulsed-field gel electrophoresis analysis on such strains.

Need for Aeromedical Evacuation High-Level Containment Transport Guidelines.

Circumstances exist that call for the aeromedical evacuation high-level containment transport (AE-HLCT) of patients with highly hazardous communicable diseases. A small number of organizations maintain AE-HLCT capabilities, and little is publicly available regarding the practices. The time is ripe for the development of standards and consensus guidelines involving AE-HLCT.

Perspectives on the Management of Children in a Biocontainment Unit: Report of the NETEC Pediatric Workgroup.

During the outbreak of Ebola virus disease that struck West Africa during 2014-2016, a small handful of expatriate patients were evacuated to specialized high-level containment care units, or biocontainment units, in the United States and Western Europe. Given the lower mortality rate (18% versus 40% for those treated in Africa) among these patients, it is likely that high-level containment care will be used in the future with increasing frequency. It is also likely that children infected with Ebola and other highly hazardous communicable diseases will someday require such care. The National Ebola Training and Education Center convened a pediatric workgroup to consider the unique and problematic issues posed by these potential child patients. We report here the results of those discussions.

Evaluating Promising Investigational Medical Countermeasures: Recommendations in the Absence of Guidelines.

Emerging and re-emerging infectious diseases pose growing global public health threats. However, research on and development of medical countermeasures (MCMs) for such pathogens is limited by the sporadic and unpredictable nature of outbreaks, lack of financial incentive for pharmaceutical companies to develop interventions for many of the diseases, lack of clinical research capacity in areas where these diseases are endemic, and the ethical dilemmas related to conducting scientific research in humanitarian emergencies. Hence, clinicians providing care for patients with emerging diseases are often faced with making clinical decisions about the safety and effectiveness of experimental MCMs, based on limited or no human safety, preclinical, or even earlier product research or historical data, for compassionate use. Such decisions can have immense impact on current and subsequent patients, the public health response, and success of future clinical trials. We highlight these dilemmas and underscore the need to proactively set up procedures that allow early and ethical deployment of MCMs as part of clinical trials. When clinical trials remain difficult to deploy, we present several suggestions of how compassionate use of off-label and unlicensed MCMs can be made more informed and ethical. We highlight several collaborations seeking to address these gaps in data and procedures to inform future clinical and public health decision making.

Biocontainment Units: Moving to the Next Phase of Evolution.

The concept and belief in the idea of "biocontainment" has undergone significant evolution during the past 20 years. The authors believe that the time is right to move to the next phase of this evolution to reassess establishment of formal standards for what constitutes a biocontainment unit and what diseases might be considered for admission to a biocontainment unit.

Distinguishing Respiratory Features of Category A/B Potential Bioterrorism Agents from Community-Acquired Pneumonia.

Differentiating between illness caused by community-acquired respiratory pathogens versus infection by biothreat agents is a challenge. This review highlights respiratory and clinical features of category A and B potential biothreat agents that have respiratory features as their primary presenting signs and symptoms. Recent world events make such a reminder that the possibility of rare diseases and unlikely events can occur timely for clinicians, policymakers, and public health authorities. Despite some distinguishing features, nothing can replace good clinical acumen and a strong index of suspicion in the diagnosis of uncommon infectious diseases.

Beyond the Dirty Dozen: A Proposed Methodology for Assessing Future Bioweapon Threats.

Background: Defense policy planners and countermeasure developers are often faced with vexing problems involving the prioritization of resources and efforts. This is especially true in the area of Biodefense, where each new emerging infectious disease outbreak brings with it questions regarding the causative agent's potential for weaponization. Recent experience with West Nile Virus, Severe Acute Respiratory Syndrome, Monkeypox, and H1N1 Influenza highlights this problem. Appropriately, in each of these cases, the possibility of bioterrorism was raised, although each outbreak ultimately proved to have a natural origin. In fact, determining whether an outbreak has an unnatural origin can be quite difficult. Thus, the questions remain: could the causative agents of these and other emerging infectious disease outbreaks pose a future weaponization threat? And how great is that threat? Should precious resources be diverted from other defense efforts in order to prepare for possible hostile employment of novel diseases by belligerents? Answering such critical questions requires some form of systematic threat assessment. Methods: Through extensive collaborative work conducted within NATO's Biomedical Advisory Council, we developed a scoring matrix for evaluating the weaponization potential of the causative agents of such diseases and attempted to validate our matrix by examining the reproducibility of data using known threat agents. Our matrix included 12 attributes of a potential weapon and was provided, along with detailed scoring instructions, to 12 groups of biodefense experts in 6 NATO nations. Study participants were asked to score each of these 12 attributes on a scale of 0-3: Infectivity, Infection-to-Disease Ratio (Reliability), Predictability (& Incubation Period), Morbidity & Mortality (Virulence), Ease of Large-Scale Production & Storage, Aerosol Stability, Atmospheric Stability, Ease of Dispersal, Communicability, Prophylactic Countermeasure Availability, Therapeutic Countermeasure Availability, and Ease of Detection. Reproducibility of scoring data was assessed by examining the standard deviations (SD) of mean scores. Results: Our results were unexpected. Several familiar biothreat diseases such as anthrax and tularemia were judged, by our experts, to be less threatening than many others owing to a number of factors including ease of detection, lack of communicability, and the ready availability of countermeasures. Conversely, several toxins were judged by experts to have very high potential as threat agents owing, in part, to their reliability, virulence, and a lack of available countermeasures. Agreement among experts, as determined by lower SD about a mean score, was greater for more familiar threats. Discussion: Our study was designed to provide a concise and east-to-apply set of criteria that could be used by NATO nations to evaluate emerging infectious disease threats with respect to their weaponization potential. Our results were unexpected. We believe that a lack of appropriate weighting factors may explain these results and suggest that future studies weigh each of the 12 proposed criteria based on the intended use of the assessment data and other situational factors. We believe that the greatest value of our study lies in a codification of the attributes of a biological weapon.

Advancing Preparedness for Highly Hazardous Contagious Diseases: Admitting 10 Simulated Patients with MERS-CoV.

The Ebola outbreak of 2014-2016 highlighted the need for the development of a more robust healthcare infrastructure in the United States to provide isolation care for patients infected with a highly hazardous contagious disease. Routine exercises and skills practice are required to effectively and safely prepare care teams to confidently treat this special population of patients. The Nebraska Biocontainment Unit (NBU) at Nebraska Medicine in Omaha has been conducting exercises since 2005 when the unit was opened. Previous activities and exercises conducted by the Nebraska Biocontainment Unit have focused on transporting and caring for up to 3 patients with Ebola virus disease or other special pathogens. Changes in regional and national mandates, as well as the increased potential for receiving multiple patients at once, at a single location, have resulted in a greater demand to exercise protocols for the treatment of multiple patients. This article discusses in detail the planning, execution, and outcomes of a full-scale exercise involving 10 simulated patients with a highly infectious pathogen transmitted by the airborne route.

Containment Care Units for Managing Patients With Highly Hazardous Infectious Diseases: A Concept Whose Time Has Come.

The concept of containment care for patients with highly hazardous infectious diseases originated in conjunction with the development of sophisticated biosafety level 4 laboratories at the US Army Medical Research Institute of Infectious Diseases in the late 1960s. Over time, the original containment facility served as a model for the development of other facilities in the United States at government and academic centers. The Ebola outbreak of 2014-2015 brought the issue of containment care into the mainstream and led to the development of such capabilities at strategic points around the country. We describe the original concepts behind development of such facilities, how the concept and acceptance has evolved over time, and how the guidelines for managing patients infected with viral hemorrhagic fevers have evolved as new information has been learned about protecting medical care providers from highly hazardous infectious pathogens.

A Brief History of Biocontainment.

The concept of clinical biocontainment, otherwise known as high-level containment care (HLCC), had its birth among a confluence of near-simultaneous events in 1969. The U.S. Army's Medical Research Institute of Infectious Diseases (USAMRIID) began construction of the first modern biocontainment unit that year, and opened the two-bed facility, often referred to as "the Slammer" in 1971. Over its 41-year existence, 21 persons exposed to highly hazardous infectious diseases were admitted to the Slammer, but none ever contracted the disease to which they had been exposed. Owing, in part, to this underutilization, some questioned the utility of HLCC units. This concern notwithstanding, Emory University and the University of Nebraska opened HLCC units in civilian academic medical centers in 2004 and 2005, respectively. These units, distinct from conventional infectious disease isolation wards found in most major medical centers, proved their worth during the West African Ebola Virus Disease (EVD) outbreak of 2014-2015. It is our opinion that such units, as well as the parallel high-level containment transport systems necessary to move patients to them, will continue to play an important role in the global response to emerging and highly hazardous contagious pathogens. Moreover, we feel that the lessons derived from their successful operation will lead to improvements in infection control procedures and practices throughout the healthcare system.