Bioterrorism Event Research Articles

1207. Vaccinia Virus Infection Acquired from an Occupational Needlestick—San Diego, California, 2019

BackgroundVaccinia virus, a virus similar to but less virulent than variola virus, is a component of smallpox vaccines and increasingly used for medical research. Vaccinia immunoglobulin intravenous (VIGIV) and tecovirimat are stockpiled in the U.S. Strategic National Stockpile (SNS) for potential smallpox bioterror events, but only VIGIV is licensed for vaccinia treatment. On January 12, 2019, CDC was consulted for worsening infection in a laboratory worker after a needlestick with vaccinia.MethodsWe investigated demographic, clinical, vaccination, and exposure history and determined likelihood of vaccinia virus infection. Identity of the specific strain was sought because some have genetic modifications that might impact virulence. Discussions among stakeholders informed treatment decisions and facilitated medication access and usage. Swabs from the lesion were tested by real-time polymerase chain reaction for orthopoxvirus DNA, which includes vaccinia.ResultsThe affected worker was an otherwise healthy 26-year-old woman who developed a pustular lesion at the needlestick site on her left index finger (Image). The patient had been injecting vaccinia virus into a mouse and had declined nationally recommended vaccination. Edema, lymphadenopathy, and fever raised concern for severe illness; neither the patient nor occupational health were certain of the vaccinia strain type. CDC, SNS, local health departments, drug manufacturers, and clinicians rapidly collaborated to make treatment decisions based on available information and ensure delivery of both biologics and administration of tecovirimat under an expanded access investigational new drug protocol. Eventually, a wound swab tested positive and the strain was determined to be one with no known impact on virulence.ConclusionWith increasing use of vaccinia in research, occupational infections may continue to occur. Health clinics should extensively counsel staff who decline vaccination and have documentation on-hand about vaccinia virus types to inform treatment decisions. This response prompted CDC to develop outreach materials specifically for occupational vaccinia exposures. Disclosures All authors: No reported disclosures.

Approach to Strain Selection and the Propagation of Viral Stocks for Venezuelan Equine Encephalitis Virus Vaccine Efficacy Testing under the Animal Rule.

Licensure of a vaccine to protect against aerosolized Venezuelan equine encephalitis virus (VEEV) requires use of the U.S. Food and Drug Administration (FDA) Animal Rule to assess vaccine efficacy as human studies are not feasible or ethical. An approach to selecting VEEV challenge strains for use under the Animal Rule was developed, taking into account Department of Defense (DOD) vaccine requirements, FDA Animal Rule guidelines, strain availability, and lessons learned from the generation of filovirus challenge agents within the Filovirus Animal Nonclinical Group (FANG). Initial down-selection to VEEV IAB and IC epizootic varieties was based on the DOD objective for vaccine protection in a bioterrorism event. The subsequent down-selection of VEEV IAB and IC isolates was based on isolate availability, origin, virulence, culture and animal passage history, known disease progression in animal models, relevancy to human disease, and ability to generate sufficient challenge material. Methods for the propagation of viral stocks (use of uncloned (wild-type), plaque-cloned, versus cDNA-cloned virus) to minimize variability in the potency of the resulting challenge materials were also reviewed. The presented processes for VEEV strain selection and the propagation of viral stocks may serve as a template for animal model development product testing under the Animal Rule to other viral vaccine programs. This manuscript is based on the culmination of work presented at the “Alphavirus Workshop” organized and hosted by the Joint Vaccine Acquisition Program (JVAP) on 15 December 2014 at Fort Detrick, Maryland, USA.

Strategies to Counteract Botulinum Neurotoxin A: Nature's Deadliest Biomolecule.

Botulinum neurotoxin serotype A (BoNT/A), marketed commercially as Botox, is the most toxic substance known to man with an estimated intravenous lethal dose (LD50) of 1-2 ng/kg in humans. Despite its widespread use in cosmetic and medicinal applications, no postexposure therapeutics are available for the reversal of intoxication in the event of medical malpractice or bioterrorism. Accordingly, the Centers for Disease Control and Prevention categorizes BoNT/A as a Category A pathogen, posing the highest risk to national security and public health as a result of the ease with which BoNT/A can be weaponized and disseminated. BoNT/A-mediated lethality results from neurons impeded from releasing acetylcholine, which ultimately causes muscle paralysis and possible death by asphyxiation with the loss of diaphragm function. Currently, the only available respite for BoNT/A poisoning is antibody-based therapy; however, this intervention is only effective within 12-24 h postexposure. Small molecule therapeutics remain the only opportunity to reverse BoNT/A intoxication after neuronal poisoning and are urgently needed. Nevertheless, no small molecule BoNT/A inhibitors have reached the clinic or even advanced to clinical trials. This Account highlights the accomplishments and existing challenges facing BoNT/A drug discovery today. Using the comprehensive body of work from our laboratory, we illustrate our nearly two-decade endeavor to discover a clinically relevant BoNT/A inhibitor. Specifically, a discussion on the identification and characterization of new chemical leads, the development of in vitro and in vivo assays, and pertinent discoveries in BoNT/A structural biology related to small molecule inhibition is presented. Lead discovery efforts in our laboratory have leveraged both in vitro high-throughput screening and rational design, and an array of mechanistic strategies for inhibiting BoNT/A has been discovered, including noncovalent inhibition, metal-binding active site inhibition, covalent inhibition, and α- and β-exosite inhibition. We contrast the strengths and weaknesses of each of these mechanistic strategies and propose the most favorable approach for success. Finally, we discuss multiple serendipitous discoveries of antibotulism small molecules with alternative mechanisms of action. Remaining challenges facing clinically relevant BoNT/A inhibition are presented and analyzed, including the current inability to reconcile toxin half-life (months to greater than one year) in neurons with in vivo pharmaceutical lifetimes and reoccurring inconsistencies between in vitro, cellular, and in vivo translation. Our Account of BoNT/A chemical research emphasizes the present accomplishments and critically analyzes the remaining obstacles for drug discovery. Importantly, we call for an increased focus on the discovery of safe and effective covalent inhibitors of BoNT/A that compete with the inherent half-life of the toxin.

Hospital management preparedness tools in biological events: A scoping review.

INTRODUCTION:The objective of the present study was to systematically review the current research knowledge on hospital preparedness tools used in biological events and factors affecting hospital preparedness in such incidents in using a scoping review methodology.MATERIALS AND METHODS:The review process was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guideline. Online databases (PubMed, Scopus, Web of Science, and Google Scholar) were used to identify papers published that evaluated instruments or tools for hospital preparedness in biological disasters (such as influenza, Ebola, and bioterrorism events). The search, article selection, and data extraction were carried out by two researchers independently.RESULTS:A total of 3440 articles were screened, with 20 articles identified for final analysis. The majority of research studies identified were conducted in the United States (45%) and were focused on CBRN incident (20%), Ebola, infectious disease and bioterrorism events (15%), mass casualty incidents and influenza pandemic (10%), public health emergency, SARS, and biological events (5%). Factors that were identified in the study to hospitals preparedness in biological events classified in seven areas including planning, surge capacity, communication, training and education, medical management, surveillance and standard operation process.CONCLUSIONS:Published evidences of hospital preparedness on biological events as well as the overall quality of the psychometric properties of most studies were limited. The results of the current scoping review could be used as a basis for designing and developing a standard assessment tool for hospital preparedness in biological events, and it can also be used as a clear vision for the healthcare managers and policymakers in their future plans to confront the challenges identified by healthcare institutes in biologic events.

Alternative fast analysis method for cellulose sponge surface sampling wipes with low concentrations of Bacillus Spores

Environmental sampling is a critical component of the post decontamination verification process following a bioterrorism event. The current work was performed to produce a less labor-intensive method for processing cellulose sponge-wipes used for sampling areas potentially contaminated with low concentrations (i.e., post-decontamination) of Bacillus anthracis spores. An alternative fast-analysis processing method was compared to the processing protocol validated by the Centers for Disease Control and Prevention (CDC) for the Laboratory Response Network (LRN). Glazed tile coupons (1102 cm2) were inoculated with 50, 500, or 5000 spores of Bacillus thuringiensis subsp. kurstaki (Btk), then sampled with cellulose sponges. Sampling was limited to a 25- by 25-cm area and performed in the same manner as the CDC sampling method. Samples were then processed using either the alternative “Fast Analysis” method or the “CDC method”. Three different analysts repeated the tests at each concentration utilizing each method. Mean recoveries, labor time, and potentially hazardous waste produced were compared for the two methods. The mean percent recoveries and standard errors for the samples processed using the “CDC method” were 39.9 ± 6.7, 43 ± 7.6, and 36.8 ± 10.1 for the 5000, 500, and 50 spore loading levels, respectively; compared to 54.2 ± 12.9, 64.2 ± 21.7, and 45.2 ± 8.6 for the “Fast Analysis” method. At each titer tested the “Fast Analysis” method resulted in a statistically significant higher percent recovery. Furthermore, analysts processed samples utilizing the “Fast Analysis” method in less than half the time and generated half as much potentially hazardous waste compared to the “CDC method”.

Essential evidence-based introductory bioterrorism content for practicing nurses.

Bioterrorism content is too often absent from nursing education post-licensure. According to the Centers for Disease Control and Prevention (CDC), bioterrorism is defined as "the deliberate release of viruses, bacteria, or other germs (agents) used to cause illness or death in people, animals, or plants." The purpose of this scholarly work was to develop and pilot a curriculum on introductory bioterrorism concepts for practicing nurses. A literature search and a review of available resources elucidated pertinent content items on bioterrorism and its associated precautions for nurses. Next, two rounds of expert panel consisting of five members rated the identified content and provided comments to validate the curriculum's content. Based on the results, content items were expanded into a curriculum that was piloted as a four hour in person educational session and nurses in attendance were invited to participate in pre-test and post-test questions. They were also asked for their perceptions of the educational session's usefulness and influence on patient care in case of a bioterrorism event. All respondents strongly agreed that the information presented would be useful to them and would influence their patient care in a bioterrorism event. Further refinement, evaluation, and implementation of the developed curriculum are recommended.

How Prepared Are We for Possible Bioterrorist Attacks: An Approach from Emergency Medicine Perspective.

Preparedness for bioterrorist attacks and early recognition of specific agents are essential for public health. Emergency departments may play an important role in this field. The large spectrum of bioterrorism involves not only disastrous terrorism with mass casualties, but also microevents using low technology but producing civil unrest, disruption, disease, disabilities, and death. It aims not only to cause mortality and morbidity, but also to lead to social and political disruption. Preparedness appears to be the most potent defense against possible bioterrorist events. In this article, we aim to create awareness against biological agents and underline the importance of emergency departments in this public health problem.

Ethical and Legal Issues in Bioterrorism Events

Abstract A coordinated response to bioterrorism events requires the participation of healthcare providers, governmental agencies, ethicists, and community members. We describe some of the ethical and considerations that should go into planning for these events.

An overview of the National Microbiology Laboratory emergency management program.

The National Microbiology Laboratory (NML) emergency management program was developed after the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak to provide a framework for the responses to public health events. The program comprises three components (Site response, Continuity and Site support) that have adopted the Incident Command System (ICS) as their management structure and follows the four phases of emergency management. All program components have extensive competency-based training for staff and exercise plans. The emergency management program ensures quality and continuous improvement through its certification in International Organization for Standardization (ISO) 9001 and structured review processes. This means that the Operations Centre can be activated and working at optimum capacity with highly trained and experienced staff within an hour of receiving notice to begin a response. The NML can also send mobile laboratories to aid Canadian or international efforts to address outbreaks or bioterrorism events.

A Review of Classical Swine Fever Virus and Routes of Introduction into the United States and the Potential for Virus Establishment.

Classical swine fever (CSF) is caused by CSF virus (CSFV) which can be the source of substantial morbidity and mortality events in affected swine. The disease can take one of several forms (acute, chronic, or prenatal) and depending on the virulence of the inoculating strain may result in a lethal infection irrespective of the form acquired. Because of the disease-free status of the United States and the high cost of a viral incursion, a summary of US vulnerabilities for viral introduction and persistence is provided. The legal importation of live animals as well as animal products, byproducts, and animal feed serve as a potential route of viral introduction. Current import regulations are described as are mitigation strategies that are commonly utilized to prevent pathogens, including CSFV, from entering the US. The illegal movement of suids and their products as well as an event of bioterrorism are both feasible routes of viral introduction but are difficult to restrict or regulate. Ultimately, recommendations are made for data that would be useful in the event of a viral incursion. Population and density mapping for feral swine across the United States would be valuable in the event of a viral introduction or spillover; density data could further contribute to understanding the risk of infection in domestic swine. Additionally, ecological and behavioral studies, including those that evaluate the effects of anthropogenic food sources that support feral swine densities far above the carrying capacity would provide invaluable insight to our understanding of how human interventions affect feral swine populations. Further analyses to determine the sampling strategies necessary to detect low levels of antibody prevalence in feral swine would also be valuable.

The use of Anthrax and orthopox therapeutic antibodies from human origin in biodefense

The use of Anthrax and orthopox therapeutic antibodies from human origin in biodefense

An Overview on Biological Weapons and Bioterrorism

Bioterrorism is the deliberate or threatened use of biological agents; viruses, bacteria, toxins or other agents to cause illness or death in people, animals, or plants. Since most priority bioterrorism agents are zoonotic in origin, there is a heightened awareness and concern about the possibility of bioterrorism involving animals. Veterinarians and livestock owners may be the first to diagnose the early cases of a bioterrorist act, as livestock can be sentinels of such an exposure. List of the most likely biological agents to be used in an act of bioterrorism had been prioritized and these agents are classified into A, B and C categories. Category A agents and disease are easily transmitted from animals to human, (except for smallpox, which has no animal reservoir) person to person, having high mortality rates and potential for a major public health impact. Category B agents and disease are moderately easy to disseminate and result in moderate morbidity rates and low mortality rates. Category C agents and diseases include emerging pathogens that could be engineered for mass dissemination. Although society has limited ability to prevent bioterrorist attacks, there still is a need to take preventative steps to reduce potential risks for such attacks. Increased laboratory scrutiny for disease agents, greater controls for investigations involving these pathogens and other security measures implemented, are necessary to restrict access to dangerous biological agents. Detection of disease in animals may be essential in predicting a bioterrorism event since most threat agents of bioterrorism are microbes causing zoonotic diseases. Veterinarians and veterinary diagnostic laboratories should become a part of nationwide active surveillance for category A, B, and C agents and diseases, as well as for new and emerging bioterrorism agents.

Preparedness activities and research needs in addressing emerging infectious animal and zoonotic diseases

Emerging infectious animal and zoonotic diseases can inflict significant losses on animal production and public health, and threaten the safety and security of the food system. Threat analysis (forecasting), which monitors the measurable risk indicators of disease emergence, should be in place before the emergence of any threat. Animal and public health authorities develop and regularly re-evaluate disease preparedness, response and recovery plans, based on the 'One Health' principle. These plans should include surveillance, biosecurity measures, communication channels and training for personnel. Scenarios for outbreaks of natural emerging infectious disease or bioterrorist events should be prepared and practised. National and international legislation should be regularly updated to provide a robust legal basis to manage outbreaks. Reference laboratories should have reliable and validated diagnostic tools for rapid, high-throughput testing. Strict biosafety, biocontainment and biosecurity control measures must be implemented in laboratories in order to prevent the accidental or malicious release of pathogens. The pharmaceutical industry should be incentivised to develop vaccines and/or antiviral drugs against disease outbreaks. Conventions between public authorities and the pharmaceutical industry should guarantee adequate stockpiling of the pharmaceuticals needed to control large-scale outbreaks. In the early phase of disease emergence (early warning), veterinarians and stakeholders play an important role in early detection at the farm level. Upon notification, veterinary authorities must take rapid response measures to limit disease spread. National and international short- and medium-term strategic research agendas should be developed, based on a comprehensive gap analysis and horizon scan. This planning will help to guide funding agencies and non-governmental organisations in their quest to support relevant research.

Further optimization of peptide substrate enhanced assay performance for BoNT/A detection by MALDI-TOF mass spectrometry

Rapid and sensitive detection of botulinum neurotoxins (BoNTs), which cause botulism, is essential in a public health emergency or bioterrorism event. We have previously developed a mass spectrometry (MS)-based functional method, Endopep-MS assay, for the fast detection and differentiation of all BoNT serotypes by affinity enriching the toxin and detecting the serotype-specific cleavage products of peptide substrates derived from the in vivo targets. To improve the performance of the Endopep-MS assay, we report here the further optimization of the peptide substrate for the detection of serotype A botulinum neurotoxins. An increased substrate cleavage was achieved by extending the original peptide N-terminus with optimized amino acid sequence, increasing the detection sensitivity of the method. In addition, the resistance of the substrate to nonspecific hydrolysis was dramatically improved by selectively substituting amino acids at the scissile bond and various other positions of the extended peptide. Moreover, incorporating the N-terminal hydrophobic residues dramatically improved the relative intensity of the cleavage products in the mass spectra. This allowed easy detection of the cleavage products, further enhancing the performance of the assay. The limit of detection for spiked serum sample was enhanced from 0.5 to 0.1 mouseLD50 and from 0.5 to 0.2 mouseLD50 for spiked stool.Graphical abstractMass spectra of optimized and old peptide substrates with BoNT/A

Expanding veterinary biosurveillance in Washington, DC: The creation and utilization of an electronic-based online veterinary surveillance system

ObjectivesTo enhance the early detection of emerging infectious diseases and bioterrorism events using companion animal-based surveillance. MethodsWashington, DC, small animal veterinary facilities (n=17) were surveyed to determine interest in conducting infectious disease surveillance. Using these results, an electronic-based online reporting system was developed and launched in August 2015 to monitor rates of canine influenza, canine leptospirosis, antibiotic resistant infections, canine parvovirus, and syndromic disease trends. ResultsNine of the 10 facilities that responded expressed interest conducting surveillance. In September 2015, 17 canine parvovirus cases were reported. In response, a campaign encouraging regular veterinary preventative care was launched and featured on local media platforms. Additionally, during the system’s first year of operation it detected 5 canine leptospirosis cases and 2 antibiotic resistant infections. No canine influenza cases were reported and syndromic surveillance compliance varied, peaking during National Special Security Events. ConclusionsSmall animal veterinarians and the general public are interested in companion animal disease surveillance. The system described can serve as a model for establishing similar systems to monitor disease trends of public health importance in pet populations and enhance biosurveillance capabilities.

Medical Allocations to Persons with Special Needs during a Bioterrorism Event.

After the bioterrorism-anthrax attacks of 2001, public health officials were tasked with planning population-wide medicine dispensing. This planning started with assumptions and then evaluations of seasonal immunization clinics. Research on the 2009 H1N1 pandemic-vaccination campaign showed that an adequately prepared public health system could have prevented over 16% of flu-associated hospitalizations. The 2011 ice storms revealed difficulties with sheltering medically fragile persons with disabilities. Later research showed that training and preparedness levels increased responders’ willingness to serve. When triaging disaster survivors to community-mass-care-services of general shelters, medical shelters, or mental health services; sorting improved up to 15% when past traumatic effects, personal care assistance, or service methodology were accounted for. The number of persons who are disabled and dependent on electric medical equipment are increasing. This current study compared the time it takes to dispense medication to two different cohorts: a general-population cohort (n=31) and a special-needs cohort (n=30). The cohort comprised entirely of persons with special needs took 4.1 compared to 2.48 minutes per person in a general population cohort (p=.057). A person with any special needs took 3.73 versus 2.43 minutes for a person with no special needs (p=.082). Modeling of service times per station and cohort type found significant delays at the medical station among persons in the general population who are pregnant (14 minutes or 840 seconds, p=.002) and persons in the special needs cohort with a language barrier (12.5 minutes or 750 seconds, p=.001). Recommendations include planning for closed Points of Dispensing Sites (PODS) to those with special needs, ensuring a sufficient number of medical dispenser in open PODS, and assigning extra capacity at the medical station area for special needs involving children, language, or pregnancy issues.

Rapid SNP Detection and Genotyping of Bacterial Pathogens by Pyrosequencing.

Bacterial identification and typing are fixtures of microbiology laboratories and are vital aspects of our response mechanisms in the event of foodborne outbreaks and bioterrorist events. Whole genome sequencing (WGS) is leading the way in terms of expanding our ability to identify and characterize bacteria through the identification of subtle differences between genomes (e.g. single nucleotide polymorphisms (SNPs) and insertions/deletions). Modern high-throughput technologies such as pyrosequencing can facilitate the typing of bacteria by generating short-read sequence data of informative regions identified by WGS analyses, at a fraction of the cost of WGS. Thus, pyrosequencing systems remain a valuable asset in the laboratory today. Presented in this chapter are two methods developed in the Amoako laboratory that detail the identification and genotyping of bacterial pathogens. The first targets canonical single nucleotide polymorphisms (canSNPs) of evolutionary importance in Bacillus anthracis, the causative agent of Anthrax. The second assay detects Shiga-toxin (stx) genes, which are associated with virulence in Escherichia coli and Shigella spp., and differentiates the subtypes of stx-1 and stx-2 based on SNP loci. These rapid methods provide end users with important information regarding virulence traits as well as the evolutionary and biogeographic origin of isolates.

Biodefense Spending and Waste: Impact on Public Health Initiatives

Abstract While the threat of bioterrorism carries with it strong emotions of fear and panic, the likelihood-adjusted fatality rates for a horrific bioterror event pale in comparison to that of an infectious disease like influenza. Based on this assumed risk of occurrence, the likelihood-adjusted fatality rate of a bioweapon attack is 900 deaths per year as compared to 36,000 deaths per year for influenza. The FY2016 budget for biodefense was $1.4 million in comparison to $1.2 million for pandemic influenza and emerging diseases. In addition to poor allocation of funds based on actual risk, the biodefense budget lacks government oversight, has poorly defined objectives and unnecessary redundancy. Streamlining the budget and appropriating funds with more emphasis on actual risk would allow an increase in essential areas of public health.

Culture-Independent Diagnostics for Health Security

The past decade has seen considerable development in the diagnostic application of nonculture methods, including nucleic acid amplification-based methods and mass spectrometry, for the diagnosis of infectious diseases. The implications of these new culture-independent diagnostic tests (CIDTs) include bypassing the need to culture organisms, thus potentially affecting public health surveillance systems, which continue to use isolates as the basis of their surveillance programs and to assess phenotypic resistance to antimicrobial agents. CIDTs may also affect the way public health practitioners detect and respond to a bioterrorism event. In response to a request from the Department of Homeland Security, Los Alamos National Laboratory and the Centers for Disease Control and Prevention cosponsored a workshop to review the impact of CIDTs on the rapid detection and identification of biothreat agents. Four panel discussions were held that covered nucleic acid amplification-based diagnostics, mass spectrometry, antibody-based diagnostics, and next-generation sequencing. Exploiting the extensive expertise available at this workshop, we identified the key features, benefits, and limitations of the various CIDT methods for providing rapid pathogen identification that are critical to the response and mitigation of a bioterrorism event. After the workshop we conducted a thorough review of the literature, investigating the current state of these 4 culture-independent diagnostic methods. This article combines information from the literature review and the insights obtained at the workshop.

Introduction to An Assessment Tool for Early Detection of Suspected Bioterrorism Attack

It is not easy to discriminate between deliberate and natural infectious disease outbreaks during the initial period of events; the formers generally cause serious damage and public panic. Thus, an early detection of a bioterrorism event is very significant, especially for those who are responsible for dealing with the bioterrorism events, in order to detect a suspected bioterrorism event earlier. This article is intended to systematically introduce a quantitative assessment tool developed by Grunow and Finke in 2002 to discriminate between deliberate and natural infectious disease outbreaks, which could be provided and utilized for the frontline medical staff and public health officers, as well as military, police, firefighter, and other staffs working in critical infrastructure which confronted by bioterror attacks.