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1.  Triage and Management of Accidental Laboratory Exposures to Biosafety Level-3 and -4 Agents 
The recent expansion of biocontainment laboratory capacity in the United States has drawn attention to the possibility of occupational exposures to BSL-3 and -4 agents and has prompted a reassessment of medical management procedures and facilities to deal with these contingencies. A workshop hosted by the National Interagency Biodefense Campus was held in October 2007 and was attended by representatives of all existing and planned BSL-4 research facilities in the U.S. and Canada. This report summarizes important points of discussion and recommendations for future coordinated action, including guidelines for the engineering and operational controls appropriate for a hospital care and isolation unit. Recommendations pertained to initial management of exposures (ie, immediate treatment of penetrating injuries, reporting of exposures, initial evaluation, and triage). Isolation and medical care in a referral hospital (including minimum standards for isolation units), staff recruitment and training, and community outreach also were addressed. Workshop participants agreed that any unit designated for the isolation and treatment of laboratory employees accidentally infected with a BSL-3 or -4 pathogen should be designed to maximize the efficacy of patient care while minimizing the risk of transmission of infection. Further, participants concurred that there is no medically based rationale for building care and isolation units to standards approximating a BSL-4 laboratory. Instead, laboratory workers accidentally exposed to pathogens should be cared for in hospital isolation suites staffed by highly trained professionals following strict infection control procedures.
doi:10.1089/bsp.2009.0002
PMCID: PMC2749272  PMID: 19634998
2.  Preparing a Community Hospital to Manage Work-related Exposures to Infectious Agents in BioSafety Level 3 and 4 Laboratories 
Emerging Infectious Diseases  2010;16(3):373-378.
Training increased willingness of healthcare workers to care for patients with all types of communicable diseases.
Construction of new BioSafety Level (BSL) 3 and 4 laboratories has raised concerns regarding provision of care to exposed workers because of healthcare worker (HCW) unfamiliarity with precautions required. When the National Institutes of Health began construction of a new BSL-4 laboratory in Hamilton, Montana, USA, in 2005, they contracted with St. Patrick Hospital in Missoula, Montana, for care of those exposed. A care and isolation unit is described. We developed a training program for HCWs that emphasized the optimal use of barrier precautions and used pathogen-specific modules and simulations with mannequins and fluorescent liquids that represented infectious body fluids. The facility and training led to increased willingness among HCWs to care for patients with all types of communicable diseases. This model may be useful for other hospitals, whether they support a BSL-4 facility, are in the proximity of a BSL-3 facility, or are interested in upgrading their facilities to prepare for exotic and novel infectious diseases.
doi:10.3201/eid1603.091485
PMCID: PMC3322039  PMID: 20202409
Viral hemorrhagic fevers; occupational exposure; curriculum; biosafety level; viruses; community hospital; perspective
3.  Framework for Leadership and Training of Biosafety Level 4 Laboratory Workers 
Emerging Infectious Diseases  2008;14(11):1685-1688.
One-sentence summary for table of contents: Training should include theoretical consideration of biocontainment principles, practical hands-on training, and mentored on-the-job experience.
Construction of several new Biosafety Level 4 (BSL-4) laboratories and expansion of existing operations have created an increased international demand for well-trained staff and facility leaders. Directors of most North American BSL-4 laboratories met and agreed upon a framework for leadership and training of biocontainment research and operations staff. They agreed on essential preparation and training that includes theoretical consideration of biocontainment principles, practical hands-on training, and mentored on-the-job experiences relevant to positional responsibilities as essential preparation before a person’s independent access to a BSL-4 facility. They also agreed that the BSL-4 laboratory director is the key person most responsible for ensuring that staff members are appropriately prepared for BSL-4 operations. Although standardized certification of training does not formally exist, the directors agreed that facility-specific, time-limited documentation to recognize specific skills and experiences of trained persons is needed.
doi:10.3201/eid1411.080741
PMCID: PMC2630756  PMID: 18976549
BSL-4 laboratory; containment laboratories; training; perspective
4.  Biosafety Training and Incident-reporting Practices in the United States: A 2008 Survey of Biosafety Professionals 
Concern over the adequacy of biosafety training and incident-reporting practices within biological laboratories in the United States has risen in recent years due to the increase in research on infectious diseases and the concomitant rise in the number of biocontainment laboratories. Reports of laboratory-acquired infections and delays in reporting such incidents have also contributed to the concern. Consequently, biosafety training and incident-reporting practices are being given considerable attention by both the executive branch and Congress. We conducted a 51-question survey of biosafety professionals in June 2008 to capture information on methods used to train new laboratory workers within biosafety level 2 (BSL-2) laboratories, animal biosafety level 2 (ABSL-2) laboratories, biosafety level 3 (BSL-3) laboratories, and animal biosafety level 3 (ABSL-3) laboratories. The survey results suggest nearly all senior scientists, faculty, staff, and students working in these biocontainment laboratories are required to have biosafety training, and three-quarters of respondents indicated a biosafety or environmental health and safety professional provides explicit instructions on reporting incidents to each new lab worker. Only half of the respondents with BSL-2/ABSL-2 laboratories at their institution and 59% of respondents from institutions with BSL-3/ABSL-3 laboratories indicated custodial or maintenance workers are required to receive biosafety training at the BSL-2/ABSL-2 and BSL-3/ABSL-3 levels, respectively. Opportunities for targeted improvement such as providing training to non-traditional laboratory workers (e.g., custodians, maintenance workers) and posting laboratory incident-reporting protocols on institutional environmental health and safety websites may exist. Variations in biosafety training requirements, incident-reporting practices, and attitudes towards laboratory safety revealed through this survey of biosafety professionals also support the development of core competencies in biosafety practice that could lead to more uniform practices and robust safety cultures.
PMCID: PMC2947438  PMID: 20890389
5.  Laboratory-associated infections and biosafety. 
Clinical Microbiology Reviews  1995;8(3):389-405.
An estimated 500,000 laboratory workers in the United States are at risk of exposure to infectious agents that cause disease ranging from inapparent to life-threatening infections, but the precise risk to a given worker unknown. The emergence of human immunodeficiency virus and hantavirus, the continuing problem of hepatitis B virus, and the reemergence of Mycobacterium tuberculosis have renewed interest in biosafety for the employees of laboratories and health care facilities. This review examines the history, the causes, and the methods for prevention of laboratory-associated infections. The initial step in a biosafety program is the assessment of risk to the employee. Risk assessment guidelines include the pathogenicity of the infectious agent, the method of transmission, worker-related risk factors, the source and route of infection, and the design of the laboratory facility. Strategies for the prevention and management of laboratory-associated infections are based on the containment of the infectious agent by physical separation from the laboratory worker and the environment, employee education about the occupational risks, and availability of an employee health program. Adherence to the biosafety guidelines mandated or proposed by various governmental and accrediting agencies reduces the risk of an occupational exposure to infectious agents handled in the workplace.
PMCID: PMC174631  PMID: 7553572
6.  The Impact of Regulations, Safety Considerations and Physical Limitations on Research Progress at Maximum Biocontainment 
Viruses  2012;4(12):3932-3951.
We describe herein, limitations on research at biosafety level 4 (BSL-4) containment laboratories, with regard to biosecurity regulations, safety considerations, research space limitations, and physical constraints in executing experimental procedures. These limitations can severely impact the number of collaborations and size of research projects investigating microbial pathogens of biodefense concern. Acquisition, use, storage, and transfer of biological select agents and toxins (BSAT) are highly regulated due to their potential to pose a severe threat to public health and safety. All federal, state, city, and local regulations must be followed to obtain and maintain registration for the institution to conduct research involving BSAT. These include initial screening and continuous monitoring of personnel, controlled access to containment laboratories, accurate and current BSAT inventory records. Safety considerations are paramount in BSL-4 containment laboratories while considering the types of research tools, workflow and time required for conducting both in vivo and in vitro experiments in limited space. Required use of a positive-pressure encapsulating suit imposes tremendous physical limitations on the researcher. Successful mitigation of these constraints requires additional time, effort, good communication, and creative solutions. Test and evaluation of novel vaccines and therapeutics conducted under good laboratory practice (GLP) conditions for FDA approval are prioritized and frequently share the same physical space with important ongoing basic research studies. The possibilities and limitations of biomedical research involving microbial pathogens of biodefense concern in BSL-4 containment laboratories are explored in this review.
doi:10.3390/v4123932
PMCID: PMC3528297  PMID: 23342380
biocontainment; biosafety level 4 (BSL-4); biological select agents and toxins (BSAT); positive pressure suit; biodefense; biosecurity; ebola virus; highly pathogenic viruses; limitations; collaboration
7.  Characterization of systemic and pneumonic murine models of plague infection using a conditionally virulent strain 
Yersinia pestis causes bubonic and pneumonic plague in humans. The pneumonic infection is the most severe and invariably fatal if untreated. Because of its high virulence, ease of delivery and precedent of use in warfare, Y. pestis is considered a potential bioterror agent. No licensed plague vaccine is currently available in the US. Laboratory research with virulent strains requires appropriate biocontainment (i.e., Biosafety Level 3 (BSL-3) for procedures that generate aerosol/droplets) and secure facilities that comply with federal select agent regulations. To assist in the identification of promising vaccine candidates during the early phases of development, we characterized mouse models of systemic and pneumonic plague infection using the Y. pestis strain EV76, an attenuated human vaccine strain that can be rendered virulent in mice under in vivo iron supplementation. Mice inoculated intranasally or intravenously with Y. pestis EV76 in the presence of iron developed a systemic and pneumonic plague infection that resulted in disease and lethality. Bacteria replicated and severely compromised the spleen, liver and lungs. Susceptibility was age dependent, with younger mice being more vulnerable to pneumonic infection. We used these models of infection to assess the protective capacity of newly developed Salmonella-based plague vaccines. The protective outcome varied depending on the route and dose of infection. Protection was associated with the induction of specific immunological effectors in systemic/mucosal compartments. The models of infection described could serve as safe and practical tools for identifying promising vaccine candidates that warrant further potency evaluation using fully virulent strains in BSL-3 settings.
doi:10.1016/j.cimid.2012.10.005
PMCID: PMC3594127  PMID: 23195858
Yersinia pestis; plague infection model; EV76; plague vaccines
8.  Challenges and Practices in Building and Implementing Biosafety and Biosecurity Programs to Enable Basic and Translational Research with Select Agents 
Journal of bioterrorism & biodefense  2013;Suppl 3(15):12634-.
Select agent research in the United States must meet federally-mandated biological surety guidelines and rules which are comprised of two main components: biosecurity and biosafety. Biosecurity is the process employed for ensuring biological agents are properly safeguarded against theft, loss, diversion, unauthorized access or use/release. Biosafety is those processes that ensure that operations with such agents are conducted in a safe, secure and reliable manner. As such, a biological surety program is generally concerned with biological agents that present high risk for adverse medical and/or agricultural consequences upon release outside of proper containment. The U.S. Regional and National Biocontainment Laboratories (RBL, NBL) represent expertise in this type of research, and are actively engaged in the development of programs to address these critical needs and federal requirements. While this comprises an ongoing activity for the RBLs, NBLs and other facilities that handle select agents as new guidelines and regulations are implemented, the present article is written with the goal of presenting a simplified yet comprehensive review of these requirements. Herein, we discuss the requirements and the various activities that the RBL/NBL programs have implemented to achieve these metrics set forth by various agencies within the U.S. Federal government.
doi:10.4172/2157-2526.S3-015
PMCID: PMC4041738  PMID: 24900945
9.  A Burkholderia pseudomallei ΔpurM Mutant Is Avirulent in Immunocompetent and Immunodeficient Animals: Candidate Strain for Exclusion from Select-Agent Lists▿  
Infection and Immunity  2010;78(7):3136-3143.
Burkholderia pseudomallei causes the disease melioidosis in humans and is classified as a category B select agent. Research utilizing this pathogen is highly regulated in the United States, and even basic studies must be conducted in biosafety level 3 (BSL-3) facilities. There is currently no attenuated B. pseudomallei strain available that is excluded from select-agent regulations and can be safely handled at BSL-2 facilities. To address this need, we created Bp82 and Bp190, which are ΔpurM derivatives of B. pseudomallei strains 1026b and K96243 that are deficient in adenine and thiamine biosynthesis but replication competent in vitro in rich medium. A series of animal challenge studies was conducted to ensure that these strains were fully attenuated. Whereas the parental strains 1026b and K96243 and the complemented mutants Bp410 and Bp454 were virulent in BALB/c mice following intranasal inoculation, the ΔpurM mutants Bp82 and Bp190 were avirulent even when they were administered at doses 4 logs higher than the doses used for the parental strains. Animals challenged with high doses of the ΔpurM mutants rapidly cleared the bacterium from tissues (lung, liver, and spleen) and remained free of culturable bacteria for the duration of the experiments (up to 60 days postinfection). Moreover, highly susceptible 129/SvEv mice and immune incompetent mice (IFN-γ−/−, SCID) were resistant to challenges with ΔpurM mutant Bp82. This strain was also avirulent in the Syrian hamster challenge model. We concluded that ΔpurM mutant Bp82 is fully attenuated and safe for use under BSL-2 laboratory conditions and thus is a candidate for exclusion from the select-agent list.
doi:10.1128/IAI.01313-09
PMCID: PMC2897367  PMID: 20404077
10.  Biosafety and biosecurity as essential pillars of international health security and cross-cutting elements of biological nonproliferation 
BMC Public Health  2010;10(Suppl 1):S12.
The critical aspects of biosafety, biosecurity, and biocontainment have been in the spotlight in recent years. There have also been increased international efforts to improve awareness of modern practices and concerns with regard to the safe pursuit of life sciences research, and to optimize current oversight frameworks, thereby resulting in decreased risk of terrorist/malevolent acquisition of deadly pathogens or accidental release of a biological agent, and increased safety of laboratory workers. Our purpose is to highlight how the World Health Organization’s (WHO) revised International Health Regulations (IHR[2005]), the Biological Weapons Convention (BWC), and the United Nations Security Council Resolution (UNSCR) 1540 overlap in their requirements with regard to biosafety and biosecurity in order to improve the understanding of practitioners and policymakers and maximize the use of national resources employed to comply with internationally-mandated requirements. The broad range of goals of these international instruments, which are linked by the common thread of biosafety and biosecurity, highlight their significance as essential pillars of international health security and cross-cutting elements of biological nonproliferation. The current efforts of the Republic of Georgia to enhance biosafety and biosecurity in accordance with these international instruments are summarized.
doi:10.1186/1471-2458-10-S1-S12
PMCID: PMC3005572  PMID: 21143822
11.  A Unique BSL-3 Cryo-Electron Microscopy Laboratory at UTMB 
This article describes a unique cryo-electron microscopy (CryoEM) facility to study the three-dimensional organization of viruses at biological safety level 3 (BSL-3). This facility, the W. M. Keck Center for Virus Imaging, has successfully operated for more than a year without incident and was cleared for select agent studies by the Centers for Disease Control and Prevention (CDC). Standard operating procedures for the laboratory were developed and implemented to ensure its safe and efficient operation. This facility at the University of Texas Medical Branch (Galveston, TX) is the only such BSL-3 CryoEM facility approved for select agent research.
PMCID: PMC3156611  PMID: 21852942
12.  Optimizing triage and hospitalization in adult general medical emergency patients: the triage project 
Background
Patients presenting to the emergency department (ED) currently face inacceptable delays in initial treatment, and long, costly hospital stays due to suboptimal initial triage and site-of-care decisions. Accurate ED triage should focus not only on initial treatment priority, but also on prediction of medical risk and nursing needs to improve site-of-care decisions and to simplify early discharge management. Different triage scores have been proposed, such as the Manchester triage system (MTS). Yet, these scores focus only on treatment priority, have suboptimal performance and lack validation in the Swiss health care system. Because the MTS will be introduced into clinical routine at the Kantonsspital Aarau, we propose a large prospective cohort study to optimize initial patient triage. Specifically, the aim of this trial is to derive a three-part triage algorithm to better predict (a) treatment priority; (b) medical risk and thus need for in-hospital treatment; (c) post-acute care needs of patients at the most proximal time point of ED admission.
Methods/design
Prospective, observational, multicenter, multi-national cohort study. We will include all consecutive medical patients seeking ED care into this observational registry. There will be no exclusions except for non-adult and non-medical patients. Vital signs will be recorded and left over blood samples will be stored for later batch analysis of blood markers. Upon ED admission, the post-acute care discharge score (PACD) will be recorded. Attending ED physicians will adjudicate triage priority based on all available results at the time of ED discharge to the medical ward. Patients will be reassessed daily during the hospital course for medical stability and readiness for discharge from the nurses and if involved social workers perspective. To assess outcomes, data from electronic medical records will be used and all patients will be contacted 30 days after hospital admission to assess vital and functional status, re-hospitalization, satisfaction with care and quality of life measures.
We aim to include between 5000 and 7000 patients over one year of recruitment to derive the three-part triage algorithm. The respective main endpoints were defined as (a) initial triage priority (high vs. low priority) adjudicated by the attending ED physician at ED discharge, (b) adverse 30 day outcome (death or intensive care unit admission) within 30 days following ED admission to assess patients risk and thus need for in-hospital treatment and (c) post acute care needs after hospital discharge, defined as transfer of patients to a post-acute care institution, for early recognition and planning of post-acute care needs. Other outcomes are time to first physician contact, time to initiation of adequate medical therapy, time to social worker involvement, length of hospital stay, reasons for discharge delays, patient’s satisfaction with care, overall hospital costs and patients care needs after returning home.
Discussion
Using a reliable initial triage system for estimating initial treatment priority, need for in-hospital treatment and post-acute care needs is an innovative and persuasive approach for a more targeted and efficient management of medical patients in the ED. The proposed interdisciplinary , multi-national project has unprecedented potential to improve initial triage decisions and optimize resource allocation to the sickest patients from admission to discharge. The algorithms derived in this study will be compared in a later randomized controlled trial against a usual care control group in terms of resource use, length of hospital stay, overall costs and patient’s outcomes in terms of mortality, re-hospitalization, quality of life and satisfaction with care.
Trial registration
ClinicalTrials.gov Identifier, NCT01768494
doi:10.1186/1471-227X-13-12
PMCID: PMC3723418  PMID: 23822525
Triage; Biomarker; Post-acute care needs; Emergency medicine; Manchester triage system
13.  Managing Potential Laboratory Exposure to Ebola Virus by Using a Patient Biocontainment Care Unit1 
Emerging Infectious Diseases  2008;14(6):881-887.
One-sentence summary for table of contents: Recommendations are needed for management of potential laboratory exposure to a Biosafety Level 4 pathogen.
In 2004, a scientist from the US Army Medical Research Institute of Infectious Diseases (USAMRIID) was potentially exposed to a mouse-adapted variant of the Zaire species of Ebola virus. The circumstances surrounding the case are presented, in addition to an update on historical admissions to the medical containment suite at USAMRIID. Research facilities contemplating work with pathogens requiring Biosafety Level 4 laboratory precautions should be mindful of the occupational health issues highlighted in this article.
doi:10.3201/eid1406.071489
PMCID: PMC2600302  PMID: 18507897
Ebola virus; Marburg virus; viral hemorrhagic fever; filovirus; biocontainment; quarantine; isolation; biosafety; laboratory exposure; synopsis
14.  The NUITM-KEMRI P3 Laboratory in Kenya: Establishment, Features, Operation and Maintenance 
Tropical Medicine and Health  2013;41(1):27-37.
A biocontainment facility is a core component in any research setting due to the services it renders towards comprehensive biosafety observance. The NUITM-KEMRI P3 facility was set up in 2007 and has been actively in use since 2010 by researchers from this and other institutions. A number of hazardous agents have been handled in the laboratory among them MDR-TB and yellow fever viruses. The laboratory has the general physical and operational features of a P3 laboratory in addition to a number of unique features, among them the water-air filtration system, the eco-mode operation feature and automation of the pressure system that make the facility more efficient. It is equipped with biosafety and emergency response equipments alongside common laboratory equipments, maintained regularly using daily, monthly and yearly routines. Security and safety is strictly observed within the facility, enhanced by restricted entry, strict documentation and use of safety symbols. Training is also engrained within the operation of the laboratory and is undertaken and evaluated annually. Though the laboratory is in the process of obtaining accreditation, it is fully certified courtesy of the manufactures’ and constructed within specified standards.
doi:10.2149/tmh.2013-01
PMCID: PMC3601200  PMID: 23533023
P3 Laboratory; Kenya
15.  Construction and Organization of a BSL-3 Cryo-Electron Microscopy Laboratory at UTMB 
Journal of structural biology  2012;181(3):223-233.
A unique cryo-electron microscopy facility has been designed and constructed at the University of Texas Medical Branch (UTMB) to study the three-dimensional organization of viruses and bacteria classified as select agents at biological safety level (BSL)-3, and their interactions with host cells. A 200 keV high-end cryo-electron microscope was installed inside a BSL-3 containment laboratory and standard operating procedures were developed and implemented to ensure its safe and efficient operation. We also developed a new microscope decontamination protocol based on chlorine dioxide gas with a continuous flow system, which allowed us to expand the facility capabilities to study bacterial agents including spore-forming species. The new unified protocol does not require agent-specific treatment in contrast to the previously used heat decontamination. To optimize the use of the cryo-electron microscope and to improve safety conditions, it can be remotely controlled from a room outside of containment, or through a computer network world-wide. Automated data collection is provided by using JADAS (single particle imaging) and SerialEM (tomography). The facility has successfully operated for more than a year without an incident and was certified as a select agent facility by the Centers for Disease Control.
doi:10.1016/j.jsb.2012.12.007
PMCID: PMC3593667  PMID: 23274136
cryo-electron microscopy; single particle imaging; electron tomography; biological safety containment
16.  Biocontainment in Gain-of-Function Infectious Disease Research 
mBio  2012;3(5):e00290-12.
ABSTRACT
The discussion of H5N1 influenza virus gain-of-function research has focused chiefly on its risk-to-benefit ratio. Another key component of risk is the level of containment employed. Work is more expensive and less efficient when pursued at biosafety level 4 (BSL-4) than at BSL-3 or at BSL-3 as modified for work with agricultural pathogens (BSL-3-Ag). However, here too a risk-to-benefit ratio analysis is applicable. BSL-4 procedures mandate daily inspection of facilities and equipment, monitoring of personnel for signs and symptoms of disease, and logs of dates and times that personnel, equipment, supplies, and samples enter and exit containment. These measures are not required at BSL-3 or BSL-3-Ag. Given the implications of inadvertent or deliberate release of high-threat pathogens with pandemic potential, it is imperative that the World Health Organization establish strict criteria for biocontainment that can be fairly applied in the developing world, as well as in more economically developed countries.
doi:10.1128/mBio.00290-12
PMCID: PMC3484385  PMID: 23047747
17.  Identification of Virulence Determinants within the L Genomic Segment of the Pichinde Arenavirus 
Journal of Virology  2013;87(12):6635-6643.
Several arenaviruses are responsible for causing viral hemorrhagic fevers (VHF) in humans. Lassa virus (LASV), the causative agent of Lassa fever, is a biosafety level 4 (BSL4) pathogen that requires handling in BSL4 facilities. In contrast, the Pichinde arenavirus (PICV) is a BSL2 pathogen that can cause hemorrhagic fever-like symptoms in guinea pigs that resemble those observed in human Lassa fever. Comparative sequence analysis of the avirulent P2 strain of PICV and the virulent P18 strain shows a high degree of sequence homology in the bisegmented genome between the two strains despite the polarized clinical outcomes noted for the infected animals. Using reverse genetics systems that we have recently developed, we have mapped the sequence changes in the large (L) segment of the PICV genome that are responsible for the heightened virulence phenotype of the P18 strain. By monitoring the degree of disease severity and lethality caused by the different mutant viruses, we have identified specific residues located within the viral L polymerase gene encoded on the L segment essential for mediating disease pathogenesis. Through quantitative reverse transcription-PCR (RT-PCR) analysis, we have confirmed that the same set of residues is responsible for the increased viral replicative potential of the P18 strain and its heightened disease severity in vivo. Our laboratory findings serve to reinforce field observations that a high level of viremia often correlates with severe disease outcomes in LASV-infected patients.
doi:10.1128/JVI.00044-13
PMCID: PMC3676128  PMID: 23552411
18.  Comparison and Analysis of Biological Agent Category Lists Based On Biosafety and Biodefense 
PLoS ONE  2014;9(6):e101163.
Biological agents pose a serious threat to human health, economic development, social stability and even national security. The classification of biological agents is a basic requirement for both biosafety and biodefense. We compared and analyzed the Biological Agent Laboratory Biosafety Category list and the defining criteria according to the World Health Organization (WHO), the National Institutes of Health (NIH), the European Union (EU) and China. We also compared and analyzed the Biological Agent Biodefense Category list and the defining criteria according to the Centers for Disease Control and Prevention (CDC) of the United States, the EU and Russia. The results show some inconsistencies among or between the two types of category lists and criteria. We suggest that the classification of biological agents based on laboratory biosafety should reduce the number of inconsistencies and contradictions. Developing countries should also produce lists of biological agents to direct their development of biodefense capabilities.To develop a suitable biological agent list should also strengthen international collaboration and cooperation.
doi:10.1371/journal.pone.0101163
PMCID: PMC4076228  PMID: 24979754
19.  Medical radiation countermeasures for nuclear and radiological emergencies: Current status and future perspectives 
Nuclear and radiological emergencies (NREs) occurred globally and recent incidences in India are indicating toward the need for comprehensive medical preparedness required both at incident site and hospitals. The enhanced threat attributed toward insurgency is another causative factor of worry. The response capabilities and operational readiness of responders (both health and non-health service providers) in contaminated environment need to be supported by advancement in R & D and technological efforts to develop prophylactics and radiation mitigators. It is essential to develop phase 1 alternatives of such drugs for unseen threats as a part of initial preparedness. At the incident site and hospital level, external decontamination procedures need to be standardized and supported by protective clothing and Shudika kits developed by INMAS. The medical management of exposure requires systematic approach to perform triage, resuscitation and curative care. The internal contamination requires decorporation agents to be administered based on procedural diagnostics. Various key issues pertaining to policy decisions, R & D promotion, community awareness, specialized infrastructure for NREs preparedness has been discussed. The present review is an attempt to provide vital information about the current status of various radiation countermeasures and future perspective(s) ahead.
doi:10.4103/0975-7406.68502
PMCID: PMC3148625  PMID: 21829316
Free radicals; linear energy transfer; radiation countermeasures
20.  Biosafety Guidelines for Handling Microorganisms in the Teaching Laboratory: Development and Rationale† 
The safe handling of microorganisms in the teaching laboratory is a top priority. However, in the absence of a standard set of biosafety guidelines tailored to the teaching laboratory, individual educators and institutions have been left to develop their own plans. This has resulted in a lack of consistency, and differing levels of biosafety practices across institutions. Influenced by the lack of clear guidelines and a recent outbreak of Salmonella infections that was traced back to teaching laboratory exposures, the Education Board of the American Society for Microbiology charged a task force to develop a uniform set of biosafety guidelines for working with microorganisms in the teaching laboratory. These guidelines represent best practices for safely handling microbes, based on the safety requirements found in the Centers for Disease Control and Prevention’s (CDC’s) Biosafety in Microbiological and Biomedical Laboratories (BMBL). Guidelines for safely handling microbes at both biosafety level 1 (BSL1) and biosafety level 2 (BSL2) were developed. The guidelines are brief by design for ease of use and are accompanied by an extensive appendix containing explanatory notes, sample documents, and additional resources. These guidelines provide educators with a clear and consistent way to safely work with microorganisms in the teaching laboratory.
doi:10.1128/jmbe.v14i1.531
PMCID: PMC3706168  PMID: 23858356
21.  Physiological-social score (PMEWS) vs. CURB-65 to triage pandemic influenza: a comparative validation study using community-acquired pneumonia as a proxy 
Background
An influenza pandemic may increase Emergency Department attendance 7-fold. In the absence of a validated "flu score" to assess severity and assist triage decisions from primary into secondary care, current UK draft management recommendations have suggested the use of CURB-65 and chest X-ray as a proxy. We developed the Pandemic Medical Early Warning Score (PMEWS) to track and triage flu patients, taking into account physiological and social factors and without requiring laboratory or radiology services.
Methods
Validation of the PMEWS score against an unselected group of patients presenting and admitted to an urban UK teaching hospital with community acquired pneumonia. Comparison of PMEWS performance against CURB-65 for three outcome measures: need for admission, admission to high dependency or intensive care, and inpatient mortality using area under ROC curve (AUROC) and the Hanley-McNeil method of comparison.
Results
PMEWS was a better predictor of need for admission (AUROC 0.944) and need of higher level of care (AUROC 0.83) compared with CURB-65 (AUROCs 0.881 and 0.640 respectively) but was not as good a predictor of subsequent inpatient mortality (AUROC 0.663).
Conclusion
Although further validation against other disease datasets as a proxy for pandemic flu is required, we show that PMEWS is rapidly applicable for triage of large numbers of flu patients to self-care, hospital admission or HDU/ICU care. It is scalable to reflect changing admission thresholds that will occur during a pandemic.
doi:10.1186/1472-6963-7-33
PMCID: PMC1819377  PMID: 17328822
22.  Simulating Henipavirus Multicycle Replication in a Screening Assay Leads to Identification of a Promising Candidate for Therapy▿ †  
Journal of Virology  2009;83(10):5148-5155.
Nipah (NiV) and Hendra (HeV) viruses are emerging zoonotic paramyxoviruses that cause encephalitis in humans, with fatality rates of up to 75%. We designed a new high-throughput screening (HTS) assay for inhibitors of infection based on envelope glycoprotein pseudotypes. The assay simulates multicycle replication and thus identifies inhibitors that target several stages of the viral life cycle, but it still can be carried out under biosafety level 2 (BSL-2) conditions. These features permit a screen for antivirals for emerging viruses and select agents that otherwise would require BSL-4 HTS facilities. The screening of a small compound library identified several effective molecules, including the well-known compound chloroquine, as highly active inhibitors of pseudotyped virus infection. Chloroquine inhibited infection with live HeV and NiV at a concentration of 1 μM in vitro (50% inhibitory concentration, 2 μM), which is less than the plasma concentrations present in humans receiving chloroquine treatment for malaria. The mechanism for chloroquine's antiviral action likely is the inhibition of cathepsin L, a cellular enzyme that is essential for the processing of the viral fusion glycoprotein and the maturation of newly budding virions. Without this processing step, virions are not infectious. The identification of a compound that inhibits a known cellular target that is important for viral maturation but that had not previously been shown to have antiviral activity for henipaviruses highlights the validity of this new screening assay. Given the established safety profile and broad experience with chloroquine in humans, the results described here provide an option for treating individuals infected by these deadly viruses.
doi:10.1128/JVI.00164-09
PMCID: PMC2682105  PMID: 19264786
23.  Evaluation of Chimeric Japanese Encephalitis and Dengue Viruses for Use in Diagnostic Plaque Reduction Neutralization Tests▿  
The plaque reduction neutralization test (PRNT) is a specific serological test used to identify and confirm arbovirus infection in diagnostic laboratories and monitor immunological protection in vaccine recipients. Wild-type (wt) viruses used in the PRNT may be difficult to grow and plaque titrate, such as the dengue viruses (DENV), and/or may require biosafety level 3 (BSL3) containment, such as West Nile virus (WNV), St. Louis encephalitis virus (SLEV), and Japanese encephalitis virus (JEV). These requirements preclude their use in diagnostic laboratories with only BSL2 capacity. In addition, wt JEV falls under the jurisdiction of the select-agent program and can be used only in approved laboratories. The chimeric vaccine viruses ChimeriVax-WNV and -SLEV have previously been shown to elicit antibody reactivity comparable to that of parental wt WNV and SLEV. ChimeriVax viruses provide advantages for PRNT, as follows: they grow more rapidly than most wt flaviviruses, produce large plaques, require BSL2 conditions, and are not under select-agent restrictions. We evaluated the ChimeriVax-DENV serotype 1 (DENV1), -DENV2, -DENV3, -DENV4, and -JEV for use in PRNT on sera from DENV- and JEV-infected patients and from JEV vaccine recipients. Serostatus agreement was 100% between the ChimeriVax-DENV serotypes and wt prototype DENV and 97% overall with ChimeriVax-JEV compared to prototype Nakayama JEV, 92% in a subgroup of JEV vaccine recipients, and 100% in serum from encephalitis patients naturally infected with JEV. ChimeriVax-DENV and -JEV plaque phenotype and BSL2 requirements, combined with sensitive and specific reactivity, make them good substitutes for wt DENV and JEV in PRNT in public health diagnostic laboratories.
doi:10.1128/CVI.00095-09
PMCID: PMC2708403  PMID: 19458204
24.  Mass Burns Disaster in Abule-egba, Lagos, Nigeria from a Petroleum Pipeline Explosion Fire 
Summary
The aim of this paper is to review the basic principles of triage in mass burns disasters and discuss the experience of the Lagos State University Teaching Hospital (LASUTH), Ikeja, Nigeria, in the December 2006 disaster at Abule-Egba, Lagos, Nigeria. It is hoped that the experience gained will help in the planning for and management of similar disasters in the developing countries with limited facilities. Burn injury has been described as the severest form of trauma and its management is very challenging as it is often accompanied by numerous pathophysiological changes. Successful management requires expert management by well-trained personnel in equipped and dedicated centres. In mass disasters the total number of victims may exceed the capability of the facility and its staff and a system for sorting out the patients and caring for those that will benefit from the facilities available needs to be developed. Other patients will either be sent to other medical facilities for further treatment or discharged after initial care for future follow-up. Documented experiences in the management of mass burns disasters from petroleum pipeline explosions from developing countries are rare. However, petroleum pipeline explosions, especially in the Lagos area of Nigeria, are relatively common. These cases have been associated with a variety of factors. The resulting morbidity and mortality have been high. LASUTH has a dedicated burns centre, which has received and managed many burn patients. Triage is the medical process of screening patients according to their need of treatment and the resources available. The aims and objectives of triage are discussed, its various levels described, and the final goals elaborated. All the burn victims involved in the 2006 disaster were studied, together with the triage carried out at different levels and the consequent sorting of the patients. Standard burns management was carried out. A total of 385 patients sustained burns of various degrees from the fire resulting from the explosion. On site, emergency department (ED) and intra-hospital triage were carried out. Ninety patients were brought to the LASUTH ED. Of these, 51 patients (56.67%) received first-aid treatment and were either discharged for out-patient follow-up or referred to secondary health care facilities. Twenty-eight (31.11%) out of the remaining 39 patients with burns in more than 70% total body surface area (TBSA) were categorized as unsalvageable and 11 (12.22%) with less than 70% TBSA as salvageable. All the patients in the unsalvageable group died (i.e. 100% mortality), while one patient died in the salvageable group (mortality rate, 9.09%). The mortality rate for the ruptured petroleum product pipeline incident was 84.16%; the fatality rate for all patients seen at LASUTH was 32.22%. The need for caution in the handling of petroleum products is discussed and the effectiveness of the triage system used is highlighted. In conclusion, burns from flammable petroleum products can be very dangerous and proper triage should therefore be carried out, with salvageable patients being managed by experts in dedicated burns centres.
PMCID: PMC3188224  PMID: 21991163
MASS BURNS; DISASTER; ABULE-EGBA; LAGOS; NIGERIA; PETROLEUM; PIPELINE; EXPLOSION FIRE
25.  Triage, monitoring, and treatment of mass casualty events involving chemical, biological, radiological, or nuclear agents 
In a mass casualty situation due to chemical, biological, radiological, or nuclear (CBRN) event, triage is absolutely required for categorizing the casualties in accordance with medical care priorities. Dealing with a CBRN event always starts at the local level. Even before the detection and analysis of agents can be undertaken, zoning, triage, decontamination, and treatment should be initiated promptly. While applying the triage system, the available medical resources and maximal utilization of medical assets should be taken into consideration by experienced triage officers who are most familiar with the natural course of the injury presented and have detailed information on medical assets. There are several triage systems that can be applied to CBRN casualties. With no one standardized system globally or nationally available, it is important for deploying a triage and decontamination system which is easy to follow and flexible to the available medical resources, casualty number, and severity of injury.
doi:10.4103/0975-7406.68506
PMCID: PMC3148628  PMID: 21829319
Chemical; biological; radiological; or nuclear event; casualty; treatment

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