Theodore J. Cieslak

Managing Potential Laboratory Exposure to Ebola Virus by Using a Patient Biocontainment Care Unit

One-sentence summary for table of contents: Recommendations are needed for management of potential laboratory exposure to a Biosafety Level 4 pathogen.

Immunization against Potential Biological Warfare Agents

The intentional release of biological agents by belligerents or terrorists is a possibility that has recently attracted increased attention. Law enforcement agencies, military planners, public health officials, and clinicians are gaining an increasing awareness of this potential threat. From a military perspective, an important component of the protective pre-exposure armamentarium against this threat is immunization. In addition, certain vaccines are an accepted component of postexposure prophylaxis against potential bioterrorist threat agents. These vaccines might, therefore, be used to respond to a terrorist attack against civilians. We review the development of vaccines against 10 of the most credible biological threats.

History of U.S. Military Contributions to the Study of Bacterial Zoonoses

Bacterial zoonoses have afflicted campaigns throughout military history, at times playing an important role in determining their outcomes. In addition, zoonotic bacteria are among the leading biological warfare threats. The U.S. military medical services have been at the forefront of research to define the basic microbiology, ecology, epidemiology, and clinical aspects of these diseases. This historical review discusses the military significance of plague, Q fever, anthrax, leptospirosis, bartonellosis, tularemia, and brucellosis and the U.S. military medical research counteroffensive. These contributions have ranged from basic molecular biology to elegant epidemiological surveys, from defining pathogenesis to developing new vaccine candidates. In an era of emerging diseases and biological weapons, the U.S. military will continue to lead a dynamic research effort to counter these disease threats.ABSTRACT Bacterial zoonoses have afflicted campaigns throughout military history, at times playing an important role in determining their outcomes. In addition, zoonotic bacteria are among the leading biological warfare threats. The U.S. military medical services have been at the forefront of research to define the basic microbiology, ecology, epidemiology, and clinical aspects of these diseases. This historical review discusses the military significance of plague, Q fever, anthrax, leptospirosis, bartonellosis, tularemia, and brucellosis and the U.S. military medical research counteroffensive. These contributions have ranged from basic molecular biology to elegant epidemiological surveys, from defining pathogenesis to developing new vaccine candidates. In an era of emerging diseases and biological weapons, the U.S. military will continue to lead a dynamic research effort to counter these disease threats.

Caring for patients with Ebola: a challenge in any care facility

The largest outbreak of Ebola virus continues unabated in West Africa. With the recent death of a patient with Ebola virus disease at a hospital in Dallas, Texas, and the sobering reality that nosocomial spread has occurred in a U.S. facility, U.S. medical centers are coming to grips with the need to prepare for care of patients with this devastating disease. The Centers for Disease Control and Prevention has developed a hospital preparedness checklist, and the latest guidelines continue to express confidence that patients with Ebola can be cared for safely in a conventional medical facility by using barrier methods (standard, contact, and droplet precautions) as the primary means of protecting medical staff (1, 2). Recent experience with several Ebola-infected patients in the United States provides validation that such patients can be cared for safely in a facility that is adequately prepared. Since the first reported outbreaks of Marburg (1967) and Ebola (1976), there has been an evolution in our thinking about the optimal personal protective measures for medical staff caring for patients infected with these viruses. From 1972 to 2010, a high-level containment care (HLCC) unit at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), often called the slammer, was considered the gold standard for such care. The units engineering controls were modeled after a biosafety level4 (BSL-4) laboratory, with positive-pressure space suits, compressed in-line air, HEPA filtration, a decontamination shower, ultraviolet light pass boxes, an airlock, and antiseptic dunk tanks for movement of items in and out of the containment area. Toilet waste was discharged into the laboratory sewer system, and the facility possessed its own autoclave, operating room, and bedside laboratory. These built-in capabilities significantly reduced logistics challenges and provided reassurance that nosocomial spread could be reduced to near zero. Given the relatively high percentage of caregivers who have died of filoviral and other BSL-4 virus infections in the field, and the prior uncertainty in whether such high infection rates might be caused by droplet or airborne spread, utilization of such a containment facility seemed reasonable. Although used on occasion to quarantine field workers potentially exposed to highly hazardous viruses, the unit was used primarily for isolating individuals exposed to a BSL-4 virus in the laboratory. During the units 38 years of operation, 21 patients were quarantined after potential exposuresand none became ill (3). Over time, we learned that the spread of filoviruses occurs primarily by direct contact with blood and body fluids (1). Thus, it was determined that a patient care facility with the full panoply of BSL-4 laboratorylike features was no longer needed. The facility was decommissioned and refurbished as a training facility for scientists working in the institutes containment laboratories. If the USAMRIID HLCC is no longer needed because patients with filoviruses may be managed safely using barrier methods, one might ask whether any HLCC or biocontainment patient facilities are needed at all (4). Currently, 4 such facilities exist in the United States, operating at a higher level of containment (and possessing more sophisticated engineering controls) than a conventional hospital isolation room but lacking some BSL-4 features present in the USAMRIID HLCC: Emory University Hospital, Atlanta, Georgia; University of Nebraska Medical Center, Omaha, Nebraska; Saint Patricks Hospital, Missoula, Montana; and the National Institutes of Health Clinical Center, Bethesda, Maryland. All except the University of Nebraska serve as referral centers for laboratories that work with BSL-4 viruses. Although patients infected with such diseases as Lassa and Marburg have been safely managed in conventional settings, the serious nature of filoviral and arenaviral infections, their rarity and unfamiliarity to clinicians in developed settings, the lack of effective treatments and vaccines, their propensity to infect health care staff, and the infection control challenges they present argue for, in our opinion, specialized containment and treatment facilities. As many medical centers are no doubt learning in their preparation drills, caring for patients with filovirus and arenavirus infections in a conventional setting presents enormous challenges (5), many of which can be mitigated through the use of specialized facilities with highly trained staff practiced in the nuanced art of safely delivering HLCC. However, even in such facilities, it is impossible to completely engineer out human error, eliminate the risk for sharps or needlestick injury, or prevent inadvertent contact contamination. Care for such patients in a conventional setting, therefore, is more than checklists and standard operating procedures. The training, policies, procedures, and logistics necessary for the provision of such care are significant, cannot be assumed, are optimally in place well in advance of actual need, and must be continually reinforced through repetitious training. Every piece of the care continuum must be well-choreographed with significant attention to detail. At a minimum, preparations must be made for patient entry and movement pathways, optimal patient location and access control, safe donning and doffing of personal protective equipment (PPE), handling and testing laboratory specimens, disposal of significant volumes of waste, safe and unexpected cleanup of spills and bodily waste, and minimizing use of sharps. Donning and doffing PPE need to be regimented and monitored, with plans in place for peer policing. Lapses inevitably occur in infection control routines in conventional medical settings, but once a patient enters the facility, there is no margin for error. Significant risk for infection control errors occurs especially during doffing potentially contaminated PPE (6). While the physical features of high-containment isolation units like that previously housed at USAMRIID (3) are formidable, low-tech measures, such as checklists and the use of doffing partners, may be as important to optimizing the safety of health care workers, whether in an HLCC unit or in a conventional facility. Owing to the very limited number of existing HLCC beds and the fact that patients with highly contagious diseases can present unannounced, conventional facilities may be required to triage these patients and even provide definitive care, despite the enormous challenges they would inevitably face. Immediate and thorough preparation is thus imperative. Despite this necessary reliance on conventional facilities, we recognize the challenges inherent in maintaining a high nationwide state of readiness over the long term. Hence, we envision the need for a network of strategically located regional referral centers serving designated catchment areas tied to BSL-4 laboratories or airport quarantine stations. As such, transport of patients to these referral centers would constitute the preferred clinical option (4). These units would be associated with major medical centers and provide day-to-day routine care, but they would have the capability for rapid conversion to an HLCC unit without adversely affecting their primary activities. These could serve as national resources, coordinated through the Department of Health and Human Services and Centers for Disease Control and Prevention, with certification (much like trauma centers) to provide a higher level of care. As such, their focus would be on continuous preparation for the next emerging outbreak.

Bioterrorism: agents of concern.

The intentional dispersal of biological agents by terrorists is a potential problem that increasingly concerns the intelligence, law enforcement, medical, and public health communities. Terrorists might choose biological agents over conventional and chemical weapons for multiple reasons, although it is difficult to predict, with certainty, which biological agents might prove attractive to terrorists. One can more confidently, however, derive a list of those few agents which, if used, would be of greatest public health consequence. It is these agents which will require the most robust countermeasures. We discuss the derivation of this short list of agents and the specific diseases involved.

Medical management of the suspected victim of bioterrorism: an algorithmic approach to the undifferentiated patient

We have purposely expanded on the well-known ATLS paradigm to aid EHCPs in their approach to a potential bioterrorism event. By building on a process that is already familiar, we hope this will aid the EHCP to remember a systematic approach to such an incident. By following this ten-step process, we believe that all EHCPs, and especially those practicing at the first echelons of care in urgent care clinics and EDs, can approach the daunting problem of biological defense with a good deal more confidence. This same model advocated for bioterrorism also may apply to natural infectious disease epidemics, particularly of emerging or re-emerging diseases, that might not be optimally managed by reliance on the conventional public health strategy that requires physician-dependent definitive diagnosis and active reporting mechanisms. The authors hope the acquired knowledge and skills one might gain will rarely be needed, but if the events surrounding the dispersal of anthrax-contaminated mail in the fall of 2001 are any indication of the future, such competencies will be invaluable.

Ring-a-ring-a-roses: Bioterrorism and its peculiar relevance to pediatrics

Some authors date this popular nursery rhyme to the bubonic plague pandemic of the Middle Ages, often referred to as the “Black Death” [1]. The ring-a-roses refers to the rose-colored rash of plague. Medieval practitioners stuffed the pockets of victims with posies and spices in an attempt to ward off the stench of death. Sneezing was a common preterminal symptom. The last line of the rhyme recalls the inevitable fate of plague’s victims. Practitioners caring for children in medieval times were accustomed to dealing with human plague. Recently, this and other diseases thought relegated to the dustbin of history have reared their ugly heads again in the form of weapons of terror. Now, pediatricians, once again, must acquire a familiarity with such diseases. Children will almost certainly be among the victims in future terrorist attacks. Timothy McVey’s characterization of children as “collateral damage” makes this point frighteningly clearly. In fact, the sarin attack in the Tokyo subway in 1995 affected 16 children and 5 pregnant women [2]; numerous high school students were among the victims of a 1984 attack in Oregon that involved deliberate contamination of restaurant salad bars with Salmonella [3]. Recent attempts by terrorists to target children specifically, such as an aborted effort to release chlorine gas at Disney World [4] further upped the ante for pediatricians.

Bioterrorism and pediatric emergency medicine

Abstract Bioterrorism as a national threat poses enormous challenges to emergency department staff and emergency medical services personnel, and requires thoughtful planning and preparations. Several issues are special or unique in contemplating this threat as it applies to pediatric victims and the pediatric emergency medicine community. This report reviews some of the general principles of medical preparedness for bioterrorism, focuses on management issues for several of the most feared threats, such as bioweapon threats, and attempts to highlight pediatric issues as applicable.

International adoptions by military families: A reexamination

The adoption of foreign-born children by U.S. families is an increasingly common occurrence, having tripled in the past 15 years. The demographic features of international adoption have changed dramatically over the same time period. Todays foreign-born adoptees originate from a myriad of nations and cultures and present challenging medical and social problems to the practitioners faced with caring for these children and advising their adoptive families. Military families, cosmopolitan and often stationed overseas, adopt a large proportion of these children from foreign lands. Consequently, military health care providers require a familiarity with the special needs of international adoptees and the unique aspects of international adoption, as practiced by military families. We previously reported on this topic more than a decade ago. Much has changed since then, prompting this update.

Biological warfare and the skin II: viruses.

In many ways, viruses lend themselves poorly to weaponization. They are generally more fastidious than bacteria and are consequently difficult to grow in quantity. Whereas many bacteria such as Bacillus anthracis may be readily cultivated on simple bloodagar plates, most viruses require cell-culture techniques. Moreover, most viruses are unable to survive ex vivo for more than a brief period of time, hindering their utility as aerosolized weapons. Nonetheless, exceptions exist. Variola virus, the causative agent of smallpox, is remarkably stable ex vivo. This agent was allegedly weaponized in great quantities by the former Soviet Union,1 and ballistic missiles carrying smallpox payloads are said to have been an important component of the Soviet biologic arsenal. Three other viruses, Marburg, Venezuelan equine encephalitis (VEE), and influenza, also captured the interest of Soviet military planners. Inheriting the defensive aspects of the old Soviet program, Russian defense experts rank these four viruses among the biologic agents as having a “high probability” for use as a biological weapon. 2 Two of these (Marburg is considered along with other viral hemorrhagic fever viruses) often present with significant dermatologic manifestations. These same two are included on the Centers for Disease Control and Prevention (CDC) list of category A agents. A more detailed discussion of the CDC list and its derivation are included in another article in this issue3 and in other sources.4 In this article, we discuss smallpox and the viral hemorrhagic fevers, as well as selected additional viral agents.