Novel EIDs or deliberately released biowarfare agents will be extremely difficult to recognize via clinical presentation alone, in an initial casualty or set of casualties. This is because these agents will not fit into the typical clinical reasoning paradigm and the downstream effects of delayed diagnosis can be significant, especially in an austere, deployed environment (Figure 3). Other health threats to consider include DNBI and environmental/occupational exposures.
A deliberate release of a biowarfare agent will likely be completed before the local commander or medical advisor are aware that it has taken place.25 However, a well-trained and vigilant medical staff, force health protection measures, preventive medicine services IAW JP 4-02 and optimal use of laboratory assets can help aid earlier recognition/mitigation and be potentially instituted even before a definitive diagnosis is made. The approach in the following sections integrates the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) steps in the management of potential biological casualties,25,27 current JTS CPGs, U.S. doctrinal documents, and NATO resources. The overall approach is summarized in Figure 4, Figure 5, and Figure 6 below.
Syndromic characterization of illnesses can provide further clues to narrow the differential diagnosis. Syndromic characterization is a constellation of signs and symptoms that, when present in a specific pattern or cluster of patients, can increase the awareness of a biothreat. Basic illness patterns should be recognizable to all personnel. Medical personnel with advanced training and experience should be able to recognize progressively more complicated syndromes that associate with specific causative agents (Table 2).
In DoD parlance, the phrase “everyone is a safety officer” is frequently used. That phrase can be expanded to biodefense: “everyone is an infection control officer”. Whether in a military deployed setting, in garrison or at home, an individual can take simple steps (community mitigation measures) to limit the spread of communicable IDs. All service members (ASMs) and combat lifesavers (CLS) should be able to recognize these basic syndromes: respiratory (cough, congestion, shortness of breath), gastrointestinal (vomiting, diarrhea, abdominal pain), neurological (confusion, weakness, altered mental status), and cutaneous (rashes). ASMs/CLS should be educated and empowered because they are crucial in stopping the chain of infection for communicable diseases by recognizing basic clinical syndromes, reporting through their chain of command, and taking community mitigation measures.
Medical personnel should be able to distinguish:
Select IDs and toxins are described in Appendix H and characterized by syndrome. These tables are examples and not intended to be totally comprehensive. Appendix A contains syndromic algorithms with potentially diagnostic clinical clues to illustrate how to narrow the differential diagnosis for some of these agents. Clinicians should be cautious at excluding one type of agent too early as there can be overlaps in syndromes during the early stages of illness.
Many biothreat induced illnesses will present as an undifferentiated febrile illness that progresses to another syndrome (cutaneous, hemorrhagic, or neurological, etc.). The progression sequence and timing can suggest different causative agents. It is important that all levels of medical personnel maintain a high index of suspicion for biothreats: initially recognizing that a biothreat may be present is necessary for all further steps in identifying it. Depending on geographic location, season, and local environment, endemic cases of bio-agents may be present commonly (many cases per year), uncommonly (few cases present every year), or rarely (cases have been identified before but do not reliably occur every year). Patients presenting with a potentially endemic disease, but at an atypical location or season, or in larger numbers than expected compared to prior years, should trigger suspicion of a potential bio-agent attack. In addition, if there is suspicion of a bioincident, action should not wait for syndromic characterization. Early fever may be the only presenting feature, so a high degree of suspicion, based with intel may be needed.
Combining the syndromic characterization of an illness (for example, an unusual cluster of unexplained fevers), with the epidemiological patterns and risk factors may provide the best clinical picture of the potential causative agent(s) and can guide further treatment and testing. It is important to note that these characteristics are an approximate guide, and the presence or absence of a specific characteristic should not be taken as definitive proof for, or against, inclusion of a biothreat in the differential diagnosis. Particularly in biological warfare attempts, agents may appear with uncharacteristic or novel epidemiological patterns or syndromic characters due to unexpected routes of exposure, or intentional modifications to the biothreats’ genome. Many potential bio-warfare agents are also endemic infectious diseases. (See Appendix C.) However clinical context is important, as an atypically large number of cases of an endemic disease or cases not associated with typical risk factors (e.g., wild rodent exposure for plague or tularemia) suggest an intentional outbreak. Smallpox is a notable exception. It was eradicated from nature in 1980, so any identified cases indicate a bio-warfare use.
MANAGEMENT OF AN INDIVIDUAL BIOLOGICAL CASUALTY
The successful management of an individual casualty is rooted in a thorough clinical history, physical examination, and using available diagnostic assets. The concept of integrated, layered CBRN defense (Protect, Understand, Mitigate) can be adapted to the managing an individual casualty using a thorough clinical evaluation throughout the medical care process with continuous reassessment (Figure 3). This means the detail gained with a thorough evaluation of an individual case can quickly adapt surveillance, infection control measures, and medical practice if it is indeed an index case of a bioincident (reference Figure 4 for examples).
The first step in managing an individual biological casualty is to PROTECT yourself, your staff, your teammates, and other patients you are treating. The PROTECT phase needs to start at triage and consists of Infection Prevention and Control (IPC) and decontamination procedures. In a known threat environment, a “PROTECT” posture can be planned for in advance, with a low threshold for implementation whenever there are potential warning signs of a bioincident. For an unknown threat environment, IPC precautions and decontamination may have to be adapted as casualties present and more is learned about the common clinical operating picture. It is critical during this step to provide timely information to the Commander, in order to protect the mission and population.
Infection Prevention and Control (IPC)
It is beyond the scope of this CPG to cover cleaning, disinfection, sterilization techniques, and the management of potentially infectious medical waste for all patient care environments and equipment. For these activities, it is recommended to reference CDC resources,31 service specific guidelines, such as Army Techniques Publication (ATP) 4-02.10,32 and specialized guidance on viral hemorrhagic fever (VHF).33-35 There is an Infection Control in the Deployed Setting course open to all branches noted in Appendix D. This CPG will primarily focus on transmission-based precautions for a variety of biothreats based on the CDC guidelines for isolation precautions.36 It is always best practice to follow the CDC guidelines; however, military medical personnel may have to adapt Personal Protective Equipment (PPE) based on the operational environment, consultation with infectious disease specialists, available resources, and the Commander’s risk tolerance. Remember that transmission-based precautions always include standard precautions. A summary of concepts/recommendations to consider are contained in Table 3.
VHFs that have a risk of person-to-person transmission include Ebola, Marburg, Lassa, Crimean- Congo Hemorrhagic Fever (CCHF) and the South American Hemorrhagic Fevers (Junin, Machupo, Chapare, Guanarito, and Sabia viruses).37 There are other VHFs that are not typically transmitted person-to-person, and these include Dengue, Yellow Fever, Rift Valley Fever, and most Hantaviruses (except Andes virus). Andes virus is a Hantavirus that is endemic in rodents in South America and has been associated with person-to-person transmission.38,39
Medical care of patients infected with VHFs that have a risk of person-to-person transmission require unique engineering controls, environmental controls, administrative controls, and PPE. As a result, management of VHF patients’ merits creation of a separate JTS CPG. Please reference the World Health Organization (WHO) VHF Handbook,33 WHO IPC Guideline for Ebola and Marburg Disease34 and CDC VHF35 web pages for more exhaustive discussions on this topic. Healthcare workers caring for patients with VHF must receive comprehensive training and demonstrate competency in performing VHF-related infection control practices and procedures. It is recommended that all roles of care consider planning for and exercise recognition, isolation, quarantine, and initial management of VHF patients.
It is imperative that medical personnel are knowledgeable and maintain good habits of IPC during routine patient care even during deployments to more austere environments to include field hospitals and shipboard medical bays. Both hand hygiene and respiratory hygiene cannot be compromised and should be enforced at all levels of triage and care. Medical personnel should also be versed and trained in the appropriate use of PPE and how to don and doff their PPE in the setting of the care of a contagious patient. By maintaining good habits in IPC during routine care, a medical team stands to be more ready and protected against a suspected biothreat.
Decontamination
Due to the previously mentioned potential time delays in presentation after exposure, casualties presenting with syndromes due to biothreats may not require decontamination.24 Even though they may not be contaminated, the casualties may be infectious, and warrant empiric transmission-based precautions. In other situations, particularly involving weaponized biothreats delivered via aerosol or powder, decontamination may be warranted. Below are some examples that involve a re-aerosolization hazard for healthcare workers:25
For the above examples, and when in doubt, removing clothing and washing exposed skin and hair with soap and water, followed by drying the skin and hair, is the most preferred method and is generally considered adequate decontamination for most biothreats.26 In addition, note that Reactive Skin Decontamination Lotion (RSDL) is U.S. Food and Drug Administration (FDA) cleared for the removal or neutralization of chemical warfare agents and trichothecene (T2) mycotoxins from the skin, but not other biothreats.19 However, RSDL is only FDA approved for use on intact skin, NOT on wounds; for contaminated/infected wounds, soap and water or water alone is the recommendation for decontamination. Additional discussion on decontamination is contained in Appendix C of Multiservice Tactics Techniques, and Procedures for treatment of Biological Warfare Agent Casualties and in Multiservice Tactics Techniques, and Procedures for Health Service Support in a CBRN Environment.25,26 For a “how-to” on the set-up of decontamination stations, reference the Field Management of Chemical and Biological Casualties Handbook.48
General Clinical Assessment and Management
For initial lifesaving care, utilize the (MARCHE)2 protocol and CRESS assessment/intervention algorithms applicable for general and for CBRN casualties (see JTS Chemical, Biological, Radiological and Nuclear Injury Response Part I: Initial Response CPG).49 MARCHE2 is designed for point of injury care in the immediate aftermath of exposure to a chemical agent. Due to incubation periods for illness and delays in patient presentation, biological agent exposure may not be recognized in a time frame where the MARCHE2 paradigm is relevant. However, CRESS could be helpful for the evaluation of casualties from toxins which behave more like chemical agents than infectious diseases. As a result, CRESS toxin criteria were created to supplement the CRESS findings for chemical agents contained in the JTS Chemical, Biological, Radiological and Nuclear Injury Response Part I: Initial Response CPG (Table 4).
As per JP 4-02, medical units must have a basic CBRN mass casualty plan that can be modified to meet varying situations, and each medical facility must be able to establish its own patient decontamination site. The vast majority of biothreat exposures would be able to be managed by standard DoD triage algorithms. However, medical units could consider layering on use of a sepsis screening tool (qSOFA or NEWS2), in the setting of a bioincident. See Appendix H for details of both scoring methods.
Once the initial PROTECT tasks have been implemented and the casualty is stabilized, a detailed clinical assessment needs to occur as operational conditions allow (UNDERSTAND). It is critical to obtain an accurate chief complaint, history of the present illness with symptom attributes/progression, exposure history, past medical history, review of systems, and conduct a detailed physical exam (see Appendix G). Once this assessment is complete, providers should utilize syndromic characterization to generate a differential diagnosis. Understanding common endemic diseases in the area of operations and available diagnostics will also help reach a leading diagnosis. In addition, always inquire about other unit members who may be ill.
Appendix A provides potentially diagnostic clinical clues (PDCs) in an algorithmic format to help narrow the differential diagnosis when epidemiologic clues are absent, and specific laboratory diagnostic tests are pending or unavailable. It is important to regularly reassess as the clinical picture may evolve and suggest an alternate diagnosis or confirm the initial leading diagnosis. It is also important to obtain technical reach-back early and as needed (Table 9). See JTS Telemedicine in the Deployed Setting, 19 Sep 2023 CPG50 for additional information for technical reach-back guidance.
Broad-spectrum empiric antimicrobial treatment should begin promptly based on the clinical scenario (MITIGATE) and should not be delayed pending confirmatory diagnostics. The early administration of appropriate antimicrobials is one of the most effective interventions to reduce mortality in patients with sepsis. Note that improved clinical outcomes from early, appropriate use of antimicrobials is not only limited to antibiotics for bacterial infections, but also applies to systemic viral51-53 fungal,54 and parasitic55 infections. Keep in mind, that in a bioweapon context, standard treatments may not work due to engineered resistance of pathogens. In addition, proper supportive care is extremely important to improve outcomes. Follow the latest Surviving Sepsis Guidelines/resources56 and the JTS Sepsis Management in Prolonged Field Care CPG.57 Specific pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP), and treatment recommendations for select biothreats are detailed in Appendix G with links to additional resources.
Clinical Laboratory
A key component to the success of the deployed health system mission and defense against potential biothreat exposure is robust, in theater, clinical laboratory support. Clinical laboratory assets are crucial in determining the cause of disease and dictating all follow-on actions including IPC, FHP measures, and definitive MCM use (see below and Appendix B for discussion on this topic). Although agent specific clinical assays are crucial to definitive diagnosis, basic clinical lab values (complete blood count (CBC), chemistries, coagulation, etc.) can help narrow the differential diagnosis as well. Providers should understand what clinical laboratory assets are available in their area of operations, what is the test menu, who are the laboratory points of contact (POCs) and predetermine if it is practical and safe to collect clinical specimens (including potential BSAT specimens) at their level depending on the threats of concern. Different clinical laboratory capabilities by role of care and service are summarized in Table 13. For example, the Army Role 3 (32-bed field hospital (FH) + Augmentation Assets) could render a presumptive diagnostic answer to many different biothreats including a number of BSAT agents.
Clinical personnel should also understand the difference between DoD clinical and environmental laboratories as there are sometimes misconceptions about their functions. The key difference is that clinical laboratories are regulated by the Clinical Laboratory Improvement Program (CLIP) per DODI 6440.02, and as such, clinical results can be utilized directly for patient care and be included in the medical record (see table below). However, that does not mean that information reported from environmental labs are not useful for the clinician to be aware of as part of the common clinical operating picture.
Evacuation Considerations
Medical evacuation in the midst of a bioincident can be very challenging, and it is difficult to generalize recommendations for all potential scenarios and would need to be addressed in specific Concept of Operations Plans and Pandemic and Infectious Disease plans. The complexity of medical evacuation during a bioincident will depend upon the operational environment (Large Scale Combat Operations (LSCO) vs. humanitarian, for example), acuity of the patient, and specific biothreat implicated (contagious vs. non-contagious). The combatant commander (CCDR), with the advice of the command surgeon, is responsible for moving casualties within the theater and deciding the extent to which evacuation assets will be committed.26 The commander, U.S. Transportation Command (USTRANSCOM) is the DoD single manager for inter-theater patient movement.26
Understand that aeromedical evacuation capabilities for contaminated and contagious HCID casualties under high-level biosafety containment are very limited. However, current theater evacuation policy permits the air transport of patients ill with, exposed to, or potentially exposed to an identified/known infectious agent using a contract transport service.26 With the additional actions required beyond the traditional medical evacuation (MEDEVAC) process, pre-planning is essential to assure casualty movement occurs in a timely fashion:
RECOGNITION & PREPARATION OF A BIOINCIDENT & INITIAL MITIGATION
The concept of integrated, layered CBRN defense (Protect, Understand, Mitigate) can also be adapted to the preparation, recognition, and mitigation of a bioincident (Figure 5 and Figure 6). Note that the “red flags” contained in Figure 5 are combined from multiple sources.16,25,27 Some of the “red flags” suggest a deliberate source causing a bioincident, while others are less specific, indicating either a natural or deliberate source.
Once a potential bioincident is recognized, initial mitigation steps need to focus on surveillance and control measures, medical situational awareness, and obtaining the appropriate resources and assistance to mitigate the event (Figure 6). For a comprehensive review of bioreponsiveness, see the NATO Smart Defence Project 1.1045 Concept of Operations. 58,59 See Table 10 for a perspective on how different medical staff critical tasks could progress for any given bioincident from pre-event to recovery.
Rapid initiation of outbreak investigations and implementation of basic control measures are critical to reduce risk in a suspected bioincident. While outbreak investigations are primarily a Preventive Medicine (PVNTMED) function,12 all tactical care providers must understand the basics of how to recognize an outbreak, understand the steps of outbreak investigation (Table 11), be able to initiate basic control measures and report up the chain of Command (Table 12). Understanding these concepts will allow earlier investigation/notification of an outbreak and will be important in a PCC environment during LSCO in the event there is a delay in mobilizing PVNTMED support. Once the disease is recognized, appropriate prophylaxis, treatment, and other measures to decrease disease spread, such as isolation (if needed for a contagious illness) are instituted. An expanded table of outbreak investigation steps for PVNTMED staff is contained in Appendix F. Outbreak response plans should be predefined and exercised by Commands to ensure all elements understand their roles during an outbreak.
CONSIDERATIONS BY ROLE OF CARE
The approaches to an individual biological casualty and bioincidents outlined above are generic and can apply to all roles of care. The composition of a bioincident response, and the specific challenges faced, will vary based on many factors including the unit’s primary mission, available medical capabilities (including countermeasures), deployed location, and ability to transfer patients to a higher level of care. Units must consider the projected morbidity/mortality of the agent, the availability of MEDEVAC and resupply, and the impacts of ongoing operations during the logistics planning. Special care should be taken with patient handoffs to ensure accurate documentation is transferred with the patient(s). Contact tracing and monitoring of those potentially exposed may need to be performed both within the medical unit and throughout the medevac process. This has the potential to restrict movement of potentially exposed personnel and place a significant administrative burden on an already strained medical system. Collective Protection (COLPRO) is a unique consideration and is summarized in Appendix H.
Identification of the causative agent of a bioincident is extremely important, and medical personnel should understand the clinical laboratory capabilities by role of care and have appropriate supplies to transport clinical samples to those laboratories (Table 13). Capabilities in Table 13 have been generalized. For more detail, reference Service-specific resources.
Other topics by role of care include:
Role 1
Role 2
Role 3
CONSIDERATIONS IN COMBINED INJURY
Trauma teams can be significantly impacted by a bioincident in the field. As a result, trauma teams may face an increased workload as they would also be responsible for diagnosing and treating infected personnel. This can lead to an overwhelmed medical system with limited resources and personnel, leading to increased mortality and morbidity. In addition, trauma teams may also be at risk of infection themselves if appropriate personal protective equipment is not used or if proper decontamination procedures are not followed.
Finally, the impact of a biological attack on trauma teams may extend beyond the immediate physical consequences. The psychological impact of treating infected personnel in a high-stress environment can lead to long-term mental health consequences, such as post-traumatic stress disorder (PTSD). Therefore, it is essential that military personnel receive adequate training and support to manage the potential physical and psychological consequences of a bioincident in the field. Consider proactive cross training of trauma teams to preserve capabilities and capacity.