BIOTHREATS  (IDs  +  TOXINS)  VS  CHEMICAL  AGENTS

Most toxins are complicated, multi-domain proteins in the tens to hundreds of kilodalton weight range, some are simpler organic molecules, and some are combinations of multiple toxic protein enzymes. The mechanisms of each toxin are unique and related to the chemical structure. Toxins that are enzymes, such as ricin and botulinum toxins, have very low LD50s (median lethal doses), making them more potent on a milligram-per-milligram basis than even the most powerful chemical weapons. Small organic molecule toxins, such as tetrodotoxin and saxitoxin, bind to molecular ion channels in mammalian cells and exert their effect by inappropriately opening or closing the ion channel, leading to higher-level tissue dysfunction. Anti-toxins are harvested antibodies designed to bind and neutralize specific toxins. If dosed early in the course of toxin-induced illness, then the illness can be halted (but usually not immediately reversed). Some protein toxins, such as botulinum toxins, can come in multiple different strains of genetic variations that result in protein structural differences that can affect the efficacy of anti-toxins or the sensitivity of immunoassay detectors.

Similar to chemical agents, toxins are of comparable or greater potency, have predictable dose-response effects, and start acting shortly after absorption into the body. Unlike chemical agents, toxins are relatively difficult to detect in the environment and can be hundreds of times larger in terms of molecular size and weight. Compared to infectious bio-agents, toxins are not transmitted person-to-person (though heavily contaminated patients could expose unprotected treatment teams) and do not replicate in the body. For that reason, toxins generally exert their effect much faster than infectious bio agents, with an asymptomatic latent period of minutes to a few days after exposure, versus the incubation period of multiple days to weeks for most infectious agents. Because toxins are generally more slowly absorbed than most chemical weapons and take time to exert their effect at a molecular level, the latent period for toxins is usually longer than that for chemical agents, most of which have noticeable clinical effects within minutes to hours. Anthrax and botulinum toxins can both be produced in the body by their associated bacteria, or introduced to the body as pre-formed toxin, though the latter is more likely with botulism, while infection with the causative bacterium is more likely with anthrax.

The clinical effects of organophosphate nerve agent poisoning can be challenging to distinguish from those of botulism toxin or Staphylococcal enterotoxin B (SEB).  Appendix E of the USAMRIID Medical Management of Biological Casualties Handbook, 9th Edition provides a comparison table. Nerve agents are generally faster acting, within seconds to minutes at high doses, while SEB can take several hours to exert effects and botulinum toxin up to several days. Nerve agents and SEB can both cause vomiting and diarrhea, while botulinum toxin exposure generally does not. Nerve agents will cause local fasciculations and generalized seizures, while botulism toxin causes gradual onset descending symmetrical flaccid paralysis with preserved mental status until the patient is hypoxic and/or hypercarbic, and SEB has minimal neurological effects. Nerve agents will cause noticeably increased oral secretions from salivary and mucous gland stimulation, while botulinum toxin can cause dry mouth and throat with swallowing dysfunction leading to aspiration. Death can occur in minutes from severe nerve agent exposures, and in days from botulinum toxin exposures, but death is rare in SEB exposure. Appropriately dosed atropine should improve peripheral, muscarinic effects of nerve agents but will have minimal effects on SEB gastrointestinal symptoms, and not improve botulism symptoms.

Clinical laboratory testing can help distinguish between illnesses caused by chemicals, toxins, and bio-agents and help identify the specific causative agent. Definitive clinical testing to identify exposure to chemical agents can take hours to days and often requires specific laboratory equipment; however, rapid testing with immunoassays is available for some agents, and indirect assessment of effects on blood or plasma acetylcholinesterase can strongly suggest the presence of nerve agent poisoning. Clinical presence and identification of bio-agents is discussed later but can provide results within hours through polymerase chain reaction techniques or immunoassays. Toxins can be relatively challenging to detect with standard clinical laboratory techniques, due to the relatively small numbers of toxin molecules required to cause clinical effects. Expert consultation is recommended to determine appropriate testing techniques and pre-testing treatment on a case-by-case basis, particularly for suspected botulinum toxin, ricin, or marine toxin exposure. Call your Poison Control Center for assistance (1-800-222-1222) if you are CONUS and the ADVISOR line if deployed.

SELECT TOXINS THAT CAN BE ENCOUNTERED IN THE ENVIRONMENT OR ARE CONSIDERED TRADITIONAL BIOTHREATS BY SYNDROME*

SELECT INFECTIOUS DISEASES BY SYNDROME 

PREPARATION AND PLANNING

The best way to prepare to address potential biothreats is to be aware of current medical intelligence assessed threats and well as surveillance data.  This information on bio-threats, is used to augment Joint Health planning as described JP 4-02 and JP 3-11. Over time, the DoD has evolved procedures to prevent endemic infectious diseases from affecting operations during deployments which include:  

  • Preparation.
  • Education.
  • Personal protective measures.
  • Vaccination.
  • Chemoprophylaxis.
  • Surveillance. 

These procedures apply to all potential biothreats whether they are biowarfare agents, endemic diseases, or emerging infectious diseases. 

Medical personnel should have education managing biological casualties via courses such as the MCBC and U.S. Military Tropical Medicine (MTM) course.  These and other relevant courses are listed in Appendix D

Education and continued education of the Force with Command interest and unit level engagement cannot be emphasized enough and can reduce the impact of bioincidents on readiness/force posture. For example, in 2003, 44 U.S. Marines were evacuated from Liberia with either confirmed or presumed Plasmodium falciparum malaria. An outbreak investigation showed that only 19 (45%) used insect repellent,5 (12%) used permethrin treated clothing, and none used bed netting . Adherence with weekly mefloquine chemoprophylaxis was reported by 55%, but only 10% had serum levels high enough to correlate with protection.2  In contrast, 2,500 U.S. Service Members deployed to Liberia to support the response to the 2014 Ebola outbreak, and there were no cases of malaria detected during deployment . The lack of malaria cases can be attributed to education, Command emphasis on FHP measures, and unit-level leadership. Prior to deployment 99.3% of service members reported receiving education on malaria prevention, 53% reported using DEET on most days, 91% reported using treated uniforms, 96% using bed nets, and 96% taking malaria chemoprophylaxis pills every day (98% received atovaquone-proguanil; 1.5% doxycycline).3  This was supported by mandated twice daily unit-level Ebola monitoring (consisting of temperature checks and review of Ebola exposures and symptoms), individuals were asked about use of antimalarials. In addition, 45% of those surveyed indicated that their unit directly observed them taking their antimalarial daily.

The DoD BPR emphasized the need for improvements in biothreat intelligence collection, analysis, and sharing.  It is recommended that medical personnel coordinate with their chain of Command, medical planner and J2 to ensure there is shared understanding of the biothreat environment and that relevant information is passed down to tactical level providers as appropriate. It is also important for medical personnel to have an understanding of medical intelligence and where to obtain it. Medical intelligence is produced by the National Center for Medical Intelligence (NCMI) and consists of the collection, evaluation, and analysis of information concerning the health threats and medical capabilities of foreign countries and non-state actors that have immediate or potential impact on policies, plans, or operations. More information on NCMI and how to access their intelligence products are contained in Appendix D.   

Medical personnel should have a basic understanding of medical logistics and request additional MCMs based on mission threats from their Joint Logistician. A basic example is given in Appendix E utilizing TPOXX (tecovirimat).  They should also have basic understanding of the Joint Deployment Formulary (JDF) which is a reference list of pharmaceutical items for support during the first 30 days of contingency operations . The JDF is intended to promote the standardization and sustainability of pharmaceutical items as components of medical assemblages and in planning and preparation for early sustainment of deployed forces.7  

FORCE HEALTH PROTECTION (FHP)

FHP is part of the joint function of protection and promotes, improves, or conserves the behavioral and physical well-being of DoD personnel. For our purposes, tactical medical providers should understand the following FHP functions contained in JP 4-026:

Casualty prevention

  • Continuous process conducted during pre-deployment, deployment, and post-deployment phases.
  • Example: pre-deployment vaccination.

Preventive Medicine (PVNTMED)

  • Involves the surveillance, identification, prevention, and control of communicable diseases, illnesses, and injuries.
  • Executing outbreak investigation.

Comprehensive Health Surveillance and Risk Management

  • Theater medical surveillance is essential for early identification of health threats to prevent, neutralize, minimize, avoid, or eliminate them.
  • Health surveillance includes actions to identify the populations at risk (PARs), identify and assess these populations’ potentially hazardous exposures, and conduct medical surveillance to monitor and report DNBI/battle injury (BI) rates.
  • Risk management involves reporting health risks to higher authority in a timely manner using risk communications while employing countermeasures to eliminate or mitigate health risks.
  • For additional information about health surveillance in DoD, both in garrison and deployed settings, refer to DODI 6490.03, Deployment Health; DODD 6490.02E, Comprehensive Health Surveillance; and MCM 0028-07, Procedures for Deployment Health Surveillance.

Biosurveillance 6

Process to gather, integrate, interpret, and communicate essential information related to all-hazards, threats, or disease activity affecting human, animal, or plant health.

Goals:

  • Achieve early detection and warning.
  • Determine most appropriate force health protection posture.
  • Contribute to overall situational awareness of the health aspects of an incident.
  • Enable better decision making at all levels.
  • Cover a range of threats such as:
    • WMD or other deliberate attacks.
    • An emerging infectious disease.
    • Pandemic.
    • Environmental disaster.
    • Widespread, food-borne illness.
  • Key processes include constant scanning of the environment and rapid evaluation to detect threats and assess severity.
  • Medical intelligence capabilities and products directly link to biosurveillance efforts Appendix E &F).
  • For more information on biosurveillance, refer to ATP 4-02.7/MCRP 4-11.1F/NTTP 4-02.7/AFTTP 3-42.3, Multi-Service Tactics, Techniques, and Procedures for Health Service Support in a Chemical, Biological, Radiological, and Nuclear Environment.

COLLECTIVE  PROTECTION

Collective Protection (COLPRO) supports all roles of care providing respiratory, percutaneous, and ocular protection in an area or shelter which eliminates the need to don individual protective equipment. COLPRO material solutions range from fixed site filtration systems, to shelter liners and filtration systems for tentage in an expeditionary setting, and finally highly mobile vehicle-mounted and decontaminable shelters which can be erected within minutes and allow for the fast-paced aggregation/disaggregation necessary for medical force elements to keep pace with the units they support in the forward area. All of these COLPRO capabilities allow time to accomplish uninterrupted, on-going damage control surgeries/damage control resuscitation of patients undergoing surgical procedures at the onset of the CBR attack, allowing time for evacuation, and ensuring contamination survivability for low density, high value equipment and on-hand medical logistics supplies.8,9

Collective protection is also instrumental in supporting the gap for prolonged care in a CBRN environment. Beyond CBR environments, COLPRO can provide elemental protection and environmental control to MTFs in a variety of climates and terrains, which may mitigate some of the related challenges. COLPRO regulates temperature and humidity, which increases medical provider endurance and improves patient outcomes, and COLPRO filtration removes pathogens from the air. These characteristics would be beneficial in any operating environment, including LSCO environments, and could also enable better clinical outcomes in prolonged care situations.

QSOFA  &  NEWS2

Both tools are described in the JTS Sepsis Management in Prolonged Field Care CPG 10 as well as the JTS Prolonged Casualty Care Guidelines. Note that current Surviving Sepsis guidelines recommend against using Quick Sequential Organ Failure Assessment (qSOFA) as compared with NEWS as a screening tool.11  However, the qSOFA has fewer variables than the National Early Warning Score (NEWS2) and is faster so may be more appropriate for use at the Role 1 or in MASCAL settings. In addition, there is evidence that in resource limited settings the qSOFA score identified infected patients at risk of death beyond that explained by baseline factors.12  Thus, while the use of NEWS2 would be better practice, qSOFA in austere settings could be a reasonable alternative.

BIOLOGICAL AGENT EXPOSURE ACRONYMS & OTHER DEFINITIONS 

References

  1. Murray CK, Horvath LL. An approach to prevention of infectious diseases during military deployments. Clin Infect Dis. 2007 Feb 1;44(3):424-30.
  2. Whitman TJ, Coyne PE, Magill AJ, et al. An outbreak of Plasmodium falciparum malaria in U.S. Marines deployed to Liberia. Am J Trop Med Hyg. 2010 Aug;83(2):258-65.
  3. Vento TJ, Cardile AP, Littell CT, et al. Compliance with malaria preventive measures by us military personnel deployed in support of Ebola control efforts in Liberia. Open Forum Infectious Diseases 2015 (Vol. 2, No. suppl_1, p. 1609).
  4. Cardile AP, Murray CK, Littell CT, et al. Monitoring exposure to Ebola and health of U.S. military personnel deployed in support of Ebola control efforts - Liberia, Oct 25, 2014-Feb 27, 2015. MMWR Morb Mortal Wkly Rep. 2015 Jul 3;64(25):690-4.
  5. DoD Biodefense Posture Review. https://media.defense.gov/2023/Aug/17/2003282337/-1/-1/1/2023_BIODEFENSE_POSTURE_REVIEW.PDF
  6. JP 4-02. Joint Health Services. https://www.jcs.mil/Portals/36/Documents/Doctrine/pubs/jp4_02ch1.pdf
  7. DoDI 6430.02, “Defense Medical Logistics Program,” August 17, 2017. https://www.esd.whs.mil/Portals/54/Documents/DD/issuances/dodi/643002_dodi_2017.pdf?ver=2017-08-29-132000-620 
  8. Department of the Army, Army Regulation 70-75, Survivability of Army Personnel and Materiel (Washington, DC: Headquarters, Department of the Army, April 2019): 3-1. https://armypubs.army.mil/epubs/DR_pubs/DR_a/pdf/web/ARN7772_AR70-75_FINAL.pdf
  9. DoD Directive 3150.09, The chemical, biological, radiological, and nuclear survivability policy (Washington, DC: Under Secretary of Defense for Acquisition and Sustainment, October 2022): 18a. https://armypubs.army.mil/epubs/DR_pubs/DR_a/pdf/web/ARN7772_AR70-75_FINAL.pdf
  10. Sepsis Management in Prolonged Field Care CPG., 28 Oct 2020https://jts.health.mil/index.cfm/PI_CPGs/cpgs
  11. Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Crit Care Med. 2021 Nov 1;49(11):e1063-e1143.
  12. Rudd KE, Seymour CW, Aluisio AR, et al. Sepsis Assessment and Identification in Low Resource Settings Collaboration. Association of the quick sequential (sepsis-related) organ failure assessment (qSOFA) score with excess hospital mortality in adults with suspected infection in low- and middle-income countries. JAMA. 2018 Jun 5;319(21):2202-2211.