Pathogens of Concern
Smallpox was eradicated in 1980, yet it remains one of the highest-priority biosecurity threats. With 30% fatality, high transmissibility, no treatment, and a largely unvaccinated global population, reintroduction would be catastrophic. Not all pathogens pose equal biosecurity concern. This chapter examines how classification systems prioritize threats based on lethality, transmissibility, weaponization potential, and historical use.
- Understand CDC Category A, B, and C biological threat agent classifications
- Recognize characteristics that make pathogens high-consequence threats
- Identify specific select agents on federal oversight lists
- Evaluate historical use of biological agents in warfare and terrorism
This chapter discusses biosecurity risks at a conceptual level appropriate for education and policy analysis. Consistent with responsible information practices:
- Omitted: Actionable protocols, specific synthesis routes, exact pathogen sequences
- Included: Risk frameworks, governance mechanisms, policy recommendations
For detailed biosafety protocols, consult your Institutional Biosafety Committee and relevant regulatory guidance.
Introduction
Thousands of pathogens exist that can infect humans. Only a subset pose significant biosecurity concern. This chapter examines how threat assessment frameworks classify biological agents, what characteristics elevate specific pathogens to high-concern status, and which agents appear on federal select agent lists requiring enhanced security.
The CDC’s biological threat agent categorization system (Categories A, B, C) provides one framework. The Federal Select Agent Program provides another, with regulatory teeth. Both systems exist because not all pathogens warrant the same level of security, oversight, or public health preparedness investment.
Understanding which pathogens matter most for biosecurity and why helps direct defensive resources appropriately.
CDC Biological Threat Agent Categories
Category A: Highest Priority Agents
Category A agents pose the highest risk to national security and public health. Characteristics include:
Can be easily disseminated or transmitted from person to person. Cause high mortality, high public health impact potential. May cause public panic and social disruption. Require special action for public health preparedness.
Anthrax (Bacillus anthracis): Spore-forming bacterium causing severe, often fatal illness. Historical use in biological warfare programs and 2001 Amerithrax attacks. Environmental persistence through spores makes it weaponization candidate. Cutaneous, inhalational, and gastrointestinal forms with inhalational having highest mortality without treatment. Vaccine and antibiotics available but inhalational anthrax requires immediate treatment for survival.
Plague (Yersinia pestis): Causes bubonic, septicemic, and pneumonic forms. Pneumonic plague is transmissible person-to-person through respiratory droplets, making it concerning bioterrorism agent. Historical use in medieval biological warfare (catapulting infected corpses) and Unit 731 attacks in China. High mortality if untreated but responds to antibiotics when caught early.
Smallpox (variola virus): Only Category A agent declared eradicated (1980). Highly contagious, ~30% fatality rate, no treatment. Permitted only in two repositories (CDC Atlanta, Vector Russia). Mass vaccination discontinued decades ago, leaving most population susceptible. Reintroduction would be catastrophic.
Tularemia (Francisella tularensis): Highly infectious bacterium requiring as few as 10 organisms to cause disease. Aerosol dissemination potential. Studied by multiple bioweapons programs. Not person-to-person transmissible but environmental persistence and low infectious dose make it weaponization concern. Treatable with antibiotics.
Botulism (Clostridium botulinum toxin): Most poisonous substance known. Prevents muscle contraction through neurotoxin action. Studied extensively by bioweapons programs including Japan’s Unit 731 and investigated by Aum Shinrikyo. Not contagious but toxin can contaminate food/water. Antitoxin available but requires early administration.
Viral Hemorrhagic Fevers (VHFs): Family of viruses causing severe, often fatal illness with vascular damage and bleeding. Category A VHFs include:
- Ebola and Marburg: Fruit bat reservoirs, up to 90% case fatality in some outbreaks. Person-to-person through direct contact with bodily fluids. No approved treatments for Marburg; limited treatments for Ebola.
- Lassa fever: Endemic to West Africa, rodent reservoir, ~1% case fatality but high case numbers.
- Argentine, Bolivian, Venezuelan, and Brazilian hemorrhagic fevers: Rodent-borne arenaviruses with regional endemicity.
Category B: Second-Highest Priority
Category B agents are moderately easy to disseminate, cause moderate morbidity and low mortality, require enhanced diagnostic capacity and disease surveillance. Examples include:
Brucellosis (Brucella species): Causes chronic debilitating illness. Studied by bioweapons programs but limited weaponization. Zoonotic from livestock.
Q Fever (Coxiella burnetii): Highly infectious, low mortality, chronic fatigue syndrome in some cases. Environmental persistence. Studied for weaponization.
Ricin toxin (from castor beans): Protein toxin easily produced from castor beans. No antidote. Historical assassination attempts and bioterrorism plots.
Food/waterborne pathogens: Salmonella, Shigella, E. coli O157:H7, Vibrio cholerae. Demonstrated in 1984 Rajneeshee attack (Salmonella). Moderate public health impact but feasible for non-state actors.
Category C: Emerging Threats
Category C agents are emerging pathogens that could be engineered for mass dissemination in future due to availability, ease of production, potential for high morbidity and mortality. Examples include:
Nipah virus: Bat-borne paramyxovirus, up to 75% case fatality, limited person-to-person transmission. Endemic to Southeast Asia. Biosafety Level 4 pathogen with pandemic potential if transmissibility increased.
Hantaviruses: Rodent-borne viruses causing hemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). HFRS endemic in Europe/Asia; HPS in Americas. 36% case fatality for HPS. Not person-to-person transmissible currently.
Tick-borne encephalitis viruses: Flaviviruses causing neurological illness. Endemic regions in Europe/Asia. Potential for weaponization through vector (tick) manipulation or direct dissemination.
Additional multidrug-resistant tuberculosis: Already significant public health burden; engineered antibiotic resistance could create untreatable pathogen.
Federal Select Agent Program
Select Agent List
Currently 63 biological agents and toxins on select agent list. Organized into:
- HHS select agents: Human pathogens and toxins
- USDA select agents: Plant and animal pathogens
- Overlap select agents: Affect both humans and animals
Inclusion criteria based on effect on human health, effect on animal or plant health, pathogenicity, virulence, dissemination potential.
Regulatory Requirements
Entities possessing select agents must:
- Register with CDC/APHIS
- Implement biosafety and biosecurity plans
- Restrict access through personnel reliability programs (background checks, security risk assessments)
- Maintain detailed inventory and transfer records
- Report theft, loss, or release
- Submit to inspections
Violations can result in civil and criminal penalties, suspension or revocation of registration, remedial actions.
Balancing Research and Security
Select agent regulations aim to balance legitimate research needs against misuse potential. Tension exists between open science culture and security requirements.
Concerns about regulations stifling research led to periodic list reviews and exemptions for attenuated strains or select toxins below concentration thresholds. But 2001 anthrax attacks demonstrated insider threat risk, justifying strict oversight.
Characteristics of High-Consequence Pathogens
Case Fatality Rate
Highly lethal pathogens cause greater panic and social disruption. Smallpox (~30%), pneumonic plague (nearly 100% if untreated), Ebola (up to 90% in outbreaks), inhalational anthrax (~85% if untreated) all have high case fatality.
But lethality alone doesn’t determine biosecurity concern. Rabies has nearly 100% case fatality but isn’t Category A due to transmission requirements.
Transmissibility
Person-to-person transmission amplifies outbreak potential. Smallpox is contagious. Pneumonic plague spreads through respiratory droplets. VHFs transmit through bodily fluid contact.
Environmental persistence (anthrax spores) or vector-borne transmission (plague via fleas) provides alternative dissemination routes.
Lack of Medical Countermeasures
Pathogens without effective vaccines or treatments pose greater threat. Smallpox eradication led to vaccination discontinuation, leaving populations vulnerable. Ebola and Marburg have limited treatment options.
Availability of antibiotics reduces bacterial threat (plague, tularemia, anthrax treatable if caught early) but requires rapid diagnosis and treatment initiation.
Weaponization Potential
Ease of cultivation, production, and dissemination matters. Anthrax forms hardy spores amenable to weaponization. Botulinum toxin can be mass-produced.
Pathogens requiring complex cultivation, specific environmental conditions, or live vectors are harder to weaponize effectively. Aum Shinrikyo’s biological weapons failures demonstrated technical barriers.
Historical Use
Agents with documented use in biowarfare or bioterrorism receive heightened scrutiny. Anthrax (2001 letters, past bioweapons programs), plague (Unit 731, medieval warfare), tularemia and botulinum toxin (multiple bioweapons programs) all have weaponization history.
Historical precedent informs risk assessment even when technical barriers exist.
This chapter is part of The Biosecurity Handbook.