253.1 🎓 醫孞生版

253.1.0.1 📌 䞀頁重點

253.1.0.1.1 CDC Categories
253.1.0.1.1.1 Category A (Highest Threat)
  • Easy dissemination + high mortality + major public health impact
  • Anthrax (Bacillus anthracis)
  • Smallpox (Variola virus)
  • Plague (Yersinia pestis)
  • Botulism (Clostridium botulinum toxin)
  • Tularemia (Francisella tularensis)
  • Viral Hemorrhagic Fevers (Ebola, Marburg, Lassa, etc.)
253.1.0.1.1.2 Category B
  • Moderate threat
  • Brucellosis, glanders, Q fever, salmonella, shigella, E. coli O157, ricin, others
253.1.0.1.1.3 Category C
  • Emerging pathogens — hantavirus, nipah, multi-drug TB, others
253.1.0.1.2 Anthrax (Bacillus anthracis)
253.1.0.1.2.1 Background
  • Spore-forming gram + rod
  • Multiple toxins: protective antigen (PA), lethal factor (LF), edema factor (EF)
  • Spores environmentally stable + weaponizable
253.1.0.1.2.2 Forms
  • Cutaneous (95% of natural cases): painless papule → vesicle → black eschar; LAP + edema
  • Inhalational (bioterrorism main): biphasic illness — initial flu-like → fulminant (mediastinitis, shock, meningitis, hemorrhage); mortality 45%+ with treatment
  • Gastrointestinal (rare): ulcerative oropharyngeal or intestinal lesions
  • Injection (IDU heroin contamination — Europe outbreaks)
  • Meningitis in severe / complication
253.1.0.1.2.3 Diagnosis
  • CXR / CT: widened mediastinum (inhalational, pathognomonic)
  • Blood + tissue cultures + Gram stain
  • PCR
  • Serology
  • BSL-3 lab
253.1.0.1.2.4 Treatment
  • Ciprofloxacin or doxycycline (oral or IV)
  • + 1-2 additional antibiotics for severe (clindamycin, meropenem)
  • 60-day course total (long; due spore persistence)
  • Antitoxin (raxibacumab, obiltoxaximab) for severe
  • Anthrax vaccine (BioThrax) for post-exposure prophylaxis + pre-exposure (military)
253.1.0.1.2.5 2001 USA Anthrax Letters
  • Inhalational + cutaneous cases
  • 5 deaths
  • Heightened post-9/11 bioterror awareness
253.1.0.1.3 Smallpox (Variola)
253.1.0.1.3.1 Background
  • Eradicated 1980 (last natural case Somalia 1977)
  • Stockpiles: CDC + Russia (declared)
  • Bioterror Category A
  • Mortality 30%+ (variola major)
253.1.0.1.3.2 Clinical
  • Sudden high fever + headache + backache + prostration → 2-4 d → maculopapular rash → vesicular → pustular → crusts
  • Synchronous progression of all lesions
  • Centrifugal distribution (face + extremities)
  • See Ch 202 for detail
253.1.0.1.3.3 Vaccine
  • ACAM2000 (live vaccinia, traditional)
  • JYNNEOS (MVA-BN, non-replicating; safer in immunocompromise)
253.1.0.1.3.4 Treatment
  • Supportive (no specific antiviral)
  • Tecovirimat (TPOXX) for smallpox; rare use
  • Vaccinia immune globulin (VIG)
253.1.0.1.4 Plague (Yersinia pestis)
253.1.0.1.4.1 Background
  • Bipolar staining “safety pin” gram-neg
  • Flea-borne (Xenopsylla) historically; rare bioterror aerosol
  • 3 forms: bubonic, septicemic, pneumonic
253.1.0.1.4.2 Clinical
253.1.0.1.4.3 Bubonic Plague
  • Flea bite → painful regional LAP (“bubo”) + fever + bacteremia
  • Inguinal common
  • 50-90% mortality untreated
253.1.0.1.4.4 Septicemic Plague
  • Bacteremia + sepsis + DIC
  • Mortality 90%+ untreated
253.1.0.1.4.5 Pneumonic Plague
  • Inhalation primary or hematogenous secondary
  • Bioterror form
  • Severe pneumonia + hemoptysis + sepsis
  • Person-to-person spread (most contagious form)
  • Mortality 95%+ untreated; 60% with treatment
  • Isolation critical
253.1.0.1.4.6 Treatment
  • Streptomycin IM (classical)
  • Gentamicin alternative
  • Doxycycline + ciprofloxacin alternative
  • 10 days
  • PEP for contacts: doxycycline / ciprofloxacin
253.1.0.1.4.7 Vaccine
  • Killed whole-cell vaccine (limited)
  • Not generally available
253.1.0.1.5 Botulism (Clostridium botulinum)
253.1.0.1.5.1 Background
  • 4 forms naturally: foodborne, infant, wound, iatrogenic
  • Bioterror: aerosolized toxin
  • Most potent biological toxin known
  • LD50 in human ~ 1 ng/kg
253.1.0.1.5.2 Clinical
  • Descending flaccid paralysis (CN first → respiratory)
  • “4 D’s”: diplopia, dysarthria, dysphonia, dysphagia
  • Sensorium clear, no fever, no sensory loss
  • Respiratory failure
  • See Ch 158 detail
253.1.0.1.5.3 Treatment
  • Heptavalent BAT (Botulinum Antitoxin) ASAP
  • Babybig for infants
  • Supportive ventilation (weeks-months)
  • See Ch 158
253.1.0.1.5.4 Detection + Response
  • Lab-confirmed multiple cases without obvious food source → bioterror suspicion
  • Public health investigation
253.1.0.1.6 Tularemia (Francisella tularensis)
253.1.0.1.6.1 Background
  • Gram-neg coccobacillus
  • Highly infectious (10 organisms can cause disease)
  • Bioterror category A
  • Natural: rabbit + tick exposure
253.1.0.1.6.2 Forms
  • Ulceroglandular, oculoglandular, oropharyngeal, pneumonic (bioterror), typhoidal, glandular
253.1.0.1.6.3 Treatment
  • Streptomycin or gentamicin IM/IV × 10 days
  • Doxycycline / ciprofloxacin alternative
  • PEP for contacts: doxycycline / cipro × 14 days
253.1.0.1.7 Viral Hemorrhagic Fevers (VHF)
253.1.0.1.7.1 Pathogens
  • Filoviruses: Ebola, Marburg
  • Arenaviruses: Lassa, Junín, Machupo, Lujo
  • Bunyaviruses: Hantavirus, Crimean-Congo HF, RVF
  • Flaviviruses: Dengue, Yellow Fever (less)
253.1.0.1.7.2 Clinical (See Ch 222, 223)
  • Fever + hemorrhage + multi-organ
  • Bioterror concern especially Ebola + Marburg + Lassa + Junin
253.1.0.1.7.3 Treatment
  • Supportive primarily
  • Specific: ribavirin (Lassa, CCHF); monoclonal Abs (Ebola — Inmazeb, Ebanga)
  • Vaccines: Ervebo (Ebola), MVA-LASV (Lassa) in trials, Marburg in 2024 emergency rollout
253.1.0.1.8 Other Bioterror Agents
253.1.0.1.8.1 Category B
  • Brucellosis, glanders (Burkholderia mallei), melioidosis (B. pseudomallei), Q fever (Coxiella), Salmonella, Shigella, E. coli O157:H7, ricin toxin, Staphylococcal enterotoxin B, Vibrio cholerae, Cryptosporidium
253.1.0.1.8.2 Category C
  • Emerging diseases that could be engineered:
    • Nipah virus
    • Hantavirus
    • Multi-drug resistant TB
    • SARS-CoV-2 (some classification)
    • Newer threats

253.1.0.2 1⃣ Bioterror Recognition + Response

253.1.0.2.1 Clues to Bioterror Attack
  • Unusual disease in unusual location (e.g., anthrax in non-endemic area)
  • Cluster of cases with similar presentation in short timeframe
  • Common exposure identified
  • Multiple casualties + critical illness without obvious natural cause
  • Unusual route (inhalational anthrax, pneumonic plague)
  • Lab confirmation of weaponized agent
  • Deliberate dispersion (e.g., letter attacks, aerosol)
253.1.0.2.2 Response
  1. Recognition by clinician
  2. Notification to local public health + CDC immediately
  3. Isolation of cases (especially pneumonic plague, smallpox, VHF, suspected bioterror)
  4. PPE for healthcare workers
  5. Specimen collection (BSL-3+ lab handling)
  6. Empirical treatment + post-exposure prophylaxis for contacts
  7. Vaccination when applicable (smallpox, anthrax)
  8. Decontamination of environment if needed
  9. Mass casualty preparation + surge capacity
  10. Forensic investigation in collaboration with FBI / law enforcement
253.1.0.2.3 National Response
  • CDC + DHHS lead public health response
  • FBI investigates as criminal act
  • National Strategic Stockpile has antitoxins + vaccines + antibiotics
  • BARDA funds countermeasure development
253.1.0.2.4 International
  • WHO coordinates global response
  • BWC (Biological Weapons Convention) — 1975 treaty banning bioweapons
  • NTI (Nuclear Threat Initiative) + others advocate

253.1.0.3 2⃣ Mass Vaccination + PEP Protocols

253.1.0.3.1 Anthrax PEP
  • Doxycycline or ciprofloxacin × 60 days
  • + Anthrax vaccine (3-dose series) for high-risk
  • Antitoxin (raxibacumab) for symptomatic
253.1.0.3.2 Smallpox PEP
  • JYNNEOS or ACAM2000 vaccine within 3-7 days of exposure
  • Effective if given before symptoms
253.1.0.3.3 Plague PEP
  • Doxycycline or ciprofloxacin × 7-10 days
  • For close contacts of pneumonic plague
253.1.0.3.4 Tularemia PEP
  • Doxycycline or ciprofloxacin × 14 days
253.1.0.3.5 VHF PEP
  • Variable by pathogen
  • Ebola: vaccine for contacts (Ervebo ring vaccination)
  • Lassa: ribavirin for symptomatic + close contacts