Healthcare Response to Weapons of Mass Destruction: Biological, Chemical and Radiological

Biological Agents





The US Centers for Disease Control and Prevention (CDC) defines three categories of biologic agents with potential to be used as weapons, based on ease of dissemination or transmission, potential for major public health impact due to high mortality, potential for public panic and social disruption, and special requirements for public health preparedness. Category A agents are of highest concern; they are (USDHS, 2015; Siegel, et al., 2007; CDC, 2000):

  • Bacillus anthracis (anthrax),
  • Yersinia pestis (plague),
  • Variola major (smallpox),
  • Clostridium botulinum toxin (botulism),
  • Francisella tularensis (tularemia),
  • Viral Hemorrhagic Fevers (VHF): filoviruses (Ebola hemorrhagic fever, Marburg hemorrhagic fever); and arenaviruses (Lassa [Lassa fever], Junin [Argentine hemorrhagic fever], and related viruses).

Anthrax


Color-enhanced scanning electron micrograph shows splenic tissue from a monkey with inhalational anthrax; featured are rod-shaped bacilli (yellow) and an erythrocyte (red). Photo courtesy of Arthur Friedlander, NIAID.


Anthrax bacteria. Courtesy of AVIPAnthrax Vaccine Immunization Program

Bacillus anthracis can cause inhalation anthrax, cutaneous anthrax, gastrointestinal anthrax and oropharyngeal anthrax (CDC, 2017c; CDC, 2017d):

Cause: Bacillus anthracis

  • Encapsulated, aerobic, gram-positive, spore-forming, rod-shaped (bacillus) bacterium (CDC, 2017c).

Systems Affected

  • Skin or cutaneous; the most common form.
  • Respiratory tract or inhalation; occurs rarely.
  • Gastrointestinal (GI) tract; occurs rarely.
  • Oropharyngeal form; the least common form (CDC, 2017c).

Transmission

  • Skin: direct skin contact with spores; in nature, contact with infected animals or animal products (usually related to occupational exposure); person-to-person transmission from contact with lesion of untreated patient possible, but extremely rare (Siegel, et al., 2007).
  • Respiratory tract: inhalation of aerosolized spores (CDC, 2017c; CDC, 2017d).
  • GI: consumption of undercooked or raw meat products or dairy products from infected animals (CDC, 2017c).
  • NO person-to-person transmission of inhalation or GI anthrax (CDC, 2017c; CDC, 2017d).
  • Spores can be inhaled into the lower respiratory tract. The infectious dose of B. anthracis in humans by any route is not precisely known. In primates, the LD50 (i.e., the dose required to kill 50% of animals) for an aerosol challenge with B. anthracis is estimated to be 8,000-50,000 spores; the infectious dose may be as low as 1-3 spores (Siegel, et al., 2007).

Reporting

Report suspected or confirmed anthrax cases immediately to your local health department or to:

  • NV State Department of Emergency Management 24 hours per day at 775-687-0400; or
  • CDC at 770.488.7100.  

Cutaneous Anthrax

Ulcer and vesicle ring; black eschar, redness remains. Courtesy of CDC.

Incubation Period

  • Usually an immediate response up to 1 day (CDC, 2017c; CDC, 2017d); it can be from 1 to 12 days (Siegel, et al., 2007).

Typical Signs/Symptoms

  • Local skin involvement after direct contact with spores or bacilli.
  • Localized itching followed by 1) painless, reddish papular lesion that develops a central vesicle or bulla in 1-2 days, the lesion become pustular during the next 3-7 days and 2) subsequently there is development of black eschar within 7-10 days of initial lesion. There can be extensive surrounding edema (Siegel, et al., 2007).

Diagnosis

  • Swabs of lesion (under eschar) for immunohistochemistry (IHC), polymerase chain reaction (PCR) and culture; punch biopsy for IHC, PCR and culture; vesicular fluid aspirate for Gram stain and culture; blood culture if systemic symptoms; acute and convalescent sera for ELISA serology (Siegel, et al., 2007).
  • Obtain specimens for culture BEFORE initiating antimicrobial therapy (CDC, 2017c; CDC, 2017d).

Treatment

  • Do NOT use extended-spectrum cephalosporins or trimethoprim/sulfamethoxazole because anthrax may be resistant to these drugs (CDC, 2017c; CDC, 2017d).
  • See Table 1. Cutaneous Anthrax Treatment Protocol for specific therapy.

Precautions

  • Standard contact precautions. Avoid direct contact with wound or wound drainage (CDC, 2017c; CDC, 2017d). Contact Precautions if uncontained copious drainage (Siegel, et al., 2007).
  • For any aerosolized powder, environmental exposures: Respirator (N95 mask or powered air purifying respirators, or PAPRs), protective clothing; decontamination of persons with powder on them (CDC, 2017c; CDC, 2017d).
  • Handwashing for 30-60 seconds with soap and water or 2% chlorhexidene gluconate after spore contact (alcohol handrubs inactive against spores) (CDC, 2017c; CDC, 2017d).
Table 1. Cutaneous Anthrax Treatment Protocol* for the 2001 Bioterrorism Attack (CDC, 2017c)
Category
Initial Therapy(oral)+
Duration
Adults* Ciprofloxacin 500 mg BID or
doxycycline 100 mg BID
60 days++
Children* Ciprofloxacin 10-15 mg/kg q 12 hours
(not to exceed 1 Gm/day) or doxycycline§:

>8 yrs & >45kg:100 mg q 12 hours
>8 yrs & 45kg: 2.2 mg/kg q 12 hours
8 yrs: 2.2 mg/kg q 12 hours
60 days++
Pregnant women*** Ciprofloxacin 500 mg BID or
doxycycline 100 mg BID
60 days++
Immunocompromised persons* Same as for non-immunocompromised
adults and children
60 days++

*Cutaneous anthrax with signs of systemic involvement, extensive edema, or lesions on the head or neck require intravenous therapy, and a multi-drug approach is recommended Table 1.

+Ciprofloxacin and doxycycline should be considered first line therapy. Amoxycillin 500 mg po TID for adults or 80 mg/kg/day divided every 8 hours for children is an option for completion of therapy after clinical improvement.

++Previous guidelines have suggested treating cutaneous anthrax for 7-10 days, but 60 days is recommended in the 2001 attack, given the likelihood of exposure to aerosolized B. anthracis.

§The American Academy of Pediatrics recommends treatment of young children with tetracyclines for serious infections (e.g., Rocky Mountain Spotted Fever).

***Although tetracyclines or ciprofloxacin are not recommended during pregnancy, their use may be indicated for life-threatening illness. Adverse effects on developing teeth and bones are dose related; therefore doxycycline might be used for a short time (7-14 days) before 6 months of gestation.

Oropharyngeal Anthrax (CDC, 2017c; CDC, 2017d)


Mediastinal widening and pleural effusion on Chest X-Ray in inhalation anthrax. Courtesy of CDC.

Incubation Period

  • Usually <1 week; may be prolonged for weeks (up to 2 months) (CDC, 2017c; CDC, 2017d).
  • Usually 1 to 7 days but up to 43 days reported (Siegel, et al., 2007).

Typical Signs/Symptoms (often biphasic, but symptoms may progress rapidly)

Initial phase

  • Non-specific symptoms such as low-grade fever, nonproductive cough, malaise, fatigue, myalgias, profound sweats, chest discomfort (upper respiratory tract symptoms are rare) (CDC, 2017c).
  • Maybe rhonchi on exam, otherwise normal (CDC, 2017c; CDC, 2017d).
  • Chest X-ray or computerized tomography scan (CT) (Siegel, et al., 2007; CDC, 2017c; CDC, 2017d):
    • mediastinal widening
    • pleural effusion (often)
    • infiltrates (rare)
    • hilar abnormalities.

Subsequent phase

  • 1-5 days after onset of initial symptoms (CDC, 2017c; CDC, 2017d).
  • May be preceded by 1-3 days of improvement (CDC, 2017c; CDC, 2017d).
  • Abrupt onset of high fever and severe respiratory distress (dyspnea, stridor, cyanosis) (CDC, 2017c; CDC, 2017d).
  • Shock, death within 24-36 hours (CDC, 2017c; CDC, 2017d).
  • If untreated, 85-90% fatal (Siegel, et al., 2007).
  • Meningitis occurs in 50% of inhalation anthrax cases (Siegel, et al., 2007).

Laboratory

  • Coordinate all aspects of testing, packaging, and transporting with public health laboratory/Laboratory Response Network (LRN) (CDC, 2017c; CDC, 2017d).
  • Obtain specimens appropriate to system affected (CDC, 2017c; CDC, 2017d):
    • blood (essential)
    • pleural fluid
    • cerebral spinal fluid (CSF).
    • skin lesion.
  • blood for culture and PCR; pleural effusion for culture, PCR and IHC; CSF if meningeal signs present for IHC, PCR and culture; acute and convalescent sera for ELISA serology; pleural and/or bronchialbiopsies IHC (Siegel, et al., 2007).

Clues to diagnosis

  • Gram-positive bacilli on unspun peripheral blood smear or CSF (CDC, 2017c; CDC, 2017d).
  • Aerobic blood culture growth of large, gram-positive bacilli provides preliminary identification of Bacillus species (CDC, 2017c; CDC, 2017d).

Treatment

  • Obtain specimens for culture BEFORE initiating antimicrobial therapy.
  • Initiate antimicrobial therapy immediately upon suspicion.
  • Do NOT use extended-spectrum cephalosporins or trimethoprim/sulfamethoxazole because anthrax may be resistant to these drugs.
  • Supportive care including controlling pleural effusions.
  • See Inhalational Anthrax Treatment Protocol in Table 2. below for specific therapy.

Precautions

  • Standard precautions (Siegel, et al., 2007; CDC, 2017c; CDC, 2017d).
  • Aerosolized powder, environmental exposures: Respirator (N95 mask or PAPRs), protective clothing; decontamination of persons with powder on them (Siegel, et al., 2007; CDC, 2017c; CDC, 2017d).
Table 2. Inhalation Anthrax Treatment Protocol* for 2001 Bioterrorist Attack
Category
Initial Therapy (intravenous)
Duration
Adults

Ciprofloxacin 400 mg q 12 hrs*
or

Doxycycline 100 mg q 12 hrs
and

One or two additional antimicrobials

IV treatment initially**. Switch to oral antimicrobial therapy when clinically appropriate:
Ciprofloxacin 500 mg po BID or

Doxycycline 100 mg PO BID

Continue for 60 days (IV and PO combined)

Children

Ciprofloxacin 10-15 mg/kg q 12 hrs ***
or

Doxycycline:
>8 yrs & >45kg:100 mg every 12 hrs
>8 yrs & 45kg: 2.2 mg/kg every 12 hrs
8 yrs: 2.2 mg/kg every 12 hrs
and

One or two additional antimicrobials

IV treatment initially**. Switch to oral antimicrobial therapy when clinically appropriate:
Ciprofloxacin 10-15 mg/kg PO every 12 hrs***
or

Doxycycline:
>8 yrs & >45kg:100 mg PO BID
>8 yrs & 45kg: 2.2 mg/kg PO BID
8 yrs: 2.2 mg/kg PO BID
and

Continue for 60 days (IV and PO combined)

Pregnant Women
Same for nonpregnant adults (the high death rate from the infection outweighs the risk posed by the antimicrobial agent).
IV treatment initially. Switch to oral antimicrobial therapy when clinically appropriate. Oral therapy regimens same for nonpregnant adults.
Immunocompromised
Persons
Same as for non-immunocompromised
adults and children
Same as for non-immunocompromised
adults and children

Gastrointestinal Anthrax

Incubation Period

  • Usually 1-7 days (CDC, 2017c; CDC, 2017d);
  • 15-72 hours (Siegel, et al., 2007).

Typical Signs/Symptoms

Initial phase

  • Nausea, anorexia, vomiting, and fever progressing to severe abdominal pain, hematemesis, and bloody diarrhea (CDC, 2017c; CDC, 2017d).
  • Acute abdomen picture with rebound tenderness may develop (CDC, 2017c; CDC, 2017d).
  • Necrotic, ulcerated edematous lesions develop in intestines (Siegel, et al., 2007).
  • Mesenteric adenopathy on computed tomography (CT) scan likely.
  • Mediastinal widening on chest X-ray has been reported (Siegel, et al., 2007).

Subsequent phase

  • 2-4 days after onset of symptoms, ascites develops as abdominal pain decreases (CDC, 2017c; CDC, 2017d).
  • Shock, death within 2-5 days of onset (CDC, 2017c; CDC, 2017d).
  • 25-60% fatal if untreated (Siegel, et al., 2007).

Laboratory

  • Coordinate all aspects of testing, packaging, and transporting with public health laboratory/LRN.
  • Obtain specimens appropriate to system affected (CDC, 2017c; CDC, 2017d):
    • blood (essential).
    • ascitic fluid.
  • Rectal swabs and stool samples (Siegel, et al., 2007).

Clues to diagnosis

  • Gram-positive bacilli on unspun peripheral blood smear or ascitic fluid (CDC, 2017c; CDC, 2017d).
  • Pharyngeal swab for pharyngeal form (CDC, 2017c; CDC, 2017d).
  • Aerobic blood culture growth of large, gram-positive bacilli provides preliminary identification of Bacillus species (CDC, 2017c; CDC, 2017d).

Treatment

  • Obtain specimens for culture BEFORE initiating antimicrobial therapy.
  • Early (during initial phase) antimicrobial therapy is critical.
  • Do NOT use extended-spectrum cephalosporins or trimethoprim/sulfamethoxazole because anthrax may be resistant.
  • Use Inhalation Anthrax treatment protocol; See Table 2 for specific treatment.

Precautions

  • Standard precautions (Siegel, et al., 2007; CDC, 2017c; CDC, 2017d).
  • Aerosolized powder, environmental exposures: Respirator (N95 mask or PAPRs), protective clothing; decontamination of persons with powder on them (Siegel, et al., 2007; CDC, 2017c; CDC, 2017d).

Oropharyngeal Anthrax (CDC, 2006e; CDC, 2001a)

Incubation Period

  • Usually 1-7 days

Typical Signs/Symptoms

Initial phase

  • Fever and marked unilateral or bilateral neck swelling caused by regional lymphadenopathy.
  • Severe throat pain and dysphagia.
  • Ulcers at the base of the tongue, initially edematous and hyperemic.

Subsequent phase

  • Ulcers may progress to necrosis.
  • Swelling can be severe enough to compromise the airway.

Laboratory

  • Coordinate all aspects of testing, packaging, and transporting with public health laboratory/LRN.
  • Obtain specimens appropriate to system affected:
    • Blood (essential).
    • Throat.

Clues to diagnosis

  • Aerobic blood culture growth of large, gram-positive bacilli provides preliminary identification of Bacillus species.

Treatment

  • Obtain specimens for culture BEFORE initiating antimicrobial therapy.
  • Do NOT use extended-spectrum cephalosporins or trimethoprim/sulfamethoxazole because anthrax may be resistant to these drugs.
  • Supportive care including controlling ascites.
  • Use Inhalation Anthrax Treatment Protocol; See Table 2. for specific therapy.

Precautions

  • Standard contact precautions.

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