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Anthrax Bacillus anthracis As a Bioterrorism Agent

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Slide 1 :

Anthrax (Bacillus anthracis) As a Bioterrorism Agent

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Anthrax A zoonotic disease of cattle, sheep, and horses Human infection results from direct contact with infected animals or animal products Spores can survive in the soil for decades Most likely would be released as an aerosol May be sent as powder/slurry resulting in limited number of exposed

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Anthrax (cont.) Weaponized by the U.S. in 1950's and 60's Major emphasis of U.S.S.R. and Iraq programs Accidental release in Sverdlovsk in 1979 (79 cases, at least 68 deaths) Aum Shinrikyo Cult in Japan tried to use several times Released via mail Fall 2001

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Pathogenesis Spore enters skin, GI tract, or lung Ingested by macrophages Transported to regional lymph nodes Germinate in regional nodes, mediastinum (inhalational) Local production of toxins Edema & necrosis Bacteremia & toxemia Seeding of other organ systems

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Anthrax Spores Bacilli form spores when nutrients are exhausted Anthrax spores germinate in an environment rich with amino-acids, nucleosides, and glucose

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What is a micron? 1 micron = 1/1,000,000 meter 1 mil = 1/1000 inch 1 inch = 25,400 microns 1 mil = 25.4 microns Eye of needle 1,230 microns Beach sand 100 – 2000 microns Human hair 40 – 300 microns

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Inhalational Anthrax Infectious dose - "conventional wisdom" 8-50,000 spores Incubation period: 1- 5 days (up to 60) Initial symptoms nonspecific (2-5 d) fever, malaise, sweat/chills non-productive cough, chest discomfort nausea, vomiting

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Syndrome hemorrhagic mediastinitis/pleural effusion rapid progression to severe respiratory distress with dyspnea, diaphoresis, stridor, cyanosis 50% of cases may rapidly develop concurrent hemorrhagic meningitis with bloody cerebral spinal fluid septicemia, toxic shock/death occur within 24-36 hours after onset of respiratory distress Inhalational Anthrax (Con’t.)

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Inhalational Anthrax (Con’t.) Historically high mortality rate Mortality in 2001 attacks – 46% Data are insufficient to identify factors associated with survival

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Diagnosis of Inhalational Anthrax Radiograph: widened mediastinum (WM) (7/10 recent cases had WM; 7 had infiltrates, 8 had pleural effusion) Sputum may be helpful Blood cultures Nasal swabs have NO clinical utility Hemorrhagic pleural effusion or meningitis may develop

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Inhalational Anthrax: Differential Diagnoses Community acquired pneumonia if infiltrate (rare) or pleural effusion present Pneumonic tularemia or plague if pleural effusion present Hantavirus pulmonary syndrome Bacterial/fungal/TB mediastinitis Fulminant mediastinal tumors Dissecting aortic aneurysm widened mediastinum but usually no fever

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Inhalational Anthrax Victim (view of chest cavity) Lung Heart

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Inhalational Anthrax Treatment Early IV antibiotics and intensive care required Mortality may still exceed 80% Current treatment of choice: Ciprofloxacin 400 mg IV q 8-12 h or Doxycycline 200 mg IV x 1 then 100 mg IV q 12 and one or two additional antimicrobials MMWR October 26, 2001

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Duration of Treatment Antibiotic treatment must be continued for 60 days as there is a high risk of recurrence due to delayed germination of spores Once clinical condition improves, oral therapy can replace parental therapy

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Anthrax Post-Exposure Prophylaxis Starting antibiotics within 24 hours after aerosol exposure is expected to provide significant protection Duration: 60 days with or without vaccine Most effective when combined with vaccination Antibiotics are still indicated even when fully immunized Long-term antibiotics necessary because of spore persistence in lung/lymph node tissue

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Cutaneous Anthrax Most common naturally occurring form (95% cases; 2000 worldwide) Deposition of spore into skin usually at site of cut or abrasion; papule forms Incubation period - 1-7 days Papule enlarges into a 1-3 mm vesicle by second day; progresses to a painless depressed black eschar in 3 to 7 days Patient may have fever, malaise, headache, and regional lymphadenopathy

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Cutaneous Anthrax

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Cutaneous Anthrax (cont.)

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Cutaneous Anthrax (cont.)

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Cutaneous Anthrax (cont.) Diagnosis based on clinical findings and culture/direct smears and FA of fluid/lesions 20% case fatality w/o antibiotic treatment; rare with treatment Updated treatment for patients without systemic symptoms and lesion not on head or neck and not with extensive edema): Ciprofloxacin 500 mg q 12 hrs or Doxycycline 100 mg q 12 hrs or Amoxicillin 500 mg q 8 hrs

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Laboratory Response Network A national system to coordinate clinical diagnostic testing for bioterrorism events LRN is organized into four laboratory levels (A-D) with progressive levels of safety, containment and technical proficiency MDH laboratory, a Level C facility, has advanced capacity for rapid identification and can rule-in and refer

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Anthrax Microbiology B. anthracis Non-motile Non-hemolytic Encapsulated Gram-positive rod

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Positive encapsulation test for Bacillus anthracis

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Anthrax - Laboratory Diagnosis Gram positive bacilli on blood smear Blood culture growth of large gram-positive bacilli Growth on sheep’s blood agar cultures

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A dissecting aortic aneurysm could also present with a widened mediastinum apparent on chest x-ray more A dissecting aortic aneurysm could also present with a widened mediastinum apparent on chest x-ray but patients are generally afebrile. ... less

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