Bacillus AnthracisAnthrax
Bacillus Anthracis From greek word
“anthrakos” Large (1 - 1.2µm in
width x 3 - 5µm in length), gram (+)
Non motile Facultative anaerobe Spore forming (oval,
endospores) Polypeptide capsule Produces 3 exotoxins
Endospores Can survive in dry
soil for decades Sporulation requires
oxygen Can be killed by:
Vegetative cells in 60 0 C X 30 min
Spores in 100 0 C X 10 min
4% Formaldehyde 4% KMnO4
Hypochlorite ( 0.5%)
Natural Infection Sources Primarily domesticated and wild animals
(sheep, cows, horses, goats) Soil rich in organic matter (pH < 6.0) in regions
where dramatic changes occur in climate Streams, insects, wild animals, birds,
contaminated wastes Undercooked meat Contact with flesh, bones, hides, hair, &
excrement Cutaneous & inhalational infections are most
common
Thos who are at increased risk Tanneries Textile mills Wool sorters Bone processors Slaughterhouses Laboratory workers Military
Biological Weapon Germany (1915) Manchuria (1937) Swerdlowsk, Russia (1979) South Africa (1978-1980) Tokyo (1983) USA, Washington (2001)
Forms of Anthrax Cutaneous anthrax
Skin Most common Spores enter to skin through small lesions
Inhalation anthrax Spores are inhaled
Gastrointestinal (GI) anthrax Spores are ingested Oral-pharyngeal and abdominal
Pathogenesis The infectious dose of B. anthracis in humans
is unknown (though for primates the LD50 is 8,000-10,000 )
Virulence factors are Capsule 3 toxins (Edema factor (EF), Lethal factor (LF) and
Protective antigen (PA))
Capsule Glycocalyx. Sticky, gelatinous polymer external to
cell wall. pX02 plasmid Made up of poly-D-glutamic acid Non-toxic on its own A-B model of toxicity. Two proteins must combine
to create the toxic complex. Protective antigen is the common protein and both EF and LF need PA to get into the cell and cause damage.
Only encapsulated B. anthracis virulent Most important role during establishment of
disease. Protects against phagocytosis & lysis during vegetative state.
Toxins pX01 plasmid PA, EF & LF (50% of proteins in the organism) A-B model
PA+LF lethal activity EF+PA edema EF+LF inactive PA+LF+EF edema & necrosis; lethal
Protective antigen (PA, 83kDa) Pag gene Binds to receptor & helps internalize other 2 proteins
Edema factor (EF, 89 kDa) Cya gene Adenylate cyclase Affects all cells
Lethal factor (LF, 87 kDa) Lef gene Metalloprotease Cleaves mitogen activated protein kinase kinsase (MAPKK) Affects only macrophages
Stages of infection Encounter: organism and body surfaces
Adhesion: generalized and receptor-specific
Initial multiplication in situ colonization
Invasion breaching of anatomic barriers
Lymphatic stage invasion of bloodstream
Generalized infection, metastases local colonizations, “tropisms” of certain organisms
Pathogenesis
Abrasion, inhalation, ingestion
IntroducedPhagocytosed by
Macrophages Regional LNs
Germinate inside macrophages
Vegetative FormsRelease
Multiply in lymphaticsBlood stream10 7 to 10 8/ml
SepticemiaDeath
Phases of symptoms
1st phase (within 7 days)
2nd phase (within 2-3 days)
Fever (> 37,7°C/100°F) Chills or night sweats Headache, cough, chest
discomfort, sore throat Joint stiffness, joint
pain, muscle aches Shortness of breath Enlarged lymph nodes,
nausea, loss of appetite, abdominal distress, vomiting, diarrhea
Meningitis
Breathing problems, pneumonia
Shock Swollen lymph
glands Profuse sweating Cyanosis (skin turns
blue) Death
Cutaneous Anthrax 95% human cases are cutaneous infections Incubation period 2-3 days Small, pruritic, non-painful papule at inoculation
site Papule develops into hemorrhagic vesicle (24-48
hrs) & ruptures Slow-healing painless ulcer (d=1-3 cm) covered
with black eschar, surrounded by edema Infection may spread to lymphatics causing local
adenopathy Septicemia may in 20% of cases 20% mortality in untreated cutaneous anthrax
Cutaneous Anthrax
Inhalation Anthrax Incubation: 1 to 7 days with acute onset (may develop in a
few hours) Very high doses of bacteria (bio-weapon aerosoles) Initial phase
Nonspecific (mild fever, malaise) Second phase
Severe respiratory distress Fever, dyspnea, cyanosis, rales, tachycardia, feeble pulse,
hypotension, mediastinal widening, eventual death Vomiting, sweating, axiety
Lesions in mediastinal lymph nodes, carried there by alveolar macrophages, causing edema, toxemia, bacteremia
Case fatality: 75 to 90% (death in 2 or 3 days if untreated)
Inhalation Anthrax
Widened mediastinum on x-ray
GI Anthrax
Oropharyngeal Abdominal (common)
Caused by deposition and germination of spores in the upper gastrointestinal tract
Local lymphadenopathy, edema, sepsis develop after an oral or esophageal ulcer
Caused by deposition and germination of spores in the lower gastrointestinal tract, which results in a primary intestinal lesion
Abdominal pain and vomiting appear within a few days after ingestion
Incubation: 2 to 5 days Severe gastroenteritis common (due to
undercooked & contaminated meat) Case fatality rate: 25 to 75%• Mucosal lesion (lesions are edematous,
with black eschar) to the lymphatic system Nausea, anorexia, vomiting, fever Progresses to severe abdominal pain and
bloody emesis and diarrhea Ascites may develop on day 2 - 4 Death 2 to 5 days after onset of symptoms Rare in developed countries
Diagnosis Gram stain Culture of B. anthracis from the blood, skin
lesions, vesicular fluid, or respiratory secretions
X-ray and Computed Tomography (CT) scan Rapid detection methods
- PCR for detection of nucleic acid- ELISA assay for antigen detection- Other immunohistochemical and immunoflourescence
Examination
Treatment • Penicillin is drug of choice (ciprofloxacin,
erythromycin, chloramphenicol, doxycycline) 60 days
• Vaccine (for laboratory workers, livestock handlers, active duty military members) BioThrax/Anthrax vaccine
• Do not incise lesions• Eschar is not dangerous after treatment• The patient must remain hospitalized until fully
cured
Prevention Annual animal vaccination Disposal of animal carcasses: disinfect with
oil, burn, bury deep, covered with quicklime. Spores will not form inside the carcass, and
putrefaction kills the Bacillus. Flies feeding on incoagulable blood may be a problem.
Gloves, masks, disinfection of materials. Health edu Death, ilness reports
Bioterrorism‘First choice’ weapono “Poor Man’s Nuke”o Availabilityo Silent, unnoticeableo Deniabilityo Slow actiono Highly lethalo Non-contagiouso Prevention (enemy can easily vaccinate
themselves prior)o UV resistant
Category A Biological weaponHigh-priority agents include organisms that pose a risk to national security because they :
· can be easily disseminated or transmitted person-to-person;
· cause high mortality, with potential for major public health impact;
· might cause public panic and social disruption; and
· require special action for public health preparedness
These agents include: Bacteria: Bacillus anthracis
(anthrax); Yersinia pestis (plague); Clostridium botulinum toxin (botulism); Francisella tularensis (tularaemia);
Filoviruses: Ebola hemorrhagic fever, Marburg hemorrhagic fever; and
Arenaviruses: Lassa (Lassa fever), Junín (Argentine hemorrhagic fever) and related viruses
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