Anthrax, Bacillus Cereus And Erysipelothrix Rhusiopathiae

Causative organism: Bacillus anthracis. It is an aerobic, spore forming, gram positive bacilli. It is an important Category A bioterrorism agent. Bacillus ceres is a facultative anaerobe.

Agents of bioterrorism

• For anthrax - biosafety level 2 is required. Lab specimen and laboratory where anthrax is stored or routinely handled or used for research purposes, biosafety level 3 is required. 
• Covid RT-PCR specimen - biosafety level 2. Covid viral culture - biosafety level 3.

Virulence Factors

• Capsule, Toxin  are plasmid encoded- pX01 - Codes for toxin and pX02 - Codes for capsule. Capsule - Polyglutamic peptide, It resists phagocytosis. Toxin – Tripartite. Protective factors - Binds to host cell receptors (Anthrax toxin receptor). Protective antigen binds to anthrax toxin receptor and facilitates endocytosis of edema factor and lethal factor. Edema factor - Mimics adenyl cyclase activity, converts ATP to cAMP. Disrupts calcium metabolism and fluid homeostasis. Leads to edema – gelatinous edema. Lethal factor - Inhibits MAP (mitogen activated protein kinase pathway) kinase pathway. Cell death and tissue necrosis.

Clinical symptoms

• Cutaneous - Least mortality. Also called Fide porter's disease as it is commonly seen in individuals who transport animal hide on their bareback. Incubation period: 1 - 12 days. Evolves in 3 stages. Stage 1 - pruritus papules. 
• Stage 2 – Bulla/blisters with surrounding non pitting edema. Stage 3 - Hemorrhagic necrotic ulcer, Forms black eschar. Mortality associated with treated case of cutaneous anthrax - <1%.

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Inhalational – Also called wool-sorters disease. Incubation  period: 4 - 43 days. Through inhalation spores go into alveoli,     alveolar capillary bed -    mediastinal lymph nodes. Mediastinal lymphadenopathy - Hemorrhagic lymphadenitis.    Hemorrhagic mediastinitis + edema. Common and earliest radiologic finding - Enlarged mediastinum.

20 to 25% of patients may have pulmonary infiltrates. Presence of pulmonary infiltrates Doesn't rule out anthrax. Gelatinous pleural effusion (mild to moderate) - Recurrent because of disturbance in lymphatic drainage through mediastinum. Pleural effusion is responsible for respiratory failure.

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Stages of Inhalation Anthrax

• Early prodromal phase - Flu-like symptoms- Fever, malaise, cough. Intermediate progressive stage. Positive blood culture-Growth is seen within 24 hrs. of inoculation. Mediastinal adenopathy, Pleural effusion. Fulminant Stage- Meningitis, Respiratory illness requiring ventilatory support. Shock. GI anthrax- Incubation: 3 to 6 days. Oropharyngeal- Difficult to distinguish from diphtheria. Evolve like a URI up to the level of pseudo membrane. Intestinal: 3 stages- Prodromal illness - fever, malaise. Progressive - Ascites and abdominal pain. Fulminant stage - massive ascites, Rapid increase in girth, Leads to shock., Colonic hemorrhage. Route of acquiring - Consuming contaminated meat 
• Meningitis - Highest mortality. Can occur with or without other forms of anthrax. Leads to hemorrhage in subarachnoid space and leptomeninges. CSF – may resemble pyogenic meningitis. Autopsy finding - Cardinal's cap.

Diagnosis

• Direct demonstration of anthrax bacilli in different specimens. Cutaneous - Sample taken for ulcers. Inhalation - Sample taken from sputum. Meningitis - Sample taken from CSF.
• Gram stain – Gram positive bacilli.  Box car shaped. May have oval shaped spores. Bamboo stick appearance.

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• Culture- Nutrient agar - Medusa head appearance of colonies.

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• Blood agar - Shows grayish white colonies. Non hemolytic. Selective media - PLET media.

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• McFadyean's reaction -Blood samples taken and stained with polychrome methylene blue. Bacilli appears blue with a surrounding purple hue (due to capsule).

• CSF – 2 types of bacilli are seen. Listeria – small bacilli. Anthrax – comparatively large bacilli. Confirmatory test - Direct immunofluorescence. 

Treatment

• Antibiotics- If there is no meningitis. Preferred agent - Ciprofloxacin ± linezolid or clindamycin. Clindamycin – preferred for skin. Linezolid – preferred for GI and inhalation anthrax. If Meningitis proven or suspected with or without other forms of anthrax. Ciprofloxacin + Meropenem +linezolid. Duration of therapy: 60 days. Pleural and ascitic fluid drainage- For pleural effusion - ICD tube is placed. Ascites - repeated large volume paracentesis.
• Anthrax antitoxin- When it is used as an adjuvant in treatment of inhalation anthrax it has better outcome than antibiotics alone. Monoclonal antibodies- Inhibits protective antigen of anthrax. Raxibacumab, Obiltoxaximab . Approved for Inhalational anthrax and post exposure prophylaxis. 

Prevention

• Pre-exposure prophylaxis: FDA approved vaccine - AVA Vaccine (Anthrax vaccine Adsorbed). Post exposure - Ciprofloxacin > Doxycycline. Pregnancy - preferred agent is ciprofloxacin.  Monoclonal antibodies - Raxibacumab and Obiltoxaximab.

Bacillus Cereus

• Facultative anaerobic bacilli. Food poisoning. Emetic - intradiegetic toxin mediated food poisoning, Ingestion of toxin through food, Preformed toxins. Duration of onset of symptoms - first 6 hours of ingestion. Severe vomiting and nausea. Also called Chinese restaurant or Chinese fried rice syndrome. Heat stable/resistant toxins.
• Diarrheal – Extradiegeti. Bacillus spores are ingested - germinate in intestine.  Profuse watery diarrhea. Onset of symptoms: 8 to 18 hours of consumption. Self-limiting. Symptoms usually lasts less than 24 hours.  Fatality - rare.
• Keratitis - Fulminant, May progress to endophthalmitis,  May lead to vision problems.  DOC – Vancomycin. Alternative - Meropenem.

Erysipelothrix rhusiopathiae

• Gram positive bacilli. Erysipeloid - Localized cellulitis, typically affects fingers. Seen in people working with sea animals. Also called whale finger or pork finger.

• Diagnosis- History of meat handling. Whole thickness skin biopsy and culture.
• DOC - Penicillin G. Vancomycin is contraindicated due to resistance.

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