ANTHRAX
:Prepared by (Section (B : Written & collected by Ayman Hesham Student at fifth year Zoonoses department
Anthrax • Malignant Pustule, Malignant Edema, Wool sorters’ Disease, Rag pickers’ Disease, Maladi Charbon, Splenic Fever • From the Greek word anthrakos for coal
Milestones in Anthrax History * Although anthrax dates back more than 3,000 years, it was
not recognized as a
disease until the 18th century. 1500 B.C - A “plague of boils” in Egypt affected the Pharaoh’s cattle. ‘Boils’ are symptomatic of anthrax. 70
Bioterrorism
Cases
60 50 40 30 20 10 0 1955
1960
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1975
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1985
1990
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2005
Anthrax Letters 2001
Analysis of the 2001 US Anthrax Attacks (2)
 Above anthrax-containing envelopes postmarked
 Above anthrax-containing envelopes postmarked
*Also believed to be three or more other envelopes that were never found
Anthrax •
Caused by the spore-forming bacterium, Bacillus anthracis
•
Zoonotic disease in herbivores (e.g., sheep, goats, cattle( follows ingestion of spores in soil
•
Human infection typically acquired through contact with anthraxinfected animals or animal products or atypically through intentional exposure
•
Three clinical forms – – –
Cutaneous pulmonary Gastrointestinal
Bacillus anthracis • Large, Gram positive, non-motile rod capsulated • Vegetative form inside host and sporulated form in the soil • Nearly worldwide distribution • Over 1,200 strains
http://www.bact.wisc.edu/Bact330/lectureanthrax
Susceptibility in animals Herbivorous animals (cattle, sheep “except Algerian sheep�, horse, camel and elephant( Pigs are intermediate Carnivore are rare Birds are very rare
Anthrax Infection & Spread •
May be spread by streams, insects, wild animals, birds, contaminated wastes
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Animals infected by soil borne spores in food & water or bites from certain insects
•
Humans can be infected when in contact with flesh, bones, hides, hair, & excrement – nonindustrial or industrial – cutaneous & inhalational most common
•
Risk of natural infection 1/100,000 – Outbreaks occur in endemic areas after outbreaks in livestock
How it attack human
Pathogenesis • The infectious dose of B. anthracis in humans by any route is not precisely known. – Rely on primate data – Minimum infection dose of ~ 1,000-8,000 spores – LD50 of 8,000-10,000 spores for inhalation • Virulence depends on 2 factors – Capsule – 3 toxins
Capsule Non-toxic on its own Most important role during establishment of disease Protects against phagocytosis & lysis during vegetative state
Toxins Edema Factor
Protective Antigen
Lethal Factor
(89 Kd protein)
(83 Kd protein)
(90 Kd protein)
Edema Toxin Increased c-AMP Tissue edema
Lethal Toxin
Macrophage lysis Inhibit WBC phagocytosis
Release Tumor Necrosis Factor
Regulators of virulent factors • Bicarbonate or CO2 stimulates capsule and PA formation • LF requires zinc ions • EF requires calmodulin, a major intracellular calcium receptor
Pathogenesis
Three 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
Cutaneous Form The most common naturally occurring form of anthrax. Ulcers are usually 1-3 cm in diameter. Incubation period: Usually an immediate response up to 1 day Case fatality after 2 days of infection: Untreated (20%) With antimicrobial therapy (1%)
Differential Diagnosis of Cutaneous Form • • • • •
Spider bite Ecthyma gangrenosum Ulcer glandular tularemia Plague Staphylococcal or streptococcal cellulitis • Herpes simplex virus
Inhalation Anthrax •
The infection begins with the inhalation of the anthrax spore.
•
Spores need to be less than 5 microns (millionths of a meter) to reach the alveolus.
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Survived spores are transported to lymph nodes.
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At least 2,500 spores have to be inhaled to cause an infection.
Mediastinal Widening and Pleural Effusion on Chest X-Ray in Inhalational Anthrax
Mediastinal widening JAMA 1999;281:1735–1745
Differential Diagnosis of Inhalational Anthrax • Mycoplasmal pneumonia • Psittacosis • Tularemia • Q fever
• Viral pneumonia • Histoplasmosis (fibrous mediastinitis( • Coccidioidomycosis
Differential diagnosis
Gastrointestinal Form • GI anthrax may follow after the consumption of contaminated, poorly cooked meat. • There are 2 different forms of GI anthrax: 1) Oral-pharyngeal 2) Abdominal • Abdominal anthrax is more common than the oral-pharyngeal form.
GIT form
Terminal ileum/cecum most commonly site Hemorrhage Necrosis
Differential Diagnosis of Gastrointestinal Anthrax • • • •
Acute appendicitis Ruptured viscus Diverticulitis Diseases that cause acute cervical lymphadenitis or acute gastritis • Dysentery
Gram Stain Analysis
Macfadyean´s reaction
X-ray
At day 1 ď ŽFind a widened mediastinum and pleural effusion.
At day 3
CT scan
• • •
Useful for inhalation and GI anthrax Even when X-rays are negative, CT scans may provide more precise information. Chest CT (Right) shows the increase in the size of the pleural effusions (accumulation of fluid in the pleural space).
PCR
Bio- Seeq plus
Treatment
(Treatment (con’t
Prevention and Control •
Humans protected by preventing disease in animals :
− − − − −
Veterinary supervision Trade restrictions Burn or bury carcasses, bedding, other materials then add on them 5% quicklime Contra indicated to open the carcasses
• • • •
Remove organic material and disinfect structures Improved industry standards Safety practices in laboratories Post-exposure antibiotic prophylaxis
•
Insect control or repellants to prevent fly dispersal
Disinfection • Preliminary disinfection – 10% formaldehyde – 4% glutaraldehyde (pH 8.0-8.5(
• Cleaning – Hot water, scrubbing, protective clothing
• Final disinfection: one of the following – 10% formaldehyde – 4% glutaraldehyde (pH 8.0-8.5( – 3% hydrogen peroxide, – 1% peracetic acid
Vaccination • BioThrax/Anthrax vaccine absorbed •
Administered subcutaneously 0.5mL at 0, 2, and 4 weeks, and at 6, 12, & 18 months, & booster doses at 1 yr intervals
?Who gets it • People who work directly with it in the lab • People who work with imported animal hides or furs in areas where standards are insufficient to prevent exposure to anthrax spores. • People who handle potentially infected animal products in high-incidence areas • Military personnel deployed to areas with high risk for exposure to the organism.
Vaccine Side Effects • Injection site reactions – Mild: 30% men, 60% women – Moderate:1-5% – Large local:1%
• 5-35% experience systemic effects – Muscle or joint aches, headache, rash, chills, fever, nausea, loss of appetite, malaise
• No long-term side effects noted
Anthrax vs. Other BW Agents: Brief Overview Disease Inhalation anthrax Brucellosis
Transmit Man to Man No No
Infective Dose (Aerosol) 8,000-50,000 spores 10 -100 organisms
Incubation Period 1-6 days
Duration of Illness
Persistence of Organism
Vaccine Efficacy (aerosol exposure) 2 dose efficacy against up to 1,000 LD50 in monkeys No vaccine
<5% untreated
Very stable - spores remain viable for > 40 years in soil Very stable
> 1 week
Low with treatment, high without
Unstable in aerosols & fresh water; stable in salt water
No data on aerosol
Death in 7-10 days in septicemic form 1-6 days (usually fatal(
> 50%
Very stable
No vaccine
High unless treated within 12-24 hours
For up to 1 year in soil; 270 days in live tissue
2-10 days (average 3-5( 10-40 days
> 2 weeks 2-14 days
Moderate if untreated Very low
For months in moist soil or other media For months on wood and sand
3 doses not protective against 118 LD50 in monkeys 80% protection against 1-10 LD50 94% protection against 3,500 LD50 in guinea pigs Vaccine protects against large doses in primates
5-60 days (usually 1-2 months( 4 hours 5 days (usually 2-3 days( 10-14 days via aerosol 2-3 days
3-5 days (usually fatal if untreated( Weeks to months
Lethality (approx. case fatality rates) High
Cholera
Rare
10-500 organisms
Glanders
Low
Assumed low
Pneumonic Plague
High
100-500 organisms
Tularemia
No
10-50 organisms
Q Fever
Rare
1-10 organisms
Smallpox
High
7-17 days (average 12(
4 weeks
High to moderate
Very stable
Venezuelan Equine Encephalitis Viral Hemorrhagic Fevers Botulism
Low
Assumed low (10-100 organisms( 10-100 organisms
2-6 days
Days to weeks
Low
Relatively unstable
TC 83 protects against 30500 LD50 in hamsters
Moderate
1-10 organisms
4-21 days
Death between 7-16 days
Relatively unstable - depends on agent
No vaccine
No
0.001 µg/kg is LD50 for type A
1-5 days
For weeks in nonmoving water and food
Staph Enterotoxin B Ricin
No
0.03 µg/person incapacitation 3-5 µg/kg is LD50 in mice
3-12 hours after inhalation 18-24 hours
Death in 24-72 hours; lasts months if not lethal Hours
High for Zaire strain, moderate with Sudan High without respiratory support < 1%
Resistant to freezing
3 dose efficacy 100% against 25-250 LD50 in primates No vaccine
High
Stable
No vaccine
T-2 Mycotoxins
No
Moderate
2-4 hours
Moderate
For years at room temperature
No vaccine
No
Days - death within 10-12 days for ingestion Days to months
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