anthrax

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

1965

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1975

1980

1985

1990

1995

2000

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

•

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.

•

Survived spores are transported to lymph nodes.

•

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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