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Anthrax and ts prevention

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 Anthrax  NABEELA RAUF  BY
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 Anthrax 

 NABEELA RAUF  

BY

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OVERVIEW

Definition Problem statement

History

Epidemiology

Pathogenesis of anthrax Types/Forms of anthrax

Symptoms Of Anthrax

Diagnosis Of Anthrax

Treatment Prevention and control of anthrax

Weaponizing anthrax

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Definition

 Anthrax is an acute bacterial

infection of animals

transmissible to man.

It is also known as Malignant Pustule, Malignant Edema,Woolsorters’ Disease,

Ragpickers’ Disease, Maladi 

Charbon, Splenic Fever 

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Problem statement

True incidence not known

World 20,000-100,000 in 1958

U.S. 235 total reported cases

1955-1994

18 cases inhalational since 1900, last

one 1976

Until 2001, last previous casecutaneous 1992

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Mortality

Inhalational 86-100% (despite

treatment) Era of crude intensive supportive

care

Cutaneous <5% (treated) – 20%

(untreated)

GI approaches 100%

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Milestones in Anthrax History

Early history

1800s

1900s

Recent years

Outbreaks in Thailand and US

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History of Anthrax (Early history)

Although anthrax dates back more than 3,000years, it was not recognized as a diseaseuntil the 18th century.

1500 B.C - A “plague of boils” in Egyptaffected the Pharaoh‟s cattle. „Boils‟ aresymptomatic of anthrax.

1600s - The “Black Bane” thought to beanthrax, in Europe kills over 60,000 cattle.

1700s - There are some accounts of humancases.

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History (1800s)

Early 1800s - The first human cases ofcutaneous anthrax in the US and UKwere reported in men who contractedthe disease after having been in contactwith infected livestock.

The disease was called Wool Sorter‟sdisease or Rag Picker‟s diseasebecause it affected workers in thosetrades.

1868 - Anthrax was observed under amicroscope.

1876 - German bacteriologist RobertKoch confirmed bacterial origin ofanthrax.

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History (1800s)

Early 1800s - The first human cases ofcutaneous anthrax in the US and UKwere reported in men who contractedthe disease after having been in contactwith infected livestock.

The disease was called Wool Sorter‟sdisease or Rag Picker‟s diseasebecause it affected workers in thosetrades.

1868 - Anthrax was observed under amicroscope.

1876 - German bacteriologist RobertKoch confirmed bacterial origin ofanthrax.

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History (Late 1900s) 1950s and 60s - U.S. biological warfare

program continues after WWII at Fort

Detrick, Maryland

1969 - President Nixon ended United States'offensive biological weapons program, butdefensive work still continues.

1970 - Anthrax vaccine for humans wasapproved by U.S. FDA.

1978-80 - The world's largest outbreak ofhuman anthrax via insect vectors orcontaminated meat struck Zimbabwe, Africa where more than 10,000 cases wererecorded and over 180 people died.

1979 - In Soviet Union, aerosolized anthraxspores were released accidentally at amilitary facility, affecting 94 and killing 64people.

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History (Recent years)

1991 - About 150,000 U.S. troops werevaccinated for anthrax in preparation for GulfWar.

1990-93 - The cult group, Aum Shinrikyo,released anthrax spores in Tokyo, fortunately noone was injured. On February 27, 2004, theleader of this group was given a sentence ofdeath at a district court in Tokyo.

1995 - Iraq produced 8,500 liters of concentratedanthrax as part of the biological weaponprogram under Saddam Hussein‟s administration.

2001 - Letters containing anthrax spores weremailed to many places in the US such as NBC,New York Times, and Media in Miami. In Florida,a man died after inhaling anthrax at the office.

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Epidemiology

Epidemological triangle

 Agent factors

Host factorsEnvoirnmental & social

factors

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 Agent factors

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 Agent

Bacillus anthracis.

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Reservoir of infection

Infected cattle

Sheep

Goats horses

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Source of infection

Tissue

Skin

Hides Hairs

Whool of animals dying of 

anthrax

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HOST FACTORS

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 AGE ,SEX, IMUNITY

 All ages and genders affected

Occurs worldwide

Endemic areas - Africa, Asia

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ENVIRONMENTAL & SOCIALFACTORS

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INCUBATION PERIOD

Time from exposure to symptoms

Very variable for inhalational

2-43 days reported

Theoretically may be up to 100 days

Delayed germination of spores

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TRANSMISSION

No human-to-human

Naturally occurring cases Skin exposure

Ingestion

 Airborne

Bioterrorism Aerosol (likely)

Small volume powder (possible)

Foodborne (unlikely)

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INHALATIONAL ANTHRAX

Handling hides/skins of infected

animals

Microbiology laboratory

Intentional aerosol release

Small volume powdered form

In letters, packages, etcQuestionable risk, probably

small

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CUTANEOUS ANTHRAX

Handling hides/skins of infectedanimals

Bites from arthropods (veryrare)

Handling powdered form inletters, etc.

Intentional aerosol releaseMay see some cutaneous if 

large-scale

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GASTROINTESTINAL

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GASTROINTESTINAL

 ANTHRAX

Ingestion of meat from infected animal Ingestion of intentionally contaminated

food

Not likely in large scale

Spores not as viable in large volumes

of water 

Ingestion from powder-contaminated

hands Inhalational of spores on particles >5 m

Land in oropharynx

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Mechanism of Infection

Anthrax spores enter body Germinate & multiple in lymph nodes PA, EF, LF excreted from bacteria PA binds to TEM8. PA nicked by protease furin

20-kDa segment off leaving 63-kDapeptide

Heptamer forms EF and/or LF binds Complex internalized by endocytosis Acidification of endosome LF or EF crosses into cytosol via PA

mediated ion-conductive channels LF cleaves MAPKK 1 & 2

EF stimulates cAMP

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Pathogenesis

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TYPES OF ANTHRAX

INHALATIONAL ANTHRAX

CUTANEOUS ANTHRAX

GASTROINTESTINAL ANTHRAX

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Inhalation Anthrax

Disease immediately followsgermination.

Spores replicate in the lymphnodes.

The two lungs are separatedby a structure called themediastinum, which containsthe heart, trachea, esophagusand blood vessels.

Bacterial toxins releasedduring replication result inmediastinal widening andpleural effusions(accumulation of fluid in thepleural space).

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Cutaneous Anthrax

95% of anthrax infectionsoccur when the bacteriumenters a cut or scratch onthe skin due to handling ofcontaminated animalproducts or infectedanimals.

May also be spread bybiting insects that have fedon infected hosts.

After the spore germinatesin skin tissues, toxinproduction initially resultsin itchy bump thatdevelops into a vesicle andthen painless black ulcer.

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Gastrointestinal Anthrax

GI anthrax may follow

after the consumptionof contaminated,poorly cooked meat.

There are 2 different

forms of GI anthrax:1) Oral-pharyngeal2) Abdominal

Abdominal anthrax ismore common thanthe oral-pharyngealform.

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SYMPYOMS OF ANTHRAX

There are two phases of symptom.

1) Early phase - Many symptoms can occurwithin 7 days of

infection

2) 2nd phase - Will hit hard, and usually occurswithin 2 or 3

days after the early phase.

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- Early Phase Symptoms - 

Fever (temperature > 100 degrees 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

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- 2nd Phase Symptoms -

Breathing problems, pneumonia

Shock

Swollen lymph glands

Profuse sweating

Cyanosis (skin turns blue)

Death

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Diagnosis Of Anthrax

Gram stain

Culture of B. anthracis from the blood, skinlesions, 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 andimmunoflourescence

examinations- These are available only at certain labs

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Treatment

Empiric Therapy Children

Ciprofloxacin 10-15 mg/kg/d IV q12°, max

1 g/d ORDoxycycline 2.2 mg/kg IV q12° 

(adult dosage if >8 yo and >45 kg)

 Add one or two antibiotics for inhalational

Weigh risks (arthropathy, dental enamel)

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Pregnant women

Same as other adults

Weigh small risks (fetal arthropathy)vs benefit

Immunosuppressed

same as other adults

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 Alternative antibiotics

If susceptible, or cipro/doxy notpossible

Penicillin*, amoxicillin *FDA Approved

Gentamicin, streptomycin

Erythromycin, chloramphenicol

Ineffective antibiotics

Trimethoprim/Sulfamethoxazole

Third generation cephalosporins

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Susceptibility testing should be

done Narrow antibiotic if possible

Must be cautious

Multiple strains with engineeredresistance to different antibiotics may

be coinfecting

Watch for clinical response after 

switching antibiotic

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 Antibiotic therapy

Duration

60 days Risk of delayed spore germination

Vaccine availability

Could reduce to 30-45 days therapy

Stop antibiotics after 3rd vaccine dose

Switch to oral Clinical improvement

Patient able to tolerate oral medications

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Other therapies

Passive immunization

 Anthrax immunoglobulin from horseserum

Risk of serum sickness

 Antitoxin

Mutated Protective Antigen Blocks cell entry of toxin

Still immunogenic, could be an

alternative vaccine

 Animal models promising

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Postexposure Prophylaxis

Who should receive PEP?

 Anyone exposed to anthrax

Not for contacts of cases,unless also exposed

Empiric antibiotic therapy

Vaccination

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Postexposure Prophylaxis

 Avoid unnecessary antibiotic usage

Potential shortages of those who needthem

Potential adverse effects Hypersensitivity

Neurological side effects, especiallyelderly

Bone/cartilage disease in children

Oral contraceptive failure

Future antibiotic resistance Individual’s own flora 

Community resistance patterns

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Postexposure Prophylaxis

 Antibiotic therapy

Treat ASAP

Prompt therapy can improve survival

Continue for 60 days

30-45 days if vaccine administered

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Postexposure Prophylaxis

 Antibiotic therapy

Same regimen as active treatment

Substituting oral equivalent for IV

Ciprofloxacin 500 mg po bidempirically

 Alternatives

Doxycycline 100 mg po bid

 Amoxicillin 500 mg po tid

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Postexposure Prophylaxis

 Antibiotic therapy

Children

Same dose adjustments as treatment

Weigh benefits vs. risks

Recommended switch if PCN-

susceptible

 Amoxicillin 80 mg/kg/day, max 500 mg

tid

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Methods of control

&

Prevention

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1.Preventive measures

Isolation & treatment of infected animals.

Carcases of animals dying of anthraxshould be burnt or burried 6 feet deep withlime.

 A dead or living animal suffring fromanthrax should not be bled or opened,for the bacilli do not produce spores except inthe presence of oxygen.

Vaccination of animals with an alum

precipitated protective antigen Control of effluents & trade wastes of 

factories that handle wool,hides,hairs of animals,these effluents should be properly

treated before discharge into streams.

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Cont..

Health education of industrial workershandling potentially contaminated material,they should wear gloves.

Prompt medical care of all skin lesions of 

workers dealing with animal tissues andhides.

Dust control and proper ventillation to carryoff the dust where wool and hair arehandled.

If there is an out break in in a dairyherd,quarantine the herd for a10 days after the appearance of last case.during thisperiod there milk should not be used.

Immunization.

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Cont..

Disinfection;anthrax spores arevery resistant.steam disinfectionis practicable for hair;wool may

be disinfected by formaldehyde& hides by binchloride of mercury,formic acid or hcl

Hair used for shaving brushes

should be disinfected by boilingfor 3 hrs,by exposure tosaturated steam for 30 min or by

dry heat at 200T for 24 hrs.

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Duckering process

Most reliable method for disinfection of wool;it isdone in 4 stages.

1.the wool is soaked insoap water solutioncontaining some alkali at 102f and thoroughly mixedwith rakes.this process cleans the wooland renders

the spores of anthrax susceptible to disinfection. The material is thoroughly mixed with 21/2%

formalin solution for 30 min.formalin destroys thespores.

 At this stage the wool or the material to be treated isdried in current of air at 106f.this drying further 

destroys the spores if any. The wool is then cooled by a current of air,where it

is kept for several days to ensure completedestruction of spores

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Control ofof infected

persons,contacts,&envoirnment

Notify to local health authority. Isolate till the lesions are healed.

Concurrent disinfection,steamsterilization of burning of all

contaminated articles. Terminal disinfection.

Quarantine;none.

Immunization.

Investigation of contacts and sourceof infection hx of exposure toinfected animals.

Treatment;penciline/tetracyclines.

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Epidemic measures

Trace source of infection and

remove it.

In

animals;vaccination,treatment,isolation,sterilization of animal

products.

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International measures

Sterilization of imported animal

feed,of hair used for shaving

brushes,animal hairs,hides and

wool before being handled byworkers

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Vaccination

Cell-free filtrate

Licensed in 1970

 At risk

Wool mill workers

Veterinarians

Lab workers

Livestock handlers

Military personnel

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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

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Vaccine Schedule

3 injections at two-weekintervals

3 injections 6 months apart

 Annual booster 

Weaponizing Anthrax:

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p gHow is it made? 

What Type of Anthrax to Use? Inhalational (lungs)

Incredibly Lethal (untreated death rate >90%)

Facile attack methods (silent, flu-like, spray dispersible, e

Cutaneous (skin) Not near as lethal (untreated death rate ~20%)

More difficult to administer (need cut or abrasion)

Gastrointestinal (intestines)

Somewhat lethal (untreated death rate ~25-60%)

More difficult to administer (one has to consume anthrax) Best Type of Anthrax for Use as Weapon:

INHALATIONAL 

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