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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