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ANTHRAX
Tropical Infectious Disease Division
Department of Internal Medicine
Faculty of Medicine Brawijaya University / Dr. Saiful Anwar GeneralHoapital
Malang
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Baci l lus anth racis
Gram + rod
Facultative anaerobe
1 - 1.2m in width x 3 - 5m inlength
Belongs to the B. cereusfamily
Thiamin growthrequirement
Glutamyl-polypeptide
capsule Nonmotile
Forms oval, central ly locatedendospores
http://www.bact.wisc.edu/Bact330/l
ectureanthrax
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Endospore Oxygen required for
sporulation
1 spore per cell
dehydrated cells
Highly resistantto h eat,
co ld, chemicaldisin fectants, dry per iod s
Protoplast carries the material
for future vegetative cell
Cortex provides heat and
radiation resistance Spore wall provides protection
from chemicals & enzymes http://www.gsbs.utmb.edu/microbook/ch0
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Where is Anthrax?
http://www.vetmed.lsu.edu/whocc/mp_world.htm
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Anthrax From the Greek word anthrakosfor coal Caused by spores
Primari ly a disease ofdom est icated & wi ld animals
Herbivores such as sheep, cows, horses, goats
Natural reservoir isso i l
Does not depend on an animal reservoir making it hardto eradicate
Cannot be regularly cultivated from soils where there isan absence of endemic anthrax
Anthrax zones Soil rich in organic matter (pH < 6.0)
Dramatic changes in climate
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Anthrax Infection & Spread May be spread by streams, insects, wild animals, birds,
contaminated wastes
Animals infected by soilborne spores in food & water or bitesfrom certain insects
Humans can be infected when in contact wi th f lesh, 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 inlivestock
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Three forms of Anthrax
Cutaneousanthrax
Skin
Most common
Spores enter to skin through small lesions
Inhalationanthrax
Spores are inhaled
Gastrointest inal(GI)anthrax
Spores are ingested
Oral-pharyngeal and abdominal
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Pathogenesis The infectious dose ofB.
anthracisin humans by anyroute 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 2factors
Capsule 3 toxins
http://www.kvarkadabra.net/index.html?/biologija/teksti/biolosko_orozje.htm
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Clinical Information
Infection
Symptoms (1st and 2nd phase)
Three forms of Anthrax infection and their
Pathology
Diagnosis
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Infection of Anthrax The estimated number of naturally occurring human cases of
anthrax in the world is 20,000 to 100,000 per year.
Humans are infected through contact with infected animals andtheir products because of human intervention.
Anthrax spores contaminate the ground when an affected animaldies and can live in the soil for many years.
Anthrax can also be spread by eating undercooked meat frominfected animals.
Anthrax is NOT transmitted from person to person.
Humans can be exposed but not be infected
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What are the symptoms for anthrax?
There are two phases of symptom.
1) Early phase - Many symptoms can occur within 7 days of
infection
2) 2nd phase - Will hit hard, and usually occurs within 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, abdominaldistress, 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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Three clinical forms of Anthrax
3 types of anthrax infection occur in humans:
1) Cutaneous
2) Inhalation
3) GI
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Cutaneous Anthrax 95% of anthrax infections occur
when the bacterium enters a cut or
scratch on the skin due to handling
of contaminated animal products
or infected animals.
May also be spread by biting
insects that have fed on infected
hosts.
After the spore germinates in skin
t issu es, toxin pro duc t ion ini t ial ly
resul ts in i tchy b ump that develops
into a vesicle and then painless
black ulcer.
http://science.howstuffworks.com/anthrax1.htm
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Cutaneous Anthrax (2)
The mo st common natural ly occurr ing form o f 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%)
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Cutaneous Anthrax (3)
CDC, Cutaneous AnthraxVesicle Development
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Inhalation Anthrax The infection begins with the
inhalation of the anthrax spore.
Spores need to be less than 5microns (millionths of a meter)to reach the alveolus.
Macrophages lyse and destroysome of the spores.
Survived spores aretransported to lymph nodes.
At least 2,500 spores have to beinhaled to cause an infection.
Inhalation Anthrax, Introduction, DRP, Armed Forces Institute of Pathology
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Inhalation Anthrax (2) Disease immediately follows
germination.
Spores replicate in the lymphnodes.
The two lungs are separated by astructure called the mediastinum,which contains the heart, trachea,esophagus, and blood vessels.
Bacter ial toxin s released dur in grepl icat ion result in mediast inalwidening and pleural ef fus ions(accumulat ion of f lu id in thepleu ral space).
Inhalation Anthrax, Introduction, DRP, Armed Forces Institute of Pathology
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Inhalation Anthrax (3) Death usually results 2-3 days after the onset of symptoms.
Natural infection is extremely rare (in the US, 20 cases werereported in last century).
Inhalat ion Anth rax is themo st lethal typeof Anthrax.
Incubation period:
17 days
Possibly ranging up to 42 days (depending on how manyspores were inhaled).
Case fatality after 2 days of infection:
Untreated (97%)
With antimicrobial therapy (75%)
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Gastrointestinal Anthrax
GI anthrax may follow afterthe consumption ofcontaminated, poorlycooked meat.
There are 2 different formsof GI anthrax:
1) Oral-pharyngeal
2) Abdominal
Abdominal anthrax is morecommon than the oral-pharyngeal form.
http://science.howstuffworks.com/anthrax1.htm
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GI Anthrax (2)
Oral-pharyngeal form - results from the deposition and
germination of spores in the upper gastrointestinal tract.
Local lumphadenopathy (an infection of the lymph glands
and lymph channels), edema, sepsis develop after an oralor esophageal ulcer.
Abdominal form - develops from the deposition and
germination of spores in the lower gastrointestinal tract,
which results in a primary intestinal lesion.
Symptoms such as abdominal pain and vomiting appear
within a few days after ingestion.
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GI Infection (3)
GI anthrax cases are uncommon.
There have been reported outbreaks in Zimbabwe, Africaand northern Thailand in the world.
GI anthrax has not been reported in the US.
Incubation period:
1-7 days
Case fatality at 2 days of infection: Untreated (25-60%)
With antimicrobial therapy (undefined) due to the rarity
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How is anthrax diagnosed?
Gram stain
Culture ofB. anthracisfrom the blood, skin lesions, vesicularfluid, 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 and immunoflourescence
examinations
- These are available only at certain labs
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Distinguishing inhalation Anthrax from
cold or influenza
Anthrax, cold, and influenza patients have similar symptoms at earlyphase such as flu-like symptoms (fever, chills, cough, and muscleaches etc.)
Symptoms o f Anthrax do not inc lude arunny nose, which is commonin cold and inf luenza .
Anthrax involves severe breath ing problems and more vomit ing.These symptom s are not very common in cold or inf luenza.
Anthrax have high white blood cell counts and no increase in thenumber of lymphocytes.
Flu usual ly have low wh i te blood cell cou nts and an inc rease in thenumber of lymphocy tes.
Inhalation anthrax has abnormality in X-ray or CT scan
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Treatment Before 2001, 1st line of
treatment was penicillin G Stopped for fear of
genetically engineeredresistant strains
60 day course of antibiotics
Ciprofloxacin
fluoroquinolone
500 mg tablet every 12h or400 mg IV every 12h
Inhibits DNA synthesis
Doxycycline
6-deoxy-tetracycline
100 mg tablet every 12h or100 mg IV every 12h
Inhibits protein synthesis
For inhalational, need anotherantimicrobial agent
clindamycin
rifampin
chloramphenico
http://nmhm.washingtondc.museum/new
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Treatment Penic i l lin and doxy cyc l ine
Intravenous administration
inhalational, gastrointestinal, and
meningeal anthrax
Cutaneous anthrax with signs of systemicinvolvement
Cutaneous anthrax:oral penicillin
Chloramphenicol, erythromycin, tetracycline,or ciprofloxacin (allergic to penicillin)
Doxycycline and tetracycline :not for pregnant
women or children
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Treatment
IV penicillin G :4 million units every 4 to 6 hrs
continued for 7 to 10 ds
Streptomycin had a synergistic effect with penicillin in
experiments
Ciprofloxacin :400 mg iv every 8 to 12 hrs
Doxycycline :200 mg iv then 100 mg iv every 8 ~12 hrs
Prophylaxis:Ciprofloxacin 500 mg or Doxycycline 100
mg by mouth twice a dayfor at least 6 wks Systemic corticosteroids for cervical edema and
meningitis
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"anthrax vaccine adsorbed" (AVA)
aluminum hydroxide-precipitated preparation of
protective antigen from attenuated, nonencapsulated
B. anthracis cultures of the Sterne strain
AVA :subcutaneously 0.5-ml dose ,repeated at 2
and 4 wks and at 6, 12, and 18 months
Boosters are then given annually
Decontamination :
vaporized formaldehyde
formaldehyde in seawater
Autoclaving and incineration
From N Engl J Med . 341(11):815-26, 1999 Sep 9
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Potential Biological Warfare Agent
US military's current M17 and M40 gas masks
provide excellent protection against the 1- to 5-
micrometers particulates needed for a successful
aerosol attack
preexposure useof the current AVA anthrax vaccine postexposure antibiotic prophylaxis
doxycycline plus postexposure vaccination survived a
lethal aerosol challenge
From Archives of Internal Medicine 158(5):429-34 1998 Mar 9