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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