Anthrax: Didi Candradikusuma

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ANTHRAX

DIDI CANDRADIKUSUMA
DIVISI PENYAKIT TROPIK INFEKSI
LAB/SMF ILMU PENYAKIT DALAM
FKUB - RSSA

History
Bio Terrorism

Sverdlovsk, Russia, 1979

94 people sick 64 died


Soviets blamed contaminated meat
Denied link to biological weapons
1992
Soviet President Yeltsin admits outbreak
related to military facility
Western scientists find victim clusters
downwind from facility

Caused by faulty exhaust filter


Center for Food Security and Public
Health, Iowa State University, 2008

South Africa, 1978-1980


Anthrax used by Rhodesian and
South African apartheid forces
Thousands of cattle died
10,738 human cases
182 known deaths
Black Tribal lands only
White populations untouched

Center for Food Security and Public


Health, Iowa State University, 2008

Aum Shinrikyo
Japanese religious cult
Supreme truth

1993
Unsuccessful attempts
at biological terrorism
Released anthrax from office building
Vaccine strain used not toxic

No human injuries

Successful attempt in 1995


Sarin gas release in Tokyo subway
1,000 injured 12 deaths
Center for Food Security and Public
Health, Iowa State University, 2008

2001 Anthrax Letters

Center for Food Security and Public


Health, Iowa State University, 2008

Center for Food Security and Public


Health, Iowa State University, 2008

Anthrax
From the Greek word anthrakos for coal
Caused by spores
Primarily a disease of domesticated & wild
animals
Herbivores such as sheep, cows, horses, goats
Natural reservoir is soil
Does not depend on an animal reservoir
making it hard to eradicate
Cannot be regularly cultivated from soils
where there is an absence of endemic anthrax
Anthrax zones
Soil rich in organic matter (pH < 6.0)
Dramatic changes in climate

Anthrax Infection & Spread


May be spread by streams, insects, wild animals,
birds, contaminated wastes
Animals infected by soilborne 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

Where is Anthrax?

http://www.vetmed.lsu.edu/whocc/mp_world.htm

Bacillus anthracis

Gram + rod

Facultative anaerobe

1 - 1.2m in width x 3 - 5m
in length

Belongs to the B. cereus


family
Thiamin growth
requirement
Glutamyl-polypeptide
capsule
Nonmotile

Forms oval, centrally located


endospores

http://www.bact.wisc.edu/Bact
330/lectureanthrax

Endospore

Oxygen required for


sporulation
1 spore per cell
dehydrated cells
Highly resistant to heat,
cold, chemical
disinfectants, dry periods
Protoplast carries the material
for future vegetative cell
http://www.gsbs.utmb.edu/microbook/ch01
Cortex provides heat and
radiation resistance
Spore wall provides protection
from chemicals & enzymes

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
http://www.kvarkadabra.net/index.html?/biologija/teksti/biolosko
_orozje.htm

M. Mock, A. Fouet, Annu. Rev.


Microbiol. 55: 647-671 (2001)

B. Anthracis cycle

M. Mourez et al. Trends


Microbiol. 10:287-293
(2002)

So, How Does It Kill Us?

Clinical Information
Infection
Symptoms (1st and 2nd phase)
Three forms of Anthrax infection
and their Pathology
Diagnosis

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 and their products because
of human intervention.
Anthrax spores contaminate the ground
when an affected animal dies and can live
in the soil for many years.

Infection of Anthrax
Anthrax can also be spread by eating
undercooked meat from infected animals.
Anthrax is NOT transmitted from person to
person.
Humans can be exposed but not be
infected.

Symptoms for anthrax


There are two phases of symptom
Early phase
Many symptoms can occur within 7 days
of infection
2nd phase
Will hit hard, and usually occurs within 2 or
3 days after the early phase.

Early Phase Symptoms


Fever (temperature > 38 degrees C)
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

2nd Phase Symptoms

Breathing problems, pneumonia


Shock
Swollen lymph glands
Profuse sweating
Cyanosis (skin turns blue)
Death

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 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 tissues, toxin production
initially results in itchy bump that
develops into a vesicle and then
painless black ulcer.

http://science.howstuffworks.com/anthrax1.htm

Cutaneous Anthrax
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%)

Cutaneous Anthrax

CDC, Cutaneous AnthraxVesicle Development

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.
Macrophages lyse and destroy
some of the spores.
Survived spores are
transported to lymph nodes.
At least 2,500 spores have to
be inhaled to cause an
infection.

Inhalation Anthrax, Introduction, DRP, Armed Forces Institute of


Pathology

Inhalation Anthrax
Disease immediately follows
germination.
Spores replicate in the lymph
nodes.
The two lungs are separated
by a structure called the
mediastinum, which contains
the heart, trachea,
esophagus, and blood
vessels.
Bacterial toxins released
during replication result in
mediastinal widening and
pleural effusions
(accumulation of fluid in the
Inhalation Anthrax, Introduction, DRP, Armed
Forces
Institute of
pleural
space).
Pathology

Inhalation Anthrax
Death usually results 2-3 days after the onset of
symptoms.
Natural infection is extremely rare (in the US, 20
cases were reported in last century).
Inhalation Anthrax is the most lethal type of
Anthrax.
Incubation period:
17 days
Possibly ranging up to 42 days (depending on
how many spores were inhaled).
Case fatality after 2 days of infection:
Untreated (97%)
With antimicrobial therapy (75%)

Gastrointestinal Anthrax
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.
http://science.howstuffworks.com/anthrax1.htm

GastrointestinaI Anthrax
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 oral or 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.

Gastrointestinal Anthrax
GI anthrax cases are uncommon.
There have been reported outbreaks in Zimbabwe, Africa
and 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

Diagnosis
Gram stain
Culture of B. anthracis from the blood, skin
lesions, 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 and
immunoflourescence examinations
- These are available only at certain labs

Treatment
Before 2001, 1st line of
treatment was penicillin G
Stopped for fear of
genetically engineered
resistant strains
60 day course of antibiotics
Ciprofloxacin
fluoroquinolone
500 mg tablet every 12h
or 400 mg IV every 12h
Inhibits DNA synthesis

Treatment
Doxycycline
6-deoxy-tetracycline
100 mg tablet every
12h or 100 mg IV
every 12h
Inhibits protein
synthesis
For inhalational, need
another antimicrobial
agent
clindamycin
rifampin
chloramphenicol

Treatment
Penicillin and doxycycline
Intravenous administration
inhalational, gastrointestinal, and meningeal anthrax
Cutaneous anthrax with signs of systemic
involvement
Cutaneous anthrax: oral penicillin
Chloramphenicol, erythromycin, tetracycline, or
ciprofloxacin (allergic to penicillin)
Doxycycline and tetracycline :not for pregnant women
or children

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 day for at least 6 wks
Systemic corticosteroids for cervical edema and
meningitis

"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

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 use of 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

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