Medical community

Anthrax

Done by :Nuha Abd Al-Rahman

College of medicine
4th stage
Supervised by :Dr.Ameel Faroq

1
2
o Introduction
o History
o Epidemiology
o Causative organism
o Transmission
o Clinical manifestation
o Management
o Prevention and control

Other names:
• Malignant pustule
• Malignant edema
•Woolsorter's disease
•Ragpicker's disease

3
Etiology
Anthrax results from infection by Bacillus anthracis, a
spore forming, Gram positive aerobic rod in the
family Bacillaceae.Fully virulent B. anthracis isolates
have two plasmids: pX01, which codes for a tripartite
protein exotoxin complex, and pX02, which encodes
the capsule genes. B. anthracis is a member of the
Bacillus cereus sensu lato group, which also contains
the closely related organisms B. cereus and Bacillus
thuringiensis, as well as a few other species. A few
B. cereus isolates that contain plasmids closely
related to pX01 have caused anthrax-like diseases.
Isolates that carry both pX01 and pX02-like plasmids
have been termed Bacillus cereus biovar anthracis.
Studies suggest that this organism may be as
virulent as B. anthracis. B. cereus that have only a
pX01-like plasmid, but can produce a capsule with
other genes, can also cause similar illnesses.

4
●History of Anthrax (Early history)
Although anthrax dates back more than 3,000
years,it was not recognized as a disease until the 18th
century.
●1500 B.C- A "plague of boils" in Egypt affected the
pharaoh's cattle .boils are symptomatic of anthrax
● 1600s- The "Black Bane" thought to be anthrax, in
Europe kills over 60,000 cattle
●1700s-There are some accounts of human cases .

History (1800s)
● Early 1800s - The first human cases of cutaneous
anthrax in the US and UK were reported in men who
contracted the disease after having been in contact
with infected livestock.
●The disease was called Wool Sorter's disease or Rag
Picker's disease because it affected workers in those
trades.
● 1868 - Anthrax was observed under a microscope.
●1876 - German bacteriologist Robert Koch
confirmed origin of anthrax.

5
History (Early 1900s)
●1915 - German agents injected horses, mules, and
cattle with anthrax . This was the first recorded use
of anthrax as a biological weapon.
●1937 - Japan started a biological warfare program
in Manchuria, including tests involving anthrax.
● 1942 - UK demonstrated experiments using
anthrax at Gruinard Island off the coast of Scotland.
●1943 - United States began developing anthrax
weapons.
●1945 - In Iran an anthrax outbreak killed more than
1million sheep.

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, but defensive
work still continues.
●1970 - Anthrax vaccine for humans was approved
by U.S.FDA.
●1978-80 - The world's largest outbreak of human
anthrax via insect vectors or contaminated meat
struck Zimbabwe, Africa where more than 10,000
cases were recorded and over 180 people died.
●1979 - In Soviet Union, aerosolized anthrax spores
were released accidentally at a military facility,
affecting 94 and killing 64 people.

6
History (Recent years)
● 1991 - About 150,000 U.S. troops were vaccinated
for anthrax in preparation for Gulf War.
● 1990-93 - The cult group, Aum Shinrikyo, released
anthrax spores in Tokyo, fortunately no one was
injured.On February 27, 2004, the leader of this
group was given a sentence of death at a district
court in Tokyo.
● 1995 - Iraq produced 8,500 liters of concentrated
anthrax as part of the biological weapon program
under Saddam Hussein's administration.
●2001 - Letters containing anthrax spores were
mailed 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.

Epidemiology
●Distribution worldwide
● Not common in West. Common in Africa (
Zimbabwe), S.E. Asia, China, South America, Turkey,
Pakistan, India
●Human to human or animal to animal transmission
is rare (not contagious)
●Grazing animals become infected through ingestion
of spores in the soil ( Carcasses become the source).

7
STAGES OF INFECTION
• Encounter: organism and body surfaces
● Adhesion: generalized and receptor-specific
●Initial multiplication → in situ colonization
●Invasión → breaching of anatomic barriers
● Lymphatic stage invasion of bloodstream
●Generalized infection, metastases.

Transmission:
●Contact with tissues of animals (cattle, sheep,
goats,horses, pigs and others) dying of the disease.
● Biting flies that have partially fed on such animals.
●Contact with contaminated hair, wool, hides or
products made from them (e.g. drums, brushes,
rugs).
● Contact with soil associated with infected animals
or with contaminated bone meal used in gardening.
● Inhalation anthrax results from inhalation of
spores in risky industrial processes—such as tanning
hides and processing wool or bone- with aerosols of
B. anthracis spores in an enclosed, poorly-ventilated
area.
● Intestinal and oropharyngeal anthrax may arise
from ingestion of contaminated undercooked meat;
there is no evidence that milk from infected animals
transmits anthrax.

8
●The disease spreads among grazing animals
through contaminated soil and feed; and among
omnivorous and carnivorous animalsvthrough
contaminated meat, bone meal or other feeds
derived from infected carcases.
● Accidental infections may occur among laboratory
workers..
●Anthrax is not transmitted person to person.
●Articles and soil contaminated with spores in
endemic areas may remain infective for many years.

Incubation Period
The reported incubation period for cutaneous
anthrax ranges from one to 20 days, but most
clinical cases tend to develop within 7-10 days.
Gastrointestinal anthrax has been seen 1-7 days
after exposure, and injectional anthrax after 1-10
days. However, most cases of injectional anthrax
occurred very soon after inoculation. The incubation
period for inhalational anthrax is highly variable.
While it was estimated to be 2-6 days in a limited
number of cases, spores may remain viable in the
lungs for several weeks (up to 100 days in nonhuman
primate models), and these spores can germinate
and cause inhalational anthrax during that time.
After one accidental release of aerosolized spores in
the Soviet Union, cases continued to appear in
exposed people for up to 6 week .

9
Clinical Signs
Four forms of disease are seen in humans:
cutaneous anthrax, injectional anthrax,
gastrointestinal anthrax and inhalational anthrax.
Any of these forms can develop into life-threatening
septicemia or anthrax meningitis, but the frequency
differs. Presumed anthrax sepsis has been reported
in a newborn, and preterm labor was seen in some
women with anthrax.

Cutaneous anthrax
Cutaneous anthrax initially appears as a papule,
which may become surrounded by small fluid-filled
vesicles that release clear or sanguineous discharge.
The central papule quickly forms a vesicle or bulla,
ulcerates, dries and develops into an eschar, which
appears as a firmly adherent, depressed black scab.
The satellite vesicles may also form ulcers.
Cutaneous anthrax lesions are usually painless, but
they are typically surrounded by significant edema,
and may be accompanied by regional
lymphadenopathy. Lesions on the eyelids are
edematous, but a central black eschar is occasionally
absent. An uncommon bullous form of cutaneous
anthrax has also been described. It appears as a
group of vesicles or bullae, which become
hemorrhagic and necrotic. Coinfections with other
organisms, including dermatophytes, can result in
cutaneous anthrax cases with an atypica
appearance. Pus is not usually seen in anthrax
lesions unless they are secondarily infected. Low

10
grade fever, malaise and headache may be apparent
in more severe cases. Swelling on the face or neck
can result in occlusion of the airways.Cutaneous
anthrax often resolves spontaneously; however, the
organisms can sometimes disseminate and cause
life-threatening illnesses including septicemia and
meningitis. Face and neck lesions are more likely to
spread to the CNS than lesions in other parts of the
body.Resolution of uncomplicated cutaneous
anthrax may take weeks, even when the infection
has been successfully treated with antibiotics. Small
lesions usually heal with minimal scarring, but large
lesions can leave significant damage. If the eyelids
are affected, even smaller lesions may result in
complications such as entropion.

Injectional anthrax
Injectional anthrax results from the subcutaneous
inoculation of B. anthracis. The cases reported to
date have mostly been associated with

11
contaminated heroin. Extensive soft tissue swelling
or edema was the most commonly reported sign,
although it was not invariably present. Some
patients also had erythema, pain, and vesicles or
necrotic areas on the skin; however, the classical
eschars of cutaneous anthrax were usually absent,
and the pain or discomfort often appeared
disproportionately mild in relation to the clinical
signs. Unusual presentations were also seen. For
instance, one case resembled impetigo.
Debridement of the lesions sometimes resulted in
disproportionate bleeding, requiring massive
transfusions in some cases. Systemic signs in some
cases included fever and/or gastrointestinal signs
such as nausea, vomiting and abdominal pain. Two
people developed peritonitis after injecting
contaminated heroin into the groin. Some cases
progressed to sepsis, pulmonary signs and
meningitis.

12
 Gastrointestinal (including oropharyngeal)anthrax
Gastrointestinal anthrax usually develops after
eating contaminated, undercooked animal tissues
including meat. Germinating spores can cause
inflammation wherever they localize, and may, in
severe cases, result in hemorrhages, obstruction or
perforation. While any part of the gastrointestinal
tract can be affected, the ileum and colon are often
involved in the abdominal form, while oropharyngeal
anthrax is characterized by clinical signs localized to
that region. The initial symptoms of the abdominal
form may be mild and can include malaise, a low
fever and mild gastrointestinal signs such as nausea,
vomiting, diarrhea and anorexia. In some cases, this
is followed by the acute onset of severe abdominal
pain, hematemesis and bloody diarrhea. Massive
ascites may be present. Some patients have a high
fever. There may also be dyspnea, cyanosis,
disorientation and other signs of septicemia.
Meningitis is also possible. Severe cases progress
rapidly to shock, coma and death. However,
abdominal anthrax may not always be severe. In one
outbreak in Thailand, 7 of 74 people with
gastrointestinal anthrax had severe symptoms, but
acute diarrhea was the only sign in the others.The
initial symptoms in the oropharyngeal form can
include fever, a sore throat, dysphagia, hoarseness,
and swelling of the neck from edema and cervical
lymphadenopathy. Neck swelling can result in airway
compromise. Lesions may seen on the mucosa of the
oropharyngeal region, including on the

13
tonsils,pharynx and hard palate. In one report, these
lesions initially appeared as areas of edema and
congestion. A central whitish area, caused by
necrosis and ulceration, developed by the end of the
first week. During the second week, a
pseudomembrane formed over the ulcer.

Inhalational anthrax
Inhalational anthrax occurs after inhaling spores. The
symptoms are nonspecific and may develop
gradually. Early, vague signs can include fever, chills,
tiredness and malaise, as well as a nonproductive
cough and mild chest pain in some cases. These
symptoms sometimes improve for several hours to a
few days; however, this prodromal period ends with
the acute onset of severe respiratory distress,
tachycardia, diaphoresis, stridor and cyanosis,
followed by fatal septicemia and shock within a day
or two. Hematogenous spread of B. anthracis after

14
inhalation can cause gastrointestinal lesions and
signs.

Anthrax meningitis
Anthrax meningitis can be a complication of any of
the other four forms of disease. After a prodromal
period of 1-6 days, typical signs of
meningoencephalitis develop rapidly. Patients
quickly lose consciousness and die, many within 24
hours. Blood is often found in the cerebrospinal
fluid.

15
Bacillus cereus carrying anthrax-like plasmids
B. cereus isolates have caused a few cases of life-
threatening, anthrax-like pulmonary disease, as well
as syndromes that resembled cutaneous anthrax.

Diagnostic Tests
Anthrax can be diagnosed by observing typical
organisms in stained clinical samples, by PCR, and by
isolating B. anthracis in culture, as in animals.
Immunohistochemistry may be available in
reference laboratories. A wide variety of clinical
samples can be collected, depending on the form of
the illness. They may include blood, fluid from skin
lesions, aspirates of lymph nodes or the spleen,
ascitic fluid, respiratory secretions, pleural fluid,
cerebrospinal fluid (in cases of meningitis), vomitus
and feces. As in animals, antibiotic treatment may
prevent isolation of the organism.Antibodies
develop late in the course of the disease, and
serology (ELISAs or other assays) is only useful for
retrospective diagnosis. Both acute and convalescent
sera
should be taken. Some patients with cutaneous
anthrax may not become seropositive. A skin
hypersensitivity test using anthraxin (AnthraxinT) is

16
used to help diagnose anthrax in some countries. It
may be helpful when a case cannot be confirmed by
bacteriology and/or serology, and it can also be
employed for retrospective diagnosis.

17
18
Treatment
Anthrax is treated with antibiotics. Naturally-
occurring strains of B. anthracis are usually
susceptible to penicillin and some other
antimicrobials. Strains used in bioterrorist attacks
are more likely to be antibiotic resistant. Guidelines
in developed countries often recommend that
antibiotics other than penicillin be used initially,
particularly for systemic disease, until the
susceptibility of the isolate has been determined.
However, penicillin is employed successfully in some
countries, especially in cases of cutaneous anthrax.
Early antibiotic treatment in a systemic illness
significantly increases the probability that the
patient will survive. Antibiotics are effective only
against the vegetative stage of B. anthracis, and do
not destroy the spores. Treatment for at least 60
days has been recommended in inhalational anthrax,
as spores might remain dormant in the lungs and
germinate during that time. A few recent
experiments in animal models have questioned
whether continued treatment is necessary once
immunity develops to B. anthracis, but until more
definitive evidence is available, most sources
continue to recommend 60 days for this form. Other
types of anthrax are usually treated for much shorter
periods, as residual spores are not a concern.Anthrax
toxins can cause damage even after the bacteria
have been eliminated. Recently developed antitoxins
seem to improve survival in animal models,

19
especially when treatment is delayed. These
antitoxins have
been recommended for systemic anthrax, and they
have also been used in some cases of injectional
anthrax. In most countries, clinical experience with
these agents is currently limited. However, older
antitoxins have been used more extensively in some
nations, such as Russia. Symptomatic and supportive
therapy may also be necessary in some anthrax
cases.
Guidelines for the treatment of anthrax, including
guidelines specifically for children, have been
published.

Control
People normally acquire anthrax from infected
animals or their tissues; thus, humans can be
protected by preventing animals from getting
anthrax. Veterinary supervision of animal slaughter
acts as an additional safeguard. In some cases, trade
restrictions may be placed on certain animal
products from countries where anthrax is common

20
and uncontrolled. Improvements in industry
standards have reduced occupational exposure for
people exposed to hides, wool, bone meal and other
anima products. However, low levels of
contamination are still reported in some facilities,
even in areas where anthrax is not endemic. The use
of face masks seems to significantly reduce exposure
among people who procees contaminated wool and
goat hair. In laboratories, good safety practices,
including the use of biological safety cabinets, should
be employed. Veterinarians should use protective
clothing and equipment when examining sick
animals. They should also avoid opening the
carcasses of suspected cases. Vaccines are available
for people at a high risk of infection. Postexposure
antibiotic prophylaxis, continued for at least 60 days,
and vaccination are recommended for people who
were exposed to aerosolized anthrax spores.
Humans can usually be vaccinated while they are
taking antibiotics, as most countries only use killed
anthrax vaccines. However, a few countries may still
employ live vaccines, which cannot be used
simultaneous with antibiotics. Postexposure
antibiotic prophylaxis, for a shorter period, may also
be needed for people who have eaten contaminated
meat. It is not generally recommended after
cutaneous exposure; however, any exposed areas
should be washed immediately, and the skin should
be monitored for early signs of infection.Cutaneous
anthrax lesions should be covered until antibiotics
have been administered for 24-48 hours.

21
Morbidity and Mortality
Anthrax is still a significant disease in some
countries, and outbreaks are seen occasionally in
humans. In Africa, estimates suggest that each cow
with anthrax can result in up to ten human cases.
However, the incidence of anthrax has declined
sharply in developed nations. In many countries, this
disease now occurs infrequently and sporadically,
mainly as an occupational hazard among
veterinarians, agricultural workers, and people who
process hides, hair, wool and bone products.
Humans seem to be moderately resistant to B.
anthracis, and antibodies can be found in some
people who have no history of this disease.
Individual resistance may vary. In rare cases, people
have had more than one episode of cutaneous
anthrax.The cutaneous form accounts for at least 90-
95% of the natural cases of anthrax. Gastrointestinal
anthrax seems to be uncommon, but outbreaks
sometimes affect dozens of people who ate the
same food. Natural cases of inhalational anthrax are
rare; however, aerosolized biological weapons would
be expected to produce a high percentage of this
form. In 2001, weaponized anthrax spores sent in
contaminated letters caused 11 cases of inhalational
anthrax and 11 cases of cutaneous anthrax in the
U.S. Injectional anthrax also seems to be rare;
however, a number of cases have been reported
recently in Europe, associated with contaminated
heroin.The mortality rate varies with the form of the
disease. Cutaneous anthrax is estimated to be fatal
in 5-30% of untreated cases, but in less than 1% of

22
patients treated with antibiotics. Mortality is higher
when there are large, multiple or extensive skin
lesions, or they involve the head, neck and upper
torso. Relatively few outbreaks of gastrointestinal
anthrax have been described in the literature. The
reported case fatality rates ranged from 4% to 60-
75% in the abdominal form, and from 12% to 50% in
the oropharyngeal form. Effective treatment is likely
to have contributed to the low mortality in some
incidents; however, severe illnesses were sometimes
much less common than mild cases. In at least one
report, fatalities were more likely in children.
Injectional anthrax associated with contaminated
heroin had an overall case fatality rate of 33%, but
some hospitals reported few or no deaths.Mortality
can be high in inhalational anthrax, unless treatment
begins very early. Earlier estimates suggested that
the case-fatality rate for this form approached 90-
100%, but newer, more intensive treatment
regimens may be more effective. In the 2001 mail-
associated bioterrorist attack, the case fatality rate
in patients with inhalational anthrax was 45%.
However, once a patient reaches the fulminant
stage, one study suggests that the mortality rate is >
90% regardless of treatment. Anthrax
meningoencephalitis is also deadly, with an
estimated case fatality rate of 92%.

23
24
Internet Resources
American Academy of Pediatrics/ Centers for
Disease
Control and Prevention (CDC). Pediatric Anthrax
Clinical
Management https://www.aap.org/en-
us/advocacy-and-
policy/aap-health-initiatives/Children-and-
Disasters/Pages/disaster-anthrax.aspx
Centers for Disease Control and Prevention (CDC).
Anthrax
https://www.cdc.gov/anthrax/
European Centre for Disease Prevention and
Control. Anthrax
https://ecdc.europa.eu/en/anthrax
Food and Agriculture Organization of the United
Nations.
Manual on Meat Inspection for Developing
Countries
http://www.fao.org/docrep/003/t0756e/t0756e00.
htm
Public Health Agency of Canada. Pathogen Safety
Data Sheets
https://www.canada.ca/en/public-
health/services/laboratory-
biosafety-biosecurity/pathogen-safety-data-sheets-
risk-

25
assessment.html

References
Afshar P, Hedayati MT, Aslani N, Khodavaisy S,
Babamahmoodi
F, Mahdavi MR, Dolatabadi S, Badali H. First
autochthonous
coinfected anthrax in an immunocompetent
patient. Case Rep
Med. 2015;2015:325093.
Aikembayev AM, Lukhnova L, Temiraliyeva G,
Meka-Mechenko
T, Pazylov Y, Zakaryan S, Denissov G, Easterday WR,
Van
Ert MN, Keim P, Francesconi SC, Blackburn JK, Hugh-
Jones
M, Hadfield T. Historical distribution and molecular
diversity
of Bacillus anthracis, Kazakhstan. Emerg Infect Dis.
2010;16(5):789-96.
Animal Health Australia. The National Animal
Health Information
System [NAHIS]. Anthrax [online]. NAHIS; 2001 Oct.
Available at: http://www.brs.gov.au/usr–
bin/aphb/ahsq?dislist=alpha.* Accessed 19 Nov
2002.
Antonation KS, Grützmacher K, Dupke S, Mabon P,
Zimmermann

26
F, et al. Bacillus cereus biovar anthracis causing
anthrax in
sub-Saharan Africa - chromosomal monophyly and
broad
geographic Distribution. PLoS Negl Trop Dis.
2016;10(9):e0004923.
Avashia SB, Riggins WS, Lindley C, Hoffmaster A,
Drumgoole
R, Nekomoto T, Jackson PJ, Hill KK, Williams K,
Lehman L,
Libal MC, Wilkins PP, Alexander J, Tvaryanas A, Betz
T.
Fatal pneumonia among metalworkers due to
inhalation
exposure to Bacillus cereus containing Bacillus
anthracis
toxin genes. Clin Infect Dis. 2007;44:414-6.
Bagamian KH, Alexander KA, Hadfield TL, Blackburn
JK. Ante-
and postmortem diagnostic techniques for anthrax:
rethinking
pathogen exposure and the geographic extent of
the disease in
wildlife. J Wildl Dis. 2013;49(4):786-801.
Baha TA, Jellab B, Aderdour L, Khoumiri R, Gaboune
L, Benfdil
N, Moutaouakil A, Raji A. Diagnosis and
management of

27
palpebral anthrax. Bull Soc Belge Ophtalmol.
2009;(312):29-36.

28