Anthrax

By: Dr. Hawine Bekele

May 23,2017
Objective
At the end of this lecture students should be able to:
know the epidemiology, microbiology, pathogenesis of
anthrax infection
Understand the transmission mode and treatment of
the infection
 be aware about the prevention methods
Outline
Introduction
Epidemiology
Microbiology
Transmission
Pathogenesis
Clinical presentation
DDX
Diagnosis
Treatment
Prevention
Introduction
Anthrax is a zoonosis infection caused by Bacillus
anthracis.
Systemic anthrax is primarily a disease of herbivores.
Humans become accidentally infected through contact
with infected animals or their products.
Most anthrax is cutaneous (95%) and the remaining
cases of the disease are inhalational and
gastrointestinal.
Anthrax was described in the early literatures of the
Greeks, Romans, Egyptians and Hindus.
The term antrakis means coal in Greek, and the disease
is named after the black appearance of its cutaneous
forms.
was the first clearly recognized bacterial pathogen
The life cycle of the organism was unravelled by
Koch, who recognized the importance of dormant
anthrax spores in the perpetuation of the organism in
soil. These studies eventually led to Koch's postulates
that have been the cornerstone for establishing a
specific pathogen as the causative agent of human and
animal diseases
John bell’s work in inhalational anthrax led to wool
disinfection processes and the term woolsloter’s
disease.
A modern concern is use of anthrax as a biologic
welfare agent.
Epidemiology
Anthrax is uncommon in western Europe, but is not
uncommon in the middle east, the Indian subcontinent,
Africa, Asia & Latin America.
In 1958, approximately 100,000 cases of anthrax
occurred world wide. Exact figures do not exist
because of reporting difficulties in Africa.
Anthrax is endemic in Africa and Asia despite
vaccination programs.
Sporadic outbreaks occurred as a result of both
agricultural and military disruptions.
During the 1978 Rhodesian civil war, failure of
veterinary vaccination program led to a human
epidemic, causing 6500 anthrax cases and 100
fatalities.
Human anthrax is often associated with agricultural or
industrial workers who came in contact with infected
animal tissue.
In the 1950s and 1960s, over 80 percent of cases in the
United States were related to products that were
manufactured from imported goat hair. Inhalational
anthrax, or woolsorters' disease, follows the inhalation
of anthrax spores generated during the early cleaning
of contaminated goat hair.
During the 20th century, improvements in industrial
hygiene, a decrease in the use of imported,
contaminated animal materials, and immunization of
at-risk workers resulted in a reduction in the incidence
of inhalational anthrax (only 18 cases in the United
States)
In 2000, 32 farms in North Dakota in the United States
were quarantined because of anthrax: a total of 157
animals died during this epizootic and a single ranch
worker who helped move dead animals developed
cutaneous anthrax.
An outbreak of cutaneous anthrax occurred in
Bangladesh in 2009 after 40 cattle and goats became ill
with anthrax . Fifty-five people from two villages
developed cutaneous anthrax, all but two of whom had
a history of slaughtering sick animals, presence at the
slaughtering site, or handling raw meat from sick
animals.
There is no racial, sexual or age predilection for
anthrax. However, because anthrax is often related to
industrial exposure and farming, the disease most often
affects young and middle aged adults.
Persons of any age can of course be affected if anthrax
is used as a bioterrorist weapon.
Microbiology
Anthrax is caused by B. Anthracis which is a
 Gram positive bacillus
 diameter of 1-1.5µm
 length of 3-10µm
 usually straight but may be slightly curved
 non motile
 catalase positive
 non haemolytic
 forms a capsule and a spore
 ground glass appearing colonies
 gray or white colour on blood agar
 Colonies measure 4-5mm in diameter and has a
comma shaped protrusions
Pathogenesis
Anthrax is primarily disease of the herbivores (goat,
cattle, sheep and horses)
Persistence of the spores is aided by nitrogen and
organic soil content, environmental PH greater than 6,
and ambient temperature great than 150c
Spores can exist indefinitely in the environment.
Optimal growth conditions result in a vegetative phase
and bacterial multiplication.
Drought or rainfall can trigger anthrax spore
germination while flies and vultures spread the spores.
Virulence depends on bacterial capsule and toxin
complex.
The capsule is a poly D glutamic acid that protects
against leukocyte phagocytosis.
Anthrax toxins are composed of 3 entities: a protective
antigen, a lethal factor and an oedema factor.
  EF is a calmodulin-dependent adenyl cyclase that
causes edema when injected subcutaneously into
experimental animals . It also impairs host defences,
including inhibition of phagocytosis .
LF causes death through an unknown mechanism
when injected into susceptible animals. It is a zinc-
dependent protease that causes lysis of macrophages .
Neither EF nor LF is toxic alone; each produces
deleterious effects only when combined with PA to
become ET and LT, respectively; PA is so named
because it is antigenic and antibodies binding PA are
protective.
In a rat model, LT was 10 times more lethal than ET .
However, ET produced more hypotension than LT and
the combination of ET and LT had an additive effect
compared to LT alone.
Protective antigen  — PA binds to a cell surface
receptor. After binding, a 20 kDa N-terminal fragment
(PA20) is proteolytically cleaved. The larger remaining
cell-bound fragment (PA63) has an exposed binding
site for either EF or LF.
In planar phospholipid bilayers, PA63 forms cation-
selective channels, suggesting that cleavage of PA20
permits insertion of PA63 as a true membrane-bound
protein with channel properties.
PA63-EF or PA63-LF can undergo receptor-mediated
endocytosis whereby EF and LF are translocated to the
cytosol. The host cell protein, low density lipoprotein
receptor-related protein 6 (LRP6), is required for
cellular uptake of complexes containing PA. LRP6
enables toxin internalization by interacting at the cell
surface with PA receptors to form a multi component
complex that enters cells upon PA binding.
Dissemination  — When introduced subcutaneously,
spores of virulent B. anthracis become vegetative
organisms and begin to multiply. Subsequent
production of an antiphagocytic capsule facilitates
local spread and exotoxin production produces
extensive brawny edema and tissue necrosis, which are
the hallmarks of cutaneous anthrax.
The rapid growth of B. anthracis during infection
requires iron. The organism's mandatory iron
acquisition in an iron-scarce environment is promoted
by local production of iron chelators.
Airborne anthrax spores greater than 5 microns in size
pose no threat to the lung, since they are either
physically trapped in the nasopharynx or cleared by
the mucociliary escalator system .
 However, spores between 2 and 5 microns in size are
deposited in alveolar ducts or alveoli. These spores are
phagocytosed by alveolar macrophages and
transported to mediastinal lymph nodes, where they
multiply and cause a hemorrhagic mediastinitis.
Gastrointestinal anthrax follows ingestion of grossly
contaminated and undercooked meat. Following
ingestion, anthrax bacilli are transported to mesenteric
lymph nodes. Subsequently, hemorrhagic mesenteric
adenitis, ascites, and septicemia may occur.
Overwhelming infection due to B. anthracis results in
rapid uncontrolled intravascular multiplication of
organisms and a fatal toxemia characterized by
hypotension and hemorrhage.
Cutaneous anthrax: humans are relatively resistant to
cutaneous invasion, but the organisms may gain access
through microscopic or gross breaks in the skin.
In cutaneous anthrax a malignant putules develope at
the infection site.
This pustule is a central area of coagulation
surrounded by a rim of vesicles filled with bloody or
clear fluid. A black eschar forms at the ulcer site and
extensive edema surrounds the lesions.
The organism multiply locally and may spread to the
bloodstream or other organs via the lymphatic.
Intestinal anthrax: primary intestinal anthrax
predominantly affects the cecum and produces a local
lesion.
Inhalational anthrax: inhalational anthrax occurs after
the person inhales spores into the lungs. Inhaled spores
are ingested by pulmonary macrophages and then
carried to hilar and midiastinal LN
The spores undergo germination and multiplication
and begins to elaborate toxins.
Anthrax in the lungs does not cause pneumonia but it
does cause hemorrhagic mediastinitis and pulmonary
oedema.
After the LN become overwhelmed bacteraemia and
death ensues.
With out treatment the mortality rate of inhalational
anthrax is approximately 95%
Clinical presentation
Cutaneous anthrax: develops 1-7 days usually 2-5 days
after skin exposure and penetration of B. Anthraxis
spores
In the most cutaneous form of anthrax, spores
inoculate a host through skin lacerations, aberations, or
biting flies.
This form most commonly affects the exposed areas of
the upper extremities, and to a lesser extent the head
and neck.
Begins as a pruritic papule that enlarges within 24-48
hrs to form a 1cm vesicle and subsequently becomes
an ulcer surrounded by an oedematous halo.
Lesions are usually approximately 2-3 cm in diameter
and have a round, regular, and raised edges
The skin in infected areas may become oedematous
and necrotic but not purulent.
Lesions are painless but on occasion are slightly
pruritic
Regional lymphadenopathy may occur and may be
painful.
The anthrax ulcer and surrounding edema evolve into
a black eschar within 7-10 days and last for 7-14 days
before leaving a permanent scar.
Oropharengeal anthrax: develops 2-7 days after
ingestion
Fever and neck swelling occur in the presence of an
oral cavity lesion
The lesions start as a edematous area that becomes
necrotic and forms a pseudomembrane within 2 weeks
Sore throat, dysphagia, respiratory distress, and oral
bleeding also occur
Soft tissue edema and dramatic cervical lymph node
enlargement follow
Intestinal anthrax: develop 2-5 days after ingestion
Abdominal pain and fever
Nausea, vomiting, malaise, anorexia, hematemesis,
bloody diarrhoea and shock
Inhalational anthrax: it begins abrubtly, usually 1-3
days after exposure and feollows a biphasic course
Initial manifestations include: myalgia, malaise,
fatigue, non productive cough, sensation of retrosternal
pressure, fever
Transient clinical improvment may occur after the first
few days, followed by rapid progression and clinical
detereoration in which the following signs and
symptoms may be present: high fever, sever SOB,
tachypnea, cyanosis, profuse diaphorosis,
hematemesis, chest pain, decreased level of
conciousness, coma and shock
DDX
Ecthyma
Glanders
Leprosy
Thyphoid
Meningitis
Mycoplasmal pneumonia
Superior vena cava syndrome
Viral pneumonia
Diagnosis
The diagnosis of cutaneous anthrax is usually
suggested by the characteristics appearance of skin
lesions. As spore germination occurs within the
macrophages at the site of inoculation, anthrax bacilli
are isolated easily from the vesicular lesion and can be
observed on gram stain.
In patients with inhalational anthrax a chest radiograph
typically shows widening of the mediastinum and
pleural effusions whereas the parenchyma may appear
normal.
The preferred diagnostic procedure for cutaneous
anthrax is gram stain.
B.anthracis grows on blood agar and staining
microbiologically differentiates the organism from
non- B.anthracis bacilli
For patients with prior antibiotic treatment bunch
biopsy at the edge of the lesion examined by silver
staining and immunohistochemical testing
Blood culture and gram stain(for patients with
systemic symptoms)
ELISA serology for B. Anthracis toxins
Chest radiography
Chest CT
Lumbar puncture(for patients with meningeal
symptoms)
Treatment
Cutaneous anthrax 7-14 days of out patient therapy
with oral doxycycline, or any quinolones
With doxycycline a loading regimen should be used
(200mgpo/iv every 12 hours for 72 hrs) in severely ill
patients it may be continued for the duration of therapy
For non bioterrorist inhalational anthrax and anthrax
meningitis the preferred drug is penicillin
Bioterrorist anthrax: any quinolone or doxycyclin for
1-2 weeks; clindamycin might be added for its anti
toxin effect
Post exposure prophylaxis- doxycycline or any
quinolone; continue for 60 days to prevent inhalational
anthrax
In patients with septic and hemorrhagic shock or
progressive respiratory insufficiencies ICU admission
might be needed.
In children levofloxacillin is safe
In pregnant women or those breast feeding can use
amoxacillin.
Prevention
Prevention of naturally-occurring anthrax in humans is
primarily dependent on the control of the disease in
animals, especially livestock. Animal vaccination is
the major means of preventing naturally-occurring
epizootics of anthrax, since widespread
decontamination of infected soil is impractical. Annual
vaccination of livestock in areas with enzootic anthrax
is recommended.
In the event of a naturally-occurring cutaneous
exposure, such as from handling an anthrax-affected
animal or its carcass, appropriate medical and public
health personnel should be notified and exposed
persons should be monitored for development of a
spot, pimple, or boil, especially in the exposed areas.
For naturally-occurring gastrointestinal exposure, such
as the consumption of meat from a poorly cooked
carcass of an anthrax-affected animal, antimicrobial
prophylaxis may be considered for a 7 to 14 day
period.
 Antimicrobial choices are the same as those
recommended for PEP to prevent inhalation anthrax.
Vaccination is not recommended following either
naturally occurring cutaneous or gastrointestinal
exposure in which there is no risk of inhalation
exposure.
The United States Advisory Committee on
Immunization Practices (ACIP) recommends the
human anthrax vaccine , anthrax vaccine adsorbed 
(AVA), for use prior to the occurrence of an event or
exposure, as well as for post-exposure prophylaxis for
inhalation anthrax in combination with antimicrobial
therapy.
THANK YOU