Anthrax. Rabies. Flashcards
what is the cause of anthrax ?
bacillus anthracis
what are the characteristics of bacillus anthracis ?
gram positive
spore forming
non motile
rod
edge of colonies can show comma shaped outgrowths on blood agar - referred to as the medusa head
spores of B anthracis can remain viable for decades
what is the reservoir of the pathogen B anthracis ?
Soil and mammals
spores live here to remain decades
Dried or processed skins and hides of infected animals may also harbor spores for years
what is the transmission of b anthracis ?
primarily a disease for the herbivores
exposure to B. anthracis or its spores inhalation - BUT RARELY INVOLVES THE LUNGS - PULMONARY ANTHRAX
usually as a result of skin contact with infected animals or infected animal products (e.g., wool, hide, meat) - CUTANEOUS ANTHRAX
Cutaneous outbreaks sometimes occur in knackery workers and those handling pet meat
Intestinal or oropharyngeal anthrax – caused by ingestion of anthrax contaminated undercooked meat. No evidence of transmission through the milk of an infected animal.
Person-to-person transmission is rare, but cases of person-to-person transmission of cutaneous anthrax have been reported
what is the pathophysiology of anthrax ?
Local germination of B. anthracis spores
multiplication of bacteria
Spreading to local/regional lymph nodes
Bacteremia → systemic spread
what sre the virulence factors for b anthracis
Antiphagocytic capsule
B. anthracis is the only bacterium that is capable of forming a polypeptide capsule
Anthrax toxin: responsible for the local and systemic manifestations of anthrax
made up of A and B subunits
The A subunit has 2 components:
EF (edema factor): cell edema
LF (lethal factor): a metalloprotease → cell death
The B subunit binds to endothelial receptors and facilitates entry of the A subunit into the host cell.
what is the incubation period for the different types of anthrax ?
cutaneous
5-7 days
inhilation (wool sorters disease)
1-3 days
gastrointestinal anthrax
2-5 days
what are the clinical manifestation of cutaneous anthrax anthrax ?
cutaneous anthrax - 95 percent
skin lesion :
painless pruritic papule
which then becomes a vesicles
then it becomes an ulcer surrounded by edema
then becomes a painless , necrotic , black eschar (skin lesion characterized by dried, necrotic skin tissue)
then there is healing of this by granulation
causing a hyper pigmented scar
this entire process usually takes : takes 3–4 weeks
usually does not progress to bacteria
LOCAL REGINAL LYMPHADENOTPAHY
IF BACTEREMIA - MENINGITIS AND SPETIC SHOCK
what are the clinical manifestation of PULMONARY ANTHRAX ?
1) prodromal phase
1-6 days
there is non specific flu like symptoms - fever malaise
2) fulminant phase
substernal chest pain
high grade fever
progressive dyspnea
hypoxia
shock
mediastinal widening due to hemorrhagic mediastinitis
LOCAL REGINAL LYMPHADENOTPAHY
IF BACTEREMIA - MENINGITIS AND SPETIC SHOCK
what are the clinical features of GASTROINTESTINAL ANTHRAX ?
nausea
vomitting
abdominal pain
severe bloody diarrhea
hematemesis
hemorrhagic lymphadenitis
ascites
LOCAL REGINAL LYMPHADENOTPAHY
IF BACTEREMIA - MENINGITIS AND SPETIC SHOCK
diagnosis of anthrax ?
cutaneous anthrax samples to collect - swab of fluid from vesicle or eschar full thickness punch biopsy blood CSF
inhalation anthrax pleural fluid swab of respiratory secretion blood csf
gastrointestinal anthrax oral and rectal swabs ascites fluid splenic or mesenteric lymph node biopsy blood csf
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confirmatory tests - microscopic examination and culture
or TWO supportive test :
- PCR
- immunohistochemistry - to detect bacterial capsule
ELISA - To detect antibodies against the B subunit of the bacterial toxin.
in acute-phase serum - Collected 7 days within the onset of symptoms
and convalescent-phase serum - Collected 2–4 weeks after the acute phase sample
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additional finding
x ray / ct
mediastinal widening
perihelia interstitial pneumonia
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perform lumbar puncture with clinical features of systemic involvement to rule out meningitis
what is the treatmnet of the different types anthrax ?
cutaneous anthrax
without systemic spread - oral mono therapy with fluroquinilone (cipro) or doxycycline
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inhalation anthrax
strict isolation in order not to contaminate the environment with spores
supportive - large pleural fusions - chest tube insertion or thoracocentesisi
intravenous multi-drug regimen of ciprofloxacin or doxycycline with one or more agents wo which the organism is typically sensitive
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gastrointestinal
ciprofloxacin, penicillin or doxycycline for 7-10 days. Patients isn’t infectious!
strict isolation in order not to contaminate the environment with spores
in case of ascites - ascitic tap
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cutaneous/ inhalation / gastrointestinal anthrax with systemic spread
antitoxin therapy - RAXIBACUMAB
OBLITOXAXIMAB
or anthrax immunoglobulin - ANTI ANTHRAX SERUM
combination of IV antibiotic :
without meningitis - ciprofloxacin and linezolid
with meningitis - CIPROFLOXACIN , linezolid and meropenem
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General measures
fluid resuscitiate
systemic glucocorticoids - if meningitis , shock not responding to fluid resuscitation and vasopressors
severe edema of head and neck
what is the prevention of anthrax ?
AVA - anthrax vaccine adsorbed
subunit vaccine - killed vaccine made from the cell-free filtrate of the nonencapsulated, attenuated strain of B. anthracis
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preexposure - AVA
post exposure - AVA along with ciprofloxacin and doxycycline
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what is the prevention of anthrax ?
AVA - anthrax vaccine adsorbed
subunit vaccine - killed vaccine made from the cell-free filtrate of the nonencapsulated, attenuated strain of B. anthracis
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preexposure - AVA
post exposure - AVA along with ciprofloxacin and doxycycline
Anti-anthrax serum is needed in the treatment of severe forms
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anti-anthrax vaccine is available It is used only in very serious epidemiological indications and has a very high efficiency.
The vaccine is cell-free and filtered, meaning that it does not contain any dead or living microorganisms in the preparation.
The immunization consists of 3 injections given subcutaneously at two-week intervals. This is followed by three new injections every 6, 12, 18 months
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ensure proper ventilation in hazardous industries and the use of protective clothing. Sterilize hair, wool or hides, bone meal or other feed of animal origin prior to processing.
immunize high risk persons, usually laborator, veterinarians, agricultural in risk areas workers who are liable to handle B.anthracis
Educate employees who are handlers of potentially infected articles in the proper care of skin abrasions. Immunization of animals in risk regions (vaccine is for animals)
contraindication of anthrax vaccine ?
AVA contraindicated in children under 18 and adults over 65 years old
pregnant and lactating
= THESE GROUP RECEIVE ANTITOXIN THERAPY WITH RAXIBACUMAB, OBLITOXAXIMAB
or
ANTHRAX IMMUNOGLOBULIN / ANTI ANTHRAX serum
EPIDEMIOLGY OF ANTHRAX
global
endemic in agricultural regions in the USA , Canada , central and south america and eastern europe
more in males
single case of anthrax should be considered an outbreak and should be managed with great urgency
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what is the etiology of rabies ?
caused by several different members of the rhabdoviridae family
genus Lyssavirus
what are the characteristics of rhabdoviridae
Rhabdoviruses are rod or bullet shaped
ssRNA
what is the transmission of rhabdoviridae
Most common animal reservoir worldwide: dogs
Most common animal reservoirs in the US: bats, raccoons, skunks, and foxes
Spread through saliva of rabid animal after bite injury / scratches Via aerosols (e.g., bat caves) is rare
what is the epidemiology of rabies ?
Found in animal reservoirs in most countries throughout the world
endemic in Asia, India, Africa, North and South America and parts of Europe.
Considerable divide between developed and developing countries in terms of human death due to rabies
what is the pathophysiology of rabies ?
Rabies virus binds the ACh receptor of peripheral nerves in the bite wound
→ migrates retrogradely along the axonal microtubules (using motor protein dynein)
→ enters the CNS
→ infects the brain
= Diencephalon, hippocampus, and brainstem are involved first
Causes acute, progressive, and fatal encephalitis
→ encephalitic rabies
In < 20% of cases, causes ascending flaccid paralysis → paralytic rabies
what is the incubation period for rabies ?
4–12 weeks
what are the clinical features of rabies ?
PRODROMAL SYMPTOMS
Flu-like symptoms (e.g., fever, malaise)
Locally: pain, paresthesia, and pruritus near the bite site
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ENCEPHALITIC RABIES (MOST COMMON TYPE)
Hydrophobia:
Rabies patients experience involuntary, painful pharyngeal muscle spasms when trying to drink;
later on in the disease, the sight of water alone may provoke nausea or vomiting.
Autonomic symptoms (e.g., hypersalivation, hyperhidrosis-A condition of excessive sweating)
CNS symptoms
Anxiety,
agitation,
and combativeness alternating with calm periods
Confusion and hallucinations
Photophobia
Seizures
↑ Muscle tone and reflexes with nuchal rigidity
Coma and death within days to weeks of the development of neurological symptoms
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PARALYTIC RABIES <20percent
what are the clinical features of rabies ?
PRODROMAL SYMPTOMS
Flu-like symptoms (e.g., fever, malaise)
Locally: pain, paresthesia, and pruritus near the bite site
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ENCEPHALITIC RABIES (MOST COMMON TYPE)
Hydrophobia:
Rabies patients experience involuntary, painful pharyngeal muscle spasms when trying to drink;
later on in the disease, the sight of water alone may provoke nausea or vomiting.
CNS symptoms
Anxiety,
agitation,
and combativeness alternating with calm periods
Confusion and hallucinations
Photophobia
Seizures
↑ Muscle tone and reflexes with nuchal rigidity
Autonomic symptoms (e.g., hypersalivation, hyperhidrosis-A condition of excessive sweating)
Coma and death within days to weeks of the development of neurological symptoms
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PARALYTIC RABIES <20percent
Flaccid paralysis -
gradually ascending and spreading from bite wound
Paraplegia and loss of sphincter tone
Similar to Guillain-Barré syndrome, can be differentiated by paresthesias or pain at a potential bite wound
Respiratory failure and death
what is the diagnostics of rabies ?
ANTEMORTEM DIAGNOSIS
Evidence of the virus can only be obtained after disease onset.
Four specimens are required for testing: serum, saliva, CSF, and skin (skin biopsy should be taken from the neck at the hairline so that it includes hair follicles and their respective cutaneous nerves.)
1) RT-PCR to detect rabies RNA
2) Cell culture to isolate the virus
3) Fluorescent antibody testing (FAT) to detect viral antigen in a smear or frozen section of a biopsy
4) Antibody testing (indirect fluorescent antibody test)
CSF testing: findings characteristic of encephalitis
Lymphocytic pleocytosis , normal glucose, small protein increase
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POSTMORTEM DIAGNOSIS
Postmortem brain tissue autopsy
Immunofluorescent staining of viral antigen in infected CNS tissue
Histopathological findings: babesh-Negri bodies (eosinophilic cytoplasmic inclusion bodies typically found in the cerebellum and hippocampus)
what’s the treatment of rabies ?
PEP (post exposure prophylaxis)
Cleaning and debridement, as with all bite wounds
washed thoroughly for approximately five minutes as soon as possible with soap and water. If available, a viricidal antiseptic such as povidone- iodine, iodine tincture, aqueous iodine solution or alcohol (ethanol) should be applied after washing. Exposed mucous membranes such as eyes, nose or mouth should be flushed well with water
Tetanus shot and antibiotic prophylaxis may be indicated
patient should be place in a private room with standard isolation
There should be concurrent disinfection of all saliva-contaminated articles
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Rabies immunoglobulin is given into the site of the wound by injection (passive immunization)
PLUS
inactivated killed rabies vaccine is given IM on days 0, 3, 7, and 14 and 28 (active immunization)
should be given in the deltoid area, as rabies neutralizing antibody titers may be reduced after administration in other sites
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Even patients who have been vaccinated against rabies should be treated after exposure!
Rabies vaccine IM on days 0 and 3.
either deep subcutaneous or intramuscular injection
No immunoglobulin - Immunoglobulin is not administered since the patient already has rabies antibodies due to the previous vaccination.
Check antibody titers on day 14.
Rabies is subject to human quarantine control
when are the instances we should administer PEP?
Administer PEP (post exposure prophylaxis)
when:
1) Bite by a known wild reservoir for rabies (e.g., bats, raccoons, skunks, foxes), if the animal is not available for testing or if the test comes back positive.
2) Bite by a domestic carnivore (e.g., dog) not available for observation or displaying symptoms of rabies
3) Pre-exposure vaccination is recommended for people whose occupation or recreational activities place them at increased risk of being bitten or scratched by animals. It is also recommended for travelers who will be spending prolonged periods in rural parts of rabies endemic areas.
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Observe/test animal and possibly administer PEP
Attack by an unvaccinated domestic carnivore without symptoms of rabies (e.g., dog) → observe animal for a 10-day period
Animal remains normal: PEP is not necessary
Animal starts to display symptoms of rabies:
1) Euthanize and study brain samples of the animal
2) Administer PEP to patient
3) PEP is stopped if test results of the animal are negative
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PEP is not required
Bite by a vaccinated domestic carnivore
Bite by an indoor domestic herbivore
what are the anti epidemic measures of rabies ?
Other individuals exposed to the source animal are identified and offered post-exposure prophylaxis.
Contacts that have open wound or mucous membrane exposure to a patient’s saliva should be offered full post-exposure prophylaxis.
if a rabies case, human or animal is believed to have been locally acquired the veterinary rabies control procedures should be implemented.
In designated areas animal owners may be required to have susceptible animals vaccinated with rabies vaccine.
suspected animal isolated and monitored for 14 days. If there are no signs, the immunization is stopped and the doses are not started on days 14 and 28.
If the animal becomes furious, dies or runs away - 5 dose