Anthrax. Rabies.

Question 1

what is the cause of anthrax ?

Answer 1

bacillus anthracis

Question 2

what are the characteristics of bacillus anthracis ?

Answer 2

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

Question 3

what is the reservoir of the pathogen B anthracis ?

Answer 3

Soil and mammals
spores live here to remain decades

Dried or processed skins and hides of infected animals may also harbor spores for years

Question 4

what is the transmission of b anthracis ?

Answer 4

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

Question 5

what is the pathophysiology of anthrax ?

Answer 5

Local germination of B. anthracis spores

multiplication of bacteria
Spreading to local/regional lymph nodes

Bacteremia → systemic spread

Question 6

what sre the virulence factors for b anthracis

Answer 6

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.

Question 7

what is the incubation period for the different types of anthrax ?

Answer 7

cutaneous
5-7 days

inhilation (wool sorters disease)
1-3 days

gastrointestinal anthrax
2-5 days

Question 8

what are the clinical manifestation of cutaneous anthrax anthrax ?

Answer 8

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

Question 9

what are the clinical manifestation of PULMONARY ANTHRAX ?

Answer 9

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

Question 10

what are the clinical features of GASTROINTESTINAL ANTHRAX ?

Answer 10

nausea
vomitting

abdominal pain

severe bloody diarrhea

hematemesis

hemorrhagic lymphadenitis

ascites

LOCAL REGINAL LYMPHADENOTPAHY
IF BACTEREMIA - MENINGITIS AND SPETIC SHOCK

Question 11

diagnosis of anthrax ?

Answer 11

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

Question 12

what is the treatmnet of the different types anthrax ?

Answer 12

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

Question 13

what is the prevention of anthrax ?

Answer 13

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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Question 14

what is the prevention of anthrax ?

Answer 14

AVA - anthrax vaccine adsorbed

subunit vaccine - killed vaccine made from the cell-free filtrate of the nonencapsulated, attenuated strain of B. anthracis

=========
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)


Question 15

contraindication of anthrax vaccine ?

Answer 15

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

Question 16

EPIDEMIOLGY OF ANTHRAX

Answer 16

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

Question 17

X

Answer 17

X

Question 18

what is the etiology of rabies ?

Answer 18

caused by several different members of the rhabdoviridae family
genus Lyssavirus

Question 19

what are the characteristics of rhabdoviridae

Answer 19

Rhabdoviruses are rod or bullet shaped

ssRNA

Question 20

what is the transmission of rhabdoviridae

Answer 20

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

Question 21

what is the epidemiology of rabies ?

Answer 21

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

Question 22

what is the pathophysiology of rabies ?

Answer 22

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

Question 23

what is the incubation period for rabies ?

Answer 23

4–12 weeks

Question 24

what are the clinical features of rabies ?

Answer 24

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

============

PARALYTIC RABIES <20percent

Question 25

what are the clinical features of rabies ?

Answer 25

PRODROMAL SYMPTOMS

Flu-like symptoms (e.g., fever, malaise)
Locally: pain, paresthesia, and pruritus near the bite site

========

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

============

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

Question 26

what is the diagnostics of rabies ?

Answer 26

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)

Question 27

what’s the treatment of rabies ?

Answer 27

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

Question 28

when are the instances we should administer PEP?

Answer 28

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

Question 29

what are the anti epidemic measures of rabies ?

Answer 29

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