1st Edition of BigBrother CNS Microbiology TextBook

CNS

MICROBIOLOGY For 3rd year

Meningitis 1

Outlines

✓ Meningitis

✓ Bacterial meningitis

✓ Fungal meningitis

✓ Viral meningitis

Meningitis

Meningitis is an inflammation of the meninges. The meninges are the three membranes that cover the brain and spinal cord. Meningitis can occur when fluid surrounding the meninges becomes infected.

The most common causes of meningitis are viral and bacterial infections. Other causes may include: • cancer • chemical irritation • fungi • drug allergies

Some viral and bacterial meningitis are contagious. They can be transmitted by coughing, sneezing, or close contact.

What are the symptoms of meningitis?

The symptoms of viral and bacterial meningitis can be similar in the beginning. However, bacterial meningitis symptoms are usually more severe. The symptoms also vary depending on age.

Main symptoms

decreased appetite- irritability- sleepiness- lethargy- fever- headaches- stiff neckseizures- sensitivity to bright light- nausea and vomiting- decreased appetite

Bacterial meningitis symptoms develop suddenly.

One of the late signs of meningitis caused by Neisseria meningitidis, is a faint rash the skin. The bacteria from a meningococcal meningitis infection reproduce in the blood and target cells around the capillaries.

Damage to these cells leads to capillary damage and mild blood leaks. This shows up as a faint pink, red, or purple rash. The spots may resemble tiny pinpricks and are easily mistaken as a bruise.

As the infection worsens and spreads, the rash will become more obvious. The spots will grow darker and larger.

Viral and bacterial infections are the most common causes of meningitis. There are several other forms of meningitis. Examples include cryptococcal, which is caused by fungal infection, and carcinomatous, which is cancer-related. These types are less common.

Meningitis rash Types of meningitis Viral meningitis

Viral meningitis is the most common type of meningitis. Viruses in the Enterovirus category cause 85 percent of cases. These are more common during the summer and fall, and they include:

coxsackievirus A- coxsackievirus B- Echoviruses

Viruses in the Enterovirus category cause millions of infections per year, but only a small percentage of people who get infected will develop meningitis. Other viruses can cause meningitis. These include: West Nile virus- Influenza- Mumps- HIV- Measles- Herpes viruses

Viral meningitis typically goes away without treatment. However, some causes do

need to be treated.

Bacterial meningitis

The most common types of bacteria that cause bacterial meningitis are:

1- Streptococcus pneumoniae, which is typically found in the respiratory tract, sinuses, and nasal cavity and can cause what’s called pneumococcal meningitis

2- Neisseria meningitidis, which is spread through saliva and other respiratory fluids and causes what’s called ―meningococcal meningitis‖

3- Haemophilus influenza, which can cause not only meningitis but infection of the blood, cellulitis, and infectious arthritis

4- Listeria monocytogenes, which are foodborne bacteria

5- Staphylococcus aureus, which is typically found on the skin and in the respiratory tract, and causes staphylococcal meningitis‖

Fungal meningitis

Fungal meningitis is a rare type of meningitis. It’s caused by a fungus that infects the body and then spreads from bloodstream to the brain or spinal cord.

People with a weakened immune system are more likely to develop fungal meningitis. This includes people with cancer or HIV.

The most common fungi related to fungal meningitis include:

1. Cryptococcus, which is inhaled from dirt or soil that is contaminated with bird droppings

2. Blastomyces, another type of fungus found in soil.

3. Histoplasma, which is found in environments that are heavily contaminated with bat and bird droppings, especially in the Midwestern States near the Ohio and Mississippi Rivers

4. Coccidioides, which is found in soil in specific areas of the U.S. Southwest and South and Central America

Most common causes of neonatal meningitis are group B beta haemolytic streptococci and E. coli

Most common causes of meningitis in young children are H. influenza type b, pneumoccoci and neisserisa.

Non-infectious meningitis

Non-infectious meningitis is not an infection. Instead, it is a type of meningitis that’s caused by other medical conditions or treatments. These include: Lupus- Head injury- Brain surgery- Cancer

Vaccination

Is there a vaccine for meningitis?

Yes, there is a vaccine for several types of bacterial meningitis. Meningococcal meningitis, caused by Neisseria meningitidis, is one version for which vaccines are available. While viral meningitis is more common, bacterial meningitis can be more dangerous if it’s not diagnosed and treated quickly. For that reason, the two primary vaccines for meningitis are for bacterial causes. The first vaccine, the meningococcal conjugate vaccine, features a vaccine that targets four of the most common types of bacterial serotypes. It lasts longer and offers greater protection, especially if you maintain booster shots.

Side effects of a meningitis vaccine include soreness, redness, and burning at the injection site. Some people may experience a low-grade fever for a day or two following the injection. Chills, headache, joint pain, and fatigue are also possible.

These five groups are considered at risk and should get a meningitis vaccine:

- College freshmen who live in dorms and haven’t been vaccinated

- Adolescents who are 11 to 12 years old

- People traveling to countries where meningococcal disease is common

- Children ages 2 or older who don’t have a spleen or who have a compromised immune system

- Teenagers should protect themselves by getting a meningitis vaccine.

Treatment

Treatment is determined by the cause of meningitis.

Bacterial meningitis requires immediate hospitalization. Early diagnosis and treatment will prevent brain damage and death. Bacterial meningitis is treated with intravenous antibiotics. There’s no specific antibiotic for bacterial meningitis. It depends on the bacteria involved.

Fungal meningitis is treated with antifungal agents.

Parasitic meningitis may either involve treating just the symptoms or attempting to treat the infection directly. Depending on the cause, this type may get better without antibiotic treatment. If it worsens, however, your doctor may try to treat the infection itself.

Viral meningitis may resolve on its own, but some causes of viral meningitis will be treated with intravenous antiviral medications.

Spread

Several types of meningitis are not contagious. Fungal, parasitic and noninfectious meningitis are not contagious.

Viral meningitis is contagious. It’s spread through direct contact with body fluids, including mucus, feces, and saliva. Droplets of infected fluid can be spread and shared with sneezing and coughing.

Bacterial meningitis, the most serious form of meningitis, can also be contagious, especially if it’s meningococcal meningitis. It’s spread through extended contact with an infected person. Schools, daycare centers, military barracks, hospitals, and college dormitories are prime locations for sharing this infection. Some types of meningitis are spread through person-to-person contact but not all.

Oxidase positive Most catalase positive

Acid from glucose and maltose sugars differentiate pathogenic and commensals

Disease

Acute bacterial (pyogenic) meningitis

❖ Person-to-person transmission by aerosolization of respiratory tract secretions

❖ Commonly colonize nasopharynx of health individuals; highest oral and nasopharyngeal carriage.

Diagnosis

Sample: CSF, blood (case), or nasopharyngeal sample (carrier)

1. Chemical examination:

CSF is under tension and turbid Due to pus cells 20000/cmm.

Proteins elevated. Glucose is reduced.

2. Microbiological examination:

- CSF is centrifuged and deposit is examined microbiologically.

- Gram stain: Gram negative dipliococci intracellulary In pus cells is diagnostic

3. Culture for differentiation: Colonies are identified morphologically, biochemical reactions.

Rapid tests for capsular polysaccharide Ag by latex agglutination kits if positive start treatment immediately

Blood culture in case of bacteremia

PCR

4. Diagnosis of carriers: nasopharangeal swab cultured on modified thayer martin media

❖ Isolated Gram negative cocci should be differtiated From commensals by biochemical reactions, serologic identification with specific anti meningococcal serum

Cryptococcus neoformans

Yeast cells with gelatinous capsule. Found in the excreta of birds specially pigeons faeces.

Opportunistic pathogen affecting mainly immunosuppressed patients. Infection occurs by inhalation where it causes subclinical lung affection or pneumonia & may spread to CNS cause meningoencephalitis.

Diagnosis

1- Examination of CSF

Physical examination: CSF is turbid and under tension. Chemical examination: Protein level is increased, glucose level is decreased and the number of leukocytes is increased (mainly mononuclear cells).

2- Microbiological examination

Direct microscopic examination: India ink wet mount of CSF sediment for demonstration of encapsulated yeast cells (gelatinous capsule around budding yeast cells).

Culture: Performed on cyclohexamide free sabouraud’s dextrose agar at 20-37oC. Colonies are creamy mucoid (because of the capsule). Organism is identified by:

• India ink staining

• Urease production (+ve).

• Pathogenicity to mice.

• DNA probes.

Latex agglutination test, enzyme immunoassay: for detection of the capsular antigen in CSF, serum , urine.

Serology: Indirect immunoflourescence for antibody detection.

Herpes simplex virus

HSV multiplies locally in the mucous membrane or abraded skin causing cytolysis, necrosis, ballooning, multinucleated giant cell formation and intranuclear inclusion bodies in infected cells. Cell fusion provides cell-to-cell spread of HSV, even in the presence of neutralizing antibodies.

Diagnosis

CSF is obtained by lumbar puncture under complete aseptic conditions in 2-3 sterile tubes. It should be immediately examined as follows:

A. Physical examination: In aseptic viral meningitis it is clear or slightly turbid due to small numbers of lymphocytes.

B. Chemical examination: for the level of proteins and glucose. In viral meningitis, proteins are slightly increased while the glucose is normal.

C. Cytological examination: Normal cell count in CSF is 0-5/cmm. In viral meningitis the number of cells does not exceed 1000/cmm and are mainly lymphocytes.

1- Tzanck smear; in which scrapings from the base of skin lesions are stained with Giemsa. The presence of MULTINUCLEATED GIANT CELLS suggests HSV infection.

2- Detection of viral antigens or viral DNA in vesicular fluid by immunofluorescence or by DNA probes or PCR.

3- A rapid diagnosis can be made by detecting HSV DNA in CSF by PCR.

4- Serologic diagnosis by detection of a rise in antibody titre may be useful in primary infection. Detection of IgM antibodies in the newborn sera indicates intrauterine infection.

5- Isolation of the virus from herpetic lesions. Cytopathic effect occurs in 1-3 days. Virus is identified by immunofluorescence or ELISA

Encephalitis

Outlines

What is encephalitis ?

Causes of encephaitis

Herpes encephalitis

Rabies virus Encephalitis is inflammation of the brain. The severity can be variable with symptoms including headache, fever, confusion, a stiff neck, and vomiting. In 2015, encephalitis was estimated to have affected 4.3 million people and resulted in 150,000 deaths worldwide.

Complications

What is encephalitis ?

seizures, hallucinations, trouble speaking, memory problems, and problems with hearing.

Causes

viruses such as herpes simplex virus and rabies as well as bacteria, fungi, or parasites.

Other causes include autoimmune diseases and certain medications. In many cases the cause remains unknown.

Diagnosis is typically based on symptoms and supported by blood tests, medical imaging, and analysis of cerebrospinal fluid.  Treatment may include antiviral medications (such as acyclovir), anticonvulsants, and corticosteroids. 

Treatment generally takes place in hospital. Some people require artificial respiration. Once the immediate problem is under control, rehabilitation may be required.

Adults with encephalitis present with acute onset of fever, headache, confusion, and sometimes seizures.  Younger children or infants present with irritability, poor appetite and fever.  Neurological examinations usually reveal a drowsy or confused person. Stiff neck, due to the irritation of the meninges covering the brain, indicates that the patient has either meningitis or meningoencephalitis.

Causes of Encephalitis

Viral encephalitis

 Viral encephalitis can occur either as a direct effect of an acute infection, or as one of the sequelae of a latent infection  The majority of viral cases of encephalitis have an unknown cause,  the most common identifiable cause of viral encephalitis is from : herpes simplex infection.  Other causes of acute viral encephalitis are rabies virus, poliovirus, and measles virus. Additional possible viral causes are : 1. Arboviral flavivirus (St. Louis encephalitis, West Nile virus),

Bunyavirus (La Crosse strain), 3. Arenavirus (lymphocytic choriomeningitis virus), reovirus (Colorado tick virus) 4. Henipavirus infections. 5. Powassan virus is a rare cause of encephalitis  It can be caused by: 1. a bacterial infection, such as bacterial meningitis. 2. or may be a complication of a current infectious disease syphilis (secondary encephalitis).  Other bacterial pathogens, like Mycoplasma and those causing rickettsial disease, cause inflammation of the meninges and consequently encephalitis.  Lyme disease or Bartonella henselae may also cause encephalitis

Bacterial encephalitis

Protozoal encephalitis

Certain parasitic or protozoal infestations, such as: 1. Toxoplasmosis 2. Malaria 3. Primary amoebic meningoencephalitis can cause encephalitis in people with compromised immune systems.  Autoimmune encephalitis signs can include: 1. Catatonia 2. Psychosis 3. abnormal movements 4. autonomic dysregulation.  Antibody-mediated anti-N-methyl D-aspartate-receptor encephalitis and Rasmussen encephalitis are examples of autoimmune encephalitis.

Autoimmune encephalitis

Anti-NMDA receptor encephalitis is the most common autoimmune form, and is accompanied by ovarian teratoma in 58 percent of affected women 18–45 years of age

Encephalitis lethargica

Encephalitis lethargica is identified by high fever, headache, delayed physical response, and lethargy. Individuals can exhibit upper body weakness, muscular pains, and tremors though the cause of encephalitis lethargica is not currently known.

Diagnosis of Encephalitis

Brain scan, done by MRI EEG Polymerase chain reaction (PCR) Lumbar puncture (spinal tap)

can determine inflammation and differentiate from other possible causes.

in monitoring brain activity, encephalitis will produce abnormal signal

this helps determine via a test using the cerebralspinal fluid, obtained from the lumbar region

testing of the cerebrospinal fluid, to detect the presence of viral DNA which is a sign of viral encephalitis

Prevention

People should only be diagnosed with encephalitis if they have a decreased or altered level of consciousness, lethargy, or personality change for at least twenty-four hours without any other explainable cause.  Vaccination is available against tick-borne and Japanese encephalitis and should be considered for at-risk individuals. 

Post-infectious encephalomyelitis complicating smallpox vaccination is avoidable, for all intents and purposes, as smallpox is nearly eradicated. 

Contraindication to Pertussis immunization should be observed in patients with encephalitis

Clinical manifestations

HSV-1 Primary infection is either asymptomatic or in the form of tonsillopharyngitis.

Reactivation: After disappearance of the primary lesions the virus persist in a latent focus (trigeminal ganglia), where it persists lifelong.

Reactivation takes the form of vesicular eruption that changes to shallow ulcers and scab forms that heals without scarring.

In HSV-1 reactivation may take one of the following forms:

1. Herpes labialis: crops of vesicles at the mucocutaneous junctions of the lips or the nose that recurred at the same site.

2. keratoconjunctivitis: corneal ulcers that may leave opacities after healing and leads to blindness.

3. encephalitis: that has a fatal outcome.

4. disseminated infections: such as pneumoniae in immunocompromized patients e.g. AIDS or transplant patients

Incubation of Rabies

Averages 2 - 16 weeks

Can be as short as 1 week or up to 1 year

The two most important factors in incubation of the virus are : 1. Bite location 2. severity and amount of the viruses

In Humans

 fever, headache, and general weakness or discomfort.

 insomnia, anxiety, confusion, slight or partial paralysis, excitation, hallucinations, hypersalivation , difficulty in swallowing, and hydrophopia (fear of water)

 Convulsions, paralysis, coma, Death.

In unvaccinated-humans

 Rabies is almost always fatal after neurological symptoms have developed  Rapid post-exposure vaccination may prevent the virus from progressing.

Brain abscess 3

Outlines

✓ Define each disease and Identify the mode of infection for each pathogen.

✓ Memorize the causative agent of each disease and its morphological characteristics.

✓ Demonstrate host parasite relationships (pathogenesis) of each disease

✓ Describe laboratory diagnosis and prevention of each disease.

✓ Explain the main clinical presentations of each disease.

Rabies

Transmission

Note

Rodents and rabbits do not transmit rabies

Bite transmission Non bite transmission

➢ bite of a rabid animal that manifests aggressive, biting behaviour induced by the viral encephalitis.

➢ bite of wild animals such as raccoons, dogs, cats, jackals, mongoose and bats.

Replicative Cycle

➢ exposure to aerosols of bat secretions containing rabies virus.

➢ transplants of corneas taken from patients who died of undiagnosed rabies.

➢ Rabies virus attaches to the acetylcholine receptor on the cell surface.

➢ After entry into the cell, the virion RNA polymerase synthesizes five mRNAs that code for viral proteins.

➢ After replication of the genome viral RNA, progeny RNA is assembled with virion proteins to form the nucleocapsid.

➢ the envelope is acquired as the virion buds through the cell membrane.

Properties

member of rhabdovirus family

Enveloped

Single antigenic type. The antigenicity resides in the envelope glycoprotein spikes

Bullet-shaped capsid virion contains an RNA-dependent RNA polymerase

Pathogenesis

The virus multiplies locally at the bite site, infects the sensory neurons, and moves by axonal transport to the central nervous system.

2. The virus multiplies in the central nervous system and then travels down the peripheral nerves to the salivary glands and other organs.

3. From the salivary glands, it enters the saliva to be transmitted by the bite.

Within the central nervous system, encephalitis develops, with the death of neurons and demyelination. Infected neurons contain an eosinophilic cytoplasmic inclusion called a Negri body, which is important in laboratory diagnosis

Note

There is no viraemic stage

Risk of developing rabies after a bite: 5- 80%. depending upon:

Severity of exposure

Location of the bite

➢

➢

stages prodrome of nonspecific symptoms Within several days Within a few days ➢ Fever

➢

➢

➢

The biting animal The incubation period varies from 2 to 16 weeks according to location of the bite. In humans can be made by

the disease progresses to

➢ Seizures ➢ Paralysis ➢ Coma death few days after

Fluorescent antibody staining of a biopsy specimen, usually taken from the skin of the neck at the hairline

Isolation of the virus from sources such as

brain tissue.

Poliomyelitis

It causes poliomyelitis which in its full blown picture affect the CNS and causes flaccid paralysis. Fortunately, most poliovirus infections are subclinical

➢ Transmission: fecal–oral route. ➢ Replication site: o oropharynx o intestinal tract. ➢ Host: Humans only natural hosts. ➢ Epidemics time: o summer o fall As a result of the success of the vaccine, poliomyelitis caused by naturally occurring "wild-type" virus has been eradicated from the entire Western hemisphere. i. The virion interacts with specific cell receptors

icosahedral naked virus

Properties

Pathogenesis

infects only primates

25-30 nm diameter.

3 antigenic types. little cross-reaction single stranded RNA

infectious RNA: RNA can bypass the cell membrane receptor

Infection occurs by the ingestion of food or drink contaminated by stools of cases or carriers. the organism multiplies in the oropharynx (tonsils) and the peyer′s patches in the intestine and is excreted in the stools. inapparent infection if infection stop at this stage

➢ Infection may continue and the virus passes to the deep cervical and deep mesenteric lymph nodes. then it invades the blood stream. viraemia is associated with mild symptoms

o Fever o Malaise o Headache o nausea o vomiting

abortive infection if the disease stopped at this stage.

➢ Aseptic meningitis may be occurred and manifests by stiffness and pain in the back and neck. It usually recovers but it may progress to paralysis

➢ Paralytic poliomyelitis in 0.1- 1 % of cases.

o In CNS, poliovirus replicates in the anterior horn cells of the spinal cord. Death of these cells results in flaccid paralysis of the innervated muscles.

o The virus also affects the brain stem, leading to "bulbar" poliomyelitis, Death may occur from respiratory paralysis.

Laboratory Diagnosis

➢ isolation of the virus from stool, throat washings is done on tissue culture. characteristic cytopathic effect)CPE( appears and can be neutralized by specific antibodies

➢ Paired serum samples are tested to demonstrate a rising antibody titre by neutralization or complement fixation tests.

Treatment Prevention

o There is no antiviral therapy. Treatment is limited to symptomatic relief and respiratory support

o Physiotherapy for the affected muscles is important.

Gamma globulins given early to unimmunized contacts are effective in preventing paralytic form of the disease

Poliomyelitis can be prevented by both:

o killed vaccine (Salk vaccine, Inactivated polio vaccine (IPV))

o live, attenuated vaccine (Sabin vaccine, oral polio vaccine (OPV))

The current version of the inactivated vaccine is called enhanced polio vaccine, or eIPV. It induces some mucosal immunity IgA, making it capable of interrupting transmission

The currently approved vaccine schedule consists of four doses of inactivated vaccine administered at i. 2 months ii. 4 months iii. 6 to 18 months iv. at 4 to 6 years

One booster (lifetime) is recommended for adults who travel to endemic areas. It is a collection off pus enclosed in a brain tissue caused by bacterial or fungal infection. It is caused by inflammation and collection of infected material coming from local (ear infection, dental abscess, infection of paranasal sinuses, epidural abscess) or remote (lung, heart, kidney) infectious sources within the brain tissue.

Brain Abscess Symptoms

Diagnosis

Bacterial infections of CNS 4

Outlines

✓ Bacterial cause of Tetanus disease

✓ Bacterial cause of Botulism disease

✓ Bacterial cause of Prion diseases

Tetanus disease

History 0f Tetanus

In 5th century B.C.: - Hippocrates described correlation between wounds and fatal muscle spasms.

In 1884: - Antonio Carle and Giorgio Rattone demonstrated transmissibility of tetanus. - Arthur Nicolaier isolated C. tetani.

In 1889: - Kitasato Shibasaburo demonstrated neutralization of tetanus.

In 1897: - Edmond Nocard demonstrated that tetanus antitoxin induced passive immunity in humans.

In 1924: - Descombey developed Tetanus toxoid vaccine used in WW2.

Morphology of

Cl. tetani

- Gram positive rods with rounded ends (drumstick with a large round end or racquet shaped bacillus)

- All species form endospore

- Motile by peritrichous flagella

Cl. tetani by gram stain

Culture

- Obligate anaerobes

- Grows well in cooked meat broth and on blood agar (β-haemolysis)

Toxins

Cl. tetani produces two types of toxins:

1) Tetanolysin which causes lysis of RBCs and has cardiotoxic effects.

2) Tetanospasmin is neurotoxin and essential pathogenic product is toxic to humans and various animals when injected parenterally, but it is not toxic by the oral route.

- It acts centrally at the level of brain stem and anterior horn cells of the spinal cord, causes increasing excitability of spinal cord neurons and muscle spasm.

- It is plasmid encoded and One antigenic type.

Pathogenesis

Incubation period: it varies from few days to several weeks (5-10 days).

- Spores usually enter through accidental small puncture wounds, burns, umbilical stumps, frostbite, and crushed body parts.

- Anaerobic environmentwhich is due to cut off of blood supply is ideal for vegetative cells to grow and release toxin.

- Growth of C.tetani is completely local (not invasive organism) , but it produces the powerful neurotoxin (tetanospasmin) that is transported to CNS , causing spastic paralysis.

Tetanospasmin:

- Reaches the CNS through retrograde axonal transport or blood.

- It is a neurotoxin causes spastic paralysis by irreversible binding to motor nerve endings blocking the release of inhibitory neurotransmitters for muscular contraction e.g. glycine and GABA muscles contract uncontrollably producing generalized muscular spasms.

- Death most often due to paralysis of respiratory muscles.

Clinical features

1) Generalized tetanus

• Spasm begin in face muscles, spreads throughout the body.

• Spasm is sudden, powerful, painful and long lasting leading to muscle tear or bone fracture.

Classic tetanic triad include:

1. Trismus (lockjaw): commonly the first tetanus-specific sign due to spasm of the lower jaw muscles preventing the mouth from opening.

2. Risus sardonicus: raised eyebrows, grinning caused by cramps of the facial muscles

3. Opisthotonus: pronounced arching of back due to spasm of the strong extensor back muscles

Tetanic triad

2) Neonatal tetanus:

- Generalized disease of newborn of inadequately immunized mothers after unsterile cutting of the umbilical cord.

– Oral or IV metronidazole 30 mg/kg day divided every 6 hours for 10-14 days OR

– Penicillin G 100,000 units /kg/day divided every 4-6 hrs for 10-14 days (alternative)

Provide supportive care

- an adequate airway must be maintained, respiratory support given and IV fluids

- sedatives and muscle relaxants.

Prevention

Tetanus is a totally preventable disease

Wound management

Active immunization:

DPT vaccine against diphtheria, tetanus, and pertussis, given at 2,4,6 months.

Booster doses are given at 18 month and upon school entry.

Booster doses of Td vaccine: tetanus and diphtheria toxoid vaccine at 10-year intervals to maintain immunity.

Passive immunization:

HTIG in a dose of 250 IU IM should be given to wounded individuals.

Botulism disease

Definition

It is a paralytic disease (flaccid paralysis) caused by a potent neurotoxin elaborated by Clostridium botulinum

First recognized and isolated in 1896 by Van Ermengem

Produces heat-labile neurotoxin that causes flaccid paralysis

Types A, B and E cause human botulism

Irreversibly inhibits the neurotransmitter acetylcholine release at peripheral nerve endings at the neuro-muscular junction. Encoded by lysogenic phage.

Quick acting toxin so IP is only 12 hours.

Mechanism of Action of Botulinum Toxin

1) Food borne (classic) botulism

- It is caused by eating canned foods that contain botulinum toxin.

- The anaerobic spores survive in canned foods .

- Germination of the spores produces dangerous toxins and gas → bulging cans

Clinical features:

Classic Triad

1- Symmetric, descending flaccid paralysis with prominent bulbar palsies

2- Afebrile

3- Clear sensorium

Bulbar palsies summarized as ( 4 Ds ) : Diplopia, dysarthria, dysphonia, dysphagi

2) Intestinal botulism (infant)

- caused by ingesting spores of the bacteria (may be in honey) which germinate and produce toxin in the intestines.

- Occurs in infants between 2 weeks- 6 months.

- Newborn and infants have poorly developed gut flora, vulnerable to colonization by Cl.botulinum .

Infants with botulism will present with: Constipation is often the first symptom . weak cry, poor feeding (poor sucking). poor muscle tone (floppy baby syndrome)

3) Wound botulism

- Spores introduced during skin popping technique by drug addicts (black tar heroine) and the C. botulinum spores germinate in the wound.

4) Inhalation botulism

Prion Diseases

Definition

- Prions are abnormal forms of a cellular protein that cause rapidly progressive neurodegenerative disorders that affect both humans and animals

- It is called prion diseases or transmissible spongiform encephalopathies (TSEs).

Pathogenesis

•Normal prion protein (PrP) is a 30-kD cytoplasmic protein present in neurons.

•Disease occurs when PrP undergoes a conformational change from its normal

αhelix-containing isoform (PrPc) to an abnormal β-pleated sheet isoform usually termed PrPsc (for scrapie).

•Associated with the conformational change, PrP acquires resistance to digestion with proteases, such as proteinase K

⚫ They are confined to CNS causing neuro-degeneration and spongiform changes due to neuronal vacuolation and neuronal loss.

⚫ They have a long IP and a chronic progressive course with dementia and end fatally.

⚫ There is no inflammatory or immune response to these diseases as they are normal human proteins.

The presence of PrPsc in peripheral lymphatic tissues:

- provides specimens for analysis without the need for brain biopsy. Postmortem histopathological studies of brain material

- to detect protease resistant PrPsc and spongiform vacuolation remain the gold standard for the diagnosis of prion disease