(Section C: Bacteriology) Lecture 22 Flashcards by Lucky Cat

Meninges

Membranes that envelop the central nervous system (brain and spinal cord)
* Includes the pia mater, arachnoid mater and dura mater

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What is between the arachnoid and pia maters?

Cerebralspinal fluid (CSF)

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Meningitis

Infection of the meninges
* Due to viral or bacteria infection

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Viral vs. Bacterial Meningitis

Viral
* Generally less severe
* Usually resolves without specific treatment

Bacterial
* Rapid
* Life-threatening

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Blood Brain Barrier (BBB)

Protective cellular structure
* Restricts passage of chemicals, toxins and microorganisms from blood to CNS
* Protects CNS from peripheral immune system

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Steps 1-5 in Bacterial Meningitis

Nasopharyngeal colonization
Invasion into blood
Multiplication in blood
Crossing of the blood brain barrier (BBB)
Invasion of the meninges

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Steps 6-10 of Bacterial meningitis

Production of pro-inflammatory cytokines/chemokines
Recruitment of leukocytes into CNS
Edema, increased cranial pressure
Inflammation
Neuronal damage

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What are the 3 methods of traversing the BBB?

Transcellular traversal
Paracellular traversal
Trojan-horse mechanism

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Transcellular travel

Microorganism crosses epithelial cells by going through the cells

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Paracellular traversal

Microorganisms cross epithelial cells by squeezing through the junctions

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Trojan-horse mechanism

Microorganisms cross epithelial cells by getting phagocytosized by macrophages and carried inside

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True or False:

Bacterial meningitis is a rare and mild disease

False, it is rare but very dangerous disease (kills in days)

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Bacterial meningitis
* Mortality rate
* Sequelae

10-25%
Brain damage, blindness, hearing loss, learning disabilities

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What are early signs in bacterial meningitis like?

May be non-specific

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What are the trademark symptoms of bacterial meningitis in adults?

High fever
Severe headache
Stiff neck
Confusion

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What are the main clinical symptoms in infants for bacterial meningitis?

(8)

Subtle, variable and non-specific
* Fever
* Constant crying
* Excessive sleepiness or irritability
* Poor feeding
* Inability to maintain eye contact
* A bulge in the soft spot on top of a baby’s head (fontanel)
* Stiffness in the baby’s body and neck
* Skin rash in cases of meningococcal meningitis

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What are risk factors for bacterial meningitis?

Lack of vaccination
Young age (infants)
Living in a community setting
Immunocompromised individuals due to disease or chemotherapy
Cranial surgery

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What are examples of community settings?

University students living in dormitories
Military personnel
Boarding schools
Childcare facilities
Prisons

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Diagnosis of bacterial meningitis

History
Symptoms
Blood tests (inflammatory markers)
Culture
Lumbar puncture
Imaging (CT)

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What is a lumbar puncture? What are signs in a lumbar puncture that point to bacterial meningitis?

Spinal tap
* Cloudy CSF
* Gram stain and culture
* Presence of white cells (neutrophils)
* Low glucose

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What are the 3 physical signs of bacterial meningitis?

Nucal rigidity
Brudzinski’s sign
Kernig’s sign

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Nucal rigidity

Inability to flex the head forward

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Brudzinski’s sign

Severe neck stiffness
* Causes a patient’s knees to flex when the neck is flexed

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Kernig’s sign

Severe stiffness of the hamstrings
* Inability to straighten the leg when the hip is flexed to 90 degrees

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Treatment of bacterial meningitis

MUST BE PROMPT * Intravenous antibiotics * Corticosteroids * Supportive therapies

What is the purpose of corticosteroids in bacterial meningitis?

To reduce swelling in the meninges * E.x. Dexamethasone

What forms of supportive therapy is given in bacterial meningitis?

* Monitoring * Oxygen * Fluids

# True or False: All bacterial pathogens have the potential to cause meningitis

True, but only few account for most cases

What are the major causes of bacterial meningitis?

1. Neisseria meningitidis 2. Streptococcus pneumoniae 3. Haemophilus influenzae 4. Listeria monocytogenes In infants (0-2 months): 5. Streptococcus agalactiae

What type of bacteria is Streptococcus agalactiae?

Group B Streptococcus

What is a shared trait among all of the major causes of bacterial meningitis?

Produce a capsule * EXCEPT for Listeria monocytogenes

# Describe: Capsule

Loose, relatively unstructured network of polymers that cover the surface of some bacteria

What are most capsules comprised of?

Polysaccharides

What is the main role of capsules in meningitis?

Protect bacteria from the complement system

Encapsulated are less likely to be...

Opsonized by through the complement system

# State: Effective response against capsules

Generation of antibodies from B cells that can recognize the capsule

What can capsules be used for?

Vaccines

What is the downfall of capsules as vaccines?

Does not provide long-term memory * Polysaccharide vaccines * T-cell independent

How do we make capsule vaccines long-term?

Conjugate vaccines * Polysaccharide conjugated to protein carrier * T cell dependent

Neisseria meningitidis * Other names * Gram stain * Shape

* "Meningococcus" * Gram negative * Diplococcus

Neisseria meningitidis * Type of pathogen * Area of colonization

* Human specific pathogen * Colonizes the nose and throat

What are the antigenic variants of N. meningitidis capsule?

* A * B * C * W135 * Y

What are antigenic variants known as?

Serotypes

What is the leading cause of bacterial meningitidis?

Neisseria meningitidis

What else can N. meningitidis cause?

Meningococcemia * Invasive meningococcal disease

# True or False: Asymptomatic carriage of N. meningitidis is common

True

Meningococcal disease

Meningitis occurs after bacteria enter the bloodstream and cross the BBB

What leads to septic shock in meningococcal disease?

Endotoxin (LPS)

# Define: Disseminated intravascular coagulation

* Widespread bood clotting * Ischemia * Clotting factors are used up, leads to small skin bleeds (purpuric rash)

What symptom results from meningococcal disease?

Disseminated intravascular coagulation

What is a characteristic of purpuric rash?

Does not fade under pressure ("glass test")

What vaccines are available for Neisseria meningitidis?

* **Menactra/Menveo:** Quadraivalent conjugate capsule vaccine from 4 serotypes of meningococcus (A, C, Y, W135) * **Bexsero:** Contains 4 recombinant protein antigens (serotype B)

What serogroup does Bexsero offer protection against? Why was this vaccine hard to develop?

Serogroup B * Capsule is poorly immunogenic

African Meningitis Belt * Serogroup

* Mostly caused by serogroup A

Streptococcus pneumoniae * Other names * Gram stain * Shape

* "Pneumococcus" * Gram positive * Cocci, grows in chains

Streptococcus pneumoniae * Area of colonization

Commonly resides asymptomatically in the nasopharynx

What diseases can Streptococcus penumoniae cause?

* Pneumonia * Ear infections * Sinusitis * Many others

What is the leading cause of bacterial meningitis in children over 2 years and adults?

Streptococcus pneumoniae

Capsule of S. pneumoniae

Many (>90) different serotypes exist

Deaths from Streptococcus pneumoniae every year

Major global pathogen * >700,000 deaths per year globally

Is there a vaccine for Streptococcus pneumoniae?

Yes

History of S. pneumoniae vaccine

* Previously 7 serotype vaccine (PCV7) * Currently Prevnar 13 (PVC13), from 13 most prevalent serotypes of penumococcus

What other vaccine is available for high-risk adults? | (Streptococcus pneumoniae)

23-valent polysaccharide vaccine for high risk adults * Poorly immunogenic in children

Haemophilus influenzae (Type B) * Other names * Gram stain * Shape

* "Hib" * Gram negative * Coccobacillus

What are the signs of Hib infection?

Upper respiratory infection, ear infection, or sinusitis

What population does Hib primarily cause meningitis in?

Children under 5

Is there a vaccine available for Hib?

Hib conjugate vaccine available * Part of routine of childhood immunization schedules * Reduced 99% of invasive Hib disease to low levels (<1 per 100,000)

What was the leading cause of bacterial meningitis before 1990s?

Haemophilus influenzae (Type B)

Listeria monocytogenes * Gram stain * Shape

* Gram positive * Rod

Listeria monocytogenes * Types of pathogen * Diseases caused

* Food-borne pathogen * Listeriosis (ranges from gastroenteritis to bacteremia to meningitis)

What population does Listeria monocytogenes result in high mortality in?

Immunocompromised individuals (includes neonates and fetus)

What is unique about the living conditions of Listeria monocytogenes?

Can grow at 4 degrees Celsius * Important for food-borne pathogens

Due to the ability to grow at low temperatures, what are Listeria monocytogenes known as?

Psychotrophs

What is the mechanism of Listeria monocytogenes invasion?

1. Invades intestinal epithelial cells 2. Replicates within the cytosol

How does Listeria monocytogenes spread in cells?

1. Actin-based motility 2. Cell-to-cell spread

Approximately what percentage of meningitis cases does Listeria cause?

<5% of meningitis cases

Streptococcus agalactiae * Gram stain * Shape * Group

* Gram positive * Cocci * Group B Streptococcus

Where do S. agalactiae reside? How is it transmitted?

* Many women carry S. agalactiae in the urogenital tract as a commensal * Can be passed from mother to infant during labor

When are women usually tested for GBS?

~36 weeks

What is done to women who are positive for GBS during labor?

Treated with antibiotics during labor * Prevents infection of the newborn

Does Listeria produce capsules?

NO, remember: LISTERIA DOES NOT PRODUCE CAPSULES

Does Streptococcus agalactiae produce capsules?

Yes