(Section C: Bacteriology) Lecture 22 Flashcards
Meninges
Membranes that envelop the central nervous system (brain and spinal cord)
* Includes the pia mater, arachnoid mater and dura mater
What is between the arachnoid and pia maters?
Cerebralspinal fluid (CSF)
Meningitis
Infection of the meninges
* Due to viral or bacteria infection
Viral vs. Bacterial Meningitis
Viral
* Generally less severe
* Usually resolves without specific treatment
Bacterial
* Rapid
* Life-threatening
Blood Brain Barrier (BBB)
Protective cellular structure
* Restricts passage of chemicals, toxins and microorganisms from blood to CNS
* Protects CNS from peripheral immune system
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
Steps 6-10 of Bacterial meningitis
- Production of pro-inflammatory cytokines/chemokines
- Recruitment of leukocytes into CNS
- Edema, increased cranial pressure
- Inflammation
- Neuronal damage
What are the 3 methods of traversing the BBB?
- Transcellular traversal
- Paracellular traversal
- Trojan-horse mechanism
Transcellular travel
Microorganism crosses epithelial cells by going through the cells
Paracellular traversal
Microorganisms cross epithelial cells by squeezing through the junctions
Trojan-horse mechanism
Microorganisms cross epithelial cells by getting phagocytosized by macrophages and carried inside
True or False:
Bacterial meningitis is a rare and mild disease
False, it is rare but very dangerous disease (kills in days)
Bacterial meningitis
* Mortality rate
* Sequelae
- 10-25%
- Brain damage, blindness, hearing loss, learning disabilities
What are early signs in bacterial meningitis like?
May be non-specific
What are the trademark symptoms of bacterial meningitis in adults?
- High fever
- Severe headache
- Stiff neck
- Confusion
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
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
What are examples of community settings?
- University students living in dormitories
- Military personnel
- Boarding schools
- Childcare facilities
- Prisons
Diagnosis of bacterial meningitis
- History
- Symptoms
- Blood tests (inflammatory markers)
- Culture
- Lumbar puncture
- Imaging (CT)
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
What are the 3 physical signs of bacterial meningitis?
- Nucal rigidity
- Brudzinski’s sign
- Kernig’s sign
Nucal rigidity
Inability to flex the head forward
Brudzinski’s sign
Severe neck stiffness
* Causes a patient’s knees to flex when the neck is flexed
Kernig’s sign
Severe stiffness of the hamstrings
* Inability to straighten the leg when the hip is flexed to 90 degrees
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?
- Neisseria meningitidis
- Streptococcus pneumoniae
- Haemophilus influenzae
- 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?
- Invades intestinal epithelial cells
- Replicates within the cytosol
How does Listeria monocytogenes spread in cells?
- Actin-based motility
- 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
