(Section C: Bacteriology) Lecture 22 Flashcards

1
Q

Meninges

A

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

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2
Q

What is between the arachnoid and pia maters?

A

Cerebralspinal fluid (CSF)

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3
Q

Meningitis

A

Infection of the meninges
* Due to viral or bacteria infection

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4
Q

Viral vs. Bacterial Meningitis

A

Viral
* Generally less severe
* Usually resolves without specific treatment

Bacterial
* Rapid
* Life-threatening

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5
Q

Blood Brain Barrier (BBB)

A

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

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6
Q

Steps 1-5 in Bacterial Meningitis

A
  1. Nasopharyngeal colonization
  2. Invasion into blood
  3. Multiplication in blood
  4. Crossing of the blood brain barrier (BBB)
  5. Invasion of the meninges
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7
Q

Steps 6-10 of Bacterial meningitis

A
  1. Production of pro-inflammatory cytokines/chemokines
  2. Recruitment of leukocytes into CNS
  3. Edema, increased cranial pressure
  4. Inflammation
  5. Neuronal damage
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8
Q

What are the 3 methods of traversing the BBB?

A
  1. Transcellular traversal
  2. Paracellular traversal
  3. Trojan-horse mechanism
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9
Q

Transcellular travel

A

Microorganism crosses epithelial cells by going through the cells

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10
Q

Paracellular traversal

A

Microorganisms cross epithelial cells by squeezing through the junctions

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11
Q

Trojan-horse mechanism

A

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

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12
Q

True or False:

Bacterial meningitis is a rare and mild disease

A

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

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13
Q

Bacterial meningitis
* Mortality rate
* Sequelae

A
  • 10-25%
  • Brain damage, blindness, hearing loss, learning disabilities
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14
Q

What are early signs in bacterial meningitis like?

A

May be non-specific

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15
Q

What are the trademark symptoms of bacterial meningitis in adults?

A
  • High fever
  • Severe headache
  • Stiff neck
  • Confusion
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16
Q

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

(8)

A

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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17
Q

What are risk factors for bacterial meningitis?

A
  • Lack of vaccination
  • Young age (infants)
  • Living in a community setting
  • Immunocompromised individuals due to disease or chemotherapy
  • Cranial surgery
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18
Q

What are examples of community settings?

A
  • University students living in dormitories
  • Military personnel
  • Boarding schools
  • Childcare facilities
  • Prisons
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19
Q

Diagnosis of bacterial meningitis

A
  • History
  • Symptoms
  • Blood tests (inflammatory markers)
  • Culture
  • Lumbar puncture
  • Imaging (CT)
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20
Q

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

A

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

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21
Q

What are the 3 physical signs of bacterial meningitis?

A
  1. Nucal rigidity
  2. Brudzinski’s sign
  3. Kernig’s sign
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22
Q

Nucal rigidity

A

Inability to flex the head forward

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23
Q

Brudzinski’s sign

A

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

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24
Q

Kernig’s sign

A

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

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25
Q

Treatment of bacterial meningitis

A

MUST BE PROMPT
* Intravenous antibiotics
* Corticosteroids
* Supportive therapies

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26
Q

What is the purpose of corticosteroids in bacterial meningitis?

A

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

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27
Q

What forms of supportive therapy is given in bacterial meningitis?

A
  • Monitoring
  • Oxygen
  • Fluids
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28
Q

True or False:

All bacterial pathogens have the potential to cause meningitis

A

True, but only few account for most cases

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29
Q

What are the major causes of bacterial meningitis?

A
  1. Neisseria meningitidis
  2. Streptococcus pneumoniae
  3. Haemophilus influenzae
  4. Listeria monocytogenes

In infants (0-2 months):
5. Streptococcus agalactiae

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30
Q

What type of bacteria is Streptococcus agalactiae?

A

Group B Streptococcus

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31
Q

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

A

Produce a capsule
* EXCEPT for Listeria monocytogenes

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32
Q

Describe:

Capsule

A

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

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33
Q

What are most capsules comprised of?

A

Polysaccharides

34
Q

What is the main role of capsules in meningitis?

A

Protect bacteria from the complement system

35
Q

Encapsulated are less likely to be…

A

Opsonized by through the complement system

36
Q

State:

Effective response against capsules

A

Generation of antibodies from B cells that can recognize the capsule

37
Q

What can capsules be used for?

A

Vaccines

38
Q

What is the downfall of capsules as vaccines?

A

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

39
Q

How do we make capsule vaccines long-term?

A

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

40
Q

Neisseria meningitidis
* Other names
* Gram stain
* Shape

A
  • “Meningococcus”
  • Gram negative
  • Diplococcus
41
Q

Neisseria meningitidis
* Type of pathogen
* Area of colonization

A
  • Human specific pathogen
  • Colonizes the nose and throat
42
Q

What are the antigenic variants of N. meningitidis capsule?

A
  • A
  • B
  • C
  • W135
  • Y
43
Q

What are antigenic variants known as?

A

Serotypes

44
Q

What is the leading cause of bacterial meningitidis?

A

Neisseria meningitidis

45
Q

What else can N. meningitidis cause?

A

Meningococcemia
* Invasive meningococcal disease

46
Q

True or False:

Asymptomatic carriage of N. meningitidis is common

A

True

47
Q

Meningococcal disease

A

Meningitis occurs after bacteria enter the bloodstream and cross the BBB

48
Q

What leads to septic shock in meningococcal disease?

A

Endotoxin (LPS)

49
Q

Define:

Disseminated intravascular coagulation

A
  • Widespread bood clotting
  • Ischemia
  • Clotting factors are used up, leads to small skin bleeds (purpuric rash)
50
Q

What symptom results from meningococcal disease?

A

Disseminated intravascular coagulation

51
Q

What is a characteristic of purpuric rash?

A

Does not fade under pressure (“glass test”)

52
Q

What vaccines are available for Neisseria meningitidis?

A
  • Menactra/Menveo: Quadraivalent conjugate capsule vaccine from 4 serotypes of meningococcus (A, C, Y, W135)
  • Bexsero: Contains 4 recombinant protein antigens
53
Q

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

A

Serogroup B
* Capsule is poorly immunogenic

54
Q

African Meningitis Belt
* Serogroup

A
  • Mostly caused by serogroup A
55
Q

Streptococcus pneumoniae
* Other names
* Gram stain
* Shape

A
  • “Pneumococcus”
  • Gram positive
  • Cocci, grows in chains
56
Q

Streptococcus pneumoniae
* Area of colonization

A

Commonly resides asymptomatically in the nasopharynx

57
Q

What diseases can Streptococcus penumoniae cause?

A
  • Pneumonia
  • Ear infections
  • Sinusitis
  • Many others
58
Q

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

A

Streptococcus pneumoniae

59
Q

Capsule of S. pneumoniae

A

Many (>90) different serotypes exist

60
Q

Deaths from Streptococcus pneumoniae every year

A

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

61
Q

Is there a vaccine for Streptococcus pneumoniae?

A

Yes

62
Q

History of S. pneumoniae vaccine

A
  • Previously 7 serotype vaccine (PCV7)
  • Currently Prevnar 13 (PVC13), from 13 most prevalent serotypes of penumococcus
63
Q

What other vaccine is available for high-risk adults?

(Streptococcus pneumoniae)

A

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

64
Q

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

A
  • “Hib”
  • Gram negative
  • Coccobacillus
65
Q

What are the signs of Hib infection?

A

Upper respiratory infection, ear infection, or sinusitis

66
Q

What population does Hib primarily cause meningitis in?

A

Children under 5

67
Q

Is there a vaccine available for Hib?

A

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

68
Q

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

A

Haemophilus influenzae (Type B)

69
Q

Listeria monocytogenes
* Gram stain
* Shape

A
  • Gram positive
  • Rod
70
Q

Listeria monocytogenes
* Types of pathogen
* Diseases caused

A
  • Food-borne pathogen
  • Listeriosis (ranges from gastroenteritis to bacteremia to meningitis)
71
Q

What population does Listeria monocytogenes result in high mortality in?

A

Immunocompromised individuals (includes neonates and fetus)

72
Q

What is unique about the living conditions of Listeria monocytogenes?

A

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

73
Q

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

A

Psychotrophs

74
Q

What is the mechanism of Listeria monocytogenes invasion?

A
  1. Invades intestinal epithelial cells
  2. Replicates within the cytosol
75
Q

How does Listeria monocytogenes spread in cells?

A
  1. Actin-based motility
  2. Cell-to-cell spread
76
Q

Approximately what percentage of meningitis cases does Listeria cause?

A

<5% of meningitis cases

77
Q

Streptococcus agalactiae
* Gram stain
* Shape
* Group

A
  • Gram positive
  • Cocci
  • Group B Streptococcus
78
Q

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

A
  • Many women carry S. agalactiae in the urogenital tract as a commensal
  • Can be passed from mother to infant during labor
79
Q

When are women usually tested for GBS?

A

~36 weeks

80
Q

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

A

Treated with antibiotics during labor
* Prevents infection of the newborn

81
Q

Does Listeria produce capsules?

A

NO, remember: LISTERIA DOES NOT PRODUCE CAPSULES

82
Q

Does Streptococcus agalactiae produce capsules?

A

Yes