CNS Microbiology Flashcards by Geun Young Park

CNS has the same amount of complement as serum because it can make it’s own (True or False)

False; can synthesize its own, but levels are <1% of serum’s

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The only MHC expression in the CNS are from what cells

Microglia

Perivascular Macrophages

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Resident innate immune cell in the CNS; expresses TLR4 and can produce TGF-b; thus is involved with BOTH pro-inflammatory activity and immune/inflammatory suppression

Astrocytes

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Resident tissue macrophages in CNS; highly phagocytic, poor APCs but do express TLR4

Microglia

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T cells (can/can’t) enter the CNS

Can only when stimulated by an antigen in the periphery

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When can B cells enter the CNS

In response to inflammation with increased permeability of BBB

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Most likely causes of BACTERIAL meningitis in NEWBORNS (3 total)

E. coli
L. monocytogenes
Strep. agalactiae (Group B)

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Most likely causes of BACTERIAL meningitis in persons >3 months old (2 total)

S. pneumoniae

N. meningitidis

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What are some examples of Non-Viral pathogens of the CNS

E. coli
H. influenzae
Neisseria meningitidis
Staphylococcus aureus
Streptococcus agalactiae (Group B)
Streptococcus pneumoniae
Listeria monocytogenes
T. pallidum
Mycobacterium tuberculosis
Cryptococcus neoformans

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CNS pathogen; Gram-negative rod; encapsulated; lactose positive and commonly found in GI tract

E. coli

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CNS pathogen; Gram-negative coccobacilli, extracellular bacteria; sometimes encapsulated; commonly found in Upper Respiratory Tract and can cause epiglottitis

H. influenzae

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CNS pathogen; Gram-positive cocci in chains; B-hemolytic; found in GI tract and lower female genital tract (thus implicated in with neonate infections during birth)

Streptococcus agalactiae (Group B)

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CNS pathogen; Gram-positive “lancet shaped” diplococcus; encapsulated; a-hemolytic; found in Upper Respiratory tract; cause of lobar CAP with rust colored sputum

Streptococcus pneumoniae

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CNS pathogen; Gram-positive cocci in clusters; beta-hemolytic; commonly found on skin and in nares; implicated with acute endocarditis, post-influenza pneumonia and food poisoning

Staphylococcus aureus

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Difference between Streptococcus pneumoniae and Streptococcus aureus/agalactiae (in regards to hemolysis)

Pneumoniae: alpha-hemolytic

Aureus/Agalactiae: beta-hemolytic

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CNS pathogen; Gram-positive rod; facultative intracellular bacteria; found in GI tract; associated with dairy products and soft cheeses

Listeria monocytogenes

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CNS pathogen; acid-fast bacilli; found in lower respiratory tract; primary infection is usually asymptomatic, but can form Ghon’s complex

Mycobacterium tuberculosis

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CNS pathogen; spirochete; spreads from oral and genital lesions; can cause deafness and “tree bark” aorta

T. pallidum (Syphilis)

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CNS pathogen; Gram-negative diplococci; encapsulated; found in upper respiratory tract; especially dangerous for sickle cell patients or those with C5-9 complement deficiencies (MAC problems)

Neisseria meningitidis

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CNS pathogen; encapsulated, round yeast; associated with inhalation around pigeon poop (ewww); can cause pneumonia-like illness as well; typically only seen in immunodeficient patients (HIV)

Cryptococcus neoformans

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CNS pathogen; spirochete etiologic agent of Lyme disease

B. burgdorferi

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CNS pathogen; protozoa spread by fecal cysts by cats or undercooked pork/lamb; escape from gut and travels to brain

Toxoplasma gondii

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Tapeworm associated with CNS infection

Taenia solium (pork tapeworm)

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Fungi that can cause CNS infection (3 total)

Aspergillus
Rhizopus
Candida

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What are the CNS pathogens that are encapsulated (5 total)

``` H. influenzae E. coli (K1 capsule) Staph. aureus Strep. pneumoniae Neisseria meningitidis Cryptococcus neoformans ```

Which type of Neisseria meningitidis capsule type has no vaccination (at least until 2015)

Group B *similar to carbohydrates in fetal brain, concerns of cross-reactive antibodies

What are the vaccines for Strep. pneumoniae

``` Pneumovax 23 (Pure Polysaccharide) Prevnar 13 (Conjugate Polysaccharide) ```

Examples of protein-based vaccines

TDaP | 4CMenB

Examples of Conjugate polysaccharide vaccines

Neisseria meningitidis H. influenzae (type B) (HiB) Strep. pneumoniae (Prevnar 13)

Unique characteristics of Meningococcal infection (skin and CNS)

Skin: Hemorrhagic skin lesions (macular or non-blanching petechiae) CNS: very high blood and CSF concentrations

Signs of Meningococcal meningitis when doing a Lumbar Puncture and CSF analysis

``` Elevated opening pressure CSF cloudy Elevated WBCs (>80% PMNs) Elevated protein (>100mg) Dec. glucose (compared to serum) ```

Pattern of hematogenous spread of viruses into the brain

Choroid plexus--> CSF--> ependymal cells--> brain tissue

inflammation of the meninges covering the brain and/or spinal cord

Meningitis

Meningitis can be infectious or non-infectious (True or False)

True (can have "aseptic" meningitis due to viruses)

Bacteria and fungal meningitis is more common than aseptic/viral meningitis (True or False)

False: Aseptic meningitis is more common (especially viral)

Inflammation of the brain

Encephalitis

Inflammation of BOTH the meninges and brain

Meningoencephalitis

Enteroviruses, which include Polio and Coxsackie, are (single/double) stranded (positive/negative) sense RNA viruses

single-stranded, positive sense RNA viruses *also naked with a icosahedral capsid

Types of Enteroviruses

Polio Coxsackie A & B Echo

Enterovirus; has 3 serotypes, transmitted fecal-oral (mostly water); spreads via MOTOR neurons; no antivirals, but two vaccines (Salk & Sabin)

Poliovirus

CNS virus; SINGLE stranded, NEGATIVE sense RNA; Bullet shaped, enveloped with helical capsid; transmitted by bite from infected animal (usually wild); chance of meningitis varies by where the bite is (head/face ~60%)

Rabies

Animal sources of Rabies virus

``` Raccoons* Bats* Skunks Foxes Dogs (developing countries) ``` *most common

Describe the viral spread of Rabies in the body

Bite--> retrograde from PNS--> Spinal cord--> Brain--> anterograde to salivary glands

Signs of Rabies infection

Fever Headache Dysphagia (inc. muscle tone) HYDROPHOBIA

Important histologic feature of Rabies virus

Negri bodies (smooth, round inclusions in neurons)

How to diagnose Rabies (both in animal and human)

Animal: brain tissue sample (2 different areas) Human: Saliva/serum/CSF/skin samples

What are 3 familes of Arboviruses

Togaviridae (Eastern/Western/Venezuelan Equine Encephalitis viruses) Flaviviridae (Yellow Fever, West Nile virus, St. Louis Encephalitis and Zika virus) Bunyaviridae (California Encephalitis)

Most common outcome of Arbovirus infection

Asymptomatic infection (even most deadly)

Describe the transmission of Arboviruses

Mosquitoes/ticks to humans

Examples of Togaviridae (family of Arboviruses) (3 total)

Eastern/Western/Venezuelan Equine Encephalitis viruses

Togaviridae and Flaviviridae are both... (what sense and what kind of genome)

Positive sense, ssRNA genome with an enveloped icosahedral capsid

Examples of Flaviviridae viruses (family of Arboviruses) (5 total)

``` Yellow Fever West Nile Zika St. Louis Encephalitis Japanese Encephalitis ```

Togaviridae virus; positive sense, ssRNA genome; enveloped; mosquitoes--> birds; EASTERN seaboard

Eastern Equine Encephalitis virus (EEV)

Togaviridae virus; positive sense, ssRNA genome; enveloped; mosquitoes--> birds; WEST of the Mississippi and SA

Western Equine Encephalitis virus (WEE)

Togaviridae virus; positive sense, ssRNA genome; enveloped; mosquitoes--> rodents or EQUINES

Venezuelan Equine Encephalitis virus (VEE)

Flaviviridae virus; positive sense, ssRNA genome; enveloped; mosquitoes--> nonhuman PRIMATES; Africa and SA; has a LIVE attenuated vaccine

Yellow Fever

Flaviviridae virus; positive sense, ssRNA genome; enveloped; mosquitoes--> BIRDS; 80% of infections are sub-clinical, rarely flaccid paralysis; NO VACCINE

West Nile virus

Flaviviridae virus; positive sense, ssRNA genome; enveloped; mosquitoes--> nonhuman PRIMATES; also SEXUAL transmission; South/Central America, Africa, Asia and Caribbean; associated with birth defects; NO VACCINE

Zika virus

Flaviviridae virus; positive sense, ssRNA genome; enveloped; mosquitoes--> birds; 30% fatal in elderly; NO VACCINE

St. Louis Encephalitis

Flaviviridae virus; positive sense, ssRNA genome; enveloped; mosquitoes--> PIGS and birds; Korea, Japan, SE Asia; INACTIVATED vaccine

Japanese Encephalitis

Which Flaviviridae viruses have vaccinations?

``` Yellow Fever (live attenuated) Japanese Encephalitis (inactivated) ```

Herpesviridae, such as HSV, are (single/double) stranded (RNA/DNA) viruses with an envelope

double stranded DNA virus

Examples of Herpes viruses

``` HSV 1/2 VZV CMV EBV HHV 6/8/9 ```

Herpesviridae virus; linear, double stranded DNA; enveloped; usually acquired either via saliva exchange or genital contact; usually a LOCALIZED infection (stay in generalized area); corneal scarring and ulcerative skin lesions near face or genitals; neonates at risk for severe disseminated infection if mother infected

Herpes Simplex virus (HSV) *HSV-1 more oral/saliva, HSV-2 is more genital contact

Where is the life-long latency of a Herpes Virus located?

DRG of sensory neurons

HSV (1/2) is transmitted more-so via saliva (oral-oral or oral-genital)

HSV-1

HSV (1/2) is transmitted more-so via genital-genital contact

HSV-2

Systemic inflammatory response due to a robust and unregulated expression of cytokines in response to an infection

Sepsis

Fundoscopic finding for HSV infection

Corneal scarring (anterograde spread from ophthalmic branch from Trigeminal)

Describe the spread of HSV-1 from primary infection to latency

Break in skin (or mucous membrane)--> sensory nerve ending--> retrograde to neuron cell body in DRG--> latency with periodic reactivation and anterograde spread

Once reactivated, retrograde spread of HSV-1 from trigeminal ganglion frequently results in meningitis (True or False)

False: rarely spreads to CNS, and if it does it results in ENCEPHALITIS

(Trigeminal/Sacral) ganglia are the principle site of HSV-1 latency

Trigeminal (remember typically oral-oral or oral-genital spread via saliva)

(Trigeminal/Sacral) ganglia are the principle site of HSV-2 latency

Sacral (remember typically genital-genital spread)

What can cause the reactivation of HSV-1

``` Stress Nerve damage Exposure to sunlight Illness Immuno-suppression ```

Signs/Symptoms of HSV-2 infection

Genital sores Painful urination/discharge Inguinal adenopathy Flu-like symptoms

Type of Herpes virus (double stranded DNA virus); DISSEMINATED infection; transmitted via respiratory droplets or direct contact with lesions; appear in successive "crops"; etiologic agent of Chicken pox; infection in ADULTS is more severe and complicated

Varicella Zoster Virus (VZV)

Describe the spread of the Varicella virus in a disseminated state

Respiratory epithelium--> regional lymph nodes--> systemic (liver, spleen, skin, brain, etc.) *latency is in spinal ganglia

Primary infection with Varicella and complications are more severe in (children/adults)

Adults

Complications of Varicella infections

Encephalomyelitis Hemorrhagic Varicella (Immunocompromised patients) Secondary Pneumonia Reyes Syndrome (acute encephalopathy)

Reactivation of Varicella Zoster Virus; vesicles and rash coalesce into large lesions, commonly thoracic dermatomes and along trigeminal nerve; post-herpetic neuralgia is common due to extensive damage to affected nerves

Shingles

Treatment for Herpes viruses (HSV 1/2 and Varicella Zoster); prodrug that gets activated by Thymidine Kinase; binds to viral DNA polymerase and prevents dGTP incorporation (stop growing DNA strand) because of no 3'OH for the next phospho-diester bond

Acyclovir (ACV)

Treatment for Herpes viruses (HSV 1/2 and Varicella Zoster); PRO-DRUG form of Acyclovir, thus a much higher bio-availability and higher oral dose with less frequent intervals

Valacyclovir

Treatment for Herpes viruses (HSV 1/2 and Varicella Zoster); PRO-DRUG form of Penciclovir, thus a much higher bio-availability and higher oral dose with less frequent intervals

Famciclovir

Treatment for Herpes viruses, Adenovirus and Poxvirus; mono-phosphorylated cytosine so it DOESN'T need to be activacted by Thymidine Kinase

Cidofovir

Viral resistance to Nucleoside analog drugs is almost EXCLUSIVE to immuno(compentent/compromised) patients

Immunocompromised patients (AIDS, Leukemia, etc.) due to chronic antiviral therapy and high levelos of viral replication

Enzyme that phosphorylates several nucleoside anti-viral drugs to active form

Thymidine kinase

Herpresvirus drug; binds directly to DNA polymerase and prevents cleavage of pyrophosphate from growing DNA strand; low therapeutic index, thus used only for ACV-resistant viruses

Foscarnet

How can you grossly tell if brain tissue has a bacterial meningitis?

``` Loses transparency (filled with pus) Adopts a cloudy/opaque coloration ```

How can bacteria spread into the meninges? (2 main ways)

Bacteremia (hematogenous spread) | Direct extension from mastoid, sinuses, skull, etc.

Signs/Symptoms of Meningitis

``` Fever and headache AMS STIFF NECK Brain edema Brain ischemia/infarcts Inc. ICP Nerve palsies Communicating hydrocephalus (Meningeal fibrosis) ```

Difference between Acute vs. Subacute/Chronic Meningitis

Acute: onset in HOURS Subacute: weeks to months

Organisms responsible for SUBACUTE/CHRONIC meningitis

TB Fungi (Cryptococcus) Spirochetes (Syphillis, Borrelia burgdorferi)

Sarcoidosis can cause chronic meningitis (True or False)

True (diagnosis of exclusion if noncaseating granulomas without infection)

Tuberculous meningitis involves a (granulomatous/nongranulomatous) inflammation mainly affecting what part of the brain?

Granulomatous; Base of brain

Tuberculous granuloma occurring within the cortex or meninges of the brain that ruptures into the subarachnoid space, causing tuberculous meningitis

Rich Focus

Common cause of meningitis in immunocompromised patients; single budding yeast with a thick capsule "halo"; brain has outer slimy consistency, yellow-gray exudate in ventricles; ~50% of cases show MULTIPLE intraparenchymal cysts, AKA "soap bubbles" due to exuberant capsular material in the brain

Cryptococcus

Key characteristics of a brain infected with Cryptococcus

Slimy consistency | Multiple intraparenchymal cysts ("soap bubbles")

The _______________________ ______________ can serve as a site of bacterial extension into the brain, forming Frontal Lobe abscesses

Paranasal sinuses (sinusitis)

The ____________________ _____________ can serve as a site of bacterial extension into the brain, forming Temporal Lobe abscesses

Middle ear (or Mastoid air cells) (Otitis or Mastoiditis)

Mechanisms of abscess formation in the brain

Direct extension (sinuses, middle ear, etc.) Implantation (head trauma) Bacteremia (usually causes MULTIPLE abscesses)

Cause of brain abscesses; usually results in MULTIPLE abscesses and preferentially localizes to gray-white junction

Bacteremia

Abscesses of the brain due to BACTERMIA like to prefer what area?

Gray-white junctions

Consequences of Brain Abscesses

``` Fever Leukocytosis Mass effect (headache, nauses, vomiting and herniation due to inc. ICP) Brain destruction Spread into ventricles ```

(Bacteria/Viruses) are most common cause of Encephalitis

Virus (Herpesviruses, Arboviruses, Rabies, HIV, etc.)

Consequences of VIRAL encephalitis

Necrosis (or Hemorrhagic) Perivascular chronic inflammation Viral inclusions

Mechanisms of CNS viral infection

``` Hematogenous Via Axons (retrograde spread) ```

Viruses that can use retrograde spread along axons to infect the CNS (2 total)

HSV-1 | Rabies

_____________ is a virus that commonly causes encephalitis of the Temporal and Frontal lobes

HSV-1 (remember is typically orally spread via saliva, so makes sense is centered around the mouth)

_____________________ is a virus that commonly infects the Anterior Horns cells

Poliovirus

____________________ virus commonly infects oligodendrocytes, causing Progressive Multifocal Leukoencephalopathy

JC (John Cunningham) virus

________________ virus commonly infects the Hippocampus and Cerebellum

Rabies

________________________ virus commonly infects the DRG

Varicella-Zoster virus (makes sense because of dermatomal distribution when reactivated)

______________ _____________________ virus usually infects the leptomeninges (Arachnoid and Pia mater)

Lymphocytic Choriomeningitis virus

Examples of Parasitic infections of the CNS

Cysticercosis (neurocysticercosis) Toxoplasmosis (STORCH infection) Amebiasis (Naegleria or Acanthamoeba) Other (Malaria Echinococcosis, Schistosomiasis)

MOST common parasitic CNS infection globally; etiologic agent is Taenia solium; due to ingestion of eggs (contaminated water or food); cysts can be either intra/extraparenchymal

Cysticercosis

Cysticercosis is caused by the ingestion of undercooked pork with Taenia solium (True or False)

False: due to ingestion of EGGS in contaminated water or food (undercooked pork with cysts caused INTESTINAL, not CNS infection)

Treatment for Naegleria fowleri

Amphotericin B

2 main pathways for transmission of an infection to a fetus

Ascending (from vagina/cervix) | Transplacental

What are the STORCH infections (can cause congenital encephalitis via transplacental spread)

``` Syphilis Toxoplasmosis Other (HIV) Rubella CMV HSV-2 ```

CNS Microbiology Flashcards

(119 cards)