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Central nervous system
General characteristics.
- CNS should be sterile
- Blood vessels and nerves that traverse the skull and vertebral column are main routes of infections
- Blood-borne invasion is the most common route of infection
- Abscesses - suppurative infection of the brain tissue
- Encephalomyelitis - inflammation of the spinal cord
- Blood-borne invasion involves blood-brain-barrier or blood-CSF-barrierBlood-brain-barrier - tightly joined endothelial cells surrounded by glial processes
- Blood-CSF-barrier - endothelium with fenestrations and tightly joined choroid plexus epithelial cells
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What are 3 ways in which microbes can cross the blood-brain-brarrier and the blood-CSF-barrier?
- infect cells that make up the barriers
- passive transport via intracellular vacuoles
- carried across via WBCs
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10 steps involved in the mechanism of CNS bacterial infection:
- 1. mucosal colonization
- 2. invasion of bloodstream (survival and multiplication)
- 3. crossing blood-brain-barrier
- 4. survival and multiplication in the meninges/brain parenchyma
- 5. bacterial products (pro-inflammatory) cause edema and increased pressure6. bacterial products recruit WBCs and there is a release of pro-inflammatory cytokines
- 7. cytokines recruit more WBCs which causes edema and increased intracranial pressure > increased permeability
- 8. infiltration of neutrophils and lymphocytes into CNS
- 9. WBCs produce even more cytokines which affects neuronal cells > neuronal injury
- 10. neuronal injury and edema > neuronal death
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Which pathogens have a relatively high percentage (>25%) of carriage rates in the CNS? (remember: S.H.I.N.E.S.!)
- S. agalactiae (Group B strep)
- H. influenzae
- I.gnore
- N. meningitidis
- E. coli K1
- S. pneumoniae
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How many WBCs (per microliter of CSF) are indicative of an acute bacterial infection?
>1,000 (neutrophils)
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What % of PMNs in CSF is indicative of an acute bacterial infection?
>50
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How many RBCs (per microliter of CSF) are indicative of an acute bacterial infection?
0-10
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How much glucose (per mg/dl of CSF) is indicative of an acute bacterial infection?
<30
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How much protein (per mg/dl of CSF) is indicative of an acute bacterial infection?
>100
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What are some causes of acute meningitis?
- viral or bacterial meningeal infection
- diseases that cause inflammation (without infection)
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What are the main symptoms of acute bacterial meningitis?
- high fever
- severe and persistent headache
- stiff neckN/V
- confusion
- sleepiness
- difficulty waking up
- In infants: irritability/tiredness, poor feeding and fever
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What are the virulence factors involved in acute post-neonatal S. pneumoniae bacterial meningitis?
- adhesins - binds to choline (CHO) on cell surfaces
- IgA protease (Iga)
- pneumolysin - cytotoxin released when bacteria is lysed; inhibit Ab binding to bacteria
- autolysin - causes release of pneumolysin
- capsule - >90 serotypes
- peptidoglycan and teichoic acid - proinflammatory > tissue damage
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What pathogen causes the most common acute post-neonatal bacterial meningitis?
S. pneumoniae
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What are the etiology/pathogenesis factors involved in acute post-neonatal S. pneumoniae bacterial meningitis infection?
- spread from person to person via aerosols or direct contact with secretions
- ubiquitous
- risk factors involved: immunosuppresion, distant foci of infection, low-levels of circulating Abs to capsular polysaccharide
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What is the clinical ID S. pneumoniae?
- gram+ lancet-shaped diplococci
- catalase-
- alpha-hemolytic
- optochin sensitive
- bile sensitive
- Quellung reaction - swelling of the capsule
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What are the vaccines that are available for acute post-neonatal S. pneumoniae bacterial meningitis infection?
- 23-valent - 23 serotypes of polysaccharide capsule that is responsible for 90% of infections
- 7-valent - 7 serotypes of polysaccharide capsule that are most prevalent in children, immunocompromised and elderly
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What pathogen is the second leading cause in acute post-neonatal bacterial meningitis in the U.S.?
N. meningitis
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What are the virulence factors involved in acute post-neonatal N. meningitidis bacterial infection?
- IgA protease
- Pili - adherence
- LOS - toxic, proinflammatory
- Capsule - most common type is serogroup B
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What are the etiology/pathogenesis factors involved in acute post-neonatal N. meningitidis bacterial meningitis infection?
- Spread from person to person or direct contact with oral secretions
- Ubiquitous
- risk factors: close contact with infected people, areas of outbreak
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What are some symptoms of acute post-neonatal N. meningitidis bacterial meningitis infection?
hemorrhagic rash with petechiae - can have complications due to disseminated intravascular coagulation, endotoxemia and shock, and renal failure
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What is the clinical ID N. meningitidis?
- gram- cocci, diplococci
- fastidious - grows on CAP
- oxidase+
- lactose+
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What are the virulence factors involved in acute post-neonatal H. influenzae B bacterial infection?
- IgA protease
- LPS
- Capsule - 6 serotypes
- serotype B - most common causative agent
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What are the etiology/pathogenesis factors involved in acute post-neonatal H. influenzae B bacterial meningitis infection?
- spread from person to person by aerosols or direct contact with oral secretions
- Ubiquitous
- Risk factors: close contact with infected people, areas of outbreak
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What is the clinical ID H. influenzae B?
- gram- pleomorphic coccobacilli
- faculative anaerobe
- encapsulated or nonencapsulated
- fastidious growth - grows on CAP, factor V
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What are the vaccines that are available for acute post-neonatal H. influenzae B bacterial meningitis infection?
- Hib vaccine
- protective immunity response by age 5
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What are the risk factors involved in college students acquiring acute bacterial meningitis?
- poor eating habits
- alcohol use
- smoking
- pulmonary infections
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Which pathogen involved in acute bacterial meningitis lacks pili and endotoxin?
S. pneumoniae
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Neonatal infection of acute bacterial meningitis can lead to permanent sequelae that includes:
- cerebral palsy
- epilepsy
- mental retardation
- hydrocephalus
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What is the clinical diagnosis of acute neonatal bacterial meningitis?
- fever
- poor feeding
- V/D
- respiratory distress
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What pathogens are involved in acute neonatal bacterial meningitis infections? (remember: L.E.S.T.!)
- L. monocytogenes
- E. coli K1
- S. agalactiae (Group B strep)
- T. gondii
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What are the virulence factors involved in chronic M. tuberculosis bacterial meningitis?
- droplet inhalation - infect lung macrophages
- disseminate to blood via lymphatics
- bacteremia > dissemination to CNS
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What are the etiology/pathogenesis factors involved in chronic M. tuberculosis bacterial meningitis?
- spread from person to person by aerosols
- reactivation of latent disease
- prevalence in urban and endemic areas
- risk factors: previous TB infection, immunosuppresion, travel to endemic areas
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What are the causes of encephalitis?
- viral infection
- fungal infection of the brain
- dissemination of bacterial infection
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What are the symptoms of bacterial encephalitis?
- sudden fever
- headache
- vomiting
- sensitivity to light
- stiff neck and backNeed immediate attention if:
- confusion
- drowsiness
- clumsiness
- unsteady gait
- irritability
- loss of consciousness
- poor responsiveness
- seizures
- muscle weakness
- sudden severe dementia
- memory loss
- withdrawal from social interaction
- impaired judgement
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What 2 pathogens are the most common causitive agents of bacterial encephalitis?
- B. burgdorferi (lyme disease)
- T. pallidum (tertiary Syphilis)
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What are the virulence factors involved in B. burgdorferi (Lyme disease) bacterial encephalitis?
- dissemination leads to inflammatory response and skin lesion at site of insect bite
- spread hematogenously > inflammatory response
- localize in brain tissue
- usually aseptic due to inflammatory response
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What are the etiology/pathogenesis factors involved in B. burgdorferi (Lyme disease) bacterial encephalitis?
- acquired from tick bite
- most common in NE U.S., and now in Midwest
- risk factors: residence in or travel to endemic areas
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What are some symptoms of B. burgdorferi (Lyme disease) bacterial encephalitis?
- skin lesion
- arthritis
- neurological problems
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What is the clinical ID of B. burgdorferi?
- difficult to gram stain and culturerequires special medium
- spirochete,microaerophilic
- serological tests with variable reliability
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What are the virulence factors involved in T. pallidum (tertiary Syphilis) bacterial encephalitis?
- primary: multiplication of bacteria at site of entry
- secondary: dissemination of bacteria to other tissues (like CNS)
- tertiary: may occur after 20-30 years
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What are the etiology/pathogenesis factors involved in T. pallidum (tertiary Syphilis) bacterial encephalitis?
STD
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What are some symptoms of T. pallidum (tertiary Syphilis)?
- genital chancre sore
- skin rash
- difficulty coordinating muscle movements
- paralysis
- numbness
- gradual blindness
- dementia
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What is the clinical ID of T. pallidum (tertiary Syphilis)?
- gram- spirochete
- immunological tests available
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What pathogen is responsible for CNS post-infectious syndrome related to bacterial meningitis (i.e. Gullian Barre Syndrome)?
C. jejuni
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What are the virulence factors involved in CNS post-infectious syndrome caused by C. Jejuni (Gullain Barre Syndrome)?
- ingestion of 800 organisms
- chemotaxis, motility, and flagella - attachment and colonization of gut epithelium
- iron acquisition
- host cell invasion
- toxin production
- epithelial disruption
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What are the etiology/pathogenesis factors involved in CNS post-infectious syndrome caused by C. Jejuni (Gullain Barre Syndrome)?
acquired from eating contaminated food
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What are the symptoms of CNS post-infectious syndrome caused by C. Jejuni (Gullain Barre Syndrome)?
- food poisoning
- acute paralysis
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What is Gullain Barre Syndrome?
demyelinating disorder characterized by immunological attack upon peripheral nerve myelin due to cross-reactivity between microbial ganglioside-like epitopes in LPS that cross-react with neural antigens
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What is the clinical ID of C. jejuni (Gullain Barre Syndrome)?
- gram- curved rod
- microaerophilic
- motile
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What is a polymicrobial abscess?
localized suppurative infection in brain; often leads to a space occupying lesion which compressing brain structures
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What are the symptoms of a polymicrobial abscess?
- headache
- drowsiness
- confusion
- hemiparesis
- seizures
- speech difficulties
- fever
- no stiff neck
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How does one go about diagnosing a polymicrobial abscess of the CNS?
- CT scan
- 4-5 days abscess is surrounded with fibrous capsule > "ring enhancing appearence" on CT with contrast
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What are the etiology/pathogenesis factors involved in polymicrobial abscess of the CNS?
- 50% are caused by anaerobes
- most common organisms involved:
- gram+:
- streptococcus spp., bacteroides spp., peptostreptococcus spp., nocardia spp., actinomyces spp.
- gram-:
- prevotella spp. fusobacterium spp. E. coli, C. koseri, P. mirabilis
acquired from normal microbiota, including GI tract - risk factors: immunocompromised. distal infections (like sinusitis)
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What is the most common Streptococcus organism recovered from culture that is involved in polymicrobial abscesses in the U.S.?
S. anginosus
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What are the most common organisms that are involved in polymicrobial abscesses in HIV/AIDS population?
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Where would the primary lesion of a middle ear infection abscess be located?
Middle and posterior cranial fossae
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Where would the abscess of a congenital heart disease be located?
middle cerebral artery
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Where would the primary lesion (abscess) of a sinus infection be located?
subdural sinus
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What are the virulence factors involved in chronic meningoencephalitis caused by C. neoformans fungal infection?
- usually asymptomatic
- reactivation of latent infection, can disseminate to CNS or remain in lungs
- capsule - evades microphages, Ab, and complement
- melanin - protects against oxidative defenses of macrophages
- phospholipase B
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What are the etiology/pathogenesis factors involved in chronic meningoencephalitis caused by C. neoformans fungal infection?
- acquired through inhalation
- found in pigeon excreta and rotting wood
- risk factors: immunosuppressed patients (i.e. HIV patients)
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What is the clinical ID of C. neoformans?
- gram+ yeast
- India ink+ (negative stain for capsule)
- Calcofluor White+ (fungal stain)
- urease+
- capsular antigen in CSF or serum
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What is the most ubiquitous virulence factor found amongst the majority of CNS pathogens?
capsule
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What are the virulence factors involved in chronic meningoencephalitis caused by C. imitis (Valley fever) fungal infection?
- once in the lungs > arthroconidia transform into spherical cells (spherules)
- acute respiratory infection occurs 7-21 days after exposure (usually resolves immediately, but can result chronic pulmonary condition or disseminate to CNS
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What % of patients who have disseminated C. imitis (Valley fever) infection also have meningitis?
25%
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What are the etiology/pathogenesis factors involved in chronic meningoencephalitis caused by C. imitis (Valley fever) fungal infection?
- acquired through inhalation, no person to person spreadendemic to SW U.S.
- risk factors: ourbreaks occur during dust storms, earthquakes and earth excavations
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What are the symptoms of chronic meningoencephalitis caused by C. imitis (Valley fever) fungal infection?
initial flu-like symptoms, can spread to CNS leading to meningitis (fatal unless treated)
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What are the virulence factors involved in chronic meningoencephalitis caused by H. capsulatum (North American Histoplasmosis) fungal infection?
- acquired through inhalation of macroconidia in soil
- prevalence in Southern U.S.
- risk factors: immunosuppressed patients (disseminated diseased seen), children <2, elderly, exposure to large inoculum
- dissemination results in chronic meningitis or encephalitis
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What are the etiology/pathogenesis factors involved in chronic meningoencephalitis caused by T. cruzi (Chagas disease) parasitic infection?
- acquired from Triatome bug
- found in southern U.S. to southern Argentina
- risk fatctors: infants: travel to endemic areas
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What are the symptoms of chronic meningoencephalitis caused by T. cruzi (Chagas disease) parasitic infection?
- sore develops at site of bite
- fever and acute encephalitis
- chronis disease develops over the course of a few years > affects heart, colon, CNS
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What are the etiology/pathogenesis factors involved in chronic meningoencephalitis caused by P. falciparum (Malaria) parasitic infection?
- aquired from bite of mosquito
- infects liver and RBCs
- risk factors: age <10, exposure to a malaria-endemic area
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What are the symptoms of chronic meningoencephalitis caused by P. falciparum (Malaria) parasitic infection?
- malarial fever
- can travel to CNS if untreated > brain lesions and coma
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What is the life cycle of P. falciparum?
sporozoites released from mosquito and infect human > sporozoites travel to liver > liver cells lyse and release merozoites which infect RBCs > asexual cycle occurs in RBCs > RBCs lyse and release gametocytes into blood stream > sexual cycle occurs in female mosquito > sporozoites > cycle begins anew
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