_Neurotropism-_Pathogens show inclination to diff CNS tissues _Bacterial (purulent)-_Acute onset (hrs-days): CSF turbid (cloudy) polymorphonuclear dominate (60,000 neutrophils) Glucose decrease w/HIgh protein increase presence of bacteria _VIral (aseptic)-Acute onset:_ CSF clear Lymphocyte dominate (500) Normal glucose w/slight protein increase _Chronic-_gradual onset (weeks-months): Lymphocyte dominate Increased protein w/possible low glucose _Encephalitis & Meningoencephalitis:_ Change in CSF (cell count, protein, & glucose) Similar to viral but MORE elevated

_0-3 months:_E.coli, Strep (group B), Listeria mono _3 months-6 years:_ Strep pneumo (#1) & Haemophilus Influenzae (#2) _Over 6 years:_ Strep Pneumonia (common) Proliferation if bacteria behind blood-brain barrier in subarachnoid space Protection from phagocytosis, Ab, & comp PMNs & proteins enter CSF=Increased pressure in subarachnoid space compress brain/SC _Symptoms_: Fever, Headache, Stiff neck (may not be in children) Bulging Fontanelle=Infants Skin rash (50% widespread pataecciae)=Neisseria Brudzinski's sign (lifting neck observe LL) Kernigs's sign (Flex/extend leg observe pain in back exudate in lumbar) _CSF-_ HIGH increase in protein w/decrease in glucose=Hypoglycorrhachia

Nervous System Pathogens Flashcards by Pedro Ramirez

Types of meningitis

Neurotropism-_{^{Pathogens show inclination to diff CNS tissues}}
Bacterial (purulent)-_{^{Acute onset (hrs-days):}}
- ^{_{CSF turbid (cloudy)}}
- ^{_{polymorphonuclear dominate (60,000 neutrophils)}}
- ^{_{Glucose decrease w/HIgh protein increase}}
- ^{_{presence of bacteria}}
VIral (aseptic)-Acute onset:
- _{^{CSF clear}}
- _{^{Lymphocyte dominate (500)}}
- _{^{Normal glucose w/slight protein increase}}
Chronic-_{^{gradual onset (weeks-months):}}
- _{^{Lymphocyte dominate}}
- _{^{Increased protein w/possible low glucose}}
Encephalitis & Meningoencephalitis:
- _{^{Change in CSF (cell count, protein, & glucose)}}
- _{^{Similar to viral but MORE elevated}}

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Bacterial Meningitis

0-3 months:_{^{E.coli, Strep (group B), Listeria mono}}
3 months-6 years: _{^{Strep pneumo (#1) & Haemophilus Influenzae (#2)}}
Over 6 years: _{^{Strep Pneumonia (common)}}
Proliferation if bacteria behind blood-brain barrier in subarachnoid space
_{^{Protection from phagocytosis, Ab, & comp}}
_{^{PMNs & proteins enter CSF=Increased pressure in subarachnoid space compress brain/SC}}
Symptoms: Fever, Headache, Stiff neck _{^{(may not be in children)}}
_{^{Bulging Fontanelle=Infants}}
_{^{Skin rash (50% widespread pataecciae)=}}Neisseria
_{^{Brudzinski’s sign (lifting neck observe LL)}}
_{^{Kernigs’s sign (Flex/extend leg observe pain in back exudate in lumbar)}}
CSF- _{^{HIGH increase in protein w/decrease in glucose=Hypoglycorrhachia}}

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Bacterial Meningitis (clinical)

Diagnose:
Specimen-CSF _{^{(chemistry, cell count, gram stain)}}
- _{^{Chemistry-Cloudy w/HIGH increase in protein & Hypoglycorrhachia}}
- _{^{Cell count-Increased WBC & neutrophils}}
- _{^{Gram stain CSF-Any bacteria is significant}}
Treat: Empiric Treatment _{^{(treat even w/o firm diagnosis)}} w/in 30 mins of assessment
_{^{Ampicillin + Cefotaxime OR Ampicillin + Gentamycin Given IV for BBB}}
_{^{Dexamethazone (corticosteroid)-Anti-inflammatory used in children to minimize rxn to free LPS (Give 10-20 before antibio)}}

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Strep Pneumoniae-General

Gram (+) encapsulated, Lancet-shaped _^(elongated) paired w/cocci _{^{(short chains)}}
Alpha hemolytic _{^{(stains green)}}
Optochin & Bile sensitive
Autolysis-Releases virulence factors
NO lancefield type due to lack of carb in cellwall
Reservoir: Humans nasopharyngeal more common children
Transmission: resp droplets & aspiration of normal flora
High risk: Children & elderly
_{^{Pts w/history of previous viral RT infection}}
- _{^{Ex. Post-influenza, asthma}}
_{^{Alcoholics & smokers}}
_{^{Chronic pulm disease pts}}
_{^{Congestive heart failure}}
_{^{Asplenic/Splenectomy pts}}
_{^{Trauma/Meningitis=CSF leakage to nose}}

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Strep Pneumoniae-Pathogenesis

Polysaccharide capsule=_{^{Anti-phagocytic (90 serotypes)-Vaccines target}}
Teichoic acid & peptidoglycan: Activate alternative complement ^{(inflammation)}
Phosphrylcholine: Unique to SP=Cell wall component
Binds to receptors of platelets activating factor ^{(found on many cells)}
Bacteria “hide” phagocytes=Spread infection

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Haemophilus Influenza-General

Type B most VIRULENT type causes:
Localized infections in URT & LRT
Bacteremia_{^{(bacteria in blood)}}
**Meningitis **
Flora=Otitis media, Sinusnitis, pneumonia
Gram (-) pleomorphic Rod w/pink stain
Grow on chocalate agar or on Blood agar w/Strep aureus that lysis RBCs=Satellite Growth
Coccobacilli encapsulated w/diff types
Requires growth factors - **Ten(hemin) & five(NAD) **
Reservoir: Humans ONLY nasopharynx capsular type B & non-typable strains COMMON (Flora)
High Risk: Anyone-Unvaccinated children 2-4 or children w/severe infections

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Haemophilus Influenza-Clinical

Polysaccharide capsule: Type B capsule made of polyribose-ribitol phosphatase (PRP)
IgA protease-Stops IgA
Endotoxin: Lipo-oligosacc (LOS) similar to Neisseria=Adherence, toxic to ciliated cells, Induce inflammation
Prevention: Hib vaccine-for type B capsular polysaccharide-_{^{(conj diphtheria or tetanus used to make it)}}
- _{^{Vaccine reduces carrier rate}}
Chemoprophylaxis_{^{(admin of meds to help minimize spread)}}: **Rifampin **eliminates carriers in HIGH risk groups by type B

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Neisseria Meningitidis

Gram (-) Diplococcus _{^{(coffee bean shape)}} Capsulated
- _{^{Anti-phagocytic cap}}
Faculative intracellular & Oxidase (+)
Ferments glucose/maltose
Found in nasopharynx _{^{(asymptomatic carriers)}}
High Risk: Crowded areas _{^{(college, military, day cares)}}
Inherited def of Comp, Properdin _{^{(activator of comp)}}, Mannose-binding lectin _{^{(Innate immunity comp activator)}}
Virulence factors: Several serotypes A,B,C,Y, & **W135 **
_{^{Type A developing countries & B,C,Y in USA}}
_{^{Type B cap NOT immunogenic (no immune response)}}
_{^{LOS (lipooligosaccharide) No O but has A (endotoxin)}}
_{^{Surface proteins-Bind to factor H=prevention of comp activation}}

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Neisseria Meningitidis (Clinical)

Meningitis: Abrupt onset fever, INTENSE headache, chills, Nuchal/Neck rigid-_{^{(Kernig’s/Brudinski’s)}}
Meningococcemia: Diffuse infection
_{^{Hemorrhagic rash (petechial)rapid progression petechiae coalesce (ecchymosis)=DIC & shock}}
_{^{Acute Meningococcemia gangrene}}
Waterhouse-Friderichsen syndrome: Adrenal destruction due to DIC
Treat: Penicillin G
- _{^{For allergies Cholramphenicol, Cefotaxime}}
Diagnose: Chocolate agar (+5% Co2) or Gram stain=Gram (-) inside PMN

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Neisseria Meningitidis (Prevention)

Prophylactic antibios for pts exposed:
Rifampin _{^{(also used w/haemophilus)}} or Cipro-treat mucus membranes
Vaccine:
Serotype A, C, Y, W135
- Conj to diphtheria toxin
- Routine vaccination age 11-18 or Traverlers
Serotype B-NOT used due to cap made of sialic acid identical to human sialic acid
- NEW vaccine for B=Recomb proteins

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Strep Agalactiae (general)

Gram + cocci, catalase (-) Capsulated
Beta Hemo=Bacitracin resistant (lance B)
CAMP (+) & Hippurate Hydrolysis (Blue-Glycine)
Normal flora of URT, GI, & Vagina _{^{(higher in African Americans)}}
High Risk: Neonates (due to delivery)
Virulence factor:
Capsule-Polysac rich in sialic acid
Anti-phagocytic & adhesion to meninges

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Strep Agalactiae (Clinical)

Universal pre-natal screening @ 35-37 weeks
Early onset disease: 1st week of life
_{^{Infection acquired in utero or during delivery}}
High risk: _{^{Pre-term, maternal intrapartum fever, previous deliveries w/GBS}}
Sepsis, pneumonia, meningitis
Late onset disease: 1 week-3 months
_{^{Infection acquired from outside source (other infants)}}
**Sepsis & meningitis **
Adults: Postpartum endometritis, wound infection, UTI in pregers

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Strep Agalactiae (Diagnose)

Treat: Penicillin G
Prevention: Intrapartum Antibios
Diagnosis:
Culture of Blood agar (Beta Hemo) LARGE area
Bacitracin resistant
CAMP test (best) positive
Hippurate hydrolysis (Blue-glycine)

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E.Coli-Neonatal purulent Meningitis

Gram (-) rod, lactose fermenter (pink)-MacConkey
Found in colon/urogenital tract
Transmission: Mother to infant @ time of delivery
Virulence: Strains that cause meningitis=Capsular Ag K1 cross reacts w/group B strep capsule
Disease: Ecoli & group B strep #1 cause of meningitis in NEW BORNS

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Listeria Monocytogenes (general)

Faculative Intracellular / Gram + rod or short chains
Motile _{^{(tumbling movement)}} & growth @ broad temp
Resistant to pasteurization temp & CAMP+
Ubiquitous (everywhere) and in GI of animals
Transmission:
_{^{Ingestion of contaminated food (meat or dairy products)}}
_{^{Vertical transmission (across placenta or delivery)}}
High risk: fetus, neonates or immunocompromised pts
Virulence: Infects various cells
_{^{Faculative intracellular-invade mononuclear phagocytic cells (moves like shigella)}}

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Listeria Monocytogenes (Clinical)

Pathogenesis:
_{^{Cell adhesion & internalization-Adhesins & Internalins}}
Evasion of phagocytosis-
- _{^{Listeriolysin (hemolytic/cytotoxic)}}
- _{^{Phospholipase C helps bacteria get OUT of phagosome}}
_{^{Replication in cytoplasm}}
_{^{Release/entry into cell-ActA protein polymerase actin to push itself to next host cell (shigella)}}
Neonatal disease _{^{(abortion or premature):}}
Early onset (10 days) infection in utero
Granulomatosis infantiseptica-_{^{Sepsis w/pus lesions & granulomas made of L.mono in multiple organs}}
Late onset (2-3 weeks) infection during delivery
_{^{Meningitis or Meningoencephalitis w/septicemia}}
Adults: _{^{Immunocomp=Flu like or Pregers/Immunocompromised (disseminated bacterimia)}}

Listeria Monocytogenes (Diagnose)

Microscopy: CSF no organism few bacteria for detection
Culture: Small zone of hemolysis on Blood agar & POSITIVE CAMP test
Culture isolation improved w/cold isolation
Treat: Penicillin or ampicillin alone or combo
Prevention: _{^{Pregers & immunocompromised}}
Avoid soft cheeses
Throughly cook left overs
Wash raw veges

Crytococcus Neoformans (general)

Monomorphic yeast spherical-oval surrounded by wide polysac cap (Urease +)
Ubiquitous BUT most linked to pigeon droppings
Transmission: Aerosolized spores-Lungs then to CNS
High risk: Immunocompromised (HIV)
Virulence: Polysac cap
Disease: Cryptococcosis_^(chronic)
Cutaneous lesions seen in disseminated infection
Initial pneumonia-> meningocephalitis
- _{^{Headache (progressive & more severe)}}
- _{^{Mental aberrations (irribality to psychosis)}}
- _{^{Motor abnormalities (paralysis)}}
- _{^{CN dysfunctions (aphasia)}}
- _{^{Cerebellar dysfunctions}}

Crytococcus Neoformans (Clinical)

Microscopic: CSF+ w/Indian ink stains thick cap surrounding budding yeast
Culture: Blood agar = Urease +
Cap Ag detection in serum or CSF latex agglutination
Treatment: Ampotericin B or Fluconazole

Picornaviridae enterovirus (General)

ssRNA (+) Icosahedral-NAKED
Resistant to harsh enviroment & Stomach acid
Entry-URT & GI
Fecal-oral transmission
Entry mediated by viral receptors that bind to host cell:
ICAM-1=Intracellular adhesion mol _{^{(Coxsackie/Echo)}}
CD-55=decay accelerating factor_{^{(Coxsackie/Echo)}}
CD-155=Polio virus adhesion
- _{^{Found on macrophages, monocytes, CNS neurons}}

Picoviridae-Coxsackie & Echo

ssRNA + icosahedral NAKED
- Coxsackie A/B
- Achovirus MANY serotypes
_Transmission: _
Coxsackie-Oral fecal + aerosol
Echovirus-Oral fecal _{^{(Common in summer-early fall)}}
Bornholm (pleurodvnia): Cox B Infection of intercostal muscles=_{^{Trouble breathing w/NO minor lung involvement}}
Presents as aseptic meningitis, upper resp infections
90% of all VIRAL meningitis
COX A=Herpangina (Hand-foot-mouth)
COX B= Myocardial, pericardial infections
- _{^{Both can cause polio-like paralytic disease}}

Picornaviridae enterovirus (Pathogenesis)

Replication of oropharynx w/primary infection in local lymphoid tissue _^(GALT)
Transient viremia_{^{ (blood)}} can infect CNS
Viruses show Dual tropism
Ex Polio-CD 155 affinity for epi/lymph of gut & CNS
- _{^{Replication in CNS “grey matter” motor neurons ant. horn of SC & brain stem}}
- _{^{Plaques form due to lytic replication w/inflammation by immune response}}
- _{^{Death of these neurons=paralysis of muscles}}

Picoviridae-Polio (general)

ssRNA (+) - Naked icosahedral ^{_{(3 serotypes-most infectious is TYPE 1)}}
Transmission: Fecal-oral
High risk: Unvaccinated in early childhood (mild) & adolescent (severe)
Asymptomatic (90-95%) _{^{w/viral shedding}}
Abortive poliomyelitis (5%) 3-4 days mild illness, headache, sore throat, nausea (spont recovery)
Non-paralytic (2%) _{^{Aseptic meningitis-fever, headache, stiff neck}}
Paralytic (1%) _{^{attacks ant horn = flaccid paralysis & Brain cells=life-threatening resp paralysis}}
Post-polio syndrome: _{^{deterioration of neurons affecting muscles (years later)}}

Picoviridae-Polio (Clinical)

Diagnose: Cell culture from stool, throat, CSF
Treatment is supportive
Prevention=Vaccine (live & inactive)
Salk vaccine (IPV 1955): Inactivated vaccine safe w/NO mucosal immunity & requires 1+ dose
Sabin vaccine (OPV): Live attenated oral only 1 dose, gives mucosal immunity w/Life long immunity
- SE: Reversion to virulent strain

Rhabodoviridae-Rabies (general)

* ssRNA (-) Enveloped helical "Bullet shaped" * **_Transmission:_** **_{^{Bite or body fluids}}** * _{^{Respiratory exposure to bat droppings}} * **_High risk:_** Animal handlers & vets * _{^{Neurotropic (cross BBB-infect nerve) due to G-protein spikes}} * _{^{Glycoprotein surface protein (N-terminal sequence)}} * **_Diagnosis:_** Sample saliva, CSF, skin * _{^{Detect Ag with Immunofluor}} * _{^{Brain biopsy = Negri bodies (inclusion bodies)}} * **_Treatment:_** Passive & active immunization * _{^{Clean wound w/soap & apply anti-rabies Ab @ site}} * _{^{Apply human (equine) rabies immunoglobulin (HRIG)}} * ^{_{Active Immuno-Inactivated virus (HDCV) made in human diploid cells (Day 1, 3, 7, 14, 28, 60)}} * **_Animal vaccination_**=_{^{Live recombo expressing G protein}}

Rhabodoviridae-Rabies (Pathogenesis)

1. Bite/wound multiplication in muscle cells 2. Passive ascent via sensory & replicates @ ***dorsal ganglion*** 3. ***Protein G*** binds to Acetylcholine receptor 4. Travels retrograde to ganglion neurons to punkinji & other CNS cells 5. Once brain infected descending infection to other organs * IP _{^{(60days-1year)}}-virus in muscle * Prodrome _{^{(2-10 days)}}-**_{^{Virus in CNS/Brain=Fever, pain @ bite}}** * Neurologic _{^{(2-7 days)}}-Diffusion of virus w/Ab in serum * **_{^{Hydrophobia, spasms, psychoactive}}** * **Coma-death** HIGH titer in brain/CNS

Clostridium Tetani-Tetanus (general)

* Gram + spore former-Slender bacillus ***"Tennis racket"*** due to terminal spores (local infection) * STRICT anaerobe-Found in soils * **_High Risk: _** * Trauma/Deep wound * Skin popping ***drug addicts*** * ***Neonatal***-Unclean cutting of umbilical cord * **_Virulence factors:_** * _{^{Cell produce-Tetanospasmin (AB) carried retrograde to CNS}} * _{^{AB toxin diffuses to inhibitory neurons-Degrades synaptobrevin=NT inhibitor (glycine/GABA)}} * ^{_{Result acetycholine secreted continuously=Unopposed contraction}}

Clostridium Tetani-Tetanus (Clinical)

* **_Tetanus-_**Strong muscle contraction **_{^{(from top to bottom)}}** * _{^{Lockjaw (Trismus) masseter muscles-Spasms (Risus sardonicus)}} * _{^{Drooling, sweating, presistent back spasms (opisthothonos)}} * ***No loss*** of consciousness * Localized confined to primary site * **_Neonatal:_** infection of umbilical stump **_{^{(mortality 90%)}}** * **_Diagnose:_** Symptoms are best way * **_Treat_**: Metronidazole or passive immunization * _{^{Penicillin inhibits the release of GABA (contraindicated)}} * **_Tetanus toxoid_**-_{^{Conj diphtheria toxoid/pertussis-DPT/DaPT}} * Booster every 10 years

Papovaviridae-JC Virus (general)

* Slow agent of CNS (gradual onset & fatal) * NAKED ds DNA * 80% seropositive humans **__{^{(Kidney/brain)}}_** * High risk: Immunocompromised & cell mediated immunity issues * **_Treat:_** Help support immunocompromised def * _{^{Primary replication in tonsils, GI & epi cells of kidney (sheds in urine)}} * Latent infection in kidney-***Bcells*** * **_{^{Viremia=Crossing BBB to CNS infect oligodendrocytes & astrocytes}}** * _{^{Loss of white matter-Myelin}}

Progressive multifocal leukoencephalopathy (JC)

* **Occurs in immunodef or immunosupression** * **_Activation of latent infection:_** * Fatal demylenating disease-white matter __{^{(multiple areas of brain)}}_ * Progressive weakness (visual, speech & personality) * **_Diagnosis:_** Detect JC virus in ***urine*** * ***MRI*** show lesions non-enhancing white matter lesion

Subacute sclerosing Panencephalitis (SSPE)

* Slow CNS agent * ***Serious late neurologic sequela*** found in measles pts * From ***defective form of measles*** virus **_{^{(paramyxovirus)}}** * **_High risk:_** Children younger than 2 **_{^{(can appear 7 yrs later)}}** * **_Symptoms:_** * personality & memory changes * Muscular jerks & blindness

Prions (General)

* Transmissible spongioform **_{^{(neurodegerative)}}** * PrP **_{^{(proteinacious infectious protein)}}** * **_No nucleic acid_**-resistant to heat, proteases, formaldehyde, radiation * Normal PrPc found on cell surface **_{^{(Alpha helical)}}** * **_PrPsc-_**scrapie prion altered conformation of PrPc * **_{^{Found in cytoplasm, protease & heat resistant, Beta sheet}}** * **Sporadic, acquired, germline mutation (alpha to beta)** * **_Transmission-_**exposure to infected tissue or medical device, inherited, transplantations, or feeding *

Prions (Pathogenesis)

* Lack of antigenicity **_{^{(no immune response)}}** * Lack of infammation & Interferon production * _{^{Generation & accumualtion of PrPsc = Neuronal dysfunction}} * Vacuolation of neurons **_{^(spongiform)}** & amyloid-like plaques/fibrils * **_Diagnose:_** EEG, CT, MRI * **_Prevention:_** Avoid exposure * Proper sterilization of neurosurgical tools/electrodes * Autoclave (121C for 1hr) * 1 M of NaOH

Prions (Disease)

* **_Kuru (Ingestion)_**-_{^{Tremors/Ataxia & later stages dementia}} * _{^{PrPsc plaques in biopsy}}-death **7-9 months** after symptoms * ***High Risk:*** Cannibals & Autopsy * **_Creutzfeldt-Jacob (Inherited)_**- Dementia & tremors in pts 50-70 years old * ***Amyloid tangles & Spongiform encephalopathy*** * **_New variant Cruetzfeldt-Jacob (ingestion):_** Contaminated beef appeard MORE plaques then CJD * **_Animal Scrapie_** = Sheep/goats