Micro Flashcards

1
Q

Difference between viral and bacterial meningitis

A

Viral is usually mild and self-resolving,
bacterial can be life-threatening.
VIRAL IS MORE COMMON

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2
Q

Bacterial meningitis CSF findings

A
low glucose
high protein (from breakdown of BBB)
high WBC (with high neutrophils)
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3
Q

Sx of viral meningitis patients

A
  • not extremely ill or encephalopathic
  • fever/malaise
  • headache
  • neck stiffness
  • low back pain
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4
Q

Causes of viral meningitis

A

enterovirus (80%) - includes Echo, Coxsackie, Enterovirus 71
Mumps - 10%
Recurrent aseptic meningitis - HSV2, HIV, VZV

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5
Q

Causes of viral encephalitis

A

30% arborvirus, via mosquitos, elderly/young
23% enterovirus, via GI/URI infx
27% HSV1, temporal lobe, acyclovir

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6
Q

Differential for viral encephalitis

A
bac meningitis
fulminant TB
RMSF, Lyme Dz
brain abscess
bacterial endocarditis
CNS vasculitis
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7
Q

HSV encephalitis

A
  • rare, usually reactivation of latent (can be acute too)
  • targets temporal lobe
  • causes necrosis, will see RBC in CSF
  • dx by PCR
  • 70% mortality without tx
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8
Q

Flaviriae family

A

Flaviviridae - SLE, West Nile, JEV
Pestiviruses - cow, pig, sheep
HCV

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9
Q

St. Louis encephalitis

A
  • caused by flavirvirus
  • causes: febrile HA, aseptic meningitis, encephalitis
  • incubation period 4-21d
  • 50% dead in 1 week, 80% dead in 2 weeks
  • no vaccine/antiviral
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10
Q

West Nile Virus

A
  • caused by flavivirus
  • from bird, localizes in salivary glands of mosquitos
  • humans are incidental hosts
  • most infx are mild w. febrile HA, myalgia, skin rash, swollen lymph glands
  • rarely serious, but no vaccine/antivirals
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11
Q

Togaviridae

A

Rubivirus - rubella, limited host range
ALphavirus - WEE, EEE, VEE
- Dz varies based on dose and host
- initially replicates in muscle/fibroblasts, fever for 2 weeks and may b/c encephalitis
- no vaccine (except for horse/labworker)

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12
Q

Bunyaviridae include

A

California encephalitis virus

La Crosse encephalitis virus

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13
Q

Replication fo Bunyaviridae

A

similar to RNA- viruses except genes are found on 2-3 separate RNA segments, replication occurs only in cytoplasm (vs. influenza)

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14
Q

Most common cause of arboviral induced pediatric encephalitis in the US

A

La Crosse virus

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15
Q

Rhabdoviridae include

A

vesiculoviruses - vesicular stomatitis
lyssaviruses - cause rabies
bullet shaped

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16
Q

Rabies

A
  • caused by lyssavirus
  • replication limited to neuronal cells, but concentration is high in salivary glands during final stages of dz
  • uniformly fatal if no tx
  • long incubation 2-3 months (why vaccine works)
  • bite –> enters muscle via pH dependent post endocytosis –> replicates locally –> through peripheral sensory nerves –> travels up spinal cord
  • prefs limbic system, midbrain, hypothalamus
  • prodromal: 2-10 days post bite, abnormal sensation around bite
  • acute neurologic phase: furious rabies, paralytic/dumb, hydrophobia
  • coma phase: 2-7 days post neurologic, death via respiratory arrest
  • vaccine is inactivated virus, Human Rabies Ig at site of wound
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17
Q

Arenaviridae includes

A

Lymphocytic choriomeningitis virus (LCMV)

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18
Q

Neuro complications and AIDS

A
  • affects 40% of AIDS pts
  • opportunistics: toxoplasmosis is most frequent, also crytococcal TB, JC (PML), CMV
  • cancer: CNS lymphoma, mets of Kaposis
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19
Q

What is ambisense replication an who has it?

A

LCMV…has 2 RNA segments for 2 proteins, has host cell ribosomes
- genome is used a template for transcription of NP and L mRNAs –> polymerase makes an anti genome for each segment –> + sense anti genome used to make a gp mRNA –> virus particles assembled and released by budding

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20
Q

Mosquito vector viruses

A

Flavi
Toga
Bunya

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21
Q

Animal vector viruses

A

Rhabdo

Arena

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22
Q

Arenaviridae transmission and dz

A
  • enter via pH dependent post endocytosis
  • ambisense replication strategy
  • transmitted via inhalation of aerosolized virus from rodent excreta/saliva
  • rarely fatal, usually an initial phase with fever/HA/NV (primary viremia) and aseptic meningitis phase 10 days later with sudden onset of deafness
  • no vaccines
  • antiviral: Ribavirin
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23
Q

Picornavirus

A
  • nonsegmented ssRNA+
  • polio, coxsackie, echo
  • mild febrile to aseptic meningitis
  • vaccine only for Polio
  • antiviral: Ribavirin
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24
Q

Paramyxovirus

A
  • nonsegmented ssRNA-
  • causes measles and mumps
  • MMR vaccine
  • no antiviral
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25
Q

Herpesvirus

A
  • linear dsDNA virus
  • HSV1/2, VZV, CMV, EBV
  • causes encephalitis
  • No vaccine
  • antiviral: acyclovir, ganciclovir, foscarnet
26
Q

Bacterial meningitis pathogens for neonates (<3mo)

A

GBS
G- enterics
Listeria

27
Q

Bacterial meningitis pathogens for 3mo - 2yo

A

S. Pneumo
Neisseria
H.I.B

28
Q

Bacterial meningitis pathogens for 2yo-18yo

A

S. Pneumo

Neisseria

29
Q

Work up for bac meningitis

A

Gram stain of CSF –> Rapid agglutination for capsule –> PCR –> Culture CSF/blood

30
Q

S. Pneumo

A
  • MCC of bac meningitis in US
  • capsulated, IgA Protease, Lancet Shaped
  • risk fx: splenic dysfunction, skull fracture/anatomic defect/cochlear implant, recurrent otitis media/AIDS
  • tx: Cephalosporin, Vancomycin (sometimes give Dex BEFORE)
  • 2 vaccines: Pneumovax and Prevnar
31
Q

Pneumovax

A
  • multivalent nonconjugated vaccine for S Pneumo
  • for high risk groups: >65yo, HIV, asplenia, transplant
  • protects against invasive pneumococcal dz
  • lasts 5-7 years, except in infants
32
Q

Prevnar

A
  • heptavalent conjugated vaccine for S. Pneumo
  • conjugated = anamnestic (memory)
  • generates Abs in kids as young as 2mo
33
Q

Neisseria Meningitides

A
  • 2nd MC bac meningitis (types B and C in the U.S.)
  • crowded areas, alcoholics, C6 deficiency
  • has capsule, LPS
  • transmitted via droplets, nasopharynx
  • rapid progression b/c endotoxin,
  • disseminated infx: petechial rash
  • Tx: penicillin G + ceftriaxone + Dex (b4)
  • Prophylaxis: ciprofloxacin
  • 2 vaccines
34
Q

Menomune

A
  • old capsular vaccine for N. Meningitides
  • A, C, Y, V135
  • for military groups and thigh risk
35
Q

Menactra

A
  • new conjugated vaccine for N. Meningitides
  • A, C, Y, V135
  • recommended for all kids 11-12yo
  • conjugated to diptheria
36
Q

H. Flu

A
  • MC bac meningitis in 6mo-5yo
  • Type B is the only capsulated strain and the only one that causes invasive dz
  • untyped = unencapsulated version causes otitis media
  • arthritis, epiglottitis, meningitis, osteomyelitis, pneumonia
  • gram stain needs CAP (not BAP) and factors V ( NAD/NADP) and factor X (Hemin)
  • conjugated type b vaccine (conjugated w diptheria) part of standard infant/childhood vaccines
  • tx: dex + 3rd gen ceph
37
Q

Listeria

A
  • causes bac meningitis
  • esp bad for pregnant women
  • G- bacillus
  • facultative intracellualr parasite
  • foodborne via unpasteurized cheese, hot dogs, deli meats
  • GI/GU, also found in genital tract, neonatal infx
  • pathogen: infects epithelial cells and monocytes/macrophages, colonize actin and move around cell and stay hidden from immune system
  • flu like in normal adults, can cause bacteremia, meningitis in IC and neonates
38
Q

Exerohilium rostratum

A
  • steroid associated fungus that causes meningitis in healthy individuals (common black mold)
  • incubates 20 days
  • culture CSF and send to CDC for PCR
  • Tx: IV voriconazole for meningitis and amphotericin B for severe cases (both for 3 months)
39
Q

Cryptococcus neoformans

A
  • MC fungal meningitis
  • inhaled via pigeon poop, causes meningitis in AIDS patients
  • inhaled, hematogenous spread, initial infx is asymptomatic pulmonary infx
  • chronic dz: meningitis with soap lesions in the brain, causes inc. ICP
  • Dx: yeast with halos in India Ink
  • Tx: amphotericin and flucytosine
40
Q

Cryptococcus gatti

A

fungus found in trees in Australia that can cause meningitis in healthy individuals

41
Q

Family Papovaviridae includes

A

Papilloma subfamily
Polyoma virus
Vacuolating Virus (Sv40 - monkey)

42
Q

Polyoma virus

A
  • circular ds DNA virus around histone
  • BK and JC viruses which are ubiquitous
  • only a problem in AIDS and transplant pts
  • transpalnt pts 90% fatality in 6 mo
  • AIDS pts changing HAART reduces fatality to 50%
43
Q

Polyoma virus pathogenesis

A
  • human cells are permissive and allow virus growth in the nucleus and release of virion by lysis (non permissive cells are transformed)
  • virulence factors include early 3 T Ag’s (small/large immortalize cell and middle/small transform cell) and late structural proteins
  • initial replication in GI or respiratory tract and secondary spread to kidney/lung/brain (kidneys are persistently infected)
  • can cause PML
44
Q

PML

A
  • Progressive Multifocal Leukoencephalopathy (PML)
  • caused by reactivated JC virus (a polyoma)
  • infects oligodendrocytes and demyelinates them
  • Sx: AIDS + clumsiness + progressive weakness + speech changes
  • Dx: PCR amplification for JC virus DNA (w. prove) from CSF/brain biopsy
45
Q

Polio epidemiology

A
  • nonenveloped icosahedral capsid, ssRNA+
  • currently in Afghanistan, Pakistan, Nigeria
  • infx in kids < 5yo, adult infx = delayed exposure to virus from inc. sanitation
  • only cases in Western world were due to revertant oral vaccine
46
Q

Polio transmission

A
  • causes Poliomyelitis ~ Flaccid paralysis
  • spread fecal-oral in the summer
  • humans are the only reservoir
47
Q

Polio dz process

A
  • incubates 7-14 days
  • initial replication is pharynx and GI
  • viremia –> enters BBB –> destroys motor neurons during replication
48
Q

Polio dz manifestation

A
  • mostly subclinical but 3 forms exist
    1. Abortive Poliomyelitis: nonspecific febrile illness 2-3 days with no CNS involvement
    2. Aseptic Meningitis (Nonparalytic Poliomyelitis): febrile illness + stiff neck with limited CNS infx
    3. Paralytic Poliomyelitis: febrile illness –> lapse of sx –> flaccid paralysis +/- attack all limbs or brainstem. Gradual recovery in 6 mo with permanent lingering paralysis (5% fatality rate) and Post-Polio syndrome with inc. weakness forever
49
Q

Polio diagnosis

A

Early rectal, throat, stool swabs
Later CSF
Vaccine components distinguished from wild virus via strain-specific polyclonal sera

50
Q

Polio Salk

A
  • Polio vaccine IPV = formalin inactivation
  • prevents reversion
  • protects against paralysis but not spread
  • 3 subQ injections + booster
  • CDC recommended for U.S.
51
Q

Polio Sabin

A
  • Polio vaccine OPV = live oral vaccine
  • live oral vaccine so possible reversion
  • oral and cheap
  • protects against paralysis AND spread
  • CDC recommended for global
52
Q

TSE

A
  • transmissible spongiform encephalopathy
  • caused by prions, infectious proteins
  • looooong incubation period
  • spongiform change, gliosis, amyloid plaque, neuronal loss
  • Dz: Kuru, CJD, GSS, FFI, varian CJD, scrapie
53
Q

Scrapie

A
  • subacute ataxia of sheep/goat
  • 1 y/o: infx of alimentary tract (lymphatic/intesting)
  • 2 y/o: infx of brain
  • 3 y/o: spongiform change and clinical dz
54
Q

Kuru

A

TSE - tremble with fear

- caused by cannibalism EW

55
Q

Prion

A
  • infectious protein capable of causing TSE

- extremely resistant to things that damage nucleic acids/viruses (radiation, nucleases, proteases, EtOH)

56
Q

Prion Theory

A
  • increase in conserved prion protein on Chr 20 in neurons and lymphocytes
  • PrPC: normal cellular form of surface gp, reduces Abeta plaques via dec. BACE1 activity
  • PrPSC: dz form that can occur via sporadic/familial mutation or via infx
  • C vs. SC: difference between PrPsc is different folding (same AA sequence) so it b/c resistant to proteases and causes inc. in intracellular aggregates and dec. stability
57
Q

How do PrP-Sc form?

A
  • P* intermediate form
  • PrP-Sc acts as template for P* causing it to fold into Sc form (so template predicts final conformation here, NOT AA SEQUENCE)
  • chain reaction happens
58
Q

CJD

A
  • MC TSE
  • akinetic mutism, cerebellar dysfunction, dementia, clonus
    1. sporadic: 60yo, bad prognosis, specific EEG
    2. iatrogenic: hGH from pituitary graft > corneal/dural grafts, NOT transmitted through blood
    3. familial: AD mutation in prion protein, 45-50 yo w. 2-4 yr survival
  • Dx: spongiform change, lack of A beta plaques, CSF to rule out tertiary syphillis and measles
59
Q

vCJD

A
  • Mad Cow Dz
  • contaminated beef and blood transfusion
  • more contagious than reg CJD
  • AD w. homzygous methionine @ codon 129
  • 29yo w. 14 mo survival + anxiety, depression, sensory (visual/akinetic mutism)
  • Dx: atypical EEG + prion + tonsilar biopsy + florid plaques + spongiform basal ganglia
60
Q

Gerstmann Straussler Scheinker Dz

A
  • AD mutation in codon 102 of prion protein
  • 48yo w. 5 yr prognosis
  • gait/ataxia changes > dementia
  • atypical EEG
  • inc. A beta plaques (vs. CJD)
61
Q

Familial Fatal Insomnia

A
  • AD mutation in codon 129/178
  • Age 49 w. 13 mo prognosis + insomnia + ANS probz
  • inc. neuronal loss but dec. spongiform change and less A beta plaques
62
Q

MC acute encephalitis

A

Herpes encephalitis