Week 31 CNS infections Flashcards
1
Q
How does the investigation of CNS infections differ?
A
First step in neuro evaluation is localization through hx and exam.
Then the ddx is determined by the localization.
2
Q
Discuss the infections of CNS compartments
A
Epidural space = epidural abcess
Subdural space = subdural empyema
Subarachnoid space = meningitis - infection of the meninges
Brain parenchyma = Brain abcess, encephalitis - infection of the parencyma.
3
Q
Discuss routes of infection for CNS infections
A
Hematogenous = most agents
Contiguous (sinus, ear, face) = bacteria
Direct inoculation (trauma/surgery) = bacteria
Via nerves = HSV, VSV
4
Q
Discuss infection and how it spreads into the brain
A
Early cerebritis results in local edema and neutrophil infiltration when breeches the blood brain barrier.
Then there is infiltration of macrophages and lymphocytes which results in central necrosis and encapsulation by a fibrotic capsule.
Presents as ring enhancing lesion on radiology.
5
Q
S&S of a cerebral abscess
A
Headache
Focal signs referring to location: motor/sensory, ataxia, cognitive, seizures….
Features of mass effect: decreased LOC, papilledema
Fever (60%)
6
Q
In what cases would a CNS infection not present with a fever?
A
Localized CNS infections (abscess)
Immunocompromised
Anti-inflammatories
Infants/older adults.
7
Q
Discuss the different time courses of infections
A
Viral and bacterial usually subacute time course, hours to days.
Fungal, myobacterium, spirochetal usually chronic time course, >1 month.
8
Q
Clinical HSV1 mechanism of CNS invation
A
Unclear whether it is a primary infection or a reactivation.
>50% are caused by a different strain than responsible for cold sores.
Spread from trigeminal ganglia through sensory fibers to the meninges of temporal lobes and orbitofrontal areas.
9
Q
Encephalitis
A
Inflammation of brain parenchyma with associated brain dysfunction
10
Q
Clinical presentation of encephalitis
A
Encephalopathy (altered LOC, personality, cognition, memory) >24 hours and evidence of inflammation.
Seizures common.
Focal neurodeficits.
High mortality with significant cognitive/physical disability in survivors.
40% infections HSV»VZV>TB
11
Q
Clinical clues to etiology of infection
A
Season:
Late summer/fall = mosquitoes/ticks, enteroviruses.
Winter = influenza
Geography
Animal/insect exposures: Bats, cats, birds/mosquitoes, ticks
Food
Sexual hx
Age
12
Q
Meningitis
A
Infection/inflammation of fluid and membranes surrounding CNS.
F Fever
A Altered mental statuss
N Neck stiffness
H Headache
13
Q
Meningitis clues to specific pathogens
A
Pneumonia prior = Strep pneumoniae
Otits/mastoiditis/sinusitis = Strep spp, gram neg anaerobes, haemophilus, enterobacteria
Immunocompromised, pregnant, >50 = Listeria, cryptococcus, HIV.
Characteristic petechial/purpuric rash = Neisseria meningitidis
Arthritis = Neisseria meningitidis
Brainstem syndrome = Listeria
Neurosurgical procedure prior = Staph, gram neg bacili
14
Q
What is the most common cause of bacterial meningitis in adults?
A
Strep pneumoniae
15
Q
Clinical evaluation signs of meningitis
A
Brudzinski’s
Kernig’s
Jolt accentuation sign
16
Q
Work up for meningitis
A
CBC, chemistries, coagulation, cultures !!STAT!!
CXR
CT head
LP: cell count, protein, glucose, gram stain, viral PCR (HSV, VSV, enterovirus), fungal/myco cultures, cryptococcal antigen, VDRL.
Some patients: Nasopharyngial aspirate, ESR/CRP, cryptococcal antigen, HIV, TB skin, viral PCR
17
Q
What is normal CSF pressure and what happens with:
1. bacterial
2. viral
3. fungal
A
Normal = 5-20 cm H2O
Bact = increases
Viral = stays the same or increases
Fungal = increases
18
Q
What is normal CSF WBC and what happens with:
1. bacterial
2. viral
3. fungal
A
Normal = 0-5
Bact = large increase 100-50000 Neuts
Viral = increases 5-1000
Fungal = increases 5-1000 Lymphocytes
19
Q
What is normal CSF protein and what happens with:
1. bacterial
2. viral
3. fungal
A
Normal = 0.2-0.45 g/L
Bact = large increase 0.4-4.4 g/L
Viral = stays the same of increases
Fungal = large increase 0.2-5.0 g/L
20
Q
What is normal CSF glucose and what happens with:
1. bacterial
2. viral
3. fungal
A
Normal = 2.2-3.9 mmol/L
Bact = decreases
Viral = stays the same
Fungal = stays the same or decreases.
21
Q
When should you do neuroimaging before lumbar puncture?
A
Focal neurological deficit
Depressed LOC
Seizures
Known mass lesion
22
Q
When should you CT head before lumbar puncture?
A
Focal neurological deficit
Depressed LOC
Seizures
Known mass lesion
23
Q
What is the major caution with LPs
A
If intracranial pressure is elevated, and LP could cause brain herniation d/t the sudden decrease in pressure in the spinal cord from removal of CSF.
24
Q
Neisseria mechanism of CNS invasion
A
Hematogenous spread.
Interaction of meningococci with brain endothelial cells.
Induction of signaling pathways in the host cells.
Cells form docking structures allowing menigococci to “roll” in like leukocytes.
25
Host defenses/response to infection
Bacterial entry into CSF ->
Cell wall components/bacterial toxins->
Microglial activation, inflammatory mediators, BBB injury ->
Vasogenic edema, neuronal injuries, seizures, ischemia.
26
What is the physical change in the meninges d/t to bacterial infection?
Subarachnoid space is markedly expanded by the presence of inflammatory cells (neuts).
27
Prognosis for acute bacterial meningitis
Mortality 10-15%
Neurological complications ~ 28%
28
Discuss chronic meningitis
Persisting beyond 1 month.
Fungal and bacterial etiologies.
Fungal: histoplasmosis, blastomycosis, coccidioidomycosis, cryptococcus gattii. In immunocompromised; cryptococcus neoformans, candida.
Bacterial: myobacterium TB, meningovascular syphilis.
Ddx: Inflammatory disease, neoplasia, chemical meningitis d/t rupture of epidermoid cyst or medications.
29
Aspergillus
Molds that can invade tissues and vasculature with increasing immunosuppression d/t neutropenia, transplant, steroids, HIV.
Usually primary to lungs or paranasal sinus.
Treat with CNS penetrating fungicidal (voriconazole), Amphotericin B, Surgical debridement.
30
Cryptococcus
Yeast found in soid and bird excrement. Opportunistic with meningitis or cryptococcoma.
Nutropenia, transplant, steroids, AIDS, exposure to birds, roosting sites, pidgeons.
Meningoencephalitis, obstructive hydrocephalus.
Usually primary to lungs.
Treat with amphotericin B + flucytosine followed by oral fluconazole.
31
Innate host defenses in CNS
Microglia
Granulocoytes (10%) entry compared to other organs.
Dendritic cells, macrophages (perivascular): reside outside the CNS and act as presenting cells to T cells.
32
Adaptive host defenses in CNS
CD20+ B cells
T cells entry via cell adhesion molecules (10%) compared to other organs. Enter through choroid plexus epithelium ,venules in parenchyma, perivascular spaces.
33
How does syphilis present on radiology
MRI brain & orbits: faint enhancement of retrobulbar optic nerve.
34
Labs for syphilis
+ serum VDRL (in 25% of patients)
CSF VDRL better test, but still not 100% sensitive.
CSF abnormal in 70% (increased lymphocytes & protein, normal or decreased glucose).
35
Clinical presentation of syphilis
Meningitis, vasculopathy/infarct.
Tabes dorsalis (sensory ataxia, dysautonomia, pain)
Light-near dissociation
Progressive cognitive impairment.
36
Treatment for syphilis
14 days penecillin
37
Taenia solium (cystericercosis)
Helminthic infection. Common worldwide cause of focal epilepsy.
Travel or living in endemic area.
Consumption of contaminated food.
Intestine -> mm, brain, liver, eye, subcu tissue.
Cysts may be asymptomatic for years.
Seizures in 80%
Focal signs in 16%
Serology 98% sensitive when 2 or more parasites, can be negative with cysts.
CSF elevated protein, lymphocytosis.
O&P
peripheral eosinophils
38
Treatment for tanenia solium (cystericercosis)
Albendazole or praziquantel for living organisms + steroids.
39
Toxoplasmosis
Intracellular protozoal parasite usually seen in immunocompromised.
Cats!
Primary infection usually asymptomatic -> chorioretinitis, pneumoitis, GI, mm -> cerebral abscesses with focal signs.
Imaging: ring enhancing lesions
Labs: IgG w/ brain lesion, CSF lymphocytosis with increased protein. PCR.
40
Treatment of toxoplasmosis
Pyrimethamine + Sulfadiazine
41
Structured approach to meningitis
CBC/blood cultures
Anitbiotics + dexamethasone (do early, but Bugs & Drugs recommends LP before abs unless LP or CT cant be done quickly)
CT if indicated
LP
Directed therapy & support
42
What is the risk of getting the following from a needle stick of a (+) patient?
1. HIV
2. Hep C
3. Hep B
HIV= 0.3%
Hep C = 1%
Hep B > 3%
43
Where are the highest rates of HIV, globally?
East/south Africa
Asia
West/central Africa
then East Europe/ Latin americal
44
Infections of CNS compartments
Epidural space = Epidural abscess
Subdural space = Subdural empyema
Subarachboid space = meningitis
Brain parencyma = Brain abscess, encephalitis
45
Cerebral abscess formation
Begins with local edema and neutrophil inflitration.
Macrophage and lymphocytes infiltrate over weeks.
Central necrosis and encapsulation by fibrotic capsule.
46
S&S assoc. w/cerebral abscess
Headache.
Focal signs.
Features of mass effect.
Fever.
47
When would CNS infections present without fever?
Localized CNS infections (abscess)
Immunocompromised
Pts on anti-inflammatory analgesics
Infants & older adults
48
Clinical presentation of CNS infections
Fever
Headache
Seizure
Confusion or altered LOC
Focal signs
Subacute time course for most viral/bact. (hours-days)
Chronic for fungal, mycobact, spirochetes (>1 month)
49
What is the mechanism that HSV1 causes CNS infection?
Spread from trigeminal ganglia via sensory fibers to meninges of temporal lobes and orbitofrontal areas.
50
Encephalitis definition
Inflammation of brain parenchyma w/associated brain dysfunction
51
Infectious causes of encephalitis
HSV >> VZV > TB
52
T2/FLAIR hyperintensities are indicative of what?
Limbic regions:
HSV, HSV6
Deep grey matter:
Arboviruses
Periventricular:
Cytomegalovirus
Juxtacortical:
Progressive multifocal leukoencephalopathy/JC virus
53
Ring enhancing lesions are indicative of what?
Immunocompetent:
Bacterial abscess
TB
Neurocystercercosis
Immunocompromised:
Toxoplasmosis
EBV
Mucormycosis
54
Clinical clues to infection etiology in CNS
Season: summer fall = ticks/mosquitoes/enterovirus, winter = influenza virus.
Geography: travel
Exposures: Bats, cats, birds, mosquitoes, ticks
Food
Sex
Age
55
Meningitis after pneumonia is due to what pathogen?
Strep. pneumoniae
56
Meningitis after otitis/mastoidits/sinusitis is due to what pathogen?
Haemophilus spp.
57
Meningitis in immunocompromised, pregnant, >50 years is due to what pathogens?
Listeria, Cryptococcus
58
Meningitis with characteristic rash is d/t what pathogen?
Neisseria meningitidis
59
What cause of meningitis are greatest in under 2 months?
GBS
60
What happens to number of cases of meningitis as childhood age increases?
Decrease
61
What is the most common cause of meningitis in adults?
Strep pneumoniae
62
Special tests for meningitis
Jolt accentuation sign.
Budzinski
Kernigs
63
Mengitis work up
CBC, Chemistries, Coag, Cultures STAT
CXR
CT head
LP
Some patients: nasopharyngeal aspirate, ESR, CRP, crptococcal antigen, HIV, TB, viral PCR
64
What LP results are typical for bacterial causes of meningitis?
Increased pressure.
Large increase of neuts.
Large increase in proteins.
Decreased glucose.
65
What LP results are typical for viral causes of meningitis?
Normal or increased pressure.
Slightly elevated WBC.
Normal or increased protein.
Normal glucose.
66
What LP results are typical for fungal causes of meningitis?
Increased pressure.
Slightly elevated lymphocytes.
Elevated protein.
Normal or decreased glucose.
67
When to do neuroimaging before LP and why
Focal neuro deficit.
Depressed LOC
Seizures
Known mass lesion.
If intracranial pressure is elevated, LP can theoretically cause brain herniation.
68
Neisseria meningitidis
2nd most common cause of community acquired bacterial meningitis in adults.
Normal inhabitant of nasopharynx.
Quad vaccine routine in BC since 2016.
Can cause invasive disease and rash.
Complications: disseminated intravascular coagulation, severe sepsis, permanent hearing loss.
69
Neisseria mechanism of CNS invasion
Hematogenous spread.
Interaction with brain endothelial cells.
Induction of signalling pathways in the host cells.
Cells form docking structures allowing meningococci to "roll in" like leukocytes.
70
Causes of acute meningitis
Bacterial
Viral
Parasitic
71
Causes of chronic meningitis
Fungal
Bacterial
72
Common acute meningitis bacteria
Listeria
E.coli.
Strep pneumo.
Neisseria.
Haemophilus.
Staph A.
Pseudomonas.
Berrelia burgdorferi
73
Common acute meningitis viruses
Enterovirus
HSV1
HSV2
EBV
VZV
HIV
74
Common acute meningitis parasites
Naegleria fowleri
Angiostrongylus cantonensis
Balamuthis mandrillaris
75
Common chronic meningitis fungi
Immunocompetent:
Histoplasmosis
Blastomycosis
Coccidoidomycosis
Cryptococcus gatii
Immunocompromised:
Cyrptoccocus neoformans
Candida
Aspergillus
76
Common chronic meningitis bacteria
Myobacterium TB
Meningovascular syphilis
77
Define chronic meningitis and Ddx
Meningitis persisting over 1 month.
Dds: Inflammatory disease, neoplasia, chemical meningitis, secondary to medications.
78
Aspergillus:
1. background
2. pathogenesis
3. clinical
4. laboratory
5. treatment
1. Molds that can invade tissues and vasculature with increasing immunosuppression
2. Neutoprenia, transplant recipients, chronic steroids, AIDS with low CD4 count
3. Intracranial spread, usually primary site lungs/paranasal sinus.
4. Serology +, PCR, bronchial lavage.
5. CNS penetrating fungicide (voriconazole), Amphotericin B, Surgical debridement.
79
Cryptococcus:
1. background
2. pathogenesis
3. clinical
4. laboratory
5. treatment
1. Yeast found in soil and bird excrement, opportunistic infection.
2. Neutopenia, transplant recipients, chronic steroids, AIDS w/low CD4, exposure to BIRDS, ROOSTING SITES, PIGEONS.
3. Meningoencephalitis, obstructive hydrocephalus. Primary site lung.
4. Inda ink CSF exam, fungal culture, LATEX AGGLUTINATION TEST CSF/SERUM, PCR.
5. Amphotericin B + Flucytosine followed by oral fluconzaole
80
What type of disease should you suspect if immunocompromised?
Neuroinfectious.
HIV pts:
CD4 <200 = crypococcal meningitis and PML
CD4 <100 = toxoplasmosis and EBV
CD4 <50 = CMV encephalitis
Congenital immunodeficiency
Hematologic malignancy
Immunosupporessive/immunomodulatory meds
81
Host defences for CNS infections
Innate: microglia, neuts, baso, eosino, dendritic cells, macrophages in perivascular.
Adaptive: CD20 B-cells. T Cells enter via cell adhesion molecules
Dendritic cells and macrophages reside outside CNS and sample spaces adjacent to ventricles. Then present to antigens to T cells.
T cells enter through choroid plexus epithelium, venules in parenchyma, perivascular spaces.
82
Syphilis imaging, serology, treatment
MRI brain & orbits = faint enhancement of retrobulbar optic nerve.
+ serum VDRL
Treat with Penicillin G for 14 days.
83
Syphilis
1. background
2. pathogenesis
3. clinical
4. laboratory
5. treatment
1. Spirochetal infection causing meningitis, vasculopathy, optic neuropathy, parenchymal lesions, dorsal root ganglionopathy.
2. Tertiary infection affects widespread systems and causes a chronic inflammatory process.
3. Meningitis, vasculopathy/infarct, Tabes dorsalis, Argyll-Roberson pupil, progressive cognitive impairment.
4. Serum VDRL, PCR, FTA, LP
5. Penicilin G
84
Tabes dorsalis
Sensory ataxia, dysautonomia, pain
85
Taenia solium (Cystercercosis)
1. background
2. pathogenesis
3. clinical
4. laboratory
5. treatment
1. Helminthic infection, common worldwide cause of focal epilepsy.
2. Travel or residence in endemic area, consumption of contaminated food. Residence in intestine -> mm, brain, liver, eye, SC tissue. Cysts may be asymptomatic for years.
3. Seizures, focal signs.
4. Serology when >2 parasites, CSF, ELISA, O&P, peripheral eosinophils
5. Albendazole or praziquantel + steroids
86
Toxoplasma gondii
1. background
2. pathogenesis
3. clinical
4. laboratory
5. treatment
1. Intracellular protozoa, almost always seen in immunosuppressed patients.
2. Definitive host is cat.
3. Primary infection asymptomatic. Chorioretinitis, pneumonitis, GI, mm, multiple cerebral abscesses with focal signs.
4. Ring enhancing lesions, IgG, LP, PCR
5. Pyrimethamine + sulfadiazine
87
Most sensitive type of imaging for CNS infections
MRI
T2 FLAIR MRI - same as T2 except CSF signal appears black. Helps to identify pathology adjacent to CSF spaces.
88
What does meningitis look like with T2 FLAIR?
Abnormal fluid is bright (edema).
Meningeal layers are inflamed and become bright on FLAIR.
Gyriform patter indicates subarachoid involvement.
Diffusion restriction of thick exudate in the subarachnoid space.
89
MRI w/T2 FLAIR:
1. Appearance of infection
2. Mechanism
3. Utility
1. Bright
2. Inflammation (abnormal water), CSF is black so you can clearly see edema.
3. Extent of inflammation
90
MRI w/Gadolinium
1. Appearance of infection
2. Mechanism
3. Utility
1. Enhancement
2. Hyperemia, BBB disruption
3. Identify abscesses
91
MRI w/Diffusion:
1. Appearance of infection
2. Mechanism
3. Utility
1. Bright
2. Restricted water diffusion due to exudate
3. Extremely sensitive for abscess vs inflammation
92
Discuss the timing of investigations and imaging in CNS infection
1. Suspect infection
2. CT: Rule out hydrocephalus or structural abnormalities that increase risk of herniation.
3. LP
4. Antibiotics
5. MRI or CT if poor treatment response
6. Clinical response
93
When to image prior to LP
Immunocompromised
Hx of CNS disease (mass, stroke, focal infection)
Seizure w/in 1 week of presentation
Focal neuro deficit
Papilledema
Altered LOC
94
What would you see on CT that prohibit LP
Radiologic signs of increased intracranial pressure:
Midline shift, Obstructive hydrocephalus, Basilar cistern compression
Increased risk of tonsillar herniation:
Posterior fossa mass.
95
What is the most important test if CNS infection is suspected?
LP prior to antibiotic initiation
96
Mneumonic for complications of neurologic infections
HACTIVE
H Hydrocephalus
A Abscess
C Cerebritis
T Thrombosis
I Infact
V Vasculitis/Ventriculitis
E Extra-axial collection
97
Extra-axial collection
Subdural empyema.
In adults, related to sinus disease, penetrating trauma, neurosurgery.
Similar imaging to abscess.
98
Approach to HIV diagnosis in adults
Confirm diagnosis:
Pt. 1- ELISA to detect HIV antibody or vial protein (p24 antigen), can have false (+). Confirm with 2nd EIA
Pt. 2 - Confirmatory Immunoblot on EIA, rules out false (+)
99
How soon can viral detection of HIV be made
10 days
100
When can antibody detection be done for HIV
Just over 20 days.
101
When is the best time to test for p24 antigen?
25-40 days
102
When is HIV antibody highest
After 3 months.
103
When is HIV RNA highest?
1 month, then lowers and plateaus around 40 days.
104
HIV testing guidelines in BC
Every 5 years ages 18-70
Every 1 year if higher risk/burden.
Once for patients >70 if no prior test.
Always offer for:
bloodwork for new or worsening condition
present w/symptoms
asked
risk for HIV
pregnant
other STIs present.
105
Key points of HIV entry and targets of therapy
Docking on cell CCR5 protein = CCR5 antagonists
Reverse transcription = Reverse transcriptase inhibitors (NRTI/NNRTI)
Integration into host DNA = Integrase inhibitors
Viral protein assembly = Protease inhibitors
106
Antiretroviral therapy
Recommended to start at time of diagnosis.
Goal is long term viral suppression = no further risk of progression/infections.
3 drug regimen: 2 NRTI + Integrase inhibitor or NNRTI or protease inhibitor.
Reduces transmission of HIV to partner
107
PrEP
HIV Pre-Exposure Prophylaxis
Dual NRTI on daily basis for those at risk of HIV transmission.
97-98% reduction in HIV infection.
Offered to elevated risk populations; M/M, HIV + partner.
108
HCV natural history
15% present with acute symptoms:
Jaundice, dark urine, clay coloured stools, fever, abdo px.
Increase AST/ALT
Leads to fibrosis of liver.
75-85% of patient develop chronic infection, remainder clear spontaneously.
In chronic 16-20% develop cirrhosis after 20 years.
109
1.HBsAG + vs -
2. anti-HBc + vs -
3. anti-HBs + vs -
4. IgM anti-HBc + vs -
1. Serum antigen + = current infection
2. HB core antibodies + = natural infection
3. HB serum antibodies + = natural infection or vaccination
4. IgM HB + = acute infection, IgM HB - = chronic infection (with serum antigens)
110
What are the phenotypic and genotypic methods used in labs for identification of pathogens?
Phenotypic: Proteomic, Biochemical, Serological
Genotypic: PCR, Sequencing
111
Types of samples tested in the lab
Swabs
GBS screen
Urine
Stool
Blood
112
Serum vs whole blood collections
Serum = serology testing (antibodies)
Whole blood = PCR testing
113
Discuss transportation of lab samples
Specimen maintenance: appropriate collection system, temperature, timing.
Moving clinical specimens: federally mandated laws
114
Types of testing used for infectious diseases
Microscopy
Cultures
Susceptibility testing
Serology
Antigens/toxin detection
Molecular (DNA/RNA) identification
115
What is the first step in bacterial identification?
Gram stain
1. Fixation
2. Crystal violet: + charge passes through cell wall and binds to - charges inside the cell.
3. Iodine: - charge binds to crystal violet
4. Decolorization: Gram (+) cell wall dehydrates, dye-iodine trapped, does not decolorize. Gram (-) cell membrane dissolves, dye-iodine washes out.
5. Counter stain: Gram (+) does not show red stain d/t presence of dye-iodine comples. Gram (-) stains pink with counter stain.
116
Ultimate use of serology assays
Screening
Confirmatory
Use of serum for detection of antibodies
117
Molecular testing
Multiplex molecular assays: 1 test to detect a number of pathogens, powerful, timely
118
Culture vs PCR
Culture - can use for antiobiotic testing
Not all organisms are clutivable.
Sterile sites looking for virus may require PCR.
PCR more sensitive for some things like shigatoxin.
119
What do staph infections look like in culture
Gram (+) in clusters
120
Which cocci are catalase + and -
Catalase (+) = Staphlococcus
Catalase (-) = Streptococcus
121
What is a gram (-) rod that is oxidase (+)
Pseudomonas
122
What test is used to determine drug susceptibility
E-test
mecA gene detection
123
Out of Tetracycline, TMP-SMX, Vancomycin for MRSA inpatient, which drug?
Vancomycin: in hospital, blood stream infection
124
Best drugs for MSSA
Cloxacillin
Cephalexin
125
Best drugs for MRSA
Oral:
TMP-SMX
Doxycycline
Linezolid
Clindamycin
IV:
Vancomycin
Daptomycin
Cetraroline (only beta-lactam that works for MRSA)
126
What tests for Hep A
IgM, IgG
127
What tests for Hep C
Antibody
RNA
128
Which virus presents with "dew drop on a rose petal" vesicle?
VSV
129
Stages of treponema pallidum (syphillis)
Stage 1: Chancre sore 3-90 days after exposure
Stage 2: Body rash 4-10 weeks after exposure
Stage 3: Affects internal organs 3-15 years after exposure
130
What is the best microbiologic test for syphillis?
Serology #1
PCR
131
Testing for syphillis
Step 1: Enzyme immune assay - can give false (+), if (+) confirm with ->
Step 2: Treponema pallidum Particle Agglutination (TPPA)
Step 3: Rapid Plasma Reagin (RPR) - tells how active the disease is.
132
Test results if never infected with syphillis
EIA = -
TPPA = -
RPR = -
133
Test results for false (+) EIA
EIA =+
TPPA = -
RPR = -
134
Test results for previously treated infection, new infections (2 weeks), or late latent infection
EIA = +
TPPA = + (if previous infection then EIA and TPPA will be (+) for life)
RPR = 1:1 or -
135
Test results for current syphillis infection
EIA = +
TPPA = +
RPR = >1:4
136
If a patient were infected with HIV in the past 2 weeks, which microbiologic test will be positive?
PCR
137
HIV testing
Rapid POC: screening test, detects HIV antibody, 1st (+) at 22 days.
4th gen EIA: screening test, detects HIV antibody and p24, 1st (+) @ 18 days.
ImmunoBlot: confirmatory test, detects multipel HIV antibodies, 1ST (+) @ 33 days.
NAAT (PCR): Confirmatory test, detects HIV RNA, 1st (+) @ 11 days **Most reliable test.
138
What is the best test to identify potential TB?
AFB stain, culture, and susceptibility testing.
139
Infection and establishment of TB latency
CD4 T cells recognize TB antigen.
Clonal expansion of activated T cells.
Cytokin secretion (INF-y) **Key in controlling TB infection
Macrophages activated
CD4 cells destroy infected macrophages, TB growth inhibited within macrophages -> granuloma
140
Natural hx of TB
New infection:
5% get primary TB
95% get latent TB infection -> if HIV (-) 5% reactivate after 2 years, if HIV (+) 5-8% reactive each year.
141
Risk factors for TB reactivation
***HIV INFECTION IS SINGLE LARGEST RISK FACTOR***
Substance use
Silicosis
Diabetes mellitus
End stage renal disease
Low body weight
Cancer
Medical immune suppression
142
How is latent TB Diagnosed?
Tuberculin skin test
Interferon gamma release assay (IGRA)
143
Diagnosis of TB
1. Clinical: BIG 4 fever, cough, night sweats, weight loss
2. Radiography: CXR, chest CT
3. Microbiology: AFB smear, culture, PCR
144
What antibiotics should immediately be used for TB
Vancomycin
145
If there is a (+) TST what is the next step?
Perform IGRA to determine if it is true latent TB infection and not from vaccine.
146
4 components of the herpes virus
1. Core - linear dsDNA *key for pathophysiology
2. Capsid
3. Tegument
4. Envelope
147
Steps of herpes infection
1. Attaches to host cell using glycoprotein
2. Envelope fuses with plasma membrane and releases nucelocapsid into cytoplasm
3. Nucleocapsid transported to nuclear pores
4. Viral DNA released into nucleus
6. Replication with symptoms or latency
148
Discuss the process of latency and reactivation
Acute infection from epithelial cells migrates to ganglia via retrograde transport.
Reactivation uses anterograde transport from ganglia to tissues.
HSV 1: from trigeminal ganglion, HSV 2 from sacral ganglion
149
Herpes classification
Alpha: neurotropic, infects epithelial cells: HSV 1/2, VZV
Beta: latent in lymphoreticular system, infects many tissues: CMV
Gamma: lymphotrophic, infects B cells: EBV
150
Basic principles of HSV infections
Once infected, infected for life.
True latency period.
Reactivation causes most disease manifestations.
Cycles between latency -> lytic cycles.
Naive patient = worse disease.
Immunosuppression = worse disease.
151
HSV1
Herpes labialis.
Infection of lips and oral mucosa.
Latency in trigeminal sensory ganglion.
90% seroprevalence by 30 years of age.
Transmission = person to person via contact with lesion or secretions. **Can transmit without lesions.
152
Complications of HSV1
Encephalitis.
HSV is #1 fatal sporadic encephalitis.
CSF shows lymphocytes, RBCs, elevated protein.
PCR gold standard for diagnosis.
Unilateral temoral lobe involvement on imaging.
***EMERGENCY*** Treat with IV acyclovir ASAP
If someone presents with encephalitis, check for HSV1!!
153
HSV2
Genital herpes.
Latency in sacral ganglia.
Seroprevalence 15-20%.
Transmission = person to person.
Transmission more likely when asymptomatic
154
Treatment for HSV 1/2
Acyclovir
Valacyclovir
155
VZV
Varicella (chicken pox) and herpes zoster (shingles)
Latency in sensory dorsal root ganglia.
Highly contagious.
Varicella: Fever, malaise, pharyngitis, loss of appetite -> rash -> macules -> papules -> vesicles -> crust
Zoster: Prodomal neuritis -> rash, limited to 1 or 2 dermatomes
156
VZV complications
Post herpetic neuralgia:
px beyond 4 months of rash
dysesthesias, allodynia, numbness
Secondary skin infections
Herpes Zoster opthalmicus
Herpes Zoster oticus: Ipsilateral facial paralysis, ear pain, vesicles
157
Treatment for VZV
Treat those at risk of complications w/ acyclovir, valacyclovir.
Need higher doses than HSV
158
CMV
Infects a broad range of cells.
Inverse relationship to SES.
Increased seroprevalence with age.
Shed in urine, blood, throat, cervix, semen, stool, tears, breast mild.
Contact with secretions, blood, verticle.
159
CMV primary infection
Usually asymptomatic (vs CMV mononucleosis: same symptoms as EBV).
Fever, fatigue, lymphocytosis, andenopathy, splenomegaly, rashes with antiboitics.
160
Diagnosis of CMV
Serology: IgM or 4xs IgG
PCR can be misleading
Compatible clinical picture
Negative monopot test
161
Treatment of CMV
Immunocompetent:
Most only need supportive care.
Antivirals for severe presentations: Ganciclovir, Valganciclovir
Immunocompromised:
Bone marrow transplant, solid organ transplant.
Antivirals
162
EBV
Infection of B cells.
90-95% seroprevalence.
Primary infection: malaise, headache, fever -> tonsilitis, pharyngitis, lymphdenopathy, splenomegaly.
Complications: rash with amoxicillin, splenic rupture
163
Diagnosis of EBV
Compatible clinical picture.
Lymphocytosis.
(+) monospot test.
Viral capsid - IgM, IgG
Acute infection: IgM (+), VCA & IgG (-)
Reactivation: VCA, IgM, IgG (+)
164
Acyclovir
Requires phosphorylation: early DNA chain termination
Inhibits HSV1, HSV2, VZV
Renal failure risk.
165
Valacyclovir
Prodrug of acyclovir.
Higher oral availability.
166
Ganciclovir
Used for CMV
Requires phosphorylation.
Cytopenia risk
167
Risks of HIV transmission from infected to non infected persons
Sexual contact:
Anal receptive 1.4%
Anal insertive 0.1%
Penile-vaginal receptive 0.08%
Penile-vaginal insertive 0.04%
Injection drug use 0.63%
Pregnancy, childbirth, breastfeeding 33%
Occupational exposure 0.23%
Blood transfusion/organ transplant 93%
168
Key structures of HIV
Capsid protein p24
Protease
Reverse transcriptase
Integrase
169
Targets of HIV drugs
Entry inhibitors
Reverse transcript inhibitors
Maturation inhibitors
Protease inhibitors
170
Discuss establishment of HIV latency
HIV in activated CD4 T cells become active infection and lead to immune depletion.
HIV in resting CD4 T cells become viral reservoir. If the virus is not replicating, we can't target it with drugs.
171
Timeline of immune suppression d/t HIV
Primary infection occurs, as HIV RNA increases you get acute HIV syndrome.
This kills CD4 cells and takes them down to < 500.
Eventually there is an HIV set point. Over time the viral load begins to increase leading to constitutional symptoms then opportunistic disease, then death as CD4 counts decline.
Asymptonatic/clinical latency during set point.
172
CD4 counts
Normal: 500-1400, usually >1000
<200: pneumocystis pneumonia, severe bact infections, TB, HSV outbreaks, Kaposi's sarcoma, esophageal candidiasis.
<100: cryptoccocal meningitis, toxoplasmosis, chronic protozoal diarrhea, histoplasmosis, extra pumonary TB, CNS lymphoma
<50: CMV, JC virus, MAC
173
Chronic immune activation of HIV
HIV production and replication
Loss of regulatory cells (Tcells)
Inflammation
all lead to comorbidities.
174
Goals of antiretroviral therapy
Reduce viral replication in order to:
restore and preserve immune function
reduce HIV transmission
reduce chronic inflammation and consequences
Viral suppression more important than CD4 count for:
preventing opportunistic infections and malignancy
reducing HIV related mortality
All people should being ART, no matter CD4 counts.
175
Impact of ART on HIV transmission
96% reduction in HIV transmission
U=U zero transmission
176
95-95-95
95% aware of HIV diagnosis, of which
95% are treated for HIV, of which
95% are virally suppressed, virus not detectable.
177
A patient presenting with encephalitis with temporal lobe enhancement on CT/MRI makes you think what?
HSV1
178
Ddx for encephalitis
Viral: HSV1 = Enterovirus > VZV, West Nile, EBV
Age matters: young - EV/EBV older - HSV1-VZV, WNV
Bacterial: Mycobacterium TB, Mycoplasma pneumoniae
Protozoa: Toxoplasma, Amebic encephalitis (water sources)
179
Young with diffuse rash think...
Nisseria
180
Gram(-) diploccoci culture in meningitis presentation
Neiseria meningitidis
181
Ddx for acute meningitis
Viral: Enterovirus > HSV2, VZV, EBV, CMV, Mumps
Bacteria: Age matters
Infants - GBS > listeria
<2 years - Strep pneumoniae > H. influenza = Neiseria
childhood - Strep pneumoniae > Neiseria >>H. influenzae
Adolexcene: Neiseria = Strep pneumonia
Adults >35 - Strep pneumo >> Neiserria >> H influenzae
Adults >65 - Strep pneumo >> listeria, GBS
182
What additional steps need to be taken for Neisseria?
Prophylactic antibiotics for close household contacts (kissing, fluid swapping).
Rifampin or Ciprofloxacin.
183
Common cause of meningitis in HIV with CD4 count <100
Cryptoccocus. yeast.
Cryptoccocal Ag (+)
CSF culture: cryptococcus neoformans
184
Ddx chronic meningitis
Bacteria:
TB
Treponema pallidum
Fungus:
Cryptoccocus, Blastomyces, Coccidoidides, Histoplasma, Aspergillus
Parasites;
helminths
185
****CRITERIA FOR CT BEFORE LP****
Immunocompromised
History of CNS disease
Papilledema
New onset of seizure
Abnormal LOC
Focal neuro deficit
But always give antibiotics first!!
