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Flashcards in Unit 3 - Week 5 Deck (130)
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1
Q

number of genes on paroviruses

A

2 genes (1 replicon + 1 capsid gene)

2
Q

number of genes on retroviruses

A

3 genes

3
Q

number of genes on papillomaviruses

A

8 genes

4
Q

number of genes on adenoviruses

A

10 genes

5
Q

number of genes on herpes viruse

A

70+ genes

6
Q

number of genes on pox virus

A

200 genes (largest possible)

7
Q

are viral genes prokaryotic or eukaryotic?

A

eukaryotic

  • cellular transcription factors that bind to enhancer/promoters to regulate expression
  • ribosomal entry site
  • open reading frame
8
Q

5 ways how virus genomes are efficient

and which way is targeted for gene therapy

A
  1. no space is wasted (no junk D/RNA)
  2. reading frames can overlap (can make more than one PRO from same mRNA)
  3. ribosomal/translational frame shifting (due to ribosome slipping 1/2 bases on RNA to make new PRO)
  4. alternative splicing of RNA
  5. cleavage of polyPRO by viral proteases (these are targets for drugs)
9
Q

virus mutations

A

high frequency b/c

  • high error rate of polymerase
  • lack of proofreading and error correction
  • lack of second strand in some viruses
  • all types of mutations occur
10
Q

pros and cons of virus mutations

A

Pro: allows for epidemiological studies (track mutations as they go), allow live vaccines to be made (since conditional lethal mutations)
Con: can produce new Ags to avoid immunity/drugs (more quickly than bacteria), and integration of viral genomes can cause disease

11
Q

5 types of virus interactions if 2+ viruses infect the same cell at the same time

A
complementation
phenotypic mixing
recombination
reassortment
interference
12
Q

virus complementation

A

when a gene function of one virus replaces a mutated gene of another

  • allows defective viruses to replicate and express genes
  • allow cell lines to support vaccine production
  • progeny are the same as parents (retain the “defective” gene of parent)
13
Q

virus phenotypic mixing

A

exchange of capsid PRO, such that psuedotypes are created

  • genetic material of one virus is in the capsid/envelope of other, or combination of both serotypes
  • now able to infect cells their original capsid couldn’t
  • progeny genome is the same as parents (so after replicate, the psudeotypes will return to regular capsids)
14
Q

virus recombination

A

exchange of genes by crossing over at regions of homology

-produces a hybrid virus which reproduces (progeny are DIFFERENT from parents)

15
Q

virus reassortment

A

rearrangement of parts of a segmented genome to form a new set of segments
-progeny are different from parents

16
Q

virus interference

A

infection by one virus tends to prevent infection of another by:
-blocking of receptors
-competition ofor resoruces
-production of interferon or other anti-viral agents (stimulation of innate immunity)
use these to create gene therapy

17
Q

development of gene therapy for viruses

A

for diseases that have a deletion of one essential gene, or cancers

  • close therapeutic gene to virus
  • grow virus in packaging cell
  • test in cells (animals - humans)
18
Q

monogenic disorders that might be treated by gene therapy

A
  • hemophilia (transfer factor VII by viral vector)
  • immune deficiencies (esp. if T or B cells)
  • retinal disorders
  • liver enzyme deficiencies
  • cystic fibrosis
19
Q

approaches to treatment of cancer by gene therapy

A
  • gene silencing
  • expression of toxic/suicide genes
  • expression of immune-stimulation or tumor suppressor genes
  • modified (cytotoxic) viruses that can replicate in tumors
20
Q

mutants whose replication is severely restricted can be made from

A

retroviruses
adenoviruses and adeno-associated
herpes simplex virus

use appropriate promoters (like cancer-specific) to allow viruses to replicate in proper places

21
Q

4 problems associated with gene therapy

A
  1. short duration of expression (transient; may get shut off b/c incorrect expression)
  2. low efficiency of gene transfer (require very high doses of virus vector)
  3. inflammation in response to virus
  4. potential for Xmal disturbances by virus
22
Q

three cases where gene therapy viruses had side effects

A
  1. Jesse Gelsinger (had fatal Ornithine Transcarbamylase deficiency and died of ARDS due to GT adenovirus)
  2. Jolee Mohr (had terrible RA and died of systemic histoplasmosis)
  3. newborns got T cell leukemia after IL-2 receptor deficiency was stopped with mouse leukemia virus
23
Q

background of hepatitis viruses

A

6 non-related viruses (A-G; not phylogenically related, just share common host hepatocyte with liver pathology)

  • all cause initial acute hepatitis on first infection, wide range of chronic severity
  • remember to rule out pharmaeutical causes of hepatitis!
24
Q

which hepatitis have vaccines available?

A

A, B, E

-badly needed for C

25
Q

which hepatitis have chronic infections of cirrhosis and cancer?

A

B and C

26
Q

which hepatitis have interferon treatments with debilitating side effects?

A

B and C

27
Q

hepatitis A virology

A

human-restricted picornavirus (ssRNA genome, naked icosahedral capsid)

  • environmentally rugged
  • single serotype with no reinfection, so there is a vaccine available (IgG, since neutralizing Ab recognize virion PRO 1 and 3)
28
Q

hepatitis A pathogenesis

A

fecal-oral transmission and replication like enterocytes

  • if low sanitation, contaminated stool to drinking water
  • mostly immunogenic and over 99% recover completely (cleared) with no chronic infection
  • rare patients develop fulminant hepatitis with 40% mortality
29
Q

hepatitis A disease/exam

A

can be very strong reaction if not immunized (out for a month)

  • fever, jaundice, gastroenteritis, tenderness around liver, dark urine, pale feces
  • predominantly portal/periportal lymphocytic infiltrate and varying degrees of necrosis
  • risk factors in elderly or preexisting liver disease
  • usually don’t need transplant (recover w/o it)
30
Q

hepatitis A serum panel:
EIA for IgM and IgG
serum ALT

A

EIA for IgM - acute
EIA for IgG - resolved/vaccinated
serum ALT - liver damage

31
Q

hepatitis A treatment/prevention

A

T: rest, fluids, monitoring and discontinue alcohol and contraindicated meds (since liver cannot process)
P: handwashing, sanitation, vaccine (Twinrix HAV and HBV), and immune serum globulin prophylaxis

32
Q

hepatitis B virology

A

human-restricted hepadnavirus (small, enveloped, partly dsDNA genome)

  • unusually stable for enveloped virus
  • replication creates incomplete “decoys” to wear out immune system
  • replication in hepatocytes leaves integrated viral DNA to establish chronic infection (due to RT)
  • one serotype, with no reinfection, so vaccine
33
Q

hepatitis B pathogenesis (including chronic infection)

A

transmitted by blood, sex, birthing

  • 90% have acute hepatitis, then clear virus
  • 1% have fulminant hepatitis
  • 9% have positive Ags for over 6 months
  • -50% resolve
  • -others have cirrhosis, (ongoing cytotoxic T cell response) kidney damage/arthritis (accumulation of Ag-Ab complexes), hepatic cell carcinoma (expression of viral transcriptional transactivators)
34
Q

fulminant hepatitis

A

acute liver failure

35
Q

hepatitis B labwork

A

if infection appears active chronic, perform liver biopsy

  • viral surface Ag = acute
  • IgG against viral surface Ag = recovered or vaccinated
36
Q

hepatitis B treatment

A

acute infection = supportive
quiescent chronic infection = monitor becore taking action
damaging chronic infection = interferon therapy via Pegasys, however very debilitating side effects with low cure rate and possible relapse

best is either prevent with vaccination or Ab prophylaxis shortly after exposure

37
Q

hepatitis C virology

A

human-restricted flavivirus (+RNA, enveloped)

  • much higher potential for chronic infection than Hep B (stronger association with primary hepatocellular carcinoma)
  • no vaccine
38
Q

hepatitis C pathogenesis

A

transmitted by blood, sex

  • infect hepatocytes and maybe B lymphocytes (both carry CD81 receptor); strong immune response
  • quasispecies due to highly mutagenic rdRNAP
  • produce 10 trillion new particles/day
  • 15% of infections clear after acute hepatitis
  • 85% have chronic infection:
  • -liver failure
  • -cirrhosis
  • -hepatocellular carcinoma
  • -100K deaths/year
39
Q

hepatitis C exam and labwork

A

acute symptoms like HBV, may even be milder

  • red flag: IV drugs, travel to Egypt
  • EIA is real or false positive, with RIBA confirmation
  • co-screen for HIV and Hep B
40
Q

hepatitis C treatment if 1 serotype

A

Ab to HCV is NOT protective (no vaccine)
-acute: judgement call for peg-alpha-IFN or waiting for spontaneous clearance
-chronic: with ongoing damage, use drug treatments
–goal is sustained viral response (SVC) like remission
–even failed treatment will reduce risk of hepatocellular carcinoma
may turn to “alternative” therapies (watch out for milk thistle, licorice, or ginseng)

41
Q

drug treatment for chronic Hep C if 1 serotype

A

ribavirin - viral chain terminator, immunomodulant
pegalyted alpha-interferon
HCV protease inhibitors (if serotype 1) - beceprevir or telaprevir; very difficult procedure with more side effects

42
Q

hepatitis C multiple serotype treatment

A

4 serotypes altogether

  • 2/3 have >50% SVR rate with 6 mo of Pegasys + ribavarin
  • 1/4 have <50% SVR with 1-2 yrs
  • new polymerase inhibitors for 1 are less effective VS 2/3, and have own side effects
43
Q

living donor liver transplant

A

option for Hep C, maybe B/D; on medical schedule due to matched family member
-treat pt with short, hard corse of interferon to clear extra-hepatic virus reservoirs
-remove infected liver (and most of virus)
-replace with partial donor liver (virus-free)
-if RNA-negative serum was achieved before transplant, recurrance rate may be as low as 10%
significant risks to donor

44
Q

defining properties of fungi

A
  • eukaryotic (80S ribosomes)
  • cell wall of chitin (NOT peptidoglycan)
  • cell membrane with ergosterol
  • some are obligate aerobes, but none are obligate anaerobes
  • require preformed organic carbon nutrient source (heterotrophs)
  • most are environmental (exception: C. albicans is normal flora)
  • can grow in drier, more acidic, and higher-osmotic-pressure environments than bacteria
  • -larger and sturdier for more superficial/cutaneous infections
45
Q

what drugs are used to target fungal cell walls

A

chitin is attacked with anti-beta-glucan drugs

46
Q

what drugs are used to target ergosterol

A

in fungi, use amphotericin B and azole drugs

47
Q

yeasts morphology and reproduction

A

one of the two major types of fungi

-single cells that reproduce by budding (daughter cell is smaller than mother)

48
Q

molds morphology

A

one of the two major types of fungi

  • grow as filaments (hyphae; microscopic) that form a mat (mycelium; macroscopic)
  • may form transverse walls (septate hyphae) that appear to be a long chain of cells, or lack walls (aseptate hyphae) that are part of one long multinuclear cell
  • mitotic growth occurs only at tip of filament with daughter cells of equal size, sexually, or via asexual spores
49
Q

molds that reproduce sexually

A

zygospores - form single large sexual spores with thick walls
ascospores - form sexual spores in a sac (ascus)
basidiospores - form sexual spores on the tip of a pedestal (basidium)

50
Q

fungi imperfecti

A

molds that reproduce asexually (usually conidia; distinct appearances of different spores)

  • arthrospores - from fragmentation of ends of hyphae
  • chlamydospores - rounded, thick-walled, resistant
  • blastospores - from budding
  • condidospores - chains of spores formed at ends of hyphae
  • sporangiospores - formed within a sac
51
Q

thermal dimorphism

A

some pathogenic fungi grow as molds in the environment, and yeasts in the human body, due to different temperatures and effects on gene transcriptions

52
Q

granuloma formation in fungi and where it’s seen

A

seen in major systemic fungal diseases (coccidiodomycosis, histoplasmosis, blastomycosis)

  • involves CMI: macrophage and helper T cells
  • can be confused with TB
53
Q

pyogenic response in fungi and where it’s seen

A

acute suppuration with neutrophils in exudate

  • aspergillosis
  • sporotrichosis
54
Q

do fungi have endotoxin?

A

no

55
Q

how are most of the important fungal pathogens transmitted, and what are the human defenses?

A

transmitted via inhalation from soil/environment

defenses are mucus, alveolar macrophages, and CMI

56
Q

are PPD-type skin tests useful for fungal infections?

A

only if delayed hypersensitivity to environmental fungi

-not useful if normal flora like C. albicans, because would already have defenses

57
Q

mycotoxicosis examples

A

from fungal toxins (not infectious)

  • amanita mushrooms - amanitin, phalloidin - hepatotoxins
  • ergotism - contaminated with Claviceps purpura making ergotamine and LSD
  • aflatoxins from Aspergillus flavus linked to hepatic carcinoma
  • -ingested via spoiled grains/peanuts
  • -metabolized by liver to carcinogenic epoxide
  • -mutates p53 tumor suppressor gene
58
Q

fungal allergies

A

immediate hypersensitivity reaction to inhaled fungal spores (usually aspergillus)

  • asthmatic RXN - rapid bronchoconstriction via IgE, eosinophilia
  • “wheal and flare” test reaction
59
Q

laboratory diagnosis - direct microscopic examination and characteristic findings

A
  • clinical specimens - sputum, lung biopsy material, skin scrapings
  • tissue broken down with 10% KOH leaving fungi intact, stained with fungal stains in KOH mount
  • -Coc. immitis - spherules in sputum
  • -Cryptococcus neoformans - wide capsule in CSF
60
Q

Sabouraud’s agar

A

culture of fungus; inhibits bacteria with low pH and antibiotics
-appearance of mycelium and sexual spores is often diagnostic

61
Q

laboratory diagnostics - DNA probe and serologic tests

A

DNA - identify cultured colonies at an earlier stage than microscopy
serologic - test for antifungal Ab in serum or spinal fluid
-useful for systemic mycoses

62
Q

what do most antifungals target?

A

ergosterol

63
Q

Amphotericin B (Fungizone)

A

most important antifungal; broad-spectrum polyene for life-threatening systemic infections

  • binds ergosterol to disrupt membranes (forms transmembrane channel for monovalent ions to leak)
  • can cause renal, heart, hepatic toxicity (liposomal prep is less toxic)
  • drug of choice for pregnancy b/c not teratogen
  • added to tissue culture to prevent fungal contamination
64
Q

Amphotericin B liposomal prep (AmBisome)

A

less toxic than Fungizone b/c releases drug more specifically to fungal cell wall

65
Q

nyastin and natamycin

A

polyenes with same mechanism as Fungizone, but too toxic for systemic use
-good for topical

66
Q

azoles

A

inhibit ergosterol synthesis for systemic and topical use

  • affect fungal cytochrome P450 and 14alpha-demethylase
  • less toxic than polyenes
67
Q

Fluconazole (Diflucan)

A

azole that inhibit ergosterol synthesis for systemic candida and cryptococcal infections

68
Q

Terbinafine and Tolnaftate

A

azoles that inhibit ergosterol synthesis for topical use

69
Q

Echinocandins

A

mycafungin (mycamine), caspofungin (cancidas), anidulafungin (eraxis), etc.

  • inhibit synthesis of beta-glucan found only in fungal cell walls (systemic)
  • effective VS Candida, Aspergillus, but NOT Cryptococcus or Mucor
  • low toxicity, high efficacy
70
Q

Creutzfeldt-Jacob disease

A

most frequent human prion disease

  • sporadic - no known cause (85-95%)
  • -NOT mad cow disease, and cannot be transmitted person-to-person
  • familial - inherited genetic risk (7-10%)
  • iatrogenic - exposure during medical procedures (<1%)
  • variant - mad cow disease
71
Q

sCJD symptoms and 2 signs

A

causes spongioform encephalopathy

  • loss of brain function resembles disease, but is very rapid in progression
  • compete dementia by 6th month, death in 1 year
  • brain shrinkage with vacuoles upon biopsy
  • 2 signs: mental deterioration and myoclonus (startle)
72
Q

model of prion self replication

A

prions are infectious, but no genetic infection

  • once formed, nucleus/seed recruits other PrPc to convert to PrPsc
  • nucleus increases in size to become amyloid fiber
  • fragmentation occurs - liberates new ends to allow amplification, and allows dissemination of infectious materials
73
Q

sCJD diagnosis

A

brain biopsy remains gold standard and only definitive diagnostic test for all forms of CJD

  • spongiform change, neuronal loss without inflammation, accumulation of PrPsc
  • abnormal electroencephalography (EEG) and MRI signal
74
Q

sCJD treatment and prognosis

A

no effective treatment for sCJD

  • median disease duration of 5-6 months
  • death occurs with 1 year of symptom
75
Q

vCJD background

A

type 4 prion for BSE

-transmitted via CNS, retina, trigeminal/paraspinal ganglia, distal ileum, bone marrow NOT muscle or milk

76
Q

vCJD symptoms/signs

A

similar clinical presentation as sCJD

  • loss of brain function progresses slower than sCJD, although very rapid in comparison to Alzheimer’s
  • peripheral pathogenesis distinct from classical CJD with prominent involvement of lymphoreticular tissues
  • FATAL
77
Q

vCJD diagnosis

A

similar to sCJD, but differences are:

  • unique type 4 PrPsc
  • tropism from lymphoid organs like tonsils
  • NO detection of 14-3-3 PRO, and different MRI/EEG signals
  • stains PrP with round amyloid core
78
Q

vCJD VS sCJD

A

vCJD has:

  • type 4 PrPsc
  • transmitted persno-to-person by blood, contaminated food
  • younger age of onset
  • less rapid progression of illness
  • peripheral pathogenesis
  • differences in neuropathology (round amyloid core VS diffuse)
79
Q

sites of virus entry

A

mucous membranes (conjunctiva, urogenital tract)
skin (scratches, IVs)
tracts (respiratory, alimentary, urogenital, anus)

80
Q

virus dissemination (primary/secondary viremia)

A

viruses spread from surface of body to lymph nodes and blood stream
1 leads to: replication in internal organs and occurs without symptoms (incubation stage)
2 leads to: dissemination to places of viral shed
-can be by direct contact or thru environment
-exposure to infected blood is common route of transmission; also skin, mucus membranes, lungs, kidneys, GIT
-brain is dead-end, but possible transmission if autopsy

81
Q

virus-host interactions (4 types)

A
  • unnoticed (immune system defeats 100%)
  • cause illness and/or induce autoimmunity (survive if immune system adequate)
  • be persistent (chronic infection)
  • be lethal (immune system cannot defeat in time)
82
Q

general patterns of infection

  • acute
  • persistent
  • latent
  • slow
  • transforming
A

Acute - virus is defeated by immune system after initial disease symptoms/shedding
*Persistent - virus remains with both virus shedding and disease symptoms
*Latent - remains in system as infectious particle, but no disease, until reactivates
*Slow - progressive shedding until final disease
Transforming - secondary disease episode is different from primary
*chronic infections

83
Q

4 major categories of fungal infection (mycoses) and examples of each

A

superficial - dermatophytosis
subcutaneous - sporotrichosis
systemic - coccidioidomycosis
opportunistic - cryptococcosis

84
Q

themes in superficial mycosis

A

caused by fungal growth on superficial skin layer

  • doesn’t need thermal dimorphism b/c grow on cool exterior as hyphae
  • common, but minor symptoms (itch, discoloration)
  • treated with topical azoles or oral griseofulvin
85
Q

dermatophytosis pathogenesis

A

superficial mycosis caused by 3 types of dermatophytes

  • infect only superficial keratinized structures (skin, hair, nails)
  • make keratinases that allow invasion of cornified cell layer
  • chronic infections if warm, humid areas (wet clothes)
  • -Tinea (jockitch, athlete’s foot, ringworm)
  • may have hypersensitive dermatophytid (“id”) vesicles on fingers (don’t have live fungus/spores)
86
Q

dermatophytosis transmission and diagnosis

A

fomites or autoinnoculation

  • diagnose by scraping skin, KOH mount, Sabouraud’s culture
  • treat all body sites simultaneously with topical/oral and examine remains for hyphae and spores
87
Q

themes in subcutaneous mycosis

A

introduced by trauma exposing subcutaneous tissue to soil/vegetation

  • slow spread from trauma site toward trunk by lymphatics
  • thermal dimorphism
  • patient presents with history of ineffective antibiotic treatment
  • use oral azoles, but if serious then amphotericin B/surgery
88
Q

sporotrichosis pathogenesis (and what 2 diseases it’s similar to)

A

subcutaneous mycosis; thermally dimorphic in vegetation (“rose-pickers” or if taking long-term corticosteroids)

  • introduced by thron puncture, and yeasts grow painless pustule/ulcer
  • draining lymphatics form suppurating subcutaneous nodules
  • symptoms wax/wane over years, may progress to disseminated disease/meningitis if immunosuppressed
  • hard to differentiate from TB or histoplasmosis
89
Q

sporotrichosis diagnosis and labs

A

painless pustle/ulcer (reddish, necrotic, nodular may extend along lymphatics from initial injury site)

  • history of field-work with ineffective antibiotics
  • if AIDS, nodules disseminated over entire body
  • if COPD+alcoholism, respiratory distress
  • tissue biopsy has round/cigar-shaped budding yeasts (looks like TB)
  • culture has hyphae with oval conidia in clusters at the tip of slender conidiophores (like daisy)
90
Q

sporotrichosis treatment/prevention

A

3-6 months itraconazole or oral azoles
-if serious, use amphotericin B
prevent with gloves

91
Q

themes in systemic mycoses

A

environmental fungi/spores in soil inhaled into lungs

  • thermal dimorphism
  • wide range of severity (asymptomatic clearance to death)
  • not person-to-person transmissible
  • Coccidioides/histoplasma/blastomyces mimic TB, but from America, not overseas
92
Q

Coccidioides pathogenesis

A

systemic mycoses that looks like TB

  • dimorphic in soil, spherules in tissue
  • grow in rainy season as noninfectious mycelia
  • in dry summers, forms hyphae with alternating anthrospores, carried on wind to be inhaled
  • endemic in SE US and Latin AMerica
  • usually geriatric population centers
  • within terminal bronchiole, arthrospores form spherules (resistant to eradication, filled with endospores to release during rupture)
  • growth leads to granulomatous lesions
93
Q

effect of Coccidioides if low dose and healthy CMI

A

asymptomatic clearance

94
Q

effect of Coccidioides if moderate dose, healthy CMI (3 possiblities)

A
  • asymptomatic containment
  • nonspecific, flulike illness and containment
  • mild pneumonia, erythema nodosum rash, but eventual containment
95
Q

effect of Coccidioides if high dose or immunosuppressed

A
  • serious pneumonia

- dangerous dissemination to bones and meninges

96
Q

acute VS chronic phases of coccidioides

A

acute: CMI (MPs) attempt to clear, usually successful unless Trojan horse
chronic: inadequate CMI clearance, infected lymphocytes/MPs create granuloma and giant cell formation (containment)

97
Q

Valley fever or desert rheumatism

A

symptomatic diseases of coccidioides

  • fever
  • arthralgia
  • erythema nodosum (rash on shins)
  • erythema multiforme (irregular, immunogenic RXN)
  • chest pain
98
Q

diagnoses of coccidioides

A

biopsies of relevant tissues - look for spherules
cultures - look for hyphae with arthrospores; highly infectious!!
serology - IgG spikes if disseminating (positives reliable, false negatives possible)
PPD (+ if exposed, cleared infection; - if unexposed or immunosuppressed)

99
Q

coccidioides treatment

A

no treatment if mild, but must treat if predisposed via amphotericin B or oral azoles

  • if persisting lung lesions, use amphotericin B
  • minimum of 6 mo drug therapy, followups for at least a year
100
Q

themes in opportunistic mycoses

A

diseases and severity are widely varied, depending on patient’s pre-existing conditions
-optimal treatment addresses both infection and underlying problem

101
Q

cyrptococcosis background

A

opportunistic mycoses (5 different serotypes, mostly cyrptococcal meningitis)

  • oval yeasts with narrow-based buds and wide polysacc capsule
  • NOT thermally dimorphic, and no human-human transmission unless transplants or needles
  • used to be rare, but then steroids and AIDS have increased (not fatal b/c amphotericin B)
102
Q

cryptococcosis pathogenesis

A

transmitted by inhalation (pigeon droppings contagious for years)

  • asymptomatic or leads to pneumonia, with intracellular infection in alveolar MPs
  • immunocompetent restricts to lungs, raises helper T cells, Ab to capsule
  • deficient CMI (esp. AIDS) may cause dissemination with cryptococcal meningitis and skin nodules
  • virulence factors: capsule, melanin in cell wall (antiphagocytic), phospholipase B
103
Q

cyrptococcosis diagnostic exam

A

meningitis with subcutaneous nodules (low inflammation, so less common fever/stiff neck)

  • CSF stain with India ink to see wide capsule
  • serologic tests for “crag” for Ag
104
Q

cryptoccosis treatment

A
amphotericin B (liposomal if kidney issues) with flucytosine for 2 weeks
-in AIDS, use fluconazole for long-term suppression (clearance not option)
105
Q

types of virus treatments

A

virucidal (detergents, cryotherapy)
immunomodulatory (alpha-interferon)
antiviral

106
Q

types of antivirals (4) and classes of anti-HIV drugs (5)

IMPORTANT

A
  • nucleoside analogs (Nucs)
  • non-nucloside analogs (Non-nucs)
  • protease inhibitors
  • entry inhibitors
  • entry inhibitors
  • nucleoside/tide RT inhibitor
  • non-nucleoside/tide RT inhibitor
  • integrase inhibitor
  • protease inhibitor
107
Q

how do antiviral drugs work?

A
  • target essential virus functions
  • target host cell defenses (intrinsic immunity)
  • activate immune response
108
Q

what drug targets viral entry and for what disease?

A

Enfuviritide (vs HIV)

109
Q

what drug targets viral uncoating and for what disease?

A

Amantadine and Rimantadine (vs Influenza A; RESISTANCE)

110
Q

what drug targets viral nucleic acid synthesis and for what disease?

A

nucleoside analogs
non-nucleoside polymerase inhibitors
non-nucleoside RT inhibitors
vs herpesvirus and HIV

111
Q

what drug targets assembly and release of viral particles and for what diseases?

A

protease inhibitors vs HIV

neuraminidase inhibitors vs influenza

112
Q

what drug targets host cell intrinsic immunity and for what diseases?

A

Peg-interferon vs HCV, HBV, etc.

apoptosis, interferon release

113
Q

important issues about antivirals

A

specificity - most drugs target only one virus
cytotoxicity - if “off” will harm hosts, and if “on” may get resistance
duration of antiviral effects - mostly competitive reversible, and cause rebound, so require lifelong treatment

114
Q

resistance to antivirals (IMPORTANT!)

A

resistance mutations often exist in a patient before drug treatment
-drug treatment selects for resistant virus strains

115
Q

factors favoring emergence of resistant variants (IMPORTANT!)

A

high rate of virus replication
high mutation rate (RNA&raquo_space;> DNA viruses)
high selective drug pressure (long term or multiple treatments)
immunosuppressed host cannot clear virus-infected cells

116
Q

how do we counter resistance to antivirals? and in which way must we beware of toxicity?

A
  • alleviate immunosuppression - lower doses of anti-T cell drugs
  • combine drugs with different targets - standard of care for HIV/HCV b/c uses different mechs to lower multiple resistance mutations
  • target host functions - infected cells may have unique profile, and virus mutations don’t impact cellular genes
  • -some cancer drugs target dividing cells AND inhibit viruses
  • -beware of toxicity!
117
Q

who should be treated for HSV-1/2 and VZV?

A
  • neonates infected w/ HSV at birth
  • people with frequent recurrences of 1/2
  • complicated infections (encephalitis, DIC, eye infections) must be treated IMMEDIATELY
  • people with zoster (w/in 3 days)
  • treat with Acyclovir
118
Q

Acyclovir background, mechs, and why there is resistance

A

nucleoside analog of guanosine effective vs HSV-1/2&raquo_space; VZV

  • trade name Zovirax, plus derivatives (more bioavailable in body)
  • pretends to be a guanine, and once triphosphorylated (via viral thymidine kinase and host kinases), it is incorporated into growing viral DNA via viral DNA polymerase
  • resistance if VTK ignores it, or viral DNA polymerase doesn’t recognize it
119
Q

who should be treated for CMV?

A

-bone marrow and organ transplant patients
-immunosuppressed people with active CMV
-CMV retinitis
treat with Ganciclovir

120
Q

Ganciclovir

A

nucleoside analog of guanosine

  • similar mech and structure to Acyclovir, but MUCH MORE TOXIC
  • -suppresses bone marrow
  • -mutagenic/teratogenic
  • -severe side effects
121
Q

Foscarnet/Foscavir

A

broad spectrum treatment for DNA virus

  • Trisodium phosphonoformate
  • inhibits viral DNA polymerase
  • effective VS all herpesvirus as second-line drug
  • IV route only, toxic to kidneys
122
Q

Cidofovir/Vistide

A

broad spectrum treatment for DNA virus

  • nucleoside analog of cytosine
  • effective VS DNA viruses (herpes, adeno, papilloma, pox)
  • IV route only, toxic to kidneys
123
Q

treatments for hepatitis B

A

treated with drugs for HCV and HIV

-Pegasys, Entecavir, Tenofovir disproxil fumarate

124
Q

who should be treated for hep B?

A
  • people with chronic active HBV disease
  • people co-infected with HCV and/or HIV
  • people who are progressing to cirrhosis, liver failure, or hepatocellular carcinoma
125
Q

treatments for influenza virus

A

Relenza, Tamiflu

  • both are sialic acid analogs that inhibit viral neuraminidase (sialidase)
  • virions remain attached to cell
126
Q

who should be treated for influenza?

A
  • hospitalized/severely ill
  • children younger than 2
  • adults over 65
  • pregnant women
  • immunosuppressed people
  • anyone suspected of having influenza
127
Q

ribavin background and mechanism

A

broad spectrum VS a whole bunch of diseases, including HCV, RSV, HSV, influenza, SARS, among ohthers
-nucleoside analog of guanosine
-oral, IV, aerosol formulations
works as an immunomodulator, IMPDH inhibitor, HCV RDRP inhibitor, and RNA mutagenesis

128
Q

treatments for HCV

A
  • combo therapy with Pegasys with ribavirin
  • not all HCV genotypes respond to drugs
  • difficult and complicated treatment, with horrible side effects
129
Q

treatments for HIV

A

AZT/Zidovudine was first drug (now antique)
-nucleoside analog of thymine
-nucleoside RT inhibitor
now use drug combos of various enzyme inhibitors
-Stribild 4 drug combo (integrase, liver enzyme, 2 RTs); only 1 pill/day

130
Q

cobicistat

A

enzyme added into Stribild (treatment for HIV)

  • drug enhancer that inhibits CYP3A4 that breaks down drugs in liver
  • boosts potency of elvitegravir (integrase inhibitor in Stribild)
  • allows pill dose of 1/day