The flashcards below were created by user
countchocula58
on FreezingBlue Flashcards.
-
Key fungal cell differences
- they are eukaryotic but
- plasma membrane has ergosterol instead of cholesterol
- cell wall of glucans and chitin
- virulence factors like exoenzymes and toxins
- larger than bacteria
- reproduce by budding or
- spores grow germ tube, becoming hypha that lace into mycelium (mat)
-
Fungal Thermotolerance
- to survive in warm host out of woods
- more virulent
- some with thermal dimorphism convert from mycelia form to yeast/sphere
- increased thermotolerance means go from cutaneous to systemic
- cell wall, capsule
-
Fungal Enzymes
- lots of different proteases, lipases, phospholipases so that they can eat any surface in nature
- can damage barriers and host cells
- collagenase, elastase, DNase, protease are better at surviving in the body
-
Fungal cell wall and capsule
- made of sugars, which is harder for us to attack than the LPS of bacteria
- resist phagocytosis
- adhesion to epithelia and
-
Mycoses
chronic, less contagious, delayed/distant responses, tropic, cell mediated immunity
-
Ringworm
- underarm ringwrom can manifest distally
- may appear weeks after infection
- hard to culture (lab must be notified) but can gram stain and fluoresce (wood’s lamp)
- usually diagnosed by history and exam
- biomarkers for polysaccharides (galactomannan)
- sometimes diagnosed by not responding to antibioitics
-
Polyenes
- amphotericin B
- membrane disruption
- binds to ergosterol and punches hole in membrane
- no known resistance
-
Azoles
- ketoconazole, fluconazole, itraconazole
- ergosterol synthesis disruption
- inhibit cytochrome P-450 3-A4
- lanosterol 14 alpha demethylase is dependent on CYP3A4
- cannot convert lanosterol to ergosterol
- toxicity for drugs that use CYP3A4 (and other CYPs)
-
Allylamines
- no examples given
- ergosterol synthesis disruption
- earlier in ergosterol synthesis
- less commonly used
-
5-fluorocytosine
- Flucytosine
- inhibits DNA replication
- take up by cytosine permease (not taken up well in our cells)
- converted to 5-fluorouracil (5-FU)
- downregulates thymidylate synthetase so there is not enough thymine for DNA replication
- inserted into RNA to miscode protein
- chemotherapy agent
-
Echinocandins
- capsofungin, micafungin
- inhibit glucan synthesis
- lack of glucan weakens cell wall to not tolerate osmotic or mechanical stress
-
Griseofulvin
- no examples given
- dirupts microtubules (spindle formation)
- concentrates in keratin rich cells by complexing keratin
-
Superficial mycosis
- pityriasis (tinea) versicolor, alters pigmentation, involves stratum corneum
- woods lamp or skin scraping
- topical therapy or systemic with an azole
-
Cutaneous mycosis
- love keratin rich
- usually itch
- Trichophyton spp, skin, hair, nails
- Microsporum spp, skin, hair
- Epidermophyton floccosum, skin, nails
- ring worm
- like warm, moist, glandular, hair shafts (armpits…)
- distal vesicles aka dermatophytids (hypersensitivity)
- Dermatophytoses aka the tineae
- tinea capitis (head), tinea corporis (body), tinea cruris (inguinal), tinea pedis (foot), tinea unguium (nails)
- if untreated or immunodeficient can cause progressive tissue injury
- diagnoses by history, exam, woods lamp, 10% hydrogen peroxide
- treat by cleaning and drying and topical azoles
- systemic azoles or griseofulvin if necassary
-
Subcutaneous mycosis
- in soil and plants, can be from penetrating injury
- rose thorn disease
- sporotrichosis is canonical of these
- self limiting unless immunosupressed
- spreads along cutaneous lymphatics
- diagnosed by serologic/delayed type hypersensitivity testing or histopathology
- if not self limited, treated by itraconazole or amphotericin B
-
Systemic mycosis
- always dimorphic fungi from birds “nitrogen enriching” soil
- spores initiate pathology
- pulmonary focus, breath in while disturbing brush/soil
- diagnosed by serologic/delayed type hypersensitivity testing or histopathology
- Coccidioidomycosis
- Histoplasmosis
- Blastomycosis
- Paracoccidioidomycosis
-
Coccidioidomycosis
- Coccidioides immitis
- dimorphic, bird poop
- SW US and latin america
- pulmonary focus but disseminates in immunocompromised
- acute inflammatory response
- self limiting but if not azoles, amphotericin B
- virulence factor is proteinases
- biopsy with stain
-
Histoplasmosis
- HIstoplasma capsulatum
- dimorphic, immitis
- midwest US
- pulmonary fous by inhalation of spores (conidia) convert to yeast
- reside in alveolar macrophages to reticuloendothelial system
- TB like lesions, walled off parts of lung
- dissemination in immunosuppressed
- treat with itraconzole, amphotericin B
- virulence factor alpha 1,3 glucan (cell wall to avoid macrophage killing)
-
Blastomycosis
- Blastomyces dermatitidis
- dimorphic, bird poop
- beaver dams in US, asia, africa, S Am
- pulmonary lesion without walled off (pneumonia)
- can disseminate to skin, CNS, gonads, bone
- virulence factor beta-glucan, alpha 1,3 glucan, WI-1 (cell wall)
- treat with azoles, amphotericin B
-
Paracoccidioidomycosis
- Paracoccidioides brasiliensis
- dimorphic, bird poop
- south america
- male predominance (estrogens protect) unless has estrogen binding protein (more virulent)
- long dormancy with reactivation
- pulmonary and chronic cutaneous ulcers
- virulence is alpha 1,3 glucan (cell wall)
- treat with azoles, amphotericin B
-
Opportunistic mycosis
- Candidasis (Candida is most common)
- Cryptococcosis
- Aspergillosis
- Mucormycosis
- Penumocystosis
-
Candidiasis
- Candida albicans, Candida tropicalis, Candida parapsilosis
- opportunistic
- pseudohyphae
- enjoy mucosal surfaces like mouth, vagina etc
- thrush
- systemic dissemination in immunocompromised tropic to CNS, retina, kidneys
- old test is germ tube test
- many virulence factors
- treat local or systemic with azoles, amphotericin B
-
Cryptoccosis
- Cryptococcus neoformans
- opportunistic
- bird poop soil, inhaled
- can cause meningitis
- virulence is surface capsule (not phagocytosable), melanin synthesis genes, myristoyl-CoA transferase
- diangose by india ink, latex agglutination, brain biopsy
- difficult to treat, amphotericin B and 5-fluorocytosine
-
Aspergillosis
- Aspergillus spp.
- opportunistic
- inhalation, asthma like hypersensitivity
- virulence by protease and aflatoxin common contaminate of grains, carcinogen, hepatic failure
- diagnosed by skin test
- treat with steroids, surgery, azoles, amphotericin B
-
Mucormycosis
- Absidia, Rhizomucor, Mucor spp.
- opportunistic
- classic in diabetes because likes high sugar high acid
- rhino to cerebral or pulmonary
- difficult to diagnose and culture
- virulence is endoprotease Arp
- treat with surgery and amphotericin B
-
Pneumocystosis
- Pneumocystis jiroveci
- opportunistic
- likes air water interface so lungs
- classic is pneumonia patient (therefore immunocompromised)
- diagnosed by bronchoscopy
- treat with trimethoprim-sulfamethoxazole or pentamideine isethionate
-
Direct specimen stain
- very fast around 30 minutes
- gram stain, blood smear for malaria, acid fast for mycobacteria, antigen detection
-
Microbial culture
- grow the specimen, can take days or weeks
- bacteria 1-3 days
- blood culture 1-2 then gram stain then subculture a few days (phenotypic ID and susceptibility) and 5 day minimum
- fungi take 4 weeks
- virus culture 2 weeks
- mycobacteria 6-8 weeks
- cannot culture HCV or herpes simplex from spinal fluid
-
Antibody detection
- aka serological assay
- for things that can’t grow like viruses
- hours for turn around
-
Nucleic acid testing
becoming standard of care
-
Commensal relationship
exist together, no reward or damage
-
Saprobe relationship
agent benefits from host without harming
-
Parasite relationship
- agent causes damage
- also a general term
-
Keys to sample
- know flora of that body region
- for lower respiratory sputum <10 epithelial cells per low power field and ≥25 leukocytes is good
- time of collection in the course of infection determines where to get sample
- adequate volume/size
- don’t swab
- very careful with blood stream collection, less than 3% skin contaminants (expensive false positives/bad for pt) get lots of blood
-
Assay turnaround time
- usually batch testing
- delayed by lots of samples coming in and what times you can do it
- suggested move to random access aka on demand
-
New technologies
- immunological methods detect antigens cheap fast easy but low sensitivity
- DNA on culture is easy cheap fast but requires culture
- DNA with amplification (PCR, LAMP, HDA TMA) sensitive, specific, costly
- Matrix assisted laser desorption ionization time of flight mass spectometry still need culture
- Film array uses blood culture ID panel with PCR
- rapid detection is not useful for bacteria or respiratory viruses, but it really improves patient care
-
Live attenuated
- repeated pass through subculture
- loss of function in our environment
- possible severe reactions
- fragile (careful storage/handling)
-
Innactivated vaccine
- whole killed or fractional subunit
- cannot replicate
- less effective, requiring multiple doses
- diminishing response
-
Smallpox vaccine
- highest rates of adverse events of any current vaccine
- usually for military
- only makes sense when small pox was really bad
- eradicated 1979
- live attenuated
-
Measles vaccine
- 2011 still 158k deaths per year worldwide (generally low income countries)
- long immunity after two doses (5% dont respond to first dose)
- MMR (false autism link) live attenuated
- recent increase in measles in US
-
Varicella Vaccine
- two doses for efficacy
- live attenuated
- chicken pox can be fatal and lead to shingles (50% effective vaccine for this)
- few adverse effects
-
Polio vaccine
- Polio destroys nuerons in anterior horn with .1% of infections leading to frank paralysis
- 1955 inactivated polio vaccine by Salk through monkeys and formaldehyde, 3 doses (injection) and 3 serotypes
- 1963 oral polio through monkey, shed in stool, 3 doses, 3 serotypes, lifelong coverage
- live attenuated
- last case in US 1979, India 2011 still in afghanistan, pakistan, nigeria
-
Bacillus Calmette-Guérin (BCG)
- TB vaccine through cows (improved)
- single intradermal injection (repeat unhelpful)
- not super effective
- live attenuated
-
Pertussis vaccine
- fractional inactivated acellular bacteria
- mainly seen in adults, who can give to chlidren
- less effective long term than whole cell but less local reactions
-
Tetanus vaccine
- fantastic efficacy, booster every 10 years
- toxoid fractional inactivated
- cases only in unvaccinated or oldies who wear off vaccine
-
Influenza A
- gene changer leading to different mix and match strains H#N#
- guess what strain every year
- inactivated subunit (tri/quadravalent) intramuscular/intradermal
- live attenuated vaccine (nasal)
- decent in young people, less good the older you get
- rare adverse reactions, mainly local (few fever, malaise) for inactivated
- live attenuated vaccine has URI symptoms in adults and asthma increase in children
- Guillain-Barré syndrome 10x as likely from flu than vaccine
- risk for pregnant women
-
HPV vaccine
- fractional inactivated subunit
- quadrivalent for 6, 11, 16, 18
- bivalent 16,18
-
Polysaccharide vaccines
- pure polysaccharide are not consistently immunogenic in children <2 yrs
- no booster response
- polysaccharide conjugate vaccines are covalently bound to diptheria toxoid (immunogenic but non toxic)
- more robust immune response, booster response
- difference shown by pneumococcal vaccine PPV23 v PCV13
- Haemophilus influenzae type b (Hib) is also polysaccharide conjugate
- pure has more local reactions and conjugate has more fever/myalgia reactions because it is stronger
-
Other fractional vaccines
-
No vaccines
- HIV
- hepatitis C
- lyme disease
- herpes simplex
- staphylococcus aureus
|
|