14. Systemic Fungal Infections or Mycoses Flashcards
(38 cards)
The Fungal (5th) Kingdom
~ ____ identified species
~ 1 ____ potential specie
> *200 Associated with ____ (commensals & pathogens)
~ ____ frequent occurring pathogens
* Eukaryotics > fungal kingdom has smalelst euk > \_\_\_\_ > \_\_\_\_ pathogen * And largest euk > armillarie ostoyae > spore disperal unit is up top, main part is below ground (filaments) > covers 9 km, estimated weight = 600 lb
99,000 million humans 12 microsporidium opportunistic
What are Fungi? • \_\_\_\_ • Cell wall (\_\_\_\_, glucan, & \_\_\_\_) • \_\_\_\_ Saprophytic & Parasitic
- No photosynthetic membranes
- Non-____
- Reproduce asexually & sexually forming spores.• From mamlaian cells > cell wall > ____ units
• Hetrotrophs > need a supply of ____
○ Sapro > living off ____; parasitic >living off ____ things
• All reproduce asexualsly, some of them are ____
• Meidcally important are asexual via ____ or ____
eukaryotic
manna
chitin
motile
polysacc carbon dead living sexual division spore production
Morphology
• Broadly divided into yeasts and molds.
• Yeast - single celled, ____.
(eg Candida albicans at ____ temperature)
• Molds consist of hyphae that form a ____.
(eg ____ capsulatum at ambient temperature)
• Dimorphic fungi: yeast
mold
Many of the medically important fungi are ____ Dimorphism frequently associated with ____
• Yeast > single cell form (TR > candidia albiacns), and other is mold (hypahe - majority of fungi exist as; spores egenrated from hypahe) Dimorphic > can swithc between form > associated with virulence > this is \_\_\_\_ depnedent; endemic ones > body T as \_\_\_\_ form, and in enviornemnt exist as \_\_\_\_ form
blastoconidia
ambient
hyphae
histoplasma
dimorphic
virulence
temporatre
yeast
mold
• Antifungal drugs
1. ____–bind ergosterol & interfere with membrane function
1. Amphotericin B – ____. Available as ____ preparation
____ spp, Rhizopus spp, ____ spp, Aspergillus spp.
Side effects & ____ toxicity
- Azoles -inhibit ergosterol ____
____ (Diflucan) – ____ spp, Cryptococcus spp (oral or iv) ____ & Voriconazole – , ____a spp, Cryptococcus spp Aspergillus spp,
____ - Candida spp, Cryptococcus spp, ____ spp. Rhizopus spp- Ergosterol; fungi equiv of choelsteorl in mmebrane
- Ampho > liver toxicity; can bind to cholesterol in ____ with lower affintiy (inihibt host too)
polyenes IV liposomal candida cryptococcus liver
synthesis fluconazole candida itraconazole candida posaconaozle asperigillus
humans
• Antifungal drugs
3. Echinocandins–inhibit ____ synthesis
____, Micafungin, Anidulafungin.
All ____. Candida spp and Aspergillus spp.
- Trimethoprim and sulfomethoxazole (co-trimoxazole, TMP-SMX)
____ synthesis inhibitors. ____ - ____ – ____ synthesis and ____ transcription. Not often used, except in combination with other drugs. ____ spp.
cell wall
caspofungin
IV
folic acid
pneumocystits
flucytosine
DNA
RNA
cryptococcus
Systemic Fungal Infections
1.Endemic – Cause infections (initially respiratory) in people with ____ immune responses.
A. ____ – Blastomyces dermatitidis
B. Coccidioidomycosis – Coccidioides immitis
C. ____ – Histoplasma capsulatum
D. Paracoccidioidomycosis – Paracoccidioides brasiliensis
E. ____ - Penicillium marneffi (opportunistic)
- Opportunistic – Cause infections in ____ individuals.
A. ____ - Candida spp.
B. Cryptococcosis - Cryptococcus spp.
C. ____ - Aspergillus spp.
D. Mucormycosis (Zygomycosis) - Zygomycetes
E. ____ – Pneumocystis jirovecii• Endemic > gelogically localized
○ Normal healthy individula > mild flu, repsiratoyr ifnections; far more drastic effects you see in immunocomporimsed in some way
• Opportunistic > requires immuno-comrposied indivudals
○ Chemo, bone transplant, etc.
○ Hospital borne infeciton > ____
normal
blastomycosis
histoplasmosis
penicilliosis
immuno-compromised
candidiasis
aspergillosis
pneumocystosis
candidiasis
Endemic mycosis
A. Blastomycosis – Blastomyces dermatitidis (____)
B. Coccidioidomycosis – Coccidioides immitis ( ____ USA, ____)
C. Histoplasmosis – Histoplasma capsulatum (Worldwide, ____)
D. Paracoccidioidomycosis – Paracoccidioides brasiliensis (____)
E. Penicilliosis - Penicillium marneffi (____)
Dimorphic – mold form at 25°C or less, yeast form at 35°C or above Mode of infection typically inhalation.
* BM and HP >\_\_\_\_ valleys > occur in drier summer months > spores are inhaled * CM > \_\_\_\_ > southwest into mexico * All are \_\_\_\_; enivornment > mold > spores >nhaled, at body temp (35) they cahange to yeast form
worldwide SW mexico temperature and tropics SA SE asia
ohio/MI river valleys
valley fever
dimorphic
Endemic mycosis - continued
A. Blastomycosis - ____
i. Morphology
____ with pear shape conidia
ii. Epidemiology
Decaying organic matter in the soil North America – Ohio & Mississippi river basins.
iii. Clinical Syndromes
Infections are rare in people ~1 per 100,000. Common in ____.
Route of infection – ____
Symptoms develop in less than half infected individuals
____ disease – mild flu to pneumonia like. ____ onset. If not treated may progress to extrapulmonary, chronic cutaneous lesions.
• See lesion with endemic > host is \_\_\_\_ in some way
blastomyces dermatitidis
mold
dogs inhalation dogs inhalation pulmonary slow
immunocompromised
Endemic mycosis - continued
A. Blastomycosis - Blastomyces dermatitidis - continued
iv. Laboratory Diagnosis
____ or tissue biopsy w/ microscopy
____
v. Treatment
Mild ot moderate cases - ____
Seirous cases - ____ (success rates 70-95%)
* Shows \_\_\_\_ yeast forms; and \_\_\_\_ ocation and \_\_\_\_ of year also invovled in diagnosis * Seirous > causing cutanoeus infections (Spread via BS) > amphotericin
sputum
chest x-ray
itraconazole
amphotericin B
round
geographical
time
B. Coccidioidomycosis – ____ immitis and C. ____
i. Morphology
• Morpho > ____ > in soil when germiantes > spores > ____ > carried in wind > inhaled > spores enlarge and form spherule > mutiple levels of mitosis > ____
ii. Epidemiology
____/Mexico
Bat & rodent ____; “____ fever”
45 infections/100,000.
25,000 new infections/year.
coccidioides posadasii hyphae arthroconidia endospores
SW US
feces
valley
B. Coccidioidomycosis – Coccidioides immitis and C. posadasii
iii. Clinical Syndromes.
____ upper respiratory flulike illness. Typically Resolves and gives ____ to reinfection
Occasionally (~ 5 % cases) secondary coccidioidomycosis can result in dissemination from the lung to to the ____, bones, joints and ____ and cutaneous tissues.
* When not cleared > respiratoyr illness; and secondary infections * Slide > lung biopsy > \_\_\_\_ > erupting and releasing the endospores which can be carried through the body
self-limiting immunity meninges subcutaneous spherule
B. Coccidioidomycosis – C. immitis and C. posadasii - continued
iv. Laboratory Diagnosis.
Microscopic visualization of ____ in sputum or biopsy.
Radiography – ____, CT scan
____ (ID) test of cultured specimen.
Note: highly virulent, must be cultured in ____.
v. Treatment
Usually ____ resolves (weeks to months)
Severe cases, often linked with immunocompromised patients, – ____ followed by ____ or posaconazole (____ yr)
* Spherules distinct > large, cannot be engulfed by \_\_\_\_ when fully developed; endospores within * Highly virulent > must be cultured in glove box * Severe > immuno comporomised, or may have a \_\_\_\_ in innate immune system > mor eporlonged treatment
spherules
chest x-ray
immunodiffusion
glove box
self
amphotericin B
itraconazole
1
macrophage
polymorphism
C. Histoplasmosis – Histoplasma ____
i. Morphology
(does not have a ____)
tuberculate macroconidia - \_\_\_\_ Intracellular blastoconidia (yeast) - \_\_\_\_
• In soil > hypahe > generates microconidia and \_\_\_\_ (condiia = spore) > inhlaed; and in lung,\_\_\_\_ engulfs > HP has a trick > covert macrophage for own use > modifies \_\_\_\_ so it can survive and divide in the phagosome; uses the amcrphage as a home
capsulatum
capsule
soil
pulmonary macrophage
macroconidia
macrophage
phagosome
C. Histoplasmosis – continued
ii Epidemiology
Infections associated with areas of disturbed soils rich in bird and bat guano (____).
H. capsulatum - ____ river valleys.
6 infections / 100.000
Mexico, Central & South America. - ____ infections.
H. duboisii – ____. Skin & bone lesions
iii Clinical Syndromes.
H. capsulatum – ____ like illness, dry cough that is normally ____ limited (~ 90 - 95 % of cases).
Chronic infection resembles ____.
In immuno-compromised patients can disseminate – ____ loss, fatigue, Mucosal ____. Can involve GI & CNS. Death if untreated.
H. duboisii – chronic disease with lesions of skin that can ____. ____
* Can be seen in gums/oral cavity * Dubosii > bone loss /c rhonci lesion of skin
caves
ohio/mississippi
pulmonary
africa
flu
self
Tb
weight
ulcers
ulcerate
osteolysis
C. Histoplasmosis – continued
iv Laboratory diagnosis Direct \_\_\_\_ of clinical material. \_\_\_\_ test (rapid) X-ray & CT scans Culture of \_\_\_\_ samples (2 -3 wks)
v. Treatment
Usually resolves ____.
Prolonged infections – ____. More severe infections – ____+ itraconazle
Famous victims: ____ (recovered).
2007 TFN-alpha gene therapy death in rheumatoid arthritis patient
• Sptum > stained; also an antigen check test of urine • Common theme among treatment of all of these TNF alpha > a tpeitn was immuno comporismed > injection of gene therapy vector > also injected \_\_\_\_ > delivery of fungi into immunocompromised patient
microscopy urine antigen clinical spontaneously itraconazole amphotericin B
bob dylan
HP
D. Paracoccidioidomycosis – Paracoccidioides ____
____ blastomycosis
i. Morphology
____ form at 25°C
Large ____ like like cells with
multiple buds at 37°C
ii Epidemiology \_\_\_\_ America As many as 10 million people infected. \_\_\_\_ rural areas. More common in \_\_\_\_. Spreading \_\_\_\_.
* With climate changing > more in sotuwhestern US * Hypahae -= mycelial; At 37 > budding form; large yeast cells * Most people will clear it \_\_\_\_ * Dunno why more common in men
brasiliensis mycelial yeast south/central humid men north
themselves
D. Paracoccidioidomycosis –
Paracoccidioides brasiliensis
iii Clinical Syndromes
____ infection with fever, malaise, weight loss, can be followed by ulceration of the mucosa of mouse and nose.
Usually ____-limiting, but can disseminated in younger or immuno- compromised patients.
iv. Laboratory Diagnosis
Direct ____ of clinical samples (skin scrapings, sputum, bronchial fluid) – “____”
Serological testing
v. Treatment
____ (6 months) - drug of choice
____ and sulfomethoxazole (co-trimoxazole) - cheaper
* Carried in \_\_\_\_ from lung > can cause ulceration of mouth and nose * Ships wheel > large yeast and you see small yeast \_\_\_\_ from the mother yeast * Usually do not need to treat > self-limiting
pulmonary
self
microscopy
ship’s wheel
itraconazole
trimethoprim
BS
budding
E. Penicilliosis – Penicillium ____
____ most common opportunistic infection in HIV-positive people in ____ Asia
i. Morphology
____ (hyaline molds)
Clearly visible ____ in cells undergoing ____.
ii Epidemiology
Endemic in Southeast Asia
Soil and also isolated from bamboo rat
* Filamenouts mold at 25 degrees * Yeast cells > divide by \_\_\_\_ > two daughter cells are the same cells > septum goes clearly down the \_\_\_\_ of the dividing yeast > helps diagnose this fungi
marneffi third SE dimorphic septum fission
fissure
middle
E. Penicilliosis
iii Clinical Syndromes Primarily associated with \_\_\_\_ Usually \_\_\_\_ at time of diagnosis. Non-specific symptoms; fever, anemia, weight loss. Skin lesions (\_\_\_\_).
iv. Laboratory Diagnosis
Direct observation of dividing yeast cells with ____ septum, in clinical samples.
Culture on ____ gives a red pigment.
Serological tests – under development
v. Treatment
____ followed by itraconazole
* Can see septum down middle of dividing yeast with sample * Saborauds aagar > standard agar for growing yeast/molds * Not diagnosed until dissemniantion > treatment starts with \_\_\_\_
HIV
disseminated
molluscum contagiosum
central
sabouraud’s dextrose agar
amphotericin B
amphotericin
Opportunistic fungal infections
A. Candidiasis - \_\_\_\_ spp. B. Cryptococcosis - \_\_\_\_ spp. C. Aspergillosis - \_\_\_\_ spp. D. Mucormycosis (Zygomycosis) - \_\_\_\_ E. Pneumocystosis – Pneumocystis \_\_\_\_
• Mor eoften found in \_\_\_\_ settings
candida cryptococcus aspergillus mucorales jirovecii hospital
A. Candida spp
Candida spp cause two classes of disease
1. ____ infections.
2. ____ infections
____ most common cause of bloodstream infections in ICUs
- C. ____ (50%)
- C. glabrata (25%)
- C. ____ (15%)
- C. tropicalis (5%)
5. Others (< 5%) • C. krusei §C. guilliermondii §C. dubliniensis §C. rugosa §C. keyfyr §C. lusitaniae
- Newly Emerged
§C. ____
2016 – 4/20/18: 257 confirmed cases. ____ resistant
60 % mortality.• Causes two types of disease > thrush/vaginal infection (mucosal infections, can be cleared up with antigfungal) and the systemic infections (life threatening, reache dblood and dissemianting to other organs)
• Globrate > different from albicans
○ Cadnida was a dumpng gorund fror a lot of yeast like groups > so specturm of species within the genus is quite ____
• Auris > 2014-2016 > found in 3 conitnents at almos thte same time; most common I CT in the US > multi drug reissntant, and can cross calsses of drugs; only found in health care settings and hospitals
mucosal
systemic
fourth
albicans
parapsilosis
auris
multi drug
large
A. Candida spp - continued i. Morphology Thermally \_\_\_\_ (except C. \_\_\_\_ & C. \_\_\_\_)
____ (< 30°C) > serum > ____ (37°C)
Can also form ____ (elongated blastoconidia), and ____
• Candia is a yeast > blastoconida at RT; and whena t higher temp in presenc eof seurm > hypahe ○ Opposite from endemic • Outline of macropaheg > phagocytosed candida cell > at 37 it has formed a hyphae and punctures out of \_\_\_\_ (defensive weapon) and can escape from within phagosome
dimorphic
glabrata
auris
pseudohypahe
biofilms
macrophage
A. Candida spp - continued
ii. Epidemiology & Transmission
Candida spp part of normal ____ for almost all people (C. albicans ~ 80 %).
Candida spp also found in environment (eg fruit, soil)
Most infections are ____ and originate from GI.
Exogenous infections – entry through indwelling ____.
Mortality rate 40 % ~ 8,000 deaths/year in US. (Nosocomial infections - ICU)
Predisposing factors:
* ____ in the toll-like receptor 1.
Other SNPs in cytokine pathways identified. Importance of innate immunity.
* ____ (often associated with induced immunosuppression)
* ____
* Indwelling catheters
* Broad spectrum antibacterials
* Most infectionsf rom person own candida flora and via the GI * Albicans can form biofilms > in the catheter; cells divid and form close contact and form a layer > cells at the bottom > antifungal cannot rach them > progresses into the \_\_\_\_ * Many of those mortality are already ill (chemo, transplants) * Some patients would get recurrent mucosal infection > SNP > TLR1 > make them omore susceptible to candida and other fungi infections (importance of innate system in abttling candida) * Neutroepnia > low NT cpiunts * BS antibacterials > wipe out \_\_\_\_ part of microbiome and candida come in and domiannte
flora
endogenous
catheters
SNP immunodeficiencies neutropenia BS bacterial
A. Candida spp - continued
iii. Clinical Symptoms
Mucosal & oropharyngeal infections have clear physical symptoms.
Systemic candidiasis – more ill defined. Fever & chills that are not responsive to ____. Infection can spread to ____, lung, liver, bone, kidneys, eye
* Mucosal ifneciton have delcined; most susepctible were HIV/AIDS > adavncenment of treating \_\_\_\_ > decrease in candida mhcosal infections * Systmeic candidia > more ill defined >realize dafter high \_\_\_\_ and don’t reposnd to \_\_\_\_
antibiotics
spleen
HIV
fever
antibacterials
