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Vocabulary flashcards covering key concepts in fungal biology, antifungal drugs, pathogenic fungi, dimorphic fungi, common mycoses, protozoa, helminths, and ectoparasites from the lecture.
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Mycosis
An infection caused by a fungus.
Mycology
The study of fungi
Eukaryotes with their own kingdom, ergosterol in membranes, cell wall has chitin/Bglucans/mannoproteins
Molds (filamentous, sex/asex repro) and yeast (round,unicellular, binary fission/budding)
Ergosterol
Sterol in fungal cell membranes; target of many antifungal meds; not present in human cholesterol.
Chitin
A polysaccharide component of fungal cell walls.
Recognized by TLR2
melanin
found near the fungal membrane, can block phagocytosis
Beta-glucan
Polysaccharide in fungal cell walls; target of antifungal meds that inhibit glucan synthesis.
Mannoprotein
Proteins in the fungal cell wall surface rich in mannose.
Sabouraud dextrose agar
Culture medium commonly used to grow fungi.
Polyenes
Antifungal target: interact w/ ergosterol, disrupts plasma membrane, cell bursts.
Amphotericin B - May bind to our cholesterol and cause toxicity :(
Amphotericin B
Polyene antifungal that binds ergosterol and disrupts fungal membranes.
Azoles
Antifungal class that inhibits ergosterol synthesis by interfering w/ yeast enzymes (ex: fluconazole).
Fluconazole
Azole antifungal commonly used to treat Candida and Cryptococcus infections.
Allylamines
Antifungal class that inhibits ergosterol synthesis (squalene epoxidase) (e.g., terbinafine).
Different MOA than azoles
Terbinafine
Allylamine antifungal; inhibits squalene epoxidase in ergosterol synthesis.
Echinocandin
Antifungal class that inhibits glucan synthesis, weakening the fungal cell wall (e.g., caspofungin).
Caspofungin
An echinocandin antifungal used against Candida and Aspergillus species.
Challenges of antifungal development
• Fungi cells are very similar to ours = similar targets (Fewer unique drug targets)
• Not all fungi rely on their “unique” structures (Chitin, etc)
• Ergosterol targeting = cross-reactivity to cholesterol (Toxicity big issue, Ampho”terrible” B)
• Fungi grow slowly in lab, difficulties in studying
• Many fungal infections are in immunocompromised, prolonged infections, toxic treatments
Candida albicans
Yeast; normal flora of mucosal surfaces (colon, vagina, oral); opportunistic pathogen causing thrush and other infections (usually immunocompromised overgrowth, normal flora disruption, vulnerable pt age)
Microscope: KOH prep and look for budding yeast and pseudohyphae
Treatment: oral/topical fluconazole to inhibit ergosterol synthesis
KOH prep
destroys human cells within lab sample
oral candidiasis
thrush: white patches, pseudomembrane that can wipe off leaving red area. common w/ chronic illness and babies
esophagitis: difficult/painful swallowing, AIDS defining infection
Cryptococcus neoformans/gattii
Only encapsulated yeast; opportunistic and neurotropic (likes to infect CNS); causes cryptococcal (fungal) meningitis, especially in the immunocompromised (HIV/AIDS very susceptible if low CD4).
Inhaled from bird droppings, soil.
Diagnose: india ink stain, capsular antigen test
Treat: amphotericin B and fluconazole (could be prophylactic)
Not related!
mycosis and mycolic acid are NOT related at all
sabouraud dextrose agar
used for growing yeast
opportunistic infections
• Immunocompromised or debilitated patient
• Break in skin or mucous membranes
• Normal microbiota OR environmental fungi
primary pathogen infections
• Healthy people
• Environmental fungus
• Soil, inhaled
• Pneumonia is usually primary manifestation
superficial / cutaneous mycoses
• Hair, skin, nails
• Most common – Dermatophytes, Malassezia
subcutaneous mycoses
• Beneath skin, but doesn’t disseminate to organs etc
• Rare
• Sporothrix
systemic mycoses
• Deep within body; internal organs
• Endemic mycoses (Histoplasma, Coccidioides)
• Immunocompromised
superficial transmission
• Person-to-person
• Animal-to-human (dogs, cats)
• Examples: dermatophytes (ringworm)
subcutaneous transmission
skin penetration (cut, wound)
deep/systemic transmission
• Opportunistic growth in immunocompromised or primary pathogen
• Candida in oral cavity, vagina, esophagus
• Primary entry – respiratory tract
major reservoir transmission
• Soil
• Decaying plant matter
• Own normal flora
• Bat/bird droppings
yeast
single celled eukaryotes
round/oval
asymmetrical, asexual reproduction(budding)
candida & malassezia can be overgrown normal flora
cryptococcus = bird droppings
blastoconidia
yeast buds
failure to detach will cause chain (pseudohyphae) formation.
common w/ candida
Capsule
Polysaccharide capsule cell; key virulence factor.
Only yeast/fungus with capsule is cryptococcus neoformans!!
India ink stain
A lab stain used to visualize the capsule of Cryptococcus in CSF.
Malassezia furfur
Yeast causing pityriasis (tinea) versicolor
shows yellow fluorescence with Wood lamp; ‘spaghetti and meatballs’ hyphae/yeast in KOH prep.
Overgrowth of normal flora, very common.
Noninvasive, stays in stratum corneum but prefers sebaceous glands
damages melanocytes - hypo/hyperpigmentation, pink patches
treat: ketoconazole, topical azoles. can prevent with selenium sulfide lotion
molds
• A single hyphae will grow from a spore
• Hyphae – branching cylindrical tubules (Grow from tips, Multinucleated, Will grow like this inside/on the host)
• Aerial (vertical) growth - spores for dissemination (Transmission of spores = infection route) Aerosols, inhalation, Inoculation in wounds/skin break
Hyphae
can be septate or nonseptate (coenocytic)
conidia
individual spores
sporangia
individual spores enclosed in sac-like membrane
Tinea versicolor
Superficial fungal infection of the skin caused by Malassezia species.
Spaghetti and meatballs
A descriptive microscopic appearance of Malassezia hyphae (spaghetti) with yeast cells (meatballs) on KOH prep.
Aspergillus fumigatus
Opportunistic mold with septate hyphae that invades tissues; inhaled conidia; can cause invasive pulmonary/ sinus infections, especially in neutropenic patients.
spores inhaled from soil, compost
infections:sinusitis, rhinosinusitis, acute pulmonary aspergillosus, cerebral aspergillosis
treatment: varies
dimorphic fungi
shape shifters!
can be fungi or yeast depending on temperature
cold = mold (infectious), warm (body temp) = yeast w/ diagnostic morphology
blastomyces, coccidiodes, histoplasma, sporothrix
Septate hyphae
Hyphae with cross-walls (septa); characteristic of many molds including Aspergillus.
Mucor/Rhizopus
Zygomycete molds; causes mucormycosis; non-septate hyphae; rapid, angioinvasive disease.
Dermatophytes
Fungi that invade keratinized tissues (hair, skin, nails); examples include Microsporum, Trichophyton, Epidermophyton.
Dimorphic fungi
Fungi that are mold in the environment and yeast in the human host, depending on temperature.
Blastomyces dermatitidis
Dimorphic fungus; causes blastomycosis; environmental mold forming yeast in tissue.
Coccidioides immitis
Dimorphic fungus causing coccidioidomycosis; environment form is mold arthroconidia; tissue forms yeast spherules with endospores in humans.
Airborne within dry dirt, dust, desert (valley fever)
diagnose: cxr/ct, microscopy/biopsy, antigen testing
treat: fluconazole, maybe amphotericin B
can cause acute pneumonia
Spherules
Large tissue yeast forms of Coccidioides that contain endospores.
Histoplasma capsulatum
Dimorphic fungus; histoplasmosis; yeast inside macrophages; associated with inhalation of soil enriched with bird/bat droppings.
Most common endemic systemic mycoses in USA
Diagnose: cxr/ct, micro/biopsy w/ silver stain. antigen detection
treatment: itraconazole, maybe amphoterican B
Microconidia
Small asexual spores produced by Histoplasma in mold form; infectious form in environment.
Sporothrix schenckii
Dimorphic fungus; “rose-handler’s disease” (sporotrichosis); lymphocutaneous infection.
direct inoculation of spores into skin (wound, etc), found in soil, decomposing plants
diagnose: culture, direct microscopy for oval/cigar shape yeast
treatment: months of itraconazole or terbinfine
Rose-handler’s disease
Sporotrichosis; cutaneous/lymphatic spread after traumatic inoculation with Sporothrix conidia.
pathogenic mechanisms of fungi
Adhesion to cells: Candida and epithelia
Biofilm formation: Catheters, prosthetics
Host tissue invasion
• Hyphal extension, angioinvasive (Aspergillus)
• Protease, lipases (Malassezia)
• Keratinase (dermatophytes)
Immune evasion
• Antiphagocytic capsule (Cryptococcus only)
• Melanin
• Antigenic variation
• Intracellular survival (Histoplasma in macrophages)
clue for fungi and parasite infections
eosinophilia
parasite overview
no vaccines for any of them
tropical or sub-tropical usually
giardiasis most common
70% of world population is infected with worms
parasitic pathogenesis overview
Parasitism – parasites benefits while the host is harmed
• Deprive host of nourishment
• Suppress or trick immune system
No vaccines
Exogenous source: Insects, non-human animals etc.
Diseases symptoms
• Some produce toxins, hydrolytic enzymes
• Some physically obstruct and damage organs due to size and number
Disease manifestations can be due to immune response
• Anaphylaxis, Immune complexes, Granulomas
Adhesion – not as tissue specific
• Some tissue tropism (preference)
• Adhesins – sucking disks – mouthparts
Most protozoans replicate intra- or extra-cellularly in the human host
• Stages of life-cycle general for each group
• Portal of entry does not always = final location!
Wide range of pathogenic mechanisms
• Subacute, chronic – MOST don’t tend to be acute and life-threatening IMMEDIATELY
• Can have asymptomatic infections
Many immune evasion strategies
Severity of disease relates to infectious dose and # organisms acquired over time
• Chronic, repeat exposures, increased burden
• Life cycle inside host?
Tissue migratory parasite: eosinophilia
protozoan
unicellular eukaryote
most have locomotion method
various shapes/sizes/locations that can be diagnostic
usually binary fission
common in developing countries, usually tropical/subtropical areas
helminth
• Worm, multicellular eukaryotes
• Tapeworm (cestode/thorny-headed) - hermaphrodites
• Roundworm (nematode) – male and female
• Fluke (trematode/flat worm) – male and female ; hermaphrodites
ectoparasites
• Parasite that lives on the external surface of a host’s body (skin, hair, or outer body structures)
• E.g., Lice, fleas, ticks, and mites
definitive host
• Host in which sexual reproduction occurs
• Not all will have one
intermediate host
supports one or more developmental cycles
dead end host
• Intermediate host that does not allow transmission to definite host
• Prevents parasite from completing development
Fecal-oral route
contaminated food/water
giardia lamblia - giardiasis
vector borne transmission
plasmodium spp. - malaria via Anopheles mosquito
wucheria bancrofti - lymphatic filiarasis nematode via mosquito
direct inoculation/contact
naegleria fowleri - direct inoculation of water with cysts deep into sinuses
sexual transmission
trichomonas vaginalis - trichomoniasis
ingestions of eggs or larvae (fecal-oral)
enterobius vermicularis (pinworm) - ingestion of eggs from contaminated surfaces
ingestion of undercooked or raw meat/fish
diphyllobothrium latum - fish tapeworm
skin penetration be larvae
hookworms (necator americanus, ancylostoma duodenale) - larve penetrate bare skin from contaminated soil
Giardia lamblia
Flagellated protozoan; causes giardiasis; acquired via ingestion of cysts in warm water, fecal contamination, etc.; leads to diarrhea and malabsorption (trophozoites attach to intestines).
very infectious - only need a couple to cause disease
hiking, camping, drinking from river, etc
diagnose: microscopy, stool antigen test
treatment: metronidazole (not a fungal -azole!)
Trophozoite
Active, feeding stage of many protozoa, including Giardia and Entamoeba.
Cyst
Dormant, hardy form of protozoa like Giardia; typically transmitted via oral ingestion.
Plasmodium species
Apicomplexan protozoa that cause malaria by infecting RBCs; transmitted by Anopheles mosquitoes to humans only; cycles (paroxysms) of fever.
Found mainly in tropics, africa, etc.
sporozoites get injected by mosquitoes → become merozoites that infect RBCs → fever and chills caused by burst RBCs every 2-3 days
diagnose: peripheral blood smears to look at RBCs
treatments: chloroquine, primaquine, prophylaxis before/during/after travel
Anopheles mosquito
Mosquito genus that transmits Plasmodium species causing malaria.
Sporozoite
Infectious stage of Plasmodium injected by the mosquito; travels to liver to initiate infection.
Merozoite
Plasmodium stage that invades red blood cells after liver stage.
Naegleria fowleri
Amoeboflagellate protozoan (ameba AND flagellated trophozoite) causing primary amoebic meningoencephalitis (PAM); typically inhaled via contaminated warm freshwater (summertime). Not communicable. Very rare but 97% fatal.
PAM first resembles bacterial meningitis. Altered taste/smell senses, brain tissue destruction. 3-7 days to death
diagnose: PCR the CSF, see trophozoites in autopsy
unsure of existing treatment
Primary amoebic meningoencephalitis (PAM)
Rapidly fatal CNS infection caused by Naegleria fowleri after nasal inoculation.
helminths
parasitic worms
multicellular eukaryotes
infections usually in warmer countries
cestodes
tapeworms.
Reproductive organs (male and female) within each segment of the worm
Proglottid – each segment
• Gravid proglottid – those containing fertilized eggs (Terminal ones are released and pass through feces)
Eggs develop into larvae: Larvae must go through at least 1 intermediate host before it can be infective again
Scolex, suckers – attachment to intestinal wall
Adult tapeworms are acquired by eating undercooked or raw meat containing larval stages
Adult tapeworms are relatively harmless despite their potential for reaching a large size
platyhelminths
• Flattened bodies with muscular suckers and / or hooks for attachment to the host
• Most are hermaphrodites, except Schistosoma
nematodes
Long cylindrical bodies and generally lack specialized attachment organs.
separate sexes. most species liberate fertilized egg from host
development from egg → larvae → adult can directly occur in 1 host
can be human specific or zoonotic
some need warm soil for ferilization
helminth transmission routes
swallowing infective eggs/larvae, active skin penetration by larvae, bite from blood sucking insect vector
Hookworm (Necator americanus)
Nematode (roundworm) that directly penetrates skin; causes iron-deficiency anemia with heavy infection.
Human only host. Usually in tropics by human fecal soil contamination, requires heavy infection of 500-1000 worms
cutaneous larvae migrans → pulmonary phase (larvae in lungs cause dry cough, wheezing, SOB) → GI phase (abd pain, lost appetite, N/V/D, iron deficiency anemia)
diagnose: eosinophilia, iron deficient anemia, eggs in stool
treament: albendazole paralyzes the worms (not fungal -azole)
Diphyllobothrium latum
Fish tapeworm; cestode; proglottids wider than long; causes B12 deficiency; acquired from undercooked fish.
Definitive host = humans, intermediate host = freshwater fish
Northern hemisphere: Scandinavia, russia, japan, canada, some USA
Human ingest raw fish containing larvae → larvae mature in small intestine and release eggs → eggs enter fresh water to embryonate (2-3 intermediate hosts: crustaceans, fish, etc)
diagnose: proglottids, eggs in stool. low B12 in serum
treatment: praziquantel (paralyzes parasite by increasing calcium permeability and it dies)
diphyllobothriasis
Disease from fish tapeworm
Most asymptomatic - Might have abdominal discomfort, diarrhea
Vitamin B12 deficiency - The tapeworm competes and causes Megaloblastic anemia
Mechanical obstruction of intestines
Malabsorption, weight loss
Proglottid
Segment of a tapeworm containing reproductive organs; shed in feces.
Praziquantel
Anthelmintic used to treat cestode and trematode infections by increasing parasite cell membrane permeability.
trematodes
flukes
humans always definitive hosts
sexual reproduction. eggs in body fluids
eggs develop into larvae in environment.
must pass through at least 1 intermediate host, must be a freshwater snail. will infect 1 human and adult fluke will be in intestine, lungs, liver, blood vessels
Schistosoma species
Blood fluke; trematode; male and female worms joined together. life cycle involves snails and cercariae, eggs gets excreted from urine or stool; causes schistosomiasis.
Acute: swimmers itch on legs/feet (were cercariae entered skin), fever, cough, eosinophilia, ebd pain
Chronic: intestine: abd pain, low appetite, blood diarrhea. urinary: abd pain, urinary frequency/urgency, can cause bladder cancer
diagnose: visualize eggs in excretions, ELISA
treatment: praziquantel (same as fish tapeworm)
parasitic immune evasion strategies
• Antigenic variation: Plasmodium, Schistosoma
• Cover surface in “self ” antigens = molecular mimicry: Schistosoma larvae
• Intracellular survival: Plasmodium, Toxoplasma, Trypanosoma
• Suppress or alter immunity
diagnostic studies for protozoa and helminth infections
• Clinical signs and symptoms, travel history, vector contact etc.
• Microscopy – Gold standard for many
— Stool (ova and parasite) – Giardia (cysts and trophozoites), Schistosoma (eggs), Diphyllobothrium
(proglottids), Hookworms (Necator)
— Peripheral blood smears –Plasmodium
—CSF/brain tissue – Naegleria fowleri
• ELISA, antigen testing
—Stool – Giardia
• Serology for antibodies
—IgM, IgG
ectoparasites
• Arthropods found either on the skin or only in the
superficial layers of the skin
• Insects (six-legged arthropods) and arachnids (eight-
legged arthropods) — Lice, flies, bedbugs, mites, ticks, spiders
• Not vectors of disease, but the cause themselves
Louse / lice
• Nits are eggs —Found attached to hair shaft:White, seen with naked eye
• Transmission: fomites - hats, combs, towels, sheets
—Common in kids
• Adult lice bite and feed on blood – puritis
botfly
• Myiasis - caused by the larvae (maggots) —Inflammatory response causes symptoms
• Usually in tropical areas
• Transmission: Adult fly deposits egg in a wound; egg hatches to produce larva. → Fly deposits the egg in nostrils, in conjunctiva, lips → Fly deposits the egg on unbroken skin and larva invades skin
• Painful, pruritic lesions that resemble furuncles (boils) → Some patients feel movement in the lesion
bedbugs
• Mattresses, crevices of wooden beds
• At night, emerge for blood meal
• Pruritic wheel – hypersensitivity to bug saliva