Mycology II Flashcards
What type of immunity is responsible for mediating systemic mycoses? Be specific.
Cell mediated immunity, especially TH1 type immune responses
Opportunistic pathogens infect what kind of patient?
Neutropenic patients (immunosuppressed, organ transplant, and cancer pts.
Endemic pathogens live as saprophytes, and enter the body through _____.
Inhalation of spores
What are the four opportunistic species we learned in class?
Candida (yeast, most common)
Cryptococcus neoformans (yeast)
Aspergillus (mold)
Zygomycetes
The species _____ is the leading cause of opportunistic infections.
Candida albicans
Candida is associated with hospital acquired infections (nosocomial infections) due to its affinity for what kind of items? What structures account for this affinity?
Plastics (catheters, central lines, etc.). Candida can form biofilms on plastic tubing due to their sticky pseudohyphae and true hyphae.
Which species of candida does NOT form pseudohyphae and true hyphae?
C. glabrata
C. tropicalis, C. parapsilosis, and C. albicans all have pseudohyphae and true hyphae
Candida appear as an _____ that produce blastoconidia and reproduce by budding.
Oval yeast
C. albicans form what special type of structure in serum at body temperature?
Germ tubes
These structures help us differentiate C. albicans from other yeasts
Identification of different Candida species is best accomplished by culturing on _____
Chrome agar
Candida –> Chrome. They both start with C. I tried.
Candida exist as a _____ in the environment, and as a _____ in mammalian hosts.
Environment: Filamentous fungi
Host: Yeast
As commensals, candida can colonize _____. As such, most candida infections are _____
EVERY MUCOSAL SURFACE
Most candida infections are ENDOGENOUS, resulting from an overgrowth of normal/commensal flora.
Exogenous acquisition is possible, but unusual (contaminated irrigation solutions, IV fluids, donor tissues, unwashed hands, etc.). Remember Candida’s affinity for plastics.
List some risk factors for Candida infection
1) Hematological malignancy
2) Neutropenia *** (Neutrophils = main line of defense)
3) GI surgery (Abx post-op wipe out normal flora –> opportunity for Candida to grow)
4) Extremes of age
5) Exposures
Candida use _____ and _____ to infect the host. What are the roles of these proteins?
Candida use ADHESINS and PROTEASES to infect the host.
Adhesins: Facilitate adhesion to host tissue via binding to fibronectin (an ECM glycoprotein)
Proteases: Destroy epithelial layer, allowing Candida to reach underlying lamina/basement membrane. This allows Candida to get between cells, evading phagocytes. Proteases are located on the hyphae or germ tube.
What are the three major clinical manifestations of Candidiasis?
1) Oropharyngeal infection (thrush)
2) Vulvovaginitis (yeast infection)
3) Cutaneous infection (Jock itch, nail/interdigital infection, diaper rash, e.g.)
Other examples: UTI, pneumonia (ventilated pts.), cardiovascular, CNS, endogenous ocular disease, bone and joint, abdominal, hematogenous)
Oropharyngeal infection (thrush) is characterized by _____ that cannot be scraped off. They are painful and can affect taste.
White plaques
These lesions can be seen around the lips and may go all the way down to the pharynx. They present as white cottage cheese like lesions (patchy to confluent), perhaps with angular chelitis.
Vulvovaginitis is a yeast infection of the _____.
Vaginal mucosa
The loss of normal flora (from douching, abx) in the healthy vagina results in the loss of _____, an organism that contributes to the vagina’s acidic pH.
Lactobacilli
What are some predisposing conditions that may lead to vulvovaginitis?
Diabetes
Pregnancy
Broad spectrum abx usage
Changes in vaginal acidity
etc.
Cutaneous disease caused by Candida most often occurs in _____ and is associated with _____.
Cutaneous disease caused by Candida most often occurs in MOIST PARTS OF THE BODY (groin, fat folds, under breasts, etc.) and is associated with POOR HYGIENE.
Additionally the skin may be weakened by trauma, burns or maceration, providing a route of entry for Candida.
Diagnosis of Candidiasis is accomplished by _____, _____, and _____.
1) Observing yeast and pseudohyphae in sputum, exudates, or tissue
2) Culture
3) Complement fixation, immunodiffusion, Beta-D-glucan test (best for Candidiasis)
What are the treatments for mucosal and cutaneous Candidiasis?
Topical antifungals - Nystatin, Miconazole for vulvovaginitis
Oral fluconazole, itraconazole
What are the treatments for deep seeded Candidiasis? How and why is C. glabrata treated differently?
Oral or IV fluconazole or echinocandin
C. glabrata is treated with amphotericin B and echinocandin because it can be resistant to fluconazole.
What non-pharmacologic measures should be taken to treat Candidiasis? What additional measures should be taken for immunosuppressed patients?
Non-pharmacologic: Remove contaminated catheters and other possibly infected material, drain abcesses
Immunosuppressed patients: Reconstitute immune system along with antifungal treatment.
Which species of Aspergillus is the most important in terms of pathogenicity?
A. fumigatus
Other species: A. flavus, A. niger, A. terreus
Describe the characteristic morphological features of Aspergillus
Branched, septate hyphae that are dichotomous and arise at acute, 45 degree angles. Appear as branches on a tree.
Distinctive conidiophore that looks like an old-fashioned shaving brush or holy water brush.
T/F Aspergillus is non-allergenic.
FALSE
Aspergillus account for a significant amount of allergic rhinitis caused by mold spores.
What structures can obstruct airways and are formed when Aspergillus colonizes the paranasal sinuses and lower airways? What patients are susceptible to the development of these structures? How are they treated?
Aspergillomas (fungus balls)
Tx: Surgical removal
Patients with preexisting pulmonary conditions are most likely to develop aspergillomas. Aspergillus grows easily in areas of previous infection.
Lagniappe: Aspergillomas can spread to other areas via blood to organs, causing an obstruction, or can grow into end-organ tissues.
_____ conidia of Aspergillus can cause pulmonary infections.
Inhaled conidia –> pulmonary infections
T/F Neutropenic patients have a low mortality rate, even when displaying invasive pulmonary aspergillosis & disseminated aspergillosis.
FALSE
These patients have a high mortality rate
The diagnosis for Aspergillosis is derived from what three methods?
1) Observation of characteristic hyphae in tissue samples
2) Culture from clinical samples on mycological agar (ID based on morphology)
3) Immunoassay for serum galactomannan
Treatment for Aspergillosis?
Posaconazole
Amphotericin B
Voriconazole
Echinocandins
(P.A.V.E.)
What class of fungus is characterized by rapid growth, grey to wooly brown colonies, broad hyaline (visualized without stain) and sparsely septate coenoccytic (multinucleated) hyphae.
Zygomycetes
Unlike Aspergillus (conidia on conidiophores), Zygomycetes have _____ within a sac or ______. What other characteristic structure, appearing rootlike, may be present?
Unlike Aspergillus, Zygomycetes have ASEXUAL CONIDIA within a sac or SPORANGIUM.
Rhizoids may also be present.
Which zygomycete is probably the most common cause of human disease?
Rhizopus arrhizus
Zygomycetes are ubiquitous in _____ and are usually acquired by _____.
Zygomycetes are ubiquitous in SOIL AND DECAYING VEGETATION and are usually acquired by INHALATION (but also from ingestion, trauma, contamination w/ sporangiospores from the environment)
What kind of patients are most at risk for Zygomycoses?
Immunocompromised patients, especially those with diabetes mellitus. Zygomycetes find ketoacidotic conditions favorable.
_____ is an acute invasive infection of the nasal cavity, paranasal sinuses and orbit that may extend into the meninges and brain. What patients does this condition manifest in most?
Rhinocerebral zygomycosis
Seen in patients with metabolic acidosis, especially DKA, and those with leukemia.
Lagniappe: It is quickly fatal in neutropenics, and may need to be removed surgically.
_____ is a rapidly progressive bronchopneumonia with lobar consolidation and cavitary lesions. It is caused by an angioinvasive zygomycete, and gives rise to thrombosis of large vessels in neutropenic patients.
Pulmonary zygomycosis
What zygomycosis can be a sign of hematogenous spread of zygomycetes or the result of contamination of a wound?
Cutaneous zygomycosis
What is the main method of diagnosis for a zygomycosis?
Identification via observation of characteristic hyphae (non-pigmented ribbons snaking thru tissue) after treatment with KOH
You’re on your rotations in third year and hear a doctor diagnose a patient with PCP (Pneumocystis carinii pneumonia). You quickly correct him because you’re a gunner. Why was he wrong in making this diagnosis?
He should call this condition PJP (Pneumocystis jiroveci pneumonia) because P. jiroveci infects humans, while P. carinii infects mice.
He continues to call it PCP because he is stubborn. You have made no difference in the world. You weep.
T/F the presence of the asexual cyst form of P. jiroveci in tissue is always abnormal.
FALSE
This form of P. jiroveci could be considered normal flora
T/F Infection of an immunocompetent person with P. jiroveci does not cause symptoms.
TRUE
If a patients CD4 count is _____, infection with P. jiroveci can cause pneumocystis pneumonia (PJP).
Less than 100
T/F P. jiroveci is only responsive to treatment with abx
FALSE
P. jiroveci is responsive to treatment with abx AND anti-parasitics.
How does PJP differ from “traditional” bacterial pneumonias?
PJP: Patchy infiltrate spread throughout the lung, primarily composed of monocytes
Traditional: Formation of consolidations, infiltrate composed primarily of neutrophils
How is diagnosis of pneumocystosis accomplished?
Obsering organism in clinical samples with a wide variety of histologic and cytologic stains. They appear like crushed ping pong balls.
How are pneumocystoses treated?
Trimethoprim-sulfamethoxazole (Bactrim)
OR
Pentamidine (anti-parasitic)
T/F Cryptococcus neoformans is less likely to be seen than C. gattii in immunocompromised patients?
FALSE
C. neoformans is seen more often in immunosuppressed patients, but both species respond to the same drugs.
Describe four morphological characteristics of Cryptococcus
Hint:
1) Shape
2) Replicative structure
3) Extracellular capsule
4) Special growth medium
1) Spherical to oval yeast-like organism
2) Replication via budding from a NARROW/THIN BASE
3) Thick extracellular polysaccharide capsule of glucuronoxylmannan (GXM, can be detected in urine –> diagnosis)
4) Grow on special Bird seed agar (causes cryptococcus to make melanin, a virulence factor)
C. neoformans is a saprophyte usually associated with soil contaminated with _____.
On the other hand, C. gattii is associated with _____.
Neoformans: Soil contaminated with PIGEON DROPPINGS
Gattii: TREES (especially eucalyptus)
T/F Cryptococcus replicated within the tissue of the host?
FALSE
After cells are inhaled, they are phagocytized by alveolar macrophages. Cryptococcus replicates within the macrophage.
Dissemination of cryptococcus to the CNS causes _____. Patients with this typically present with _____.
Chronic meningitis
Present with headaches
Why is T-cell mediated immunity (TH1 response specifically) so important for cryptococcoses?
Cryptococcus replicates in the macrophages of the lung after being phagocytized. T cells are involved in the activation of macrophages via IFN-gamma. Without activation, macrophages don’t kill as efficiently, providing a place for replication of Cryptococcus.
T/F Healthy people infected with C. neoformans have mild, subclinical lung infections that are self limiting, while this is not the case for C. gattii
TRUE
In immunocompromised patients, the yeast of Cryptococcus cause _____. What other conditions do the lesions of this look like? How do we distinguish cryptococcal infection from these other conditions?
Chronic meningo-encephalitis
Lesions may resemble a brain tumor, abcess, degenerative CNS disease, any mycobacterial/fungal meningitis.
To distinguish, cryptococcal antigen in the CSF is checked.
Symptoms of cryptococcoses?
Classic symptoms of meningitis (headache, nuchal rigidity, disorientation) but is a CHRONIC infection
What is the cause of the neuropathology associated with cryptococcoses?
Capsular material interferes with CSF circulation, increasing ICP.
How is cryptococcosis diagnosed?
1) Clinical samples (usually CSF) show yeast forms with thick refractive capsules, but can be missed so…
2) Test for antigen in blood via Latex bead test
3) Growth on Sabouards agar as white colonies or on Birdseed agar as dark colonies. Growth on birdseed agar is the main form of ID.
Treatment for Cryptococcisis?
Amphotericin B & 5-FU (must be maintained in HIV+ patients)
Oral fluconazole as an alternative
T/F Endemic fungi are dimorphic
True!
Describe the thermal dimorphism of Histoplasma capsulatum
Room temp: Mold produces a large thick-walled spherical macroconidia with spiked walls and oval-shaped microconidia
Body temp: Intracellular thin walled yeast
What characteristic does Histoplasma capsulatum share with the cryptococcals?
Both hide out in macrophages! After inhalation, they are phagocytized by macrophages. Cryptococcus replicates there, Histoplasma capsulatum microconidia getminate into a yeast.
The mold of histoplasma is found in areas of high _____
Nitrogen! Bird or bat shit. Outbreaks associated with bird roosts, caves, decaying buildings.
How is histoplasmosis contracted?
Through inhalation of microconidia after soil/dust is disturbed.
T/F The illness caused by histoplasmosis is independent of the patient’s immune status and exposure load
FALSE
For immunocompetent individuals:
Light exposure –> Most are asymptomatic
Heavy exposure > Flu-like illness, resolves without treatment, though rare complications may occur (ARDS, mediastinal fibrosis, pericarditis, arthritis)
What are the three forms of disseminated histoplasmosis? Describe their characteristics.
Chronic: Wt. loss, fatigue, oral ulcers, hepatosplenomegaly
Subacute: Same sx as chronic +fever, bone marrow involvement, CNS, adrenals, heart valves. Death in 2-24 months.
Acute: Sepsis-like syndrome, bleeding oral & GI ulcers, meningitis, endocarditis. Death in days to weeks.
What are the four diagnostic tests for histoplasmosis? Which is the preferred method?
1) ID yeast in sputum, exudates, or tissue
2) Culture mold (takes weeks tho)
3) Serological test for histoplasmin (fungal ag) in serum or urine. Preferred method!
4) Complement fixation/immunodiffusion looking for antigen
Treatment for histoplasmosis?
Oral azoles and amphotericin B
Describe the dimorphic morphology of Blastomyces dermatitidis
Room temp: White to tan mold w/ round oval conidia on terminal hyphal branches.
Body temp: Non-encapsulated yeast
T/F The blastoconidia of Blastomyces dermatitidis are exhibit broad based budding.
True! (Broad Based Budding Blastomyces)
Blastomyces dermatitidis are typically found in _____, and are breathed in when this is disturbed.
Decaying organic matter (leaf litter)
Why it’s seen in hunters and farmers.
Cutaneous blastomycoses skin lesions resemble _____. Need a biopsy to accurately diagnose.
Squamous cell carcinoma
How is blastomycosis diagnosed?
1) Broad based budding yeast in tissue
2) Fungal culture –> observe dimorphism (takes months, uncommon method)
3) Immunological testing for antibodies (Preferred method)
Treatment for blastomycosis?
Amphotericin B
Itraconazole
Fluconazole
Describe the thermal dimorphism of Coccidiodes immitis
Room temp: Mold w/vegetative hyphae producing barrel shaped arthroconidia
Body temp: Arthroconidia become rounded, grow into spherules
How is coccidiomycosis contracted?
Conidia form within the hyphae break apart into barrel shaped conidia. These become airborne and when inhaled cause infection?
In what environment is Coccidiodes immitis found?
Desert areas (southwest US, northern Mexico, South America)
Mold is found in soil, grows faster in bat and rodent shit (nitrogen).
Cycles of rain/drought promote mold growth and subsequent arthrospore disposal (seasonal fungi).
Coccidiomycosis is ommonly referred to as _____ or _____
Valley fever or San Joaquin fever
Primary infection by cocciodes immitis causes _____ or _____. 10% of infected patients develop a _____
Causes asymptomatic pulmonary disease or a self-limited flu-like illness.
T/F Primary infection in cocidiomyosis does not generate a strong immunity, leaving the patient vulnerable to subsequent reinfection.
FALSE
Primary infection in coccidiomycosis generates a strong spwcific immunity. There is therefore no reinfection.
Secondary infection in coccidiomycosis resembles TB in that it is characterised by a _____ in the lungs and _____ on the skin
Nodular cavitary disease in the lungs
Granulomas on the skin
How is coccidiomycosis diagnosed?
1) Observation of endosporulation spherules in sputum, exudates, or tissue
2) Biopsy (Most common)
3) Immunological testing (very uncommon)
Coccidiomycoses are NEVER cultured because of their highly infectious nature.
How is coccidiomycosis treated?
Amphotericin B
Itraconazole
Ketoconazole
