L8 Flashcards
Fungi fill an important niche in nature:
Principle decomposers (saprophytic) - secrete digestive enzymes
Make up their own
Kingdom - Fungi are Eukaryotes
Most fungi are
free living in nature and are acquired from the environment - a few are part of normal human flora.
Most fungi are
• Mostly strict aerobes (a few are facultative anaerobes)
Fungi cause disease by
• Cause disease by inducing an inflammatory response or through direct invasion or destruction of tissues (some produce toxins)
Fungus have
defined nucleus
Fungal Cell membrane consists of
ergosterol
• Mammaliancellscontaincholesterol
Fungal Cell walls are unique
- With chitin, mannan and glucan
* Different from cell wall of plants and bacteria
Fungi of medical importance - 3 major categories
Yeast- unicellular fungi • Example: Candida albicans
• Molds- multicellular fungi • Mycelium (vegetative)
• Dimorphic fungi- exits as both mold and yeast
Fungal – Molds (multicellular)
Filamentous fungi- (mycelial - vegetative form)
molds - reproduction
asexuallybyconidiathatformonthetips
of growing hyphae
• Sexual reproduction through the development of spores
Dimorphic fungi determined by
Thermally dimorphic- Temperature determines whether mold or yeast
Fungi are encountered by three ways
Incidental contact in the environment
• Most healthy people develop no symptoms
• High inoculum exposures and/or immunosuppression can result in infection
Normal human flora (commensal organisms)
• Usually yeasts
• Disseminated infections in immunocompromised hosts
Contact with infected individual – (dermatophyte)
Innate immunity provides
great protection against fungi
• Most fungal infections are
mild and self-limiting
• Intact skin and mucosal surfaces are
primary barriers
-Desiccation, epithelial cell turnover, fatty acids and/or low pH of skin- important in limiting fungi
• Bacterial normal flora compete with
fungi and inhibit growth
Alterations in normal flora (antibiotics) or compromised skin/mucosal surfaces (trauma, etc.) allow for
entry and infection
T cell-mediated immunity is required to eliminate
fungal infections.
Phagocytosis and killing by Neutrophils is primary mechanisms for containing
fungal infections
Some fungi are too large to be
phagocytized -Phagocytic cells secrete enzymes and reactive oxygen species that can digest or kill large fungi
Antibodies participate in
killing some fungi
• minor component to protection, can even be detrimental
Fungal Diseases examples
thrush, Oral histoplasmosis
Endemic mycoses-
infections caused by geographically restricted fungi (true pathogens)- cause serious systemic infections in healthy individuals
Opportunistic mycoses-
cause life-threatening systemic disease in immunosuppressed patients.
Subcutaneous mycoses-
fungal disease of the skin, subcutaneous tissue, and lymphatics.
Superficial cutaneous mycoses-
common fungal infections limited to the skin and skin structures.
Histoplasmosis- endemic mycoses
Histoplasma capsulatum (Mississippi and Ohio River Valleys) Bird and bat poop
Endemic mycoses - Blastomycosis-
Blastomyces dermatitidis (Mississippi river valley and southeastern and North Central States) Soil mold
Coccidioidomycosis- endemic mycoses
Coccidioides (Southwestern United States) Dessert soils
Endemic mycoses description
Common infections restricted to geographical areas
• Mostly asymptomatic- or mild self- limited symptoms
• Cell-mediated immunity (CD4- T- Cells) required for clearance
• Lung is primary site of entry
Histoplasmosis-
Histoplasma capsulatum description
Dimorphic soil fungus- mold in environment with macroconidia (tuberculate) and microcondidia (infectious form). At 37 °C (body temp.) assumes a yeast like form
• 90% of people have been infected in USA
• Grows in soil with high nitrogen content fertilized by birds and in caves where bat guano (poop) is present
• Clusters of infection (outbreak)- demolition of old buildings that disrupts soil
Histoplasma capsulatum In lungs, transforms into
yeast phase
-poorly understood process but essential for disease process.
Histoplasma capsulatum Reticuloendothelial (macrophage) system infection
Remains viable in macrophages-
modulates phagolysosomal pH
Histoplasmosis - Disease manifestation depends on
number of conidia inhaled and the host response (cell-mediated immune response)
Histoplasmosis - • Most infected people have no or only
mild symptoms
Histoplasmosis - • Ifalargeamountisinhaledevenhealthypeopleget
severe pneumonia
Histoplasmosis - • Somepatientsdevelop
fever,chills,anorexia,fatigueanddry cough:
• If healthy- infection can clear on its own without antifungal treatment
Histoplasmosis - • PatientswithCOPDareat
higherriskofcomplications- • Chronic cavitary pulmonary histoplasmosis, which is eventually fatal
Disseminated Histoplasmosis - Occurs in nearly everyone infected with
H. capsulatum- usually asymptomatic
Disseminated Histoplasmosis - Symptomatic disease more likely in people with
AIDS (cell-mediated immune deficiencies) or with immunosuppressive therapy
Disseminated Histoplasmosis - Acute disseminated histoplasmosis-
fever, chills, fatigue, mucous membrane ulcers, hepatosplenomegaly, pancytopenia, sepsis syndrome.
Disseminated Histoplasmosis - Chronic progressive disseminated histoplasmosis-
happens in older adults- patients die if not treated
Diagnosis of Histoplasmosis - Growth of organism (definitive) -
from sputum, blood, tissues, or body fluids. Can take up to 6 weeks
Diagnosis of Histoplasmosis - Histopathological analysis (with a special stain) of
small intracellular yeasts in bone marrow, liver, lung, or lymph nodes is quicker.
Treatment of Histoplasmosis - In healthy patient- self limited no
treatment needed
Treatment of Histoplasmosis - Mild-to-moderate infections-
Itraconazole for 3 to 12 months
Treatment of Histoplasmosis - Severe infections-
amphotericin B to contain, then switch to itraconazole
Blastomycosis - Dimorphic (fungus in environment, yeast at 37∘C)
yeast have a thick cell wall and broad- based budding
Blastomycosis - Endemic to
Mississippi River Valley and Southeastern states
Soil and decaying wood a likely source
Blastomycosis - Mostly
sporadic cases- sometimes small outbreaks
Blastomycosis infection - Disease occurs when
inhaled into the lungs- multiplies leading to pneumonia
Blastomycosis- infection - Skin lesions also
commonly occur- dissemination - spread by blood
Blastomycosis- infection - Granulomas can develop
• Yeast remains viable and reactivate later
Blastomycosis- infection - Cell-mediated immunity is necessary for
clearance-yeast are phagocytosed by macrophages and neutrophils
Blastomycosis- infection - Diagnosis and treatment
similar to histoplasmosis
Coccidioidomycosis - Valley fever - Found in
dessert soil and burrows
of desert animals
Coccidioidomycosis - Valley fever - Proper environmental conditions allow
“blooms” to form (perfect storm of rainfall, heat, and wind)
Coccidioidomycosis - Valley fever- In endemic areas-
80% of population have been infected
Coccidioidomycosis - Valley fever- San Jaquin Valley Fever-
real problem for prison population- efforts to keep dust levels down
Coccidioidomycosis - Valley fever - Dimorphic - not
temperature dependent
Coccidioidomycosis - Valley fever - Arthroconidia (mold form) are highly
infectious; inhaled into alveoli (lungs)
Coccidioidomycosis - Valley fever - In tissues- transform into large
spherules (50-
100 𝝻m) filled endospores (100’s)
Coccidioidomycosis - Valley fever - Arthroconidia are
phagocytosed and killed, but spherules (yeast) resist phagocytosis
Coccidiomycosis infections - Most healthy people have
no or only mild symptoms
Coccidiomycosis infections - When symptomatic-
Desert rheumatism or Valley Fever
Coccidiomycosis infections - Acute pulmonary infection-
self-limiting (no treatment required)
Coccidiomycosis infections - symptoms
Chest pain, cough, fever and chills
• Joint pain (arthralgias), stiff neck, muscle aches
• Erythema nodosum (rash and painful lumps-lower legs)
• Can become disseminated disease
• Chronic pulmonary infection can occur months or years later
Coccidiomycosis infections - Cell-mediated immunity
(CD4 T-cells) is needed to control (AIDS patients are more susceptible)
Disseminated Coccidiomycosis - Increased risk in:
dark-skinned individuals, pregnant women, and immunocompromised
Disseminated Coccidiomycosis - Can result in
cutaneous, subcutaneous, and osteoarticular infections that spread to other organs (CNS)
Disseminated Coccidiomycosis - Chronic meningitis can be a
complication • Fatal if not treated • Requires life-time antifungal therapy • Antifungals have severe side effects- light sensitivity • Skin cancers results
Coccidiomycosis- diagnosis - Can be cultured-
growth within several days
Coccidiomycosis- diagnosis - Mold on plates can be highly infectious-
laboratory workers should
be warned coccidomycosis is suspected
Coccidiomycosis- diagnosis - Histopathological analysis possible-
presence of spherules in tissues is diagnostic.
Coccidiomycosis- treatment - Itraconazole or fluconazole for
12-24 months depending on extent of
disease.
coccidiomycosis - treatment - Amphotericin B-
if infection is severe
Opportunistic fungal pathogens-Not considered true
pathogens - only cause disease when host defenses are decreased
• Patients at high risk for fungal infections:
Immunocompromised patients
Otherriskfactors
Immunocompromised patients
Immunosuppressive therapy- organ and stem cell transplant
• Hematological malignancies
• HIV infection
• Corticosteroids and other immunosuppressive drugs (Humara)
Candidiasis - Reproduce by forming
buds or blastoconidia
Candidiasis - Some form
hyphae in vivo (non temp- dependent dimorphism)
Candidiasis - Dimorphism exception –
mycelial (hyphae) not yeast form found in tissues
Candida albicans- Most frequent
opportunistic fungal pathogen
Candida albicans- Most infections are
endogenous (derived from host’s normal flora)
• Colonized: gastrointestinal tract (mouth to rectum), vagina, and skin
Candida albicans-Do not cause infection unless
normal flora is disrupted or
patient is immunocomprimised:
• Broad spectrum antibiotics biggest culprit, followed by skin macerations
• Decreased T-cell function increases mucosal infections (AIDS patients)
Candida albicans- T-Cell-mediated immunity keeps
Candida in check on mucosal surfaces (Neutrophils) main host defense against invasion through mucosa
Candida albicans- Neutropenia (low neutrophils) -
candida can spread to many organs (eyes, kidneys, heart, brain, liver, and spleen) - disseminated infections
Candidiasis- yeast infections - Mucosal (Thrush)-
Thick, white plaques on oropharyngeal and vaginal
mucosa
• Sometimes ophthalmic
Candidiasis- yeast infections - Cutaneous (Intertriginous candidiasis)- Proliferation of
candida in warm moist areas of skin (groin, under breasts)
• Babies – Diaper Rash
Candidiasis- yeast infections - Systemic infection (Disseminated candidiasis)
- Can follow superficial infections and central intravenous catheters, renal failure requiring dialysis
- Microabscesses in multiple organs - meningitis, eyes, liver and spleen abscesses, spine, heart on prosthetic valves
- All systemic infections of candida are life-threating and require therapy
Candidiasis- diagnosis - Mucosal candidiasis-
thrush
• Microscopic examination of scrapping- budding yeasts and pseudohyphae • Culture on blood agar plates- growth within 24 hrs.
Candidiasis- diagnosis - Invasive (disseminated) candidiasis -
hard to document
• Culture from blood (not very sensitive)- may require biopsy of involved tissue • Germ-tube test- elongated buds from yeast when exposed to calf serum
Candidiasis- treatment - Mucosal infections-
topical antifungal creams
• Systemic therapy for severe cases
Cadidiasis - treatment - Systemic infections-
always require systemic antifungal (min. of 2 wks)
• Fluconazole and Echinocandin - most common
• Amphotericin B- used for some invasive candidiasis
Cryptococcosis – Cryptococcus neoformans
Environmental yeast
Cryptococcosis – Cryptococcus neoformans - Expresses a huge
polysaccharide capsule in host
Cryptococcosis – Cryptococcus neoformans - Found worldwide in
soil contaminated with bird excreta
Cryptococcosis - cryptococcus neoformans - Approximately 20% of cases are
in seemingly immunocompetent patients.
Cryptococcosis - Yeast are inhaled into
alveoli- producing asymptomatic lung
infection
Cryptococcosis- In lungs, yeast produce
polysaccharide capsule- major virulence factor- prevents phagocytosis by macrophages
Cryptococcosis - T-Cell mediated immunity is
crucial for control of infection- capsule can prevent appropriate response
Cryptococcosis - Most often presents as Meningitis-
resulting from hematogenous spread from asymptomatic lung infection.
Cryptococcosis- Meningitis is subacute to
chronic (worsening headache, fever, cranial nerve palsies, mental status changes)
Cryptococcosis - AIDS patients with meningitis also present with
diffuse pulmonary infiltrates, skin lesions, and widespread visceral infection (internal organs).
Cryptococcosis- diagnosis - • Can easily be cultured on
agar media within a few days- easily identifed
Cryptococcosis- diagnosis - Observation of
encapsulated budding yeast in cerebrospinal fluid (India ink
on slide).
Cryptococcosis- diagnosis - • Latex agglutination test for
capsular polysaccharide- sensitive and specific
Cryptococcosis- treatment - Meningitis -
Amphotericin B and flucytosine (several weeks) followed by fluconazole for several months
Cryptococcosis- treatment - Since the advent of
antiretroviral drugs to treat HIV infections-
cryptococcosis meningitis is rare
Cryptococcosis- treatment - • Pulmonary infections –
fluconazole
Aspergillosis- Aspergillus fumigatus or flavus - Filamentous fungi-
mycelium of septate
hyphae
• Fluffy mold
Aspergillosis- Aspergillus fumigatus or flavus - Reproduce by forming
conidia and aerial conidiophores (sexual reproduction)
Aspergillosis- Aspergillus fumigatus or flavus - • Ubiquitous in
soil, manure, decomposing vegetation
Aspergillosis - Entry - Conidia are inhaled into
upper and lower respiratory tracts -
germinate into hyphae
Aspergillosis - Entry - • Macrophage can kill conidia that reach
aveoli- unable to kill hyphal form
Aspergillosis - Entry - Neutrophils line up along
hyphae and secrete reactive oxygen intermediates that kill the fungus
Aspergillosis - Invasive infection only occurs in
immunocompromised host
Aspergillosis - infection - Angioinvasive fungus-
hyphae invade through blood vessel walls
Tissue infarction, hemorrhage, and necrosis
Aspergillosis - infection - Invasive pulmonary aspergillosis-
Fever, pleuritic chest pain, cough with blood, and difficulty breathing
Aspergillosis - infection - Sinus invasion-
acute facial pain
Aspergillosis - infection - Dissemination is common-
necrotic skin lesions and brain abscess (rarely found in blood)
Aspergillosis - diagnosis - Growth on Sabouraud agar in
a few days (issue with contamination- common in laboratory)
Aspergillosis - diagnosis - Tissue biopsy- to confirm
tissue invasion (identify septate hyphae in tissue)- not specific for Aspergillus
Aspergillosis - treatment - • Voriconazole-
drug of choice
Aspergillosis - treatment - • Amphotericin B or echinocandin are also
used
Superficial and cutaneous mycoses - limited to
limited to (epidermis) skin and skin structures • Dermatophytes (tinea)
• Subcutaneous mycoses- involve the
skin, subcutaneous tissue and lymphatics
• Sporotrichosis
• Myocytomas
• Chromoblastomycosis
Superficial Mycoses - Colonization of
stratum corneum by Malassezia (yeast)- normal flora
Superficial Mycoses - • Usually
asymptomatic
Superficial Mycoses - Seborrheic dermatitis
• Patches with greasy scales
in facial hair and scalp (dandruff)
Superficial Mycoses - Tinea versicolor (misnomer)
•
Hypopigmented or hyperpigmented patches on chest or neck with scaling
Dermatophyte Skin Infections - • Most common
fungal infections in humans
Dermatophyte Skin Infections - • Infect
keratinized tissues (nails, hair and skin)- Keratinase enzyme • Restricted to non-viable skin- can’t grow at body temperature (37∘C)
Dermatophyte Skin Infections - Clinical diseases called
tineas- (ringworm, athletes foot, jock itch) • Latin for “worm”
Dermatophyte Skin Infections - • May be
acute or chronic
Dermatophyte Skin Infections - Three etiological genera- (molds)
Microsporum
• Trichophyton
• Epidermophyton
Dermatophytes - Encounter - Different ecological niches
Geophilic – found in soil
• Zoophilic – domestic and wild animals
• Anthropophilic – exclusively in humans and their habitat • Often cause chronic infections
• May be difficult to treat
Dermatophytes - Encounter - • Not members of the
normal flora
Dermatophytes - Encounter - • Crowding facilitates
spread- contagious
Dermatophytes - Encounter - • Survives on
locker room floors
Dermatophytes -Entry - Innate immunity to
pathogenic fungi is high for most people
Dermatophytes -Entry - Skin and mucosa are excellent
barriers to fungi • Dry, cell sloughing, fatty acids, low pH
• Bacterial flora hostile to fungal colonization
Dermatophytes -Entry - • Skin trauma required
Continuous moist conditions important
• Infections more common when skin is occluded with nonporous materials
• Increases hydration and temperature of skin interferes with stratum corneum function
Dermatophytes-Damage - • Hyphae grows
outward in centrifugal pattern
Dermatophytes-Damage - Viable fungal elements
at inflamed margin
• Central area has few/no viable fungi
• Healing tissue refractory to infection
Dermatophytes-Damage - • Systemic infections extremely
rare
Inability of dermatophytes to grow at human body temperature • Presence of non-specific serum factors
• Transferrin binds iron needed for organism to grow
Subcutaneous Mycoses - • “Mycoses of implantation”
Organisms usually enter skin via thorns or splinters • Infections evolve over several weeks
Subcutaneous Mycoses - • Generally localized with
few systemic symptoms • Lesions usually heal following antifungal treatment
Subcutaneous Mycoses - Immunocompromised patients
•
Widespread cutaneous and visceral infections
Subcutaneous Mycoses - • Thermally dimorphic
fungus (environment - mold, tissues - yeast)
Subcutaneous Mycoses - • Found in
soil, moss, decaying wood and vegetation
Subcutaneous Mycoses - Sporotrichosis-
“rose picker’s disease” • Fungus is introduced by trauma (thorn prick)
• Starts as small lesion (ulceration and/or erythema)
• Can spreads through lymphatic vessels- Lymphocutaneous sporotrichosis
Subcutaneous Mycoses - Disseminated disease
only in immunocompromised patients • Afflicts joints, brain, and spine (very serious)
Subcutaneous Mycoses - Successfully treated with
antifungals- Itraconazole for 3-6 months
Other Subcutaneous Mycoses - Mostly occur in
rural tropical areas of the world (Madagascar and Brazil)
Other Subcutaneous Mycoses - • Caused by
soil mold
Other Subcutaneous Mycoses - Mycetoma (Madura foot)
Chronic infection with sinus tract nodules and
discharge of visible grains (colonies of fungus)
• Can infect the bone or muscle
Other Subcutaneous Mycoses - Chromoblastomycosis
Caused by “dematiaceous fungi” (black fungus) • Scaly, wart-like lesions usually on feet
• Usually require surgical intervention or amputation
Treatment of Fungal infections - Azoles
- Itraconazole, ketoconazole, clotrimazole, miconazole
• Interfere with ergosterol synthesis • Fungistatic
Treatment of Fungal infections - Polyenes-
- Lipophilic – bind to cell wall ergosterol and forms channels
- Amphotericin B • Nystatin
- Hamycin
