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Pathology: ID & Micro (Fungi & Parasites)

Characteristics & Concepts of Medically Important Fungi ..................................................................................................... 2

Superficial / Cutaneous Fungal Infections .............................................................................................................................. 5
Opportunistic Mycoses ........................................................................................................................................................... 8
Pathogenic Mycoses ............................................................................................................................................................. 12
Introduction to Parasitology ................................................................................................................................................. 14

Characteristics & Concepts of Medically Important Fungi
 Candida: 3 -4 most common cause of blood
rd th
What is a fungus?
 Eukaryotic (hard to treat; close relationship to other euk) stream infection
 Heterotrophic: feed off of other sources  Aspergillis: most common cause of infectious
pneumonic mortality in BMT recipients
 Polymorphic: different shapes/forms
 PCP/PJP, crytococcus: among most common
 Cell wall: complex, heteropolysaccharides/peptides, target of AIDS-defining infections in HIV pts
antimicrobial therapy
 Cell membrane: contains sterols, commonly ergosterol (target of ampho B)
 Reproduction: all reproduce asexually, 75% have sexual cycle

Fungi contain chitin but not cellulose (plants have both)

Taxonomy based on characteristics of sexual reproduction; 4 classes cause human infections:

 Zygomycetes (mucoralis is order): lower fungi, reproduce sexually
o Rhizopus
 Ascomycetes: reproduce sexually
 Bacidiomycetes: reproduce sexually, basically mushrooms, one exception (Cryptococcus neoformans)
 Deuteromycetes: (deutero = “other”), sexual function has been lost (Candida spp.)

Morphologic Forms
 Yeast: unicellular fungus, reproduces by asexual budding (generation time = hours)
o Budding: create daughter cell, leave mother cell
 Filamentous: fungus whose vegetative form is a mass of individual hyphae (mold)
o Hyphae: characteristics used for dx in laboratory
Branching Septation
 dichotomous = “Y-shaped”  septate, e.g. Apergillus,
 right-angled = “T-shaped”  non-septate, zygomycetes, e.g. rhizopus)
 If NON-SEPTATE, think ZYGOMYCOSIS  AMPHOTERICIN is immediate response
 BRANCHING SEPTATE hyphae in immuncompromised with PNEUMONIA  Aspergillus
 Pseudohyphae: look like hyphae but not filamentous (yeast elongating)

Dimorphism: ability of some fungi to exist in two different morphological forms

Classic dimorphism: e.g. Histoplasmosis

 MOLD in ENVIRONMENT (room temp), YEAST in US
 Taken up by Mϕ, cell-mediated immunity critical
Candida: opposite of classic dimorphism
 YEAST in environment, MOLD in us

Structure of a fungus
 Protects against host response
 Cryptococcal antigen: capsular antigen can be detected from LP in CSF via latex agglutination assay or ELISA.
Extremely sensitive test, targets glucuronxylomannan, produced in huge amounts in cryptococcal infections
Cell Wall:
 Rigid, heteropolysaccharide wall, very resistant to hydrolysis, strength & stability

 NOT a barrier to environment (cell membrane): like a chain link fence
 Multi-layered: glucans: inner fibrillar/inner matrix of cell wall; glycopeptides: inner/outer layers.
o 90% polysaccharide, 10% peptides
o 1,3-β-glucans: enchinocandins target this specific component of cell wall (Candida, Aspergillus)
o Also mannans, chitin, 1,6-β-glucans
 Can monitor mannans or glucans as markers in detection of invasive fungal infections
 Composition varies between different forms of fungi; target of cell/humoral immune response
 Important receptors for cells, intracellular matrices, and HARDWARE (catheters!)

Septum / septae FUNGUS SEPTAE

 Ingrowth of cell wall; appears to divide hyphae into individual cells; different Zygomycetes Few/none
septae for different organisms Ascomycetes Simple
Basidiomycetes Elaborate
Cell membrane
 Typical bilayer membrane; this is the real barrier between fungal cell/environment
 Sterols incorporated into lipid portion; most common is ergosterol, help maintain fluidity
 TARGET for drugs (ampho B = targets ergosterol in membrane directly, alloamines/azoles target biosynthesis)

Other structural features: ER/ribosomes, unstacked Golgi, simple mitochondria, membrane bound vacuoles,
 most haploid in vegetative form

Sexual reproduction: via fusion of hyphae (see picture on right)
Asexual reproduction:
 asexual spores, germinate  colony with identical genetic composition to parent
 more resistant to organism, better dispersion
 can be infective respiratory inoculum in patients (esp. immunocompromised e.g.
AIDS pt, raking leaves  aspergillosis)
 Sporangiospores: asexual spores, produced in sac-like cell called
sporangium by zygomycetes
 Condida: asexual spores (not sporangium) by all other major
groups (e.g. Aspergillus)

Mycoses & Humans

 Virulence: varies widely between fungi; depends on host status
 Cause wide spectrum of infection ( -osis = disease)
 Transmission: endogenous flora, natural environment; most not
 Pathogenic morphologic forms can be varied; different than those in vitro

Fungal structure Examples

Budding yeast forms only Crypto, histo, blasto, sporo
Budding yeast + hyphae Candida, tinea versicolor
Hyphae Aspergillosis, zycomycosis, dermatophytosis
Spherule Coccidiomycosis
(Large spherical structure with internal spores)

Virulence factors:
 Cell surface receptors (epithelial cells, endothelial cells, caths, etc.)
 Hydrolytic enzymes, host mimicry
 Polysaccharide capsule (Cryptococcus)
 Melanin production: inhibits oxidative response (dampens host response)

H&E Differentiate host response, not sensitive for fungi detection
PAS (periodic acid-Schiff) Stains acid polysaccharide cell wall of fungi
GMS (Gomorri’s methenamine silver) Deposits silver on fungal cell wall, better sensitivity of detection
Mucicarmine / Alcican blue Specific for Cryptococcus capsule
(Fontana Masson) Melanin in cell wall of some fungi

Classification by Host Response / Disease

1. Superficial: no inflammation, cosmetic

 E.g. tinea versicolor: very superficial blanching, “spaghetti & meatballs” (hyphae & clusters of yeast)

2. Mucocutaneous: inflammation occurs but no invasion of deeply viable tissue

 E.g. dermatophytosis: tinea corporis, ringed, papulosquamous (silvery, raised) eruption
o Tinea: initially thought was worm (“ringworm”)

3. Subcutaneous: localized infection following trauma

 Chromoblastomycosis (“copper pennies” + sheets of PMNs)
 Mycetoma (highly destructive, muscles/tendons/bones)
 SPOROTRICHOSIS: much more common than the other two
o Traumatic inoculation  single lesion  lymphocutaneous propogation (up lymphatic)
o Working with hay, prick from ROSE PETAL

4. Deep mycoses: life-threatening

OPPORTUNISTIC Common fungi Compromised PMN Candida, aspergilla,
PATHOGENIC More virulent fungi Can be CMI (cell-mediated Histoplasmosis, other
immunocompetent immunity) endemic mycoses

Diagnosis: key features of certain organisms
Zygomycosis / Rhizopus
Non-septate hyphae
(give ampho B)
Branching septate hyphae
(pneumonia in immunocomp pt)
Hyphae + pseudohyphae + yeast form Candida
Capsule Cryptococcus

Superficial / Cutaneous Fungal Infections
1. Dermatophytosis
2. Onchomycosis (nail infection)
3. Tinea versicolor (superficial, variable color, nape of shoulder  across chest)

Superficial mycosis Cutaneous mycosis

Layer affected Superficial straum corneum Epidermis/dermis
Host response No host response Inflammatory response
Example Tinea versicolor Dermatophytoses

Cutaneous fungal infections

Dermatophytes cause most cutaneous fungal infections Dermatophytes

Infections often named by region of body that they inhabit (see table)  Microsporum spp
 Tinea capitis: only children (adults- change in cebaceous glands  stop  Epidermophyton floccosum
getting tinea capitis infections)  Trichophyton spp
 Tinea = “ringworm” (not actually worm) – NOT name of species! Tinea… Dermatophyte
infection of…
Also classified by environmental reservoir Pedis Foot
 Anthropophilic(humans) – e.g. T. tonsurans Capitis Head
 Zoophilic (animals) – e.g. M. canis Corporis Body
 Geophilic (soil) – e.g. M. gypseum Barbae Beard
Cruris Groin
What causes what? Unguium Nail
 Trichophyton (most in US): EVERYTHING (more or less) Manuum hand
o capitis, barbae, corporis, cruris, pedis, unguium
 Microsporum (more common worldwide): capidtis, corporis, cruris, pedis,
o NOT UNGUIUM (no nails)
 Epidermophyton floccosum (only spp of this genus): TINEA CRURIS (groin)

Pathogenesis / Host Defense

 Dermatophytes use keratin as nutrient source
 Inflammatory host responses responsible for involvement of surrounding tissues
 Cellular immunity is key factor in host defense (iron metabolism too)

Hair invasion (arthrocondia = asexual spores)

Type of invasion Athrocondia form… Cuticle Clinically Examples
M. canis
More inflammation
Ectothrix Outside of hair shaft Destroyed M. gypseum
More likely to grow back
T. equinum
Can pull out hair with bulb, without pain.
Endothrix Within hair shaft Intact T. tonsurans
Less likely to grow back

Infections: if possible, can use skin scraping + wet mount to dx

1. Tinea pedis:
a. most common (70% adults worldwide); often Trichophyton rubrum
b. 3 clinical forms: interdigital, moccasin, vesiculobullous (can treat topically)
c. Can have 1 hand + 2 feet: tinea pedis et manuum
d. Can have onychomycosis along with tinea pedis (need to treat systemically)
2. Tinea corporis:
a. non-glabrous skin (trunk, extremities)
b. “Ringworm” – erythematous, round, scaly patch; red, raised, advancing border +/- papules/pustules
c. Itchy (pruritic)
3. Tinea cruris:
a. Invasion of hair follicles (can confuse with cutaneous candida)
b. Predisposition: tinea pedis/onchyomycosis at same time (transfer?)
4. Tinea capitus:
a. Infants, children, young adolescents, in US mostly urban (AA/Hispanic preschoolers)
b. Can transmit child-child or animals/humans
c. Usually Trichophyton (T. tonsurans especially) in US; Microsporum canis most common worldwide
d. Variety of manifestations (pustles/papules/etc) on scalp
i. Inflammation  scaling, alopecia, erythema/exudate/edema
ii. Ectothrix: “black dot alopecia” (some patches preserved)
iii. Endothrix: total hair loss
iv. Kerion (scalp condition; thickened raised area with set of spongy lesions) forms
1. increased cell-mediated immune response; all Mϕ & mono not PMNs)
2. Severe inflammation, hair loss, cervical lymphadenopathy
e. Need to hit hair follicles: systemic + cutaneous treatment

Lab Dx of Dermatophyte Infections

 KOH of scale scraped from leading edge of lesion (destroys most cellular debris)
 Culture to confirm; special agar (Sabouraud dextrose) for up to 4 weeks
 Wood’s light: UV light, M. canis will fluoresce blue-green

Treatment of Dermatophyte Infections:

Tinea Capitis: Topical + Systemic Tx
1. Oral antifungals (griseofulvin, others)
2. Ketaconozale shampoo (reduce fungal shedding)
3. Prevent spread (clean contaminated brushes, pillows; selenium sulfide for other family members)
4. Kid is OK to go to school as soon as he’s on treatment

Tinea pedis, corporis, cruris, manuum: Topical Tx

1. Miconazole, clotrimazole, etc.
2. Oral if extensive/severe/recalcitrant infection

Onchyomycosis: infection of nail plate and/or nail bed that interferes with normal nail function
Epidemiology: mostly dermatophytes (T. rubrum, others)

Presentation: pain, dysfunction, paronychia (skin infection around nails)

 Increased risk: diabetes (bad!), HIV/AIDS, compromised hosts, elderly

Clinical classifications: PSO/DSO/WSO
Immunocompromised hosts
PREVALENCE Most common (90%) 10%
(early HIV infection indicator)
Proximaldistal Dorsal surface of nail
(hyphae under nail plate, spread
INVASION (starts at cuticle, spreads to
proximally, digest stratum plate attacked
entire nail bed)
corneum of nail bed & nail plate)
Whole nail involved / Minimal inflammation
PRESENTATION Proximal parts relatively intact
obliterated (not attacking viable tissue)
HOST RESPONSE Cell-mediated immunity
T. rubrum (most common)
SPECIES T. tonsurans, T. mentagrophytes, E. T. rubrum T. mentagrophytes

Diagnosis: KOH + culture of nail

Treatment/prevention: need ORAL THERAPY (get into nail bed, e.g. griseofulvin)

Tinea Versicolor
Superficial mycotic infection
 Young, middle-aged adults
 Upper trunk/neck/arms; often manifests as depigmentation (“ sun spots” because they don’t tan)

Malassezia furfur is causative agent

 Lipophilic yeast (needs olive oil or something in the agar to grow)
 May also cause fungemia with parenteral lipid solutions (e.g. in babies)
 might be involved in other conditions too

Opportunistic Mycoses
Candida, Aspergillus, Zygomycetes, Cryptococcus, Pneumocystis

Mycoses: 2 groups based on ability of host’s non-immune cells to phagocytose & kill the challenging fungal spore/yeast
Mucocutaneous candidiasis
Altered T-cell function
(e.g. AIDS)
Opportunistic compromised Pneumocystosis
mycoses hosts only Altered phagocytic Invasive candidiasis
activity (quantitative or Aspergillosis
qualitative defects) Zygomycosis
Histoplasmosis (Histoplasma capsulatum)
Blastomycosis (Blastomyces dermatitidis)
Coccidiomycosis (Coccidioides immitis)
deep, systemic normal hosts Cellular/T=cell function
Paracoccidiomycosis (Paracoccidoides brazilensis)
mycoses – Latin America, N. Brazil
Penicilliosis (Penicillium marneffei)

 Opportunist (causes wide range of infection)
 Candida is genus, albicans is most common member
o Albicans is Germ tube POSITIVE, others aren’t
 Hyphae + pseudohyphae + yeast
 Components of normal flora on mucosal surfaces (skin/oral/GI tract/female GU)
 Causes infection only in compromised hosts
Mucocutaneous Deeply invasive
THINK NORMAL MUCOSAL DISTRIBUTION.  Candidemia: #3-4 for blood infections overall
oropharyngeal (thrush), esophageal  Endocarditis, hepatosplenic candidiasis
candidiasis, candida epiglottis (chronic/disseminated),
presentation cutaneous, onchyomycosis, keratitis,  Acute disseminated candidiasis (high burden  septic shock)
vulvovaginal.  Renal candidiasis (filtering out candida sets up shop)
 Altered barriers (vascular/urinary cath, peritoneal dialysis,
 Underlying disease (HIV/diabetes)
trauma, burns, cytotoxic drugs)
 Corticosteroids
Risk factors  Neutropenia, BMT/solid transplants, surgery
 Pregnancy, elderly (↓ immune)
 Broad spectrum Abx
 Antibacterial Abx (kill normal flora)
 Hyperalimentation, hemodialysis
Topical if not serious
 Clotrimazole, etc. Need SYSTEMIC Tx (Fluconazole, etc.)
Systemic if serious (e.g. if esophageal) (Ampho B as salvage b/c of toxicity)
IV if needed

Mucocutaneous candidiasis
Smear / scrape:
 Mucosal: mucosal surfaces; white pseudomembranous placque
hyphae + pseudohyphae
 Cutaneous: intertriginous (where 2 areas of skin rub together) areas: scalded
+ budding yeast
lesions, punctuate satellite lesions
o Diaper dermatitis, paronychial/onchyomycosis, moist areas
o Diabetes
 Chronic mucocutaneous candidiasis: genetic inherited disorder, big scarring; disfiguring
o ↓ cellular immunity to Candida + polyendocrinopathies
 (DM I, adrenal insufficiency, hypothyroid/gonad/parathyroid/etc.)
o Intractable candida: mucocutaneous surfaces (oropharynx, face, toes, fingers, intertriginous areas)
o “Autoimmune-polyendocrinopathy-candidosis-ectodermal dystrophy” (APCED)

o Tx: fluconazole but worry about resistance in long term use
Invasive candidiasis
 Pathogenesis:
1. Adherence/colonization 
2. Penetration through mucosa  angioinvasion / access to venous caths 
3. Hematogenous dissemination 
4. Replication in tissues (necrosis +/- abscess formation) Dx in Tissues:
 Host response: hyphae + pseudohyphae
1. Immune competent: acute + chronic inflammatory cells + budding yeast
2. Neutropenic: no abscesses form, lots of hyphae
If you suspect invasive candidiasis:
Candida Albicans (to check for involvement of vitriol –
 GERM TUBE POSITIVE species (form hyphae; others are negative) candida endophthalmitis)
 Virulence factors:
o surface receptors (epithelial/endothelial cells; extracellular matrices, hardware)
 can act as immunomodulator
 sticky for cardiac valves, caths, etc.
o Hydrolytic enzymes, host mimicry
o dimorphic (yeast in environment  colonizes  sets up shop as hyphae)

Aspergillus spp (Aspergillosis)

 Filamentous; common in environment
 All infections OPPORTUNISTIC
Treatment of aspergillosis
 Voriconizole / ampho B
Clinical presentations
 Need host immune
1. Toxin-mediated:
response: reverse immune
o aflatoxins (extremely carcinogenic; cause hepatocellular carcinoma) suppression!
–on stored grains/peanuts; not elaborated inside a patient
2. Allergic syndromes (atopic pts)
3. Colonizations / saphrophytic
o fungal ball = “aspergilloma” in old TB cavity or impacted paranasal sinuses
4. Infections (deep infections)
o Keratitis (post corneal trauma)
o Invasive disease: pulmonary +/- dissemination

Invasive Aspergillosis
 Risk factor: PMN FUNCTION depression Conidia = asexual spores
o Quantitiative (neutropenia)
o Qualitiative (function: CGD, post-BMT, high dose corticosteroids, HIV)

 Pathogenesis: Invasive Aspergillosis:

1. Inhaled (conidia)  alveoli   “Angular dichotomously
 Normal host: phagocytosis (Mϕ, killing) branching septate hyphae”
 Compromised host: may or may not phagocytose; don’t kill o = Y-shaped with
2. germinate  hyphal invasion of lung parenchyma  septae
3. Angioinvasion (thrombosis, ischemia, infarction)   Angioinvasion, thrombosis
4. Hematogenous dissemination (sometimes)  areas of necrosis

 Role of host defenses

1. Neutropenia: angioinvasion, infarction, dissemination, hemorrhage

2. Immunosuppresion: inflammatory necrosis, local invasion

 Radiology: (not specific for aspergillus – anything that invades a large blood vessel - but commonly present)
1. Halo sign (dense nodule = infarction; delicate structure of local ischemia around it)
2. Air crescent sign (e.g. in recovery; infarcted area
where aspergillus was, separated by a crescent of air
from surrounding parenchyma)

Aspergillus fumigates

Pathology: has characteristic structure:

 Culture: condiophores, vesicles, phialides, conidia
o Powdery surface colonization on plate
 Tissue: septate hyphae (filamentous)
o Note: culture is diagnostic form, tissue just
highly suggestive
Virulence factors
 Adherence receptors, hydrolytic enzymes, complement inhibition; etc.
 Toxins: not afalotoxin in vivo but others

Aspergillus niger
 Commonly saprophytic (in fungus balls; lives off of dead tissue)
 Black color; commonly found in environment

Zygomycosis (mucormycosis)
 Opportunistic; caused by several zygomycetous fungi (Rizopus is most
common species)
 Pathology: wide, non-septate hyphae that branch at right angles
o Invasion of blood vessel walls/nerves; extensive necrosis in
advance of fungus
 Rapid-growing “LID-LIFTERS” (both in lab and in vivo!)
 Sporangiophores have large “sporangia” sacs filled with sporangiospores
(asexual spores)

Disease Description At risk patient

Saphrophytic / Old TB or other lung cavity; no invasion or
Post-TB, bronchiectasis, etc
colonization dissemination.
FAST course – need to diagnose quickly and get biopsy
1. Inhalation (asexual spores from environment) 
Rhinocerebral paranasal sinuses 
Diabetes mellitus + ketoacidosis

zygomycosis 2. tissue invasion (nerves, blood vessels)  cranial nerve

palsies, thrombosis, necrosis 
3. invasion of orbit & eye  extension to brain.
Pulmonary +/-
Marked by angioinvasion Neutropenia

Cryptococcus neoformans
At risk: T-cell-compromised (corticosteroids, transplants, HIV with CD4 < 100)

1. inhale yeast (environment)  lung replication  CD4/CD8 recruited  usually cleared (specific response)
2. If immunocompromised (T-cells)
a. Progressive pulmonary infection
b. Hematogenous dissemination (cross BBB to BRAIN)

 Normal host: chronic inflammation +/- granulomatous response; resolve w/o calcification
 Compromised: mild to non-inflammatory response
 Gelatinous lesion (ENCAPSULATED) Diagnosis of cryptococcus
 Spherical yeast cells with:  Antigen test or direct
o clear area (capsule), obs. in CSF
o narrow/pinched mother-daughter attachment
 Need PAS/GMS (H&E doesn’t really work) Clinically:
 confusion, decreased
Radiography: disseminated infection concentration, headache
(increased ICP)
Virulence factor: CAPSULE
 Glucuronxylomannan with different side chains (different serotypes) Treatment:
o Produced in excess: detectable as ANTIGEN FOR RAPID Dx  AMPHO B + 5FC
 Inhibits phagocytosis; poor in vivo antigen
 Others: phenoloxidase (produces melanin, which inhibits oxygen-dep killing & is stainable)

Pneumocystis carinii/jiroveci
 Opportunistic
o CELL-MEDIATED IMMUNITY is key (not neutropenia) Diagnosis of PCP
 Alveolar-interstitial pneumonia (fever, dyspnea, non-productive cough)  Bronchioalveolar lavage:
o Extrapulmonary dz is uncommon cysts of trophozoites
o Tachypnea + hypoxia  DFA (mAb available)
 Risk factors: immunosuppresion, corticosteroids, HIV infection, elderly  PCR

Radiography Treatment:
 No nodules or infarcts  TMP+SMX
 Interstitial / alveolar involvement, multilobar
 Delicate proteinaceous debris in alveoli, blocks oxygen exchange (alveolar / interstitial disease)
o Trophozoites from cyst damage & create interstitial rxn / debris

Pathogenic Mycoses
Histoplasma, Coccidiodes, Blastomyces, Paracoccidiodes

 Can cause infection in normal host; all are endemic dimorphic fungi
o Contact with organism in well-defined ecological niches
Organism Niche Geography
Histoplasma capsulatum Soil, caves (bird/bat feces) Ohio/Mississippi Valley regions
Coccidiodes immitus Desert soil SW USA (Sonora desert)
Blastomyces dermatitidis Water North/Central, SE USA
Paracoccidiodes brasiliensis unknown South America (Venezuela, N. Brazil)

General features:
 Entry = inhalation (asexual spores from environment); NOT PERSON-PERSON (even if mimics TB)
 Asymptomatic or mild in most hosts
 Disseminated progressive infection: 1/1000 infections Dermatophytes are
o More frequent in T-CELL COMPROMISED transmissible, others
 Pathology: chronic inflammation, granuloma formation generally aren’t

Histoplasmosis (Histoplasma capsulatum)

 Range: Asx to life-threatening
 Histoplasma capsulatum: dimorphic fungus Histo radiography
 Mostly soil/caves in Central USA  acute = infiltrate
o Nature/room temp: filamentous;  chronic = cavitary
 makes micro/macroconidia (microconidia = infectious)
o In vivo/37C: yeast

 Pulmonary entry
o Acute: (90-95% have asx or mild resp sx; 5%: moderate mild to severe resp dz)
o 1/1000: disseminated infections (more common in T-cell compromised);
 Severity/progression: related to host status
 Disease of the reticuloendothelial system: Mϕ lining lung, spleen, LN, bone marrow

 Early / active infection: intracellular budding yeast cells (in Mϕ & monocytes)
 Normal hosts: Granulomas (fibrosis, calcification in old lesions); Few intracellular yeasts
 Immunocompromised (e.g. HIV+): poorly formed granulomas; Many intracellular yeasts
In vivo yeasts
Diagnosis: DNA probes Cell response Location Disease
Histoplasmosis Monocytes Intracellular Lung dz
Culture: SLOW; takes weeks. Molecular Candida glabrata Lymphocytes Extracellular UG / bloodstream opportunist
probes are faster.
 See conversion to yeast at 37C (reverse of candida); macroconidia + hyphae
 Organism is HIGHLY TRANSMISSIBLE in this form (careful! Advise!)

Virulence factors: evades killing by phagocytes; replicates in phagolysosome (neutralize acid environment?)

Blastomycosis (Blastomyces dermatitidis)
 Pneumonia + other presentations
 Water in NE/central USA
 Less propensity for reticuloendothelial system than histoplasmosis
 Hyphae (25C)  large yeast, double wall, broad-based budding (in vivo, 37C)

Coccidiomycosis (Coccidiodes immitis)

 Soil of Sonoran desert of SW USA

Characteristic structure
 Hyphal form at room temperature
o Arthrocondia: little boxcar units
 hydrophobic & easily transmitted (room temp)
 Dispersed throughout environment
 Spherules in tissues (very characteristic); invasive

Clinical presentation: infects lungs, usually mild,

 sometimes can disseminate (brain, joints, other organs)
Tx: antifungal drugs (sometimes for life)

Virtual Rounds
Little boy with itching scalp; hair falling out. Exam: Tinea capitis: High temp cycle for clothes, systemic Tx +
small areas of inflammation/erythema/scratching; pull Trichophyton spp ketoconazole shampoo, selenium sulfide
hair out including bulb. shampoo for other kids
Migratory farm worker, was working with moss. sporotrichosis Azole
Multiple cutaneous lesions, draining.
sICU pt: came back from surgery starting to spike high Candida (if germ tube +, Fluconazole. If liver enzymes elevated,
temperatures, came back as yeast. albicans) can’t use (use echinocandins) Think of
eyes (call ophthalmologist); think of cath
(make sure it’s clean)
Oncology: AML pt in high dose chemo; cough/high Aspergillus Voriconazole; if liver enzymes elevated,
spiking temperature / pleuritic pain. See halo sign on maybe ampho B
radiography. See branching septate hyphae from
bronchioalveolar lavage
14 year old diabetic girl. Acidotic, sinus infiltration that Zygomycosis Ampho B. Debride, correct underlying
shows black, darkened, necrotic nasal turbinate on immune deficit
biopsy. Broad, non-septate hyphae
24 yo IV drug user; minimal access to medical care. Cryptomycosis Ampho + 5 FC. Worried about
Headache. Get LP with antigen test, positive meningitis, increased ICP
Pt with high risk for HIV. Shortness of breath, 85% Pneumocystis (PCP/PJP) TMP+SMX
O2Sat, diffuse interstitial infiltrate with no nodules.

Introduction to Parasitology
Parasite: organism living in complete dependency in or on another living organism (host)
 Host shields parasite from outer world; provides food (parasite’s “restaurant”) Major themes of
 Generally protozoa, worms, arthropods parasitology
Host:  Attachment/invasion
 Host cell invasion
 Definitive: host where sexual reproduction of parasite occurs
 Host-parasite
 Intermediate: host for immature parasite stage / asexually-reproducing stage interaction
Vector: disease-causing parasite is conveyed from this host to another host  Obtaining nutrients
 Immune evasion
Parasitism: most common way of life (>50% all spp);  Encystation/eggs
 all living creatures have parasites (tiny viruses to big tapeworms)  Behavioral changes
 Humans: found in variety of tissues/organs
 man-made ecological changes responsible for perpetuating/intensifying most infectious/parasitic diseases

Epidemiology: huge burden; most morbidity from chronic infection; mortality figures high (malaria in Africa > CVD in US)

Attachment/invasion of host
Attatchment: Parasite needs mechanism to interact with host & prevent its expulsion
 Molecular (receptor-ligand)
o e.g. Plasmodium & RBC molecules; falciparum/vivax use different molecules
 Physical interaction:
o e.g. hookworm, attach with sharp teeth/hooklets
o Feces eggs in soilstepped on  footlungaspirate (weird!)  GI tract

Invasion: Obligate intracellular parasites need host cell to survive & replicate Mechanisms of invasion
 Helminths: different modes of invasion 1. receptor/ligand interaction
1. Direct from environment– worms penetrate skin directly, go to 2. subvert host cell transmembrane
blood (shistosomes, hookworm) signaling pathway
2. Along vector bite path – bite  bloodstream (brugia) 3. modify host cytoskeleton
3. Dispersed from vector bite – enter skin, then go all around through tissue (onchocerca)
Host cell invasion
 Apicomplexan invasion (Toxoplasma gondii)
o glides along surface  apical tip (rhoptry neck) invades; forms
moving junction  rest of parasite pulled in behind (like boat in
Panama canal) – see picture to right
o Result: parisotophorous vacuole. Parasite proteins not
expressed in vacuole, but later help it survive

 Attraction of lysosomes (Trypanosoma cruzi / Chagas dz)

o Secretes molecules to attract lysosome in endothelial/cardiac
cells, gets inside (can also enter via parisotophorous vacuole & fuse)
Host-parasite interaction
Host: Dynamic interaction; host tries to reject, can release cytokines (e.g. IL-8)
 can de-differentiate cells to suite needs
o e.g. Trichinella worm; de-differentiates host muscle by shutting off muscle-specific genes – better for parasite,
huge inflammatory response for host)
 can redecorate host cells to suit needs
o e.g. Plasmodium falciparum: inserts protein into RBC PM; bind to host endothelium so they don’t get destroyed by
spleen (sequestered)

Obtaining nutrients
By definition, parasites obtain nutrients from their hosts
 E.g. plasmodium digests Hb from RBC; some protozoa (Toxoplasma) can’t synthesize purines on own

Immune evasion
1. Interfere with host immune system to co-exist
 Block Ag processing by inhibiting protease cleavage in APC; induce suppressor Mϕ & Treg cells, induce tolerance,
use superantigens, inhibit T/B activation
Clearing: Ab / CMI can be important, or innate/Mϕ can be important (Depends on parasite; intracellular = more innate)

2. Some protozoa can multiply within Mϕ (have to escape lysosome digestion)

Activated Mϕ (T-cell help)  kills parasite; fusion of phagosome with lysosome
Toxoplasma gondii
Naïve T-cells  parasite lives in endosome; doesn’t fuse with lysosome
Trypanosoma cruzi Killed or escapes phagosome to divide in cytoplasm
Leishmania Doesn’t care: resists lysosome enzymes; lives in phagosome
3. Antigenic variation: African trypanosomes express hundreds of VSG (surface proteins); can’t make vaccine
 Waves of infection: one VSG type cleared; another takes over; cleared, etc.

Encystation: eggs/cysts
 Environmentally stable forms (good for transitioning between hosts) Good for diagnosis:
o Thick walled cysts (protozoa, esp. intestinal) stool ova & parasite exams
o Eggs (worms) (“stool O&P”)
 Can be signature forms:
o oocysts in cryptosporidium
o Schistosome eggs
 lateral spur = mansoni; end-spur = haematobium, round = hepatica)

Host behavior
Parasites can alter host behavior
 E.g. Toxoplasma gondii: from cat feces; rats eat it, stop being afraid of other animal
scents (makes it easier for cat to catch them!)

Mechanisms of Pathogenesis
1. Direct cellular damage
 Need to balance host cell damage & needs from host cell
 Direct damage from lysing cell during egress; secreting pore-forming How do parasites cause disease?
peptides, secreting proteolytic enzymes 1. Direct cellular damage
 E.g. Toxoplasma lyses cells during egress – necrotic cell death; invades 2. Mechanical
adjacent cells during the process obstruction/compression
3. Host immunological response
2. Mechanical obstruction/compression 4. Other disease mechanisms
 Helminths are prototype: obstruct GI tract or lymphatics
o e.g. Ascaris  intestinal obstruction in kids in developing countries
o e.g. lymphatic filariasis: block LN, backup of lymph  elephantiasis
 Parasite-filled abscesses/cysts compress vital organs
o e.g. pork tapeworm: brainmass effect seizures
o Encephalitis/brain abscesses in HIV  cerebral Toxo

3. Host immune response

 Eosinophilia (helminths) irritate GI lining, increase bowel permeability, produce more eosinophils
 Granulomas (around destroyed larvae or eggs)  colon/rectum walls, elsewhere (back up fluids, damage)
 Cytokines: IL-8, TNF-α, etc.
 Damage from parasite itself can be minimal; host immune reaction  extreme & harmful
o Schistosomiasis: eggs in bladder  granulomatous rxn  fibrosis  obstruction; carcinoma!

 Anemia, fever, organomegaly, malnutrition, diarrhea, rash, etc.

Intestinal protozoa
 Fecal-oral route; cyst-tryphozite stages (Giardiasis, amebiasis, crytptosporidiois)
o Cyst: resistant wall (infective, found in feces)
o Trophozoite: metabolically active & mobile (non-
 Secretory: small intestine, ↑Cl- secretion from crypt cells
o E.g. giardia (cyst ingested, releases trophozites, differentiates
into cyst again in gut lumen in response to bile  shed in
watery diarrhea  infective).
 Villus blunting, infiltrating lymphocytes, secretory diarrhea
 Invasive / malabsorptive: esp. colon
o Normally need brush border, good epithelium
o Damage to brush border (break junctions/ulcerate)  malabsorption
o Dysentery: diarrhea + blood/mucus in stool
 E.g. Entamoeba histiolytica: protozoa; common cause of dysentery in developing countries;
 Trophozoite / cyst life cycle
 invades host intestinal mucosa; can spread to liver to make abscesses (lung, brain too)
 Can cause colitis (flask-shaped ulcers – spread laterally)

Trypanosoma brucei: African Sleeping Sickness

 Parasitic protozoa; 2 subspecies
T.b. rhodesiense T.b. gambiense
Geography East africa West africa
Chancre: Inflammatory reaction at site Winterbottom’s sign: Enlarged lymph nodes
of tsetse fly bite in neck
Early Sx/ Signs
Rashes with fever if fair-skinned
Kerandel’s sign: press hard on hands; severe pain shortly after release
Cross BBB to CNS Quickly More slowly

 Transmitted by tsetse flies; prefer to bite humans

o disseminate everywhere post infection & multiply wherever blood is
 Epi: 100% FATAL IF UNTREATED; 500k+ infected; thousands permanently disabled from treatment

 Sx: confused with malaria (high, spiking fever)

o CNS involvement:
 Neuro problems: conflicting psych Sx(agitation, indifference, irritability, uncontrolled sex
impulses, violence)  motor system distrubrances (paralysis, tremors, twitching, slurring), pain,
itching (leads to suicide in some!)
 Sleep disturbances (reverse sleep cycle: insomnia + irresistible urge to sleep)
 Seizures, incontinence, total body cachexia (CNS-mediated apoptosis), coma, death

 Tx: need early treatment (otherwise could cross BBB  CNS involvement; white matter encephalitis
o Early stage: without CNS involvement
 Suramin (rhodesiense) or Pentamidine (gambiense), good prognosis
o Late stage: CNS involvement
 Melarsoprol – arsenical; HIGH TOXICITY: 4-12% MORTALITY
 Eflornithine – expensive, injections x14d; phase III trials for oral underway (good for preventing
unwanted hair growth in women too!)