Ascomycota

• ascomycota have a sac like structure called an ascus that usually produce sexual spores called ascospores
• structure of the ascus is used in identification of the group
• ascospores usually protected from nature
• piedraia (skin infection), aspergillus, penicillum, acremonium, pseudallescheria, ajellomyces, coccidoides, spo rothrix, pneumocystis (AIDS), blastoschizomyces, candida, arthoderma, cladophialophora

Basidiomycota

• Basidiomycota: produce exogenous spores on a basidium via meiosis
• usually the basidiospores are exposed to nature
• very complex life cycles
• filobasidiella (cryptococcus): meningitis (has a capsule, look for indian ink stain)
• malassezia: (superficial infections, very rare systemic 
• trichosporon: (superficial infections, very rare systemic)

Zygomycota

• although superficially like ascomycetes, they do not have septate hyphae
• produce zygospores sexually
• Rhizopus and Rhizomucor (mucor): zygomycosis: bread mould

Laboratory: Culture Media

Fungi

• Sabouraud Dextrose Agar (SDA or SAB agar): used for primary inoculation of most specimens, usually incubated at 25C to 30C
• Brain Health Infusion Agar (BHI): (with or w/o blood): used for isolation of certain pathogens. Usually incubated at 35-37C
• Blood Agar (as above)
• Potato Dextrose Agar (PDA): one of many media used to assist in the sporulation of fungi for identification. Used secondary to primary isolation (room temp for several weeks)
• Bird-seed agor or Niger Seed agar:ident of cryptococcus neoformans (only). 25C to 30C

Tinea Versicolor

• chronic, usually asymptomatic - lesions tan or hypopigmented
• superficial scaly, macules and patches: trunk and proximal extremities
• organism: malassezia furfur: lipophilic
• KOH exam -spaghetti and meatballs
• H&E: spores and hyphae w/i stratum corneum

KOH Preparation

• glass microscope, slide, cover slip, KOH (plus or minus ink), alcohol lamp, #15 blade, and microscope
• obtain scale, place on glass slide, add 1-2 drops of KOH, add coverslip, heat gently, examine under low power 

Tinea Nigra

• superficial, asymptomatic infection of stratum corneum
• brown to black macules --> on palms usually (looks like melanoma)
• agent: exophiala werneckii: brown (dematiaceous) mould; environmental isolate (dead/decaying vegetation)
• treatment: over the counter azoles or rx azoles

Black Piedra

• caused by: piedraia hortae
• tropical areas
• hard, brown to black nodules on hair shafts (like nits)
• culture: pigmented, brown to black mold colonies, small and velvety with reddish diffusible pigment
• Treatment: trim below nodule/topical antifungals

White Piedra

• trichosporon beigelii
• ubiquitous in soil, water, plants, mammals, birds - normal flora in mouth, skin and nails in humans
• infects hair like black piedra but light brown to white nodules that are less compact (may rarely cause severe systemic infections in immunocompromised) 
• mold, but looks like a yeast in culture (white colonies)
• trim infected hair. topicals also useful (systemic disease - > poor prognosis. resistant to antifungals, but fluconazole + amphotericin B may be useful)

Fungal (Dermatophyte) Infections

(microsporum and trichophyton sp's)

• cutaneous mycoses
• glabrous skin: tinea corporis
• groin: tinea cruris
• hands: tinea manuum
• feet: tinea pedis
• Face: tinea faciei
• Scalp: tinea capitis
• nails: onychomycosis/tinea unguium
• beard: tinea barbae
• steroid treated: tinea incognito

Other Skin Tineas

(dermatophytes)

• cutaneous mycoses
• include Tinea corporis, manuum (hand), cruris (likes thigh and abdomen), faciei(kids more inflamm.), incognito, pedis (atheletes foot, loves btw toes)
• all look relatively similar w/ annular erythematous scaly patch and central clearing
• tinea incognito sometimes looses some of its features
• treated topically
• 2 foot, 1 hand with tinea pedis and tinea manuum

Systemic Antifungal Treatments 

(cutaneous mycoses)

• tinea capitis
• onychomycosis
• majocchi's granuloma
• immunosuppressed patients
• extensive tinea versicolor or other dermatophyte infection

CDC Bioterrorist Agents

Category A

• easily disseminated or transmitted person to person
• high mortality, w/ potential for public health impact
• require special action for publich health preparedness
• Viruses: Variola Major (small pox), Filovirus (ebola, marburg), arena viruses (Lassa, Junin)
• Bacteria: Bacillus Anthracis (anthrax), Yersina pestis (plague), Francisella tularensis (Tularemia)
• Toxins: Clostridia botulinum toxin (Botulism)

CDC Bioterrorist Agents

Category B

• moderately easy to disseminate
• moderate morbidity and low mortality
• require improved diagnostic capacity and enhanced surveillance
• Viruses: Alphaviruses (VEE, EEE, WEE)
• Bacteria: Coxiella burnetii (Q fever), Brucella spp. (brucellosis), Burkholderia mallei (glanders)
• Toxins: Rinus communis (caster beans) ricin toxin, clostridium perfringens epsilon toxin, Staphylococcus enterotoxin B
• Food/waterborn pathogens: salmonella spp., vibrio cholerae, shigella dysenteriae, ecoli O157:H7, cryptosporidium parvum, etc

CDC Bioterrorist Agents

Category C

• Emerging pathogens that could be engineered for mass dissemination in the future because of: 
• Availability
• ease of production and dissemination
• potential for high morbidity and mortality and major public health impact
• Viruses: Nipah, hantaviruses, tick-borne hemorrhagic fever viruses, tick borne encephalitis viruses, yellow fever
• Bacteria: multi-drug resistant mycobacterium TB

Tularemia (Francisella tularensis)

• caused by a gram-neg coccobacillus
• can be picked up from infected animals; could be aerosolized
• low infections dose
• no current vaccine - investigational
• medications for prophylaxis and treatment
• case fatality in untreated cases aprox 35%
• rabbit hunters?
• something with chest xrays

 Moulds

• hyphae filamentous (hair like structure)
• reporduce asexually by apical(tip) cell division (mitosis) to elongate
• septate and aseptate
• reproduction: more hypae (cell div) and spores

Yeast

• usually single celld or multiple cells that are pinched off
• reproduce by fission
• blastospore (blastoconida) formation is pinching off of reporudctive elements (budding > mother, daughter cells)
• examples: candida (human flora, animals, env), accharomyces (bakers yeast)

Superficial Mycoses

• infect only outermost skin
• Tinea versicolor (pityrias vesicolor): Malassezia furfur
• Tinea Nigra (pityriasis nigra): exophiola werneckii
• Piedraia: piedra hartae (black piedraia) and trichosporon beigelli (white pieadra)
• bedside tests used to diagnose

Trichophyton tonsurans

• tinea capitis (cutaneous mycoses)
• most common agent in USA
• endothrix infection (invades hair shaft)
• does not fluoresce w/ woods light

Microsporum Canus

• Tinea Capitis (cutaneous mycoses)
• second most common (esp in pets)
• causes ectothrix infection (surround hair shaft)
• fluoresces with woods light
• often shows circ patch of hair loss on scalp
• sometimes presents with black dots
• check for lymphadenopathy in cervical region as support in diagnosis

Kerion

• tinea capitis (cutaneous mycoses)
• inflammatory form char by folliculitis and abscess formation
• may lead to permanent hair loss
• must treat quickly

Onychomycosis

• Tinia unguium (cutaneous mycoses)
• infection of tinea beneath nail plate
• must be treated systemically 
• need to confirm diagnosis w/ nail clipping before treatment

Fungal Folliculitis

(Majocchi's Granuloma)

• cutaneous mycoses
• ring worm; wraps around hair folicle 
• forms rings of dots
• see hair shaft full of fungus in histo
• she only had pics for this shit 

Superficial Yeast Infection

• cutaneous yeast infection
• diaper dermatitis (around holes), candida intertrigo, thrush (circles on tongue), angular cheilitis (peneche)
• all caused by candida on moist skin areas
• rash caused by immune system
• macerated erythematous patches on exam w/ satalite lesions
• Ang cheilitis in corner of mouth (not herpes because bilateral and stays)
• KOH exam shows psuedohyphae
• treat with azoles, pyriloes or allylamines

Chromoblastomycosis

• sub-cutaneous fungal infection by pigment producing organisms (dematiaceous)
• traumatically induced
• presents as verrucous plaque on extremities (nodular to)
• pathology shows mixed inflamation w/ nodular bodies (copper pennies, sclerotic bodies)

Entamoeba histolytica

• causes amebiasis
• transmitted by ingestion of cysts and lives in large intestine
• infections liver (common), lung and brain (uncommon)
• Diarrhea, dysentery, abdominal pain, tenesmus
• Lab: trophozoites, antigen detection, PCR on feces or tissue, cysts in feces(does not imply acute disease) and serology
• Clinical carrier: asymptomatic, may still shed cysts
• Intestinal amebiasis: abd pain, cramping, colitis, diarrhea
• Extraintestinal amebiasis: fever, leukocytosis, rigors, abscess formation, right lobe common, elevated righ hemidiaphragm, hepatomegaly
• trophs in tissue aspirate (anchovy paste or sauce)
• treat with metronidazole

Malaria Clinical features

• fever-regularly periodic: may not occur until one or more weeks into illness; cold - hot - sweats
• Anemia: most severe in P. falciparum because RBCS of all ages effected
• Spenomegaly: enlarges during acute phase of attack; may achieve enormous size with repeated attacks
• Jaundice: depends on severity of hemolysis
• malariae causes quartan (every 72 h) fever 
• falciparum causes daily (quotidian), than tertian (48s)

Antimalarial Compounds

• Quinoline related compounds: nonenzyme inh of polymerization of heme results in parasite toxicitiy
• Anti-folate agents
• Artemisinin compounds: interact with heme to produce carbon centered free radicals that alkylate protein and damage the microorganelles of malaria parasites (kill all parasite stages)
• Antibiotics
• Blood schizonticies: quinolines, artemisinins, antifolates
• tissue schizonticides: primaquine, artemisinin (these for liver phase)
• chloroquine resistant (vivax) and sensitive malaria
• primaquine for prevention of vivax: associated w/ methemoglobinemia and hemolisis (check G6PD)

Babesia microti

• bites from ixodes dammini ticks causes babesiosis
• protozoa that infects RBCs
• Malaise, fever with periodic headache, rigors, sweats, fatigue, weakness
• occasionally hemolytic anemic, hepatomegaly, splenomegaly
• lab: blood smear, xeno-diagnosis (hamsters)
• cells show tetrads
• treat with clindamycin + quinine

Toxoplasma gondii 

• blood and tissue protozoa: toxoplasmosis
• ingestion of infected raw meat or oocyte contaminated with cat feces
• infects lungs, heart, lymphoid, CNS and eye (human infection is ubiquitous)
• mono syndrome, CNS toxo, congenital toxo
• lab: serology (ELISA for IgM; IgG will only indicate exposure) and biopsy(trophozoites or cysts) and radiography response to treatment
• CNS toxo in immunosuppressed (aids) CNS lesions, chorioretinitis, pneumonitis, myocarditis
• if treatment neaded most drugs only active on tachyzoites

Congenital Toxoplasmosis

• caused by blood and tissue protozoa: toxoplasma gondii
• triad: hydrocephalus, cerebral calcifications, and choriorentitis
• usually from acute maternal infection
• more severe if acquired in early pregnancy
• usually asymptomatic, but may manifest later after birth
• strabismus, chorioretinitis, encephalitis, microcephaly, hydrocephalus, psychomotor retardation
• anemia, jaundice, hypothermia, thrombocytopenia, diarrhea, and pneumonitis
• To in ToRCHeS 

Naelgleria spp

(Acanthamoeba in skin and eye)

• direct contact (water to nose) causes amoebic meningoencephalitis
• sites of infection: skin, dessemination, CNS
• Amoebic meningoencephalitis, Brain abscess and keratitis
• lab: biopsy, wet prep, iodine smear
• treatment: largely ineffective, Naegleria (Ampho B, miconazole and rifampin
• found in places where water temp doesnt go below 80 degrees (lake in ctrl FL or Tx)

Cutaneous and Mucocutaneous

Leishmaniasis 

• L. torpica, mexicana and brazilienes
• caused by bites of sandfly (injection or promastigote) 
• chronic ulcer, may heal w/o treatment but usually leaves scar (may hide in places you cant see)
• lab: skin scraping, demonstration of amastigotes, smear, biopsy
• cutaneous: papule at site of bite (up to 2 months), red irritated, pruritic, enlarges and ulcerates and may heal w/o treatment
• mucocutaneous: primrary looks similar to cutaneous but 80% untreated go to mucocutaneous and destroy mucous membranes (L brazil)
• visceral: l donovani (dumdum fever): rapidly fatal, chronic debilitating or asymptomatic self limiting (incubation several wks to year)
• antimony compounds, ampho B

Trypanosoma cruzi

• bites of reduviids (kissing bug) causes American Trypanosomiasis (Chagas) disease
• bites and than poops on you (trypomastigote) 
• clin symp: uni lateral periorbital edema (Romana sign), Megadiseases
• Lab: thick and thin films, lympho node biopsy, xeno, serology or PCR
• if not a mega disease they talk about Mud hut

Tryponosoma brucei gabiense

or rhodiense

• African trypanosomiasis from bite of tsetse fly
• Gambiense-slow, CNS decline, lymph node involv, fever, myalgia, arthalgia, Winterbottom sign, lethargy, meningoencephalitis and retard
• lab: thick and thin smears, aspirates, CSF exam, +/- serology
• suramin or pentamidine for blood and lymphatic stages, melarsoprol for CNS

Giardia lamblia and intestinalis

• intest dwelling protozoan causing Giardiasis
• caused by ingestion of cysts and lives in small intestine (found in lake water; beavers)
• also in bile duct and gallbladder
• clin symp: diarrhea (mild to severe, abdominal cramps, flatulence, steatorrhea, malabsorption, and weight loss
• Lab: trophozoites and cysts in feces, duodenal aspirtate and string (looks like a ghost)
• key words: patient w. diarrhea after camping, IgA deficiency or St. petersburg russia
• incubation 1-4 wks;spont recovery after 10-14 days
• metronidazole and nitazoxanide

Trichomonas vaginalis

• sexual intercouse (protozoa) causes trichomoniasis
• only in vagina, prostate and urethra
• clin symp: vaginitis (frothy discharge)
• Wet mount for trophozoites, PCR
• has flagella and use hanging drop test
• Metronidazole, tinidazole

Balantidium coli 

• balantidiasis caused by ingestion of cysts
• large intestine and rare to leave
• clin symp: asymptomatic or GI symp
• Lab: trophozoites and cysts in feces, macro and micro nuclei
• only member of ciliated group patho to humans
• similar to amebiasis (E. histolytica)
• swine and monkey reservoirs
• fecal oral transmission
• substandard hygienic conditions and contact w. swine are risk factors
• treat with tetracycline
• clin: asymp cfarriage, abd pain and tenderness, tenesmus, nausea, anorexia, watery stools w. blood and pus

Cryptosporidium parvum

• cryptosporidiosis
• ingestion of only 10 oocysts. in small intestine
• bilary and resp tract in immunocompromised
• watery diarrhea, abdominal pain, anorexia, fever, nausea, weight loss
• Lab: oocysts in feces, string test, parasite in intestinal biopsy, ACID FAST (for all spori)
• one of most common waterborne diseases in industrialized countries (even w/ water chlorination 30-35% of people have been exposed)
• can be fatal in immunocompromised
• usually self limiting (nitazoxanide or paromomycin)
• other acid fast spori are isospora belli, and cyclospora cayetanensis (biliary in aids)

Microsporidiosis

• enterocytozoon, encephalitozoon, trachipleistophora, nosema, vittaforma
• ingestion and inhalation of spores; sexual or ocular contact may also result in infection
• invades small intestine epithelium
• lives in cornea, bilary tracl, muscle, disseminated
• can cause chronic diarrhea and wasting
• Lab: spores in feces, body fluids, biopsy, look like small red footballs, not tech Acid Fast 

Intestinal Helminths

buzzwords

• Round worms (Nematodes), round 
• Tapeworms (Cestodes), flat
• Flukes (trematodes), leaf shaped 
• Long pearly white worm: Ascariasis
• Infection-Autoinfection: strongyloidiasis
• Itchy-butt: enterobiasis
• Polar plugs: trichuris

Strongyloides Stercoralis

• Strongyloidiasis
• skin transmission and autoinfection in GI tract
• lives in small intestine; can go to lungs and brain
• diarrhea, eosinophilia, pulm infiltrates (shifting), CNS symptoms
• lab: stool, duodenal sampling, serology, Ova and parasite exam on sputum
• can get it from walking around barefoot (move up to lungs, coughed up swolled and into GI
• can be seen w/ recurrent enteric bacteremia when penetrates GI
• thiabendazole or ivermectin

Hook worms

• acynlostoma duodenale and necator amercanus 
  (different locations)
• round worm
• transmission through skin and habitat small intestine
• can go to lungs during maturation
• cause diarrhea, eosinophilia and pulmonary infiltrates
• iron deficiency anemia
• lab: serology (ELISA), stool 
• albendazole

Ascaris lumbricoides

• Ascariasis (long pearly white worm) (round worm)
• oral ingestion and lives in small intestine
• matures in lungs; can go to biliary tract
• diarrhea, eosinophilia, pulm infiltrates, abd pain, fever
• abdominal pain can be seen 
• Lab: stool, serology (ELISA)
• treat with albendazole or mebendazole

Enterobius Vermicularis

• Enterobiasis (Itchy Butt)
• oral ingestion and lives in small intestine
• vaginitis also possible
• clinical symptoms: pruritus, -anal, vaginal, rectal prolapse ine severe cases
• scotch tape technique (tape to morning anus), colonscopy
• may need to test/treat entire family
• Albendazole 

Trichuris trichiura

• Trichuriasis "Whipworm"
• oral ingestion, small intestine -> large intestine
• no extraluminal
• clin symp: asymptomatic with low worm burden, abdominal pain, distention, bloody diarrhea, weakness, weight loss, rectal prolapse
• lab: stool for eggs
• Not Common in states
• areas where human feces used as fertilizer
• anemia and eosinophlilia in sever infections
• albendazole

Diphyllobothrium latum

• Diphyllobothriasis Fish Tapeworm
• oral ingestion and inhabits small intestione (no extraluminal)
• asymptomatic, nausea, vomiting, cramping, peripheral neuroptathy
• lab: stool for eggs or worms, may see macrocytic anemia
• segmented flat worm
• scolax attaches to small intestine and its segments can break off
• raw or pickled fish, cestode, eggs or worms in stool, must treat even if worm is passed
• niclosamide, praziquantel

Taenia solium

• cysticercosis (new onsent seizure in immigrant)
• oral ingestion of contaminated meats (pork tapeworm )
• Intestines: infrequent sympt of abdominal discomfort, indigestion
• Muscle, brain, lungs, eye, cystercercosis, neurocystercercosis
• biopsy of soft tissue, or imaging and serology
• lab: proglottids in stool
• ingestion of water or veggies with eggs from human feces
• may cause autoinfection not just person to person
• symptoms generally based on areas of penetration
• inflam reaction from death of larvae and release of antigenic material

Taenia saginatum

• Beef Tape worm
• oral ingestion contaminated meats
• intestines: infrequen symptoms of abdominal discomfort, indigestion
• NO cysticercosis
• Biopsy of soft tissue, Neuro: imaging, serology, proglottids in stool, eggs in stool
• treat w.  praziquantel for both this and solium (pork tapeworm)
• no second part of cycle

Schistosomiasis

• caused by S. mansoni, haematobium or japonicum
• free living, penetrates skin
• signs and diagnosis vary
• tissue and blood helminths
• eggs with lateral spine (knife) is mansoni, no spine at all is japon, and one sharp at end is haematobium
• free swimming penetrate skin, make way to portal blood than to venus plexus (mesenteric for mansoni); heamatomea goes to bladder plexus
• Katayama syndrome in all three
• treat with praziquantel

Schistosoma mansoni

• Schistosomiasis
• small branches of inferior mesenteric vein, lower colon
• acute: katayama fever: fever cough abdominal pain, diarrhea, hepatosplenomegaly, eosinophilia. sometimes CNS issues
• skin penetration: dermatitis, allergic pruritus, edema
• Hepatic and intestinal abnormalities: abd pain, diarrhea, bloody stool, periportal fibrosis, portal hypertension (ascites and hepatosplenomegaly)
• lab diagnosis: eggs in stool, rectal biopsy for eggs tracks, serology

Schistosoma haematobium

• Schistosomiasis
• looks like cobblestoning of bladder and tumor
• vesical, prostatic, uterine plexuses, occasionally portal 
• acute: Katayama fever: fever, cough, abdominal pain, diarrhea, hepatospenomegaly, eosinophilia. sometimes CNS issues
• skin penetration: dermatitis, allergic pruritus, edema
• urine symptoms: hematuria, frequency, dysuria
• long term: hematuria, bacteriuria, bladder scarring, obstructive uropathy
• lab diagnosis: eggs in urine. bladder biopsy for eggs. sometimes eggs in stool, if gone to mesenterics

Schistosoma japonicum

• Schistosomiasis
• superior mesenteric vein around small intestine
• Acute: katayama fever: fever, cough, abdominal pain, diarrhea, hepatospenomegaly, eosinophila. sometimes CNS issues
• skin penetration: dermatitis, allergic pruritus, edema
• Long term: hepatosplenic disease, portal HTN, bleeding varices, ascites, pseudotubercles in liver
• Cerebral: lethargy, speech impairment, visual defects, seizures
• Lab diagnosis: eggs in stool, rectal biopsy, serology

Echinococcus granulosus

• Echinococcosis, hemilinth?
• Hyatid cyst
• Cestode
• transmitted oral ingestion of contaminated meats, fecal oral (humans dead end intermediate), ingest egg larval and oncospere hatches
• associated with people who own dogs (also sheep or cattle)
• may take years to manifest--slow growing cysts
• depends on site of cysts: liver, brain or lung
• imaging and serology (low sens)
• do not want to aspirate or rupture cysts
• albendazole

Trichinella spiralis

• trichinosis
• oral ingestion of contaminated meats  (pork or arctic explorer eating walrus)
• inhabits duodenal and jejunal mucosa of flesh eating mammals (infectious larval form in striated muscles)
• influenza like: fever, diarrhea, myalgias, eosinophilia, periorbital edema
• psychosis, meningoencephalitis, CVA
• Diagnosis: outbreak tracing, larvae in biopsy specimen, serology
• no treatment if in tissue, mebendazole if in intestines and sever with steroids and mebendazole
• microwave, smoking, drying meat do not kill larvae

Filariasis

• Wuchereria bancrofti; or brugia malayi/onchocerca volvulus
• insect bite
• adults in lymphatic system or subcutaneous tissue
• W. bancrofti and b malayi-lymphatic filariasis (elephantiasis)
• o volvulus-african river blindnes (snowflake opacity)
• volvulus is bite of black fly or hanging groin
• diangosis: skin snips (onchocerca), eosinophilia, parasite in blood smear
• treat with tetracycline

Loa Loa

• Loiasis
• worms penetrate bite wound
• calabar swelling episodic angioedema, " worm crawling across my eye"
• diagnosis: clinical observation of worm, eosinophilia, worms in blood, serology
• diethylcarbamazine (CDC only)

Parasite Drugs

• Benzimidazoles: damages cytoplasmic microtubules in the absorptive and intestinal cells of nematodes but not host
• Nitroimidazoles: DNA helix disruption, inhibiting nucleic acid synthesis
• Praziquantel: increases cell membrane permeability
• Nitazoxanide: unknown, but thought ot be electron transport disrutpion
• Diethylcarbamazine: CDC only

Subcutaneous Mycoses

• chromoblastomycosis
• sporotrichosis
• mycetoma

Chromoblastomycosis

• subcut fungal infection by pigment producing organism (dematiaceous)
• traumatically induced
• presents as verrucous enlarging plaque on extremities (nodular)
• pathology shows mixed inflam w/ nodular bodies (copper pennies, sclerotic bodies)

Sporotrichosis

• sporanthrix schenckii
• subcutaneous mycoses
• lives in soil, plants and decaying vegitation
• ofetn occurs after handing conaminated plant material (roses, traumatically induced)
• clinically shows erythematous nodules and verrucous lesions usually extending up extremity following lymph drainage (sporotrichoid spread)
• cigar shaped yeast forms
• splendore -hoeppli bodies (asteroid)
• treat with itraconazoles; oral potassium iodine in saturated solution (SSKI)

Mycetoma

• subcutaneous mycoses infection
• chronic granuloma disease of skin and subcutaneous tissue
• traumatically induced 
• char by granulomas and abscesses w/ grans: eumycote-fungal( containe large aggregates of fungal hyphae
• actinomycotic bacterial
• typically affects lower extremities but can occur in almost any body region

Deep Mycoses

• hisoplasmosis (ohio vally
• blastomycosis (lung inf to skin, broad base budding)
• coccidioidomycosis (valley fever, dry climate)
• cryptococcosis (only immunocompromised

Blastomycoses

• located in miss river basin and great lakes
• dimorphic 
• no person to person but lab aquired possible
• inhalation of conidia is infection phase
• thick yeast cell wall (double contoured) and BAD-1 adhesion and immune modulate
• pulmonary: high fever, lobar infiltrates and cough and chronic pneumonia that looks like TB
• cutaneous: papular, pustular or ulcerative, painless, due to hematogenous dissemination from lung
• can culture aspirtate, biopsy or sputum/fluid
• Itraconazole or ampho B

Histoplasmosis

(histoplasma capsulatum)

• ohio/miss river valley, mexico and americas
• mold form (tuberculate macroconidia); yeast intracell
• soil w/ bird and bat droppings
• inhalation, phagocytosis and conversion to yeast form
• Acut pulmonary or life threatening (most asymp), and acute disseminated
• chronic pulm and chronic disseminated (usually middle age to elderly men)
• visualize with met silver or PAS or histoplasm urinary Ag test
• Itraconazole or Ampho B treatment

Coccidiomycosis 

(L. immitis)

• endemic to deserts and america (soil with droppings)
• Jan joaguin valley fever (can see eosinophilia)
• mold form alternating arthroconidia and yeast with spherules w/ endospores
• small innoculum causes disease (16-42% have had)
• primary: asymp; flu like with various allergic rx
• secondary: >6wk symptoms, pulm nodules and cavities, progressive pulm disease (5%)
• primary dissemination
• extrapulm: cut., bones, joints and meningitis
• lab: dont culture, endosporulating spherules
• -azole or ampho B

Paracoccidiodomycosis 

(p brasiliensis)

• along river from amazon jungle
• inhalation or traumatic inoc 
• yeast form has budding mariners or pilot wheel
• peak incidence of infection 10-19 but disease more common in men 30-50
• acute and chronic pulm )nodular, infiltrate, fibrotic)
• extrapulm: skin, mucosal, liver, spleen, CNS, Bones
• culture confirmed w/ thermal dimorphism testing or exo Ag testing
• Itraconazole or Ampho B

Penicillium morneffei

• endmic mycosis
• dimorphic fungi
• endemic in thailand and south china
• risk fact: aids or severe immunocompromised
• disease: pulm, lymphadenopathy, skin lesions (disseminated)
• treat with photericin B and flucytosine (have to start agressive

Oppurtunistic Pathogens

• candidiasis
• cryptococcosis
• mucormycosis

Candidiasis 

(C albicans; glabrata and others)

• psuedohyphae (except glabrate), blastocandidia (buds) and chlamydospores
• human colinization in GI, vag, urethra, skina nd nail
• most infections are endogenous (can be exogenous)
• mucosal: thrush, gastroenteritis, chronic mucocutaneious (def in T cell, severe, unrelenting oral lesions, vaginitis, disfiguring glanulamtos skin lesions), diaper rash, vulvovaginitis
• cutaneous and nails: intetrigo and puronychia and onychomycosis

Invasive Candidiasis

• candidema w/ hematogenous spread
• 3rd most common cause of blood stream infection
• high mortality rate: 61%
• pathogenesis: caused by breakdown of barriers, antibiotics, primary neutropenia and HIV
• infective endocarditis, endopthalmits/chorionephritis (all candida pts must have eye exam), disseminated skin lesions (painles pustules on erythematous base), diskitis and vert osteomyelitis, chronic hepatosplenic and CNS infection
• culture (budding yeast w/ psuedohyphae, gram tube test for albicans. chromogenic media
• surgery and alternative antifungal (azole resist) or topical for cutaneous

Cryptococcosis

• C. neoformans (ubiquitous and pidgeon droppings) and gattii (tropical, eucolyptus trees)
• encapsulated buddying yeast
• infect lungs, disseminates to CNS in immunocompr
• pulmonary: variable, nodules and fulminent pneumo
• cerebromeningitis: crypto highly neurotropic
• fever, headiche, meningism and vision change
• gatti does parenchymal lesions
• indian ink does not penetrate: forms halos (capsle)
• serum cryptococcal Ag
• usually has high opening CSF pressure on LP
• ampo B, flucytosine and fluconazole
• might need LPs to asses CSF sterility and maintain ventricular pressure

Aspergillosis

• mold, not yeast
• ubiquitous in air, soil, decaying matter, and hospitals
• conidia go into alveolar space and attach to damaged epithelium where they swell and germinate
• hyphae spread thru lung parenchyma and blood vessels causing hemorrhage and necrosis
• at risk: systic fibrosis, chronic lung, neutropenia, immunocompromised
• Allergic respons, aspergillomas (fungal balls), chronic cavitary pulm asperg (CCPA), invasive sinopulm asperg/disseminated
• diagnosis: moniliaceous, septate, dichotomously branching hyphae, asp galactomaman Ag (spec)
• voriconazole, ampho B, surgery
• prevention: filter air, wear mask dont have potted plants

Mucormycosis

• Rhizopus most common (bread mold)
• infections acute and rapid progressing, angio invasive and mortality rate of 70-100%
• can be in hospitals during construction, air conditioners and very immunocompromised hosts
• at risk: solid organ or bone marrow transplant, diabetes, deferoxamine therapy, neutropenia
• ingestion or contamination of wounds causes tissue infarction and nercosis (halmark)
• Rhizopus makes ketone reductase that allows growth in high glucose env (deferoxamine promotes growth)
• 6 clinical syndromes: rhino-orgbital-cerebral, pulm, cutaneous, GI (stomach),
• diagnose with histopathologic evidence and ribbon like aspetate, non pigmented broad hyphae with irregular branching
• ampho b, posoconazole, combo therapy

Polyenes

• binds ergosterol causing membrane disruption (cytolysis)
• Ampho B: for invasive fungal infections
• adverse rxs: infusion related toxicitiy, renal failure (dont give w/ corticosteroids/acetameniphine)
• an electrolyteddisturbance (K and Mg way down)
• Lipid and liposomal preparation have fewer adverse effects and allow for higher doses
• Nyastatin given topically for mucosal and cutaneous candidiasis

Griseofulvin

• disrupts mitotic spindle causing arrest of metaphase of cell division (defective DNA and no replication)
• Gold standard for Tinea capitis: used for dermatophytes when itraconazole not usable
• adverse effects: photosensitivity, drug eruptions, leukopenia, GI distress and exacerbates SLE, porphyria

Flucytosine

• deaminate to 5 flurouracil in fungi, inhibits purine and pyrimidine uptake and DNA synthesis
• rapid resistance; use with other antifungal songs
• well absorbed (joints and CSF included)
• used with ampho B for cryptococosis
• adverse rx: cytopenias (dec in WBCs, RBCs, platelets), gI distress, rash and confusion

Azoles

• less toxic than polyenes and inhibit lanosterol synthesis (late step in ergosterol syn) via p450
• Ketoconazole: oral abs with acidic pH, poor CSF penetration but broad spectrum
• Miconazole: topical treatment of cut/mucos candidias
• Clotrimazole: cutan/mucosial infections
• Fluconazole: oral/IV; litte adverse effects (GI, rash, and rare hepatitics), for endemic mycoses
• Itraconazole: oral only, high levels in nail plate
• Voriconazole: Iv/oral; broad spectrum, many drug interactions, skin reactions (Steve johnsons syndrome)
• Posaconazole: oral only, avoid grape fruit juice

Echinocandins

• 1,3 D glucan syn inhibitor (cell wall component)
• capsofungin, micofungan and anidulofungi
• candidias and aspergillus but no activity against cryptoccus neoforms
• advese rxns: fever, high liver function tests and anemia and occasional maculopapular rash

Terbinafine

• squalene epoxidase inhibitor
• interrupts fungal ergosteral biosynthesis (minimal mammalian toxicitiy)
• minimal p450 interaction
• broad spectrum; oral and topical
• onychornycosis, tinea pedis and dermatophytes
• adverse rxs: LFTs, neutropenia, lymphopenia and local irritation