Systemic Mycoses

Regarding fungal pathogenesis, which one of the following is most accurate?A) Ingestion of Amanita mushrooms typically causes kidney failure.B) The host response to infection by the systemic fungi, such as Histoplasma and Coccidioides, consists of granulomas formation.C) The fever seen in systemic fungal infections is caused by endotoxin-induced release of interlukin-1.D) Ingestion of aflatoxin produced by Aspergillus flavus can cause adenocarcinoma of the colon.E) A positive result in the skin test to fungal antigens, such as coccidioidin, is caused by an immediate hypersensitivity reaction.

B

Where does Histo Hide?

within macrophages

Blasto buds (broadly)

Blastomycosis

Paracoccidio parasails with the captain's wheel all the way to Latin America

Paracoccidiomycosis

Sporothrix schenkii yeast form

0

Sporothrix schenkii mould form

Sporothrix schenckiiColony

Sporotrichosis - lymphocutaneous

What am I?Only dimorphic fungi NOT acquire via pulmonary route•Lesions progress along the lymphatic tract•Found in soil, lives on plant debris•Gardeners, greenhouse workers, brick-layers are often exposed through traumatic implantation•non-healing lesions develops at site of inoculation 1-2 weeks after exposure----Must isolate this fungus from the lesions for Dx----A dematiaceous mould

Sporothrix schenkii

...

Trigger WordsSporothrix schenckii

RosesThorn prickSphagnum mossSplinterGardenerLymphocutaneous nodules

Paracoccidioidomycosis Oral lesion

Paracoccidioidomycosis

Progession of Disease:Dissemination results in ulcerative granulomatous lesions of buccal, nasal, and GI mucosa concomitant strong lymph node involvement.Acquisition:Pulmonary Inhalation of infectious conidiaEndemic Areas:Humid, high rainfall areas w/ acidic soil conditions such as Central and South America

Paracoccidoides brasiliensisMariner's Wheel

Paracoccidoides brasiliensisColony morphology

Trigger WordsParacoccidoides brasiliensis

Captain's Wheel morphologyUlcerative lesions of oral and nasal mucosaCentral and South AmericaMultiple-budded yeastsSouth American Blastomycoses

What am I?•Found in dry, hot, alkaline soil of semiarid regions of Southwest USA, Mexico, Central & South America•AKA San Joacquin Valley Fever•Isolation of mould form. Rarely is yeast form isolated.•Inhalation of arthroconidia----Barrel-shaped non-sequential arthroconidia----No conversion necessary

Coccidioides immitis

Barrel shaped arthroconidia

Coccidiodes immitis

Symptoms of Valley fever include:

Fatigue (tiredness)CoughFeverShortness of breathHeadacheNight sweatsMuscle aches or joint painRash on upper body or legs

How soon do the symptoms of Valley fever appear?

Symptoms of Valley fever may appear between 1 and 3 weeks after a person breathes in the fungal spores.

Who gets Valley fever?

Anyone who lives in or travels to the southwestern United States (Arizona, California, Nevada, New Mexico, Texas, or Utah), or parts of Mexico or Central or South America can get Valley fever. Valley fever can affect people of any age, but it's most common in adults aged 60 and older. Certain groups of people may be at higher risk for developing the severe forms of Valley fever, such as:People who have weakened immune systems, for example, people who: Have HIV/AIDS Have had an organ transplant Are taking medications such as corticosteroids or TNF-inhibitorsPregnant womenPeople who have diabetesPeople who are Black 5, 6 or Filipino7

Disseminated Coccidoidomycosis

•Granulomatous lesions of face•Healed and active lesions seen

Tissue FormCoccidioides spherules - KOH

Coccidioides immitis colony

Coccidioides immitis colony reverse side

Self-limiting respiratory illness aka

Coccidioidomycosis

How do the yeast form of Coccidioides immits reproduce?

AsexualFragmentation of fertile hyphae

P. marneffei colony

Hyphae. A. Nonseptate hyphae with multiple nuclei. B. Septate hyphae divide nuclei into separate cells. C. Electron micrograph of septum with a single pore. D. Multipore septum structure. (Reproduced with permission from Willey JM: Prescott, Harley, & Klein's Microbiology, 7th edition. McGraw-Hill, 2008.)

Asexual mold forms. A. Arthroconidia develop within the hyphae and eventually break off. B. Chlamydoconidia are larger than the hyphae and develop with the cell or terminally. C. Sporangioconidia are borne terminally in a sporangium sac. D. Simple conidia arise directly from a conidiophore. (Reproduced with permission from Willey JM: Prescott, Harley, & Klein's Microbiology, 7th edition. McGraw-Hill, 2008.)

The fungal cell wall. The overlapping mannan, glucan, chitin, and protein elements are shown. Proteins complexed with the mannan (mannoproteins) extend beyond the cell wall.

P. marneffeiyeast form in tissue

P. marneffei microscopic mould form

Penicillium marneffei lesions in HIV positive patients

What am I?Endemic in SE AsiaOpportunistic pathogen in HIV ptsYeast cells divide by fission-----observe a transverse septumConversion to Yeast takes up to 14 daysCauses deep-seated infection local or disseminated in immunocompromised ptsSpecifically infects pts w/ AIDS who live in or visit endemic areas of SE ASIA

Penicillium marneffei

A bone marrow specimen was obtained from an immunocompromised patient who tested positive for HIV. The organism grew rapidly at 3 days showing a mold form at 25C, displaying conidiophores with four to five terminal metulae with each having four to six phialides. The conidia at the end of the phialides were oval and in short chains. They appear as a fan or broom when vewing under 10X and 40X. At 37C, the yeast form grew more slowly, showing conidia that formed hyphal elements breaking at the septa to produce oval arthroconidia. This thermo-dimorphic mold is most likely:A) Paecilomyces spp.B) Penicillium marneffeiC) Rhizomucor spp.D) Aspergillus fumigatus

B) Penicillium marneffeiOther Penicillium spp. are differentiated from P. marneffei (thermally dimorphic) through conversion from the mold to yeast phase.P. marneffei are seen as yeast at 35C-37C on 5% sheep blood agar or in BHI broth. Other Penicillium spp. do not display a yeast phaseP. marneffei are recovered from blood, skin, lymph nodes, bone marrow, and internal organs of immunocompromised patients.

Spherical conidia on short hyphal strands resemble lollipops

•B. dermatididis

Tissue Form - yeast PhaseBlastomyces dermatitidis

Examine with calcoflour white or KOH

What am I?•Likes moist, acidic soil with a high humus content-Bird droppings, rotting wood, decaying vegetation•Endemic in N. America around the Great Lakes; Southeast US; upper Mississippi tributaries; and S. Canada-Hyperendemic area in north central WisconsinMissouri, esp SE Mississippi County•Bud singly and have a Broad Base of Attachment (BBB)•Inhalation of conidia---Disease can be pulmonary and extrapulmonary

Blastomyces dermatidis

Pulmonary Blastomycosis

-Begins as pulmonary disease-Upper lobes-NO cavitation-Presents as acute pneumonia-Mass like infiltrate on XRAY

Extrapulmonary Blastomycosis

-Bad prognosis-Skin and mucous membrane involvement (systemic)-Non-healing lesions on face, hands, legs----heaped borders-Disseminate to RES system or liver-CNS in immunocompromised

Trigger WordsBlastomyces dermatidis

Broad-Based Budding yeastGranulomahealthy and immunocompromisedMississippi River Valleyrotting wood

Transmission of Blastomycosis

-Inhalation of conidia-NO P2P

Blastomyces dermitididis - broad based yeast cells in tissue

endemic in Great Lakes to eastern coast, broad budding yeast

Yeast Phase in Culture•Wrinkled, cream to tan colony

What am I?•Found in moist, acidic soils with high nitrogen content•Geographically found in the drainage basins of the Ohio, Mississippi, & Missouri rivers.•Disease starts as pulmonary infection.• Usually resolves itself.----Can involve liver and bone marrow•Organisms spread via macrophages----Inhibited by cycloheximide

Histoplasma capsulatum

H. capsulatum yeast form

H. capuslatum mould form microscopic macroconidia

Histoplasma in lung tissue

Case:A chicken farmer living in southern Ohio has a mild respiratory infection with flu-like symptoms that resolve within 10 days. Two months later, numerous diffuse, small calcific densities are seen on a chest radiograph.

What three clinical presentations can be seen in infections with H. capsulatum?

1)Bone2)Acute pulmonary---viable and may remain quiescent for years3)Asymptomatic--intact immune system; areas of calcification in the spleen, lung, liver

How does H. capsulatum (yeast form) reproduce?

Teleomorph sexualConidiogenous cells

Trigger wordsHistoplasma capsulatum

Bird and bat droppings"Cincinnati spleen"granulomaslung and spleenOhio River ValleyMississippi River Valleyyeasts inside macrophages

Your patient is a 30-year-old woman who is in her third trimester of pregnancy, is of Filipino origin, and lives in the Central Valley of California. She complains of severe low back pain of several weeks in duration. An X-ray reveals a lesion in the fourth lumbar vertebra. Material from a needle biopsy of the lesion is examined by a pathologist who calls to tell you the patient has coccidioidomycosis. Of the following, which one did the pathologist see in the biopsy?A) Nonseptate hyphaeB) Septate hyphaeC) Spherules containing endosporesD) Yeasts with a single budE) Yeasts with multiple buds

C

Each of the following statements concerning Histoplasma capsulatum is correct EXCEPT:A)The natural habitat of H. capsulatum is the soil, where it grows as a mold.B) H. capsulatum is transmitted by airborne conidia, and its initial site of infection is the lung.C) Within the body, H. capsulatum grows primarily intracellularly within macrophages.D) Passive immunity in the form of high titer antibodies should be given to those known to be exposed.

D

A dimorphic fungus that typically is acquired by inhalation of asexual spores:A) Histoplasma capsulatumB) Candida albicansC) Aspergillus fumigatusD) Sporothrix schenckii

A

Each of the following statements concerning fungi is correct EXCEPT:A)Yeasts are fungi that reproduce by budding.B) Molds are fungi that have elongated filaments called hyphae.C) Thermally dimorphic fungi often exist as yeasts at 37°C and as molds at 25°C.D) Both yeasts and molds have a cell wall made of peptidoglycan.

Which one of the following is NOT a characteristic of histoplasmosis?A)Person-to-person transmissionB)Specific geographic distributionC)Yeasts in the tissueD)Mycelial phase in the soil

Which one of the following fungi is MOST likely to be found within reticuloendothelial cells, such as macrophages?A)Histoplasma capsulatumB)Candida albicansC)Cryptococcus neoformansD)Sporothrix schenckii

Each of the following statements concerning Blastomyces dermatitidis is correct EXCEPT:A)B. dermatitidis grows as a mold in the soil in North America.B) B. dermatitidis is a dimorphic fungus that forms yeast cells in tissue.C) B. dermatitidis infection is commonly diagnosed by serologic tests because it does not grow in culture.D) B. dermatitidis causes granulomatous skin lesions.

Regarding coccidioidomycosis and Coccidioides immitis, which one of the following is most accurate?A) C. immitis is a mold in the soil and a yeast in the body.B) The diagnosis of acute coccidioidomycosis can be made by detecting IgM antibodies in the patient's serum.C) Travelers to the Philippines are at high risk of acquiring the disease.D) The nodules of erythema nodosum are a typical finding in disseminated coccidioidomycosis.E) Infection typically occurs when arthrospores enter the skin (e.g., through a wound caused by a rose thorn).

An 18yr old Iowan dirt bike racer, who recently raced for the first time in the desert south west, presents in September with cough, malaise, low-grade fever, myalgias, and chest pain. Rales are heard and respiratory infiltrates are noted on radiograph. Sputum stained with calcofluor white and viewed on an ultraviolet microscope shows large blue-white fluorescing spherical structures with round cells inside. What is the most likely causative agent?a. Candida albicansb. Coccidoides immitisc. Histoplasma capsulatumd. Influenza Ae. Mycoplasma pneumoniaef. Streptococcus pneumoniae

b. Coccidiodes immitis (from the description of the spherules and endospores in the sputum along with huge potential for exposure in a person new to the endemic area)

Upon direct examination of a sputum specimen, several spherule were noted that contained endospores. Growth on Sabouraud dextrose agar showed aerial mycelial elements. The septate hyphae produced barrel-shaped arthroconidia. What is the most likely ID?A) Penicillium marneffeiB) Scopulariopsis spp.C) Cryptococcus neoformansD) Coccidioides immitis

D) Coccidioides immitisCoccidioides immitis endospores are often confused with yeast cells but they do not bud. C. immitis is endemic in the southwestern U.S.Since the arthroconidia are highly infectious, an open plate should not be used, and a slide culture test shouldNOT be performed.Rather, tube media is used for testing, and all work should be performed in a BSC.

A bone marrow sample obtained from an immunocompromised patient revealed small intracellular cells using a Wright's stain preparation. Growth on Sabouraud-dextrose agar plates at 37C designates the organism as dimorphic. The mold phase produced thick, spherical tuberculated macroconidia.What is the most likely ID?A) Histoplasma capsulatumB) Sepedonium spp.C) Sporothrix schenkiiD) Coccidioides immitis

A) Histoplasma capsulatumThermally dimorphic H. capsulatum produce microconidia and hyphal fragments at 37C (yeast phase), whereas at 25C (mold phase) the organism displays large, thick-walled, round macroconidia with knobby or knoblike projections.The yeast form is able to survive within circulating monocytes or tissue macrophages that can be demonstrated with Giemsa's or Wright's stain.

A logger undergoing chemotherapy for cancer has developed pneumonia and skin lesions. Biopsy of the skin lesions demonstrates the presence of large yeasts with thick cell walls and broad-based buds. What is the most likely causative agent?(A) Aspergillus fumigatus(B) Blastomyces dermatitidis(C) Coccidioides immitis(D) Histoplasma capsulatum(E) Sporothrix schenckii

(B) Blastomyces dermatitidis Blastomyces has a double refractile wall and buds with a broad base of attachment to the mother cell.

Dimorphic molds are found in infected tissue in which form?A) Mold phaseB) Yeast phaseC) EncapsulatedD) Latent

B) Yeast phaseDimorphic molds are in teh yeast form in infected tissues because they are in the yeast form at 37C.Specimens are cultured and incubated at both room temperature and 35C-37C. To prove that a mold growing at room temperature (or 30C) is a dimorphic fungus, conversion to the yeast form must be demonstrated via subculture and incubation at 37C

The mycelial form of which dimorphic mold produces thick-walled, rectangular, or barrel-shaped alternate arthroconidia?a. Coccidioides immitisb. Sporothrix schenckiic. Histoplasma capsulatumd. Blastomyces dermatitidis

a. Coccidioides immitisThe mold form of C. immitis shows barrel-shaped arthroconidia separated by empty cells (ghost cells) that cause an uneven staining effect when they are examined under a microscope. S. schenkii, H. capsulatum, and B. dermatidis produce conidia that are round or oval in shape in the mold phase.

The yeast form of which dimorphic fungus appears as oval or elongated cigar shape?A) Coccidioides immitisB) Sporothrix schenckiiC) Histoplasma capsulatumD) Blastomyces dermatitidis

B) Sporothrix schenckiiS. schenkii is usually acquired by humans through thorns or splinters because it is commonly found on living or dead vegetation.It is called "rose gardener's disease" because gardeners, florists, and farmers are most often infected. S. schenkii is often recovered from exudates of unopened subcutaneous nodules or open draining lesions

The yeast form of which dimorphic mold shows a large parent yeast cell surrounded by smaller budding yeast cells?A) Paracoccidioides brasiliensisB) Sporothrix schenkiiC) Coccidioides immitisD) Histoplasma capsulatum

A) Paracoccidioides brasiliensisP. brasiliensis yeast forms are sometimes seen as "mariner's wheel" because multiple budding cells completely surround the periphery of the parent cell.

A normally healthy 8-year-old boy from Florida is visiting friends on a farm in Iowa during the month of July. He presents July 28 with a fever, cough, and lower respiratory symptoms(no URI symptoms). He has been ill for 4 days. His chest sounds are consistent with pneumonia, so a chest radiograph is obtained. The radiograph shows small, patchy infiltrates with hilar adenopathy. His blood smear shows small, nondescript yeast forms inside monocytic cells. What is the most likely causative agent?a. Aspergillus fumigatusb. Blastomyces dermatidisc. Coccidoides immitisd. Histoplasma capsulatume. Pneumocystis carinii

D) Histoplasma capsulatumHistoplasma is endemic in iowa and fits the description of a facultative intracellular parasite circulating in the reticuloendothelial system.

A 15yr old dirt biker visiting sunny southern California has pneumonia caused by an organism whose environmental form consists of hyphae that break up into arthroconidia, which become airborne. What is the agent?a. Aspergillus fumigatusb. Blastomyces dermatidisc. Coccidoides immitisd. Histoplasma capsulatume. Sporothrix schenkii

What is a mass of fungal filaments called?(A) Pseudohyphae(B) Hyphae(C) Mycelium(D) Septum(E) Yeast

A florist presents with a subcutaneous lesion on the hand, which she thinks resulted from a jab wound she received while she was making a sphagnum moss-wire frame for a floral wreath. The nodule has ulcerated and not healed despite use of antibacterial cream, and a new nodule is forming above the original lesion. What is most likely to be an appropriate treatment for this infection?(A) Oral itraconazole or potassium iodide(B) Miconazole cream(C) Cortisone cream(D) Oral griseofulvin(E) Penicillin

A) Oral itraconazole or potassium iodideThis is a classic case of lymphocutaneous sporotrichosis in which the florist is infected via puncture wound. The drug of choice is either itraconazole or KI. Topical antifungals are not effective, and the cortisone cream would probable enhance the spread of the disease.

Coccidioides

Form in Tissue Seen by Microscopy Spherule Geographic Location Southwestern United States and Latin America Important Clinical Findings Valley fever in immunocompetent; dissemination to bone and meninges in immunocompromised, pregnant women, African Americans, and FilipinosLaboratory Diagnosis Culture at 20°C grows mold with arthrospores; serologic test for IgM and IgG

Histoplasma

Form in Tissue Seen by Microscopy Yeasts within macrophagesGeographic Location Ohio and Mississippi River valleys; worldwide; associated with bird and bat guanoImportant Clinical Findings Cavitary lung lesions; granulomas in liver and spleen; pancytopenia and tongue ulcer in immunocompromisedLaboratory DiagnosisCulture at 20°C grows mold with tuberculate macroconidia; serologic test for IgM and IgG; urinary antigen

Blastomyces

Form in Tissue Seen by MicroscopyYeasts with single broad-based bud Geographic Location Central and southeastern United States; AfricaImportant Clinical Findings Ulcerated lesions of the skinLaboratory DiagnosisCulture at 20°C grows mold

Paracoccidioides

Form in Tissue Seen by MicroscopyYeasts with multiple buds Geographic Location Latin America, especially BrazilImportant Clinical Findings Ulcerated lesions of the face and mouthLaboratory DiagnosisCulture at 20°C grows mold; serologic test for IgM and IgG

ClassificationDimorphicInfectionSystemicTemperature for optimum growthYeast: 37CMold: 25-30CGrowth RateSlowObverse ColonyPurple/creamywhite dark to tan w/ agewooly cottony or granularwhite ball in centerround smoothReverseDark red pigment in centerHyphaeSeptateFruiting Bodiessmall Microconidia: 3-5umTUBERCULATED MACROCONIDIA: 8-16umSpecial features-inhibited by cyclohexamide-small; oval to round budding cells often found clustered within histiocytes-smooth or spiny microconidia on short branches or on side of hyphae directlyMould phase25C--->wooly white to brown colonies; hyaline septate hyphae37C--->creamy white coloniesTissue/yeast phase-NO capsule-oval yeasts (2-4um) intracellular in Macrophages-narrow neck on bud-small, round to oval budding cells occasional abortive hyphae-RES CELLS (Reticuloendothelial)

Coccidoides immitis

ClassificationDimorphicInfectionSystemic(skin, joints, bones, lymph, CNS)Temperature for optimum growthMould: 25C or 37CYeast: 37-40CConverted to spherule phase in modified converse media at 40C in 5-10% CO2Growth RateModerateObverse ColonyWhite to tan to dark grayyoung colonies tenaciousold colonies cottony tend to grow in concentric ringsblue/white powdergray with agemoist/gray membrane white adn cottony aerial myceliaReverselayereddark burnt orange/brownHyphaeSeptateFruiting BodiesArthroconidiaSpecial featuresAlternating ArthroconidiaBarrel shaped arthroconidiaspherules--->vary in size; may contain endospores; others may be empty; adjacent spherules may resemble B.dermatidis; endospores may resemble H.capsulatum but show no evidence of budding-NO dark pigment, NO pseudohyphae, NO blastoconidia, NO conidiophoresMould phase25C: Hyaline septate hyphae and arthroconidia (3X6um)---alternating (separated by a disjunctor cell) hyaline conidia"Tangled christmas lights"Tissue/Yeast phaseLarge, thick walled spherules (10-100um) containing endospores-no budding

Blastomyces dermatitidis

ClassificationDimorphicInfectionSystemicTemperature for optimum growthMould: 25-30CYeast: 35-37CGrowth RateSLOWObverse Colonywhite to dark tanyoung colonies tenaciousold colonies glabrous and woolyhairlike myceliaturns tan w/ age14 days to matureReverseWrinkledTan or white creamHyphaeSeptateFruiting BodiesConidia(ChlamydospoSpre if old)Special featuresBROAD BASED BUDDING8-15um diameter-cells usually large double refractile when present-round or pear shaped chlamydospore, thick wall on older culture-conidia lollipop-Blastoconidia attached by BROAD BASE-single small conidia-buds usually single; however several may remain attached to parent cells-wet mount okay to useMould phase25C-Hyaline septate hyphae and short conidiophores bearing single base to piriform conidia (2-10um)-thin delicate stringy hyphae-Round or pear shape conidia = LOLLIPOPTissue/Yeast phase37C-Shows thick wllaed oval to round, single budding yeastlike cells (3-30um)-usually single buds(8-15um)-Calcoflour white and KOH-Blastoconidia attached by Broad BASE (average 4-5um)-Double contoured and bud remains attached until it expands to same size as the parent cell

Sporothrix schenckii

ClassificationDimorphicInfectionSubcutaneousTemperature for optimum growthMould:25-30CYeast:35-37CGrowth RateModerate/fast ~7 daysObverse Colony25C; moist white mold w/ thin branching-white/pale orange-black initially-older--->leather or velvety +often dark w/ narrow white border-NO cottony aerial hyphaeReversecolonies w/ dark surface will usually have reverse that is dark in center and light in peripheryHyphaeSeptateFruiting BodiesConidiaSpecial features-small; oval to round CIGAR-SHAPED-slender, tapered condiophore rising at right angles---apex of conidiophore often smaller-Mould phase: conidia developing a rosette pattern at the ends of delicate conidiophores in addition to dark walled conidia produced along sides of hyphaeMould Phase25Cmoist white w/ thin branching hyphae"Hyphae w/ sleeves"-rosette/grapelike vines-Conidia are on denticlesYeast/Tissue phase37Cdeeply staining bodiesCIGAR SHAPED YEAST-amorphic yeast buds may be observed

Paracoccidioides brasiliensis

ClassificationDimorphicInfectionSystemicTemperature(for optimal growth)Mould: 25-30CYeast: 35-37CGrowth RateSLOW (mycelial 21 days)long latent periodObverse (appearance)-Heaped, wrinkled, moist and yeast like-glabrous, leathery, folded or velvety-surface heaped with crater formations-white to beigeReverse (appearance)-light or brownishHyphaeSeptateFruiting BodiesMicroconidiaChlamydospores (INTERCALATING and terminal)Special features-usually only forms septate branched hyphae-cells usually large and surrounded by smaller buds around periphery ("MARINER'S WHEEL") (5-60um diameter)-smaller cells may be present (2-5um) and may resemble H.capsulatum-buds have pinched off appearance-few microconidia sometimes seen along hyphae-branching hyphae w/ intercalary and terminal chlamydospores-Wet prep of yeast at 37C easy to see****MUST CONVERT Mould to yeast to ID*******Mould phase25-30CHyaline septate hyphae and rare globose conidia and chlamydospores---intercalary chlamydospores and/or terminal****few microconidia observed along hyphae****Yeast/Tissue phase37CYeast cell w/ multiple buds-multiple budding yeast (15-30um or larger)-multiple blastoconidia budding from single large yeast--MARINER's WHEEL"(5-60um diameter)--------Mother cell in center with daughter cell as buds

Heat changes body shape:"Yeast in the HEAT and....

Mould in the COLD!

Stages of Coccidioides immitis. A: Arthrospores form at the ends of hyphae in the soil. They germinate in the soil to form new hyphae. If inhaled, the arthrospores differentiate into spherules. B: Endospores form within spherules in tissue. When spherules rupture, endospores disseminate and form new spherules. (Reproduced with permission from Brooks GF, Butel JS, Ornston LN. Jawetz, Melnick & Adelberg's Medical Microbiology, 20th ed. New York, NY: McGraw-Hill Education; 1995.)

Coccidioides immitis—arthrospores. Barrel-shaped, rectangular arthrospores appear blue with lactophenol-cotton blue stain. Arthrospores are also called arthroconidia. (Used with permission from Dr. Hardin, Public Health Image Library, Centers for Disease Control and Prevention.)

Coccidioides immitis—spherule. Long arrow points to a spherule in lung tissue. Spherules are large thick-walled structures containing many endospores. Short arrow points to an endospore. (Used with permission from Dr. L. Georg, Public Health Image Library, Centers for Disease Control and Prevention.)

Asexual spores of Histoplasma capsulatum. A: Tuberculate macroconidia. B: Microconidia.(Reproduced with permission from Brooks GF, Jawetz E. Medical Microbiology, 19th ed. New York, NY: McGraw-Hill Education; 1991.)

Histoplasma capsulatum. Yeasts are located within the macrophage. (Reproduced with permission from Brooks GF, Jawetz E. Medical Microbiology, 19th ed. New York, NY: McGraw-Hill Education; 1991.)

Histoplasma capsulatum—yeasts within a macrophage. Long blue arrow points to one of many yeasts within the cytoplasm of a macrophage. Short blue arrow points to nucleus of the macrophage. Giemsa stain. (Used with permission from Dr. J.T. McClellan, Public Health Image Library, Centers for Disease Control and Prevention.)

Blastomyces dermatitidis. A: Yeast with a broad-based bud at 37°C. B: Mold with microconidia at 20°C. (Reproduced with permission from Brooks GF, Jawetz E. Medical Microbiology, 19th ed. New York, NY: McGraw-Hill Education; 1991.)

Blastomyces dermatitidis—broad-based budding yeast. Arrow points to the broad base of the budding yeast. (Used with permission from Dr. L. Ajello, Public Health Image Library, Centers for Disease Control and Prevention.)

Paracoccidioides brasiliensis. Note the multiple buds of the yeast form of Paracoccidioides, in contrast to the single bud of Blastomyces.

Paracoccidioides—yeasts with multiple buds resembling a "ship captain's wheel." Methenamine silver stain. (Used with permission from Dr. Lucille Georg, Public Health Image Library, Centers for Disease Control and Prevention.)

Sporotrichosis. Cutaneous tissue revealing the small spherical and elongated budding yeast cells (3-5 µm) of S. schenckii, which are stained black by the Gomori methenamine silver (GMS) stain. 400×.

Global distribution of endemic mycoses. Each is caused by a dimorphic environmental mold and undergoes morphogenesis within the host. (Reproduced with permission from Lee PP, Lau Y-L: Cellular and molecular defects underlying invasive fungal infections—revelations from endemic mycoses. Front Immunol 2017;8:375.)

Coccidioides species and Coccidioidomycosis. A: In culture at ambient temperatures, C. posadasii produces hyaline, septate hyphae, and arthroconidia. 400×. B: Large spherules containing endospores can be seen in this section of lung tissue. H&E 200×.

Blastomycosis and B. dermatitidis. A: Note the large, spherical thick-walled yeast cells (8-15 µm in diameter) in this section of a cutaneous abscess. H&E 400×. B: In culture at ambient temperatures, B. dermatitidis produces hyaline, septate hyphae, and single conidia. 400×.

Paracoccidioidomycosis. Large, multiply budding yeast cells (15-30 µm) are observed in cutaneous lesion. KOH 400×.

Histoplasma capsulatum. A. Mold phase with hyphae, microconidia, and tuberculate macroconidia. B. A yeast cell is multiplying (note budding) within a macrophage phagocytic vacuole. (Reproduced with permission from Willey JM: Prescott, Harley, & Klein's Microbiology, 7th edition. McGraw-Hill, 2008.)

Geographic distribution of systemic fungal infections in the United States.

A thermally dimorphic fungus shows a filamentous mold form with tuberculate macroconidia at room temperature, and a yeast form above 35 degrees. Which organism best fits this description?A) Histoplasma capsulatumB) Paracoccidioides brasiliensisC) Candida albicansD) Coccidioides immitis

A) Histoplasma capsulatumThe yeast phase of H. capsulatum develops as small budding cells seen in macrophages.The yeast phase of P. brasiliensis develops large cells that bud creating a structure resembling a mariner's wheelCoccidioides immitis prodcues very large spherules.At 25C P.brasiliensis produces single small conidia, and C. immitis produces arthroconidia. Candida spp. are not dimorphicH. capsulatum is found in soil containing excrement of birds and bats. It is endemic in the Ohio and Mississippi river valleys, and the most common systemic mycosis in North America.

Blastomyces dermatitidis. Large thick-walled yeast cells are shown in this sputum. Note how the blastoconidia retain a broad attachment to the mother cell before separating. (Reproduced with permission from Connor DH, Chandler FW, Schwartz DQ, et al: Pathology of Infectious Diseases. Stamford, CT: Appleton & Lange, 1997.)

Coccidioides immitis. A. Lung tissue with a large thick-walled spherule containing multiple endospores. The smaller spherule to its left has ruptured releasing endospores. (Reproduced with permission from Connor DH, Chandler FW, Schwartz DQ, et al: Pathology of Infectious Diseases. Stamford, CT: Appleton & Lange, 1997.) B. Mold phase in which alternate cells have differentiated to form barrel-shaped arthroconidia. (Reproduced with permission from Nester EW: Microbiology: A Human Perspective, 6th edition. 2009.)

Life cycle of Coccidioides immitis. The nature cycle takes place in desert climates with modest rainfall. Hyphae differentiate into arthroconidia, which break loose and may be suspended in the air. Soil disruptions and wind facilitate spread and the probability of inhalation into human lungs. In the human host environment, in vivo differentiation produces cleavage planes and eventually huge spherules. The spherules rupture releasing endospores, which can then repeat the in vivo cycle.

Serologic tests in coccidioidomycosis.

Histoplasma capsulatum. This peripheral blood smear shows two monocytes with multiple organisms stuffed within their cytoplasm. Note the size of the yeast cells, which is very small for fungi. (Reproduced with permission from Connor DH, Chandler FW, Schwartz DQ, et al: Pathology of Infectious Diseases. Stamford, CT: Appleton & Lange, 1997.)

Features of Systemic Fungal Pathogens

Fungi system view. Localized disease (left) is caused by local trauma or the superficial invasion of flora resident on the oropharyngeal (thrush), gastrointestinal, or vaginal mucosa. Systemic fungal disease (right) most often begins with inhalation of conidia followed by dissemination to other sites.

You are asked to evaluate the antifungal therapy of a patient with an enlarged liver and spleen. The laboratory finding shows that culture of a lymph node biopsy yielded a small (4 mm) yeast at 35°C, which at 25°C grew as a mold with tuberculate macroconidia. The patient most probably acquired this infection in:A)Semitropical regions of North and South AmericaB)Ohio and Mississippi River valleysC)Arid deserts of America and AfricaD)Lower Sonoran life zoneE)Worldwide

A young Phoenix woman has developed fever, cough, and after 1 month of illness has an infiltrate in the upper lobe of her right lung. A sputum specimen digested with KOH was negative but the culture grew a mold with alternating arthroconidia.This infection was most likely acquired by inhalation of:A)SpherulesB)YeastsC)Sexual, macroconidaD)Asexual, arthroconidiaE)Asexual chlamydoconidia

Trigger wordsCoccidoides immitis

Self-limiting respiratory illnessSan Joaquin River ValleyAmerican Southwest desertsInhale arthrospores in dustSpherules with endosporesSkin test for antigen exposure

Which of the following procedures is recommended to confirm that an unkown mould is one of the pathogenic dimorphic fungi?A) animal inoculationB) conversion from yeast to mould formC) demonstration of sexual and asexual reproductionD) molecular testing

D) molecular testingSeveral monomorphic molds resemble the filamentous phase of dimorphic molds, so it is important to differentiate.Animal inoculation is not realistic in a routine clinical microbiology laboratory, and conversion from mold to yeast form may take several days. Note: conversion is NOT from yeast to mold form as stated in item B.Confirmatory identification is typically done by DNA probe.[Mahon 2015, p603]

Laboratory workers should always work under a biological safety hood when working with cultures of:A) Streptococcus pyogenesB) Staphylococcus aureusC) Candida albicansD) Coccidioides immitis

D) Coccidioides immitisThe arthroconidia of Coccidoides immitis are highly infectious; cultures must be handled with care to minimize aerosols.[Murray 2013, p668]

Structures important in the microscopic identification of Coccidioides immitis are:A) irregular staining, barrel-shaped arthrospores B) tuberculate, thick-walled macroconidia C) thick-walled sporangia containing sporangiospores D) small pyriform microconidia

A) irregular staining, barrel-shaped arthrosporesThe mycelial phase of Coccidoides immitis produces alternating, barrel-shaped arthrospores.[Larrone 2011, p272]

Which of the following is the most useful morphological feature in identifying the mycelial phase of Histoplasma capsulatum?A) arthrospores every other cellB) 2-5um microsporesC) 8-14um tuberculate macroconidiaD) 5-7um nonseptate macroconidia

C) 8-14um tuberculate macroconidiaThe presence of tuberculate macroconidia indicates a presumptive identification of Histplasma capsulatum. The identification must be confirmed using nucleic acid probes or exoantigen testing[Larrone 2011, p158]

A mold grown at 25°C exhibited delicate septate hyaline hyphae and many conidiophores extending at right angles from the hyphae. Oval, 2-5 pm conidia were formed at the end of the conidiophores giving a flowerlike appearance. In some areas "sleeves" of spores could be found along the hyphae as well. A 37 C culture of this organism produced small, cigar-shaped yeast cells. This organism is most likely:A) Histoplasma capsulatum B) Sporothrix schenckii C) Blastomyces dermatitidis D) Acremonium falciforme

B) Sporothrix schenckii The characteristics listed define Sporothrix and differentiate it from other dimorphic fungi.[Larrone 2011, p166]

Which of the following is a dimorphic fungus?A) Blastomyces dermatidisB) Candida albicansC) Cryptococcus neoformansD) Aspergillus fumigatus

A) Blastomyces dermatidisDimorphic molds include Blastomyces, Histoplasma, Coccidioides, Paracoccidioides, Penicillium marneffei, Sporothrix.[Larrone 2011, p157]

A mold is isolated from a bone marrow culture of a patient who travelled to southeast Asia. The isolate produced a red pigment that diffused into the medium. The technologist should suspect:A) Blastomyces dermatidisB) Aspergillus nigerC) Penicillium marneffeiD) Rhizopus species

C) Penicillium marneffeiPenicillium marneffei is a dimorphic fungi that produces a diffusible red pigment and is endemic in Southeast Asia.[Larrone 2011, p164]

Which of the following scenarios presents the greatest risk for Coccidioidomycosis?A) Missouri cattle rancherB) Wyoming rabbit rancherC) Central Valley California migrant workerD) pregnant woman with several housecats

C) Central Valley California migrant workerValley fever, or San Joaquin fever, are all caused by Coccidioides immitis, which is seen in high, dusty high desert, such as those found in southeast California, Arizona, and New Mexico. Sandstorms are responsible for spreading the spores.[Mahon 2015, p604]

Examination of a fungal culture from a bronchial washing reveals white, cottony aerial mycelium. A tease preparation in lactophenol cotton blue shows the structures shown in the image:(IMAGE)The most rapid test for definitive identification is:A) Maldi-Tof mass spectrometryB) animal inoculation C) exoantigen test D) slide culture

A) Maldi-Tof mass spectrometryMALDI-TOF mass spectrometry testing for identification of bacteria and fungi can be completed in minutes.[Mahon 2015, p251]

Many fungal infections are transmitted to man via inhalation of infectious structures. Which of the following is usually contracted in this manner?A) Sporothrix schenckii B) Trichophyton rubrum C) Malassezia furfur D) Histoplasma capsulatum

D) Histoplasma capsulatumHistoplasma capsulatum is the only choice that is transmitted by inhalation. [Murray 2013, p670]

In a patient with lung and skin lesions, a travel history to which of the following regions would be most compatible with the potential diagnosis of blastomycosis?A) Brazil (Amazon river basin)B) MalaysiaC) Northern WisconsinD) Southern ArizonaE) Western Washington state

C) Northern WisconsinBlastomycosis is caused by the dimorphic fungus, Blastomyces dermatitidis, which commonly resides in soil and is acquired through inhalation. Pulmonary infection is most common and can be acute or indolent. Extrapulmonary extension via hematogenous spread from the lungs is common, with skin lesions and osteomyeltis most common.In patient with AIDS, CNS involvement, usually as a brain blastomycosis are reported from North America with the most common regions bordering the Mississippi and Ohio river basins, the upper Midwest and Canada bordering the Great Lakes, and a small area of New York and Ontario bordering the St. Lawrence River. Outside of North America, most blastomycosis cases are in Africa. Coccidiomycosis is endemic in Southern Arizona

A 24-year-old female student at the Ohio State University is seen in the emergency department for shortness of breath and chest pain. She has no significant past medical history and grew up Cincinnati. Her only medication is an oral contraceptive. As a component of her evaluation, she receives a contrast-enhanced CT scan of the chest. Fortunately, there is no pulmonary embolism (she is diagnosed with viral pleuritis), but there are numerous lung, mediastinal, and splenic calcifications. Based on these findings, which of the following remote infections was most likely?A) BlastomycosisB) CoccidioidomycosisC) CryptococcosisD) HistoplasmosisE) Tuberculosis

D) HistoplasmosisAll of these pathogens are typically inhaled and cause pulmonary infection, which may resolve spontaneously or progress to active disease. Resolved infection with blastomycosis, coccidioidomycosis, Cryptococcus, and tuberculosis will often leave a radiographic lesion that typically looks like a solitary nodule and may be confused with potential malignancy. Latent tuberculosis is often suggested by the radiographic finding of a calcified lymph node that is typically solitary. Of the listed infections, histoplasmosis is most likely to resolve spontaneously in an immunocompetent individual leaving multiple mediastinal and splenic calcifications. These represent calcified granulomas formed after an appropriate cellular immunity response involving IL-12, TNF-α in combination with functional lymphocytes, macrophages, and epithelial cells. In endemic areas, such as the Ohio and Mississippi River Valleys in the United States, 50%-80% of adults have evidence of previous infection without clinical manifestations. In patients with impaired cellular immunity, the infection may disseminate to the bone marrow, spleen, liver, adrenal glands, and mucocutaneous membranes.Unlike tuberculosis, remote Histoplasma infection rarely reactivates.[Harrison's Chap. 236 ]