PCC SOM 2026 Microbiology F.03 Systemic Mycoses PDF

PCC SOM 2026 MICROBIOLOGY F.03 SYSTEMIC MYCOSES reactivation, constituting a latent form of the disease. MICROBIOLOGY LECTURE LECTURER: DR. ARLENE QUITASOL DATE: MAY 13, 2024 TOPIC OUTLINE I. SYSTEMIC MYCOSES II. COCCIDIOIDOMYCOSIS III. HISTOPLASMOSIS IV. BLASTOMYCOSIS V. PARACOCCIDIOIDOMYCOSIS VI....

PCC SOM 2026 MICROBIOLOGY F.03 SYSTEMIC MYCOSES reactivation, constituting a latent form of the disease. MICROBIOLOGY LECTURE LECTURER: DR. ARLENE QUITASOL DATE: MAY 13, 2024 TOPIC OUTLINE I. SYSTEMIC MYCOSES II. COCCIDIOIDOMYCOSIS III. HISTOPLASMOSIS IV. BLASTOMYCOSIS V. PARACOCCIDIOIDOMYCOSIS VI. CHECKPOINT SYSTEMIC (ENDEMIC) MYCOSES Include the following: o COCCIDIOIDOMYCOSIS o HISTOPLASMOSIS o BLASTOMYCOSIS o PARACOCCIDIOIDOMYCOSIS Caused by a thermally dimorphic fungus (Grows as a mold at 25 oC, and as a yeast at 37 oC) Infections are initiated in the lungs following inhalation of conidia Most infections are asymptomatic or mild and resolve without treatment Small but significant number of patients develop pulmonary disease, which may involve dissemination from the lungs to other organs. With rare exceptions, these mycoses are not transmissible among humans or other animals Initial host defenses are provided by the alveolar macrophages, which are usually capable of inactivating the conidia and inducing a robust immune response Leads to granulomatous inflammation and the production of both antibodies and cell-mediated immunity. Induction of Th1 cytokines (eg, interleukin-12, interferon-γ, and tumor necrosis factor α) will amplify the cellular defenses, activating macrophages, and enhancing their fungicidal capacity. In an immunocompetent host, these responses lead to resolution of the inflammatory lesions. Residual granulomata may retain dormant organisms with the potential for subsequent NOTE TAKER: BALDOS | FERRER | PADAYAO *Please refer to the last page for an enlarged image COCCIDIOIDOMYCOSIS Caused by Coccidioides posadasii or Coccidioides immitis Phenotypically indistinguishable, cause similar clinical manifestations, and are not differentiated in the clinical laboratory Endemic in semiarid regions of the Southwestern United States, Central America, and South America Infection is usually self-limited Dissemination is rare but always serious, and it may be fatal MORPHOLOGY AND IDENTIFICATION Most infections are probably due to C. posadasii However, since the two species cannot be readily identified in the laboratory and since the clinical manifestations are the same with either C. immitis or C. posadasii, only the former, more familiar species name will be used C. immitis produces a white to tan cottony colony. Hyphae form chains of arthroconidia (arthrospores), which often develop in alternate cells of a hypha Chains fragment into individual arthroconidia, which are readily airborne and highly resistant to adverse environmental conditions Page 1 | 10 PCC SOM 2026 MICROBIOLOGY F.03 SYSTEMIC MYCOSES COCCIDIOIDOMYCOSIS: DIRECT MICROSCOPY Small arthroconidia (3 × 6 μm) remain viable for years and are highly infectious. Following their inhalation, the arthroconidia become spherical and enlarge, forming spherules that contain endospores. Coccidioides species and Coccidioidomycosis. In culture at ambient temperatures, Coccidioides posadasii produces hyaline, septate hyphae, and arthroconidia. 400×. ENDOSPORULATING SPHERULES Coccidioides species and Coccidioidomycosis. Large spherules containing endospores can be seen in this section of lung tissue. H&E 200×. In histologic sections of tissue, sputum, or other specimens, the spherules are diagnostic of Coccidioides immitis. Spherules have a thick, doubly refractile wall and may attain a size of 80 μm in diameter. Spherule becomes packed with endospores (2-5 μm in size) Wall ruptures to release the endospores, which may develop into new spherules NOTE TAKER: BALDOS | FERRER | PADAYAO PATHOGENESIS AND CLINICAL FINDINGS Inhalation of arthroconidia leads to a primary infection Asymptomatic in 60% of individuals Other 40% of individuals develop a self-limited influenza-like illness with fever, malaise, cough, arthralgia, and headache VALLEY FEVER, SAN JOAQUIN VALLEY FEVER, or DESERT RHEUMATISM After 1–2 weeks, about 15% of these patients develop hypersensitivity reactions, which present as a rash, erythema nodosum, or erythema multiforme. Radiographic examination: o Patients typically show hilar adenopathy along with pulmonary infiltrates, pneumonia, pleural effusions, or nodules. Pulmonary residua occur in about 5%, usually in the form of a solitary nodule or thin-walled cavity Less than 1% of persons infected with C. immitis develop secondary or disseminated coccidioidomycosis, which is often debilitating and life-threatening. Page 2 | 10 PCC SOM 2026 MICROBIOLOGY F.03 SYSTEMIC MYCOSES Risk factors for systemic coccidioidomycosis include: o Heredity o Sex o Age o Compromised cell-mediated immunity Males are more susceptible than females, with the exception of women who are pregnant Young and the aged are also at greater risk Because cell-mediated immune responses are required for adequate resistance, patients with AIDS and other conditions of cellular immunosuppression are at risk for disseminated coccidioidomycosis. Some individuals develop a chronic but progressive pulmonary disease with multiplying or enlarging nodules or cavities. Dissemination will usually occur within a year after the primary infection. Spherules and endospores are spread hematogenously or by direct extension. Extrapulmonary sites may be involved, but the most frequent organs are the skin, the bones and joints, and the meninges. Coccidioidomycosis in AIDS patients often presents with a rapidly fatal diffuse reticulonodular pneumonitis. Blood cultures are often positive for C. immitis DIAGNOSTIC LABORATORY TESTS SPECIMENS AND MICROSCOPIC EXAMINATION Specimens for culture include: o Sputum o Exudate from cutaneous lesions o Spinal fluid o Blood o Urine o Tissue biopsies Materials should be examined fresh (after centrifuging, if necessary) for typical spherules. KOH or calcofluor white stain will demonstrate spherules and endospores Structures are often found in histologic preparations stained with H&E, GMS, or PAS NOTE TAKER: BALDOS | FERRER | PADAYAO CULTURES Cultures on IMA (Inhibitory Mold Agar) or Brainheart infusion blood agar slants can be incubated at room temperature or at 37°C. Media prepared with antibiotics and cycloheximide to inhibit contaminating bacteria or saprophytic molds Because the arthroconidia are highly infectious, suspicious cultures are examined only in a biosafety cabinet Identification must be confirmed by detection of a C. immitis-specific antigen or use of a specific DNA probe TREATMENT In most persons, symptomatic primary infection is self-limited and requires only supportive treatment, although itraconazole may reduce the symptoms Patients with severe disease require treatment with amphotericin B administered intravenously. Regimen may be followed by several months of oral therapy with itraconazole Cases of coccidioidal meningitis have been treated with oral fluconazole, which has good penetration of the central nervous system Azoles are not more efficacious than amphotericin B, but they are easier to administer and associated with fewer and less severe side effects. Newer lipid emulsions of amphotericin B promise to deliver higher doses with less toxicity. Surgical resection of pulmonary cavities is sometimes necessary and often curative. EPIDEMIOLOGY AND CONTROL Isolated from the soil and indigenous rodents Infection rate is highest during the dry months of summer and autumn, when dust is most prevalent High incidence of infection and disease may follow dust storms. Increased precipitation in the spring months of these years was suggested as an environmental stimulus. Page 3 | 10 PCC SOM 2026 MICROBIOLOGY F.03 SYSTEMIC MYCOSES HISTOPLASMOSIS Histoplasma capsulatum - dimorphic soil saprophyte Most prevalent pulmonary fungal infection in humans and animals. H. capsulatum grows as a mold in association with soil and avian habitats, being enriched by alkaline nitrogenous substrates in guano. MORPHOLOGY AND IDENTIFICATION At temperatures below 37°C, primary isolates of H. capsulatum often develop brown mold colonies, but the appearance varies. Many isolates grow slowly, and specimens require incubation for 4–12 weeks before colonies develop Hyaline, septate hyphae produce microconidia (2 to 5 μm) and large, spherical thick-walled macroconidia with peripheral projections of cell wall material (8–16 μm) In tissue or in vitro on rich medium at 37°C, the hyphae and conidia convert to small, oval yeast cells (2 × 4 μm). In tissue, the yeasts are typically seen within macrophages, as H. capsulatum is a facultative intracellular parasite HISTOPLASMOSIS: DIRECT MICROSCOPY Histoplasmosis and Histoplasma capsulatum: Small, oval yeast cells (2–4 μm) packed within macrophages. Giemsa’s stain. 1000×. Histoplasmosis and Histoplasma capsulatum: In culture at ambient temperatures, Histoplasma capsulatum produces hyaline, septate hyphae bearing microconidia and large, spherical macroconidia. 400×. Small, narrow base budding yeast cells inside macrophages NOTE TAKER: BALDOS | FERRER | PADAYAO PATHOGENESIS AND CLINICAL FINDINGS After inhalation, the conidia develop into yeast cells and are engulfed by alveolar macrophages, where they are able to replicate Within macrophages, the yeasts may disseminate to reticuloendothelial tissues, such as the liver, spleen, bone marrow, and lymph nodes. Initial inflammatory reaction is granulomatous In over 95% of cases, the resulting cell-mediated immune response leads to the secretion of cytokines that activate macrophages to inhibit the intracellular growth of the yeasts Acute pulmonary histoplasmosis o Develop among immunocompetent persons who inhale a heavy inoculum o A self-limited flu-like syndrome with fever, chills, myalgias, headaches, and nonproductive cough. Page 4 | 10 PCC SOM 2026 MICROBIOLOGY F.03 SYSTEMIC MYCOSES On radiographic examination o Hilar lymphadenopathy o Pulmonary infiltrates or nodules Symptoms resolve spontaneously without therapy, and the granulomatous nodules in the lungs or other sites heal with calcification Chronic pulmonary histoplasmosis o Occurs most often in men and is usually a reactivation process, the breaking down of a dormant lesion that may have been acquired years before o This reactivation is usually precipitated by pulmonary damage such as emphysema Severe disseminated histoplasmosis develops in a small minority of infected individuals-particularly infants, the elderly, and the immunosuppressed, including AIDS patients. Reticuloendothelial system is involved, with lymphadenopathy, enlarged spleen and liver, high fever, anemia, and a high mortality rate without antifungal therapy. Mucocutaneous ulcers of the nose, mouth, tongue, and intestine can occur. In such individuals, histologic study reveals focal areas of necrosis within granulomas in many organs. Yeasts may be present in macrophages in the blood, liver, spleen, and bone marrow. DIAGNOSTIC LABORATORY TESTS SPECIMENS AND MICROSCOPIC EXAMINATION Specimens for culture include: o Sputum o Urine o Scrapings from superficial lesions o Bone marrow aspirates o Buffy coat blood cells. Blood films, bone marrow slides and biopsy specimens may be examined microscopically. In disseminated histoplasmosis, bone marrow cultures are often positive. Small ovoid cells may be observed within macrophages in histologic sections stained with fungal stains, such as GMS or PAS, or in Giemsastained smears of bone marrow or blood. NOTE TAKER: BALDOS | FERRER | PADAYAO DIAGNOSTIC LABORATORY TESTS CULTURE Specimens are cultured in rich media, such as glucose-cysteine-blood agar at 37°C and on SDA (Sabouraud Dextrose Agar) or IMA at 25–30°C. Cultures must be incubated for a minimum of 4 weeks The laboratory should be alerted if histoplasmosis is suspected because special blood culture methods, such as lysis centrifugation or fungal broth medium, can be used to enhance the recovery of H. capsulatum. Because the mold form resembles saprobic fungi, the identification of H. capsulatum must be confirmed by in vitro conversion to the yeast form, detection of a species-specific antigen, or PCR testing for specific DNA sequences. IMMUNITY Following initial infection, most persons appear to develop some degree of immunity. Immunosuppression may lead to reactivation and disseminated disease. AIDS patients may develop disseminated histoplasmosis through reactivation or new infection TREATMENT Acute pulmonary histoplasmosis is managed with supportive therapy and rest. Itraconazole: treatment for mild to moderate infection In disseminated disease, systemic treatment with amphotericin B is often curative, though patients may need prolonged treatment and monitoring for relapses. Patients with AIDS typically relapse despite therapy that would be curative in other patients. AIDS patients require maintenance therapy with itraconazole. EPIDEMIOLOGY AND CONTROL Incidence highest in the US, where the endemic areas include the Central and Eastern states and in particular the Ohio River Valley and portions of the Mississippi River Valley. Page 5 | 10 PCC SOM 2026 MICROBIOLOGY F.03 SYSTEMIC MYCOSES BLASTOMYCOSIS: DIRECT MICROSCOPY Numerous outbreaks have resulted from exposure to large inocula of conidia BLASTOMYCOSIS Blastomyces dermatitidis o Thermally dimorphic fungus that grows as a mold in culture, producing hyaline, and branching septate hyphae and conidia. o At 37°C or in the host, it converts to a large, singly budding yeast cell Chronic infection with granulomatous and suppurative lesions that is initiated in the lungs Dissemination may occur to any organ but preferentially to the skin and bones. NORTH AMERICAN BLASTOMYCOSIS o Disease caused by Blastomyces dermatitidis o Endemic, and most cases occur in the United States and in Canada. o Despite this high prevalence in North America, blastomycosis has been documented in Africa, South America, and Asia MORPHOLOGY AND IDENTIFICATION Grown on SDA at room temperature o White or brownish colony develops, with branching hyphae bearing spherical, ovoid, or piriform conidia (3–5 μm in diameter) on slender terminal or lateral conidiophores o Larger chlamydospores (7–18 μm) may also be produced. In tissue or culture at 37°C o Grows as a thick-walled, multinucleated, spherical yeast (8–15 μm) that usually produces single buds o The bud and the parent yeast are attached with a broad base, and the bud often enlarges to the same size as the parent yeast before they become detached. o The yeast colonies are wrinkled, waxy, and soft. NOTE TAKER: BALDOS | FERRER | PADAYAO Large, broad-base, unipolar budding yeast-like cells Blastomycosis and Blastomyces dermatitidis: Large, spherical thick-walled yeast cells (8–15 μm in diameter) in this section of a cutaneous abscess. H&E 400×. Blastomycosis and Blastomyces dermatitidis: In culture at ambient temperatures, B. dermatitidis produces hyaline, septate hyphae, and single conidia. 400×. PATHOGENESIS AND CLINICAL FINDINGS Human infection is initiated in the lungs Mild and self-limited cases have been documented Most common clinical presentation o PULMONARY INFILTRATE in association with a variety of symptoms indistinguishable from other acute lower respiratory infections (fever, malaise, night sweats, cough, and myalgias). Page 6 | 10 PCC SOM 2026 MICROBIOLOGY F.03 SYSTEMIC MYCOSES Patients can also present with chronic pneumonia Histologic examination o Distinct pyogranulomatous reaction with neutrophils and noncaseating granulomas. o When dissemination occurs, skin lesions on exposed surfaces are most common o May evolve into ulcerated verrucous granulomas with an advancing border and central scarring Border is filled with microabscesses and has a sharp, sloping edge. Lesions of bone, the genitalia (prostate, epididymis, and testis), and the central nervous system also occur; other sites are less frequently involved. Although immunosuppressed patients, including those with AIDS, may develop blastomycosis, it is not as common in these patients as are other systemic mycoses. DIAGNOSTIC LABORATORY TESTS Specimens consist of: o Sputum o Pus o Exudates o Urine o Biopsies from lesions Upon microscopic examination, wet mounts of specimens may show broadly attached buds on thick-walled yeast cells. In culture, colonies usually develop within 2 weeks on Sabouraud’s or enriched blood agar at 30°C Identification is confirmed by conversion to the yeast form after cultivation on a rich medium at 37°C Serologic tests o Not as useful for the diagnosis of blastomycosis as they are in the case of the other endemic mycoses TREATMENT Severe cases of blastomycosis are treated with amphotericin B. In patients with confined lesions, a 6-month course of itraconazole is very effective. NOTE TAKER: BALDOS | FERRER | PADAYAO EPIDEMIOLOGY Relatively common infection of dogs (and rarely other animals) in endemic areas. Blastomycosis cannot be transmitted by animals or humans. Unlike C. immitis and H. capsulatum, Blastocystis dermatitidis has only rarely (and not reproducibly) been isolated from the environment, so its natural habitat is unknown. PARACOCCIDIOIDOMYCOSIS Paracoccidioides brasiliensis o Thermally dimorphic fungal agent of paracoccidioidomycosis, also known as SOUTH AMERICAN BLASTOMYCOSIS, which is confined to endemic regions of Central and South America MORPHOLOGY AND IDENTIFICATION Cultures of the mold form grow very slowly and produce chlamydospores and conidia. At 36°C, on rich medium, it forms large, multiply budding yeast cells (up to 30 μm). Yeasts are larger and have thinner walls than those of B. dermatitidis. The buds are attached by a narrow connection Paracoccidioidomycosis. Large, multiply budding yeast cells (15–30 μm) are observed in cutaneous lesion. KOH 400×. Page 7 | 10 PCC SOM 2026 MICROBIOLOGY F.03 SYSTEMIC MYCOSES Paracoccidioidomycoses Direct Microscopy: Multiple, narrow base, budding yeast cells Paracoccidioides brasiliensis. Microscopic morphology (LPCB): Large, 20-60 μm, round, narrow base budding yeast cells with multiple budding “STEERING WHEELS” *LPCP: Lactophenol Cotton Blue PATHOGENESIS AND CLINICAL FINDINGS P. brasiliensis is inhaled, and initial lesions occur in the lung. After a period of dormancy that may last for decades, the pulmonary granulomas may become active, leading to chronic, progressive pulmonary disease or dissemination. Most patients are 30–60 years of age, and over 90% are men. DIAGNOSTIC LABORATORY TESTS In sputum, exudates, biopsies, or other material from lesions, the yeasts are often apparent on direct microscopic examination with KOH or calcofluor white. Cultures on Sabouraud’s or yeast extract agar are incubated at room temperature and confirmed by conversion to the yeast form by in vitro growth at 36°C. NOTE TAKER: BALDOS | FERRER | PADAYAO TREATMENT Itraconazole appears to be most effective Ketoconazole & trimethoprim-sulfamethoxazole are also efficacious. Severe disease can be treated with amphotericin EPIDEMIOLOGY Occurs mainly in rural areas of Latin America, particularly among farmers. Disease manifestations are much more frequently in males than in females However, infection and skin test reactivity occur equally in both sexes. Since P. brasiliensis has only rarely been isolated from nature, its natural habitat has not been definitively determined. As with the other endemic mycoses, paracoccidioidomycosis is not communicable CHECKPOINT 1. The following are systemic mycoses: A. Coccidioidomycosis B. Histoplasmosis C. Blastomycosis D. Paracoccidioidomycosis E. AOTA 2. Risk factors for systemic coccidioidomycosis include the following EXCEPT: A. Heredity B. Sex C. Age D. Compromised humoral-mediated immunity 3. Coccidioidomycosis is also referred to as: A. VALLEY FEVER B. SAN JOAQUIN VALLEY FEVER C. DESERT RHEUMATISM D. AOTA 4. Spherules observed in histologic sections of tissue, sputum, or other specimens are diagnostic of? A. Coccidioides immitis B. Histoplasma capsulatum C. Blastomyces dermatitidis D. Paracoccidioides brasiliensis Page 8 | 10 PCC SOM 2026 MICROBIOLOGY F.03 SYSTEMIC MYCOSES 5. Most prevalent pulmonary fungal infection in humans and animals A. Coccidioidomycosis B. Histoplasmosis C. Blastomycosis D. Paracoccidioidomycosis 6. In tissue, the yeasts are typically seen within macrophages A. Coccidioides immitis B. Histoplasma capsulatum C. Blastomyces dermatitidis D. Paracoccidioides brasiliensis 7. Thermally dimorphic fungus that grows as a mold in culture, producing hyaline, and BRANCHING septate hyphae and conidia. A. Coccidioides immitis B. Histoplasma capsulatum C. Blastomyces dermatitidis D. Paracoccidioides brasiliensis 8. North American Blastomycosis A. Coccidioides immitis B. Histoplasma capsulatum C. Blastomyces dermatitidis D. Paracoccidioides brasiliensis 9. South American Blastomycosis A. Coccidioides immitis B. Histoplasma capsulatum C. Blastomyces dermatitidis D. Paracoccidioides brasiliensis 10. Narrow base budding yeast cells with multiple budding “STEERING WHEELS” A. Coccidioides immitis B. Histoplasma capsulatum C. Blastomyces dermatitidis D. Paracoccidioides brasiliensis 1.E 2.D(Cell-mediated) 3.D 4.A 5.B 6.B 7.C 8.C 9.D 10.D NOTE TAKER: BALDOS | FERRER | PADAYAO Page 9 | 10 PCC SOM 2026 MICROBIOLOGY NOTE TAKER: BALDOS | FERRER | PADAYAO F.03 SYSTEMIC MYCOSES Page 1 | 10