SYSTEMIC MYCOSES `

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MICROBIAL DISEASES AND DIAGNOSIS - SYSTEMIC MYCOSES

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SYSTEMIC MYCOSES `

  1. 1. SYSTEMIC MYCOSES M.THILAKAR LS1154 THIRD YEAR., M.SC. LIFE SCIENCES, BDU.
  2. 2. MYCOSES ● Mycoses are classified clinically as follows: ● SYSTEMIC : (Infections of internal organs of the body) – Primary mycoses (coccidioidomycosis, histoplasmosis, blastomycoses, histoplasmosis). – Opportunistic mycoses (surface and deep yeast mycoses, aspergillosis, mucormycoses, phaeohyphomycoses, hyalohyphomycoses, cryptococcoses, penicilliosis, pneumocystosis). ● SUPERFICIAL : (Infections confined to the skin or mucous membranes that do not invade into deeper tissues or organs) – Subcutaneous mycoses (sporotrichosis, chromoblastomycosis, Madura foot (mycetoma). – Cutaneous mycoses (pityriasis versicolor, dermatomycoses).
  3. 3. ● Fungi that are able to cause systemic illness in healthy people are rare and confined to specific geographic locations across the world. ● Fungal infection of internal organs. ● Primarily involve the respiratory system. ● Infection occurs by inhalation of air- borne conidia. ● By Dimorphic fungi. ● More than 95% are self limiting & asymptomatic. ● Rest are symptomatic & disseminate by hematogenous route. SYSTEMIC MYCOSIS
  4. 4. ● These infections are caused by inhalation of the fungus, which exhibits dimorphism. (i.e. can exist as a yeast or a mold). ● The organisms are acquired by – Inhalation of the conidia from soil, and – Develop in the lungs as yeasts. ● Change in temperature determines the form. That fungus is a mold when grown at 25°C but grows as yeast at body temperature. (Thermal dimorphism). ● Starting from foci in the lungs, – The organisms can then be transported, hematogenously or lymphogenously, to other organs (including the skin, where they cause granulomatous, purulent infection foci) ● Therapeutics : – Amphotericin B and – Azoles
  5. 5. Agent infection Dissemination Drug of choice Blastomyces dermatitidis Blastomycosis (southern states of America) Skin and bone Later nervous system and visceral organs Amphotericin B itraconazole Coccidioides immitis Coccidioidomycosis (southern states of America, Mexico and the northern- most countries of South America) Skin, bones, joints, subcutaneous tissues, and visceral organs Amphotericin B Paracoccidioid oes brasiliensis Paracoccidioidomyc osis Oro-nasal mucosa latter spleen, liver, intestine and skin Amphotericin B + sulfas or azoles Histoplasma capsulatum Histoplasmosis Acute pneumonia (cave disease) Chronic pneumonia (smoker) Disseminated (immunocompromised) Primary cutaneous (lab accidents) Amphotericin B PRIMARY SYSTEMIC MYCOSIS
  6. 6. SPECIE MOLD FORM YEAST FORM OPPORTUNISTIC Cryptococcus neoformans - No pseudohyphae; encapsulated Candida albicans - Blastoconidia, chlamydoconidia, pseudohyphae + germ tube Aspergillus Uniseriate/biseriate - SYSTEMIC (Dimorphic) Histoplasma capsulatum Tuberculate macroconidia Small intracellular yeast Blastomyces dermititidis Lollipop forms Large yeast cells w/ broad based buds; double contoured wall Coccidiodes immitis Thick walled; arthroconidia Round walled spherules; Barrel shape Paracoccidiodes brasiliensis Similar to lollipop forms Mariner’s wheel-multiple blastoconidia budding from sides of large blastospore Micky mouse cap IDENTICAL FEATURES
  7. 7. PRIMARY SYSTEMIC MYCOSES (DIMORPHIC)
  8. 8. PRIMARY SYSTEMIC MYCOSES • Infections of internal organs of the body. • Caused by dimorphic fungi. • The following are the Systemic mycoses : 1. Blastomycosis, 2. Coccidioidomycosis 3. Histoplasmolysis 4. Paracoccidioidomycosis
  9. 9. 1.BLASTOMYCOSIS ● Caused by : Blastomyces dermatitidis ● Inhalation of conidial spores. ● Causes a chronic granulomatous infection. ● Primary infection : Pulmonary blastomycosis. ● Secondary infection : May spread to other organs including skin (Cutaneous mycosis). ● Osteoarticular blastomycosis : Occurs in about 30% of patients with the spine, pelvis, cranial bones, ribs and long bones most commonly involved.
  10. 10. BLASTOMYCOSIS
  11. 11. DIAGNOSIS ● SPECIMENS : – Bronchial secretion, Urine, – Scrapings from infection foci, Sputum, – Skin scrapings, Bone marrow, – Pleural fluid and blood and Cerebrospinal fluid. ● MICROSCOPIC EXAMINATION : – 10% KOH and Parker ink or calcofluor white mounts. (Skin, Body fluids). – PAS digest, Grocott's methenamine silver (GMS) or Gram stain (Tissue sections) – Positive direct microscopy demonstrating characteristic yeast-like cells from any specimen
  12. 12. ● CULTURE : – On blood or Sabouraud agar must be incubated for several weeks or – Brain heart infusion agar supplemented with 5% sheep blood. ● ANTIBODIES DETECTION : – Using the complement fixation test and – Agar gel precipitation.
  13. 13. Broad based budding and thickened cell walls and globose shape are characteristic of the yeast form of Blastomyces dermatitidis One-celled conidia formed on short conidiophores. Blastomyces dermatitidis
  14. 14. THERAPY ● Amphotericin B is the therapeutic agent of choice. ● Untreated blastomycoses : Lethal always.
  15. 15. 2.COCCIDIOIDOMYCOSIS ● Caused by : C. immitis (Dimorphic) ● Inhalation of arthrospores. ● Primary infection : Lungs. ● Secondary infection : – May spread to other organs including skin. – Other silent infections (60% of infected persons) to severe pneumonia. – May produces granulomatous lesions in skin, bones, joints, and meninges.
  16. 16. COCCIDIOIDOMYCOSIS Extension of pulmonary coccidioidomycosis showing a large superficial ulcerated lesion Chronic cutaneous granulomatous lesions of the face, neck and chin
  17. 17. MORPHOLGY ● In cultures : Grows as mycelial form; ● In body tissues : neither buds nor produces mycelia. ● Spherical structures (spherules) with thick walls and a diameter of 15–60 micro meter, each filled with up to 100 spherical-to-oval endospores.
  18. 18. DIAGNOSIS ● SPECIMENS : – Bronchial secretion, Urine, – Scrapings from infection foci, Sputum, – Skin scrapings, Bone marrow, – Pleural fluid, blood and Cerebrospinal fluid. ● MICROSCOPIC EXAMINATION : – 10% KOH and Parker ink or calcofluor white mounts. (Skin, Body fluids). – PAS digest, Grocott's methenamine silver (GMS) or Gram stain (Tissue sections). – A positive direct microscopy demonstrating spherules (10- 80um) with endospores (2-5um).
  19. 19. ● CULTURES : – On blood or Sabouraud agar must be incubated for several weeks or – Brain heart infusion agar supplemented with 5% sheep blood. ● ANTIBODIES DETECTION : – Using the complement fixation test and – Agar gel precipitation.
  20. 20. Culture of Coccidioides immitis showing a suede-like to downy, greyish white colony with a tan to brown reverse.
  21. 21. Tissue section showing typical endo sporulating spherules of C. immitis Coccidioides immitis Coccidioides immitis showing typical single- celled, hyaline, rectangular to barrel-shaped, alternate arthroconidia
  22. 22. THERAPY ● Amphotericin-B ● Anoralazole derivative may be used.
  23. 23. 3.HISTOPLASMOSIS ● Caused by : Histoplasma capsulatum (dimorphic fungus) ● Natural habitat (as Spore) : Soil. ● In human tissues it forms : Yeast cells. ● The sexual stage or form of this fungus is called Emmonsiella capsulata ● Inhalation of Spores (conidia) into the respiratory tract, ● Taken up by alveolar macrophages, and become yeast cells that reproduce by budding. ● It affects the reticulo-endothelial system (RES). ● Observed in AIDS patients.
  24. 24. HISTOPLASMOSIS
  25. 25. DIAGNOSIS ● SPECIMENS : – Bronchial secretion, Urine, – Scrapings from infection foci, Sputum, – Skin scrapings, Bone marrow, – Pleural fluid, blood and Cerebrospinal fluid. ● MICROSCOPIC EXAMINATION : – 10% KOH and Parker ink or calcofluor white mounts. (Skin, Body fluids). – PAS digest, Grocott's methenamine silver (GMS) or Gram stain (Tissue sections). – A positive direct microscopy demonstrating characteristic yeast-like cells from any specimen should be considered significant.
  26. 26. ● CULTURE : – On blood or Sabouraud agar must be incubated for several weeks or – Brain heart infusion agar supplemented with 5% sheep blood. ● ANTIBODIES DETECTION : – Using the complement fixation test and – Agar gel precipitation.
  27. 27. Culture of Histoplasma capsulatum
  28. 28. Tissue morphology of H. capsulatum var. capsulatum (left) showing numerous small narrow base budding yeast cells (1-5um diam) inside macrophages and H. capsulatum var. duboisii (right) showing larger sized budding yeast cells (5-12 um in diam).
  29. 29. THERAPY ● Amphotericin B is only indicated in severe infections, especially the disseminated form.
  30. 30. 4.PARACOCCIDIOIDOMYCOSIS Ulcerated lesion on the pharyngeal mucosaExtensive destruction of facial features Ulcerated lesion on the nasal mucosa
  31. 31. ● Caused by Paracoccidioidies brasiliensis (dimorphic fungus) [Produces thick-walled yeast cells (10–30 micro meter in Diameter), most of which have several buds]. ● Inhalation of spore-laden dust. ● Natural habitat is : soil. ● Primary : chronic granulomatous infection foci are found in the lung, occasionally Gastro intestinal mucosa. ● Starting from these foci, the fungus can disseminate hematogenously or lymphogenously into the skin, mucosa, or lymphoid organs. ● The disease in its inception and development is similar to blastomycosis and coccidioidomycosis. ● The only etiological agent, Paracoccidioides brasiliensis is geographically restricted to areas.
  32. 32. DIAGNOSIS ● SPECIMENS : – Bronchial secretion, Urine, – Scrapings from infection foci, Sputum, – Skin scrapings, Bone marrow, – Pleural fluid, blood and Cerebrospinal fluid. ● MICROSCOPIC EXAMINATION : – 10% KOH and Parker ink or calcofluor white mounts. (Skin, Body fluids). – PAS digest, Grocott's methenamine silver (GMS) or Gram stain (Tissue sections). – A positive : 20-60 um, round, narrow base budding yeast cells with multiple budding "steering wheels" from any specimens.
  33. 33. ● CULTURE : – On blood or Sabouraud agar must be incubated for several weeks or – Brain heart infusion agar supplemented with 5% sheep blood. ● ANTIBODIES DETECTION : – Nil.
  34. 34. Multiple, narrow base, budding yeast cells "steering wheels" of P. brasiliensis. GMS stained lung section (left) and phase contrast of cells from a culture (right).
  35. 35. THERAPY ● The therapeutic agents of choice – Areazol derivatives(e.g.,itraconazole), – Amphotericin-B, and – Sulfonamides. Ends lethally unless treated.
  36. 36. SUMMARY
  37. 37. OPPORTUNISTIC MYCOSES
  38. 38. OPPORTUNISTIC MYCOSES ● ANY fungus found in nature may give rise to opportunistic mycoses. – Candidiasis – Cryptococcosis – Aspergillosis – Zygomycosis ● Other: – Trichosporonosis, – Fusariosis, – Penicillosis.
  39. 39. 1.CANDIDIASIS ● 70% of all human Candida infections are caused by C.albicans. ● The rest by – C. parapsilosis, – C. tropicalis, – C. guillermondii, – C. kruzei, ● and a few other rare Candida species.
  40. 40. MORPHOLOGY & CULTURE ● Pseudohyphae are observed frequently and septate mycelia occasionally. ● C. albicans can be grown on the usual culture mediums. ● After 48 hours of incubation on agar mediums, round, whitish, somewhat rough-surfaced colonies form. ● They are differentiated from other yeasts based on morphological and biochemical characteristics.
  41. 41. PATHOGENESIS ● Candida is a normal inhabitant of human and animal mucosa (commensal). ● Candiasis usually develop in persons whose immunity is compromised, most frequently in the presence of disturbed cellular immunity. ● The mucosa are affected most often, less frequently the outer skin and inner organs (deep candidiasis). ● Skin is mainly infected on the moist, warm parts of the body. ● Candida can spread to cause secondary infections of the lungs, kidneys, and other organs. ● Candidial endocarditis and endo phthalmitis are observed in drug addicts.
  42. 42. Forms of candidiasis ● 1. Oropharyngeal candidiasis ● 2. Cutaneous candidiasis ● 3. Vulvovaginal candidiasis and balanitis ● 4. Chronic mucocutaneous candidiasis ● 5. Neonatal and congenital candidiasis ● 6. Oesophageal candidiasis ● 7. Gastrointestinal candidiasis ● 8. Urinary tract candidiasis ● 9. Meningitis ● 10. Ocular candidiasis
  43. 43. Oropharyngeal candidiasis: including thrush, glossitis, stomatitis and angular cheilitis (perleche)
  44. 44. Cutaneous candidiasis: including intertrigo, diaper candidiasis, paronychia and onychomycosis
  45. 45. Ocular candidiasis
  46. 46. DIAGNOSIS ● SPECIMENS : – Bronchial secretion, Urine, – Scrapings from infection foci, Sputum, – Skin scrapings, Bone marrow, – Pleural fluid, blood and Cerebrospinal fluid. ● MICROSCOPIC EXAMINATION : – 10% KOH and Parker ink or calcofluor white mounts. (Skin, Body fluids). – PAS digest, Grocott's methenamine silver (GMS) or Gram stain (Tissue sections). – Native staining.
  47. 47. ● CULTURES : – On blood or Sabouraud agar must be incubated for several weeks or – Brain heart infusion agar supplemented with 5% sheep blood. ● ANTIBODIES DETECTION : – Agglutination, - Gel precipitation, – Enzymatic immunoassays, – Immunoelectrophoresis.
  48. 48. Typical moist colonies of Candida
  49. 49. THERAPY ● Nystatin and azoles can be used in topical therapy. ● In cases of deep candidiasis, – Amphotericin B is still the agent of choice, often administered together with 5-fluorocytosine. ● Echinocandins (e.g., caspofungin) can be used in severe oropharyngeal and esophageal candidiasis.
  50. 50. 2.ASPERGILLOSIS ● Aspergilloses are most frequently caused by Aspergillus fumigatus, A. flavus, A. niger, A. nidulans, and A. terreus are found less often ● Aspergilli are ubiquitous in nature. ● By inhalation of spores. ● Ingestion of products contaminated with Aspergillus
  51. 51. PATHOLOGY ● Portal of entry : Bronchial system, but the organism can also invade the body through injuries in the skin or mucosa. ● The following localizations are known for aspergilloses: – Aspergillosis of the respiratory tract, – Endophthalmitis develops two to three weeks after surgery, – An eye injury, – Cerebral aspergillosis develops after hematogenous dissemination, – Less in : Endocarditis, Myocarditis, and Osteomyelitis.
  52. 52. FORMS OF ASPERGILLOSIS ● 1. Pulmonary Aspergillosis: including allergic, aspergilloma and invasive aspergillosis. ● 2. Disseminated Aspergillosis ● 3. Aspergillosis of the paranasal sinuses ● 4. Cutaneous Aspergillosis.
  53. 53. DIAGNOSIS ● SAMPLES COLLECTION : Sputum, Bronchial washings and Tracheal aspirates ● MICROSCOPICAL EXAMINATION : – Sputum, washings and aspirates make wet mounts in either 10% KOH & Parker ink or Calcofluor and/or Gram stained smears; – Tissue sections should be stained with H&E, GMS and PAS digest. – Methenamine silver stain. ● CULTURE : SDA ● ANTI BODY DETECTION : – Agglutination, Immunodiffusion and ELISA. ● MOLECULAR BASED DETECTION : – PCR Detection of Aspergillus sp.
  54. 54. Aspergillosis of the lung. Methenamine silver stained tissue section showing dichotomously branched, septate hyphae (left) and a conidial head of A. fumigatus (right)
  55. 55. THERAPY ● High-dose amphotericin B is the agent of choice. ● Azoles can also be used. ● The echinocandin (caspo fungin) has been approved in the treatment of refractory aspergillosis as salvage therapy. ● Surgical removal of local infection foci (e.g., aspergilloma) is appropriate.
  56. 56. 3.CRYPTOCOCCOSIS ● C. neoformans is an encapsulated yeast. ● The individual cell has a diameter of 3–5 micro meter and is surrounded by a polysaccharide capsule several micrometers wide. ● C. neoformans can be cultured on Sabouraud agar at 30–35 C with an incubation period of three to four days
  57. 57. PATHOLOGY ● Normal habitat of the pathogen : Soil, Frequently found in bird drop pings. ● The portal of entry : Respiratory tract. ● The organisms are inhaled and enter the lungs, resulting in a pulmonary cryptococcosis that usually runs an in apparent clinical course. ● From the primary pulmonary foci, the pathogens spread hematogenously to other organs, above all in to the central nervous system (CNS), for which compartment C. neoformans shows a pronounced affinity. ● A dangerous meningoencephalitis is the result.
  58. 58. Nodular skin lesion caused by C. neoformans. Ulcerated skin lesion in an HIV+ patient
  59. 59. DIAGNOSIS ● SAMPLE COLLECTION : – Cerebrospinal fluid (CSF), biopsy tissue, sputum, bronchial washings, pus, blood and urine.. ● MICROSCOPICAL EXAMINATION : – India ink (Encapsulated Yeast), PAS digest, GMS and H&E, mucicarmine stain ● CULTURE : – SDA (Creamy mucoid colony), Bird seed agar. ● ANTIBODY DETECTION : – Latex agglutination test.
  60. 60. Bird seed agar plate showing the typical brown colour effect seen with C. neoformans.
  61. 61. THERAPY ● Amphotericin B is the agent of choice in CNS cryptococcosis, ● Often used in combination with 5-fluorocytosine.
  62. 62. 4.ZYGOMYCOSIS ● Mucormycoses are caused mainly by various species in the genera Mucor, Absidia, and Rhizopus. ● More rarely, this type of opportunistic mycosis is caused by species in the genera Cunninghamella, Rhizomucor, and others. ● All of these fungal genera are in the order Mucorales and occur ubiquitously. ● They are found especially often on disintegrating organic plant materials.
  63. 63. MORPHOLOGY ● Mucorales are molds that produce broad, nonseptate hyphae with thick walls that branch off nearly at right angles ● They grow on all standard mediums. ● High, Whitish-gray to Brown, “fuzzy” Aerial mycelium. ● Culturing is best done on Sabouraud agar.
  64. 64. PATHOGENESIS ● Patients with immune deficiencies or metabolic disorders (diabetes). ● The pathogens penetrate into the target organic system with dust. ● The infections are classified as follows according to their manifestations : – Rhino-cerebral mucor mycosis – Pulmonary mucor mycosis – Disseminated mucor mycosis – Gastrointestinal mucor mycosis, – Cutaneous mucor mycosis
  65. 65. Zygomycosis caused by Basidiobolus ranarum Ulcerated cutaneous zygomycosis
  66. 66. DIAGNOSIS ● SAMPLE COLLECTION : ● Skin scrapings, Sputum and ● Needle biopsies from pulmonary lesions; ● Nasal discharges, scrapings, and Biopsy tissue ● MICROSCOPICAL EXAMINATION : – Nonseptate, ribbon-like hyphae which branch at right angles, sporangium ● CULTURE : – SDA (cotton candy appearence). ● There is no method of antibody-based diagnosis.
  67. 67. THERAPY ● Amphotericin B is the antimycotic agent of choice. ● Surgical measures as required.
  68. 68. SUMMARY
  69. 69. MY REFERENCES ● Medical Microbiology (2005) by Keyeser . ● Medical Microbiology (2007) by Jawetz. ● Human Microbiology (2002) by S.Hardy. ● Microbiology (2002) by Prescot ● www.mycology.adelaide.edu.au ● Pictures are adopted from “The University of Adelaide” website.
  70. 70. End

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