Systemic mycoses

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Systemic mycoses

  1. 1. SYSTEMIC MYCOSESWednesday, January 11, 2012
  2. 2. SUMMARY OF DEEP MYCOSES DISEASES AND SAPROPHYTIC PHASE PARASITIC PHASE ETIOLOGIC AGENT Blastomycosis budding yeast with septate mycelium; conidia are Blastomyces dermatitidis broad base bud pyriform, globose or double colonies are white or beige, fluffly or glaborous Histoplasmosis septate mycelia microconidia; small single budded Histoplasma capsulatum tuberculate macroconidia yeast colonies are white and buff Coccidioidomycosis septate mycelium fragment to spherule (10-20 u) with Coccidiodes arthroconidia; colonies are endospores immitis buff or white and moth Paracoccidiodomycosis similar to B. dermatitidis large multiple budding Paracoccidioides yeastWednesday, January 11, 2012
  3. 3. CHARACTERISTICS TO REMEMBER Monomorphic Dimorphic No change in form/state Change in form in in response to stimulus response to stimulus like like temperature. temperature. Example Example, yeast at 25° C yeast at 37° C and and 37° C mycelium at 25° C Examples: Mycelium = Examples: Histoplasma capsulatum; Blastomyces dermatitidis; Aspergillus species; Yeast Paracoccidiodes brasiliensis; = Cryptococcus species Coccidiodes immitisWednesday, January 11, 2012
  4. 4. FACTORS AFFECTING DIMORPHISM Temperature Oxidation-reduction potential Availability of sulfhydril groups CO2 tensionWednesday, January 11, 2012
  5. 5. Histoplasma capsulatum Dimorphic Mycelial phase: 25° C Macroconidia (8-14μm) Microconidia (2-4μm)Wednesday, January 11, 2012
  6. 6. Histoplasma capsulatum At 37°C or at body temperature = budding yeast 2-3 x 3-4 μm Found predominantly in histiocytesWednesday, January 11, 2012
  7. 7. LIFE CYCLE soil with high nitrogen content, associated with the guano of bats and starlings rotting guano mixed with soil & feathers of the birds open environment, soil is nitrogen rich with a rainfall of 35-50 inches and 67-87% relative humidity caves, the main habitat of bats, which are the reservoir of Histoplasma capsulatumWednesday, January 11, 2012
  8. 8. LIFE CYCLEWednesday, January 11, 2012
  9. 9. CLASSIFICATION OF HISTOPLASMOSIS TYPE OF SPECIFIC COMMENTS INFECTION DISORDER • Asymptomatic or • Occurs with mild like flu normal exposure illness • Acute pulmonary • Occurs with Normal Hosts histoplasmosis heavy exposure • Pericarditis, • Rare mediastinal complications fibrosisWednesday, January 11, 2012
  10. 10. CLASSIFICATION OF HISTOPLASMOSIS TYPE OF SPECIFIC COMMENTS INFECTION DISORDER • Occurs in • Disseminated individuals who histoplasmosis have an immune Opportunistic defect Infection • Occurs in • Chronic individuals who pulmonary have a structural histoplasmosis defectWednesday, January 11, 2012
  11. 11. CLASSIFICATION OF HISTOPLASMOSIS TYPE OF SPECIFIC COMMENTS INFECTION DISORDER • Occurs in • Disseminated individuals who histoplasmosis have an immune Opportunistic defect Infection • Occurs in • Chronic individuals who pulmonary have a structural histoplasmosis defectWednesday, January 11, 2012
  12. 12. CLINICAL FORMS & SYMPTOMS TYPE OF INFECTION SPECIFIC DISORDER • Asymptomatic or flu-like syndrome Primary acute • Chest pain, shortness of breath and hoarseness • Radiologically, discrete lung lesion may or may not develop • Large pulmonary lesions develop Chronic cavitary • lesions may exist in a relative quiescent state • Often mistaken for tuberculosis • Only small percentage progress into this clinical forms • Disease of reticuloendothelial system in which organs infection may Severe disseminated develop • In massive dissemination, it could be fatalWednesday, January 11, 2012
  13. 13. HISTOPLASMOSISWednesday, January 11, 2012
  14. 14. LABORATORY DIAGNOSIS Direct Examination: KOH; Wright/Giemsa Culture: SDA; Smith and Goodman (for contaminated specimen); Yeast Extract = place the CM in a plastic bagWednesday, January 11, 2012
  15. 15. LABORATORY DIAGNOSIS Skin test with histoplasmin Ag CF test Immunodiffusion testWednesday, January 11, 2012
  16. 16. TREATMENT & PREVENTION Amphotericin B for disseminated infection Itraconazole for immunocompromised patients Cleaning of bat droppingsWednesday, January 11, 2012
  17. 17. Blastomyces dermatitidis 2 phases: asexual & sexual Blastomyces dermatitidis (asexual phase) Ajellomyces dermatitidis (sexual phase) Dimorphic fungusWednesday, January 11, 2012
  18. 18. Blastomyces dermatitidis MYCELIAL FORM The mycelial phase at 25° C showed typical pyriform microconidia , which are about 2-4 microns in diameter. YEAST FORM At 37° C and at body temperature, this organism is a yeast 8-15 microns in diameter. Buds are produced singly and are attached to parent cell by broad base.Wednesday, January 11, 2012
  19. 19. LIFE CYCLE The mode of transmission: inhalation of the spores or the microconidia Natural habitat: remains an enigma Favors environment with high nitrogen content, acid pH, abundant moisture, and perhaps enriched with animal excretaWednesday, January 11, 2012
  20. 20. LIFE CYCLEWednesday, January 11, 2012
  21. 21. BLASTOMYCOSIS Chicago Disease = Gilchrist’s disease = North American BlastomycosisWednesday, January 11, 2012
  22. 22. CLINICAL FORMS SYMPTOMSPulmonary • Fever, cough and hoarseness • Productive cough, fever and weight loss after several months • Radiographically resembles tuberculosisSystemic • Extension of pulmonary form • Common sites of involvement are liver and spleen • Granulomatous lesions are presentCutaneous • Indicates systemic disease • May result from direct inoculation from the soilWednesday, January 11, 2012
  23. 23. TESTS IMPORTANT FEATURES1. Direct Microscopic 20% KOH • specimen is sputum for pulmonary form and skin for cutaneous form • Biopsy material can also be used • Look for the presence of broad based buds2. Culture Saborauds, Mycosel or Mycobiotic Agar • Fluffy, whitish brown fungus with pyriform spores • Culture is not routinely done3. Skin Test Blastomycin • Has a tendency of high cross reactivity • Little diagnostic valueWednesday, January 11, 2012
  24. 24. Wednesday, January 11, 2012
  25. 25. TREATMENT & PREVENTION Amphotericin B has been used but with erratic results 2-hydroxystilbamidine Ketoconazole, less nephrotoxicity Prevent fomite inhalation in endemic areaWednesday, January 11, 2012
  26. 26. Coccidioides immitis Amphotericin B has been used but with erratic results Asexual phase: Coccidiodes immitis Sexual phase: not known MYCELIAL STAGE (25°C) septate hyphae mature in a manner such that alternate cells develop into arthroconidia being separated by vacuolized cells  arthroconidia separate readily and have a “barrel” shape appearanceWednesday, January 11, 2012
  27. 27. Coccidioides immitisWednesday, January 11, 2012
  28. 28. Coccidioides immitis YEAST FORM In tissue and at body temperature: Develops into spherules (sporangia; 10-60μm) filled with endospores (2-5μm)Wednesday, January 11, 2012
  29. 29. LIFE CYCLEWednesday, January 11, 2012
  30. 30. COCCIDIOMYCOSIS Posada’s Disease = San Joaquin Valley Fever = Desert Rheumatism TREATMENT & PREVENTION Generally difficult to manage regardless of drug use Amphotericin B is the drug of choice Itraconazole and fluconazole have been tried with little success Prevent spores inhalationWednesday, January 11, 2012
  31. 31. CLINICAL FORMS SYMPTOMSPrimary Pulmonary • Occurs 7-28 days after inhalation of single spore • Positive skin test • Flu-like fever, malaise and cough • 10% develop erythrema nodosum or erythrema multiformeBenign Form • Precipitin and complement fixation titers appear • Development of well defined lung cavitation • Exist for years and could be unnoticedDisseminated Form • 1 in 500 patients progressed into this state • Fungi spreads into various organs • Prognosis is graveWednesday, January 11, 2012
  32. 32. TESTS IMPORTANT FEATURES1. Direct Microscopic 10-20% KOH • sputum, tissue or skin are used as specimen • look for the presence of spherules2. Culture Saboraud’s medium with or without antibiotics • room temperature, white fluffy fungus • arthrospores are dangerous to work with • Never try the organism in the petri dish but always on the bottle or test tube • Examine on the 3rd or 4th day, but must kill organisms with formalin before attempting to make an LPCB mount • Can prepare exoantigen3. Others Skin test • conversion back to skin test positive (anergy) is an indication of grave prognosisWednesday, January 11, 2012
  33. 33. Wednesday, January 11, 2012
  34. 34. Paracoccidioimycosis brasiliensis Dimorphic Mycelial stage (25°C): no typical sporulation Yeast stage (37°C): with several budding cells attached to the parent cell, some in a “mariner’s wheel” arrangement about 2-30μmWednesday, January 11, 2012
  35. 35. LIFE CYCLE Transmitted by inhalation of the spores Restricted to South and Central America Isolated in acidic soil and its growth requires increased humidity natural habitat remains to be elucidatedWednesday, January 11, 2012
  36. 36. Wednesday, January 11, 2012
  37. 37. PARACOCCIDIODOMYCOSIS South American Blastomycosis = Lutz- Splendore-Almeida’s Disease A chronic granulomatous disease of skin, mucous membranes, lymph nodes and internal organs Central and South America more specifically in BrazilWednesday, January 11, 2012
  38. 38. PARACOCCIDIODOMYCOSIS Females are as susceptible to infections as males, but the incidence of clinical disease in males is nine times higher Primary pulmonary disease is often inapparent Disseminated disease often causes ulcerative lesions of the buccal, nasal and occasionally gastrointestinal mucosa.Wednesday, January 11, 2012
  39. 39. TESTS IMPORTANT FEATURES1. Direct Microscopic 10-20% KOH • 1-2 drops are used • demonstration of multiple budding yeast2. Culture Saboraud’s • At room temperature it grows a non spore forming septate fungus Brain Heart Infusion at 35° C • It produces yeast that is seen in tissue3. Others • Paracoccidioidin skin test • Complement fixation test • Immunodiffusion test Dr. Supachai BasitWednesday, January 11, 2012
  40. 40. TREATMENT & PREVENTION Amphotericin B Itraconazole Long term therapy is required Prevent inhalation of dust in endemic areaWednesday, January 11, 2012
  41. 41. Cryptococcus neoformans Monomorphic: always in yeast form whether at 25° or at 37° C. Unique feature: acidic mucopolysaccharide capsuleWednesday, January 11, 2012
  42. 42. LIFE CYCLE The etiologic agent of cryptococcosis has been recovered in large numbers from the excreta debris of pigeon roosts, thus it appears to survive well in a dessicated, alkaline, nitrogen-rich and hypertonic environment There is a close relationship to the habitats of pigeon, but the organism does not infect the birdWednesday, January 11, 2012
  43. 43. Dr. Supachai BasitWednesday, January 11, 2012
  44. 44. CRYPTOCOCCOSIS Busse-Buschke’s Disease, Torulosis, European Blastomycosis The disease is worldwide in distribution. This yeast has been repeatedly isolated from sites inhabited by pigeons, particularly their roosts and droppings. Pigeons are not naturally infected.Wednesday, January 11, 2012
  45. 45. CRYPTOCOCCOSIS Primary pulmonary cryptococcosis is usually inapparent but may be chronic, subacute or acute. The clinical entity is most often seen in cryptococcal meningitis. Osseous and cutaneous disease can be present without apparent neurologic involvement.Wednesday, January 11, 2012
  46. 46. CRYPTOCOCCOSIS: CUTANEOUS FORMWednesday, January 11, 2012
  47. 47. CRYPTOCOCCOSIS: NEUROLOGIC FORMWednesday, January 11, 2012
  48. 48. TESTS IMPORTANT FEATURES1. Direct Microscopic India Ink Stain • Cerebrospinal fluid (CSF) is used as specimen • The organisms appear as yeast about 8-12 microns in diameter, which are usually surrounded by clear capsules2. Culture Saboraud’s medium with or without antibiotics • either at room temperature or at 35° C, the colonies develop after 1-3 weeks incubation as shiny, slimy, light tan yeast colonies3. Others Latex Agglutination Test Urease Test Positive Dr. Supachai BasitWednesday, January 11, 2012
  49. 49. IN CULTUREWednesday, January 11, 2012
  50. 50. TREATMENT & PREVENTION Amphotericin B in combination with 5-fluorocytosine have been successful Fluconazole is as effective too Clean pigeon droppings Avoid visiting caves without protective gearsWednesday, January 11, 2012

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