Opportunistic Fungal Infections


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Opportunistic Fungal Infections

  1. 1. Opportunistic Fungal Infections Dr.T.V.Rao MD
  2. 2. Opportunistic Mycosis <ul><li>Opportunistic mycosis a fungal or fungus-like disease occurring in an animal / human’s with a compromised immune system. Opportunistic organisms are normal resident flora that become pathogenic only when the host's immune defenses are altered, as in immunosuppressive therapy, in a chronic disease, such as diabetes mellitus, or during steroid or antibacterial therapy that upsets the balance of bacterial flora in the body. </li></ul><ul><li>T.V.Rao M.D </li></ul>
  3. 3. Common Opportunistic Fungus <ul><li>We find the highest frequency of opportunistic fungal infections come in the following order: 1.Candidiasis 2.Aspergillosis 3.Cryptococcosis </li></ul>
  4. 4. Candida as Opportunistic Infection
  5. 5. Candidosis <ul><li>Candidiasis also called as Monoliasis, </li></ul><ul><li>Can infect Skin, Mucosa, or Internal Organs </li></ul><ul><li>Called as Yeast Like fungus </li></ul><ul><li>Currently important cause of opportunistic fungal infection. </li></ul>
  6. 6. What are Candida <ul><li>Normal flora </li></ul><ul><li>Exist in Mouth, Gastrointestinal tract. </li></ul><ul><li>Vagina, skin in 20 % of normal </li></ul><ul><li>Individuals. </li></ul><ul><li>Colonization increases with age,in pregnancy </li></ul><ul><li>Hospitalization </li></ul><ul><li>Immunity Depends on T lymphocytes, and effective Immunity </li></ul><ul><li>Important etiological agent presenting as opportunistic infection in Diabetus and HIV patients </li></ul>
  7. 7. Morphology and Culturing <ul><li>Ovoid shape or spherical budding cells and produces pseudo mycelium </li></ul><ul><li>Routine cultures are done on Sabouraud's Glucose agar, </li></ul><ul><li>Grow predominantly in yeast phase </li></ul><ul><li>A mixture of yeast cells and pseudo mycelium and true mycelium are seen in Vivo and Nutritionally poor media. </li></ul>
  8. 8. Macroscopic and Microscopic appearance of Candida spp
  9. 9. Pseudohypal structures in Candida
  10. 10. Normal Flora to Pathogenic fungi <ul><li>As Candida is present in practically all humans, it has many opportunities to cause endogenous infections in compromised host - so, Candida infections continues to most frequent opportunistic fungal infection. </li></ul>
  11. 11. Systemic Candidosis <ul><li>Occurs in Patients who carry more yeasts in Mouth, Gastrointestinal system, </li></ul><ul><li>Predisposed with Individuals with </li></ul><ul><li>1 On antibiotic or/and Steroid Therapy </li></ul><ul><li>2 Immunosupressed </li></ul><ul><li>3 Recipients with organ transplantation </li></ul><ul><li>4 Infancy – Old age – Pregnancy </li></ul><ul><li>On Antibiotic therapy </li></ul><ul><li>5 Indisposed with trauma Occluding lesions, </li></ul><ul><li>6 Immuno Supression, Major event in AIDS patients </li></ul><ul><li>7 Diabetus mellitis. </li></ul><ul><li>8 Zink and iron deficiencies </li></ul>
  12. 12. Pathogenesis and Pathology <ul><li>Mucosal infections occur superficially –Discrete white patches on mucosal surface. </li></ul><ul><li>Can affect tongue </li></ul><ul><li>Infants and old persons are affected </li></ul><ul><li>In Immune compromised /AIDS. Oral candidois is commonly seen </li></ul><ul><li>Vaginal Candidosis causes itching soreness white discharge, White colored lesions, </li></ul><ul><li>Pregnancy in advanced stage, </li></ul><ul><li>Majority experience one episode in a life time </li></ul><ul><li>T.V.Rao MD </li></ul>
  13. 13. Predisposition after Surgery and Therapeutic Approaches <ul><li>Post operative Immuno Supression </li></ul><ul><li>Use of IV catheters </li></ul><ul><li>Use of cytotoxinc drugs and cortosteriods </li></ul><ul><li>Use of Urinary Catheters </li></ul>
  14. 14. Important species of Candida in Human infections <ul><li>C.albicans </li></ul><ul><li>C.tropicalis </li></ul><ul><li>C.glabrata </li></ul><ul><li>C.Krusei </li></ul>
  15. 15. Prominent Infections with Candida
  16. 16. Oral Thrush produced by Candia albicans
  17. 17. Many cases of AIDS are suspected by observation of Oral Cavity
  18. 18. Laboratory Diagnosis <ul><li>Skin scrapings, </li></ul><ul><li>Mucosal scrapping, </li></ul><ul><li>Vaginal secretions </li></ul><ul><li>Culturing Blood and other body fluids, </li></ul><ul><li>Observations </li></ul><ul><li>Microscopic observation after Gram staining. Gram + yeast cells. </li></ul>
  19. 19. Laboratory Diagnosis <ul><li>Isolation of Candida from various specimens confers diagnosis </li></ul><ul><li>Serology </li></ul><ul><li>Molecular Methods </li></ul>
  20. 20. Microscopy <ul><li>Gram staining – A rapid method </li></ul><ul><li>KoH preparation </li></ul><ul><li>Methylamine silver staining </li></ul>
  21. 21. Culturing <ul><li>Easier to culture on Sabouraud's dextrose agar </li></ul><ul><li>Culturing in routine Blood culture Media </li></ul><ul><li>Culturing urine - A semiquative estimations are essential Colony forming units essential in attributing infections </li></ul><ul><li>T.V.Rao MD </li></ul>
  22. 22. Easier Identification of species as C.albicans <ul><li>Germ tube test identifies C.albicans from other Candida species. </li></ul><ul><li>Majority of Diagnostic laboratories depend on this test. </li></ul>
  23. 23. Emerging Methods for detection of Candida Infections <ul><li>Molecular Methods </li></ul><ul><li>PCR </li></ul>
  24. 24. Cryptococcosis.
  25. 25. Cryptococcus neoformans <ul><li>A Capsulated yeast – A true yeast.. </li></ul><ul><li>A sporadic disease in the past. </li></ul><ul><li>Most common infection in AIDS patients. </li></ul>
  26. 26. Structure of C.neoformans
  27. 27. Morphology <ul><li>A true yeast </li></ul><ul><li>Round 4 – 10 microns </li></ul><ul><li>Surrounded by Mucopolysaccharide capsule. </li></ul><ul><li>Thick in vivo </li></ul><ul><li>Negative staining with India Ink and Nigrosin </li></ul><ul><li>60% of the infected prove positive by India Ink preparation on examination of CSF </li></ul><ul><li>KoH preparations in Sputum and other tissues, </li></ul><ul><li>PAS and Mucicaramine staining helps confirmation. </li></ul>
  28. 28. As Seen in India Ink preparation
  29. 29. Culturing <ul><li>CSF -Culturing on Sabouraud's agar, and incubated at 37 0 c for upto to 3 weeks </li></ul><ul><li>Cultures appear as Creamy, white, yellow </li></ul><ul><li>Brown colored </li></ul><ul><li>Simple urease test helps in confirming the isolate. </li></ul>
  30. 30. Cryptococcus neoformans Serotypes <ul><li>A true yeast </li></ul><ul><li>4 serotypes - A,B,C,D </li></ul><ul><li>A and D - C.neofromans var neoformans </li></ul><ul><li>B and C - C.neoformans var gatti. </li></ul><ul><li>Many infections are caused by </li></ul><ul><li>C.neofromans var neoformans. </li></ul><ul><li>Found in wild/Domesticated birds. </li></ul><ul><li>Pigeons carry C.neofromans , </li></ul><ul><li>Birds do not get infected. </li></ul>
  31. 31. Pigeons and Red river gum tress harbors the Cryptococcus in nature
  32. 32. Life cycle of C.neofromans
  33. 33. Pathogenesis <ul><li>Enters through lungs - inhalation of Basidiospores of C neoformans </li></ul><ul><li>Enters deep into lungs, Men acquires more infections, and women less infected. </li></ul><ul><li>Self limiting in most cases, </li></ul><ul><li>Pulmonary infections can occur. </li></ul><ul><li>Present as discrete nodules - Cryptococcoma. </li></ul><ul><li>T.V.Rao MD </li></ul>
  34. 34. Pathogenesis <ul><li>Can infect normal humans </li></ul><ul><li>Abnormalities of T lymphocyte function aggravates, the clinical manifestations. </li></ul><ul><li>In AIDS 3- 20% develop Cryptococcosis. </li></ul><ul><li>Present with Chronic meningitis , Meningo encephalitis </li></ul><ul><li>Manifest with – head ache low grade fever, </li></ul><ul><li>Visual abnormalities ,Coma – fatal </li></ul><ul><li>Treatment reduces the morbidity and cure in non immuno supressed expected. </li></ul>
  35. 35. Pathogenesis <ul><li>Can manifest with involvement of ,Skin, </li></ul><ul><li>mucosa,organs,Bones,and as Disseminated form. </li></ul><ul><li>Can mimic like Tuberculosis , </li></ul>
  36. 36. Laboratory Diagnosis . <ul><li>CSF Microscopic observation under India Ink preparation </li></ul><ul><li>Direct microscopy - Gram staining </li></ul><ul><li>Cultures on Sabouraud dextrose agar, </li></ul><ul><li>Serological tests for detection of Capsular antigen </li></ul><ul><li>CSF findings mimic like Tuberculosis </li></ul><ul><li>IN CSF - latex test for detection of Antigen </li></ul><ul><li>Blood cultures, </li></ul><ul><li>ELISA </li></ul>
  37. 37. Treatment <ul><li>Immune competent - Fuconazole,Itraconazole </li></ul><ul><li>Immune Deficient – Amphotericin B </li></ul><ul><li>Flu cytosine </li></ul><ul><li>AIDS patients are not totally cured , Relapses are frequent with fatal outcome . </li></ul><ul><li>Rapid resistance with Fluconazole. </li></ul><ul><li>Avoid contact with Birds </li></ul>
  39. 39. Aspergillosis <ul><li>In nature > 100 species of Aspergillosis exist, Few are important as human pathogens </li></ul><ul><li>1 A.fumigatus </li></ul><ul><li>2 A.niger </li></ul><ul><li>3 A.flavus </li></ul><ul><li>4 A.terreus </li></ul><ul><li>5 A.nidulans </li></ul>
  40. 40. Fungal spores enters through respiratory tract
  41. 41. Morphology <ul><li>Cultured as Mycelial fungus </li></ul><ul><li>Separate hyphae with distinctive sporing structures </li></ul><ul><li>Spore bearing hyphae – Conidiophores terminates in a swollen cell vesicle surrounded by one or two rows of cell ( Streigmata ) from which chains of asexual conidia are produced </li></ul>
  42. 42. Pathogenesis - varied clinical presentations <ul><li>Allergic Aspergillosis – Atopic individuals, with elevated IgE levels </li></ul><ul><li>10-20% of Asthmatics react to A.fumigatus </li></ul><ul><li>Allergic alveoitis follows particularly heavy and repeated exposure to larger number of spores </li></ul><ul><li>Maltsters Lung – causes allergic alveolitis, who handle barley on which A.claveus has sporulated during malting process </li></ul><ul><li>T.V.Rao MD </li></ul>
  43. 43. Pathogenesis <ul><li>Aspergilloma – A fungal ball, fungus colonize Preexisting (Tuberculosis ) cavities in the lung and form compact ball of Mycelium which is later surrounded by dense fibrous wall presents with cough, sputum production </li></ul><ul><li>Haemoptysis occurs due to invasion of blood vessels </li></ul>
  44. 44. Pathogenesis <ul><li>Invasive Aspergillosis </li></ul><ul><li>occurs in immunocompromised with underlying disease </li></ul><ul><li>Neutropenia Most common predisposing factor </li></ul><ul><li>A.fumigatus is the most common infecting species </li></ul><ul><li>In Bone marrow recipients leads to high mortality </li></ul><ul><li>Lung sole site in 70 % of patients </li></ul><ul><li>Fungus invades blood vessels, causes thrombosis septic emboli </li></ul><ul><li>Can spread to Kidney and heart. </li></ul>
  45. 45. Pathogenesis <ul><li>Endocarditis A rare complication </li></ul><ul><li>Open heart surgeries are risk factors </li></ul><ul><li>Poor prognosis </li></ul><ul><li>Paranasal granulomas </li></ul><ul><li>Caused by A.flavus,A,fumigtus </li></ul><ul><li>may invade paranasal sinuses spread to bone to orbit of the eye, and Brain </li></ul><ul><li>T.V.Rao MD </li></ul>
  46. 46. Zygomycosis
  47. 47. Zygomycosis <ul><li>Also called as Mucor Mycosis or Phycomycosis </li></ul><ul><li>Saprophytic mould fungi </li></ul><ul><li>Major Causative agents Rhizopus, </li></ul><ul><li>Mucor, </li></ul><ul><li>Absidia. </li></ul><ul><li>Patents may manifest with Rhinocerbral Zygomycosis </li></ul><ul><li>T.V.Rao MD </li></ul>
  48. 48. Morphology <ul><li>Majority are with Broad aseptate mycelium with many number of asexual spores inside a sporangium which develops at the end of the aerial hyphae </li></ul>
  49. 49. Mucor <ul><li>Microscopy </li></ul><ul><li>Non septate hyphae </li></ul><ul><li>Having branched sporangiophores </li></ul><ul><li>with sporangium at terminal ends </li></ul><ul><li>T.V.Rao MD </li></ul>
  50. 50. Rhizopus <ul><li>Microscopy </li></ul><ul><li>Shows non septate hyphae </li></ul><ul><li>Sporangiophores in groups </li></ul><ul><li>they are above the Rhizoids </li></ul>
  51. 51. Important Clinical Manifestations <ul><li>Rhino cerebral Zygomycosis associate with Diabetus mellitus, leukemia, or lymphomas </li></ul><ul><li>Causes extensive Cellulitis, and tissue destruction. </li></ul><ul><li>T.V.Rao MD </li></ul>
  52. 52. Mucormycosis <ul><li>Cellulitis causes extensive tissue destruction. </li></ul><ul><li>Spread from Nasal mucosa to turbinate bone,paranasal sinuses ,orbit, and Brain </li></ul><ul><li>Rapdily fatal if untreated </li></ul>
  53. 53. Other Manifestations <ul><li>Severe immuno compromised may manifest as primary cutaneous lesions </li></ul><ul><li>Rarely infects Burns patients </li></ul><ul><li>But lesions can be less severe than Brain lesions </li></ul>
  54. 54. Laboratory Diagnosis <ul><li>Histopathology more reliable than culturing </li></ul><ul><li>A certain Diagnosis needs Biopsy </li></ul><ul><li>Nasal discharges Sputum, rarely contain many fungal elements </li></ul>
  55. 55. Histological sections <ul><li>Contain non septate hyphae in thromboses vessels or sinuses surrounded by leukocytes or giant cells </li></ul><ul><li>T.V.Rao MD </li></ul>
  56. 56. Microscopy <ul><li>In Koh preparation shows broad aseptate branching mycelium, and distorted hyphae </li></ul><ul><li>But staining with Methenamine silver is more sensitive. </li></ul><ul><li>Staining with PAS not helpful </li></ul>
  57. 57. Culturing <ul><li>Always depend on clinical history and presentation for certain diagnosis </li></ul><ul><li>Cultured on Sabouraud's dextrose agar. </li></ul><ul><li>T.V.Rao MD </li></ul>
  58. 58. Pathology and Pathogenesis <ul><li>Spread from nasal mucosa </li></ul><ul><li>Spread to turbinate bones Para nasal sinuses , orbit, brain </li></ul><ul><li>Associated with uncontrolled diabetes mellitus </li></ul><ul><li>In leukemia patients , Lymphoma patients, </li></ul><ul><li>Leads to fatal outcome, </li></ul><ul><li>Improved with Anti fungal treatment. </li></ul><ul><li>Spread to lungs disseminated infection,. </li></ul>
  59. 59. Treatment <ul><li>Early Diagnosis highly essential for effective cure </li></ul><ul><li>High doses of I V Amphotericin B </li></ul><ul><li>Surgical interventions </li></ul><ul><li>Control of Diabetus a basic requirement for better clinical outcome </li></ul>
  60. 60. PNEUMOCYSTOSIS Identified as most Important opportunistic fungal infection in the Era of AIDS
  61. 61. Pneumocystosis <ul><li>Pneumocystis jiroveci – causes pneumonia in immunocompromised </li></ul><ul><li>In the past considered as Protozoan </li></ul><ul><li>Now Molecular biologic studies prove as Fungus Related to Ascomycetes </li></ul><ul><li>Many Animals harbor in lungs in Rats, Ferrets, Rabbits, </li></ul><ul><li>Causes the diseases in human if immunocompromised </li></ul>
  62. 62. Species <ul><li>Pneumocystis carnii found in rats </li></ul><ul><li>Pneumocystis jiroveci in human species </li></ul>
  63. 63. Predisposing factors <ul><li>Corticosteroid therapy </li></ul><ul><li>Transplant recipients </li></ul><ul><li>Antineoplastic therapy </li></ul><ul><li>Transplant recipients </li></ul><ul><li>When retroviral treatment is not started,a major cause of death in AIDS patients . </li></ul><ul><li>Infections of the other organs is on raise, Spleen,Lymphnodes, Bone marrow, </li></ul>
  64. 64. Morphology <ul><li>Spherical, Elliptical </li></ul><ul><li>4- 6 microns, contains 4 to 8 nuclei </li></ul><ul><li>Stained with </li></ul><ul><li>Silver stain, toludine blue, Calcoflour white </li></ul><ul><li>Trophozites present in a tight mass </li></ul><ul><li>P.Jiroveci is an extracellular pathogen </li></ul><ul><li>T.V.Rao MD </li></ul>
  65. 65. Life cycle of P.Jiroveci
  66. 66. Pathogenesis <ul><li>P.Jiroveci is extracellular pathogen, </li></ul><ul><li>In AIDS patients – infiltration of alveolar spaces with plasma cell leads to interstitial plasma cell pneumonias </li></ul><ul><li>Plasma cells are absent in AIDS related Pneumocystis pneumonia </li></ul><ul><li>Blockade of oxygen exchange interface, results in Cyanosis </li></ul>
  67. 67. Diagnosis <ul><li>Ideal specimens </li></ul><ul><li>1 Bronchoalveloar lavage </li></ul><ul><li>2 Lung biopsy </li></ul><ul><li>3 Induced sputum </li></ul><ul><li>Stains preferred </li></ul><ul><li>1.Giemsa </li></ul><ul><li>2 Toludine blue </li></ul><ul><li>3 Methenamine silver </li></ul><ul><li>4 Calcofluor white </li></ul><ul><li>X ray of Chest supports the Diagnosis </li></ul><ul><li>T.V.Rao MD </li></ul>
  68. 68. Diagnosis <ul><li>Culturing yet not possible </li></ul><ul><li>Direct Fluorescent method with Monoclonals a rapid and emerging method </li></ul><ul><li>Serology – For epidemiological purpose only to establish prevalence of Infection. </li></ul>
  69. 69. Immunity - Pneumoctistis <ul><li>In the absence of immuno Supression P.Jiroveci does not cause disease . </li></ul><ul><li>Cell Mediated immunity plays a dominant role in resitance to Infection. </li></ul><ul><li>Infection not seen until CD4 counts drop to </li></ul><ul><li><400/microliters . </li></ul>
  70. 70. Treatment <ul><li>Acute cases are treated with Trimethoprim-Sulphamehoxazole </li></ul><ul><li>Pentamidine, Isothionate are very effective compounds </li></ul>
  71. 71. Prophylaxis <ul><li>Treating with TMP-SMZ </li></ul><ul><li>Aerolized Pentamidine is effective and locally reaches higher concentration in the lungs. </li></ul>
  72. 72. Pencillium marneffi Causes serious disseminated infection, Papular skin lesions in AIDS Common in South east Asia
  73. 73. Morphology <ul><li>A dimorphic fungi </li></ul><ul><li>Mould at 25 0 c </li></ul><ul><li>Yeast at 37 0 c </li></ul><ul><li>Intracellular yeast like appearance as in Histoplasmosis </li></ul><ul><li>The fungi are associated with Bamboo rat </li></ul>
  74. 74. Typical microscopic appearance of P.marneffi
  75. 75. Dimorphic chaterization of Pencillum marneffi
  76. 76. Pathology and Pathogenesis <ul><li>Inhalation of Conidia </li></ul><ul><li>Primary site of infection RES </li></ul><ul><li>Present with Chills, Fever Malaise Hepato splenomegaly </li></ul><ul><li>Probably AIDS defining infection </li></ul><ul><li>T.V.Rao MD </li></ul>
  77. 77. Laboratory Diagnosis <ul><li>Microscopy </li></ul><ul><li>Tissues, skin Lymph node bone marrow </li></ul><ul><li>Use of special stains </li></ul><ul><li>Culturing on Sabouraud dextrose agar </li></ul><ul><li>Immunoblot methods </li></ul><ul><li>PCR </li></ul><ul><li>T.V.Rao MD </li></ul>
  78. 78. Treatment <ul><li>Some times Amphotericin B may be considered. </li></ul><ul><li>Major Antifungal treatments are speculative </li></ul>
  79. 79. Other Opportunistic Mycoses
  80. 80. Other Opportunistic Fungus <ul><li>Advances in Medicine have resulted in increase in fungal infections </li></ul><ul><li>Devastating systemic infections have been caused by species of </li></ul><ul><li>1. Fusarium </li></ul><ul><li>2 Paecilomyces </li></ul><ul><li>3 Bipolaris </li></ul><ul><li>4 Curvilaria </li></ul><ul><li>5 Alternaria </li></ul>
  81. 81. Created as Educative Material for Graduate Medical Students Dr.T.V.Rao MD Email [email_address]