Opportunistic Fungal Infections

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