Fungal Infections

Opportunistic Fungal Infections Dr.T.V.Rao MD 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 Common Opportunistic Fungus  We find the highest frequency of opportunistic fungal infections come in the following order: 1.Candidiasis 2.Aspergillosis 3.Cryptococcosis Candida as Opportunistic Infection 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. 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 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. Macroscopic and Microscopic appearance of Candida spp Pseudohypal structures in Candida 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. 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 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 Predisposition after Surgery and Therapeutic Approaches  Post operative Immuno Supression  Use of IV catheters  Use of cytotoxinc drugs and cortosteriods  Use of Urinary Catheters Important species of Candida in Human infections     C.albicans C.tropicalis C.glabrata C.Krusei Prominent Infections with Candida Oral Thrush produced by Candia albicans Many cases of AIDS are suspected by observation of Oral Cavity Laboratory Diagnosis  Skin scrapings,  Mucosal scrapping,  Vaginal secretions  Culturing Blood and other body fluids,  Observations Microscopic observation after Gram staining. Gram + yeast cells. Laboratory Diagnosis  Isolation of Candida from various specimens confers diagnosis  Serology  Molecular Methods Microscopy  Gram staining – A rapid method  KoH preparation  Methylamine silver staining 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 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. Emerging Methods for detection of Candida Infections  Molecular Methods  PCR Cryptococcosis. Cryptococcus neoformans  A Capsulated yeast – A true yeast..  A sporadic disease in the past.  Most common infection in AIDS patients. Structure of C.neoformans 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. As Seen in India Ink preparation Culturing  CSF -Culturing on Sabouraud's agar, and incubated at 370 c for upto to 3 weeks  Cultures appear as Creamy, white, yellow Brown colored Simple urease test helps in confirming the isolate. 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. Pigeons and Red river gum tress harbors the Cryptococcus in nature Life cycle of C.neofromans 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 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.    Pathogenesis  Can manifest with involvement of ,Skin, mucosa,organs,Bones,and as Disseminated form. Can mimic like Tuberculosis, 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 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 ASPERGILLOSIS 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 Fungal spores enters through respiratory tract 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 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 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 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. 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 Zygomycosis 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 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 Mucor  Microscopy Non septate hyphae Having branched sporangiophores with sporangium at terminal ends T.V.Rao MD Rhizopus  Microscopy Shows non septate hyphae Sporangiophores in groups they are above the Rhizoids Important Clinical Manifestations  Rhino cerebral Zygomycosis associate with Diabetus mellitus, leukemia, or lymphomas  Causes extensive Cellulitis, and tissue destruction. T.V.Rao MD Mucormycosis  Cellulitis causes extensive tissue destruction.  Spread from Nasal mucosa to turbinate bone,paranasal sinuses ,orbit, and Brain  Rapdily fatal if untreated Other Manifestations  Severe immuno compromised may manifest as primary cutaneous lesions  Rarely infects Burns patients  But lesions can be less severe than Brain lesions Laboratory Diagnosis  Histopathology more reliable than culturing  A certain Diagnosis needs Biopsy  Nasal discharges Sputum, rarely contain many fungal elements Histological sections  Contain non septate hyphae in thromboses vessels or sinuses surrounded by leukocytes or giant cells T.V.Rao MD 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 Culturing  Always depend on clinical history and presentation for certain diagnosis  Cultured on Sabouraud's dextrose agar. T.V.Rao MD 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,. 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 PNEUMOCYSTOSIS Identified as most Important opportunistic fungal infection in the Era of AIDS 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 Species  Pneumocystis carnii found in rats  Pneumocystis jiroveci in human species 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, 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 Life cycle of P.Jiroveci 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 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 Diagnosis  Culturing yet not possible  Direct Fluorescent method with Monoclonal's a rapid and emerging method  Serology – For epidemiological purpose only to establish prevalence of Infection. 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. Treatment  Acute cases are treated with Trimethoprim-Sulphamehoxazole  Pentamidine, Isothionate are very effective compounds Prophylaxis  Treating with TMP-SMZ  Aerolized Pentamidine is effective and locally reaches higher concentration in the lungs. Pencillium marneffi Causes serious disseminated infection, Papular skin lesions in AIDS Common in South east Asia Morphology  A dimorphic fungi  Mould at 250 c  Yeast at 370c  Intracellular yeast like appearance as in Histoplasmosis  The fungi are associated with Bamboo rat Typical microscopic appearance of P.marneffi Dimorphic chaterization of Pencillum marneffi 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 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 Treatment  Some times Amphotericin B may be considered.  Major Antifungal treatments are speculative 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 Created for Benefit of Medical and Paramedical Students in the Developing World Dr.T.V.Rao MD Email doctortvrao@gmail.com