2Opportunistic organisms Opportunistic organisms are normal resident flora that become pathogenic only when the host's immune defense reduses.In immunosuppressive therapy,In a chronic disease such as diabetes mellitus,During steroid or antibacterial therapy that upsets the balance of bacterial flora in the body.
3Opportunistic Mycosis Opportunistic mycosis is a fungal or fungus-like disease occurring in an animal or human’s with a compromised immune system.Opportunistic fungal infections are:Candidiasis Aspergillosis Cryptococcosis
4CANDIDA SP Candidia can infect skin, mucosa, or internal organs It is as Yeast Like fungusIt is an important cause of opportunistic fungal infection.
5Candida► Candida is found in normal flora,exist in mouth, gastrointestinal tract, vagina, skin in 20 % of normal individuals.►Colonization increases with age,in pregnancy,hospitalization…..►Candida is an important etiological agent presenting as opportunistic infection in Diabetes and HIV patients.
6Morphology and Culturing The shape is ovoid or spherical budding cells and produces pseudo myceliumRoutine cultures are done on Sabouraud's dextrose agar,Grow predominantly in yeast phaseA mixture of yeast cells and pseudo mycelium and true mycelium are seen in vivo and nutritionally poor media.
7Macroscopic and Microscopic appearance of Candida spp
9Candida as Pathogenic fungi Systemic CandidosisOccurs in Patients who carry more yeasts in mouth,and gastrointestinal system,Predisposed with individuals1. On antibiotic or/and steroid therapy2. Immunosupressed3. Recipients with organ transplantation4. Infancy – Old age – Pregnancy5. Diabetes mellitus7. Zink and iron deficiencies
10Pathogenesis and Pathology Mucosal infections occur superficially –Discrete white patches on mucosal surface.Can affect tongueInfants and old persons are affectedIn Immune compromised /AIDS, oral candidois is commonly seenVaginal candidosis causes itching soreness white discharge, white colored lesions,In pregnancy in advanced stage,Majority experience one episode in a life time
11Important species of Candida in human infections C.albicansC.tropicalisC.glabrataC.krusei
14Many cases of AIDS are suspected by observation of oral cavity
15Laboratory Diagnosis Skin scrapings, Mucosal scrapping, Vaginal secretionsCulturing blood and other body fluids,ObservationsMicroscopic observation after Gram staining.Presence of Gram + yeast cells.
16Laboratory Diagnosis Isolation of Candida from various specimens Easier to culture on Sabouraud's dextrose agarSerology, molecular methods,PCR
17CRYPTOCOCCUS NEOFORMANS A capsulated yeast – A true yeast..A sporadic disease in the past.Most common infection in AIDS patients.
19Morphology A true yeast Round 4 – 10 microns Surrounded by Mucopolysaccharide capsule.Thick in vivoNegative staining with India Ink and Nigrosin60% of the infected prove positive by India Ink preparation on examination of CSFKoH preparations in Sputum and other tissues,PAS and Mucicaramine staining helps confirmation.
21CulturingCSF-Culturing on Sabouraud's agar, and incubated at 370 C for upto to 3 weeksCultures appear as creamy, white, yellowbrown colored*Simple urease test helps in confirming the isolate.
22Cryptococcus neoformans Serotypes A true yeast4 serotypes - A,B,C,DA and D - C.neofromans var neoformansB and C - C.neoformans var gatti.Many infections are caused byC.neofromans var neoformans.Found in wild/Domesticated birds.Pigeons carry C.neofromans,Birds do not get infected.
24PathogenesisEnters through lungs by inhalation of “basidiospores” of C.neoformansEnters deep into lungs, pulmonary infections can occur.Men acquires more infections, and women less infected.Self limiting in most cases,Present as discrete nodules - Cryptococcoma.
25Pathogenesis Can infect normal humans Abnormalities of T lymphocyte function aggravates, the clinical manifestations.In AIDS 3-20% develop Cryptococcosis.Present with chronic meningitis , meningo encephalitisManifest with – head ache low grade fever,Visual abnormalities ,Coma – fatalTreatment reduces the morbidity and cure in non immuno supressed expected.
26Clinical manifestation 1.Pulmonary Cryptococcosis2.Central Nervous System Cryptococcosis3.Cutaneous Cryptococcosis4.Cryptococcosis of bone5.Ocular Cryptococcosis6.Other forms (Cryptococcus neoformans is often isolated from urine of patients with disseminated infection. Occasionally, signs of pyelonephritis or prostatitis may be observed. Other rare forms of cryptococcosis include adrenal cortical lesions, endocarditis, hepatitis, sinusitis, and localized oesophageal lesions) .
27Laboratory Diagnosis.CSF Microscopic observation under India Ink preparationDirect microscopy - Gram stainingCultures on Sabouraud dextrose agar,Serological tests for detection of Capsular antigenCSF findings mimic like TuberculosisIN CSF - latex test for detection of AntigenBlood cultures,ELISA
28Avoid contact with Birds TreatmentImmune competent Fluconazole,ItraconazoleImmune DeficientAmphotericin B,FlucytosineAIDS patients are not totally cured , Relapses arefrequent with fatal outcome.Rapid resistance develops with Fluconazole.Avoid contact with Birds
29ASPERGILLUS SPIn nature > 100 species of Aspergillus exist, Few are important as human pathogens1 A.fumigatus2 A.niger3 A.flavus4 A.terreus5 A.nidulans
31Morphology Cultured as Mycelial fungus Separate hyphae with distinctive sporing structuresSpore 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
32Pathogenesis Clinical presentations Allergic Aspergillosis – Atopic individuals, with elevated IgE levels10-20% of Asthmatics react to A.fumigatusAllergic alveoitis follows particularly heavy and repeated exposure to larger number of sporesMaltsters Lung – causes allergic alveolitis, who handle barley on which A.claveus has sporulated during malting process
33PathogenesisAspergilloma – 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 productionHaemoptysis occurs due to invasion of blood vessels
34Pathogenesis Invasive Aspergillosis occurs in immunocompromised host with underlying diseaseNeutropenia is the most common predisposing factorA.fumigatus is the most common infecting speciesIn bone marrow recipients leads to high mortalityFungus invades blood vessels, causes thrombosis septic emboliCan spread to Kidney and heart.
35ZYGOMYCETESThe ilness is called Zygomycosis,also called as Mucor Mycosis or PhycomycosisSaprophytic mould fungiMajor Causative agents of ZygomycosisRhizopusMucorAbsidia
36MorphologyMajority are with broad aseptate mycelium with many number of asexual spores inside a sporangium which develops at the end of the aerial hyphae
37Mucor Microscopy ► Non septate hyphae ►Having branched sporangiophores with sporangium atterminal ends
38Rhizopus Microscopy ► Shows non septate hyphae ► Sporangiophores in groups are above theRhizoids
39Important Clinical Manifestations Rhino cerebral Zygomycosis associate with Diabetus mellitus, leukemia, or lymphomasCauses extensive Cellulitis, and tissue destruction.
40Mucormycosis Cellulitis causes extensive tissue destruction. Spread from nasal mucosa to turbinate bone,paranasal sinuses ,orbit, and brainRapdily fatal if untreated
42Pathology and Pathogenesis Spread from nasal mucosaSpread to turbinate bones,para nasal sinuses , orbit, brainAssociated with uncontrolled diabetes mellitusIn leukemia patients , Lymphoma patients,Leads to fatal outcome,Improved with anti fungal treatment.Spread to lungs disseminated infection,.
43Treatment Early Diagnosis highly essential for effective cure High doses of I V Amphotericin BSurgical interventionsControl of Diabetes a basic requirement for better clinical outcome
44PNEUMOCYSTISIdentified as the most Important opportunistic fungal infection in persons with impaired immune systems & AIDS
45PneumocystisPneumocystis is a genus of unicellular fungi found in the respiratory tracts of many mammals and humans.The organism was first described in 1909 by Chagas and then a few years later by Delanöes, who ultimately named the organism in honor of Dr. Carini after isolating it from infected rats.The name was Pneumocystis carinii
46PneumocystisYears later, Dr. Otto Jirovec and his group isolated the organism from humans, and the organism responsible for P.carinii pneumonia (PCP) was renamed after him and P.carinii change to Pneumocystis jiroveci
47PneumocystisThe taxonomic classification of the Pneumocystis genus was debated for some timeIt was a trypanasome then a protozoan and today it is accepted as a fungus.The organism is found in 3 distinct morphologic stages, as follows:The trophozoite (trophic form), The sporozoite (precystic form)and the cyst, which contains several intracystic bodies
49PathogenesisPneumocystis jiroveci pneumonitis (PCP) is a common opportunistic disease that occurs almost exclusively in persons who have profound immunodeficiency. PCP was and still is the most common life-threatening opportunistic infection occurring in patients with HIV disease.
50Pathogenesis►The portal of entry for P carinii has not been firmly established; however, because the organism has been found only in the lung, inhalation is a likely mode of transmission. ►In most individuals, the organism is dormant and sparsely dispersed in the lung, with no apparent host response (latent infection). ►In susceptible (immunocompromised) hosts, the organism occurs in massive numbers.Pathogenesis
51Clinical manifestation ► Tachypnea and fever are consistent features of the pneumonitis, and diffuse bilateral alveolar disease can be observed by radiography. ► Diagnosis requires the identification of P carinii in pulmonary tissue or lower airway fluids. ► Such specimens may be obtained by lung biopsy, inducement of sputum, bronchoalveolar lavage, or needle aspiration of the lung. ► The Gomori, Giemsa, fluorescence-labelled antibody, or toluidine blue stains may be used to identify the organism.Clinical manifestation
52http://www.doctorfungus.org Pneumocystis carinii Title: EM Image of Pneumocystis cariniiDisease(s): Pneumocystis pneumoniaLegend: An electron micrograph of P. carinii cyst from rat lung tissue.Genus/Species: Pneumocystis cariniiImage Type: Microscopic Morphology
53http://www.doctorfungus.org Pneumocystis carinii Title: Pneumocystis carinii-infectedRat Lung Tissue Disease(s): Pneumocystis pneumoniaLegend: An H&E stain of a rat lung infected with P. carinii. It does not show any organisms, but shows the proteinaceous exudate which results from Pneumocystis infection, and ultimately causes reduced gas exchange.Genus/Species: Pneumocystis cariniiImage Type: Microscopic Morphology
54http://www.doctorfungus.org Pneumocystis carinii Title: Pneumocystis carinii Silver Stain Disease(s): Pneumocystis pneumoniaLegend: A silver stain of P. carinii cysts from rat lung tissue showing the typical 'deflated ball' shape.Genus/Species: Pneumocystis cariniiImage Type: Microscopic Morphology
55http://www.doctorfungus.org Pneumocystis carinii Title: EM Image of Pneumocystis carinii Disease(s): Pneumocystis pneumoniaLegend: An electron micrograph of a P. carinii troph from rat lung tissue, showing its bindingto a type I pneumocyte.Genus/Species: Pneumocystis cariniiImage Type: Microscopic Morphology
56Treatment pentamidine isethionate trimethoprim-sulfamethoxazole Four drugs currently available for therapy ofP carinii pneumonitis are:pentamidine isethionatetrimethoprim-sulfamethoxazoleatovaquonetrimetrevateTrimethoprim-sulfamethoxazole is preferred because of its low toxicity and greater efficacy.
57Pencillium marneffiCauses serious disseminated infection, Papular skin lesions in AIDSCommon in South east Asia
58Morphology A dimorphic fungi Mould at 250 c Yeast at 370c Intracellular yeast like appearance as in HistoplasmosisThe fungi are associated with Bamboo rat