Opportunistic mycoses

1. Opportunistic mycoses Dr. Pendru Raghunath Reddy

2. Opportunistic mycoses Occurrs in human’s with a compromised immune system Causative agents 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

3. Candida species Cryptococcus neoformans Aspergillus species Zygomycosis (Rhizopus, mucor , absidia ) Penicillium species Fusarium species Alternaria species *** ANY fungus found in nature may give rise to opportunistic mycoses *** Causative agents

4. Aspergillosis Aspergillus species are ubiquitous saprophytes in nature In nature >300 species of Aspergillus exist, few are important as human pathogens 1 A.fumigatus 2 A.niger 3 A.flavus 4 A.terreus 5 A.nidulans

5. Pathogenesis This mold produces abundant small conidia that are easily aerosolized Following inhalation of these conidia, atopic individuals often develop severe allergic reactions to the conidial antigens In immunocompromised patients, the conidia may germinate to produce hyphae that invade the lungs and other tissues

6. Fungal spores enters through respiratory tract

7. The Aspergillus species can cause a variety of clinical syndromes Pulmonary aspergillosis Allergic asthma Bronchopulmonary aspergillosis Aspergilloma 2. Invasive aspergillosis 3. Superficial infections

8. Allergic asthma In some atopic individuals, development of IgE antibodies to the surface antigens of Aspergillus conidia elicits an immediate asthmatic reaction upon subsequent exposure Bronchopulmonary aspergillosis The conidia germinate and hyphae colonize the bronchial tree without invading the lung parenchyma The condition is made worse by the development of hypersensitivity to the fungus

9. Aspergilloma 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 Cases of aspergilloma rarely become invasive

10. Invasive aspergillosis In invasive aspergillosis , the fungus first causes pneumonia, actively invades the lung tissue and disseminates to involve other organs, for example, the brain, kidneys or heart This form occurs in severly immuno compromised individuals who have a serious underlying illness Neutropenia is the most common predisposing factor and A. fumigatus is the species most frequently involved

11. Superficial infections Sinusitis Mycotic keratitis Otomycosis

12. Laboratory diagnosis Specimens Sputum, other respiratory specimens, lung biopsy specimens Microscopic examination KOH mount The fungus appears as non-pigmented septate mycelium, 3-5 µm in diameter with chatracteristic dichotomous branching and an irregular outline Rarely the characteristic sporing heads of Aspergillus species are present

13. Culture Aspergillus species grow readily on SDA without cycloheximide at 25-37 C Colonies appear after 1-2 days of incubation Species are identified according to the morphology of their conidial structures Skin tests Skin tests with Aspergillus species antigen are useful for the diagnosis of allergic broncho pulmonary aspergillosis

14. Treatment Invasive aspergillosis is treated with intravenous amphotericin B In recent years, intravenous formulations of azoles, such as voriconazole , are being evaluated

15. Zygomycosis Also called as Mucormycosis , Phycomycosis It is an invasive disease caused by zygomycetes , principally by the species of Rhizopus , Mucor , Rhizomucor , Absidia These fungi are ubiquitous theromtolerant saprophyte; spores are present in air and dust The conditions that place patients at risk include acidosis, leukemias , lymphoma, corticosteroid treatment, severe burns, immunodeficiencies

16. Clinical manifestations There are a number of different clinical varieties of mucormycosis Rhinocerebral Mucormycosis Thoracic Mucormycosis Other sites of invasion

17. Rhinocerebral Mucormycosis Results from germination of the sporangiospores in the nasal passages and invasion of the hyphae into the blood vessels, causing thrombosis, infarction and necrosis The disease can progress rapidly with invasion of the sinuses, eyes, cranial bones and brain Blood vessels and nerves are damaged, and patients develop edema of the involved facial area, a bloody nasal exudate , and orbital cellulitis It is almost invariably associated with acute diabetes mellitus or with debilitating diseases such as leukemia or lymphoma

18. Thoracic Mucormycosis This follows inhalation of the sporangiospores with invasion of the lung parenchyma and vasculature In both locations, ischemic necrosis causes massive tissue destruction Other sites of invasion Primary cutaneous infections such as skin infections following burns or surgery have also been reported Subcutaneous zygomycosis cases are also reported

19. Laboratory diagnosis Secimens Nasal discharge, sputum and biopsy specimens Microscopy KOH mount, may reveal the characteristic broad, aseptate , branched mycelium and sometimes distorted hyphae They are seen much more clearly when stained with methenamine -silver stain The hyphae of these fungi do not stain with PAS

20. Broad, aspetate hyphae in tissue sections

21. Culture The fungi are readily isolated on SDA with antibiotics without cycloheximide , producing abundant cottony colonies Identification of the species is based on the sporangial structures

22. Mucor

23. Treatment Intravenous amphotericin B combined, where appropriate with surgical drainage

24. Penicillosis There are more than 150 species; most important species Penicillium marneffei Penicillium marneffei – thermally dimorphic fungi Penicillium species are saprophytes; present in the environment and grow on various substrates such as bread, jam, fruit and cheese

25. Pathogenesis and clinical features P. marneffei has been reported to be an important opportunistic pathogen in the HIV infected It causes disseminated infection with multiple organ involvement

26. Laboratory diagnosis The yeast are small, oval, 2-4 µm in diameter The mycelia form produces red diffusible pigment and morphologically resembles other members of the Penicillium species Penicillum species possess septate hyphae with branched conidiophores, with two rows of sterigmata bearing chains of rows; the appearance is like a brush or broom

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28. Dimorphic chaterization of Pencillium marneffei

29. Mycelial growth of P. marneffei Microscopic examination

30. Treatment Penicillosis can be treated with amphotericin B and followed by oral itraconazole