Opportunistic Mycoses: Pathogenesis & Clinical Presentation PDF

OPPORTUNISTIC MYCOSES DR EMMANUEL O. IREK CONSULTANT MEDICAL MICROBIOLOGIST ABUAD MSH OBJECTIVES Identify the opportunistic mycoses Categorize invasive fungal infections Enumerate management strategies 02/11/2025 2 Why opportunistic mycoses??...

OPPORTUNISTIC MYCOSES DR EMMANUEL O. IREK CONSULTANT MEDICAL MICROBIOLOGIST ABUAD MSH OBJECTIVES Identify the opportunistic mycoses Categorize invasive fungal infections Enumerate management strategies 02/11/2025 2 Why opportunistic mycoses?? They are mycotic agents that thrive on the body’s low immunity from any condition to cause a disease state Numerous Though some can be pathogenic to immunocompetent With rising immunosuppressed patients globally, it becomes imperative to understand these special group that can give a clinical nightmare or dilemma Trouble with diagnosis, resistant bugs and treatment modalities increasing morbidity and mortality due to these……. 02/11/2025 3 Predisposing Conditions Pathogen Conditions associated with: Candida Antibiotic therapy, catheters, diabetes, corticosteroids, immunosuppression Aspergillus Leukemia, Tb, corticosteroids, immunosuppression, IV drug abuse Cryptococcus Diabetes, TB, cancer, corticosteroids, immunosuppression 02/11/2025 4 Zygomycetes Diabetes, cancer, IV therapy,  Opportunistic Infections Disease Causative organisms Incidence Candidiasis Candida spp. Common Cryptococcos Cryptococcus Rare/Common is neoformans Aspergillosis Aspergillus fumigatus Rare/common Zygomycosis Rhizopus, Mucor, (Mucormyco Rhizomucor, Rare sis) Absidia etc. Rare among Pneumocysto 02/11/2025 Pneumocystis jirovecii immunocompete 5 sis  Invasive fungal infections Candida Endogenous (mostly) Aspergillus Exogenous Cryptococcus Zygomycetes Rare filamentous species Histoplasmosis Reactivation Blastomycosis KEYS TO INVASION ARE TISSUE DAMAG Coccidioidomycosis AND PRESENCE IN NORMALLY STERILE Paracoccidioidomycosis SITE 02/11/2025 6 Candidiasis Part of man’s normal flora ( GIT, Vagina, skin) Could also be transmitted sexually and as a nosocomial infection. Today it’s the most important opportunistic systemic mycoses worldwide Fatality is recognised Can infect virtually all organs; Skin, mucosa, or internal organs Colonization increases with age, in pregnancy and with hospitalization Can infect virtually all organs; Skin, mucosa, or internal organs Colonization increases with age, in pregnancy and with hospitalization 02/11/2025 7  Candida Species Candida albicans C. dublinensis C. tropicalis C. krusei C.parapsilosis C.glabrata C.gullermondii C.lusitaniae C.kefyr 02/11/2025 9 Candidiasis – Pathogenesis Pathogenesis: Candida overgrows in colonized sites Invades non colonized sites due to breach in skin and mucosal barriers Dissemination can ensue Occurs when there is loss of normal bacterial microbiota and also when cell mediated immunity and neutrophil function is impaired Candida cells elaborate polysaccharides, proteins, and glycoproteins that not only stimulate host defenses but facilitate the attachment and invasion of host cells Biofilms 02/11/2025 10  Candidiasis- Pathogenesis 2 Invasive Disease Defense mechanisms of the body against candidiasis is by phagocytosis, mostly in polymorphonuclear cells, less in macrophages and T-cells (CD4) Invasive disease usually begins with candidemia Blood borne Candida If compromised, infection spreads and causes focal infection in many organs - kidney, skin, eye, heart, liver, meninges Mortality of candidemia is 30-40%. 02/11/2025 11 Candidiasis- Pathogenesis 3 Chronic mucocutaneous candidiasis (CMC) It is a group of syndromes were there is persistent, severe, and diffuse granulomatous cutaneous candida infections. These infections affect the skin, nails and mucous membranes Most patients with CMC have defects related to cell- mediated immunity, but the defects themselves vary widely Autoimmunity and hypoparathyroidism 02/11/2025 12 Clinical Presentation 1. Oropharyngeal candidiasis: (Oral thrush, glossitis, stomatitis and angular cheilitis) Risk factors??? 2. Cutaneous candidiasis: (intertrigo, diaper candidiasis, paronychia and onychomycosis) Risk factors??? 3. Vulvovaginal candidiasis and balanitis Risk factors??? 4. Candidemia (Candida septicemia) and disseminated candidiasis Risk factors??? Transient vs Continuous 02/11/2025 13 Manifestations of Systemic (Disseminated) Candidiasis Oesophagitis Diarrhoea Bronchopulmonay candidiasis Pyelonephritis Cystitis Endocarditis Myocarditis Endophthalmitis Meningitis Arthritis osteomyelitis Peritonitis 02/11/2025 14 Clinical Manifestation CMC thrush Nappy rash 02/11/2025 15 Diagnosis of Candidiasis Specimens Blood CSF Peritoneal fluid Urine ????? Respiratory secretions Wound effluents Direct microscopy; KOH or calcofluor white Culture on SDA, Chromagar at ??temperature; True hyphae with ???? PCR MALDI-TOF Serology β-(1,3)-D-glucan, 02/11/2025 16 Mannan Candida – Lab diagnosis 02/11/2025 17 Treatment Oral thrush- nystatin, azoles Systemic candidiasis- amphotericin B ± flucytosine, fluconazole, or caspofungin Chronic mucocutaneous candidiasis responds well to oral ketoconazole and other azoles Rx may be lifelong Remove the identified inciting event 02/11/2025 18  Cryptococcosis Phyla Basidiomycota A true yeast Cryptococcus neoformans Occurs worldwide in soil and in bird (pigeon) droppings Cryptococcus gatti –trees Cryptococcus gattii has emerged as a cause of cryptococcal meningitis in immunocompetent hosts. Prominent feature: thick mucopolysaccharide capsule, which causes evasion from phagocytosis; melanin Mortality noted C. neoformans is the leading cause of meningitis with an estimated one million new cases and 600,000 deaths per year 02/11/2025 19 Cryptococcosis – Pathogenesis Cryptococcus is acquired by inhalation of desiccated aerosolized yeast cells or possibly the smaller basidiospores (sexual) Activates neutrophils for phagocytosis on getting to the lungs Inhaled yeast cells in otherwise healthy humans can cause asymptomatic or self limiting pneumonia Neurotropism- CNS Meningoencephalitis May present as discrete nodules in brain - Cryptococcoma 02/11/2025 20 Cryptococcosis Main risk factors are: T-cell deficiency e.g HIV (AIDS patients: 3-20%) Corticosteroid therapy, Organ transplantation Diabetes mellitus Hematological malignancy (30% in patients with CNS lymphomas) 02/11/2025 21  Life cycle of C. neoformans Found in wild/Domesticated birds (Pigeon) and eucalyptus 02/11/2025 22 tree. Pigeons carry C.neoformans, but do not get infected. Cryptococcosis – Clinical manifestation Primary infection in lungs (may mimic TB) Can spread to skin, eye, adrenals, bone and prostate Cryptococcal meningitis is most common disseminated manifestation Chronic meningitis: Differentials brain tumor, brain abscess, degenerative central nervous system disease, or any mycobacterial or other fungal meningitis CSF findings ???? Meningism, headaches, disorientation Cryptococcoma; signs of SOL AIDS 5-8% 02/11/2025 23 Cryptococcosis – Diagnosis Specimens…….? Negative staining with India ink /Nigrosin 60% of infected diagnosed positive by India Ink preparation on examination of CSF Cerebrospinal fluid examination may reveal an increase in lymphocytes, low glucose levels, and elevated protein……..?? Cultures on Sabouraud dextrose agar-mucoid, brownish colonies Serology: detection of Cryptococcal antigen in serum or CSF (CRAG)-90% of cryptococcal meningitis Latex agglutination Enzyme immunoassay Prognostic 02/11/2025 24  Cryptococcosis Treatment Induction Maintenance Consolidation Amphotericin B 5-Flucytosine Fluconazole effective for prevention of recurrence prevention Relapses with fatal outcomes common in AIDS 02/11/2025 25  Aspergillosis Only few of the > 100 species of Aspergillus are important human pathogens Aspergillus spp. are molds (saprophytes), living in soil and on plants Especially abundant during construction and when dust is spread around they have small conidia that are aerosolised Most common species are: A.fumigatus, A.flavus, A.niger, A.terreus, A.nidulans 02/11/2025 26  Aspergillosis – Risk factors Chronic granulomatous disease of childhood (inability to form toxic free radicals after phagocytosis) Haematological malignancies e.g acute leukemia. Bone marrow and organ transplantation(25 – 40%) IV drug abuse HIV/AIDS Diabetes mellitus Tuberculosis COPD Alcoholism Corticosteroid therapy 02/11/2025 27 Aspergillosis - Pathogenesis Disease spectrum is wide Ubiquitous Incubation; between 36 hours to months Spore size, organism growth rate, adherence to host epithelial surfaces and toxin/enzyme production are factors that the organism contributes to disease type and severity Alveolar macrophages in lungs engulf and kill conidia when capable Otherwise germinate, produces hyphae and invades 02/11/2025 28  Aspergillosis – Clinical manifestation 1 Allergic Bronchopulmonary Aspergillosis – Atopic individuals, with elevated IgE levels (10-20% of Asthmatics react to A. fumigatus) Asthma, recurrent chest infiltrates, eosinophilia, and both type I (immediate) and type III (Arthus) skin test hypersensitivity to Aspergillus antigen Aspergilloma – A fungal ball, fungus colonize preexisting cavities from TB, sarcoidosis, emphysema in the lung and form compact ball of mycelium surrounded by dense fibrous wall Asymptomatic Symptomatic- cough, dyspnea, weight loss, fatigue, and hemoptysis. (rarely invasive) 02/11/2025 29 Aspergillosis – Clinical manifestation 2 Invasive Aspergillosis: Aspergillus develop in lung tissue causing invasive infection (spreading through the tissue and involving blood vessels); then spread can occur to other organs gastrointestinal tract, kidney, liver, brain, or other organs, producing abscesses and necrotic lesions chronic necrotizing pulmonary aspergillosis for moderate immunocompetence Non-invasive Aspergillus species may involve the nasal sinuses, the ear canal, the cornea, or the nails 02/11/2025 30 Aspergillosis –Diagnosis Specimens Respiratory secretions Bronchoalveolar lavage Lung biopsy Serum /blood rarely Investigations Direct microscopy; KOH and calcofluor white???? Cultures on SDA at ???? Speciation based on conidial arrangement Histology Serum antigen tests for galactomannan and 1-3 beta – D – glucan Ancillary tests MRI of brain Diagnosis of aspergilloma is radiological (CT scan) 02/11/2025 31 Aspergilloma 02/11/2025 32 02/11/2025 33 Aspergillosis – Treatment Amphotericin B Itraconazole and new triazoles such as posaconazole for Amphotericin resistant species 5 -Flucytosine Steroids for Allergic attacks in ABPA Surgery may be indicated Prevented by avoiding exposure to conidia (abundant in constructions and uncompleted buildings) 02/11/2025 34 Zygomycosis Phylum Glomeromycota Molds found everywhere with high mortality Major agents are Rhizopus, Rhizomucor, Absidia, Mucor Major risk factors: - Diabetic ketoacidosis Haematologic malignancies 3rd degree burns Corticosteroids therapy. Bone marrow transplantation dialysis with the iron chelator deferoxamine 02/11/2025 35  Zygomycosis – Pathogenesis Acquired through inhalation of spores There is impaired phagocytosis by alveolar macrophages and polymorphonuclear leucocytes. Neutrophil dysfunction and accumulation of sugar and acids enable relentless growth of organisms Hyphae invades the walls of blood vessels once a primary infection is established results in the dissemination of mycotic thrombi and the formation of metastatic foci in many organs Invasiveness is appreciated in tissues 02/11/2025 36  Zygomycosis – Clinical presentation 1 A life-threatening form of zygomycosis known as the Rhinocerebral mucormycosis Begins in the paranasal sinuses following inhalation of sporangiospores, may extend to involve the orbit, palate, face, nose, brain Results in septic necroses of tissues of nasopharynx and orbit Pulmonary zygomycosis: Follows inhalation of sporangiospores into the lungs Fever, shortness of breath, cough haemoptysis Direct inoculation of traumatic breaks in the skin and mucous membranes may lead to primary mucocutaneous infection 02/11/2025 37 Rhinocerebral mucormymycosis 02/11/2025 38 Zygomycosis – Diagnosis Specimens: skin scrapings from cutaneous lesions sputum and needle biopsies from pulmonary lesions; nasal discharges, scrapings and aspirates from sinuses in patients with rhinocerebral lesions Biopsy tissue - disseminated disease Direct microscopy : aseptate to pauci-septate hyphae of zygomycetes with KOH Culture: rapidly growing molds Morphology varies among the species. 02/11/2025 39 02/11/2025 40  Zygomycosis Treatment early diagnosis; reversal of underlying predisposing risk factors, if possible; surgical debridement; and prompt antifungal therapy (Amphotericin B, Capsofungins) Prognosis: Very poor 02/11/2025 41 Other Opportunistic Fungal Infections Pneumocystis jiroveci Penicillium marneffei Fusarium Bipolaris Exophiala Scedosporium Sporothrix Wangiella Curvularia Alternaria 02/11/2025 42 Mass spectrometry identification of microorganisms by a mass spectrometric profile of the proteins, largely rRNA proteins, of the organism This is placed into the mass spectrometer, wherein this spot will be activated by a laser The matrix absorbs much of the energy from the laser and converts it into heat. The heat vaporizes the outer portion of the specimen The molecules move through a vacuum space at a different rate based on the mass-to-charge (m/z) ratio, and this “time of flight” is determined by the arrival of the different molecules at the detector A summation of the time of flight for all molecules present will produce a spectrum Best match in database to identify organism 02/11/2025 43 Mass spectometry 02/11/2025 44 RECAP??????? 02/11/2025 45