Common Opportunistic Fungi

1. Common Opportunistic Fungi • Candida albicans • Cryptococcus neoformans • Aspergillusfumigatus • Pneumocystisjiroveci • Mucor sp. • Rhizopus sp. • Sporothrixschenkii

2. Mycology of Opportunistic Fungi • Candida albicans • Dimorphic fungus • Classic finding is budding yeast with pseudohyphae (non-septate) • Cryptococcus neoformans • Non-dimorphic yeast • Has a very thick capsule that contains melanin

3. Mycology of Opportunistic Fungi • Aspergillusfumigatus • Septatehyphaethat branch at acute angles • Pneumocystisjiroveci • Yeast that was once thought to be a protozoan due to its troph/cyst lifecycle, lack of cell wall ergosterol, and inability to culture it. • Yeast is disk shaped and can be seen with methenamine silver stain.

4. Mycology of Opportunistic Fungi Rhizopus • Mucor and Rhizopus spp. • Irregular, broad, usually nonseptatehyphae that branch at wide angles. • Sporthrixschenkii • Dimorphic cigar-shaped yeast. • Hyphae are septate and form “Daisy petal” conidia

5. Question A 30 year old patient with advanced HIV infection comes into clinic complaining that food is sticking in the back of his throat and in his chest when he tries to swallow. You look in his mouth and see patches of whitish material on the surface that can easily be removed and leaves a red base. On microscopic examination, a budding yeast with pseudohyphae is observed. The organism most likely to cause this is: A. Cryptococcus neoformansB. Candida albicansC. RhizopusD. Aspergillusfumigatus E. Sporothrixschenkii

6. Question A 30 year old patient with advanced HIV infection comes into clinic complaining that food is sticking in the back of his throat and in his chest when he tries to swallow. You look in his mouth and see patches of whitish material on the surface that can easily be removed and leaves a red base. On microscopic examination, a budding yeast with pseudohyphae is observed. The organism most likely to cause this is: A. Cryptococcus neoformansB. Candida albicansC. RhizopusD. Aspergillusfumigatus E. Sporothrixschenkii

7. Epidemiology C. Albicans Crytococcusneoformans Found Soil Pigeon droppings Distributed around the world Studies show that they grow well in high radiation areas (Chernobyl). Use the radiation for energy • Can be systemic and superficial • Forms • Yeast w/ pseudohyphae at 20C • Germ tube at 37C • Normal gut flora • Infection prevalent in immunocompromised • Located around the world

8. Epidemiology Aspergillusfumigatus Mucor and rhizopus Found in Soil Digestive systems Plant surfaces Rotten veggies • Infection occurs mostly in immunocompromised • Found in • Soil • Decaying matter (compost heaps)

9. Epidemiology Pneumocystisjiroveci Sporothrixschenckii Dimorphic fungus Lives on Vegetation (rose gardener’s disease Found in Plants Decomposing organic matter Transmission Prick causing break in skin • Yeast form • Transmission • inhalation • Infections prevalent in • Immunocompromised • Bone Marrow Transplant

10. Question • A 57 year old male from New York is undergoing heavy chemotherapy.  He is not supposed be in contact with the environment during this short term heavy regimen but decides to go on a walk across a bridge with his wife. His wife comments that it is unfortunate that the bridges have to be covered in spikes to fend off birds.  The man undergoing chemotherapy comes down with a serious case of meningitis a few days later. What is the most likely cause? A. Candida Albicans B. Cryptococcus Neoformans C. Mucor D. Aspergillous

11. Question • A 57 year old male from New York is undergoing heavy chemotherapy.  He is not supposed be in contact with the environment during this short term heavy regimen but decides to go on a walk across a bridge with his wife. His wife comments that it is unfortunate that the bridges have to be covered in spikes to fend off birds.  The man undergoing chemotherapy comes down with a serious case of meningitis a few days later. What is the most likely cause? A. Candida albicans B. Cryptococcus neoformans C. Mucor D. Aspergillous

12. Candida albicans • Opportunistic infection common in immunocompromised patients (neonates, pt on steroid tx, diabetics, and AIDS). • Secretion of aspartylproteinases(Sap proteins)- Family of 10 proteinases • Aspergillusfumigatus • Invasive aspergillosis is common an opportunistic infection. • Allergic reaction leading to bronchospasm esp. in patients with asthma or CF. • Aspergillomas in lungs following TB infections. • Aflatoxinswhich are linked with hepatocellular carcinoma. • -Metabolized by the liver to a reactive epoxide intermediate or hydroxylated to become the less harmful aflatoxin M1. • - leads to hepatic necrosis and cirrhosis Pathogenesis

13. Pathogenesis • Cryptococcus neoformans • Transmitted via aerosol droplets and disseminates in the blood. • Facultative intracellular pathogen common in AIDS patients. • Encapsulated fungi which also uses melanin production to evade the host immune • system. Therefore it is able to elicit a profound immune response which begins to attack the host. • Mucorand Rhizopus spp. • Most common in DKA and leukemia patients. • Fungi proliferates in the blood vessel walls where there is excess ketone and glucose, then • penetrates the cribiform plate and enters the brain. • Once the spores begin to grow, fungal hyphae invade blood vessels, producing tissue • infarction, necrosis, and thrombosis. Neutrophils are the key host defense against these fungi; thus, individuals with neutropenia or neutrophil dysfunction (diabetes, steroid use) are at highest risk.

14. Pathogenesis • Pneumocystisjiroveci • Common in AIDS patients. • Attachment of P. jiroveci to alveolar epithelial cells is associated with proliferation of the organism and impaired lung cell replication, perhaps through secretion of proteolyticenzymes such as chymase or reactive oxygen species. • Sporothrixschenckii • Rose gardeners disease- fungi often introduced traumatically via a stick with a rose thorn. • Sporotrichosis is a subcutaneous infection, and it starts following entry of the infecting fungus through the skin via a minor injury (as in penetration by a rose thorn carrying the fungus) and may affect an otherwise healthy individual. Following entry, the infection may spread via the lymphatic route (nodular lymphangitis may develop). Patients infected with Sporothrixschenckii may be misdiagnosed aspyodermagangrenosum due to the large ulcerations observed during the course of sporotrichosis.

15. Question Patient is a 4 month old female presenting with diffuse rash covering her groin and buttock. Given her age and the distribution of the rash you suspect diaper rash caused by a Candida albicansinfection. What is the pathogenesis of C. albicans? A. Sap proteins B. Asp proteins C. Capsule D. Melanin production E. Aflatoxins

16. Question Patient is a 4 month old female presenting with diffuse rash covering her groin and buttock. Given her age and the distribution of the rash you suspect diaper rash caused by a Candida albicansinfection. What is the pathogenesis of C. albicans? A. Sap proteins B. Asp proteins C. Capsule D. Melanin production E. Aflatoxins

17. Clinical Manifestations • Cryptococcus neoformans • Meningitis, headache, fever • Skin lesions • Candida albicans • Mucosal: thick white adherent plaques • Disseminated: unexplained fever, sepsis or organ dysfunction

18. Clinical Manifestations • Aspergillusfumigatus • Fever, pleuritic chest pain, cough, hemoptysis, dyspnea, sinus and orbit infection • Disseminated: necrotic skin lesions and brain abscess, seizure, stroke • Mucor and Rhizopus spp. • Headache, facial pain, black necrotic eschar on face

19. Clinical Manifestations • Pneumocystisjiroveci • Pneumonia with dyspnea, dry cough, fatigue, and mild or absent fever • Sporothrixschenckii • Local pustule or ulcer • Widespread cutaneous and/or life-threatening visceral infection in immune-compromised patients

20. Question A 62 year old female patient with history of rheumatoid arthritis, diabetes and had a hip replacement 1 month prior presents to your office with a sinus infection for the past week which has progressed to a severe eye infection. You collect samples for gram staining and mycology. A mold is grown with irregular nonseptatehyphae branching at wide angles. What is the causative agent and the recommended treatment? • Aspergillusfumigatusand amphotericin B • Aspergillusfumigatusand trimethoprim-sulfamethoxazole • Penumocystisjiroveciand trimethroprim-sulfamethoxazole • Rhizopus and/or mucor treat with amphotericin B and surgical debridement of infected tissue • Candida albicansand fluconazole

21. Question A 62 year old female patient with history of rheumatoid arthritis, diabetes and had a hip replacement 1 month prior presents to your office with a sinus infection for the past week which has progressed to a severe eye infection. You collect samples for gram staining and mycology. A mold is grown with irregular nonseptatehyphae branching at wide angles. What is the causative agent and the recommended treatment? • Aspergillusfumigatusand amphotericin B • Aspergillusfumigatusand trimethoprim-sulfamethoxazole • Penumocystisjiroveciand trimethroprim-sulfamethoxazole • Rhizopus and/or mucor treat with amphotericin B and surgical debridement of infected tissue • Candida albicansand fluconazole

22. Diagnosis and Treatment Candida albicans • Dx: • Culture shows dimorphic (pseudohyphae and budding yeast) at 20⁰C and Germ tubes at 37 ⁰C • Tx: • Vaginal: topical azole • Oral/esophageal: fluconazole, caspofungin, or swishing and swallowing Nystatin • Systemic: amphotericin B, fluconazole, or caspofungin Aspergillusfunigatus • Dx: • Culture shows acutely branching septate hyphae and condidiophore with fruiting bodies • Tx: • Caspofungin for invasive aspergillosis • Amphotericin B

23. Diagnosis and Treatment continued Cryptococcus neoformans • Dx: • Culture on Sabouraud’’s agar • Unequally budding yeasts (5-10 μm) with wide capsular halos seen on india ink stain. • Latex agglutination for capsular antigen is more specific • “Soap bubble” lesions seen in brain • Tx: • Flucytosine and amphotericin B for systemic infx • Fluconazole for cryptococcal meningitis because it can cross the BBB Mucor and Rhizopus species • Dx: • Mucor shows Irregular, broad, nonseptate hyphae that branch at wide angles. • Tx: • Amphotericin B for systemic infx

24. Diagnosis and Treatment continued Pneumocystis jiroveci • Dx: • CXR shows diffuse, bilateral infiltrates • Lung biopsy or lavage will show disk-shaped yeast with methenamine silver stain • Tx: • TMP-SMX, pentamidine or dapsoneis sulfa-allergic. Sporothrixschenckii • Dx: • Culture shows dimorphic, cigar-shaped budding yeast • Tx: • Iatraconazole or potassium iodide

25. Question • A 36 year old HIV positive male presents to your clinic with fever, headache and photophobia. Physical exam reveals that while supine, passive flexion of the patients neck results in flexion at the hip and the patient is unable to extend their knee when their hip is flexed at 90 degrees. Culture reveals unequally budding yeast with wide halos. • What is the preferred treatment for this patients infection? • A. Nystatin • B. Fluconazole • C. Terbinafine • D. Metronidazole • E. Caspofungin

26. Question • A 36 year old HIV positive male presents to your clinic with fever, headache and photophobia. Physical exam reveals that while supine, passive flexion of the patients neck results in flexion at the hip and the patient is unable to extend their knee when their hip is flexed at 90 degrees. Culture reveals unequally budding yeast with wide halos. • What is the preferred treatment for this patients infection? • A. Nystatin • B. Fluconazole • C. Terbinafine • D. Metronidazole • E. Caspofungin