Opportunistic Fungi

1. Opportunistic Fungi KaterynaKiselova Catherine Qualls John Schmeelk Charanjeet Singh

2. Aspergillus Epidemiology: endemic and opportunistic, found ubiquitously in soil and decomposing matter Allergic bronchopulmonaryaspergillosisin asthma and CF patients Aspergillomas in the lung cavities especially after TB infection Some species of aspergillusproduce aflatoxins, which are associated with hepatocellular carcinoma Invasive or disseminated disease in immunocompromisedpatients especially in the lungs. Branching of the septatehyphae branch at about 45 degrees or less

3. Allergic Brocho-pulmonary Aspergillosis • From spores floating in the air • Some persons develop an asthma type reaction (Type one hypersensitivity IgE mediated) • They can also manifest a type 4 hypersensitivity (delayed type cell mediated allergic reaction) • Tx corticosteroids

4. Aspergillomas • Persons with lung cavitations from TB or malignancy can grow an ‘aspergillus fungal ball’. It can be about the size of a golf ball • Tx these require surgical removal

5. Aflatoxin • Mycotoxins • The toxin produced by aspergillus is specifically an aflatoxin • This has a worldwide significance since aspergillus grows ubiquitously contaminating peanuts, grains, and rice • NB: half the cancers south of the Sahara are liver cancers and 40% of screened foods contain aflatoxin

6. The immunocompromised host • Who’s immunocompromised • Chemo pts. (neutropenic) • Pts. on high dose steroids for prevention of graft verus host • End stage AIDS pts • CD4 counts below 50 cells/microL • The problem with invasive aspergillosis • Insidious onset (usually at an advanced state when discovered) • Often asymptomatic or with low grade fever • Commonly assoc with a pneumococcal infection • Characterized by multiple nodular infiltrates on chest CT • High mortality rate • Tx aggressive regimen: voriconazole, amphotericin B, and caspofungin

7. Mucor/Rhizopus • Epidemiology: found in the soil, plant surfaces, rotten vegetables • Disease mostly seen in ketoacidotic diabetics and leukemic patients. • Mucormycosis • Fungi proliferate in the blood vessel walls when there is excess ketone and glucose, penetrate cribiform plate entering the brain • Leading to Rhinocerebral and frontal lobe abscess • Patient presents with headache, facial pain, black necrotic eschar on face, and may have cranial nerve involvement • There is also a pulmonary mucormycosis • TxAmphotericin B and surgery

8. Candida albicans • Systemic or superficial fungal infection • Yeast with pseudohyphae in culture 20 degrees C. • Normal flora of nasopharynx, skin, vagina

9. Clinical manifestations • Oral and esophageal thrush in immunocompromised(neonates, steroids, diabetes, AIDS) • Vulvovaginitis (high pH, diabetes, use of antibiotics) • Diaper rash • Endocarditis in IV drug users • Disseminated candidiasis (to any organ) • Chronic mucocutaneouscandidiasis

10. Diagnosis • Germ tube formation at 37 degrees C is diagnostic

11. Treatment • Nystatin for superficial infections • Amphotericin B for serious infections • Azoles (fuconazole, Ketoconazole, miconazole, itraconazole, voriconazole)

12. Cryptococcus Neoformans

13. Cryptococcus neoformans • Heavily encapsulated yeast • Found in soil and pigeon droppings • Most cases occur in immunocompromised persons ( 10% of AIDS patients develop cryptococcosis) • Route of transmission: - following inhalation spreads via the blood to the BRAIN!!

14. Cryptococcus neoformans Causes: • Meningitis : headache, nausea, confusion, staggering gait and cranial nerve deficit • Skin ulcers • Pneumonia • Bone lesions

15. Cryptococcus Neoformans • Diagnosis: • Stain CSF with India ink • Culture on Sabouraud’s agar • Latex agglutination test detects polysaccharide capsular antigen

16. Cryptococcus neoformans • Treatment: • Cryptococcal meningitis in AIDS patients - Amphoterecin B • Flucytosine for 2 weeks followed by fluconazole for 8 weeks to bring CD4+ counts up to at least 100 • Immunocompetent patients: fluconazole

17. Pneumocystisjiroveci • Causes diffuse interstitial pneumonia • PCP • Yeast (originally classified as a protozoan) • Inhaled

18. Pneumocystisjiroveci • Diagnosis • Diffuse, bilateral CXR appearance • Dx. with lung biopsy or lavage • Disk-shaped yeast form on methenamine silver stain of lung tissue • Treatment • TMP-SMX, pentamidine, dapsone • Start prophylaxis when CD4 <200 in HIV pt. • TMP-SMX (Bactrim, Co-trimoxazole)

19. Sporothrixschenckii • Dimorphic, cigar-shaped budding yeast that lives on vegetation • “Rose gardener’s disease” – traumatically introduced into skin, typically by thorn

20. Sporothrixschenkii • Signs and symptoms • Local pustule or ulcer with nodules along draining lymphatics (ascending lymphangitis) • Little systemic illness • Treatment • Itraconazole or potassium iodide • “Plant a rose in the pot”

21. Question 1 A 45-year old woman is admitted to the hospital with an unremitting sore throat. She has undergone radical mastectomy for breast carcinoma and recently underwent adjuvant chemotherapy. Two weeks before, she received a seven-day course of amoxicillin-clavulanic acid for a recurrent urinary tract infection. Examination of her palate reveals several patches of white, creamy, curd like friable lesions on the tongue and other mucosal surfaces.  All of the following therapies would be effective for this infection EXCEPT: A. ketoconazole B. oral fluconazole C. topical nystatin D. oral griseofulvin E. clotrimazole

22. Question 2 A bird enthusiast, who also happens to have AIDS, is fascinated by a great number of pigeons he sees in a park. As he is taking pictures of these magnificent birds he finds it difficult to avoid stepping into pigeon droppings. Several days later, he presents with headache and vomitting. India ink stain of his CSF reveals yeast cells with a surrounding halo. What is the most appropriate treatment for this patient ? A. TMP- SMX B. Amphoterecin B and flucytosine C. Cefazolin D. Rifampin E. Nystatin

23. Question 3 A 64 year old female presents to your office complaining of “sores on her hand.” A picture of her lesion can be seen below. Upon further questioning, you discover your patient is an avid gardener and recently won first prize at the local gardening club for her spectacular roses. The patient exhibits no systemic symptoms of disease. Culture of the organism reveals dimorphic, cigar-shaped budding yeast. What drug should you prescribe to your patient to treat her condition? • TMP-SMX • Topical NSAIDs • Topical bacitracin • Itraconazole • Ceftriaxone

24. Question 4 A 35 year old male, previously diagnosed with HIV comes to your office. He has been non-compliant with his anti-retroviral medications and, as a result, his CD4 count has dropped to 100/cmm. Because his CD4 count has dropped below 200, you start him on a prophylactic antibiotic to prevent pneumonia caused by an opportunistic fungi. This fungi, which was previously classified as a protozoan, causes diffuse interstitial pneumonia in immunocompromised patients. What antibiotic did you prescribe this patient? • Amphotericin B • TMP-SMX • Vancomycin • Penicillin G • Rifampin

25. Question 5 • Which hypersensitivity is/are associated with Allergic broncho-pulmonary aspergillosis? • A. Type I • B. Type II • C. Type III • D. Type IV • E. Type I and potentially Type IV

26. Question 6 • The aflatoxin associated with Aspergillus is thought to be linked to which cancer? • A. thyroid • B. brain • C. colon • D. Liver • E. esophagus