1. Opportunistic Fungal Infections
The Fungi
Opportunistic Fungal Infections

2. Cryptococcus neoformans: cryptococcosis
Source: soil, especially mixed with pigeon droppings and nesting sites; window ledge, air conditioners, barns
Inhalation is route of infection
Many cases asymptomatic; not all cases in immunocompromised patients

3. Saprobic and Parasitic cycle of Cryptococcus neoformans

4. C. neoformans Disease or Elimination

5. Cryptococcosis: Disease Forms
Pulmonary: scant, blood-tinged sputum, cryptococcoma on X ray. May heal, remain stable, or disseminate. Often incidental finding at autopsy
Disseminated primarily in patients with e.g., malignant neoplasms, organ transplants, AIDS
Meningitis: often presenting sign: headache, diplopia, vertigo, nausea, vomiting; may have granulomas or lesions in CNS

6. Cryptococcosis: Pathology
Organism has mucopolysaccharide capsule; lesions mucoid.
May see macrophages, giant cells with ingested yeast, plasma cells, small lymphocytes, but usually not granulomas
In brain gray matter, see multiple organisms with no inflammatory response

7. Pulmonary Cryptococcosis

8. Small Lesion of Cutaneous Cryptococcosis

9. Cryptococcal Meningitis MRI: Subarachnoidal Lesions

10. Cryptococcus neoformans Meningitis (A. DIC, B. anti-Melanine IF, C
Cryptococcus neoformans Meningitis (A. DIC, B. anti-Melanine IF, C. HE staining)

11. Encapsulated Yeast of Cryptococcus neoformans (India ink)

12. Cryptococcosis: Diagnosis
Morphology: 3-6 X 5-10 mm budding yeast cells with capsule; variable size common
Capsule stains in tissue with mucicarmine, yeast with PAS, GMS
Culture CSF, sputum; yeast grows rapidly
India ink prep for CSF now outmoded
Detection of soluble capsular antigen by latex agglutination in CSF or serum is standard

13. Scanning EM of Replicating Cryptococcus neoformans and its Melanine Ghost

14. Cryptococcus neoformans Melanine as a Virulence Factor

15. Aspergillus spp.: aspergillosis
A. fumigatus, A. flavus most common species in infection
Source: organic debris
Infection by inhalation of conidia

16. Asexual Fruiting Structure of Aspergillus Species in Culture

17. Aspergillosis: Disease Forms-I
Primarily 3 types:
---Allergic: allergic bronchopulmonary aspergillosis; organism grows in bronchi, mucous membranes red, congested. Patient has immediate and delayed hypersensitivity, eosinophilia, IgG and IgE antibodies
---Aspergilloma (fungus ball): severe bouts hemoptysis, IgG and IgE antibodies

18. Aspergillosis: Upper Right Lobe Cavity with Fungal Ball

19. Aspergilloma in Apex of Lung at Autopsy

20. Aspergillosis: Disease Forms-II
Invasive: immunocompromised patients; e.g. leukemia, lymphomas, renal transplant, AIDS; necrotizing pneumonia, organisms invade blood vessels causing thrombosis; emboli break off, distributed throughout body organs, rapidly fatal

21. Cutaneous Aspergillosis (in a patient with acute leukemia and marked neutropenia)

22. Aspergillosis: MRI Brain Scan (allogeneic bone marrow transplant recipient with severe graft-versus-host disease and steroid-induced diabetes mellitus)

23. Aspergillosis: Pathology and Diagnosis
Hyphae invade bronchial walls, parenchyma; cause acute, necrotizing purulent pneumonia
Morphologic: hyphae of uniform size, 3 to 4 mm with dichotomous branching (45o); stain with GMS, PAS, H&E. Also KOH, calcofluor
Culture: observe characteristic fruiting bodies
Serology: difficult to interpret; antigenemia assays under development

24. Branching Septate Hyphae of Aspergillus fumigatus in Tissue

25. Aspergillus Aflatoxin
Aflatoxin, produced by A. flavus is a crop contaminant
Aflatoxin is carcinogenic; hepatocellular carcinoma in animals consuming contaminated feeds
No evidence this is a virulence factor in humans

26. Candida albicans: Candidiasis
Source: unlike other fungal infections, source is endogenous; organism lives in human g.i. tract, vaginal tract, on skin
Primarily an opportunistic infection following e.g., antibacterial antibiotics, indwelling catheters, immunosuppressive conditions, especially AIDS; burns

27. Human Candidasis

28. Incidence of Candida Fungemia at Barnes Hospital (1978 - 1990)

29. Budding Candida Yeast Cells and Pseudohyphae in Sputum

30. Candidiasis: Disease Forms
Superficial: referred to as thrush in oropharyngeal, cutaneous, vulvovaginal disease; also produces onychomycosis, keratitis, conjunctivitis
“Deep” local infections: esophagitis, urinary tract infection, g.i. candidiasis
Hematogenously disseminated: bloodstream, phlebitis, endocarditis, meningitis, endophthalmitis, osteomyelitis

31. Candidiasis: Oral Thrush over the Tongue

32. Severe Candida Esophagitis at Autopsy

33. Extension of Candida Vaginitis onto the Perineum

34. General Cutaneous Candidiasis

35. Candida Paronychia and Onychomycosis

36. Generalized Candidiasis Spinal, Liver-Kidney-Spleen, Endophthalmitis, Blood

37. Candida granuloma

38. Candidiasis: Pathology
Presence of pseudohyphae indicative of invasive disease
Most typical lesion is suppuration with central necrosis and many neutrophils
Vascular invasion not marked
In neutropenic patients may see only necrosis and edema

39. Candida Biofilm Fomation on Catheter Surface

40. Candidiasis: Diagnosis
See budding yeast cells (4-6 X 6-10 mm) and pseudohyphae in clinical material
Stain unevenly with Gram stain; use GMS stain for tissue
Blood culture best for invasive disease; among most common blood isolates now
Can do species identification biochemically; germ tube test for C. albicans

41. Candida spp. and disease

42. Zygomycosis: Source and Disease
Source: inhalation of airborne spores of a variety of fungi; occasionally direct skin inoculation
Disease: Rhinocerebral (patients in metabolic acidosis); pulmonary and disseminated (primarily diabetics, leukemia, lymphoma)
Cutaneous, subcutaneous uncommon in U.S.

43. Zygomycosis: Pathology
Inflammatory reaction with abscesses, suppurative necrosis, blood vessel invasion.
See broad, hyaline, usually aseptate hyphae in tissue

44. Zygomycosis: Diagnosis
Hyphae in tissue branch randomly, irregular diameters, mm in diameter; use KOH, PAS, GMS
Culture: representative specimens; colonies grow well, identify by spores, spore-bearing structures
Serology: none available

45. Zygomycosis (Coenocytic hyphae stained with Gomori methenamine silver)

46. Pneumocystis jirovecii (carinii)
Once thought to be a protozoan; rRNA shows is more closely related to fungi
Found worldwide; person-to-person transmission?; most persons infected asymptomatically as children as shown by serologic evidence
Disease occurs in debilitated, malnourished, immunocompromised patients

47. Pneumocystis jirovecii Life Cycle

48. Pneumocystis jirovecii
Leading cause of morbidity and mortality in patients with AIDS
Clinically: fever, shortness of breath, cough, cyanosis; extrapulmonary spread to lymph nodes, bone marrow, spleen, liver in AIDS
Pathology: alveoli filled with “foamy” contents; organism as cysts with 2-8 sporozoites, which can exit and form new cysts

49. Bilateral Infiltrates of Pneumocystis jirovecii Pneumonia

50. Pneumocystis jirovecii Pneumonia- Frothy Alveolar Exsudate

51. Pneumocystis jirovecii (Gomori methenamine silver-stained lung biopsy)

52. HIV Infections & Pneumocystis jirovecii Pneumonia- Hemorrhagic Spleen Abscess

53. Pneumocystis jirovecii
Diagnosis: examine sputum, BAL; see cysts in tissues with GMS stain, also fluorescent monoclonal antibody available
Therapy: patients with AIDS receive long-term prophylactic therapy with trimethoprim-sulfamethoxazole (antibacterial antibiotic); also used for therapy along with newer drugs