Opportunistic Fungal Infections atf.pdfnn

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1. Opportunistic Fungal
Infections
Jason Ryan, MD, MPHAfraTafreeh.com

2. Fungal Infections
•Pneumonia
•Only in specific geographic areas
•Histoplasmosis, Blastomycosis, Coccidioidomycosis
•Skin
•Tinea versicolor, tinea pedis, sporothrix
•Opportunistic
•Candida, Aspergillus, Cryptococcus, Mucormycosis,
PneumocystisAfraTafreeh.com

3. Candida Albicans
•Normal flora of mouth, intestine, skin, vagina
•Common contaminant of sputum culture
•Overgrowth disease
•Oral thrush
•Esophagitis
•Vulvovaginitis
•Diaper rash
•Disseminated disease
•Endocarditis
•Disseminated candidiasisAfraTafreeh.com

4. Candida Albicans
•Dimorphic
•Forms pseudohyphae
•Elongated, budding yeast cells
•Forms germ tubes (“germ tube test”)
•Yeast with hyphae growing out
•Differentiates candida
Images courtesy of Y Tambe/Wikipedia
Germ TubesAfraTafreeh.com

5. Pseudohyphae
Images courtesy of Y Tambe/WikipediaAfraTafreeh.com

6. Candida
Overgrowth Diseases
•Oral thrush
•Inhaled steroid patients (asthma)
•Esophagitis
•HIV/AIDS patients
•White pseudomembrane on EGD
•Vulvovaginitis
•“Yeast infection”
•Itching, discharge (“cottage cheese” appearance)
•Women taking antibiotics at risk (decreased normal flora)
•Diaper rash
•Beefy, red plaques with satellite papules
James Heilman, MD/WikipediaAfraTafreeh.com

7. Candida
Systemic Diseases
•Endocarditis (rare)
•Almost always IV drug user
•Candidemia
•From blood can spread to any organ systemAfraTafreeh.com

8. Candidemia
•Immunosuppressed patients
•Neutropenic patients from chemo
•Patients in the ICU
•Central lines
•Total parenteral nutrition (TPN)/Hyperalimentation
•IV drug usersAfraTafreeh.com

9. Candida
Treatment
•Vaginal disease/diaper rash
•Topical azole
•Oral thrush
•Nystatin “swish and swallow”
•Fluconazole
•Esophagitis
•Fluconazole
•Resistant cases: voriconazole, caspofungin
•Candidemia/endocarditis
•Fluconazole (stable, not immunocompromised)
•Caspofunginor Amphotericin BAfraTafreeh.com

10. Chronic mucocutaneous
candidiasis
•Rare disorder
•Mutations in autoimmune regulator (AIRE) genes
•T-cell dysfunction
•T cells fail to react to candida antigens
•Chronic skin, mucous membrane candida infections
•Child with recurrent thrush, diaper rashAfraTafreeh.com

11. Candida Immunity
•T-cells important for mucosal defense
•Example: HIV patients often get thrush (↓CD4)
•Neutrophils important for systemic defense
•HIV patients rarely get candidemia
•No candidemiain CMC
•Chemo patients at risk for candidemia(neutropenia)
PirofskiL, CasadevallA; Rethinking T cell immunity in oropharyngeal candidiasis
J. Exp. Med. Vol. 206 No. 2 269-273AfraTafreeh.com

12. Aspergillus
•Aspergillusspecies ubiquitous in nature
•A. fumigatus,A. flavus, andA. terreus
•Inhalation of spores (conidia) common
•Disease requires immunocompromise
•Usually chemo, stem cell transplantAfraTafreeh.com

13. Aspergillus
•Catalase positive
•Common infection in chronic granulomatous disease
•Monomorphic fungi
•Do not forms yeast cells
•Forms “branching septate hyphae”
•V shaped branches
•Visible septae
•Tips of some hyphae grow spores (conidiophore)AfraTafreeh.com

14. Aspergillus
Image courtesy of CDC/Public Domain
Image courtesy of Wikipedia/Public Domain
Image courtesy of KGH/WikipediaAfraTafreeh.com

15. Aspergillus Disease
•Aspergillosis
•Lung disease that can progress to systemic illness
•Neutropenic patients
•Allergic bronchopulmonary aspergillosis
•Allergic reaction in CF/Asthma patients
•Aspergilloma
•Fungus invades pre-formed cavities (TB)
•Hepatocellular carcinoma
•AflatoxinsAfraTafreeh.com

16. Aspergillosis
•Severe lung disease
•Classic case:
•Neutropenic patient
•Fever, cough
•Pleuritic chest pain
•Hemoptysis
•Multiple nodules/densities/infiltrates on imaging
•Can disseminate to any organ
•Heart (endocarditis); Brain (abscesses; mycotic aneurysms)
•Treatment:
•Voriconazole, Caspofungin, or Amphotericin B AfraTafreeh.com

17. ABPA
Allergic bronchopulmonary aspergillosis
•Hypersensitivity (allergic) reaction to aspergillus
•Type I (IgE)
•Type III
•Lungs become colonized with Aspergillus
•Occurs predominantly in asthma and CF patients
•ABPA patients:
•Increases Th2 CD4+ cells
•Synthesis interleukins (IL-4, IL-5)
•Eosinophilia
•IgE antibody productionAfraTafreeh.com

18. ABPA
Allergic bronchopulmonary aspergillosis
•Classic case
•Asthma or CF patient
•Recurrent episodes cough, fever, malaise
•Brownish mucus plugs, hemoptysis
•Peripheral blood eosinophilia
•High IgE level
•Diagnosis: Skin testing aspergillosis
•Treatment: Steroids AfraTafreeh.com

19. Aspergilloma
•Fungus ball
•Caused by Aspergillus fumigatus
•Grows in pre-formed cavities
•Pulmonary TB is most common association
•Often asymptomatic
•Can cause hemoptysis
•Diagnosis: Imaging plus sputum culture
•Treatment: Observation vs. surgeryAfraTafreeh.com

20. Hepatocellular Carcinoma
•Aflatoxin produced by aspergillus
•Can contaminate corn, soybeans, and peanuts
•High rates of dietary intake associated with HCC
•Industrialized countries screen for aflatoxin
•Exposure from:
•Food from non-industrialized countries
•Locally grown foodsAfraTafreeh.com

21. Cryptococcus Neoformans
•Exists only as yeast
•Thick capsule
•Main disease is meningitis
•HIV/AIDS
•Immunocompromised (Chemo, post-transplant)
•Present in soil and pigeon droppings
•Inhaled →lungs →blood stream →meninges
•Rarely can cause pneumonia
•Rarely can spread to other tissuesAfraTafreeh.com

22. Cryptococcus Neoformans
•Can be cultured on Sabouraud's agar
•India ink staining shows capsules as “halos”
•Latex agglutination test
•Detects polysaccharide capsular antigen
India Ink stain shows yeast with “halos”
Image courtesy of Crisco 1492AfraTafreeh.com

23. Cryptococcal Meningitis
•Indolent symptoms over weeks
•Fever, headache
•Can cause ↑ICP
•Risk of herniation with LP
•Must do CT or MRI
•Treatment:
•Amphotericin B +/-Flucytosine
•Fluconazole
•Sometimes intrathecal therapy usedAfraTafreeh.com

24. Mucormycosis
•Rare fungal infection of nose, eyes, brain
•Caused by Rhizopus sp. and Mucor sp.
•Fungi have enzyme: ketone reductase
•Thrive in high glucose, ketoacidosis conditions
•Serum from DKA patients stimulates growth
•Risk factors:
•Diabetes, especially DKA
•Treatment with steroids
•Leukemia
•Stem cell transplant patientsAfraTafreeh.com

25. Mucormycosis
•Disease from inhaled spores
•Enters nose or alveoli
•Angioinvasive fungus: Invades vessel walls
•Classically starts in sinuses
•Spreads to adjacent structuresAfraTafreeh.com

26. Mucormycosis
Clinical features
•Severe sinusitis
•Fever, discharge, congestion, sinus pain
•Necrosis of the palate
•Erythema/cyanosis of skin over sinuses
•Black eschars
•Orbital pain/swelling
•Facial numbness (cranial nerve damage)
•Cavernous sinus thrombosisAfraTafreeh.com

27. Mucormycosis
Clinical features
•Classic case:
•Patient with DKA
•Fever, headache, eye pain
•Diagnosis: mucosal biopsy
•Treatment:
•Surgical debridement
•Amphotericin BAfraTafreeh.com

28. Mucormycosis
•Broad hyphae
•Irregularly branched, rare septations
•Different fromAspergillus:
•Narrow, regular (v-shaped) branching, many septations
Image courtesy of Yale Rose/FlickrAfraTafreeh.com

29. PCP
Pneumocystis jirovecii
•Causes diffuse interstitial pneumonia
•Requires immunocompromise
•Classically HIV
•AIDS-defining illness
•Yeast →inhaled
•Usually no symptoms if immune system intact
•CXR will show diffuse, bilateral interstitial infiltratesAfraTafreeh.com

30. PCP
Pneumocystis jirovecii
•Diagnosed by microscopy
•Sputum sample, BAL, or biopsy
•Sent for staining or fluorescent antibody testing
•Staining required to visualize →cannot be cultured
•Special stains used
•Silver stains often used
Image courtesy of Yale Rosen/Wikipedia
CDC (Dr. Francis Chandler)/Public DomainAfraTafreeh.com

31. PCP
Pneumocystis jirovecii
•Treatments
•TMP-SMX (first line)
•Dapsone
•Pentamidine
•Prophylaxis
•TMP-SMX when CD4 <200cells/microL
•High dose steroid or other immunosuppressed patientsAfraTafreeh.com