Marine Mammal Mycology Flashcards
Causative agent of lacaziosis
Lacazia loboi (causes lobomycosis in humans) (F8, Path)
The prevalence of mycotic infections in marine mammals is changing.
What changes are occuring?
What are some thoughts on why this is occuring?
Current Status of Fungal Infections in Marine Mammals
· Survey: 63% human care, 37% stranded; Mucorales cases has tripled and Asper cases have dropped; majority of cases were animals in human care in semitropical and tropical regions
o Why more mucor? Unknown, maybe genetics, location, construction, use of stronger abx, overuse of glucocorticoids
· Clinicians believe Candida is on the rise but is diagnosed on cytology or culture and not always associated w/ inflammation but treated frequenctly but mucor cases more mortality and more accurately reflected in medical records
o Lots of GI Candida cases in stranded marine mammals (seals, porpoises)
· Rise in cryptococcal and coccidioidal infections in marine mammals of PNW
Theories to Explain the Change in Incidence of Fungal Infections
· Human care: genetics, oxidants like ozone/chlorine, exposure to soil particles (construction), use of broad spec abx, corticosteroids, cyclosporine, social/environmental stresses
· Free-ranging: immunosuppressive viruses (i.e. morbillivirus, herpesvirus), pollutants, starvation, high parasitic load
· Question of immunocompetency
· Hygiene theory
What makes fungal pathogens so virulent?
Identify some of the virulant traits of the following fungal pathogens:
Aspergillus
Cryptococcus neoformans
Candida
Virulence and Pathogenicity
o Ability to grow at 37C and adapt to host environment (i.e. dimorphic fungi)
Most common ambient isolates grow in 20-30C range
o Aspergillus - Production of proteolytic enzymes and toxins that enhance tissue invasion; sequester iron to promote hyphal growth and viability
o Cryptococcus neoformans – antiphagocytic, downregulates cell and humoral immune reponses; intracellular and extracellular; phenoloxidase/melanin synthesis w/ presence of capsule => opportunistic; produces laccase which interferes w/ oxidation by phagocytes
o Candida – normal flora of humans and animals; responsible for infections from superficial sites; forms biofilms…nosocomial
o Sterol regulatory element binding proteins (SREBPs) – help tolerate hypoxic environments in host tissues and demonstrate antifungal resistance
How are fungal infections transmitted to marine mammals?
What fungal pathogens cause epidemics in marine mammals?
What are the dermatophytes that affect marine mammals?
Modes of Transmission
o Many are ubiquitous in environment
o Some are normal microbiota of most mammals in pathogenic forms (i.e. Cryptococcus neoformans in feces)
o Inhalation, trauma, ingestion settle into lungs, skin, alimentary tract
o Candida spp – normal resident of mucous membranes; gains entry when barrier compromised
o Poorly communicable between animals – rarely cause epidemics
Except
· Blastomyces dermatitidis in bottlenose dolphins
· Paracoccidioidomycosis ceti (previously L. loboi) in an Amazon river dolphin
· Dermatophytes in pinnipeds
o Dermatologic fungal infections in marine mammals: Microsporum canis, Sporothrix schencki, Trichophyton sp, Trchosporon pullulans, Epidermophyton floccusum (manatee)
What are the two most devastating filamentous fungal infections in marine mammals?
How are these acquired? Why are cetaceans predisposed?
What yeasts are common pathogens of marine mammals?
The Opportunistic Fungi
- Most devastating filamentous:
- Mucormycosis (Mucorales): entry of zygospores by inhalation or through wound or intestinal tract breaches
- Aspergillosis: inhalation of conidia into lungs allergic, necrotizing, mycelial masses, invasive dz
- Normal immune system – shouldn’t be harmful to inhale
- Cetaceans lack turbinates (principal filtering mechanism of airborne particles in all other mammals) fungal conidia and spores are able to more easily gain access to lower pulmonary system
- Immunosuppressed or stressed –> more likely to get systemic infection
- Fungi can remain dormant so previous infection increases risk as well
o Other filamentous:
- Fusarium, dematiaceous, other Mucorales (Mucor, Rhizopus, Rhizomucor, Cunninghamella, Lichtheimia, Saksenaea, Apophysomyces)
- Poor prognosis response to antifungals
- Mucormycosis less common than aspergillosis suggests that they possess fewer and/or milder virulence factors
- Common sites of infection: wounds, brain, respiratory
- Increase in incidence of mucormycosis with increased use of voriconazole
o Yeasts:
- Candida spp most common (C. albivans and non-albicans Canida [NACs])
- Major contributory factor is use of antibiotics and antifungals
- C. glabrata and C. tropicalis
- Innate resistance to older generation azoles and echinocandins – leaving voriconazole and posaconazole as main choices of tx
- Cryptococcus neoformans and C. gattii
- More common in humans, less so in marine mammals
- Rise in stranded mms in PNW
- Inhalation lungs, LNs
How do the dimorphic fungi affect marine mammals?
What are their geographic ranges?
The Dimorphic (Endemic) Fungi
o Histoplasmosis, coccioidomycosis, blastomycosis
o Can infect any mammals including those w/ healthy immune systems
o Mold in soil, transform into yeasts or endospores in respiratory tract
o Geographic distribution
o Granulomatous disease
o Histoplasmosis (Histoplasma capsulatum)
Requires high nitrogen containing soils
US, Caribbean, Central and South America, Mid East, Asia
Endemic to chicken coops, caves
Inhale spores changes to yeast in lungs phagocytized by macrophages disseminate hematogenously
Latent disease
Rarely appear sick
Mimcs TB
o Coccioidomycosis (Coccidioides immitis or posadasii)
Inhalation of dust containing arthrospores
Dimorphic (endospores and spherules in tissue; mycelial in culture)
SW USA?
o Blastomycosis (Blastomyces dermatitidis)
Mold in soil inhalation, body temp yeast in lungs
Likes organis debris and humidity
Mid-Atlantic, Carolinas, Mississippi River valley, Africa, Arabian Peninsula, Indian subcontinent
Likes bone and kidney
Describe the clinical signs of fungal infections in marine mammals.
What are your fungal differentials for the following conditions:
Multifocal white crusts on the skin of cetaceans
Acute death of cetaceans
Oral-esophageal white plaques
Ring lesions on pinniped fur
Clinical Manifestations
· Nonspecific, any tissue, origin sometimes unknown
· Characteristic presentations:
o Paracoccidioidomycosis ceti (formerly lobomycosis) caused by P. brasiliensis
Multifocal white crusts involving large areas of skin in bottlenose dolphins
o CNS mycoses (Asper, Mucor) acute death
o Oral-esophageal candidiasis white, raised to red circular lesions in oral cavity (esp tongue) and esophagus
o Dermatophytes in pinnipeds ring lesions in fur, nail lesions; overall superficial
Describe the clinical features of fungal infections.
What diagnostic may be useful?
Describe the morphology of fungal organisms and how it can be useful in identifying disease in marine mamamls.
How can you confirm efficacy and prevent toxicity with antifungal drugs?
· Often indistinguishable from bacterial or viral infection
· Later stages of mucormycosis once it reaches tissues muscle and liver specific enzymes escalate due to tissue infarction
· Allergic bronchopulmonary asper or endemic fungal infections chronic granulomatous disease (leukocytosis, monocytosis, eosinophilia, hyperproteinemia with hypergammaglobulinemia)
o Can see eosinophils in routine blowhole cytology
· Cultures – limited use due to possible contamination from air
· More convincing if:
o Presence of hyphae in association w/ inflammation on respiratory cytology
o Ability of isolate to grow at 37C on culture
o Presence of inflammatory blood profile
· Serology may help but demonstration of invasiveness requires ID of fungal elements in clinical specimen
o Bronchoscopy/ BAL, Biopsy (submit histo and culture)
o PCR
o Ultrasound, CT, radiographs as well
· Candida in blowhole, stomach or stool may be confusing but if there is budding yeast, hyphae or pseudohyphae, or inflammation – the fungus may be a colonizer
· Comparing inflammatory cell to epithelial cell number
· Positive culture + hyphae on cytology + inflammation = considered diagnostic
· Mucorales do not produce yeast phase in respiratory speciments unlike dimorphic pathogens
· Morphology of hyphae is most important in examining clinical specimens:
o Mucorales wide angle branching ribbonlike (nonseptate or poorly septate) hyphae
o A. fumigatus septate hyphae
o Candida true hyphae or pseudohyphae and blastoconidia
o (LOOK FOR PICS IN TERIO)
· Confirmation: biopsy, fungal culture
· Antifungal susceptibility testing; repeat throughout treatments (usually very long term)
· Measure blood levels of antifungal drugs
What is the mechanism of azole antifungals?
What side effects are common?
Fluconazole is useful for which organism in cetaceans?
What about itraconazole?
What about voriconazole? Is it contraindicated in any particular fungal infection?
What is the standard therapy for mucormycosis in dolphins?
What is the mechanism of echinocandins?
What are the risks of polyenes and when should they be considered?
What is teh mechanism of terbinafine? What particular fungal organisms would it be useful for?
Specific Therapies
· Azoles
o Imidazoles – 2 nitrogen atoms w/in five member ring
o Triazoles – 3 nitrogen atoms
o Target ergosterol biosynthesis pathway and trigger formation of toxic byproducts that may be lethal to fungi
o All raise host blood hepatic transaminases that reverse when discontinued
o Often administered with liver protectors which stabilize hepatocyte membrane (i.e. silymarin)
o Fluconazole (Diflucan)
Candida krusei is resistant; other candida resistance is increasing
o Itraconazole (Sporanox)
Wider spectrum than fluconazole
Active against yeast and molds except fusarium and scedosporium spp
Hepatic transaminases and GI upset
o Voriconazole (Vfend)
Similar spectrum to itra but extens to several emerging molds including some Fusarium and Scedosporium spp; except Lomentospora prolificans
Preferred treatment for invasive aspergillos but can be quite hepatotoxic
Contraindicated with Mucorales
o Posaconazole (Noxafil) and isavuconazole
Activity against yeasts and molds including Asper spp and Mucorales
Drug of choice for treatming mucormycosis in bottlenose dolphins
Delayed release tablet
· Flucytosine (Acntoil)
o Active against Candida, Cryptococcus, some filamentous fungi
o GI side effects, hepatotoxicity, bone marrow suppression
· Echinocandins
o Newer, synthetic derivatives of lipopeptides produced by fungi
o Inhibit 1-3BD glucan synthase which is critical for production of 1-3BC flucan (important for cell wall integrity
Leads to cell lysis
o Less toxicity
o Synergistic with other antifungals
o Spectrum: Candida and Asper spp
· Polyenes
o Amphotericin B, Ambisome, Nystatin
o Considered standard therapy esp for invasive asper and mucor
o Nephrotoxicity
Liposomal formulation by be safer
o Amphotericin B can be nebulized
Seems to be tolerated and somewhat effective in marine mammals
o Nystatin relatively safe
· Terbinafine (Lamisil)
o Squalene expoxidase inhibitor highly hydrophobic, accumulates in hair, skin, nails, fatty tissue
o Treats onychomycosis
o Broad spectrum
o Treats range of cutaneous and SQ mycoses such as sporothrix, eumycetoma, chromoblastomycosis
· Combination therapies
o Azoles plus terbinafine show promise for treatment of patients w/ asper, mucorales, fusarium, resistant candida
o Triazole and polyene combos may be antagonistic (in vitro and some animal models)
