Fungi Pt. 1

Mycoses

fungal infections difficult to diagnose and treat because

• Signs often missed and misinterpreted

• Resistant to antifungal agents

• Un-reported → information on occurrence and spread lacking

Fungi and spores

almost everywhere → majority experience mycosis at some point

Mycosis treatment a

acquired via inhalation, trauma, ingestion, typically not contagious

Dermatophytes 

skin, exception to mycosis being contagious 

Mycosis epidemics

due to mass exposure to env. source of fungi

Fungal meningitis

contaminated steroids, many symptoms

Mycoses

caused by presence in the body of either true pathogens or opportunists

Toxicoses

acquired through ingestion

Ex: if poisonous mushrooms are eaten 

Allergies 

most often result from inhalation of fungal spores 

True pathogens

ability to attack and invade tissues

True pathogens dimorphism 

change between unpathogenic and pathogenic, switch based on env. changes 

True pathogens yeast form 

usually replicative form 

True pathogens hyphal form

filamentous, associated with infection

Opportunistic

usually not pathogenic but given opportunity can cause infection

Often commensal: take advantage of a weakness in host’s defense

EX: dermatophytes often occur in individual’s susceptible to opportunistic fungi

infection can be difficult to diagnose

Factors that predispose individuals to opportunistic mycoses

Medical procedures: surgery, resources go to healing

Medical therapies: immunosuppressive therapies, weaken immune system

Preexisting conditions: inherited immune defects, weakened immune system  

Lifestyle factors: poor diet and hygiene, inc risk of chronic diseases 

Mycoses diagnosis

patient history

definitive diagnosis 

Definitive diagnosis 

requires isolation, lab culture, morphological analysis → medium has to favor fungal growth over bacterial growth

Immunological tests not useful 

prevalence of fungi in environment makes it hard to distinguish between infection and simple exposure, false-positives due to existing antibodies 

Antifungal therapies

often target fungi cell wall

Mycoses difficult to heal

fungi often resist oxidative damage of T cells during cell-mediated immune response

Biochemistry is similar to human cells (eukaryotes)→ antifungal drug can harm human tissue

Ergosterol

fungi version of cholesterol→ cell membrane fluidity, often drug target, needed for membrane stability

Azole drugs

blocks biosynthesis of ergosterol

EX: capsofungin, flurocytosin 

low dose → fine, high dose → affects human cholesterol 

Echinocandins

disrupt function of the (1→3)- Beta-D glycan synthase complex (involved in cell wall synthesis)

Amphotericin B

gold standard

forms aggregates in cell membrane with ergosterol → pores cause leakage of cellular contents 

5-FC

Used ini combination with other 3 drugs 

disrupts RNA (via 5-FUTP) and DNA (via 5-FdUMP) synthesis 

looks like cytosine, fungi can’t tell the difference → incorporate into genome → poison themselves 

Systemic mycoses

infections spread throughout body, acquired through inhalation

Systemic mycoses pulmonary infection

initially disseminates via blood to rest of the body

Systemic mycoses causes

¼ pathogenic, dimorphic fungi of the devision Ascomycota: Blastomyces, Coccidioides, Histoplasma, Paracoccidioides

Blastomycosis

causative agent is Blastomycosis dermatitides, mold with actual hyphae

Blastomycosis endemic

Southwestern U.S.

Blastomycosis transmission

found in soils rich in organic matter, inhalation of fungal spores, budding yeast enter blood stream → colonize organs

Blastomycosis manifestations

pulmonary blastomycosis most common

Blastomycosis treatment

amphotericin B

Pulmonary blastomycosis symptoms 

initial pulmonary lesions, asymptomatic 

when develop, often vague

Pulmonary blastomycosis complications

disease resolves in most, can become chronic

Secondary blastomycoses signs/symptoms

cutaneous, osteroarticular

Secondary blastomycoses complications

AIDS patients may develop meningitis

Coccidioidomycosis

causative agent is coccidioides immitis, mold, arthoconidia (spores), exclusively in Southerwestern U.S. 

Coccidioidomycosis transmission 

found in desert soils, rodent burrows, archaeological remains, mines, inhalation of arthospores (asexual spores), spherules filled with endospores rupture and spread

Coccidioidomycosis arthospores

asexual, germinate in lung and produces more spores which are release into surrounding tissue

Coccidioidomycosis signs/symptoms

few or no symptoms

Coccidioidomycosis complications

can develop into severe or chronic pulmonary disease

secondary infections in immunocompromised individuals 

Coccidioidomycosis treatment 

in health individuals resolve and require no treatment 

amphotericin B preferred 

Histoplasmosis

causative agent is histoplasma capsulatum, most common fungal pathogen affect humans, found mostly in eastern U.S. also Asia and Africa, likes high nitrogen env, mold with aerial hyphae 

Histoplasmosis transmission 

found in most soils with increased level of nitrogen from bird droppings, inhalation of macro and micro canidia (spores), budding yeast phagocytosed → blood stream 

Histoplasmosis pathogenesis

attacks alveolar macrophages → dispersed beyond lungs via blood and lymph

Histoplasmosis complications

clinical about ¼ disease: chronic pulmonary histoplasmosis, chronic cutaneous histoplasmosis, systemic histoplasmosis, ocular histoplasmosis

Histoplasmosis signs/symptoms

most are asymptomatic

Histoplasmosis treatment

in healthy individuals can resolve require no treatment

Amphotericin preferred