11 - Fungal disease

Impacts on human and animal health 

  • Social and economic effects (eg. crop pathogens, ringworm) 

  • Deep mycoses added to WHO neglected tropical disease list 

  • Changing due to emergence of new diseases 

  • 1970s onwards chytridiomycosis - greatest disease driven loss of biodiversity ever 

  • 2007 white nose syndrome of bats 

  • Ecosystem effects 



Mycotoxins

  • Natural chemicals produced by fungi that can have adverse effects on the health of animals 

  • Eg. aflatoxins 

  • Affect animal health via plants 

  • Crop losses lead to poor nutrition, starvation 

  • Direct poisoning - potent effects, target organ often liver

  • Various species of fungi involved, in specific conditions (eg. poorly managed fermentation with silage)

  • Feeding spoiled haylage can lead to a range of disease including hypersensitivity, allergic pulmonary disease, kidney, liver damage, CNS alterations, seizures, death 


Mycoses 

  • Superficial mycoses (dermatophytosis) 

  • Eg. ringworm: 

  • Fungal infection of keratinised tissue (skin, nails, fur, hair, claws) 

  • Tinea, Trichophyton, Microsporum 

  • Each species has a preferred host:

  • Geophilic - soil 

  • Anthropophilic - humans 

  • Zoophilic - other animals 

  • Zoonosis 


Dermatophytes 

Growth and sporulation forms 

Cause: ringworm, tinea corporis, capitis, pedis 

  • Parasitic cycle - humans 

  • Saprophytic cycle - in soil 


Microsporum canis

  • Common fungal infection in cats and dogs (zoonotic) 

  • Difficult to manage in multi pet households 

  • Extensive hair loss - due to fungi digesting keratin 

  • Clinical signs - multifocal alopecia, crusting, scaling, pruritus 


Diagnosis: 

  • Tape impression smears 

  • Woods lamp 

  • Culture hair plucks 


Treatment 

  • Topical treatment - antifungal washes, griseofulvin (toxicity) 

  • Environmental decontamination 


Trichophyton mentagrophytes 

  • Guinea pigs 

  • Some genetic variants possess potential of human to human transmission 



Trichophyton verrucosum 

  • In livestock 

  • Economic losses - hide / leather industry 

  • Persistent chronic infection - favours cold dark conditions



Malassezia 

  • 14 species of yeast like fungi 

  • Linked with inciting factors - chronic infection, allergic infections or endocrine disease 

  • Common in skin fold dermatitis 

  • Tape impression smears 










Deep mycoses 

  • Eg. Histoplasmosis, Sporotrichosis, Cryptococcosis 


  • Many ascomycetes are dimorphic - can grow in hyphal or yeast form - depends on the environment 


Candida auris 

  • Causes serious infections 

  • Often resistant to medicines - multiple drug resistance 

  • Complicated treatment - easily misidentified as other Candida species

  • Commonly acquired in hospitals by patients with a weakened immune system



Dimorphism and Histoplasma spp. 



  • Stealth pathogen due to immune evasion (Histoplasma)




Interdependent phases of survival

Host, pathogen, environment 

  • It is a neglected disease impacting on equine health and human livelihoods 



Histoplasma transmission and pathogenesis 

  • In humans - usually in respiratory pneumonia form 

  • Horses - debilitation, lung and ocular disease 



  • Diverse genome 

  • Limited info going in 




Sporothrix schenckii

  • Emerging in South America

  • Zoonotic infection with feline and human infections  

  • Deep cutaneous infection 









Cryptococcus gattii 

  1. Associated with trees or soil around trees 

  • Humans and animals can become infected after inhaling airborne, dehydrated yeast cells or spores

  1. Travel through respiratory tract and enter lungs of the host 

  2. Small size of the yeast and/or spores allows them to become lodged deep in the lung tissue 

  • Environment inside the host signals for C. gattii to transform into its yeast form and then the cells grow trick capsules to protect themselves 

  1. The yeasts then divide and multiply by budding 

  • After infecting the lungs, C. gatti can travel through the bloodstream 

  1. Either on their own or within a macrophage cells - to infect other areas of the body, typically the CNS 



Cryptococcal cell mediated damage to host 


Diagnosis 

→ Halo effect around yeast cell - Indian ink stain of CSF


→ Chocolate coloured colonies on bird seed agar 


→ mucoid colonies on SAB 


  • Cryptococcal antigen lateral flow assay 



Fungal disease treatment and prevention 

  • Vaccine candidates are sparse 

  • Limited number of drugs and toxicity problems 

  • Not suitable for environmental use 

  • Fungal disease usually secondary to underlying disease / immunosusceptibility


  • Diagnostic methods - efficacy varies 

  • Quarantine 

  • Good hygiene and sanitation

  • Management in free-ranging wildlife if different from pets or farm animals 



Antifungal target within fungal cell 

















  • Limited number of antifungal agents

Polyenes - disruption of fungal cell membrane binding to ergosterol 

  • Eg. Amphotericin, nystatin 


Azoles - interrupts enzymatic synthesis of ergosterol 

  • Eg. Fluconazole, Itraconazole, Ketoconazole


Allylamines - inhibit fungal squalene - a key precursor to ergosterol 

  • Eg. Butenafine, terbinafine 


Echinocandins - cell lysis by disrupting fungal cell glucan synthesis resistance to osmotic forces

  • Eg. Caspofungin 




Fungal infections of plants 


Panama disease / banana wilt  

  • Caused by Fusarium oxysporum 

  • Resistant to fungicides 

  • Control is limited to phytosanitary measures 

  • 2010 outbreak of the strain Tropical Race 4 -  threatened the Cavendish banana (most popular cultivar) 

  • Vectors - water, soils residues, replanting of suckers, farming tools and transport, leaf trash 



Wheat blast 

  • Caused by Magnaporthe oryzae 

  • Spreads via infected seeds, crop residues, spores 

  • Common in South America and Asia 














Leaf rust 

  • Caused by Puccinia triticina 

  • Can lead to up to 20% yield loss

  • In temperate zones it is destructive on winter wheat because the pathogen overwinters 

  • Most prevalent of all the wheat rust diseases 






Emerging infectious diseases 


Rapid worldwide mobility 

  • Globalisation 

  • Implications for international disease management 

  • Humans, animals and pathogens move round globalised world 








White nose syndrome of bats 

  • Pseudogymnoascus destructans (geomyces desctructans) 

  • Skin infection of bats 

  • Originated in Eurasia 

  • Identified in USA and Canada in 2006 

  • 5-6 million dead bats 

  • Rapid spread, high mortality, population impact 


Concerns: 

  • Ecosystem services from bats to US agriculture - worth $4-50 billion per year 

  • Bats eat insects 

  • Pollination (chiropterophilous plants)

  • Seed dispersal 



Pseudogymnoascus destructans

  • Previously known as Geomyces destructans 

  • Fungus can also live as saprotroph in soil 

  • So in animal host dies - no problem for fungus 


Clinical signs and effects 

  • Hibernation in mammals correlated with reduced immune response 

  • Susceptibility factor 


  • Bats hibernate for around 6 months each year 

  • Fungus invades skin of hibernating bats 

  • Destroys tissues 

  • Wing tissue crucial for heat dissipation, water regulation, gas exchange, and blood pressure regulation 

  • Bats overheat, use up food reserves too fast 


  • Disrupts hydration and hibernation 

  • Awake during hibernation, starve and die 

  • Bat-to-bat transmission 

  • Bats can recover if moved from hibernation to warm environment, given food and water; wing tissue regenerates 

  • Not practical for typical US bat colonies of 104 to 105 bats 




P. destructans in Europe 

  • Found on bats but no mass mortality 

  • Bats hibernate in smaller groups 

  • Less extreme winters 

  • Adaptation to co-exist with fungus? 



Chytridiomycosis 

  • Frogs and other amphibians 


  • Chytridiomycota 

  • Chytrid fungus 

  • Motile zoospores - lives in water 

  • Batrachochytrium dendrobatidis Bd 

  • Frogs and toads

  • B. salamandrivorans Bsal 

  • Salamanders and newts 

  • Infects keratinised tissue

  • Skin in adults; limited effects on tadpoles 

  • Regions affected: Australia, the Caribbean and North, Central and South America. Also present in Africa and Europe 


Ecological emergency

  • Food chain birds / mammals 

  • Key predator of mosquitoes therefore impacts on burden of dengue / malaria 


Clinical signs and effects 

  • Fungus invades the skin 

  • Problems with respiration and regulation of body hydration 



Chytridiomycosis life cycle 






Transmission 

  • Worldwide through trade in amphibians 

  • Pharmaceutical industry - toads for pregnancy testing

  • Food 

  • Pets 

  • Spread since 1930s

  • Original source probably South Africa (Xenopus laevis)

  • Also possible pathogen hypervirulence evolved through recombination of previously isolated populations 

  • Research in Institute of Integrative Biology into how it spreads within sites in Spain