Microbiology- Fungal Diseases Flashcards
Describe the classification of fungi
Kingdom Fungi are part of the eukaryotic crown group.
An independent group of organisms equal in rank to that of
plants and animals
Describe the close relationship between fungi and humans
They are sister taxa
Describe the importance of fungi
Fungi are intrinsic to the function of the planet: Food- Source of protein Antimicrobials- ability to cure disease Recycling- break down wood for termites Forest Survival Symbiosis with algae.
Describe fungi as foes
Amphibian extinction- worse infectious disease in terms of impact on biodiversity.
Bat extinctions- white nose syndrome
Forest loss- chestnut extinction in North America
Crop failures and famine
Human Disease
Describe the Ophiocordyceps
unilateralis
aka ‘zombie fungus’
use ants as vehicle to climb higher up the plant- spores burst out ant- infect more ants.
How many fungal species are there
150,000 described species in Kingdom Fungi,
estimated 1-5 million
(~5% described)
Describe the daily assault of fungi that we experience
Every breath we take is loaded with fungal spores.
What are the two main classes of pathogenic fungi
ASCOMYCOTA (mould)
Basidiomycota (mushrooms)
Describe some of the pathogenic fungi that belong to the classification of ascomycota
Aspergillus fumigatus
Invasive pulmonary aspergillosis
Candida albicans
Blood-stream infections
Describe some of the pathogenic fungi that belong to the classification of basidiomycota
Cryptococcus neoformans
Cryptococcus gattii
Cryptococcal meningitis- large killer in immunocompromised patients
Pulmonary cryptococcosis
What is a key characteristic of most fungal pathogens
Most fungal infections are opportunistic and are aquired from
the patients environment.
“The molds form a part of the class of parasites which are ready to take possession of our organism whenever it presents a vulnerable point or a point of weak resisting power”
What do fungi particularly like
Fungi do well in diverse nutritive sources- like humans. However, as fungi have been around for billions of years, our immune systems have evolved to protect us from fungal disease (macrophages ingest spores from air). If the barrier is broken and they can grow at 37 degrees Celsius, then they will cause disease.
Describe the extent and issue of spore dispersal in the air
air samples may contain up to 200k/m3 and dispersed over large distances; commensal organisms and skin colonisers transmitted by contact
How do we sample and analyse aerolised fungi
Puchet’s aeroscope
Describe how fungi digest their food
Fungi secret hydrolytic enzymes which can break
down biopolymers to be absorbed for nutrition
Fungi do not require stomachs to
accomplish digestion!
Fungi live suspended in their own food source
Fungi are saprophytic.
Describe the relative ease of transmission of fungi amongst humans
Commensal organisms &
skin colonisers
transmitted by contact.
Touch is a key vector for fungi.
Describe the different types of diseases caused by fungi
allergies, mycotoxicoses and mycoses (superficial, cutaneous or systemic)
Which of these fungal diseases is the most serious
Mycoses
Superficial- may dig in- cutaneous- may go further into bodies and organs- systemic- hard to clear- need fast diagnosis for appropriate treatment.
Describe how fungal pathogens may cause allergies
Fungal spores are among the most numerous and diversified airborne micro-organisms that we breathe/contact. Lungs may become sensitised to the spores- producing a hypersensitive reaction.
Describe some common fungal allergies
Inhalation of/contact with fungal spores may induce a wide range of allergic diseases:
Rhinitis
Dermatitis
Asthma
Allergic broncho-pulmonary aspergillosis (ABPA) caused by Aspergillus fumigatus (found in compost).
Describe the severity of ABPA
ABPA occurs in 2.5% of asthmatics; a burden of ~900,000 in Europe, ~5 million worldwide,
What is meant by mycotoxicosis
A toxic reaction caused by ingestion or inhalation of a mycotoxin
What are mycotoxins
Mycotoxins are secondary metabolites of moulds that exert toxic
effects on animals and humans
Describe the symptoms of mycotoxicosis
Breathing problems, dizziness, severe vomiting, diahorrea, dehydration,
Hepatic and renal failure 6 days later
What is the therapy for mycotoxicosis
Gastric lavage and charcoal, liver transplant
What is the purpose of these secondary metabolites for the fungi
For protection from predation (snails) or bacteria.
Describe the effects of Psilocybin
(Psilocybe
semilanceata)
Typical symptoms include visual distortions of color, depth and form,
progressing to visual hallucinations. The effects are similar to the
experience following consumption of LSD, although milder.
Potential drug for those who are clinically depressed and are not responding to standard treatment.
What is Aflatoxin
Aflatoxin produced by Aspergillus flavus
is amongst the most carcinogenic natural
compound known.
Contaminates grain pre- and post-harvest.
Majority of cases in Africa and SE Asia.
Aflatoxin causes 28% (172,000 cases per year) of the worldwide burden of
hepatocellular carcinoma. People with liver damage caused by hepatitis B virus
are particularly at risk
How can we reduce the incidence of aflatoxin poisoning
Improve storage of harvest products (corn , peanuts)- dry storage areas.
What distinguished allergies and mycotoxicosis from mycosis
In allergies and mycotoxicosis- the fungi does not colonise us.
How do we classify mycoses
Mycoses are classified by the level of tissue affected: Superficial Cutaneous Subcutaneous Systemic
Describe the characteristics of superficial mycoses
Superficial cosmetic fungal infections
of the skin or hair shaft
No living tissue is invaded and there
is no cellular response from the host
No other symptoms- except change in pigmentation of the skin.
List some superficial mycoses infections
INFECTION CAUSATIVE ORGANISM
Black piedra (Piedraia hortae) White piedra (Trichosporon beigelii) Dandruff (Malassezia globosa) Tinea nigra (Phaeoannellomyces werneckii)
Describe Malassezia globose (dandruff)
produces oleic acid which causes inflammation of the stratum corneum & ‘dandruff
What is the use of selenium sulphide
Antifungal effect- useful for dandruff and treatment of superficial mycoses.
Describe the cutaneous mycoses (dermatophytes)
Dermatophytes, or keratinophilic fungi.
Produce extracellular enzymes (keratinases) which are capable of hydrolyzing keratin.
Inflammation is caused by host response to metabolic
by-products
Live in the dead, horny layer of hair, skin and nails.
Describe some cutaneous mycoses
Tinea capitis (head/neck) Tinea pedis (feet = athletes foot) Tinea corporis (body) Tinea cruris (groin = jock itch) Tinea unguium (finger/toenails)
Fungi like warm/moist areas.
Describe tinea capitis
Superficial fungal infection of the skin of the scalp, eyebrows, and eyelashes, with a propensity for attacking hair shafts and follicles
The most common paediatric dermatophyte infection
~25% of children in schools over Africa; >200 million children affected
globally
Disfiguring, affects childrens self esteem and time at school
Several synonyms are used, including ringworm of the scalp and tinea tonsurans. In the United States and other regions of the world, the incidence of tinea capitis is increasing.
brake on childhood development- miss school- easily treated BUT in some areas, the treatment simply is not accessible.
Describe the impact of athlete’s foot
Trichophyton rubrum the world’s most prevalent dermatophyte
70% of the population will be infected with tinea pedis at some time
Describe tinea corporis
Tinea corporis Trichophyton sp. ‘ring worm’ Cutaneous mycoses treated with antifungal creams (miconazole / clotrimazole) or orally (griseofulvin.
Describe the characteristics of tinea corporis
These are superficial cosmetic fungal infections of the skin or hair shaft. No living tissue is invaded and there is no cellular response from the host. Essentially no pathological changes are elicited. These infections are often so innocuous that patients are often unaware of their condition. The superficial (cutaneous) mycoses are usually confined to the outer layers of skin, hair, and nails, and do not invade living tissues. The fungi are called dermatophytes. Dermatophytes, or more properly, keratinophilic fungi, produce extracellular enzymes (keratinases) which are capable of hydrolyzing keratin.
any keratinised or external mucosal surface
What is meant by subcutaneous mycoses
Chronic, localized infections of the skin and
subcutaneous tissue following traumatic
implantation of the aetilogic agent
List some examples of subcutaneous mycoses
Sporotrichosis (Sporothrix)
Chromoblastomycosis (several sp.)
Mycetoma (several sp.)
Describe mycetoma
Mycetoma is a chronic infection of the skin, subcutaneous tissue and sometimes bone characterised by discharging sinuses filled with organisms. It is generally found on the foot where it is given the name watering can foot.
Mycetoma may be due to several fungi (when it is called eumycetoma) or actinomycetes (actinomycetoma). Actinomycetes are bacteria producing filaments like fungi. Both the fungi and the actinomycetes are found in soil and plant material in tropical regions.
The organism is inoculated into the skin by a minor injury, for example, a cut with a thorn when barefoot. It is not endemic in New Zealand but mycetoma is occasionally diagnosed in native Pacific Islanders.
Disfigurations similar to leprosy- dust is also a vector.
Describe Sporotrichosis
Ongoing epidemic of cat-transmitted
Sporotrichosis in Brazil- cat-scratches.
What may mycoses effect
Superficial, cutaneous and subcutaneous affect the skin or mucous membranes and systemic (or deep)
How many fungi can cause systemic mycoses
Around 200
Describe the fungi that can cause systemic mycoses
Caused by primary pathogenic and opportunistic pathogens
The primary pathogens have relatively well-defined geographic ranges; the opportunistic fungi are ubiquitous.
They are dimorphic- in their natural habitat (the soil)- they grow as mycelia and release spores into the air. these spores are inhales by humans and at 37 degrees Celsius they grow as yeast cells.
Aerosolised from soil, bird droppings or vegetation.
List the primary pathogens
Coccidioides immitis
Histoplasma capsulatum
Blastomyces dermatiditis
Paracoccidioides brasiliensis
List the opportunistic pathogens
Cryptococcus neoformans Candida Aspergillus Penicillium marneffei The zygomycetes Trichosporon beigelii Fusarium
Describe the impact of fungal diseases
More people die from the top 10 fungal diseases than do
from Malaria or TB
How many pathogenic candida species are there
> 100 identified Candida species
Five species predominate as pathogens
How may candida species colonise humans and the hospital environment
Colonise humans:
(20-25%) oral colonisation of healthy subjects
Gastrointestinal tract
Respiratory tract
Vagina
Urethra
Skin
Fingernails
Hospital environment:
Floors
Food
Hands
Describe candida auris
very resistant to disinfectants and dangerous infection
Describe the characteristics of candida albicans
Opportunistic commensals
In healthy individuals:
Candida is an opportunistic commensal. Virtually all of us carry it in our gastrointestinal and genitourinary tracts – to lesser extent on our skin. (oral thrush, vaginitis, diaper rash)
When immune systems are weak ( for example during cancer chemotherapy, HIV infection or in neonates) or when the competing flora are eliminated (following antibiotic treatment) C. albicans colonises and invades the tissues of the human body (superficial, mucosal, systemic)- (esophagitis, candidisasis- disseminated all over body).
Candidiasis can range from superficial disorders such as diaper rash to invasive, rapidly fatal infections in immunocompromised hosts
Describe superficial candida infections
Involvement may be localized to the mouth, throat, skin, scalp, vagina, fingers, nails, bronchi, lungs, or the gastrointestinal tract
In healthy individuals, Candida infections are usually due to impaired epithelial barrier functions and occur in all age groups, but are most common in the newborn and the elderly. They usually remain superficial and respond readily to treatment.
Cutaneous candidiasis involves infection of the skin with candida. It may involve almost any skin surface on the body, but usually occurs in warm, moist, creased areas (such as armpits and groins). Nappy rash is most commonly due to Candida albicans. Cutaneous candidiasis is fairly common.
Antibiotics and oral contraceptives increase the risk of cutaneous candidiasis. Candida can also cause infections of the nail, referred to as onychomycosis, and infections around the corners of the mouth, called angular cheilitis.
Describe mucosal candida infections
Candida spp. are part of the normal mouth flora in 25-50% of healthy individuals [1650]. Such carriage is referred to as asymptomatic colonization.
OPC, on the other hand, goes beyond mere carriage to the presence of symptomatic infection. This transformation from asymptomatic colonization to symptomatic disease occurs most often in people in the extreme of their lives (neonates and the elderly)
Mucocutaneous candidiasis occurs in three forms in persons with HIV infection: oropharyngeal, esophageal, and vulvovaginal disease.
Despite the frequency of mucosal disease, disseminated or invasive infections with Candida and related yeasts are surprisingly uncommon
What is essential for bloodstream fungal conditions
Rapid diagnosis- often prescribed antibiotics, contributing to a lot of unnecessary deaths.
Describe systemic candida infections
Systemic Candidiasis is not a disease seen in normal healthy individuals. There are a large number of reasonably well-characterised risk factors for Systemic Candidiasis. Some of the risk factors may include renal failure and haemodialysis, while other risk factors may be due to various therapies such as chemotherapy or gut-related surgery. Both neutropenia and chemotherapy-induced injury to the gut wall dramatically increase the risk for Systemic Candidiasis. In the non-cancer setting, catheters, gut-wall surgery, and prematurity are arguably the most significant factors.
How may aggressive chemotherapy and catheters increase the risk of fungal infections
Chemo- tyrosine inhibitors for leukaemia damage macrophages- spores not cleared in lungs
Catheters- biofilm for growth and spread of fungi
Describe invasive pulmonary aspergilla
Looks like cancer or TB- haziness of lungs- ‘aspergillus ball’- needs to be surgically removed.
Patients with damaged lungs are susceptible- flu- TB- aspergillus presents as co-infection.
Which patients are vulnerable to IPA
Neutropenic / transplant HIV/AIDS Diabetic Congenital susceptibility e.g. CARD-9, Dectin-1, IL-17- need fully functioning receptors to combat aspergillus. Influenza Leukaemia
What is key to remember about systemic fungal infections
There are few signs and symptoms
in patients that are specific for
systemic fungal infection
Begin with a high index of suspicion
How can we acquire sample to diagnose fungal conditions
Skin
Sputum
Bronchoalveolar lavage- essential in patients with cystic fibrosis- high incidence of fungal growth in lungs.
Blood
Vaginal swab/smear
Spinal fluid- distinguish between fungal meningitis (C. neoforms) and bacterial meningitis
Tissue biopsy
What is the gold standard for diagnosis
Seeing is believing
The gold standard for diagnosis
Rapid and cheap
Describe the issues with culturing fungi
Slow Prone to contamination Requires skilled sample collection Positive ID Allows susceptibility testing
Describe non-culture methods
DNA targeted assays (PCR)- body/antigen assays to detect enolase, proteinase, mannan and glucan (cell wall components and carbohydrate motifs).
Describe Cryptoccocosis Diagnostics
Recent development of a lateral flow assay for the semiquantitative detection of cryptococcal antigen is revolutionising point-of-care diagnosis.
What are the targets for antifungal medications
membrane function, cell wall/nucleic acid synthesis and membrane ergosterol biosynthesis
Describe resistance
Target site conformational changes Target site overexpression Absence of target Efflux pump overexpression Regulation of stress response pathways Genomic plasticity- aneuploidy/hypermutation Unknown mechanism Same azoles used clinically as in agriculture- pre-existing resistance.
