9 Fungal Infection Flashcards
Q: What are fungi? Genetics? (2) Similarities to us? meaning? (2) Give an example of an important fungi.
A: a kingdom part of the eukaryotic crown group
- several chromosomes
- massive complex genome
-similar metabolism- so anything that works on yeast is likely to have a similar effect on us (difficult to work with them as pathgens)
saccharomyces cerevisiae (brewers yeast)
Q: How can the fungi group further divide? (2) Describe each.
A: into 2 phyla
- Basidiomycota: consists of many of the mushrooms that we find
- Ascomycota: moulds, contains 90% of all human fungal infections
Q: Out of the Basidiomycota, which fungus causes the largest burden of disease? Disease? Mechanism? (2)
A: Cryptococcus neoformans -> causes CRYPTOCOCCAL MENINGITIS which is a form of minigitis in people with AIDS
- These cryptococci can be inhaled into the lungs - alveolar macrophages are usually good at mopping up fungal cells as we inhale them
- Cryptococcus can get into the brain (a sugar rich environment) and cause meningitis
Q: Name 2 fungi in the phyla Ascomycota and their corresponding diseases.
A: aspergillus fumigatus
-invasive pulmonary aspergillosis
candida albicans
-blood stream infections
Q: Describe fungi in terms of pathogenic behaviour.
A: most fungal infections are opportunistic - live in environment without the need for us - but are ready to take possession of our organism whenever it presents a vulnerable point or a point of weak resisting power
Q: Every lung full of air we breath in is? What do we need to do?
A: filled with fungal spores
-ensure they get removed otherwise they could digest away at lung or even get into blood
Q: How do fungi digest their food? How? Name?
A: extracellularly (effectively suspended in its food source)
- produce hydrolytic enzymes which are pumped out into the environment
- said substances= powerful polymer degrading substances which rot the material around them
SAPROPHYTES
Q: What do fungi produce in terms of reproduction? Air sample? What happens?
A: -produce a large number of spores
- contained as many as 200,000 spores per m^3
- dispersed over large distances
Q: What type of fungi are transmitted via contact? (2)
A: commensal organism and skin colonisers
Q: What are the 3 classes of fungal disease?
A: 1. allergies
- mycotoxicoses
- mycoses= active disease causing agent = 3 types
Q: Describe fungal allergies. Examples (4).
A: inhalation/contact with fungal spores may induce wide range of allergic diseases
- Rhinitis
- Dermatitis
- Asthma
- Allergic Broncho-Pulmonary Aspergillosis (ABPA)
Q: What is Allergic Broncho-Pulmonary Aspergillosis (ABPA) caused by? Where does it thrive? Occurs in what percentage of asthmatics?
A: Aspergillus fumigatus
- grows in compost and likes high heat including our body temperature
- 2.5%
Q: What are mycotoxins? What do they cause? Symptoms? (6) Therapy? (2)
A: secondary metabolites of moulds that exert toxic effects on animals and humans (important in defending fungi)
cause mycotoxicoses= toxic reaction caused by inhalation or indigestion of mycotoxins
- breathing problems
- dizziness
- severe vomiting
- diahorrea
- dehydration
- hepatic and renal failure 6 days later
- gastric lavage and charcoal
- liver transplant
Q: Give an example of a non lethal mycotoxin. What does it cause? Treatment?
A: Psilocybin produced by Psilocybe semilanceata => a trip/sought after effects
- visual distortions of colour, depth, form
- progressing to visual hallucinations
time
Q: Give an example of a lethal mycotoxin. Produced by? Nature? Growth? Effect? (2) Increased risk?
A: AFLATOXIN produced by Aspergillus flavus is the most carcinogenic natural compound known
Contaminates grain
If you get aflatoxin poisoning and you have liver damage from hepatitis B then you are at particular risk of cancer
South-East Asia - higher rates of liver cancer possibly due to greater exposure to aflatoxin (consistent low levels of exposure)
Q: What are mycoses? Types? (4)
A: disease caused by fungi which is classified by the level of tissue affected (superficial, cutaneous, subcutaneous, systemic)
Q: What are superficial mycoses? Host response?
A: common and occurs on keratin rich tissue (skin or hair shaft)
No living tissue is invaded - no cellular response from host
Q: Give an example of a superficial mycoses. Causes? Treatment?
A: Malassezia globosa
- produces oleic acid which causes inflammation of stratum corneum and ‘dandruff’
- selenium sulfide inhibits fungal growth (doesn’t kill)
Q: What is cutaneous mycoses also called? Caused by? Result? (3) 5 examples.
A: -dermatophytocis and dermatomycosis
-dermatophytes or keratinophilic fungi
- Produce keratinases which are capable of hydrolysing keratin
- Inflammation is caused by host response to metabolic by-products
- Tinea - latin for ring worm (phenotype)
- tinea capitis (head/neck)
- tinea pedis (athletes foot)
- tinea corporis (body)
- tinea cruris (groin= jock itch)
- tinea unguium (finger/toe nails)
Q: What is tinea capitis? Affects?
A: cutaneous mycoses/ ringworm of scalp, eyebrows and eye lashes with a propensity for attacking hair shafts and follicles
25% chn in schools over africa (disfiguring)
Q: What is the most paediatric dermatophyte infection?
A: tinea capitis
Q: What is tinea pedis? Caused by? What proportion of the population will be infected with it at some point?
A: Incredibly infectious cutaneous mycoses/ athletes foot
-Trichophyton rubrum
70%
Q: What is the worlds most prevalent dermatophyte?
A: Trichophyton rubrum which causes athletes foot
Q: What is tinea corporis also known as? What is it? Treatment? (3)
A: ring worm
-cutaneous mycoses
antifungal creams: -miconazole -clotrimazole orally -griseofulvin = systemic antifungal
Q: What is subcutaneous mycoses? Occurrence? Treatment? 3 examples.
A: chronic, localised infections of the skin and subcutaneous tissue following traumatic implantations of the aetilogic agent (including stratum corneum)
- rare
- seen in combat blast related wounds
often very hard to treat- amputation is the usual option
- Sporotrichosis
- Chromoblastomycosis
- Mycetoma
Q: What is Mycetoma?
A: chronic infection of the skin, subcutaneous tissue and sometimes bone, characterised by discharging sinuses filled with organisms
Q: What is Sporothrix schenckii and what does it cause? Epidemic?
A: fungi that causes subcutaneous mycoses= sporotrichosis
ongoing epidemic in brazil -> causes subcutaneous mycoses in cats -> can transmit to humans (zoonosis)
Q: What are the 2 types of fungi that causes deep/systemic mycoses? Difference?
A: primary= able to establish infection in a normal healthy host (rarer)
opportunistic= require compromised host in order to establish infection (always around us waiting to take advantage)
Q: Name 2 fungi that cause ‘primary’ deep/systemic mycoses. Opportunistic?
A: coccidiodes immitis
histoplasma capsulatum
cryptococcus neoformans (form of meningitis) candida
Q: Where are the rates of deep/systemic mycoses high?
A: immunosuppressed patients in hospitals
Q: What is Candida a cause of? Colonisation? Species?
A: common cause of blood stream infections
20-25% of healthy humans have it
6 species predominate as pathogens:
- C. albicans (widespread)
- C. krusei
- C. glabrata
- C. parapsillosis
- C. tropicalis
- C. auris
Q: What is Candida albicans? Where? (3) Can be? (3)
A: opportunistic commensal
Pretty much all of us have it in our gastrointestinal and genitourinary tracts and skin -> not harmful in healthy humans
but can be harmful in immunosuppressed people -> C. albicans can colonise and invade host tissues
can be: superficial, mucosal, systemic
Q: Where can we get superficial Candida infections? (10) Usually due to? Age? (2) Treatment?
A: Mouth, throat, skin, scalp, vagina, fingers, nails, bronchi, lungs or the GI tract
Usually due to impaired epithelial barrier function
occurs in all age groups but most common in the new born and elderly
respond readily to treatment
Q: What are mucosal Candida infections? Age? Who’s at risk? Forms? (3) What happens when it becomes systemic?
A: symptomatic infections
Occurs in the new born and the elderly
Mucocutaneous candidiasis occurs in three forms in people with HIV:
- Oropharyngeal
- Oesophageal
- Vulvovaginal
might see high mortality rates
Q: Where are Systemic Candida Infections not normally seen? Risk factors? (3)
A: in normal healthy individuals
Main Risk Factors:
- Chemotherapy
- Gut-related surgery
- Catheters (candida can form biofilm)
Q: What is Invasive aspergillosis (IA)? Where? (2). Name 2 risk factors.
A: emerged as the major clinical problem of common mycology
-common in transplant related settings- CF patients= commonly colonised as lung function is impaired
- stem cell transplant
- lymphatic leukaemia
Q: What’s the difficulty in diagnosing systemic fungal infections? 4 stages of diagnosing?
A: few signs and symptoms in patients that are specific for systemic fungal infection
- sample acquisition
- microscopy (gold standard)
- culture = grow fungus on plate
- identification
Q: Where can sample acquisition be from? (7)
A: -Skin
- Sputum
- Bronchoalveolar Lavage (good for pulmonary infection eg IA)
- Blood (systemic)
- Vaginal swab/smear
- Spinal fluid (meningitis)
- Tissue biopsy
Q: What are the benefits of microscopy in diagnosis? (2) Requirement?
A: cheap and fast
Need to have a well established fungal infection to be able to see it down the microscope
Q: What are the downsides to a ‘culture’ in terms of diagnosis? (3) When does it occur? allows?
A: slow and prone to contamination and can be difficult to understand
Once it has been identified under the microscope, it can be cultured -> allows susceptibility testing
Q: What are non-culture methods of diagnosis? (3)
A: Antibody and Antigen-based assays can be used to detect fungal polysaccharides:
- Glucan
- Mannan
- Endolase
- Proteinase
Crytoccocosis diagnostics= lateral flow assay-> means no lumbar puncture needed for fungal meningitis
PCR (DNA)
Q: What are the targets of antifungal treatment? (3) Explain each.
A: cell membrane
-fungi use ergosterol instead of cholesterol
DNA synthesis
-some compounds may be selectively activated by fungi, arresting DNA synthesis
cell wall
-unlike mammalian cells, fungi have a cell wall
Q: What are the 2 main classes of Cell Membrane Active Antifungals? 3 examples. Method?
A: -polyene antibiotics eg Amphotericin B = common but toxic since we’re similar to fungi
-azole antifungals eg itraconazole and flucaonazole= Azole is the main drug group
Main attack against the cell membrane is to INHIBIT THE SYNTHESIS OF ERGOSTEROL = Ergosterol is the main sterol in the fungal membrane
Q: What is the main class of Fungal DNA/RNA Synthesis Inhibitors?
A: Pyrimidine analogues are commonly used for this
-eg Flucytosine = not great as fungus evolves resistance to it rapidly
-> often combined with azoles
eg fluconazole + flucytosine for Cryptococcal meningitis = combination therapy
Q: What is the main class of Cell Wall Active Antifungals? example? Downside? Main components of fungal cell wall?
A: echinocandins- caspofungin = works by the non-specific inhibition of b 1, 3 glucan synthase
expensive
MAJOR COMPONENTS: Glucans and Chitin
Q: How is the uses of antifungal drugs in agriculture leading to increases in drug resistant infections in humans? Example.
A: strains become resistant and then go on to infect immunosuppressed patients
Aspergillus fumigatus is common in environment but can opportunistically infect immunosuppressed patients (CF/transplant)
frontline treatment is triazole which is also used as antifungals on crops -> mutations -> resistant strains