Lecture 13. Fungal Pathogens 2 Flashcards
What are examples of subcutaneous mycoses?
Chromoblastomycosis
Sporotrichosis
What is chromoblastomycosis?
A chronic localised disease of the skin and subcutaneous tissues causative organisms are Cladophialophora sp., Fonsecaea sp., and Phialophora sp.
What causes chromoblastomycosis infections?
Are caused by the traumatic implantation of fungal elements into the skin and are chronic, slowly progressive and localised
What are chromoblastomycosis infections characterised by?
Crusted, warty lesions usually involving the limbs world-wide distribution but more common in bare footed populations living in tropical regions
How is chromoblastomycosis diagnosed?
Presence in skin scrapings and/or biopsy tissue of brown pigmented, planate-dividing, rounded sclerotic bodies from a patient with supporting clinical symptoms
How can chromoblastomycosis be treated?
Can involve surgical removal of tissue (though requires removal of a margin of uninfected tissue to prevent local dissemination) Fluorocytosine (a pyrimidine analog) & the azoles thiabendazole & itraconazole are effective (can require treatment for 6 to 12 months)
What is sporotrichosis?
Primarily a chronic mycotic infection of the cutaneous or subcutaneous tissues and adjacent lymphatics
What is sporotrichosis characterised by?
Nodular lesions which may ulcerate
How are sporotrichosis infections caused?
Caused by the traumatic implantation of the fungus into the skin, or very rarely, by inhalation into the lungs
Where can sporotrichosis infections also spread (secondary spread)?
Secondary spread to joints, bone and muscle is not infrequent, and the infection may also occasionally involve the central nervous system, lungs or genitourinary tract
What is pulmonary sporotichosis?
Rare, usually caused by the inhalation of conidia
What are the symptoms of pulmonary sporotrichosis?
Non-specific: include cough, sputum production, fever, weight loss and upper-lobe lesion
Haemoptysis (coughing up blood) may occur and it can be massive and fatal
What is the natural course of the lung lesion caused by pulmonary sporotrichosis?
Gradual progression to death
How is sporotrichosis diagnosed?
Tissue biopsy will contain very low numbers of narrow base budding yeast cells (2-5μm)
How is sporotrichosis treated?
Cutaneous lesions respond well to saturated potassium iodide itraconazole & terbinafine have also proved to be effective
What is terbinafine?
An allylamine - a synthetic antifungal agent
It is highly lipophilic in nature and tends to accumulate in skin, nails, and fatty tissues
What is the mechanism of action of terbinafine?
As with the other allylamines, terbinafine inhibits ergosterol biosynthesis via inhibition of squalene epoxidase. This enzyme is part of the fungal sterol synthesis pathway that creates the sterols needed for the fungal cell membrane
What is Crytpococcus neoformans?
Serious pathogenic yeast
What is the sexual form of Cryptococcus neoformans called?
Filobasidiella neoformans (worth noting C. neorformans can reproduce both sexually and asexually)
What is the pathology of C. neoformans?
It appears as an oval yeast 5-6 µm in diameter, forms buds with a thin neck, and is surrounded by a thick capsule. It does not produce pseudohyphae and chlamydospores. The capsule enables the yeast to resist phagocytic engulfmen
What are Cryptococcus infections normally, and how do they become symptomatic?
Cryptococcus infections are usually mild or subclinical but, when symptomatic, usually begin in the lungs after inhalation of the yeast in dried bird faeces.
What is C. neofromans associated with?
Pigeon and chicken droppings and soil contaminated with these droppings
Where is Cryptococcus found and where does it grow?
Cryptococcus, found in soil, actively grows in the bird faeces but does not grow in the bird itself
What stage of infection does C. neoformans infection usually stop at?
Usually the infection does not proceed beyond this pulmonary stage
What happens to an immunosuppressed individual that has a Cryptococcus infection?
The infection may spread through the blood to the meninges and other body areas, often causing cryptococcal meningoencephalitis (a very severe and usually fatal infection). Any disease by this yeast is usually called cryptococcosis.
What is extrapulmonary cryptococcosis?
In conjunction with a positive HIV antibody test, is a good indicator disease for AIDS
What is the infection cycle of C. neoformans?
It is thought that infection of humans generally occurs when basidiospores produced by C. neoformans in nature are inhaled into the lungs
Inhaled spores are deposited into the alveoli and germinate to establish a dormant infection or disseminate to the central nervous system
Once dissemination has occurred, viable cells can be cultured from the cerebrospinal fluid of affected individuals
What is Pneumocystis carinii originally thought to be and why?
Originally thought to be a protozoan based on its appearance and sensitivity to antiprotozoan drugs
How were scientists able to show that P. carinii was more closely related to fungi than protozoa?
Through analysis of its ribosomes and cell wall
How is P. carinii thought to be transmitted?
From person to person by the respiratory route
What are P. carinii infections almost always?
Asymptomatic
What can P. carinii cause in people with highly depressed immune responses (such as people with leukimias or infected with HIV)?
Often lethal pneumonia called PCP (Pneumocystis carinii pneumonia)
What is the causative agent of blastomycosis?
Dimorphic fungus Blastomyces dermatitidis (dimorphic = having two distinct forms, as in some fungal pathogens of humans, which are yeast-like in the host, but mycelial in culture)
Where is Blostomyces dermatitidis endemic to?
Southeastern and South-Central states of North America
What have outbreaks of blastomycosis been associated with?
Occupational or recreational activities around streams or rivers with high content of moist soil enriched with organic debris and/or rotting wood
How is blastomycosis infection acquired?
Via inhalation of the conidia, which transform into the yeast form once in the lungs
How many days after initial infection does it take for a blastomycosis infection to show and what does this infection cause?
After 30 to 45 days an acute pulmonary disease indistinguishable from a bacterial pneumonia may occur
How many cases of blastomycosis are asymptomatic?
At least 50% of primary infections
What is histoplasmosis and what is the causative agent of histoplasmosis?
Condition caused by infection with the dimorphic endemic fungus Histoplasma capsulatum
What is the most common cause of fungal respiratory infections in the world?
Histoplasma capsulatum
What do the majority of acute cases of infection from H. capsulatum follow?
A sub-clinical and benign course in normal hosts
Who is most at risk of having a disseminated and potentially fatal infection from H. capsulatum?
Immunosuppressed individuals, children <2 years old, the elderly and people exposed to a very large inoculum
Since the advent of the HIV epidemic, what has H. capsulatum become?
One of the most frequent opportunistic diseases
How is histoplasmosis acquired and where does it infect?
Through inhalation of Histoplasma capsulatum microconidia
The lungs are thus the most frequently affected site and chronic pulmonary disease may occur
This clinical picture is frequently associated with pre-existing chronic lung diseases such as emphysema and occurs most frequently in elderly men. All stages of this disease may mimic tuberculosis.
What can histoplasmosis cause when it becomes disseminated?
Skin lesions and lesions in internal organs
How does H. capsulatum enter the body and what triggers the transformation from yeast into parasite?
The mould or mycelial form exists in the soil, where it absorbs nutrients from dead organic matter and produces infectious spores
When these spores are inhaled and encounter the warm moist environment of the lungs, they undergo a transformation to the yeast or parasitic form
What does aspergillosis refer to?
The broad range of disease states whose etiologic agents are members of the genus Aspergillus
What type of organism are Aspergillus spp. and what infections are they associated with in the immunocompromised?
Aspergillus spp. are ubiquitous organisms, progressively associated with a growing spectrum of infections in immunocompromised hosts
Which specie of Aspergillus is responsible for over 9-% of the cases of invasive aspergillosis?
Aspergillus fumigatus
What are three most prevalent aspergillosis diseases?
Allergic bronchopulmonary aspergillosis
Pulmonary aspergilloma
Invasive aspergillosis
What does allergic bronchopulmonary aspergillosis produce?
Allergy to the spores of Aspergillus moulds
In which groups of people is allergic bronchopulmonary aspergillosis common in?
Asthmatics (up to 20% of asthmatics might get this at some time during their lives)
Cystic fibrosis patients, as they reach adolescence and adulthood
What is aspergilloma?
A disease in which Aspergillus grows within a cavity of the lung, which was previously damaged during an illness such as tuberculosis
How do aspergillomas form?
Any lung disease which causes cavities can leave a person open to developing an aspergilloma
The spores penetrate the cavity and germinate, forming a fungal ball within the cavity
Illness is caused by secretion of toxins/other products (elastases, proteases)
What are the symptoms of aspergilloma?
No symptoms (especially early on)
Weight changes, chronic cough, brain fog, and feeling rundown are common symptoms later on
Coughing of blood (hemoptysis) can occur in up to 50-80% of affected people
How is aspergilloma diagnosed?
Diagnosis made by X-rays, scans of lungs and blood tests
Is invasive aspergillosis asymptomatic or fatal?
Often fatal
Is there any good diagnostic test for invasive aspergillosis?
No
When does treatment for invasive aspergillosis have to start?
When the condition is only suspected
When is invasive aspergillosis usually clinically diagnosed?
In a person with low defences such as bone marrow transplant, low white cells after cancer treatment, AIDS or major burns
There is also a rare inherited condition that gives people low immunity (chronic granulomatous disease) which puts affected people at moderate risk
What are the symptoms of invasive aspergillosis?
Fever and symptoms from the lungs (cough, chest pain or discomfort or breathlessness) that do not respond to standard antibiotics
How can invasive aspergillosis be localised?
Through the use of X-rays and scans which are usually abnormal in sufferers
What is bronchoscopy and what is it used for?
Inspection of the inside of the lung with a small tube inserted via the nose
Often used to help to confirm the diagnosis of invasive aspergillosis
What is one of the most effective antibiotics that is used to treat and control systemic pathogenic fungi?
Amphotericin B, a polyene
How does amphotericin B control systemic pathogenic fungi growth?
Binds to membrane sterols & affects the integrity of the fungal cell membrane
What is the downside of using amprotericin B?
This antibiotic can give rise to serious side effects e.g kidney toxicity
How can exposure to fungi be eliminated?
Using air filtration in restricted local environments (only works rarely)
What two categories can fungal virulence factors be divided into?
Virulence factors that promote fungal colonisation of the host; and virulence factors that damage the host
What are examples of virulence factors that promote fungal colonisation?
The ability to adhere to host cells seems to play a role in fungal virulence
Some fungi produce capsules allowing them to resist phagocytic engulfment
Candida albicans stimulates the production of a cytokine called GM-CSF and this cytokine can suppress the production of complement by monocytes and macrophages
C. albicans also appears to be able to acquire iron from red blood cells
Some fungi are more resistant to phagocytic destruction
What are examples of virulence factors that damage the host?
Secretion of enzymes to digest cells, triggering cytokine release, resulting in an inflammatory response and extracellular killing by phagocytes that cause further destruction of host tissues
Many moulds secrete mycotoxins that may cause a variety of effects in humans and animals if ingested including loss of muscle coordination, weight loss, and tremors. Some mycotoxins are mutagenic and carcinogenic
What are aflatoxins?
Produced by certain Aspergillus species, are especially carcinogenic
What is the mould Stachybotrys chartarum and what does it cause?
Stachybotrys chartarum is a mycotoxin producer
Has been implicated as a potential serious problem in homes and buildings as one of the causes of “sick building syndrome.”
What are the mycotoxin symptoms in humans?
Dermatitis, inflammation of mucous membranes, cough, fever, headache, and fatigue
