Lecture 13. Fungal Pathogens 2

Question 1

What are examples of subcutaneous mycoses?

Answer 1

Chromoblastomycosis
Sporotrichosis

Question 2

What is chromoblastomycosis?

Answer 2

A chronic localised disease of the skin and subcutaneous tissues causative organisms are Cladophialophora sp., Fonsecaea sp., and Phialophora sp.

Question 3

What causes chromoblastomycosis infections?

Answer 3

Are caused by the traumatic implantation of fungal elements into the skin and are chronic, slowly progressive and localised

Question 4

What are chromoblastomycosis infections characterised by?

Answer 4

Crusted, warty lesions usually involving the limbs world-wide distribution but more common in bare footed populations living in tropical regions

Question 5

How is chromoblastomycosis diagnosed?

Answer 5

Presence in skin scrapings and/or biopsy tissue of brown pigmented, planate-dividing, rounded sclerotic bodies from a patient with supporting clinical symptoms

Question 6

How can chromoblastomycosis be treated?

Answer 6

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)

Question 7

What is sporotrichosis?

Answer 7

Primarily a chronic mycotic infection of the cutaneous or subcutaneous tissues and adjacent lymphatics

Question 8

What is sporotrichosis characterised by?

Answer 8

Nodular lesions which may ulcerate

Question 9

How are sporotrichosis infections caused?

Answer 9

Caused by the traumatic implantation of the fungus into the skin, or very rarely, by inhalation into the lungs

Question 10

Where can sporotrichosis infections also spread (secondary spread)?

Answer 10

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

Question 11

What is pulmonary sporotichosis?

Answer 11

Rare, usually caused by the inhalation of conidia

Question 12

What are the symptoms of pulmonary sporotrichosis?

Answer 12

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

Question 13

What is the natural course of the lung lesion caused by pulmonary sporotrichosis?

Answer 13

Gradual progression to death

Question 14

How is sporotrichosis diagnosed?

Answer 14

Tissue biopsy will contain very low numbers of narrow base budding yeast cells (2-5μm)

Question 15

How is sporotrichosis treated?

Answer 15

Cutaneous lesions respond well to saturated potassium iodide itraconazole & terbinafine have also proved to be effective

Question 16

What is terbinafine?

Answer 16

An allylamine - a synthetic antifungal agent
It is highly lipophilic in nature and tends to accumulate in skin, nails, and fatty tissues

Question 17

What is the mechanism of action of terbinafine?

Answer 17

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

Question 18

What is Crytpococcus neoformans?

Answer 18

Serious pathogenic yeast

Question 19

What is the sexual form of Cryptococcus neoformans called?

Answer 19

Filobasidiella neoformans (worth noting C. neorformans can reproduce both sexually and asexually)

Question 20

What is the pathology of C. neoformans?

Answer 20

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

Question 21

What are Cryptococcus infections normally, and how do they become symptomatic?

Answer 21

Cryptococcus infections are usually mild or subclinical but, when symptomatic, usually begin in the lungs after inhalation of the yeast in dried bird faeces.

Question 22

What is C. neofromans associated with?

Answer 22

Pigeon and chicken droppings and soil contaminated with these droppings

Question 23

Where is Cryptococcus found and where does it grow?

Answer 23

Cryptococcus, found in soil, actively grows in the bird faeces but does not grow in the bird itself

Question 24

What stage of infection does C. neoformans infection usually stop at?

Answer 24

Usually the infection does not proceed beyond this pulmonary stage

Question 25

What happens to an immunosuppressed individual that has a Cryptococcus infection?

Answer 25

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.

Question 26

What is extrapulmonary cryptococcosis?

Answer 26

In conjunction with a positive HIV antibody test, is a good indicator disease for AIDS

Question 27

What is the infection cycle of C. neoformans?

Answer 27

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

Question 28

What is Pneumocystis carinii originally thought to be and why?

Answer 28

Originally thought to be a protozoan based on its appearance and sensitivity to antiprotozoan drugs

Question 29

How were scientists able to show that P. carinii was more closely related to fungi than protozoa?

Answer 29

Through analysis of its ribosomes and cell wall

Question 30

How is P. carinii thought to be transmitted?

Answer 30

From person to person by the respiratory route

Question 31

What are P. carinii infections almost always?

Answer 31

Asymptomatic

Question 32

What can P. carinii cause in people with highly depressed immune responses (such as people with leukimias or infected with HIV)?

Answer 32

Often lethal pneumonia called PCP (Pneumocystis carinii pneumonia)

Question 33

What is the causative agent of blastomycosis?

Answer 33

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)

Question 34

Where is Blostomyces dermatitidis endemic to?

Answer 34

Southeastern and South-Central states of North America

Question 35

What have outbreaks of blastomycosis been associated with?

Answer 35

Occupational or recreational activities around streams or rivers with high content of moist soil enriched with organic debris and/or rotting wood

Question 36

How is blastomycosis infection acquired?

Answer 36

Via inhalation of the conidia, which transform into the yeast form once in the lungs

Question 37

How many days after initial infection does it take for a blastomycosis infection to show and what does this infection cause?

Answer 37

After 30 to 45 days an acute pulmonary disease indistinguishable from a bacterial pneumonia may occur

Question 38

How many cases of blastomycosis are asymptomatic?

Answer 38

At least 50% of primary infections

Question 39

What is histoplasmosis and what is the causative agent of histoplasmosis?

Answer 39

Condition caused by infection with the dimorphic endemic fungus Histoplasma capsulatum

Question 40

What is the most common cause of fungal respiratory infections in the world?

Answer 40

Histoplasma capsulatum

Question 41

What do the majority of acute cases of infection from H. capsulatum follow?

Answer 41

A sub-clinical and benign course in normal hosts

Question 42

Who is most at risk of having a disseminated and potentially fatal infection from H. capsulatum?

Answer 42

Immunosuppressed individuals, children <2 years old, the elderly and people exposed to a very large inoculum

Question 43

Since the advent of the HIV epidemic, what has H. capsulatum become?

Answer 43

One of the most frequent opportunistic diseases

Question 44

How is histoplasmosis acquired and where does it infect?

Answer 44

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.

Question 45

What can histoplasmosis cause when it becomes disseminated?

Answer 45

Skin lesions and lesions in internal organs

Question 46

How does H. capsulatum enter the body and what triggers the transformation from yeast into parasite?

Answer 46

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

Question 47

What does aspergillosis refer to?

Answer 47

The broad range of disease states whose etiologic agents are members of the genus Aspergillus

Question 48

What type of organism are Aspergillus spp. and what infections are they associated with in the immunocompromised?

Answer 48

Aspergillus spp. are ubiquitous organisms, progressively associated with a growing spectrum of infections in immunocompromised hosts

Question 49

Which specie of Aspergillus is responsible for over 9-% of the cases of invasive aspergillosis?

Answer 49

Aspergillus fumigatus

Question 50

What are three most prevalent aspergillosis diseases?

Answer 50

Allergic bronchopulmonary aspergillosis Pulmonary aspergilloma Invasive aspergillosis

Question 51

What does allergic bronchopulmonary aspergillosis produce?

Answer 51

Allergy to the spores of Aspergillus moulds

Question 52

In which groups of people is allergic bronchopulmonary aspergillosis common in?

Answer 52

Asthmatics (up to 20% of asthmatics might get this at some time during their lives) Cystic fibrosis patients, as they reach adolescence and adulthood

Question 53

What is aspergilloma?

Answer 53

A disease in which Aspergillus grows within a cavity of the lung, which was previously damaged during an illness such as tuberculosis

Question 54

How do aspergillomas form?

Answer 54

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)

Question 55

What are the symptoms of aspergilloma?

Answer 55

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

Question 56

How is aspergilloma diagnosed?

Answer 56

Diagnosis made by X-rays, scans of lungs and blood tests

Question 57

Is invasive aspergillosis asymptomatic or fatal?

Answer 57

Often fatal

Question 58

Is there any good diagnostic test for invasive aspergillosis?

Answer 58

No

Question 59

When does treatment for invasive aspergillosis have to start?

Answer 59

When the condition is only suspected

Question 60

When is invasive aspergillosis usually clinically diagnosed?

Answer 60

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

Question 61

What are the symptoms of invasive aspergillosis?

Answer 61

Fever and symptoms from the lungs (cough, chest pain or discomfort or breathlessness) that do not respond to standard antibiotics

Question 62

How can invasive aspergillosis be localised?

Answer 62

Through the use of X-rays and scans which are usually abnormal in sufferers

Question 63

What is bronchoscopy and what is it used for?

Answer 63

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

Question 64

What is one of the most effective antibiotics that is used to treat and control systemic pathogenic fungi?

Answer 64

Amphotericin B, a polyene

Question 65

How does amphotericin B control systemic pathogenic fungi growth?

Answer 65

Binds to membrane sterols & affects the integrity of the fungal cell membrane

Question 66

What is the downside of using amprotericin B?

Answer 66

This antibiotic can give rise to serious side effects e.g kidney toxicity

Question 67

How can exposure to fungi be eliminated?

Answer 67

Using air filtration in restricted local environments (only works rarely)

Question 68

What two categories can fungal virulence factors be divided into?

Answer 68

Virulence factors that promote fungal colonisation of the host; and virulence factors that damage the host

Question 69

What are examples of virulence factors that promote fungal colonisation?

Answer 69

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

Question 70

What are examples of virulence factors that damage the host?

Answer 70

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

Question 71

What are aflatoxins?

Answer 71

Produced by certain Aspergillus species, are especially carcinogenic

Question 72

What is the mould Stachybotrys chartarum and what does it cause?

Answer 72

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."

Question 73

What are the mycotoxin symptoms in humans?

Answer 73

Dermatitis, inflammation of mucous membranes, cough, fever, headache, and fatigue