Week 2: Fungal Infections (Dr. Kaur)

Question 1

Four stages of host-pathogen interactions

Answer 1

• Pathogen invading the host system
• Pathogen evading the host system’s defenses
• Pathogen proliferating in the host system
• Host system’s immune response to the invader

Question 2

Classification of pathogens based of damage response framework

Answer 2

Class 1: Pathogens that cause damage only in situations of weak immune responses.

Class 2: Pathogens that cause damage either in hosts with weak immune responses or in the setting of normal immune responses.

Class 3: Pathogens that cause damage in the setting of appropriate immune responses and produce damage at both ends of the continuum of immune responses.

Class 4: Pathogens that cause damage primarily at the extremes of both weak and strong immune responses.

Question 3

In which classes do invasive fungi belong?

Answer 3

Class 2: Candida albicans, Cryptococcus neoformans

Class 4: Aspergillus fumigatus

Question 4

Pathogenic fungal species: Characteristics

Answer 4

(i) ability to grow at or above mammalian body temperature
(ii) ability to reach internal tissues by penetrating or evading host barriers
(iii) ability to lyse tissues and absorb their components
(iv) ability to evade host immune defenses

Question 5

Candidiasis: Where is it normally found? Patho?

Answer 5

• Usually live as harmless commensals in the gastrointestinal and genitourinary tract and are found in over 70% of the population

-Patho:
• Cell wall adhesins: promote binding, reduce clearance
• Morphogenesis into invasive filaments
• Secretion of degradative enzymes

Question 6

Aspergillosis:

• Where is it commonly found
• Mode of nutrition
• How is it transmitted & patho of infection
• Diagnosis

Answer 6

• commonly found in soil
• saprophytic mode of nutrition (obtain its nutrients from dead and decaying matter)

-They are transmitted by the inhalation of fungal spores.
• Host colonization using adhesins, sialic acid
• Host tissue damage by degradative enzymes
• Conidia germination in phagosomes

-Diagnosis
Direct Microscopy, Cultural isolation, Antigen detection, Serology

Question 7

Cryptococcus neoformans

• Virulence factors
• Diagnosis & treatment

Answer 7

-Virulence factors:

(a) Capsule formation: The polysaccharide capsule is mainly composed of two types of polysaccharides: glucuronoxylomannan (GXM) and glucuronoxylomannogalactan (GXMGal)
• Not required for the regular life of yeast, but required for the virulence
• Inhibits phagocytosis, masks epitopes
• confers protection against some stress factors, such as dehydration and free radicals

(b) Melanin production:
• confers resistance to multiple stress factors, such as free radicals, ionizing radiation, and heat
• In the host: plays a key role in the dissemination from the lung to the brain
• Changes the host cytokine production and protects against macrophages
• Melanin deficient strains are less virulent

(c) ability to grow at 37 degrees

-Diagnosis & Treatment:
•Blood, cerebrospinal fluid, or sputum sample examined under a microscope, tested with an antigen test, or cultured.
• Chest x-ray or CT scan of your lungs, brain
• asymptomatic infections or mild-to-moderate pulmonary infections: treatment = fluconazole.
• severe lung infections or infections in the central nervous system (brain and spinal cord): initial treatment is amphotericin B in combination with flucytosine. After that, patients usually need to take fluconazole for an extended time to clear the infection