Flashcards in Week 228 Fungal Disease Deck (49)
What is a CD4 test used to measure?
1) used to measure baseline viral load on first diagnosis of HIV
2) used to monitor the progress of HIV (CD4 as a % of total WBC)
3) used as an absolute measure of the body's ability of fight opportunistic infection
Reduced albumin levels can mean what?
- liver damage
- kidney disease
- severe inflammation / shock
According to WHO what CD4 result requires treatment?
200 and below
What is parainfluenza?
A group of 5 viruses causing respiratory illness including:
Croup (in children)
What does Coxiella burnetii cause and how?
Involves a hardy spore that can acquired from sheep/cattle and can live I skimmed milk for 40months!
Human infection via inhalation, proliferating in lungs & bacteraemia follows (can also present as self-limiting febrile illness similar to pneumonia)
What commonly passes on Psittacosis?
Budgies / Pigeons
What is Brucellosis?
G-ve, nonmotile, non-spore-forming, rodshaped bacterial infection
They function as intracellular parasites causing chronic disease
Assoc with unpasteurised milk and soft cheeses (goats)
What does HAART stand for in relation to HIV treatment?
Highly Active AntiRetroviral Therapy
A combination of drugs that treat HIV and AIDS
What classes of drug does HAART include?
- Nucleoside (-tide) reverse transcriptase inhibitors
- Non-Nucleoside (-tide) reverse transcriptase inhibitors
- Protease inhibitors
- Fusion / Entry inhibitors
- Integrase inhibitors
How do non-nucleoside & nucleoside (-tide) reverse transcriptase inhibitors work?
Attach to reverse transcriptase enzyme on HIV virus (necessary to convert RNA to DNA in order to infect CD4 cells) so that the conversion is prevented thereby preventing viral replication within CD4 cells
How do protease inhibitors work?
Block proteolytic cleavage thereby preventing HIV viral replication
Besides HIV what else are protease inhibitors used to treat?
How do fusion/entry inhibitors work?
They prevent HIV virus entering CD4 cells by preventing the surface proteins from binding
How do Integrase inhibitors work?
Prevent HIV's DNA being incorporated into CD4 cells DNA - useful in cases where resistance to other drugs exists
What organism causes Pityriasis Versicolour and what are the key features?
Areas of hyper- or depigmented skin mainly on trunk or proximal limbs (may have flaky skin also) usually during hot spells in weather
What are the principle treatments for Pityriasis Versicolour?
Oral itraconazole or fluconazole
What are the 3 principle Dermatopytosis organisms?
Microsporum (hair and skin)
Epidermophyton (skin and nails)
Trichophyton (skin, hair and nails)
What is the clinical manifestation of a skin dermatopytosis infection?
Circular, itchy, scaly, erythematous lesions
What species of Candida is most commonly connected with Candidiasis infection?
Candida albicans (80-90% of cases)
What is unpleasant symptom is typical of oesophageal candidal infections?
Dysphagia. The infection can be very painful
What factors predispose individuals to candidiasis infections (particularly systemic infections)?
In-dwelling lines / Abdo surgery
Persistently moist skin (superficial infections)
What is the mode of transmission of Aspergillosis infection?
Inhalation of spores (found in soil and other organic materials)
What is Cryptococcosis associated with and how does it usually present?
Caused by Cryptcoccus neoformans inhalation, assoc with pigeon droppings. Usually presents as CNS infection though usually originates in lungs either asymptomatic or as mild chest infection
(Particularly AIDS patients)
What causes Pneumocyctosis and which people are most susceptible?
Pneumocystis pneumonia (PCP) Is caused by Pneumocystis jiroveci
One of most significant AIDS related diseases
How do you treat Pneumocystis jiroveci?
Although P jiroveci has now been found to be a fungus it does not respond to most anti-fungal treatments largely due to lack of ergosterol in membrane. Only anti fungal group it does respond to is Echinocandins e.g. Caspofungin
Drug of choice = co-trimoxazole
Why do anti-fungals carry higher risk of toxicity than antibiotics?
Fungi have eukaryotic cells so anti fungal actions are less specific to exogenous organisms than antibiotics (which act on prokaryotic bacterial cells)
What are the main features that differentiate a fungal plasma membrane from a human eukaryotic cell membrane?
Embedded: ergosterols (cholesterol based) and proteins
What are fungal cell walls made up of (and are hence targets for antifungals)?
Ergosterols (among other things but these are the main targets of antifungals)
What two basic growth forms do fungi take?
Yeast: unicellular, growth via budding
Filamentous: multicellular, reproduction complex via production of hyphae and spores, growth via hyphae
Name one yeast fungus that always remains a yeast
Name one yeast fungus that on infection causes pseudo-hyphae?
Name some filamentous fungi that always remain filamentous (I.e. Hyphae formation)
Aseptate e.g. Mushrooms
Dermatophytes/Tinea (Microsporum, Epidermophyton, Trichophyton)
Name a group of filamentous fungi that are yeast-like although it truly filamentous
True pathogens e.g. Histoplasmosis
What aspect of fungal cells contribute to their virulence?
Exoenzymes which all fungal cell organelles combine to produce
What are the 2 broad groups of azoles?
Imidazoles (largely topical) e.g. Clotrimazole and Miconazole
Triazoles (systemic) Fluconazole (most commonly used fungicide), Itraconazole and Voriconazole
Generally what are the Azoles used for treating?
Candida, Cryptococcus, Dermatophytes
How do Azoles act?
Inhibit membrane synthesis by inhibiting fungal cytochrome p450
Which azole has a negative inotropic effect? (Reduces heart contractility and strength)
(can also cause liver damage, should be taken in empty stomach)
What is Clotrimazole commonly used to treat?
Candidal infections (Canesten cream)
Name two more antifungal groups that inhibit membrane synthesis and give the main example of each
Echinocandins e.g. Caspofungin
Allylamines e.g. Terbinafine
How does Capsofungin (Echinocandin) act on the fungi membrane?
Inhibits 1, 3 beta-glucan synthase reducing glucan in the cell wall
What is Capsofungin typically used to treat?
Aspergillus and Candida
Also ONlY standard treatment effective in Pneumocystis (PCP)
How does Terbinafine (Allylamine) act on the fungi membrane?
Inhibits ergosterol synthesis by inhibiting squalene epoxidase
What is Terbinafine particularly good at treating and why?
As it is a lipophilic drug which concentrates in the skin and adipose tissue
(Topical or oral)
How do Polyene antifungals work? Name 2
Inhibit membrane function by binding to ergosterol and causing pores through which cations flux
Amphotericin B (1st line immunocompromised fungicidal)
What must you gone aware of with Amphotericin B?
It is highly toxic so often combined with Flucytosine to make AmbiSome
Name 3 conditions treated with AmbiSome and explain why safer in combo
Some fungal meningitis in HIV patients
Safer because only activated on contact with fungus therefore more specific and less toxic
Want 2 conditions is Nystatin commonly used to treat?
Superficial candidiasis - Nappy rash and Oral thrush (swill in mouth to coat oral mucosa)