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PHAY00011 > Infectious Disease I > Flashcards

Infectious Disease I Flashcards

Viral and fungal infections

1
Q

Two big classifications of viruses and examples.

A

Genome DNA virus - adenoviridae, herpesviridae

Genome RNA virus - orthomyxoviridae, coronaviridae

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2
Q

Why do viruses need the host to multiply?

A

No ribosomes, amino acids, tRNA, ATP synthesis

Many lack polyermase

No cell division -> need host for transcription and translation

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3
Q

Basis structure of virus

A
  1. Protein coat (capsid)
  2. Membrane - only in some envelope viruses
  3. Genome
  4. Some has extra proteins
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4
Q

Meaning of T and P in viral genome packing into a protein coat.

A

T = triangulation number -> how many particles (60xT) come together to form a symmetrical object

P = pseudo triangulation number -> number of different proteins made the object

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5
Q

HIV life cycle

A

GP120 bind to CD4 receptors on CD4+ T cells -> allow entering into cells

Viral particles uncoat -> exposre genome

Viral reverse transcriptase transcribe the genome

Genome integrate into host cell genome

Translated by host cells materials -> viral proteins -> migrate to surface -> form capsid

Bud out with host cell membrane and glycoproteins on surface

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6
Q

Components of HIV.

A

Glycoprotein 120 + Glycoprotein 41 -> cell wall surface

Lipid membrane - from host cells

Matrix protein - P18

Capsid protein - P24

Reverse transcriptase enzymes

Genomes

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7
Q

What are the 3 main genes present on the 3 reading frames of HIV genome?

A

gag = codes for coat proteins

pol = codes for viral enzymes

env = codes for envelope proteins

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8
Q

What genes on HIV genome play part of the way to allow the insertion of viral genome into human genome?

A

LTR = long terminal repeats

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9
Q

Why is the presence of 3 reading frames beneficial for HIV?

A

allow the genome to be more compacted to fit into viral small cells

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10
Q

What does gag gene code for ?

A

matrix protein, capsid protein, nucleocapsid proteins

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11
Q

What does pol gene encode for?

A

proteinase enzymes

reverse transcriptase enzyme

integrase enzymes

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12
Q

What are the roles of the viral proteinase enzymes?

A

cleave long proteins -> small products -> become functional

Smaller products can be: matrix proteins, capsid proteins, nucleocapsid proteins, integrase and reverse transcriptase (into both subunits)

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13
Q

What cut the glycoprotein (GP160) of the viral envelope?

A

cellular enzyme

produce GP120 and GP41

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14
Q

What are the 4 strategies for viral infection?

A

1/ Not treat = allow immune system to manage

2/ Vaccines = provide protection in advance

3/ Virucides = prevent transfer via surfaces

4/ Antivirals = treat infection + reduce viral replication

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15
Q

Examples of polymerase inhibitors class of antivirals.

A

Aciclovir

Ganciclovir

Penciclovir

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16
Q

Briefly state the mechanism of action of aciclovir and other polymerase inhibitor antivirals.

A

Mimic the structure of nucleotide (esp guanine)

Only enter viral infected cells -> get phosphorylated into aciclovir-TP

Binds to viral DNA polymerase only -> prevent further DNA replication through 2 mechanisms

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17
Q

What are the two mechanisms that aciclovir-TP use to prevent DNA replication?

A

Chain termination

Substrate induced inhibition

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18
Q

Explain why aciclovir can only specifically target viral infected cells?

A

Only viral thymidine kinase (TK) can efficiently phosphorylate aciclovir into aciclovir-TP

Become negative charge -> cannot get out of infected cells

Human polymerase does NOT recognise aciclovir-TP

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19
Q

Explain how aciclovir can stop DNA replication through the chain termination mechanism.

A

Structure of aciclovir: similar to nucleotide but no -OH groups in the 3’ position. There is -OH in the 5’ position

ACV-TP can bind to the replicating DNA as a substrate - 5’ OH presence

Cannot allow the next bases to bind - no 3’ OH presence

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20
Q

Does ACV-TP affect human polymerase?

A

not inhihibit beta-polymerase and weakly inhibit alpha-polymerase

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21
Q

What compounds can be used to potentiate the effects of aciclovir?

A

Compounsd that can reduce dGPT concentration

Competition between ACV and dGPT -> increase ACV-TP that can incorporate into the DNA

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22
Q

Explain the substate-induced inhibition of aciclovir.

A

viral DNA polymerase cannot remove aciclovir

enzyme bound to the template-primer structure and cannot get out -> dead-end ternary complex

Next nucleotide bind to the complex -> prevent the dissociation of enzyme -> prevent further DNA replicaiton

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23
Q

What is the suicide inhibitor refered to?

A

The next nucleotide that try to get associated to the chain after ACV-TP

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24
Q

What viral infection does aciclovir most effective at?

A

Herpes Simplex virus

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25
Q

What viral infection is ganciclovir effective against?

A

Cytomegalovirus

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26
Q

What viral infection is penciclovir effective against?

A

Herpes Zoster

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27
Q

What is the main issue of the use of polymerase inhibitor? What is the solution?

A

Low bioavailability

Mkae prodrugs -> hydrolyses to generate drugs in the body

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28
Q

How does the resistance towards aciclovir arise?

A

mutation of thymine kinase -> TK minus

Viruses have to rely on inefficient cellular enzyme to convert substrate to MP

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29
Q

Examples of proteinase inhibitors.

A

Saquinavir

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30
Q

Briefly describe the mechanism of action of proteinase inhibitors?

A

Mimic structure of the enzyme substrate

Bind to proteinase -> cannot be cleaved by the enzyme

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31
Q

Define scissile bond.

A

The bond between proteins that cleaved by proteinases

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32
Q

What does the binding of substrate to proteinase depend on?

A

Amino acid sequence

Shape, polarity, position of the chain being exposed to the enzye

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33
Q

Name an antiviral example that inhibit the entry and exit of the viruses into and out of host cells.

A

Amantadine

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34
Q

What viral infections do amantadine effective against?

A

Influenzae virus

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35
Q

Describe the mechanims of action of amantadine.

A

Interacts with matrix proteins and blocks the pores.

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36
Q

What are the proteins does amantadine interact?

A

Haemagluttinin (HA)

Neuraminidase (NA)

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37
Q

Why do viruses have good resistance development?

A

Mutations to prevent activity of antivirals

High replication rate -> high mutation rate

Poor proof reading function of viral reverse transcriptase.

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38
Q

Solution to tackle viral fast development of resistance.

A

HARRT triple therapy = give 3 different drugs with 3 different targets

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39
Q

Therapeutic aims of antivrial therapies.

A

Decrease viral load

Delay viral evolution

Preserve immune function

Delay symptoms

Prolong survivals

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40
Q

Importance of antigenic shift and antigenic drift

A

Immune system cannot recognise the antigens

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41
Q

Define antigenic shift and antigenic drift

A

antigenic shift - genes from animals incorporating into virus infecting human

antigenic drift - changes of sequence by mutation

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42
Q

Three main types of fungal infections.

A

Cutaneous infections

Subcutaneous infections

Systemic infections

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43
Q

Structure of fungal cell membrane

A

Lipids

Glycoproteins

Sterols - mainly ergosterol

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44
Q

Structure of fungal cell wall

A

Chitin

Mannan

Glucan

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45
Q

Two major forms of pathogenic fungi

A

Yeasts - unicellular - ovoid or spherical -> resemble bacteria shape on agar but larger

Molds - multicellular - filamentous - hyphae branching -> extend into and above medium on agar for nutrients and reproduction

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46
Q

Define dimorphism of pathogenic fungi?

A

Fungi can exist as either yeast or mold forms

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47
Q

What are the different modes of fungi growth?

A

Asexual production (main) - formation of conidia at the tip of hyphae on top of conidiophore -> spread

Sexual production - fusion of haploid nucleus of 2 strains -> meiosis -> produce ascospores -> spread

48
Q

How can fungal infection arise?

A

From host flora -> use of antimicrobials or immunocompromised -> infection of endogenous fungi

From environment

49
Q

What does exogenous fungal infection depend on?

A

Virulence of the organisms

Immune status of the host

50
Q

How does the host innate immune system provide defence against fungi?

A

Skin + mucosal surfaces -> barrier

Skin turnover, pH and water availability -> vital

Bacterial host flora

51
Q

How is fungal infection diagnose and specific strain identified?

A

Case representation + laboratory finding

10% sodium hydroxide + fluorescent dye -> confirm fungal infection

Detection of fungal antigens in body fluid -> can be helpful

Morphology confirm the specific fungal species

52
Q

What fluorescent dye that can be used to confirm fungal infection?

A

Calcofluor white -> bind to chitin

53
Q

Why is culture not always suitbale for fungal infection diagnosis?

A

Time consuming for growth

54
Q

What normally cause cutaneous fungal infections?

A

Dermatophytes like Microsporum, Tricophyton and Epidermophyton

55
Q

Examples of cutaneous fungal infection.

A

Tinea pedis = athlete’s foot = infection of foot

Tinea corposis = ringworm = infection of body

Tinea capitis = infection of head skin

Tinea crusis = jock itch = infection of crotch

Tinea ungunium = infection of nail

56
Q

How does cutaneous fungal infection arise?

A

Direct contact through small break in skins

Injuries

Skin maceration at locations where moisture levels are high

57
Q

Factors that can dictate fungal infections

A

Genetic and hormonal factors

Age

58
Q

Common clinical features of cutanous fungal infection.

A

Lesions - characteristic ring pattern + outward growth

59
Q

How can the diagnosis of dermatophyte infection be confirmed?

A

Scrap infected skin

Treat with potassium hydroxide

Observe under microscope -> if branching septate of hyphae appears -> confirm

60
Q

How is cutaneous fungal infection treated?

A

Topical antifungal creams containing azoles or allylamides

Nail infection might req systemic antifungals (terbinafine or itraconazole) for 3 - 4 months

61
Q

Why is relapse common for cutaneous fungal infection?

A

Not having good hygiene

Treatment not fully successful

62
Q

Fungi that cause candidiasis,

A

Candida - round or oval yeast

Candida albicans - majority of candida infections

63
Q

Candida do not usually cause infection, so what can promote it?

A

Broad-spectrum antibiotics - kill body normal flora -> promote growth on mucosal surfaces + macerated skin

Immunocompromised -> access to bloodstream

Use of central venous catheters -> entry point

64
Q

Where do Candida albicins normally colonise?

A

GI tract

Vagina

Skin

65
Q

Clinical features of mucosal candidiasis.

A

Raised white plaques on musoca of mouth, throat and vagina -> thrush

Vaginal candidiasis = itch + burning pain + white discharge

66
Q

Indicators of full-blown AIDs.

A

Oral candidiasis spread to oesophagousq

67
Q

How is candidiasis diagnosed?

A

scrapings of lesions -> show budding yeast cells

easy culture

68
Q

Consequences of systemic infection of candida.

A

Fever

Sepsis

Organ dysfunciton

69
Q

Diagnosis method of Candida systemic infection.

A

NOT blood culture - insensitive

Tissue biopsy -> culture

70
Q

Treatment of oral candidiasis

A

Miconazole

Nystatin suspension

71
Q

Treatment of severe candidiasis

A

Oral fluconazole

72
Q

Treatment of vaginal candidiasis

A

OTC intravaginal antifungal - clotrimazole, miconazole

Oral antifungal - fluconazole, itraconazole

73
Q

Management of vulval symptoms of vaginal candidiasis

A

Topical clotrimazole

74
Q

Treatment of disseminated infections of Candida

A

Echinocardin or fluconazole - if not taken azole recently

Alternative: amphotericin B

75
Q

Define aspergillosis. What is it caused by? Where can the microorganism be found?

A

Fungal infection caused by aspergillus species - filamentous fungus

Not part of normal flora

Common found in buildings undergoing construction works

76
Q

Who are at risk of developing aspergillosis?

A

Neutropenic

On corticosteroids

On immunosuppresisive drugs

Transplant patients

77
Q

Pathogenesis of aspergillus species.

A

Spores inhaled

Germinate hyphae in the respiratory tract

invade blood vessels + tissues -> causing haemorrhage and necrosis

ONLY OCCUR IN PROFOUNDLY IMMUNOCOMPROMISED

78
Q

Diagnosis of aspergillosis.

A

Evidence of haemorrhagic infarction and necrosis

Signs of lung or sinus infection

Staining -> septate hyphae branching throughout tissue

79
Q

Signs and symptoms of invasive pulmonary aspergillosis

A

Fever

Chest pain

Cough (with or without blood)

Shortness of breath

Sinus infection with facial pain

CT scans + Chest X-ray -> multiple pulmonary nodules + haemorrhage around the nodules + necrosis

80
Q

Complications of dissemination of aspergillus infection

A

Necrotic skin lesions

Brain abscess -> stroke, seizures, change in mental state

81
Q

Treatment of aspergillosis.

A

1st-line: Amphotericin B

2nd-line: Voriconazole

3rd-line: Itraconazole

Initiate based on only clinical presentation and CT scan result

82
Q

Prophylaxis regimen to prevent aspergillosis in high risk individuals

A

Air filtration in isolation room

Antifungals - voriconazole or posaconazole

83
Q

Name different classes of antivirals.

<Hint: 3 classes>

A

Polymerase inhibitors - aciclovir

Proteinase inhibitors - saquinavir

Host entry and exit inhibitors - amantadine

84
Q

Name different classes of antifungals.

<Hint: 6 classes>

A

Azoles - fluconazole, itraconazole, posaconazole, voriconazole.

Polyenes - nystatin and amphotericin B

Allylamines - terbinafine

Echinocardins - caspofungin, micafungin

Pyrimidine inhibitors - flucytosine

Griseofluvin

85
Q

Mechanism of action of azoles.

A

Prevent the synthesis of ergosterol

Interfere with P450-dependent demethylation of lanosterol to produce ergosterol

Disrupt membrane function + increases permeability

86
Q

Name the 5 available systemic azole agents

A

Ketoconazole

Fluconazole

Itraconazole

Posaconazole

Voriconazole

87
Q

Effectiveness of itraconazole

A

Agaisnt Candida, Cryptococcus, Aspergillus and dermatophytes

Require taken with food

88
Q

Effectiveness of fluconazole

A

Narrower spectrum of activity

Excellent against Candida

Use to treat Candida and Cryptococcus infections + prophylaxis

89
Q

Effectivness of voriconazole

A

Broad spectrum

Used for manage aspergillosis infection and prophylaxis

90
Q

Effectiveness of posaconazole

A

Broadest spectrum - against yeasts and molds

Must be taken with food

91
Q

Main concerns with the use of azoles.

A

Promote hepatitis

Long list of interactions (except for posaconazole)

92
Q

Mechanism of action of polyenes antifungals

A

Binds to ergosterol in membrane

Cause increase in membrane permeability -> leakage of content

Fungicidal

93
Q

Why do polyene antifungal can induce toxicitiy?

A

Can bind to cholesterol in human cell membranes

94
Q

Name 2 available polyene antifungals

A

Nystatin

Amphotericin B

95
Q

Main considerations for Nystatin.

A

Only be used topically

Swish and swallow method to treat mucosal infection

96
Q

Administration requirements of amphotericin B

A

require to make colloidal suspension with sodium deoxychlolate -> for IV

due to poor water solubility

97
Q

Severe adverse effects of amphotericin B

A

Prolonged administration -> nephrotoxicity + anaemia

Infusion route -> fever, chills , myalgias -> require slow infusion rate

98
Q

Explain why amphotericin B can cause those adverse effects.

A

Bind to lipoproteins

Penetrates into cerebralspinal fluid and other body fluids

99
Q

Effectiveness of amphotericin B

A

Broad-spectrum

Effective against: yeast, molds, Candida, Cryptococcus

100
Q

Mechanism of action of allylamines.

A

Inhibit squalene epoxidase

Prevent conversion of squalene -> erogsterol

Increase toxic products from squalene -> cell death

101
Q

Examples of allylamines.

A

Terbinafine

Butenafine

102
Q

Effectiveness of allylamines.

A

Active against dermatophytes

Generally active against Candida albicans

103
Q

The use of allylamines in fungal infections management

A

Normally reserved for infections do not respond to other agents

NOT used for systemic infections

104
Q

Pharmacokinetics of allylamines.

A

PO -> distributed into the skin, nails, fat

Long half-life = 400 hours

105
Q

Common adverse effects of allylamines.

A

GI tract disturbances

106
Q

Mechanism of action of echinocardins.

A

Target the synthesis of beta-1,3-D-glucan - a component of cell wall in Candida and Aspergillus

Cause cell lysis and death

107
Q

Examples of echinocardins

A

Caspofungin

Micafungin

108
Q

The use of echinocardins in fungal infections management.

A

Only available as IV

Not be used with cyclosporine

Drug of choice for certain candida infections and aspergilllosis

Use with voriconazole or used in succession

109
Q

Name the only pyrimidine inhibitors antifungal

A

Flucytosine

110
Q

Mechanism of action of flucytosine

A

Converted into 5-fluorouracil in the fungal cells

Disrupt proteins and DNA synthesis -> fungistatic agent

111
Q

Resistance development against flucytosine and solution

A

Down regulation of enzymes involved in the conversion of flucytosine into 5-fluorouracil

Must be used in combination with other antifungal drugs

112
Q

Side effects of flucytosine.

A

Dose-related bone marrow suppression

Hepatoxicity

113
Q

The use of flucytosine in fungal infections management

A

Systemic mycoses

Meningitis caused by Cryptococcus neoformans and Candida albicans

114
Q

Mechanism of griseofluvin.

A

Oral agent

Accumulate in newly synthesised keratinised tissue

Interferes with microtubule function -> prevent mitotic spindle formation -> prevent mitosis.

115
Q

The use of griseofluvin in fungal infections management.

A

Treatment of dermatophytes infections of the nails

Not used commonly anymore

116
Q

Why does griseofluvin have a lot of drug interactions?

A

Induce hepatic CYP450

PHAY00011 (9 decks)

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