v. TB - The Superbug Flashcards

1
Q

Tuberculosis (TB) = Tuberculosis (TB) = one of top 10 causes of death globally, leading cause from single ______ agent

A

infectious

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2
Q

2018 - TB = ___ million deaths; estimated 10 million indv developed TB

30 high TB _____ countries (WHO)

1.7 billion people (23% of world pop) = ____ TB infection

A

1.6
burden
latent

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3
Q

SA epidemiology:

A

SA epidemiology: Incidence in 2018: 520/100 000 ppl; MDR/RR TB: 3.4% (new cases) & 7.1% (previously treated cases) [MDR - Mutlidrug resistant]

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4
Q

What are the risk factors?

A

Diabetes, malnutrition, tobacco smoking, alcohol abuse, underlying social determinants (overcrowding etc.)

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5
Q

Mycobacterium tuberculosis complex:

Human TB - Group of genetically v closely related variants (10 species); Includes:

A

M. Tuberculosis (L1-4, L7); M. Africanum (L5, L6)

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6
Q

Mycobacterium tuberculosis complex:

> __% of human TB caused by M. Tuberculosis

A

90

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7
Q

Mycobacterium tuberculosis complex:

  • Africa harbours largest diversity of human-adapted ____
  • Although several attributes of M. Tuberculosis (inc transmissibility, drug resistance, mortality) have been linked w/ specific strains, findings = ______ ______ _______
A

MTBC
inconsistent btwn studies

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8
Q

What is the description of M. Tuberculosis complex?

A

Nonmotile, non-sporing, non-capsulated, straight/slightly curved rods about 3 x 0.3 um in size. In sputum & other clinical specimens, may occur singly or in small clumps

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9
Q

M. Tuberculosis complex:

In liquid cultures, often grow as twisted rope-like colonies termed _______ cords.

A

serpentine

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10
Q

Slow generation tome (divides once in 24h); Optimal growth temp = 35-37 deg, obligate aerobes, _______ intracellular pathogen

A

facultative

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11
Q

Structure of cell wall:

A

Mycobacteria

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12
Q

Mycolic acid:

A
  • Long chain fatty acid, unique to mycobacteria, form thick, waxy layer difficult to penetrate
    (resist acids & alkalis)
  • aids in biofilm formation
  • Immune system - specifically modulated immune response, aids in antibiotic resistance, resistance to attacks by osmotic lysis, lysozyme resistance, forms outer membrane
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13
Q

M. Tuberculosis complex =
Acid fast Bacteria:

Not classified as gram +ve or -ve (stains v weakly or not at all) therefore, DNA based molecular ________ groups mycobacteria w/ gram +ve BUT distinction btwn mycobacterial cell wall and standard gram ____ cell wall

A

taxonomy
+‘ve

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14
Q

Acid fast staining procedure (Ziehl Neelsen stain): promote uptake of dye -

  1. Primary stain: carbon ______ - apply heat -> allow penetration of stain thru wall
  2. De-stain w/ acid alcohol: mycolic acid residues retain primary stain even after ______ to acid-alcohol -
    RESISTANCE TO ____________ REQ TO BE TERMED ACID FAST
  3. Counterstain w/ _______ blue to highlight background for easier microscopic rec
A

fuchsin
exposure
DECOLORISATION
methylene

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15
Q

Latent TB infection versus TB disease:

A
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16
Q

Resistance to antibiotics:
Mycobacteria =

A

inherently resistance to numerous antibiotics: attributable to cell wall - low rate of diffusion thru cell wall

16
Q

Resistance to antibiotics:
Acquired resistance:

A

Acquired resistance: almost exclusively thru chromosomal mutations in genes req for antibiotic action - genes encoding protein target of drugs, enzymes req for prodrug activation

17
Q

Resistance to antibiotics:
Eg. Rifampicin resistance:

A

Single-nucleotide substitution mutation in small region or rpoB (gene encoding Beta subunit of DNA-dependant RNA Polymerase)

18
Q

Resistance to antibiotics:

  • Resistance in MTB complex:
A

Rifampicin resistance determining region (RRDR) - around 96% of mutations conferring rifampicin resistance confined w/in a 81 base pair region of rpoB gene.

18
Q

Resistance to antibiotics:

Molecular tech to diagnose TB and provide _______ susceptibility: Xpert MTB/RIF and MTBDRplus (binding probes extend across the RRDR)

A

rifampicin

19
Q

Pathogenesis of Resistance:

A
19
Q

What are 1st line drugs?

A

Rifampicin, isoniazid, ethambutol, pyrazinamide

20
Q

What is Mono-resistant TB?

A

Resistance to only 1 anti-TB drug w/o resistance to other drugs

21
Q

What is Poly-drug resistant TB?

A

Poly-drug resistant TB: resistane to more than 1 anti-TB drug other than both isoniazid and rifampicin

22
Q

What is Multi-drug resistant TB (MDR-TB)?

A

Multi-drug resistant TB (MDR-TB): resistance to isoniazid’s and rifampicin with or without resistance to other anti-TB drugs

23
Q

What is Rifampicin resistance TB (RR-TB)?

A

Resistance to at least rifampicin with or without resistance to other drugs. This category includes MDR-TB, rifampicin mono-resistant TB, pre-XDR-TB
and XDR-TB

24
Q

What is Pre-extensively drug resistant TB (Pre-XDR-TB)?

A

Pre-extensively drug resistant TB (Pre-XDR-TB): TB caused by M. Tuberculosis strains that fulfil the definition of MDR/RR-TB and are also resistant to any flouroquinolone

25
Q

What is Extensively drug resistant TB (XDR-TB)?

A

TB caused by M. Tuberculosis that fulfil the definition of MDR/RR-TB and that are also resistant to any flouroquinolone and at least one additional
Group A drug

26
Q

Grouping of DR TB drugs:
Group A:

A
27
Q

Grouping of DR TB drugs:
Group B:

A
28
Q

Grouping of DR TB drugs:
Group C:

A