v. TB - The Superbug Flashcards
Tuberculosis (TB) = Tuberculosis (TB) = one of top 10 causes of death globally, leading cause from single ______ agent
infectious
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
1.6
burden
latent
SA epidemiology:
SA epidemiology: Incidence in 2018: 520/100 000 ppl; MDR/RR TB: 3.4% (new cases) & 7.1% (previously treated cases) [MDR - Mutlidrug resistant]
What are the risk factors?
Diabetes, malnutrition, tobacco smoking, alcohol abuse, underlying social determinants (overcrowding etc.)
Mycobacterium tuberculosis complex:
Human TB - Group of genetically v closely related variants (10 species); Includes:
M. Tuberculosis (L1-4, L7); M. Africanum (L5, L6)
Mycobacterium tuberculosis complex:
> __% of human TB caused by M. Tuberculosis
90
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 = ______ ______ _______
MTBC
inconsistent btwn studies
What is the description of M. Tuberculosis complex?
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
M. Tuberculosis complex:
In liquid cultures, often grow as twisted rope-like colonies termed _______ cords.
serpentine
Slow generation tome (divides once in 24h); Optimal growth temp = 35-37 deg, obligate aerobes, _______ intracellular pathogen
facultative
Structure of cell wall:
Mycobacteria
Mycolic acid:
- 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
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
taxonomy
+‘ve
Acid fast staining procedure (Ziehl Neelsen stain): promote uptake of dye -
- Primary stain: carbon ______ - apply heat -> allow penetration of stain thru wall
- De-stain w/ acid alcohol: mycolic acid residues retain primary stain even after ______ to acid-alcohol -
RESISTANCE TO ____________ REQ TO BE TERMED ACID FAST - Counterstain w/ _______ blue to highlight background for easier microscopic rec
fuchsin
exposure
DECOLORISATION
methylene
Latent TB infection versus TB disease:
Resistance to antibiotics:
Mycobacteria =
inherently resistance to numerous antibiotics: attributable to cell wall - low rate of diffusion thru cell wall
Resistance to antibiotics:
Acquired resistance:
Acquired resistance: almost exclusively thru chromosomal mutations in genes req for antibiotic action - genes encoding protein target of drugs, enzymes req for prodrug activation
Resistance to antibiotics:
Eg. Rifampicin resistance:
Single-nucleotide substitution mutation in small region or rpoB (gene encoding Beta subunit of DNA-dependant RNA Polymerase)
Resistance to antibiotics:
- Resistance in MTB complex:
Rifampicin resistance determining region (RRDR) - around 96% of mutations conferring rifampicin resistance confined w/in a 81 base pair region of rpoB gene.
Resistance to antibiotics:
Molecular tech to diagnose TB and provide _______ susceptibility: Xpert MTB/RIF and MTBDRplus (binding probes extend across the RRDR)
rifampicin
Pathogenesis of Resistance:
What are 1st line drugs?
Rifampicin, isoniazid, ethambutol, pyrazinamide
What is Mono-resistant TB?
Resistance to only 1 anti-TB drug w/o resistance to other drugs
What is Poly-drug resistant TB?
Poly-drug resistant TB: resistane to more than 1 anti-TB drug other than both isoniazid and rifampicin
What is Multi-drug resistant TB (MDR-TB)?
Multi-drug resistant TB (MDR-TB): resistance to isoniazid’s and rifampicin with or without resistance to other anti-TB drugs
What is Rifampicin resistance TB (RR-TB)?
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
What is Pre-extensively drug resistant TB (Pre-XDR-TB)?
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
What is Extensively drug resistant TB (XDR-TB)?
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
Grouping of DR TB drugs:
Group A:
Grouping of DR TB drugs:
Group B:
Grouping of DR TB drugs:
Group C:
