TB Flashcards
what were the 7 impacts of COVID-19 on global TB control?
1) increased stigma to TB symptoms such as a cough
2) resources diverted and focused on the management of of covid.
3) reduction in TB notifications to as low as 40% n some countries.
4) loss of employment and livelihoods aggravating poverty, major risk for tb.
5) shrinking global economy putting a strain on the money available for TB responses.
6) excess deaths which would otherwise be prevented.
What are 3 reasons WHO and UN TB treatment targets were not met?
1) Poverty
2) health systems
3) HIV (TB is an opportunistic disease that re-activates in the immunosuppressed)
what is TB causes by?
what are this bacterias properties?
how can TB stay dormant?
- TB is caused by mycobacterium tuberculosis
- waxy (mycotic acid rich) cell wall
- gram positive
- acidfast (this gives the bacteria the ability to resist decolonisation by acid during staining procedures.
- slow generation time when using different staining.
- it has a complex metabolic response in latent/persistent state.
4 steps in the pathogenesis of tuberculosis?
1- transmission
2- primary infection
3- latent infection
4- active disease
transmission and primary infection?
transmission = airborne infectious aerosol
primary infection = occurs when someone inhales MTBand it goes deep into the lung and alveoli.
latent infection and active disease?
latent infection = a granuloma forms which contains MTB and macrophages and other immune cells surround it.
active disease = granuloma breaks up and releases MTB into surrounding area.
what are the 5 factors that can influence tuberculosis to go from a primary infection to active disease?
HIV
TNF-a
IFN-y
Vitamin D
immune immaturity.
what are the factors influencing infection?
- number of infection bacilli
- exposure
- immune system
what are the 2 ways that we can diagnose tuberculosis infection?
1) Mantoux test (tuberculin skin test)
2) interferon gamma release assays (IGRA)
what Is the most common type of TB?
how do you diagnose pulmonary tuberculosis disease?
- the most common TB case are pulmonary TB disease
- diagnose = ‘sputum smear positive’ these patients are believed to cause the majority of transmission.
what are the typical symptoms of pulmonary TB?
- cough of 2-3 weeks (not responding antibiotics)
- fever
- sputum production
- night sweats
- weight loss
what are the 2 types of sputum smears?
- auramine stain
- Ziehl Nielsen stain
How do solid and liquid sputum cultures compare?
What are 2 positives of sputum culture?
What are 3 negatives of sputum culture?
Solid sputum culture has less sensitivity, and very few bacteria can grow
Liquid sputum culture has very sensitive, but it is so rich that even other bacteria can grow, leading to false positives
2 positives of sputum culture:
1) Additional 20-30% diagnostic yield
2) Susceptibility testing
3 negatives of sputum culture:
1) Expensive
2) Slow
3) Biohazard
What are 6 advantages of the Xpert MTB/RIF: Rapid Automated TB Culture System?
What is a disadvantage?
6 advantages of the Xpert MTB/RIF: Rapid Automated TB Culture System:
1) A two-hour test
2) Detects TB bacilli
3) Determines RIF resistance
4) 95% sensitive
5) 95% specific
6) Little technical expertise
A disadvantage is that it is expensive
What is TB-MBLA?
What is it used for?
How does it do this?
- Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) is a molecular test
- This test can be used to monitor treatment response
- It can measure the number of MTB without growing them in culture and monitor how many remain after treatment
how will primary Tb appear on X-ray?
what is this complex?
- with a Ghon complex
- this complex consists of:
- small (often calcified) focus of pulmonary infection
- associated lympandenopathy
how does secondary TB appear on X-ray?
- cavitation = almost always secondary disease
- military TB = can be primary or post primary disease
what is military and cavitation?
- Miliary TB is a potentially fatal form of disseminated secondary TB
- organism draining through lymphatics end up in venous blood stream and going to lungs
- Cavitations are a feature of secondary TB
- Cavitation is a dangerous consequence of pulmonary TB associated with poor outcomes, treatment relapse, higher transmission rates, and development of drug resistance.
However, in the antibiotic era, cavities are often identified as the extreme outcome of treatment failure and are one of the least-studied aspects of TB
How is TB classified?
What is miliary TB classified as?
What is extrapulmonary TB?
- Tuberculosis may be classified according to site of disease as pulmonary or extrapulmonary
- Miliary disease has been classified as both an extrapulmonary and a pulmonary form of TB
- Extrapulmonary TB is TB that occurs anywhere other than the lungs
What was the original treatment of TB?
Why is it not used as much for TB anymore?
Streptomycin was one of the original medications used for TB
It isn’t used as much for TB anymore due to Streptomycin resistance being developed in some TB bacilli
What are the 4 drugs used in the intensive phase of TB treatment?
What are the 2 drugs used in the continuation phase of TB treatment?
4 drugs (all orals) used in the intensive phase of TB treatment (first 2 months):
1) Rifampicin (R)
2) Isoniazid (H)
3) Pyrazinamide (Z)
4) Ethambutol (E)
2 drugs (all orals) used in the continuation phase of TB treatment (4 months)
1) Rifampicin (R)
2) Isoniazid (H)
what is the current first line anti-TB drug?
how does it work?
dose
Rifampicin
Rifampicin is highly bactericidal against rapidly replicating and non-replicating bacteria
It works by Inhibiting bacterial DNA-dependent RNA polymerase
Rifampicin is also crucial to short courses of chemotherapy
Rifampicin has a current single daily oral dose (10mg/kg)
Rifampicin Induces liver enzymes (CYP450) increasing clearance of other drugs:
1) Warfarin
2) OCP (oral contraceptive pills)
3) Anti-retroviral therapy interaction
what are the 3 toxicities of rifampicin?
1) Hepatitis
2) Itch, rash, GI upset
3) Discolouration of urine, tears, sweat,
what is the 2nd first line TB drug?
how does it work?
dose
Isoniazid is highly bactericidal against rapidly replicating bacteria
It Inhibits mycolic acid biosynthesis in cell wall (amongst others)
Isoniazid is a pro drug activated by KatG enzyme
Isoniazid has an easily tolerated orally in single daily dose (5mg/kg)
what are the 3 toxicities of Isoniazid?
1) Hepatitis
2) Peripheral neuropathy – minimized by using pyridoxine (vitamin B6)
3) Resistance – overall 10%, varies by population
what is the 3rd first line treatment of TB?
action?
dose?
Pyrazinamide is bacteriostatic (prevents bacterial growth), but bactericidal at acid pH (e.g. inside cells)
It inhibits fatty acid synthetase I
In combination therapy, Pyrazinamide accelerates sterilizing effects of isoniazid and rifampicin, allowing 6-month treatment
The dose for pyrazinamide is once daily dose (15-35 mg/kg/day)
what are the 2 toxicities of Pyrazinamide?
1) hepatitis
2) Hyperuricemia (lab test); can exacerbate gout
* Hyperuricaemia is an abnormally high level of uric acid in the blood, associated especially with the disease gout
what is the 4th first line treamtn of TB
action
dose
Ethambutol is bacteriostatic (prevents bacterial growth)
Ethambutol inhibits Arabinosyl transferase
The dose of Ethambutol is a usually well tolerated Single daily dose (15mg/kg)
Ethambutol is mainly added to regimen to help prevent resistance to other drugs what is the
What is a toxicity of Ethambutol?
A toxicity of Ethambutol is Optic neuritis (uncommon at < 15 mg/kg)
What did 3 clinical trials try to use to reduce treatment duration of TB?
Why did they not work?
There were 3 major clinical trials published on 2014
All attempted to use 8-methoxyfluoroquinolones to reduce treatment duration
All failed because of high rates of post-treatment relapse in experimental arms
What are 2 mutations that cause Isoniazid resistant TB strains?
What mutation causes Rifampicin resistant TB strains?
Which resistance usually comes first?
1) katG mutations account for 50-90% of ISONIAZID RESISTANT TB strains
2) inhA mutations account for ~31% of ISONIAZID RESISTANT TB strains
rpoB mutations account for 96% of RIFAMPICIN RESISTANT TB strains
Resistance to Isoniazid usually precedes resistance to Rifampicin
What are 3 examples of drug-resistant TB?
What are they each resistant to?
3 examples of drug-resistant TB:
1) MDR-TB
* Resistant to Rifampicin and Isoniazid
2) Pre-XDR-TB
* Additional second line drug resistance to: any injectable second line drug treatment or fluoroquinolone
3) XDR-TB
* Additional second line drug resistance to: any injectable second line drug treatment or fluoroquinolone
Global distribution of MDR-TB
Global distribution of MDR-TB:
- 30 high burden countries defined in 2015
- 45% of global total of MDR-TB cases originate in - India, China & Russian Federation
- Highest incidence per 100,000 in Eastern Europe & Central Asia
UK MDR-TB data:
~50-90 per year
1.6% of total TB cases
~90% acquired overseas
Describe the Second-line treatment for ”multi-drug resistant” TB?
1) Intensive phase
* 8 months
* At least 5 drugs (May include injectable)
2) Continuation phase
* 12 months
* At least 4 drugs All oral
What are 3 negatives of second-line drugs?
1) Less effective – patients are infectious for longer, and cured more slowly
2) More toxic – patients have more side-effects and may require several regimen changes during therapy
3) Not well studied - the best doses and combinations are incompletely understood
What studies are under investigation of multi-drug resistant TB?
what does this study highlight the use of?
Studies are currently underway to reduce the treatment of multi-drug resistant TB from 20 months to 9 – 12 months
- highlights the use of clofazimine and a high dose of 4th generation fluoroquinolone.
What is Nix-TB?
Nix-TB is a pivotal TB trial that tests the three-drug BPaL regimen, consisting of bedaquiline, pretomanid and linezolid – collectively referred to as the BPaL regimen
