Tuberculosis Flashcards
What is the causative agent of tuberculosis?
Mycobacterium tuberculosis
Mycobacterium bovis
Incubation period is 2-10 weeks
What is the characteristic of mycobacterium?
strict aerobes
rod shaped
Waxy cells wall due to mycolic acid
Acid fast: Bright red in Ziehl Nelson stain
Cell wall is hard so able to resist weak disinfectants
Able to survive on dry surfaces
How is TB transmitted?
Via inhalation of droplets
How does TB bypass phagocytosis?
Once digested by the phagasome it prevents the phagolysosome complex from being formed by releasing proteins.
What is the primary stage of TB
Most people are asymptomatic
May have flu like symptoms
3 weeks after exposure cell mediated immunity is induced:
- Immune cells surround the site of infection creating a granuloma which is the barrier against bacteria and prevent it from spreading
- tissue inside the middle dies as a a result this is knows as caseous necrosis.
Risk factors of TB
Close contacts
Children
Immunosuppression
Why do people die of TB
Delay in treatment
Inadequate treatment and disease control
Drug resistance
How does infection occur
Patient is ill within few weeks or months (active TB)
Mostly immune system deals with it (asymptomatic)
Some bacteria don’t get killed by immune system and stay in body at low levels , this is called latent TB and this reactivate to become active TB
If left untreated 65% die in 5 years
Chemotherapy can cure
What is latent TB
Asymptomatic
Don’t feel ill
Can’t spread TB to others
Usually have a positive TB test reaction or positive TB blood test
May be reactive later on in life
What is the treatment for latent tb
If aged 65 or under treatment recommended
Latent TB it’s not alway6s treated if its drug resistant
Rifampicin and isoniazid for 3 months
Isonoziad on its own for 6 months
Who with latent tb should be treated
Long term steroid
Chemotherapy
Tnf inhibitors
This is because there is a risk of infection becoming active
Clinical symptoms of Tb
Pulmonary involvement:
Cough for more than 3 weeks
Sputum/blood
Breathless
Suspect active tb:
Weight loss
Malaise
Fever
Night sweats
What are the extra-Pulmonary involvements of tB?
Swollen neck glands
Confusion
Bone pain
What is the mantoux tuberculin skin test?
The skin test requires two visits.
On the first visit, a small amount of tuberculin is injected into the skin on the lower part.
On the second visit they are invited to come back within 72 hours and results depend on the size of the raised swelling
TST size of induration
Less than 5mm: negative
At least 5mm: positive if ( hiv positive, immunosupressants)
At least 10mm: positive if recently migrated from a country, used injected drugs, work in a hospital
15mm: definitively positive
Is TB curable?
Tb is curable with antibiotics. The sooner the illness is diagnosed and treated better
Treatment of TB
Avoid delay-prompt treatment
Empirical- waiting for culture Shultz
Long treatment period- slow growing organisms
Must complete course
How to determine if it is a supervised or unsupervised regime?
Consider risk factors for adherence:
- continuous self- administration for 6 months
- compliance is the main thing for succcess
DOT directly observed therapy:
- street or homeless people
- people who have had it twice
Drug treatment rationale: why is combination drug therapy used in TB
To suppress emergence of single drug- resistant mutants
Drug treatment rationale: what is the benefit of combined formulations?
To increase the chance of adherence
Why is the TBA TREATMENT long?
The bacterium grows slowly
Why is pyranzinamide used?
To kill intracellular persisters
Why is ethambutol used?
Added in case of emergence of resistance to isoniazid - it is bacteriostatic (used with other drugs)
Why is there multi drug resistant tb
These are characterised as resistant to two or more antibiotics.
This is due to inappropriate treatment
Incorrect use
Poor quality medicines
what is the patient education for TB
What medication should be taken
Tb infection control measures
Consequences of not taking their medicine]\
What is the requirements when staying in contact with tb
-each person needs a key worker
- key workers can keep treatment on course
How is tb controlled
Identify new entrants for tb screening:
Port of arrival reports
New registrations with primary care
What is the mechanism of action of isoniazid
Bactericidal action by inhibiting mycolic acid cell wall synthesis through app-reductase
Mechanism of action of rifampicin
Bactericidal action by binding to binds to B subunit of RNA polymerase inhibiting elongation of mRNA
What is the moa of pyranzinamide
Bacteriostatic and Bactericidal :
- inhibits semi dormant bacilli residing in TB lesions
- pro drug converted into its active form pyranzinoic acid by pyrazinamidase
- disrupts bacterial membrane energetic inhibiting membrane transport
- can also inhibit fatty acid synthesis in replication
Moa of ethambutol
Interferes with arabinogalactan biosynthesis
It is bacteriostatic
Resistance mechanisms to isoniazid
Two main molecular mechanisms associated with gene mutations in Katg and inha
Resistance mechanisms of rifampacin
Have mutations in rpoB gene coding for the B subunit
Resistance mechanisms of pyrazinamide
Most strains contain mutations in the pncA gene
Resistance mechanism of ethambutol
Mutations in the embB gene
What is the definition of MDR-TB
Multidrug resistant drug
