Lecture 1 Flashcards
What tests are you required to do if you enter the UK for, a country with common TB infections ?
Sputum test and x-ray
Define latent
You are infected with the bacteria but do not have the signs or symptoms
What patients are at more risk if they develop TB?
HIV patients
What are the symptoms of TB?
More than 3 weeks cough that is getting worse persistent and productive, temperature,fever, night sweats and chills - occurring at different times of the day, unexplained weight loss and coughing up blood
How do we diagnose TB?
X-rays, clinical examination, PCR test (rapid within 2 hrs)
How do we diagnose latent TB?
Tuberculin Skin Test (Mantoux test), molecular tests (interferon gamma release assay)
What is the tuberculin skin test ?
Tuberculin injected sc into forearm possible if skin lesion >10 mm diameter post 48-72 hrs
Describe stage 1 of TB
Inhaled in droplets, settle in alveoli of the lung, start to grow, stimulates an immune response and macrophages come out,they are phagocytosed by macrophages but they do not kill the bacilli
Describe stage 2 of TB
Asymptomatic/ mild fever, body isn’t effective at removing TB, bacteria multiple in size, macrophages in lungs 7-21 days, macrophages burst and incoming macrophages phagocytose release M.TB and the cycle repeats. This continues for 3-4 weeks
Describe stage 3 of TB
At 6 weeks symptoms of disease start to appear, cell mediated response initiated (T cell, B cell, fibroblasts), collagen fibres form around affected sites, granulomas (tubercules) formed in lung
Describe stage 4 of TB
Bacteria multiply inside macrophage, granuloma burst - uncontrolled lysis. Bacteria spread - new sites of infection process repeats. Enzymes released - destroys local tissues causing lesions
What is disseminated TB?
Spreads throughout body and can infect multiple organs
Name the 1st line treatments for active TB
Combination of 4 drugs over 6-9 months
Rifampicin and isoniazid - 6-9 months
Pyrazinamide and ethambutol for the first 2 months
Name the 1st line treatment for latent TB
Isoniazid 6 months or Rifampicin and isoniazid for 3 months
Describe the MoA of Rifampicin
Bactericidal to all metabolising cells
Targets mRNA production
Inhibits RNA polymerase
Oral
Absorption affected by food
What are the side effects of Rifampicin?
Liver damage, hypersensitivity, increased activity of other drugs eg.contraceptive pill. Red colour in body fluids e.g. urine
Define the MoA of isoniazid
TB specific
Synthesis of mycolic acid
Pro drug
Oral
Bactericidal to active growing bacilli
Bacteriostatic to very slow growing bacilli
Metabolised in the liver, excreted in the kidneys
Side effects of isoniazid
Hypersensitivity, peripheral neuropathy, liver toxicity, increased efficacy of hormonal birth control
Define MoA for pyrazinamide
Pro drug
Bactericidal to dormant bacilli
Precise mechanism/action is unclear
Oral
Side effects of pyrazinamide
Joint pain, liver damage and hypersensitivity
Define MoA of ethambutol
Bacteriostatic against growing bacilli
Increased permeability by affecting synthesis of arabinogalactan in cell wall
Oral
50% excreted unchanged in the urine
Side effects of ethambutol
Nerve neuritis and joint pain
How is TB prevented ?
Immunisation, BCG vaccine (live attenuated) given to high risk groups such as areas with high incidence, HIV positive, children with parents from a high risk country
Why is it difficult to treat TB?
Thick cell wall - antibiotics need to penetrate layer of mycolic acid
Intracellular - antibiotics need to get inside the macrophage
Long periods of treatment - side effects
Slow growing aren’t metabolically active
Define MDR-TB
Strains resistant to at least the 1st line drugs Rifampicin and isoniazid
Define pre XDR
Strains resistant to more than two 1st line drugs rifampicin and isoniazid aid resistant to any group A fluroquinolones
Define XDR-TB
Strains resistant to more than more two 1st line drugs rifampicin and isoniazid and also resistant to any group A fluroquinolones and also at least one additional group A drug
What shaped bacteria is TB
Rod shaped bacteria
What is the doubling time of TB?
15-24 hours
When TB becomes infected in the lungs what is it known as?
Pulmonary TB
When TB spreads to other organs what is it known as?
Extrapulmonary
What is the TB cell wall rich in?
Lipids, lipoarbinomanan, arabinoglactan , mycolic acid, => thick waxy lipid cell wall
What is the TB cell wall resistant to?
It is very hydrophobic
Resistant to drying, weak disinfectants, some antibiotics
Describe process of the PCR test for active TB
Someone spits into a cartilage, and it gets led into a machine
Rapid (within 2 hrs)
Sensitive to low levels of bacteria
Can detect rifampicin resistance
Can detect isoniazid resistance
