Tuberculosis: Pathogen, Pathology, Treatment Flashcards
Describe the incidence of TB over time.
Massive decline in incidence of TB in Europe in 19th century prior to any diagnostic test to identify disease or any drug to treat disease
Due to improvement in living standards, reduction in poverty, reduction in overcrowding . Further decline as a result of BCG, streptomycin.
Resurgence of TB in recent years.
Explain the reasons for the recent resurgence of TB.
1) Poverty: Failure to deal with extreme poverty in some of the poorest part of the world
2) Health systems: e.g. Soviet Union
During it, TB was managed by strong but authoritarian programs so when it collapsed, programmes collapsed too (particularly in prison populations).
3) HIV (esp. in Africa): HIV predisposes to “overt TB in people also infected with M. TB”.
Mycobacterium-tuberculosis:
- Structure
- Generation time
- Special features
- Structure: Acid-fast, fungus-like, gram positive bacterium with waxy cell wall.
- Generation time: Slow (17 h)
- Special features: Myobacterium TB has complex metabolic responses in latent/persistent state.
Explain the implications of the structure of TB on diagnosis and treatment.
Outer cell wall very thick and waxy (difficult to penetrate).
- Good from diagnostic POV (on miscroscope slide, dyes cannot penetrate very well so can use dyes to identify M. TB).
- Bad for treatment (drugs cannot get in very well so cannot kill TB cell)
Define generation time.
Time taken by the bacteria to double in number during a specified time period
What is the implication of the generation time of M. TB on diagnosis and treatment.
♦ Diagnosis: If using growth of TB cells to confirm is patient has infection, have to wait several days, sometimes several weeks to get confirmation.
♦ Treatment: Cellular processes drugs are trying to interrupt are very very slow (so
need to treat patients for long time in order to get results)
Summarise the pathogenesis of tuberculosis.
1) Transmission
2) Primary Infection
3) Latent Infection (majority never get to 4)
4) Active Disease (does not always occur, may not be sick for entire lifetime)
Identify factors which increase likelihood of developing active disease once the infection is latent.
♠ HIV
♠ Cancer chemotherapy (in general, depressed immune system)
♠ anti-TNFα treatment (in general, depressed immune system)
♠ low IFNγ (in general, depressed immune system)
♠ vitamin D deficiency
♠ Immune immaturity/senescence
How is TB transmitted ?
person inhales droplet nuclei containing tuberculosis bacteria (e.g. from someone sneezing or coughing, i.e. aerosol).
How many TB organisms does someone with TB approximately have per mL sputum ? What is the size of their droplet nuclei ? How many bacteria are there per droplet ?
10^8 organisms/mL sputum.
Droplet nuclei <5μm
Each with ~6 bacilli
What are the main factors influencing infection to TB ?
1) Number of infecting bacili (i.e. bacterial load)
2) Duration of Exposure
3) Strength of immune system (probably the most important factor once infected, in determining whether you ever actively fall sick)
High bacterial load, long exposure and a weak immune system would all contribute to a high probability of developing TB.
A weak immune system would further increase the probability of actually displaying the active illness.
Describe the timeline of TB.
1) Primary Infection
2) Primary disease (if get active disease soon after infection, especially in children). This is non-infectious
3) Secondary disease (years later, after TB rests in lymph nodes in the lungs. Due to endogenous reactivation following depression of the immune system, usually infectious especially if smear positive i.e. can see bacteria you are coughing out
4) Can potentially be cured, but if so can get re-infected later
5) If re-infection following cure, can get secondary disease due to exogenous re infection, which is usually infectious especially if smear positive.
6) Potentially death
How is TB infection diagnosed ?
1) Tuberculin Skin Test (TST) (= Mantoux test): inject protein from TB under skin. If you have encountered it before, localised inflammation, arm becomes red. Otherwise ignore that small protein load and mark goes away.
2) Interferon Gamma Release Assays (IGRA): take blood sample, which you stimulate using TB antigens and if blood able to produce high quantity of interferon soon after, evidence of reprimed immunological response.
These two^ can diagnose asymptomatic TB.
3) Sputum smear microscopy (a little insensitive, requires high amount of pathogens)
4) Sputum culture (gold standard, can use liquid or solid media)
5) Molecular Testing (“GeneXpert”): take sputum sample, put it into cartridge, place into machine, runs PCR to detect nucleic acids of TB cells from sputum sample.
What is the difference between pulmonary TB and clinical (i.e. active illness) TB ?
85% of clinical TB are pulmonary TB
What type of TB patient contributes to the majority of TB transmission ?
Sputum smear positive pulmonary TB patients contribute to most of the community transmission of TB.
Why is being smear positive so significant in transmission ?
Because smear positive means sufficient bacteria in the lungs that they actually cough them out and can see them on microscope.
Important because can more quickly transmit disease + can be more severe TB .
