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M. Tuberculosis (Scientific basis of disease anatomy physiology …

- - - - Neutrophils may be involved initially but soon the response is dominated by macrophages with surviving intracellular bacteria.
        
        Causes granulomatous inflammation. Majority of the damage to host is done by the immune system rather than the bacterium
    - - Inability of the immune system to eradicate the bacilli.
        
        Tissue destruction occurs as a result of the immune system trying to resolve the infection (recruitment and death of immune cells), rather than any action of the bacterium. This process represents TYPE IV HYPERSENSITIVITY
  - - - This pattern is known as the primary complex
  - - - protected by thick waxy outer layer - neither gram + or -. Identified by acid-fast test - Ziehl-Neelson stain
        
        Acid fast organisms like Mycobacterium contain large amounts of lipid substances within their cell walls called mycolic acids. These acids resist staining by ordinary methods such as a Gram stain (can appear Gram + or -)
  - - - Some travel to the draining lymph nodes (usually at the hilum) via the lymph in the interstitium
        
        At the lymph nodes, presentation of bacterial antigens result in a cell-mediated response of mainly Th1 CD4+ cells.
        
        These release cytokines (inc IFN-gamma ) that recruit and activate macrophages
        
        This results in formation of granulomas (aggregation of macrophages) in the lymph nodes
        
        In most individuals, the bacteria are eventually killed and both primary sites heal by fibrosis, often followed by calcification: RESOLUTION.
        
        However: in some individuals (esp children) the infection may persist
        
        1 more item...
        
        If any sensitised T cells reach the Ghon focus via the bloodstream, granulomas develop there as well
        
        Macrophages in granulomas become activated - enlarged with pink cytoplasm (epithelioid macrophages - resemble epithelium cells) enabling them to secrete more enzymes and kill more efficiently.
        
        Macrophages may fuse together to form giant cells (with many nuclei) - sometimes called Langhans cells
    - - usually occurs in the lungs.
        
        Persistent from first infection (or reactivated years later)
        
        true re-infection
        
        can occur at other sites via bloodspread. This doesn't lead to miliary TB, but persistence in certain favourable environments
- - - - Multi-drug resistant TB (MDR-TB)
        
        to more than one anti-TB drug
        
        at least isoniazid and rifampicin
      - Drug resistant TB
        
        to at least one first-line agent
      - Extensively drug resistant TB (XDR-TB)
        
        resistant to isoniazid and rifampicin
        
        resistant to any fluoroquinolone
        
        resistant to at least one injectable second-line drug
  - - - Continuation phase:
        
        Daily INH and RIF for 90-126 doses (18 weeks)
        or
        
        three-times-weekly INH and RIF for 54 doses (18 weeks)
- - - - Recommended for:
        
        children in countries with high prevalence of TB
        
        healthcare workers who may be at risk of exposure
        
        children in areas with higher risk of TB - eg some areas in London
        
        children with parent/grandparent from country with higher rate of TB
        
        living for 3 months or more in a country with a higher rate of TB
        
        being in prolonged close proximity with someone who has pulmonary TB
      - Not recommended for:
        
        immunosuppressed/compromised
        
        pregnant women
        
        generally not recommended in eg the USA (people not at risk)
        
        not part of routine NHS vaccination schedule - only given if expected to have increased risk
        
        Variable effectiveness against adult pulmonary TB.
        More effective against the severe forms of disease (70-80%) (eg TB meningitis
        
        not given over the age of 35 - ineffective.
      - Made from a weakened strain of Mycobaterium bovis (causing TB in cattle, and badgers) - initiates immune response
        
        Global shortage of BCG since 2015 - manufacturing problems in the SSI in Denmark, who make the vaccine. Unlicensed form (in the UK) of BCG being used, and still recommended. Prelicensed by the WHO, and licensed in other EU countries. [the supplier, InterVax, hasn't applied for UK license yet).
    - - Mantoux test (aka tuberculin skin test)
- - - - chest x-rays
        
        phlegm sample
    - - CT, MRI or ultrasound of the affected part of the body
        
        internal examination via endoscopy/laparoscopy
        
        urine and blood tests
        
        biopsy (tissue/fluid taken from the affected area)
        
        lumbar puncture
    - - Mantoux test: injection of small amont of PPD tuberculin under the skin.
        
        if sensitive to TB (ie pre-exposed) skin reaction - hard red lump at test site.
        
        if not exposed, no reaction.
        
        A very strong skin reaction may indicate active TB infection
        
        a small reaction may occur if you've had the BCG
      - Interferon Gamma Release Assay (IGRA)
        
        Blood test. May be useful if positive Mantoux test but had BCG