Tuberculosis - Lecture notes week 8 - respiratory PDF

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Tuberculosis

Epidemiology  Seen commonly in: o Elderly  commonly acquired when younger and stays with them for life, sprouting again due to other reasons o Less developed countries o Immunocompromised  Prevention o Public health measures  e.g. no spitting o Early detection to prevent development and spread  x-rays can identify before symptoms even show Microbiology  Mycobacterium tuberculosis o Colonise in fluffy white appearance o Slow growing  takes weeks to colonise o Need to use special stains in order to identify:  Ziehl Neelsen Stain  Pink rod-like bacteria among blue cell components  Presents as resistant to alcohol and acid  Auramine staining  Fluorescent stain  yellowish/green  Not as specific but more sensitive o Likes apex of lungs  higher oxygen concentration  Other mycobacteria: o M. Bovis  Causes TB in Cows  can cause mild infection in humans o M. Kansasii o M. Chelonae o M. Abscessus o M. Fortuitum o M. Leprae  causative organism of leprosy Progression of infection  Inhaled pathogen due to transmission through coughing up pathogen: o Can be caught by epiglottis and swallowed, preventing the infection  90-95% of infected individuals will control the infection and suppress the pathogen o Develop a TB lesion  Ghon complex  this is a lesion on the lung, along with an enlarged lymph node into mediastinum  Weill not be able to feel lymph node as is not peripheral, but may appear on imaging  The healed Ghon complex may cause calcification o However, the pathogen remains in the system as dormant, but can spread haematogenously:  DNA can be detected in tissues by in situ PCR in order to prevent reoccurrence o Reactivation of TB can occur later in life:

 Cell-mediated immunity gets weaker as we get older  Immunosuppression or HIV can cause reactivation  Smoking also increase risk of reinfection  Progresses to primary progressive TB (cavitary TB)  5-10% of infected individuals will be unable to suppress initial infection and will develop primary progressive TB o This develops cavities of TB which open into the bronchi, enabling the spread of M.Tuberculosis by coughing Types of TB / Complications  Miliary TB o This is still in the lung but is wide spread lesions, appearing like millet seeds on x-ray  CNS TB o Fairly common o Can spread to brain parenchyma  haematogenous spread o Necrotic structures in the brain  Typically affects base of brain, affecting lower cranial nerves o Can cause meningitis  slower onset  Renal TB o Renal parenchyma replaced by calcified material, preventing function  Testicular TB o Resembles Tumour but easily treatable  Bone and joint TB Pathogenesis  microscopic appearance  Formation of a granuloma o Central causeous necrosis o This is surrounded by a thin layer of macrophages  epithelioid cells  Thought to be like epithelium when named but nothing alike o Surrounding this is a collection of highly activated lymphocytes o Also amongst the lymphocytes are various giant cells Immunity to TB  Not s sterilised immune response  infection is controlled but dormant pathogen remains  Cell-mediated immunity is crucial  pathogen grows and develops inside cell o Macrophages are the key controlling cell o T cell production of interferon gamma o Cytokines involved in this process are all key  Immune response: o Pathogen invades APC (dendritic or macrophage) and survives within the vacuole o This causes MHC II presentation which binds to specific receptor on T cells o The APC produces IL-12 and IL-18 because of the pathogen within it  these act on the bound T cells, causing them to proliferate and develop into T-Helper cells o These T-Helper cells now produce Interferon-gamma and TNF  key cytokines involved in the augmentation of APC and ability to kill the pathogen  Resistance to TB can be due to lack of IFNγ or IL-12/18 deficiency  deficiencies in mediator cytokines Detection  Mantoux Reaction

TB given under skin, so that it cannot spread anywhere or cause harm but can tell if there has been a reaction o If there has been TB before, and dormant TB is visible, then skin will react to this, producing many granulomas and forming a raised mark (>1.5cm)  T spot test o Separated WBCs are counted and added to microtiter plate wells that have been coated with monoclonal antibodies to IFNγ o Disease-specific antigens are added, causing the release of IFNγ from sensitised T cells  captured by antibodies o Wells are washed and conjugated secondary antibodies are added to bind to any of the captured IFNγ o Substrate is added to visualise the IFNγ  produces highly visible spots o The spots can then be counted  1 spot is 1 T cell o

Treatment  The drug treatment has a long duration of 6 months, using a combination of drugs to reduce the rise of resistance o At least two drugs to which bacilli are sensitive must be present  drug resistance is increasingly common o Some drugs are only effective when bacilli are dividing rapidly and lack effect against slower growing forms such as pyrazinamide  Current regimen: o Rifampicin, Isoniazid, Pyrazinamide and ethambutol  Drop ethambutol is sensitive to Rifampicin and Isoniazid  Stop pyrazinamide after 2 months  Continue Rifampicin and Isoniazid for another 4 months  Give prophylactic Pyridoxine to prevent neuropathy caused by Isoniazid  Complications:  Rifampicin induces cytochrome p450 and thus alters metabolism of many drugs, such as steroids  Rifampicin, Isoniazid and Pyrazinamide are metabolised in the liver, increasing the potential for toxicity  Ethambutol can affect vision  Rifampicin turns urine reddish...