Lecture 8.2 - Mycobacterium Tuberculosis PDF

Mycobacterium species: Culture: Properties of mycobacterium tuberculosis: ◦Aerobes ◦Cell wall - mostly lipids (60%) including mycolic acid ◦These lipid, polysaccharides and peptides form a waxy cell surface which is hydrophobic and resistant to disinfectants, acids and alkali...

Mycobacterium species: Culture: Properties of mycobacterium tuberculosis: ◦Aerobes ◦Cell wall - mostly lipids (60%) including mycolic acid ◦These lipid, polysaccharides and peptides form a waxy cell surface which is hydrophobic and resistant to disinfectants, acids and alkali ◦The lipids also prevent penetration of the cell wall with most chemical dyes for example dyes used in Gram staining ◦Classified as acid-fast bacteria ◦Ziehl-Neelsen stain. Smear is fixed, stained with carbol-fuchsin, decolourised with acid-alcohol and counterstained with methylene-blue. Acid- fast bacilli appear pink in a contrasting background. ◦Need in excess of 10,000 organisms per ml of sputum to visualise the bacteria (x1000 magnification) Facts and figures: ◦Infection with mycobacterium tuberculosis (TB) is one of the top 10 causes of deaths in the world. ◦1/4 of the world's population is believed to have been exposed to TB at some point (latent TB) ◦People infected with TB have a 5-10% lifetime risk of falling ill with TB ◦Immunocompromised individuals e.g. people with HIV, malnutrition, diabetes, old age ahev higher risk of developing active infection ◦Social risk factors e.g. homelessness, drugs, alcohol, prison, migration ◦In 2022, an estimated 10.6 million people fell ill with TB, and 1.3 million people died from the disease (including 167,000 people with HIV) ◦In 2022, an estimated 1.3 million children became ill with TB. Child and adolescent TB is often overlooked by health providers and can be difficult to diagnose and treat. Rates of TB worldwide:  Transmission: ◦Person to person by inhalation of droplets in the air containing bacteria from cough, sneeze, split of infected person Infection: ◦Primary disease - granuloma formation ‣ Mycobacterium tuberculosis is phagocytosed by alveolar macrophages ‣ M.tuberculosis survive in the macrophages by producing sulfolipids which inhibit fusion of phagocytic vesicles (phagosomes) with lysosomes ‣ The presence of M.tuberculosis initiates an inflammatory response causing lymphocytes and macrophages to migrate to the area where they surround the area of infection forming a granuloma in an attempt to wall off the bacteria and prevent spread ‣ After 3-4 weeks many macrophages within the granuloma die releasing the bacteria and forming a caseous centre surrounded by macrophages and lymphocytes ‣ Tissue damage occurs due to the destruction of the organism and phagocytes which release degradative enzymes and reactive oxygen species such as superoxide radicals Latency: ◦The granuloma may undergo fibrosis and calcification and bacteria may persist but they do not multiply ◦The bacteria may be eradicated ◦Affected individuals may be asymptomatic or have mild flu-like illness ◦Once latent, most people remain non-symptomatic and are not contagious ◦5-10% go on to active infection and are contagious ◦In some individuals, the bacteria keep multiplying in the centre of the granuloma which may rupture, releasing the bacteria into the bronchiole, resulting in respiratory infection and haematogenous spread to other systems of the body. Reactivation: ◦Mainly occurs in granulomas in the lungs although can happen at any site ◦M.tuberculosis growth causes caseation necrosis (destruction of lung tissue resulting in cavities where bacteria grow) ◦Large numbers of bacteria are present in the lungs and as a result are shed when the person sneezes or coughs ◦Haematogenous spread to other parts of the body and miliary tuberculosis (immunocompromised) Reasons for reactivation: ◦Immunocompromised (medication/infection, for example HIV) ◦Elderly ◦Severe stress ◦Malnutrition ◦Alcoholism ◦Migration Incidence of extrapulmonary TB: ◦Only 10% of immunocompetent individuals who have latent TB develop active infection ‣ Extrapulmonary TB accounts for 15-20% of the active TB cases ◦In HIV positive individuals ‣ Extrapulmonary TB accounts for 50-60% of the active TB cases  Extrapulmonary TB: ◦Meninges - meningitis ◦Kidneys - sterile pyuria (elevated WBC in urine) ◦Liver - hepatitis ◦Lumbar vertebrae - Pott's disease ◦Miliary Tuberculosis (normally in immunocompromised individuals) Common symptoms of TB: ◦Fever ◦Night sweats ◦Cough ◦Haemoptysis ◦Chest pain ◦Weakness ◦Weight loss Diagnosis: ◦Chest X-ray ◦Sputum sample (Ziehl-Neelsen stain, also called acid fast stain) ◦Sputum culture (Lowenstein Jensen culture) ◦Bronchoalveolar lavage (culture) ◦PCR ◦Xpert MTB/RIF - diagnoses rifampicin resistance (a surrogate marker for MDR-TB) and takes approximately 90 minutes ‣ The Xpert MTB/RIF assay is a nucleic acid amplification (NAA) test Skin test for diagnosis of TB: ◦Mantoux skin test ‣ Intradermal injection of purified protein derivative ‣ Measure size of area of induration after 48-72 hours ‣ Positive result may be due to infection, non-TB mycobacteria, latent infection or vaccination with BCG ‣ False negative could be due to immunocompromised status Blood test: ◦Interferon Gamma Release assay (IGRA) ◦Fresh blood from the patient is mixed with antigen derived from Mycobacterium tuberculosis. The white blood cells from a person with active or latent infection will release interferon gamma which can be measured ‣ Detects evidence of exposure to Mycobacterium tuberculosis ‣ Specific to Mycobacterium tuberculosis ‣ Indicator of latent infection as well as active infection with Mycobacterium tuberculosis ‣ IGRA test does NOT distinguish between latent and active infection ‣ Negative in subjects who have received BCG vaccine as this is an attenuated strain of Mycobacterium bovis which is different from Mycobacterium Tuberculosis  Treatment: ◦Treatment can be between 6-18 months ◦Respiratory TB ‣ 2 months treatment (killing phase) with - Rifampicin, Isoniazid, Pyrazinamide, Ethambutol Patient may be non-infectious in 2-3 weeks ‣ 4 months treatment (kill remaining bacteria and stop relapse with - Rifampicin and Isoniazid ◦Longer treatments may be need for resistant bacteria Antibiotic resistance: ◦Resistant to first line antibiotic (RifampicinIsoniazid/Isoniazid) ‣ Treatment no longer than 6 months ◦Muti drug resistant TB (MDR-TB) resistant to 2 first line antibiotics ‣ Add a second line antibiotic e.g. Flouroquinolone ◦Extensively drug resistant TB (XDR-TB) resistant to first and second line antibiotics ‣ High mortality Notification: ◦TB is a notifiable disease ◦Contract tracing ◦Outcome Prevention of TB: ◦Vaccination ◦Reporting ◦Contact tracing ◦Chest X-ray (for pulmonary TB) BCG vaccine: ◦Live attenuated strain of Mycobacterium bovis (Bacillus Calmette Guerin) ◦BCH vaccination was routine in the UK as the death rate due to TB was high ◦With better diet, living conditions and knowledge about prevention and vaccination, it was almost eradicated by the 1980s. The incidence started to increase due to immigration, homelessness, HIV etc ◦BCG vaccination is now recommended for all babies up to one year old who are born in areas in the uk where rate of TB is high or they have parents or grandparents who were born in areas of the world with high TB rates ◦BCG is also recommended for children and adults under the age of 35 years who are at risl of catching TB