Tuberculosis Revised by Dr. Magdy Awny 2018

What is Tuberculosis? “Tuberculosis is defined as an infectious disease caused by a bacterium; that most commonly affects the lungs.” M. Tuberculosis is an OBLIGATE aerobe and a facultative intracellular parasite. Tissues attacked are characterized by high oxygen tension. acultative intracellular parasites are capable of living and reproducing either inside or outside cells.

How is T.B spread? Tuberculosis is an airborne disease When a person with active TB disease : coughs, sneezes, speaks, or sings. People nearby may breathe in these bacteria and become infected. When a person breathes in TB bacteria, the bacteria can settle in the lungs and begin to grow.

Extra-pulmonary TB In some cases, a TB infection can spread from the lungs to other parts of the body. It is more common in people with weakened immune systems particularly people with an HIV infection. A TB infection can spread to: Lymph nodes that are near the lungs (lymph node TB) Bones and joints (skeletal TB) The digestive system (gastrointestinal TB) The bladder and reproductive system (genitourinary TB) The nervous system (central nervous system TB)

Pathogenic Life Cycle of M. tuberculosis infection It initiates when fine aerosol particles containing the bacteria coughed up by an individual with active disease are deposited in the lower lungs of a new host. The bacteria recruit macrophages to the surface of the lung, which become infected, and serve to transport the bacteria across the lung epithelium to deeper tissues. A new round of macrophage recruitment to the original infected macrophage is initiated, forming the granuloma, an organized aggregate of differentiated macrophages and other immune cells. The granuloma in its early stages expands infection by allowing bacteria to spread to the newly arriving macrophages. As adaptive immunity develops, the granuloma can restrict bacterial growth. However, under many circumstances, the infected granuloma macrophages can undergo necrosis, forming a necrotic core that supports bacterial growth and transmission to the next host. 

(clinical/pneumonia) Mycobacterium tuberculosis produces two distinct types of disease: primary and post primary tuberculosis. Mycobacterium Lungs Primary Spontaneous resolve with scar Latent T.B (Granuloma) Active T.B (clinical/pneumonia)

lymphocytes (CD4 + CD8 + B cells) Caseating granuloma = central area of caseous necrosis + macrophages lymphocytes (CD4 + CD8 + B cells) Caseation is a process of coagulation necrosis. Organisms are contained and constrained within caseating granulomas, but not all are killed. Gohn complex

Pathogenesis of TB: Infection - Immunity

Active vs. latent immune system stop bacteria inactive bacteria remain alive in the body and become active later. (latent TB infection) People with latent TB infection: Have no symptoms Don’t feel sick Can’t spread TB bacteria to others May develop active TB disease if they do not receive treatment for latent TB infection Usually have a positive skin test Have a normal chest x-ray and a negative sputum smear

Active vs. latent immune system can’t stop bacteria active bacteria multiply in the body causing active TB disease. People with weak immune systems : Babies and young children People infected with HIV, the virus that causes AIDS Substance abuse Diabetes mellitus Cancer of the head or neck Severe kidney disease Certain medical treatments (such as corticosteroid treatment or organ transplants)

People are more susceptible to TB infection People with lower or compromised immune systems such as people living with HIV, children, the elderly or people with poor nutrition. Persons from high TB burden countries (Russia, Southeast Asia, Latin America, and the Philippines) Persons living in crowded conditions with low ventilation such as in prisons Persons in close contact with someone who has infectious TB Persons with medical conditions such as diabetes and certain types of cancers. Drug users

Diagnosis CHEST X-RAY: can reveal evidence of active tuberculosis pneumonia. Other times, the X-rays may show : scarring (fibrosis) hardening (calcification) in the lungs, suggesting that the TB is contained and inactive.

Batceriological diagnosis (sputum test) Examination of the sputum on a slide (smear) under the microscope can show the presence of the tuberculosis-like bacteria. Bacteria of the Mycobacterium family stain positive with special dyes and are referred to as acid-fast bacteria (AFB).

Get Tested Tuberculin skin tests (Mantoux test): also known as the PPD (purified protein derivative) test. Small amount of purified extract from dead tuberculosis bacteria is injected under the skin. -ve skin test: No infection. Infected immunocompromised patient. +ve skin test: Infected patient. Recently vaccinated.

Symptoms of Tuberculosis Feelings Of Sickness Or Weakness Fever Night Sweats Coughing Chest Pain Weight Loss Coughing Up Of Blood. Symptoms Of TB Disease In Other Parts Of The Body Depend On The Area Affected.

Prevent development of Treatment Prevent development of Drug resistance Cure the pt. Prevent transmission Prevent death Prevent relapse

Isoniazid Rifampin Ethambutol Pyrazinamide: Mechanism of action - kills actively growing tubercle bacilli by inhibiting the biosynthesis of mycolic acids which are major components of the cell wall of M. tuberculosis. - INH is bactericidal to rapidly-dividing mycobacteria, but is bacteristatic if the mycobacterium is slow-growing. Rifampin Inhibits DNA-dependent RNA polymerase activity in susceptible cells. It interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. Has bactericidal activity against slow and intermittently growing M. tuberculosis organisms (both intracellular and extracellular ) Ethambutol Diffuses into actively growing M. tuberculosis such as tubercle bacilli. Ethambutol (ETH) inhibits arabinosyl transferases involved in cell-wall biosynthesis. Pyrazinamide: The target of pyrazinamide is the mycobacterial fatty acid synthase I gene involved in mycolic acid biosynthesis.

Isoniazid Rifampin Ethambutol Pyrazinamide: Hepatitis, joint pains Side effects Isoniazid Peripheral neuropathy, hepatitis in patients above age of 40, rashes and fever. Peripheral neuritis is corrected by supplementation of 25 to 50 mg per day of pyridoxine (vitamin B6) Rifampin Loss of appetite, nausea, hepatitis, orange coloration of urine and other body fluids, reduced effectiveness of the oral contraceptive pills Ethambutol Visual disturbances (poor vision and color perception) Pyrazinamide: Hepatitis, joint pains

Rules For Anti TB drugs The preferred 6-month treatment program for drug-sensitive tuberculosis in adults and children consists of isoniazid,rifampin, pyrazinamide, and ethambutol (or streptomycin) for 2 months, followed by isoniazid & rifampin (for sensitive organisms) for 4 additional months. The combination of isoniazid and rifampin for 9 months is equally effective for sensitive tuberculosis. HIV-infected patients may benefit from longer (9–12-month) treatment regimens. An initial 5- or 6-drug regimen may be appropriate in patients likely infected with multidrug-resistant strains.

MDR TB Multidrug-resistant TB (MDR TB) is TB that is resistant to at least two of the best anti-TB drugs, isoniazid and rifampin.( first-line drugs ) Drug resistance is more common in people who: Have spent time with someone with drug-resistant TB disease Do not take their medicines as directed by their doctor or nurse Develop active TB disease again, after having taken TB medicines in the past Come from areas where drug-resistant TB is common Treatment takes much longer than regular TB. And, people with MDR TB are at greater risk of dying from the disease Duration: The standard TB treatment takes between six to nine months. However, treatment for MDR takes up to 24 months One-fifth of all warts disappear within six months

vaccine Bacille Calmette Guerin also known as BCG It is derived from Mycobacterium bovis which is closely related to Mycobacterium tuberculosis but offers some protection from developing active tuberculosis, especially in infants and children. Relationship between TB and HIV. TB kills up to half of all AIDS patients worldwide. People who are HIV-positive and infected with TB are up to 50 times more likely to develop active TB in their lifetime than people who are HIV-negative.

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