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  • There are several other species and subspecies that are included in the Mycobacterium tuberculosis complex because of their close genetic relationship to tuberculosis: [Review the slide content]
    With the exception of M. pinnipedii, all of the species in the Mycobacterium tuberculosis complex have been shown to cause disease in humans; however, M. tuberculosis is by far the most prevalent
    Mycobacterium tuberculosis is the organism responsible for most of the tuberculosis infection and disease seen in the Caribbean
    Image Credit: CDC Public Health Image Library/Dr. George P. Kubica
  • Pose question to participants “How is TB transmitted?”
    Solicit their responses then proceed to review slide content
    Transmission is the spread of organisms, such as M. tuberculosis, from one person to another
    The primary mode of transmission for tuberculosis is through inhalation of infectious particles
    Less frequently, TB can be transmitted by:…[Review slide content]
    *Slide Animation
    Image Credit: Cartoon from clip art.; Graphic from CDC Core Curriculum. 2000.
  • Review the slide content
    Tuberculosis disease can develop very soon after infection or many years after infection
    In individuals without HIV co-infection, about 5% of people who have been recently infected with M. tuberculosis will develop TB disease in the first year or two after infection. Another 5% will develop disease later in their lives. The remaining 90% will stay infected, but free of disease for the rest of their lives
    It’s important to remember that not all patients with active TB disease will have a positive Mantoux TST (approx. 75% will have +TST and this percentage is lower in HIV infected patients). Never stop evaluating a patient for active TB simply because the Mantoux TST is 00mm!
    The chest X-ray will often show abnormalities suggestive of active TB but may be within normal limits for some patients with active disease, particularly if they also have HIV. This will be covered in more detail in Module 4 on Case Finding and Diagnosis
    Image Source: Centers for Disease Control and Prevention (CDC)
  • If the immune system is compromised, then the bacilli multiply and spread to other sites in the body. People who have TB infection but not TB disease are NOT infectious - in other words, they cannot spread the infection to other people
    Persons with LTBI have a low bacillary load (e.g., ≤~103)
    It is very important to remember that TB infection is not considered a case of TB
    Image Source: Centers for Disease Control and Prevention (CDC)
  • This next section describes the pathogenesis of TB (the way TB infection and disease develop in the body)
    At first, the tubercle bacilli multiply in the alveoli and a small number enter the bloodstream and spread throughout the body (dissemination)
    Bacilli may reach any part of the body, including areas where TB disease is more likely to develop. These areas include the upper portions of the lungs, as well as the kidneys, the brain, and bone
    Disseminated TB refers to TB that simultaneously involves multiple organs. While “miliary” is given as an example of disseminated TB, it really refers to a radiographic manifestation of disseminated TB. It’s important to note that not all patients with disseminated TB have a miliary pattern on CXR
    Image source: I-TECH
  • This slide shows different sites where TB has caused disease outside of the lungs
    Image Sources:
    Radiographic images: Francis J. Curry National Tuberculosis Center
  • Tuberclosis

    1. 1. 1 Prepared by : Amera saeed
    2. 2. Introduction  TB is one of the oldest recorded human afflictions  Still one of the biggest killers among the infectious diseases  The bacillus causing tuberculosis, Mycobacterium tuberculosis, was identified and described on March 24, 1882 by Robert Koch
    3. 3.  One-third of the world's population is currently infected with TB  with 8 to 10 million new cases each year.  2 million TB related deaths/year Epidmiology Incidence and prevelance
    4. 4. M. tuberculosis M. bovis M. africanum M. microti M. canettii M. caprae M. pinnipedii Etiology Human tuberculosis (TB) is caused by infection with members of the Mycobacterium tuberculosis complex, which includes :
    5. 5. Characteristics of M.tuberclosis  Slightly curved,rod shaped bacilli  Aerobic, Non motile  Thick lipid cell wall,resist decolorization with acidified alcohol “ Acid fast bacteria”  Multiplies slowly”every 18 - 24 hrs”  Can remain dormant for decades
    6. 6.  Person-to-person through the air by a person with TB disease of the lungs  Less frequently transmitted by: • Ingestion of Mycobacterium bovis found in unpasteurized milk products • Laboratory accident How is TB Transmitted? Source: CDC, 2000
    7. 7. The probability that TB will be transmitted from one person to another depends on a number of factors  The concentration of TB bacteria in the air  The environment in which exposure to the bacteria occurs  The length of time of exposure  Person‘ s immune system
    8. 8. Risk factors  Co infection with HIV  Diabetic person  Persons undergo chemotherapy  Person undergo organ transplantation  Extreme ages,children and geriatric  Malnutration
    9. 9. Pathogenesis
    10. 10. Active TB Disease Germs:  Awake and multiplying  Cause damage to the lungs Person:  Most often feels sick  Contagious (before pills started)  Usually have a positive tuberculin skin test  Chest X-ray is often abnormal (with pulmonary TB) Granuloma breaks down and tubercle escape and multiply TB
    11. 11. Germs:  Sleeping but still alive  Surrounded (walled off) by body’s immune system Person:  Not ill  Not contagious  Normal chest x-ray  Usually the tuberculin skin test is positive Latent TB infection(LTBI(
    12. 12. Spread of TB to Other Parts of the Body 1. Lungs (85% all cases) 2. Pleura 3. Central nervous system • (e.g., brain, meninges) 4. Lymph nodes 5. Genitourinary system 6. Bones and joints 7. Disseminated  (e.g., miliary) © ITECH, 2006
    13. 13. Extrapulmonary TB Pleura Lymph Node Brain Spine
    14. 14. Symptoms
    15. 15. Diagnosis  Medical history  Physical examination  Sputum smear microscopy Acid fast staining (Ziehl–Neelsen stain) Fluorochrome stain using fluorescence microscopy  Culture  Immunological tests  TB skin test(Tuberculin skin test )  TB blood tests  Chest radiograph (X-ray)  PCR
    16. 16. Bacteriologic Examination of Clinical Specimens  The bacteriologic examination has five parts:  Specimen collection, processing, and review  AFB smear classification and results  Direct detection of M. tuberculosis in clinical specimen using nucleic acid amplification (NAA)  Specimen culturing and identification  Drug-susceptibility testing
    17. 17. Specimen Collection, Processing, and Review  At least three consecutive sputum specimens are needed, each collected in 8- to 24-hour intervals, with at least one being an early morning specimen.  If possible, specimens should be obtained in an airborne infection isolation (AII) room or other isolated, well-ventilated area (e.g., outdoors)
    18. 18. Specimen Collection Methods  Coughing  Induced sputum  Bronchoscopy  Gastric aspiration Specimen Collection, Processing, and Review
    19. 19. Sputum smear microscopy a. Ziehl-Neelsen stain  fixed smear covered with carbol-fuchsin, heated, rinsed,  decolorized with acid alcoholb. b. Fluorochrome stain with phenol- auramine  modified acid alcohol step  potassium permanganate counter staining; fluorescent  Mycobacteria visible with 20 or 40X magnification  SMEAR POSITIVITY MEANS AT LEAST 10,000 ORGANISMS/mL SPUTUM Fluorochrome stain
    20. 20. Culture (Gold Standard( a. Solid media Lowenstein Jensen (egg based) Middlebrook 7H11 (agar based)  can detect colony morphology, mixed infections; can detect 10- 100  organisms/mL; 3-8 weeks incubation to detect organisms b. Liquid broth Middlebrook 7H12, BACTEC systems  1-3 weeks of incubation to detect organisms M.Tuberclosis on Lowenstein Jensen media Buff colonies
    21. 21. TB skin test(Tuberculin skin test(  Called the Mantoux tuberculin skin test  Result depends on the size of the raised, hard area or swelling  Also depends on the person’s risk of being infected with TB bacteria and the progression to TB disease if infected.
    22. 22.  TB blood tests (Interferon-Gamma Release Assays, IGRAs(  Measures how strong a person’s immune system reacts to TB bacteria  Two IGRAs  QuantiFERON®–TB Gold In-Tube test (QFT- GIT  T-SPOT®.TB test (T-Spot)
    23. 23.  IGRAs are the preferred method of TB infection testing for  People who have received bacille Calmette–Guérin (BCG). BCG is a vaccine for TB disease.  People who have a difficult time returning for a second appointment to look for a reaction to the TST.  TB blood tests (interferon-gamma release assays, IGRAs(
    24. 24. TB treatment is challenging, requiring accurate and early diagnosis, drug‑resistance screening and the administration of effective treatment regimens for at least 6 months through ( Directly Observed Therapy (DOT) and follow‑up support.   Treatment for tuberculosis (TB) depends on which type you have, although a long course of antibiotics is most often used Treatment 
    25. 25.  The goals of TB treatment are to: 1. Shorten the clinical course of TB 2. Prevent complications 3. Prevent the development of latency and/or subsequent recurrences 4. Decrease the likelihood of TB transmission Treatment 
    26. 26.  First-line anti-TB drugs recommended in a four-drug combination for the treatment of drug-susceptible TB.  Second-line anti-TB drugs for drug-resistant TB. Treatment 
    27. 27. First line
    28. 28. Drug (year of discovery) Target Effect activity Isoniazid (1952) Enoyl-(acyl carrier protein) reductase Inhibit mycolic acid synthesis bactericidal Rifampicin (1963) RNA polymerase Beta subunit Inhibit transcription bactericidal Pyrazinamide (1954) Exact target unknowen Disrupt plasma memb. Disrupt energy memb. bacteriostatic Ethambutol (1961) Arabinosyl transferase Inhibit arabinogalactan biosynthesis bacteriostatic First-line anti-TB drugs
    29. 29.   First line
    30. 30. Spectrum of  drugs
    31. 31. 1st line drugs summary
    32. 32. Regimens Of Antituberculosis Drugs Active disease Treatment requires a minimum of 6 months in two phases Intensive phase Isoniazid,rifampin,ethambutol and pyrazinamide”given for 2 months” Continuation phase Isoniazid and rifampin”for 4 months Latent disease Daily isoniazid therapy for 9 monthes “Monitor the patient for signs and symptoms of hepatitis and peripheral neuropathy”
    33. 33. Regimens Of Antituberculosis Drugs
    34. 34. Second line Drug target effect Para-amino salicylic acid )PAS`) Dihydro _pteroate synthase Inhibits folate biosynthesis Ethionamide Enoyl-[acyl-carrier- protein] reductase Inhibits mycolic acid biosynthesis Ofloxacin DNA gyrase and DNA topoisomerase Inhibits DNA supercoiling Kanamycin 30S ribosomal subunit Inhibits protein synthesis Amikacin 30S ribosomal subunit Inhibits protein synthesis Cycloserin d-alanine racemase and ligase Inhibits peptidoglycan
    35. 35. Second line  
    36. 36. Resistance  Two types  Primary”intrinsic” resistance Infection with strains naturally resistant to one or two drugs  Hydrophobic cell wall  Drug modifying enzymes  Drug efflux system  Acquired resistance Infection with strains that become drug resistant d.t inappropriate or inadequate treatment
    37. 37. Drug resistance in TB  MDR (Multi-Drug Resistant) Simultanous resistance to 2 or more drugs from 1st line  XDR (Extensive Drug Resistance) Strains not only resistant to 1st line but also resist fluoroquiolones and one of injectible drugs
    38. 38. Treating Extensively Drug Resistant TB
    39. 39. Targets for new drugs
    40. 40. Development of anti TB drugs
    41. 41. New drugs
    42. 42. Schematic showing the site of action of various tuberculosis drug candidates 
    43. 43. How can tuberculosis be prevented?  The BCG vaccine. It usually protects children and infants from the disease, but its effects wear off when the patient reaches adulthood.  Eating a healthful diet that boosts the immune system  Having regular TB tests if you work or live in a high risk environment  Completing a TB medication regimen.  If you are infected, stay home, cover your mouth, and ensure proper ventilation.