tuberculosis.pptx8888888888888888888888888

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1. TUBERCULOSIS Presented by: P A.MARRAH

2. Learning Objectives Introduction Etiology Risk Factors Transmission Sites Pathogenesis of Tuberculosis. Types of Tuberculosis Clinical Diagnosis

3. What is TB? Tuberculosis is a chronic infectious disease that can affect almost any part of the body but is mainly an infection of the lungs. Tuberculosis (TB) is a disease caused by an organism called Mycobacterium tuberculosis . About one-third of the world's population has latent TB, which means people have been infected by TB bacteria but are not (yet) ill with disease and cannot transmit the disease .

4. Etiology: CAUSATIVE ORGANISM Tubercle bacillus or Koch’s bacillus called Mycobacterium tuberculosis causes tuberculosis in the lungs and other tissues of the human body. The organism is a strict aerobe and thrives best in tissues with high oxygen tension such as in the apex of the lung. Out of various pathogenic strains for human disease included in Mycobacterium tuberculosis complex, currently the most common is M. tuberculosis hominis (human strain).

5. M. tuberculosis causes most TB cases Mycobacteria that cause TB: M. tuberculosis M. bovis M. africanum M. microti M. canetti Mycobacteria that do not cause TB e.g., M. avium complex M. tuberculosis Types of Mycobacteria

6. M. tuberculosis bovis (bovine strain ) used to be common pathogen to human beings during the era of consumption of unpasteurised milk but presently constitutes a small number of human cases Infection with M. avium-intracellulare (avian or bird strain) is common in patients with HIV/AIDS

7. Risk Factors: More common in developing countries of Asia, Africa and Latin America. Malnutrition. Inadequate medical care. Poverty. Crowding. Chronic debilitating conditions like uncontrolled diabetes. Alcoholism and immunocompromised states. In the western countries, there has been a resurgence of tuberculosis due to HIV-AIDS.

8. TB is spread from person to person through the air via droplet nuclei M. tuberculosis may be expelled when an infectious person: Coughs Sneezes Speaks Sings Transmission completed when another person inhales droplet nuclei TB Transmission

9. Mode of Transmission: Human beings acquire infection with tubercle bacilli by one of the following routes: Inhalation of organisms present in fresh cough droplets or in dried sputum from an open case of pulmonary tuberculosis.

10. 2. Ingestion of the organisms leads to development of tonsillar or intestinal tuberculosis.

11. 3. Inoculation of the organisms into the skin may rarely occur from infected postmortem tissue.

12. 4. Transplacental route results in development of congenital tuberculosis in foetus from infected mother and is a rare mode of transmission.

13. TB is not spread Sharing drinking containers or eating utensils. Smoking or sharing cigarettes with others Saliva shared from kissing. Touching someone By having sex Through blood, urine, feaces , water, or insect bites. **** AIRBONE******

14. Sites: PULMONARY REGION – 85 % EXTRA-PULMONARY SITES- 15 % Lymph Nodes (most common) G.U.T Bones & Joints Intestine Meninges Skin

15. Pathogenesis of Tuberculosis: EVOLUTION OF TUBERCLE The sequence of events which take place when tubercle bacilli enters body: TUBERCLE BACILLI ENTRY If bacilli enters through blood Neutrophils are evoked initially which are rapidly destroyed by the organisms . Later by macrophages and T cells . If the tubercle bacilli are inhaled into the lung alveoli Macrophages predominate the picture from the beginning.

16. Tubercle Bacilli engulfment by Macrophages Macrophages try to kill the bacteria or die away themselves. Macrophages present bacilli to CD4+T lymphocytes Activated lymphocytes release lymphokines. IL-1, IL-2, Interferon- γ TNF- α PROLIFERATION OF MORE T CELLS ACTIVATES MACROPHAGES FIBROBLAST PROLIFERATION If Poorly degradable bacilli are present

17. ACTIVATED MACROPHAGES TRANSFORM TO EPITHELIOID CELLS AFTER 2-3 DAYS SOME MACROPHAGES, UNABLE TO DESTROY TUBERCLE BACILLI, FUSE TOGETHER AND FORM MULTINUCLEATED GIANT CELLS.- LANGHAN TYPE Around the mass or cluster of epithelioid cells and a few giant cells, a zone of lymphocytes and plasma cells is formed which is further surrounded by fibroblasts. The lesion at this stage is called HARD TUBERCLE due to absence of central necrosis.

18. Within 10-14 days, the centre of the cellular mass begins to undergo caseation necrosis , characterized by cheesy appearance and high lipid content. This stage is called SOFT TUBERCLE which is the hallmark of Tuberculous lesions Caseation Necrosis

19. *** The soft tubercle which is a fully-developed granuloma with caseous centre does not favour rapid proliferation of tubercle bacilli. Acid-fast bacilli are difficult to find in these lesions and may be demonstrated at the margins of recent necrotic foci and in the walls of the cavities.

20. Fate of Tubercles: The fate of a granuloma is variable: COLD ABSCESS: The caseous material may undergo liquefaction and extend into surrounding soft tissues, discharging the contents on the surface. This is called cold abscess although there are no pus cells in it.

21. 2. SINUS TRACTS: - In tuberculosis of tissues like bones, joints, lymph nodes and epididymis , sinuses are formed and the sinus tracts are lined by Tuberculous granulation tissue.

22. 3. SIZE INCREASE: The adjacent granulomas may coalesce together enlarging the lesion which is surrounded by progressive fibrosis.

23. 4. CALCIFICATION & OSSIFICATION: - In the granuloma enclosed by fibrous tissue, calcium salts may get deposited in the caseous material (dystrophic calcification) and sometimes the lesion may even get ossified over the years. dystrophic calcification

24. Types of Tuberculosis: Infection with tubercle bacilli is of 2 main types: Primary Tuberculosis. Secondary Tuberculosis.

25. Primary Tuberculosis: The infection of an individual who has not been previously infected or immunised is called Primary Tuberculosis or Childhood Tuberculosis.

26. Sites: The most commonly involved tissues for primary complex are: Lungs and Hilar lymph nodes . Other tissues which may show primary complex are Tonsils and Cervical lymph nodes Small intestine and mesenteric lymph nodes.

27. Primary complex or Ghon’s complex Primary complex or Ghon’s complex is the lesion produced in the tissue of portal of entry with foci in the draining lymphatic vessels and lymph nodes.

28. Ghon's Complex in Lungs: It consists of 3 components: Pulmonary component It is 1-2 cm solitary area of primary Tuberculous foci. Subpleural focus in the upper part of Lower lobe. Lymphatic vessel component - Lymphatics draining the lung lesion contain phagocytes containing bacilli. Lymph node component Enlarged hilar and tracheo -bronchial lymph nodes in the area drained. The affected lymph nodes are matted and show caseation necrosis.

29. Fate Of Primary Tuberculosis Primary complex may have one of the following sequelae: Fibrosis, Calcification and Ossification.

30. 2. Progressive primary tuberculosis : Caseous material is disseminated through bronchi to the other parts of the same lung or the opposite lung.

31. 3. Primary Miliary Tuberculosis: Bacilli may enter the circulation through erosion in a blood vessel and spread by haematogenous route to other tissues and organs. The lesions may be seen in organs like the liver, spleen, kidney, brain and bone marrow.

32. Secondary Tuberculosis The infection of an individual who has been previously infected or sensitized is called Secondary TB, or Post-Primary or Reinfection or Chronic Tuberculosis.

33. The infection may occur from : Endogenous source such as reactivation of dormant primary complex; or Exogenous source such as fresh dose of Reinfection by the tubercle bacilli. Secondary tuberculosis occurs most commonly in lungs. Other sites and tissues which can be involved are lymph nodes, tonsils, pharynx, larynx, small intestine and skin.

34. Infection with M. avium -intracellular occurs more frequently in cases of AIDS. Patients with HIV infection previously exposed to tuberculous infection have particularly high incidence of reactivation of primary tuberculosis.

35. Morphological Features of Secondary TB The lesions in secondary pulmonary tuberculosis usually begin as 1-2 cm apical pleura. It occurs by lymphohaematogenous spread of infection from primary complex to the apex of the affected lung where the oxygen tension is high and favourable for growth of aerobic tubercle bacilli. The pattern of lesions in such cases is similar to that of primary tuberculosis.

36. FATE OF SECONDARY PULMONARY TUBERCULOSIS 1. The lesions may heal with fibrous scarring and calcification.

37. 2. The lesions may produce progressive secondary pulmonary tuberculosis with the following pulmonary and extrapulmonary involvements: i ) Fibrocaseous tuberculosis ii) Tuberculous caseous pneumonia iii) Miliary tuberculosis iv) Tuberculous empyema

38. FIBROCASEOUS TUBERCULOSIS: The original area of tuberculous undergoes peripheral healing and massive central caseation necrosis which may: SOFT CASEOUS LESION WITHOUT DRAINAGE INTO A BRONCHUS OR BRONCHIOLE TO PRODUCE A NON-CAVITARY LESION (CHRONIC FIBROCASEOUS TUBERCULOSIS). BREAK INTO A BRONCHUS FROM A CAVITY (CAVITARY OR OPEN FIBROCASEOUS TUBERCULOSIS)

39. CAVITARY OR OPEN FIBROCASEOUS TUBERCULOSIS CHRONIC FIBROCASEOUS TUBERCULOSIS

40. PROGNOSIS OF CAVITARY OR OPEN FIBROCASEOUS TUBERCULOSIS The cavity may communicate with bronchial tree and becomes the source of spread of infection (‘OPEN TUBERCULOSIS’). May implant tuberculous lesion on the mucosal lining of air passages producing ENDOBRONCHIAL AND ENDOTRACHEAL TUBERCULOSIS . Ingestion of sputum containing tubercle bacilli from endogenous pulmonary lesions may produce LARYNGEAL AND INTESTINAL TUBERCULOSIS.

41. ENDOTRACHEAL TUBERCULOSIS INTESTINAL TUBERCULOSIS LARYNGEAL TUBERCULOSIS

42. TUBERCULOUS CASEOUS PNEUMONIA The caseous material from a case of secondary tuberculosis in an individual with high degree of hypersensitivity may spread to rest of the lung producing caseous pneumonia

43. MILIARY TUBERCULOSIS This is lymphohaematogenous spread of tuberculous infection from primary focus or later stages of tuberculosis. The spread may occur to systemic organs or isolated organ. The spread is either by entry of infection into pulmonary vein producing disseminated or isolated organ lesion in different extra-pulmonary sites (e.g. liver, spleen, kidney, brain, meninges , genitourinary tract and bone marrow).

44. TUBERCULOUS EMPYEMA The caseating pulmonary lesions of tuberculosis may be associated with empyema. Empyema may heal by fibrosis and obliterate the pleural space (thickened pleura by chronic pleuritis). Occasionally, pleural cavity may contain caseous material and develop into tuberculous empyema.

45. EMPYEMA

46. Clinical Features: SYSTEMIC FEATURES: FEVER, NIGHT SWEATS, FATIGUE, LOSS OF WEIGHT AND APPETITE. REFERABLE TO LUNGS: PRODUCTIVE COUGH HAEMOPTYSIS, PLEURAL EFFUSION, DYSPNOEA, ORTHOPNOEA etc.

47. Diagnosis of Tuberculosis The diagnosis is made by the following tests: i ) AFB microscopy of diagnostic specimen such as sputum, aspirated material.

48. ii) Mycobacterial culture: T raditional method on LJ medium for 4-8 weeks.

49. iii) Molecular methods- PCR . iv) Complete Haemogram- Lymphocytosis and raised ESR. v) Radiographic procedures e.g. chest X-ray showing characteristic hilar nodules and other parenchymal changes).

50. vi) Mantoux skin test: This test is done by intradermal injection of 0.1 ml of tuberculoprotein , purified protein derivative (PPD).

51. Delayed type of hypersensitivity develops in individuals who are having or have been previously infected with tuberculous infection which is identified as an indurated area of more than 15 mm in 72 hours.

52. The test may be FALSE POSITIVE: in atypical mycobacterial infection and previous BCG vaccination, FALSE NEGATIVE: in weakened immune system. sarcoidosis, some viral infections, Hodgkin’s disease, Recent tuberculous (8-10 weeks of exposure) infection

53. CAUSES OF DEATH IN PULMONARY TUBERCULOSIS Pulmonary insufficiency, Pulmonary haemorrhage, Sepsis due to disseminated miliary tuberculosis, Cor Pulmonale Secondary Amyloidosis.

54. LTBI vs. TB Disease Latent TB Infection (LTBI) TB Disease (in the lungs) Inactive , contained tubercle bacilli in the body Active , multiplying tubercle bacilli in the body Gene Xpert is usually not detected Gene Xpert is usually detected Chest x-ray usually normal Chest x-ray usually abnormal Sputum smears and cultures negative Sputum smears and cultures may be positive No symptoms Symptoms such as cough, fever, weight loss Not infectious Often infectious before treatment Not a case of TB A case of TB

55. Treatment of Tuberculosis Before Treatment stress importance of compliance/concordance (helps the pt and prevent spread of resistance). Check FBC, LFT, Renal Fxn .(drugs like isoniazid, can cause hepatitis,and refampicin can cause mild elevations of liver enzymes for taking higher dose),(drugs like the aminoglycosides can cause nephrotoxicity) Test colour vision (Ishihara Chart), Visual Acuity ( Snell’sChart ), before and during treatment as Ethambutol may cause (Reversible) ocular toxicity. Always weigh and check the height of the pt. For Children check their Z-Score and Use the MUAC. Check for HIV 1& 2, HBV & HCV and Diabetes Mellitus Note, because pt usually forget to take pills so consider DIRECT OBSERVATIONAL THERAPY

56. Paediatric Tuberculosis Treatment Regimen Four drugs regimen: RHZE for 2mths, followed by a two drugs HR regimen for 4mths for all children with suspected or confirmed PTB or peripheral lymphadenitis living in areas of low HIV prevalence or low H resistance or HIV Negative; Three drugs regimen: RHZ FOR 2moths, followed by a two drug HR regimen for 4 mths for children with suspected or confirmed PTB or TB peripheral lymphadenitis living in areas of low HIV prevalence or low H resistance or HIV Negative ;

57. Treatment Cont ’ In cases of suspected or confirmed TB Meningitis, spinal TB with neurological signs or osteo -articular TB, treat for 12mths with a four drug regimen RHZE for 2 mths , followed by a two drug HR regimen for 10 mths . In infants aged (0-3mths) with suspected or confirmed PTB or TB peripheral lymphadenitis, treat promptly with the standard regimen well dosages adjusted

58. TREATMENT of PTB Rx of Pulmonary TB last for Six months and can be divided into 2 phases 1. Initial Phase: 8wks on four (4) drugs depending on susceptibility): A. Rifampicin 600-900mg (child 15mg/Kg) B. Isoniazid 15mg/Kg Max 900mg + Pyridoxine 50mg/24 or 10mg (if diabetic, malnourished, chronic renal failure, HIV+ve or Alcoholic) C. Pyrazinamide 2.5g PO.or 2g <50Kg D. Ethambutol 30mg/Kg PO or Streptomycin 0.75-1g/24h IM.

59. Continuation Phase This is a Sixteen weeks on 2 drugs Rifampicin and Isoniazid at the same doses. Note: Give prophylaxis of Pyridoxine throughout treatment. Note also Steroids are indicated in Meningeal and pericardial disease. SIDE EFFECT OF THE ANTI TB DRUGS Rifampicin:- Hepatitis (small rise in the Liver enzyme AST is acceptable , stop if Bilirubin rises) Orange/Red discoloration of urine and tears Isoniazid:- Hepatitis, Peripheral neuropathy, agranulocytosis . Ethambutol :- Optic neuritis( colour vision is the first deterioration) Pyrazinamide:- Hepatitis, arthralgia( Acute gout; porphyria)

60. All TB Suspected Cases TB screening using the Screening tool: Ask : Cough, fever, chest pain, night sweats, weight loss, Tb contact Xpert MTB/RIF Assay MTB detected RR not detected MTB detected RR detected MTB Not Detected Error/ invalid/ indeterminate Link to DRTB unit for Second line Anti-TB and collect culture DST sample Repeat Xpert with fresh sample DR-TB First Line Anti-TB => Consider alternative diagnosis; => if patient is seriously sick or diagnosis is still in doubt; refer for further investigation => Use opinion of a senior clinician to decide on “clinical diagnosis of patient”. Collect 2 sputm samples for GXP and smear No action required, treat for ARI if present. No symptoms: Report as negative TB screen 2 or more symptoms: Report as positive TB screen

61. DSTB & DRTB Difference between DSTB & DRTB Drug S usceptible TB (DSTB) is a form of TB that responds to 1 st line drugs for treatment of TB (RHZE) Drug Resistant TB (DRTB) is a form of TB that develops resistance to any 1 st line drugs (RHZE). There are different types of DRTB, classification is according to the resistance pattern.

62. Main reasons of developing TB drug resistance : DSTB treatment interruption. Inadequate , incomplete or poor treatment quality of DSTB that allows the selection of mutant resistant strains. High prevalence of drug-resistant TB in the community increases the risk of drug-resistant TB exposure in the community.

63. DRTB classifications Drug-resistant tuberculosis is a disease caused by M. tuberculosis strains resistant to one or more anti-TB drugs. Monoresistance : resistance to one first-line anti-TB drug only other than Rif and Isoniazid. Polydrug resistance: resistance to more than one first-line anti-TB drug (other than both isoniazid and rifampicin). Multidrug resistance (MDRTB) : resistance to at least both isoniazid and rifampicin. Extensive drug resistance (XDRTB) : resistance to any fluoroquinolone and to one of the second-line injectable drugs ( capreomycin , kanamycin and amikacin), in addition to multidrug resistance. Rifampicin resistance: resistance to rifampicin detected using phenotypic or genotypic methods, with or without resistance to other anti-TB drugs.

64. Prevention of TB ICF – Intensive Case Finding TB screening, contact tracing, Involve patients & community in advocacy campaigns, access to Rapid TB diagnosis and treatment IPT – INH Preventive Therapy for PLHIV, TB Contacts New Combined Regimen of Isoniazid (INH) and Rifapentine(RPT) administered weekly for 12wks as DOT. This regimen is recommended for aged >/= 12yrs. IPC – Infection Prevention and Control PPE , Safe sputum collection, Cough etiquette, Triage TB suspects to fast track or separation, Improve ventilation Capacity building and innovation.

65. Hand and Cough Hygiene