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  1. 1. Tuberculosis DR NWOKOMA
  2. 2. Outline  Burden of TB  The organism  Transmission and organ involvement  Pathogenesis of TB  Clinical features  Investigations  chemotherapy
  3. 3. Burden of TB  TB is found globally  About a third of the world population is infected  ~ 1 person is infected per second  Most are asymptomatic and only about 10% of those infected are likely to develop active disease  Burden is worse in poorer countries
  4. 4. Burden of TB  Untreated, Mortality ~ 50-67%  Treated and well supported mortality ~ 5%  Relapse rate of 2-3% amongst those considered cured after standard therapy  Major drain on economy : loss of man- hour and school absenteeism  About 8 m of nearly 2 billion infected individuals become symptomatic every year
  5. 5. Burden of TB  Accounts for ~ 2m deaths per year, 90% of this occurs in developing countries  Age 15-54 years mostly affected (75% of cases) WHO declared TB as an emergency in 1993  HIV/AIDS has compounded the problem of TB  Drug resistance is very high ~ 20%  Multiple drugs: HAART and anti TB ◦ Interactions ◦ expense
  6. 6. Burden of TB Re-emergence of TB due to:  Poverty  Neglect of the disease  Collapse of health facilities in depressed economy  HIV/AIDS scourge
  7. 7. The organism  Causative organism: Mycobacteria spp. (tuberculosis>>>> bovis>> africanum > microti)*  An obligate aerobic organism ◦ Acid fast Bacilli (due to presence of mycolic acid** in the cell wall)  *others are called non tuberculous mycobacteria e.g. M. leprae  ** mycolic acid is also responsible for caseous granuloma
  8. 8. The organism Organism is slow growing (division: 15-20 hours vs ~20min. in E. coli) Discovered by Robert Koch in 1882 Genome sequenced in 1998
  9. 9. Transmission and organ involvement  usually by inhalation of aerosols  The risk of infection of a susceptible individual is high with close, prolonged, indoor exposure to a person with sputum smear-positive PTB.  At risk people include: ◦ Immuno-compromised people  HIV/AIDS, severe malnutrition, immuno- supressant, DM, leukaemia, lymphomas ◦ Close contacts including health care workers
  10. 10. Sources of PTB infection 1. Drivers using Air Conditioned cars 2. Domestic servant, house keepers or house help 3. Gardeners 4. Personal cooks 5. Hostel (especially in the universities)
  11. 11. Transmission and organ involvement  M. bovis usually by ingestion of un- pasteurised infected milk  Organ involvement is broadly divided into: ◦ Pulmonary (75%) or ◦ extra-pulmonary  Sites other than lung = Extra-pulmonary TB
  12. 12. Pathogenesis of TB  Primary infection  in people who have not had any previous exposure to tubercle bacilli  multiplication of tubercle bacilli in the lungs.  The resulting lesion is the Ghon focus.  Lymphatics drain the bacilli to the hilar lymph nodes.  Ghon focus & related hilar lymphadenopathy form the primary complex.  size of infecting dose and strength of immune response
  13. 13. Pathogenesis of TB  immune response stops the multiplication of bacilli.  a few dormant bacilli may persist.  A positive tuberculin skin test only evidence of infection.  In a few cases the immune response is not strong enough to prevent multiplication  disease occurs within a few months.
  14. 14. Post-primary TB  occurs after a latent period of months or years  following primary infection.  either by reactivation of dormant tubercle bacilli acquired from a primary infection or by  reinfection.  Reactivation may be in response to a trigger
  15. 15. Post-primary TB  extensive lung destruction with cavitation; positive sputum smear; upper lobe involvement;  usually no intrathoracic lymphadenopathy.  Patients with these lesions are the main transmitters of infection in the commmunity
  16. 16. Clinical features  cough for more than 2 or 3 weeks;  sputum production;  weight loss.  Respiratory: chest pain, haemoptysis, breathlessness.  Constitutional: fever, night sweats, tiredness, loss of appetite,
  17. 17. Extrapulmonary TB  Common Less common  Pleural effusion Empyema  Lymphadenopathy Male genital tract (usually cervical) epididymitis, orchitis)  Central nervous Female genital tract (meningitis, cerebral tuberculoma) (tubo-ovarian, endometrium)  Pericarditis (effusion/constrictive) Adrenal gland  Gastrointestinal Kidney (ileocaecal, peritoneal) Skin (lupus vulgaris, tuberculids, miliary)  Spine, other bone and joint
  18. 18. Investigations  three sputum samples for microscopy  Chest Xray  CLASSICAL PATTERN ATYPICAL PATTERN  upper lobe infiltrates interstitial infiltrates (esp lower zones)  bilateral infiltrates  cavitation intrathoracic lymphadenopathy  pulmonary fibrosis and shrinkage no cavitation no abnormalities
  19. 19. Investigations  culture from clinical specimens (e.g. sputum,  lymph node aspirate, cerebrospinal fluid)  the gold standard for the definitive diagnosis of TB.  culture can also be tested in vitro for sensitivity to anti-TB drugs  Löwenstein Jensen,  liquid culture media and automated systems (e.g. Bactec)
  20. 20. Ziehl-Nelsen stain of M. tuberculosis
  21. 21. Drug classes  Drugs are grouped as first-line or second line based on:  Availability e.g. Fluoroquolones  Toxicity e.g cycloserine  Efficacy e.g PAS
  22. 22. chemotherapy  Prolonged therapy is the rule!  Hitherto,  INH + PAS for 18-24 months  Even short course lasts 6 months!  Short course consists of 4 initial drugs for the first 2 months
  23. 23. First line drugs  INH  Ethambutol  Rifampicin  Pyrazinamide
  24. 24. INH (H) RIF (R) EMB (E) PZA (Z) Multi-drug Resistant TB (MDR-TB) First-line • Resistant to the most effective first-line drugs (INH and RIF) • Need aggressive management of side effects • Requires 18 to 24 months of treatment given under direct observation and with assistance Other 2nd-line Injectable Quinolone OFX LFX MFX SM KM AMK CM ETH CS PAS Second-line Third-line Other agents AMX/CLV Clofazamine Clarithromycin
  25. 25. Second line drugs  Amikacin, Kanamycin, Capreomycin  Viomycin  Ethionamide  Ciprofloxacin, Moxifloxacin  Para-aminosalicylic Acid
  26. 26. Standardised therapy Regimen Intensive phase Duration (months) INH, Rif, PZM, Etham 2 months all drugs 4 months of INH & Rif INH, Rif. - 9 months INH, Rif, PZM, Strept. 2 months all drugs 4 months of INH & Rif.
  27. 27. PRINCIPLES OF CHEMOTHERAPY I. 4 drug combination therapy is advocated for newly diagnosed cases of PTB while 5 drug therapy is used for resistant cases during the intensive phase therapy. II.The use of short course chemotherapy (SCC III.Drugs should be given in correct dosage based on age and weight. IV.Instruct and ensure that drugs are taken regularly preferably by directly observed treatment short- course (DOTS). V.Patient should be duly informed about the range and common side-effect of the drugs in use and should be sought for by the attending physician while patient is on treatments
  28. 28. PRINCIPLES OF CHEMOTHERAPY I. Drugs should be given for the required duration of the regimen in use. II. Drugs should be given once on an empty stomach using DOTS III.The role of TB supervisors cannot be over-emphasized. IV.All TB cases should have HIV -serological tests done . V. There is a role for counselling in TB management. VI.There are clear indications for adjuvant steriod use in TB managements. VII.Treatment should be given to all TB patients free of charge since majority of TB cases cannot afford to buy the drugs 
  29. 29. DOTS IN TB MANAGEMENT  DOTS (Directly Observed Treatment, Short-course) is the WHO- recommended strategy for the detection and cure of TB.  DOTS combines five elements: political commitment, microscopy services, drug supplies, monitoring systems, and direct observation of treatment.  TB can be readily and inexpensively cured with DOTS.  TB cost of the drugs and their administration is very small.  Every infectious patients cured reduces the risk to everyone of contracting TB  .
  30. 30. DOTS IN TB MANAGEMENT DOTS can successfully and permanently cure more than nine in every 10 TB patients who complete the treatment. DOTS can produce cure rates of 95 percent even in the poorest countries. DOTS prevents new infections and the development of MDR-TB. DOTS can add years of life to an HIV- positive person: TB drug treatment can be as effective in curing TB in HIV- positive as in HIV- negative TB patients.
  31. 31. ADJUVANT STEROLD USE IN TB INDICATIONS: 1. Tb pericarditis 2. Tb pleural effusion 3. Tb meningitis 4. Tb laryngitis 5. Tb of the adrenal gland 6. Renal tract tb 7. Severe hypersensitivity to anti-tb drugs. 8. Massive lymph node enlargement with pressure effect.
  32. 32. INDICATION FOR SURGERY IN TB 1. Patient with PTB, cured or on treatment, has recurrent severe haemoptysis as a result of an Aspergilloma. 2. Surgical drainage of a tuberculous empyema or massive tuberculous pleural effusion has failed to clear with chemotherapy. 3. Rarely, there is surgery to relieve intestinal obstruction secondary to adhesions from treated abdominal tuberculosis. 4. Rarely, pericardiectomy is considered due to constrictive pericardities that could have developed years after TB pericarditis. 5. Rarely, there is removal of mediastinal glands in children causing compression of the trachea or large bronchi or biospy of a mass for histological diagnosis of EPTB.