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Tuberculosis management, pathophysiology and treatment.pptx

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martin osodo

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Pulmonary Tuberculosis
Introduction Leading cause of infectious death Disease caused by bacteria of Mycobacterium tuberculosis complex Often affecting lung but can also involve other organs Airbone spread by inhalation of inhalation of droplet nuclei produced by infectious individual with pulmonary TB
Causative agent Complex has 11 subgroup Most important: M. tuberculosis (sensu stricto). M. africanum isolated in cases in East, West and Central Africa Rod-shaped, non-spore-forming, thin aerobic bacterium Acid-fast bacilli once colored cannot be decolorized by acid alcohol(high content mycolic acid and long chain cross-linked fatty acids)
Epidemiology In 2019, an estimated 10 million people developed TB and 1.5 million died from the disease. 97% in low and middle income countries, Asia(6.4m), Africa (2.4m) 8% associated with HIV co-infection of these 76% from Africa More in males than females In Kenya, upto 100,000 cases are reported annually.
Pathogenesis Droplet nuclei aerosolized by coughing, sneezing or speaking Remain in the air for several hours reaching terminal airway when inhaled. Exogenous factors for spread: Probability of contact Duration of contact Intimacy of contact Degree of infectiousness of the case Smear positive contact Cavitary pulmonary disease HIV and TB co-infection: less infectious Smear-negative/culture-positive vs culture-negative/extrapulmonary disease
Exogenous factors for spread: Degree of immune-competence: cancer pt on tx, HIV, pt on immunosuppressants Risk of developing disease Innate defense and cell-mediated immunity Primary TB disease occurring following infection: children/immuno-compromised Secondary TB infection occurs, bacilli are contained, reactivates later in life
Infection begins when the droplet reach the alveoli Myeloid dendritic cells are infected, macrophages phagocytose the bacilli. The bacilli survive within the phagosome, replicates then ruptures releasing more bacilli that are ingested by other phagocytes. Then bacilli disseminate widely in the lymphatic vessel to other parts of the lung or other organs attacking more macrophages. The bacilli are presented to T lymphocytes in the draining lymph node where cell-mediated and humoral immunity
Macrophage activating response T cell response that leads to activation of macrophages that kill the mycobacteria Macrophages present bacteria to T lymphocytes which in turn are activate to T-helper 1 (produce IFN gamma activating more macrophages), T-helper 2: IL-4, 5, 10, 13) Tissue damaging response delayed type hypersensitivity leading to destruction of macrophages containing mycobacteria. Granulomas are formed named tubercles Some lesions may heal by fibrosis Latent TB infection(LTBI): balance that lead to infection containment
Tuberculosis management, pathophysiology and treatment.pptx
Clinical presentation Pulmonary TB: primary TB fever and pleuritic chest pain, hilar lymphadenopathy, ghon focus vs ghon complex, middle and lower lobes secondary fever, night sweats, weigh loss, cough, purulent sputum with blood streaking, hemoptysis, localized in apical, posterior segment of upper lobes, superior segments of lower lobes.
Extrapulmonary TB Lymphadenitis FNA, Excision for diagnosis Pleural involvement straw-colored fluid, exudative, ADA if low excludes TB Genitourinary dysuria, hematuria, flank pain, Spine TB(Potts)- involving two or more adjacent bones TB Meningitis occur in HIV seropositive, over 1-2 weeks, cranial nerve palsy, CSF lymphocytes, high protein and low glucose Gastrointestinal pain, hematochezia or mass TB peritonitis Pericarditis fever, retrosternal dull pain, effusion, constrictive pericarditis Miliary TB hematogenous spread,
Post TB complications Bronchiectasis Aspergilloma Chronic pulmonary aspergillosis
TB and HIV TB causes 1/3 of HIV related deaths Develops within weeks in HIV patients Can be typical or atypical Atypical: diffuse infiltrate, little or no cavitation, pleural effusion, more intrathoracic lymphadenopathy Extrapulmonary TB is more common TB immune reconstitution disease Prevention: DO NOT INITIATE ART in the first 8 weeks of TB treatment, give prednisolone 1.5mg/kg for 2 weeks then half dose for 2 more weeks
Diagnosis AFB microscopy(ZN, florescence microscpy) examine 2 to 3 sputum samples Cultures and DNA testing Culture on liquid media 2-3 weeks Nucleic acid amplication genexpert Drug suscebility testing TST vs IGRA WHO recommends using of any to screen for TB esp. if initiating PTP
Treatment Rifampicin: 600mg/day, cytochrome p450 inducer reduces bioavailabity of other drugs Isoniazid 300mg/day hepatotoxity and peripheral neuropathy(pyridoxine 50mg/day) Ethambutol 15mg/kg/day optic neuritis Pyrizinamide 15-30mg/kg/day hyperuricemia Others Streptomycin 750mg to 1 g/day Rifabutin used in case of nnrti or pi Rifapentin Floroquinolones: levo, gati, moxifloxacin
monitoring LFTs, symptoms of hepatitis Stop all meds if ASTs are 5-6fold elevated Reintroduce meds once LFTs normalizes one at a time
Kenya guidelines

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Tuberculosis management, pathophysiology and treatment.pptx

  • 2. Introduction Leading cause of infectious death Disease caused by bacteria of Mycobacterium tuberculosis complex Often affecting lung but can also involve other organs Airbone spread by inhalation of inhalation of droplet nuclei produced by infectious individual with pulmonary TB
  • 3. Causative agent Complex has 11 subgroup Most important: M. tuberculosis (sensu stricto). M. africanum isolated in cases in East, West and Central Africa Rod-shaped, non-spore-forming, thin aerobic bacterium Acid-fast bacilli once colored cannot be decolorized by acid alcohol(high content mycolic acid and long chain cross-linked fatty acids)
  • 4. Epidemiology In 2019, an estimated 10 million people developed TB and 1.5 million died from the disease. 97% in low and middle income countries, Asia(6.4m), Africa (2.4m) 8% associated with HIV co-infection of these 76% from Africa More in males than females In Kenya, upto 100,000 cases are reported annually.
  • 5. Pathogenesis Droplet nuclei aerosolized by coughing, sneezing or speaking Remain in the air for several hours reaching terminal airway when inhaled. Exogenous factors for spread: Probability of contact Duration of contact Intimacy of contact Degree of infectiousness of the case Smear positive contact Cavitary pulmonary disease HIV and TB co-infection: less infectious Smear-negative/culture-positive vs culture-negative/extrapulmonary disease
  • 6. Exogenous factors for spread: Degree of immune-competence: cancer pt on tx, HIV, pt on immunosuppressants Risk of developing disease Innate defense and cell-mediated immunity Primary TB disease occurring following infection: children/immuno-compromised Secondary TB infection occurs, bacilli are contained, reactivates later in life
  • 7. Infection begins when the droplet reach the alveoli Myeloid dendritic cells are infected, macrophages phagocytose the bacilli. The bacilli survive within the phagosome, replicates then ruptures releasing more bacilli that are ingested by other phagocytes. Then bacilli disseminate widely in the lymphatic vessel to other parts of the lung or other organs attacking more macrophages. The bacilli are presented to T lymphocytes in the draining lymph node where cell-mediated and humoral immunity
  • 8. Macrophage activating response T cell response that leads to activation of macrophages that kill the mycobacteria Macrophages present bacteria to T lymphocytes which in turn are activate to T-helper 1 (produce IFN gamma activating more macrophages), T-helper 2: IL-4, 5, 10, 13) Tissue damaging response delayed type hypersensitivity leading to destruction of macrophages containing mycobacteria. Granulomas are formed named tubercles Some lesions may heal by fibrosis Latent TB infection(LTBI): balance that lead to infection containment
  • 10. Clinical presentation Pulmonary TB: primary TB fever and pleuritic chest pain, hilar lymphadenopathy, ghon focus vs ghon complex, middle and lower lobes secondary fever, night sweats, weigh loss, cough, purulent sputum with blood streaking, hemoptysis, localized in apical, posterior segment of upper lobes, superior segments of lower lobes.
  • 11. Extrapulmonary TB Lymphadenitis FNA, Excision for diagnosis Pleural involvement straw-colored fluid, exudative, ADA if low excludes TB Genitourinary dysuria, hematuria, flank pain, Spine TB(Potts)- involving two or more adjacent bones TB Meningitis occur in HIV seropositive, over 1-2 weeks, cranial nerve palsy, CSF lymphocytes, high protein and low glucose Gastrointestinal pain, hematochezia or mass TB peritonitis Pericarditis fever, retrosternal dull pain, effusion, constrictive pericarditis Miliary TB hematogenous spread,
  • 12. Post TB complications Bronchiectasis Aspergilloma Chronic pulmonary aspergillosis
  • 13. TB and HIV TB causes 1/3 of HIV related deaths Develops within weeks in HIV patients Can be typical or atypical Atypical: diffuse infiltrate, little or no cavitation, pleural effusion, more intrathoracic lymphadenopathy Extrapulmonary TB is more common TB immune reconstitution disease Prevention: DO NOT INITIATE ART in the first 8 weeks of TB treatment, give prednisolone 1.5mg/kg for 2 weeks then half dose for 2 more weeks
  • 14. Diagnosis AFB microscopy(ZN, florescence microscpy) examine 2 to 3 sputum samples Cultures and DNA testing Culture on liquid media 2-3 weeks Nucleic acid amplication genexpert Drug suscebility testing TST vs IGRA WHO recommends using of any to screen for TB esp. if initiating PTP
  • 15. Treatment Rifampicin: 600mg/day, cytochrome p450 inducer reduces bioavailabity of other drugs Isoniazid 300mg/day hepatotoxity and peripheral neuropathy(pyridoxine 50mg/day) Ethambutol 15mg/kg/day optic neuritis Pyrizinamide 15-30mg/kg/day hyperuricemia Others Streptomycin 750mg to 1 g/day Rifabutin used in case of nnrti or pi Rifapentin Floroquinolones: levo, gati, moxifloxacin
  • 16. monitoring LFTs, symptoms of hepatitis Stop all meds if ASTs are 5-6fold elevated Reintroduce meds once LFTs normalizes one at a time

Editor's Notes

  • #3: the mycobacterial cell wall, lipids (e.g., mycolic acids) are linked to underlying arabinogalactan and peptidoglycan. This structure results in very low permeability of the cell wall, thus reducing the effectiveness of most antibiotics. Another molecule in the mycobacterial cell wall, lipoarabinomannan, is involved in the pathogenhost interaction and facilitates the survival of M. tuberculosis within macrophages.
  • #15: All pulmonary TB re-treatment cases should have sputum TB culture and drug susceptibility testing to exclude drug resistance and especially multi-drug resistant TB. (2013, Kenya Guidelines)