Tuberculosis in Short

Pulmonary TB: 

Pulmonary TB Chest Department Ain Shams university TUBERCULOSIS

Etiology: 

Etiology Mycobacterium tuberculosis, an acid fast bacillus with three types known to infect man causing pulmonary TB: The human type, commonest The bovine type The africanum type Recently, the three are identified as the mycobacterium tuberculosis complex

Organism: 

Organism Mycobacterium tuberculosis: Slender or slightly curved rods. Non sporogenous, non capsulated bacilli. Stained by Zeil-Neelsen acid-fast stain:→ red staining rods against blue background. Cultural Characteristics : Obligate aerobe. CO2 enhance growth. 35-37 degree Celsius Grow only on enriched media containing an egg-potato base or serum albumin base. It has a slow rate of growth

PowerPoint Presentation: 

Robert Koch was the first to see Mycobacterium tuberculosis with his staining technique in 1882.

PowerPoint Presentation: 

Each year, 1% of the global population is infected. 5-10% of those infected become sick or infectious. Populations infected: Africa: 35% Americas: 18% Eastern Mediterranean: 29% Europe: 15% South-east Asia: 44% Western Pacific: 35% Disease information: Distribution

TB epidemiology: Egypt: 

TB epidemiology: Egypt

TB epidemiology: Egypt: 

TB epidemiology: Egypt

Pathogenesis: 

Pathogenesis Infected droplet nuclei: 1-5 Um (spitted infected sputum mixed with dust) LRT epithelium Alveoli ↓ ↓ Induce inflammatory response Macrophages

Pathogenesis: 

Pathogenesis Inflammatory response → Primary focus Lympho-hematogenous spread → Lymphangitis + Lymphadenitis. Some bacilli may escape to the circulation and seeds in distal organ. Alveoli → Alveolar Macrophage → Ingest bacilli Completely destroyed Lie dormant

Clinical Presentation: 

Clinical Presentation

Primary TB “Entrance of Bacilli into the body for the 1st time”: 

Primary TB “ Entrance of Bacilli into the body for the 1 st time ” Usually in children: school age Clinically: Flu like, ± Cough, pass un-noticed. Pathologically: “Primary Complex” Parenchymatous: limited Nodal component: prominent Lymphangitis.

Primary TB : 

Primary TB Fate: Spontaneous resolution (self limited): in most cases. Progression: → Post-primary. Other sequele: broncholith, bronchiectasis, collapse and bronchiectasis of the upper lobe(epituberculosis), and obstructive emphysema If detected and diagnosed: Full treatment.

Hyper-sensitivity Manifestations of TB : 

Hyper-sensitivity Manifestations of TB Erythema Nodosum. Phlyctenular conjunctivitis. Middle Lobe Syndrome. Pleural Effusion. Tuberculin Test.

Post Primary TB: 

Post Primary TB General manifestations: insidious , acute Fever, Loss of weight, Loss of appetite, Toxemia? Pulmonary manifestation: Productive cough. Hemoptysis. Dyspnea & Tachypnea. Chest wheeze.

Diagnosis of TB: 

Diagnosis of TB DIAGNOSIS OF INFECTION:by tuberculin skin testing DIAGNOSIS OF DISEASE: Clinical picture CBC, ESR CXR Bacteriological diagnosis Histopathological diagnosis

Tuberculin test: 

Tuberculin test Mantoux test. Interpretation: -ve (less than 5 mm),+ve: ( >or =5mm in recent contact with active TB ,HIV or risk with unknown status, and in pt with fibrotic CXR consistent with healed TB

Tuberculin test CONT’D: 

Tuberculin test CONT ’ D > OR =10 mm in all patients who didn ’ t belong to the above criteria but belong to the following groups: IV drug users, pt with a medical condition with high risk of progression of latent disease,residents and employees of high risk congregate settings, foreign born into high prevalence countries, children or adults exposed to high risk categories

Tuberculin test CONT’D: 

Tuberculin test CONT ’ D > 15 mm in persons who don't meet any of the above criteria False positive: BCG False negative

Bacteriological diagnosis: 

Bacteriological diagnosis Specimen collection Identification : conventional(morphology of mycobact TB complex,Staining, Culture, Biochemical reactions, Pathogenecity to rabbit, Adding glycerol Rapid identification techniques( bactec radiometric assay, DNA probing, Lipid chromatography of the cell wall, direct sequencing of PCR products, PCR

Bacteriological diagnosis cont’d: 

Bacteriological diagnosis cont ’ d Drug susceptibility testing: conventional (1%), non conventional (direct detection at DNA level, luciferase reporter assay

Global Burden of TB: 

Global Burden of TB About one third of the world’s population is infected by Mycobacterium Tuberculosis , which kills more people than any other infectious agent. Tuberculosis poses a major problem for developing countries as follows: Deaths from TB comprises 25% of all avoidable deaths in developing countries. 95% of all TB cases and 98% of TB deaths occur in developing countries. 75% of TB cases in developing countries are in the economically productive age group (15-50 years).

PowerPoint Presentation: 

Why Does the Burden of TB Increase Inadequate health services. Improper management practices resulting in poor case detection, diagnosis & treatment. Demographic changes: increasing world population & changing age structure. Impact of HIV pandemic.

Control & Prevention: 

Control & Prevention General:  overcrowding, improve nutrition, health education  standard of living, pasteurization of milk. Case finding & treatment BCG Chemoprophylaxis

Control & Prevention: 

Control & Prevention Case finding: High yield group: Symptoms > 4 weeks. Contacts with TB case. Medical personal, inhabitant of nursing homes…. Danger group: (pre employment CXR then annually) Workers with children, schoolteachers, food server…  CXR / MMR , Sputum examination.

Control & Prevention: 

Control & Prevention BCG vaccination: It does not prevent infection with TB. Prevents fulminating forms as miliary & TB meningitis. Compulsory given to infants in the first 30 days of life. A booster dose is given at school age.

Control & Prevention: 

Control & Prevention Chemoprophylaxis: Prevent progression of infection to disease. Given to high risk group: Infant of mother with TB. Close contacts to TB case: Child +ve TT & normal CXR. Adult +ve TT & healed lesion CXR. Tuberculin reactors under risky conditions (immunosuppression). Isoniazide (INH) 6 months daily 5mg/kg.

Treatment Of Tuberculosis: 

Treatment Of Tuberculosis

Treatment: Aim: 

Treatment: Aim Cure the patient. Prevent death. Decrease the transmission of TB bacilli. Prevent the development of resistance. Prevent TB replase.

Principles of anti-TB Treatment:: 

Principles of anti-TB Treatment: Proper ttt regimen: combination, dosage, duration. Assure regular intake of drugs: DOTS. Prevent & monitor appearance of side effects. Monitor the efficacy of ttt: sputum conversion. Proper ttt of associated diseases e.g. DM. Good adequate diet. Isolation of patients who are excreting tubercle bacilli. Regimens consist: initial phase  continuation phase.

Principles of anti-TB Treatment:: 

Principles of anti-TB Treatment: Hospitalization: complications, associated diseases, non compliant patient, re-treatment regimen. Follow up: During ttt: improvement of symptoms , compliance of patient, sputum examination (4X) , x-rays, appearance of side effects or complications. After Cure: regular ttt  renewal of symptoms irregular ttt clinical,bacteriological & radiological.

Principles of anti-TB Treatment:: 

Principles of anti-TB Treatment: 1st line drugs: used in the initial & maintenance phases Rifampicin, Isoniazide, Pyrazinamide, Ethambutol & Streptomycin. 2nd line drugs: used in patients with known or suspected drug resistance. Para-amino salicylic acid, Thiacetazone, Ethionamide, Cycloserine & Kanamycin. Recent drugs: Quinolones, Rifabutin, Rifapentine.

PowerPoint Presentation: 

WHO treatment categories: Alternative TB treatment Regimen TB Patient TB Cat. Continuation phase Initial phase 6 HE (or) 4 HR (or) 4H3R3 2EHRZ (SHRZ) New smear positive PTB New severe forms of extrapulmonary TB I 5H3R3E3 (or) 5HRE 2SHRZE/ 1 HRZE Sputum smear positive (relapse, treatment failure, treatment after interruption) II 6 HE (or) 4 HR (or) 4H3R3 2 HRZ New smear negative PTB New less severe forms of extrapulmonary TB III Not Applicable Use 2 nd line drugs Chronic Case IV

Current regimens for treatment of drug susceptible tuberculosis:: 

Current regimens for treatment of drug susceptible tuberculosis: Continuation phase Initial phase Regimen 4 months of isoniazid & rifampicin 2 months of isoniazid, rifampicin, & pyrazinamide, with or without ethambutol Daily * 24 weeks of twice weekly isoniazid & rifampicin 18 weeks of thrice weekly isoniazid & rifampicin 2 weeks of daily isoniazid, rifampicin, pyrazinamide & streptomycin or ethambutol 8 weeks of thrice weekly isoniazid, rifampicin, pyrazinamide & streptomycin or ethambutol Intermittent

MDR TB: 

MDR TB

Suggested regimens for patients with different patterns of MDR-TB:: 

Suggested regimens for patients with different patterns of MDR-TB: Comments Minimum duration (months) b Suggested regimen Pattern of drug resistance in extensive diseases, an additional agent may be added 18 EMB, PZA, FQN, AMK Isoniazid and rifampicin (± streptomycin) surgery should be considered 18 PZA, FQN, AMK plus 2 a Isoniazid, rifampicin and ethambutol (± streptomycin) surgery should be considered 18 – 24 EMB, FQN, AMK plus 2 a Isoniazid, rifampicin and pyrazinamide (± streptomycin) surgery should be considered 18 – 24 FQN, AMK plus 3 a Isoniazid, rifampicin, ethambutol and pyrazinamide (± streptomycin) Additional agents: a ethionamide, PAS, cycloserine , ß-lactams , clarithromycin , linezolid , clofazimine . b After sputum conversion.

Recent lines of treatment for Multidrug-Resistant Tuberculosis (MDR): : 

Recent lines of treatment for Multidrug-Resistant Tuberculosis (MDR): Linezolid has been the first oxazolidinone to be developed & approved for clinical use. It is active against a range of bacteria, but its primary clinical role is the treatment of infections caused by aerobic Gram-positive organisms, including resistant strains such as vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus & penicillin-resistant pneumococci. linezolid has a good activity against M. tuberculosis .

Recent lines of treatment for multidrug-resistant tuberculosis (MDR): : 

Recent lines of treatment for multidrug-resistant tuberculosis (MDR): The most limiting problem related to the prolonged use of linezolid in MDR-TB is toxicity. linezolid is considered as a valid alternative in patients with MDR-TB. The prolonged use of the drug is frequently associated with toxicity, mainly anemia & peripheral neuropathy. A half-dose reduction is plausible in patients who developed toxicity

Formulations, dosing, type of activity & evidence of clinical evaluation of agents available for MDR-TB treatment:: 

Formulations, dosing, type of activity & evidence of clinical evaluation of agents available for MDR-TB treatment: Type of antimycobacterial activity Average daily dose Formula Drug bactericidal at acid pH 15 – 30 mg/g 1000 – 2000 mg daily tablet (500 mg) Pyrazinamide bacteriostatic 15 – 30 mg/kg 800 – 1600 mg Daily tablet (100, 400 mg) Ethambutol bactericidal against exponential phase bacilli 20 – 40 mg/kg (1 g) once daily 1 g vial, iv or im injection Streptomycin bactericidal against exponential phase bacilli 15 – 30 mg/kg (1 g) once daily 500 mg and 1 g vial, iv or im injection Amikacin/kanamycin bactericidal against exponential phase bacilli 15 – 30 mg/kg (1 g) once daily 1 g vial, iv or im injection Capreomycin bacteriostatic 8 – 12 g/day in two or three doses granules (4 g packets); tablet 500 mg p -Aminosalicylic acid bacteriostatic 10 – 15 mg/kg usually 500 – 750 mg in two doses capsule (250 mg) Cycloserine

Formulations, dosing, type of activity & evidence of clinical evaluation of agents available for MDR-TB treatment:: 

Formulations, dosing, type of activity & evidence of clinical evaluation of agents available for MDR-TB treatment: bactericidal 15 – 20 mg/kg usually 500 – 750 mg/day in single daily or two divided doses tablet (250 mg) Ethionamide/ prothionamide weakly bactericidal 500 – 1000 mg daily tablet (500 and 750 mg) Ciprofloxacin weakly bactericidal 400 – 800 daily tablet (400 mg) Ofloxacin bactericidal 500 – 1000 daily tablet (500 mg) Levofloxacin bactericidal 400 mg daily tablet (400 mg) Gatifloxacin bactericidal 400 mg daily tablet (400 mg) Moxifloxacin bactericidal against exponential phase bacilli 3000/750 mg in three doses tablet (1000/250 mg) Co-amoxiclav bacteriostatic 1000 mg tablet (500 mg) Clarithromycin bacteriostatic 1200 mg in two doses tablet and vial (600 mg) Linezolid

Mycobacterium vaccae immunotherapy for treating Tuberculosis: : 

Mycobacterium vaccae immunotherapy for treating Tuberculosis: In 2007, Mycobacterium vaccae was evaluated to assess the effects of Mycobacterium vaccae as an adjunct to chemotherapy for treating tuberculosis & it was concluded that there is no benefit from immunotherapy with Mycobacterium vaccae in people with tuberculosis.

Tuberculosis & Comorbidities: 

Tuberculosis & Comorbidities

Tuberculosis & HIV:: 

Tuberculosis & HIV: Tuberculosis has a greater impact worldwide on morbidity & mortality in HIV-1-infected individuals than all other opportunistic infection. In fact, the rising incidence of tuberculosis in many regions of the world is closely related to the HIV epidemic. Approximately 1/3 of the 40 million people infected with HIV-1 are co-infected with Mycobacterium tuberculosis ( M. tuberculosis, M. africanum , M. bovis , M. canetti or M. microti - MTB). The prevalence of HIV in tuberculosis patients in Africa has been reported to be around 40 percent & the incidence of HIV is more than 8 times higher in HIV-positive than in HIV-negative people.

Interaction of HIV & MTB:: 

Interaction of HIV & MTB : The influence of HIV & MTB on immunoregulation by the host is bidirectional. The incidences of post-primary tuberculosis & reactivation tuberculosis are increased in HIV-infected patients in comparison to HIV-seronegative individuals. Further, it is likely that tuberculosis enhances immunodeficiency in patients with chronic HIV infection. Despite adequate therapy of tuberculosis, the subsequent morbidity & mortality is increased in patients with HIV infection in comparison to HIV-seronegative patients with tuberculosis.

Interaction of HIV & MTB:: 

Interaction of HIV & MTB : While most opportunistic infections, including all other mycobacterial diseases, occur in the advanced stages of HIV infection, patients can develop tuberculosis at any stage, regardless of the levels of circulating CD4+ T-cells. More than 50 percent of cases with pulmonary tuberculosis occur in patients with CD4 counts of more than 200 cells/µl in the peripheral blood. However, the incidence of disseminated tuberculosis is much higher in patients with advanced immunodeficiency. Recently, it was shown that the risk of developing tuberculosis is already significantly increased in the first year following HIV-antibody seroconversion.

Follow up after completion of therapy: 

Follow up after completion of therapy Most relapses occur in the first 2 years after completion of therapy. 6 months intervals: incases who show clinical & bacteriological response within the 1 st 2 months of therapy. Closer and more routine in: Patients whose response to therapy was slower. Drug resistance TB. Encourage patients to report promptly any symptoms of recurrent cough, fever, or weight loss.

Chemotherapy cont’d: 

Chemotherapy cont ’ d Corticosteroids are indicated in TB of the serous membranes, meningitis, very ill patients, and to control drug hypersensitivity reactions.

SURGICAL ttt: 

SURGICAL ttt MASSIVE HEMOPTYSIS LOCALIZED BRONCHIECTASIS EMPYEMA BRONCHOPLEURAL FISTULA, BRONCHOSTENOSIS TUBERCULOMA FOR DIAGNOSIS COLLAPSE THERAPY GROSSLY CASEOUS ln requiring evacuation In MDR: IF BACILLI ARE RESISTANT TO ALL BUT 2-3 WEAK DRUGS WITH A LOCALIZED CAVITY AND REASONABLE LUNG FUNCTIONS

Special problems: 

Special problems WITH PREGNANCY WITH DIABETES MELLITUS WITH HIV

PowerPoint Presentation: 

Thank You