Transcript Definition
Tuberculosis Definition Tuberculosis (TB) is a chronic granulomatous bacterial infectious disease usually caused by Mycobacterium tuberculosis and occasionally by Mycobacterium bovis and Mycobacterium africanum Epidemiology TB is the second leading infectious disease that causes most deaths in the world It is estimated that about two billion people i.e. one third of the world’s population are infected with M.Tuberculosis Each year more than eight million new cases are reported and nearly three million people die due to mismanagement of the disease Management of TB is worsening due to the spread of drug- resistant organisms and also due to rapid spread of HIV infection. Types of Tuberculosis Primary tuberculosis: The infection of an individual with tubercle bacilli who has not been previously infected or immunized is called primary tuberculosis Secondary tuberculosis: The infection of an individual who has been previously infected or sensitized is called secondary or post-primary or reinfection. The causes for secondary tuberculosis may be, Treatment failure during primary infection May be the patient is immunocompromised Depending upon the organ involved, tuberculosis is classified into, Pulmonary tuberculosis The organ involved is lung and is the most common type of tuberculosis. Extra pulmonary tuberculosis (Milliary TB) Tuberculosis of skin, bone, kidney, intestine, liver, spinal chord, eyes, male genital tuberculosis, female genital tuberculosis and tubercular meningitis of brain. Tuberculosis in this type spreads from lung to other organs through haematogenous route and forms millets on the organs hence it is also called as milliary TB. Etiology Acid fast bacilli or tubercle bacilli, Mycobacterium tuberculosis Mycobacterium bovis Mycobacterium africanum Mycobacterium avium complex Spread of infection Air borne disease Infected patients coughs, sneezes, splits expels germs which remain suspended in air Healthy person inhales infected air and get infected Pathogenesis Aerobic bacterium- grows successfully in tissues having highest oxygen tension (lung apices) Infected droplets get lodged in the terminal alveoli Multiplication of bacilli Formation of granuloma Pathogenesis . . . After 4-6 weeks- development of immune response Progression of disease, signs and symptoms May spread to other organs through blood leading to extra pulmonary TB AIDS- progressive weakening of immune system- more chances of primary infection, reinfection and reactivation of disease Laboratory detection Tuberculin test (Mantoux test) Intradermal tween-80 stabilized PPD injection Evaluated after 48-72 hours Diameter of induration determines interpretation Laboratory detection Microbiological test Ziehl neelsen staining Sample-early morning sputum Acid fast bacilli found under microscope Laboratory detection…. Chest X-ray Management Goals: To cure the infection and relieve the signs and symptoms To prevent the individual from death due to active TB or its late effects To prevent TB relapse To prevent the transmission of infection to others Treatment categorization TB PATIENTS CHARACTERISTICS TREATMENT CATEGORY Category 1 New sputum smear-positive pulmonary TB Category 2 Newly diagnosed seriously ill patients with severe forms of TB Relapse Treatment failure Return after default (interrupted treatment) Category 3 Category 4 Sputum smear-negative pulmonary TB with limited parenchymal involvement Extra pulmonary TB (less severe forms) Chronic cases The essential anti TB drugs RECOMMENDED DOSE (mG/KG) ESSENTIAL ANTITB DRUG MODE OF ACTION POTENCY DAILY INTERMITTENT Isoniazid (H) Bactericidal High 5 10 15 Rifampacin (R) Bactericidal High 10 10 10 Pyrazinamide (Z) Bactericidal Low 25 35 50 Streptomycin (S) Bactericidal Low 15 15 15 Etambutol (E) Bacteriostatic Low 15 30 45 Thiacetazone (T) Bacteriostatic Low 03 3x/wk 2x/wk NOTAPPLICABLE Principal activity and site of action of major anti-TB agents AGENT Isoniazid ACTIVITY Bactericidal SITE OF ACTION Intracellular bacilli extracellular bacilli bacilli in caseous lesions Rifampacin Bactericidal Intracellular bacilli extracellular bacilli bacilli in caseous lesions Pyrazinamide Streptomycin Etambutol Bactericidal Bactericidal Bacteriostatic Intracellular bacilli Extracellular bacilli Intracellular Extracellular Recommended treatment regimens TB Treatment category 1 2 3 TB patient TB Treatment regimens Initial Phase New smear-positive PTB and 2 SHRZ (EHRZ) seriously ill extra pulmonary or 2 SHRZ (EHRZ) smear negative pulmonary (severe 2 SHRZ (EHRZ) TB) 2 E3H3R3Z3 2 SHRZE/ 1 HRZE Sputum smear-positive: relapse, treatment failure and return after 2 SHRZE/ 1 HRZE default 2 S3H3R3Z3E3/ 1 H3R3Z3E3 Smear-negative PTB and Extra 2 HRZ or 2 H3R3Z3 pulmonary TB (Less severe) 2 HRZ or 2 H3R3Z3 2 HRZ or 2 H3R3Z3 4 Continuation Phase 6 HE 4 HR 4 H3R3 4 H3R3 5 H3R3E3 5 HRE 5 H3R3E3 6 HE 2 HR/4 H 2 H3R3/ 4 H 2 H3R3Z3 4 H3R3 Chronic case (still sputum-positive NOT APPLICABLE after supervised re-treatment) (REFER TO SPECIAL CENTRE IF SECONDLINE DRUGS AVAILABLE) Isoniazid It is a potent bactericidal agent Kills 90% of the total population of bacilli Most effective against the metabolically active, continuously growing bacilli MOA- impairs the cell-wall mycolic acid synthesis and mycobacterial DNA synthesis Due to good tissue penetration activity, it distributes into the CNS, tuberculous abscesses and intracellular sites Drug interactions Isoniazid.... INH increases serum concentration of phenytoin, Carbamazepine, primidone and barbiturates INH decreases serum levels of ketoconazole Prednisolone decreases serum concentration of INH Counseling points Isoniazid.... Ask patient to take this medication on empty stomach About ADRs- Common: peripheral neuropathy Rare: convulsions, pellagra, joint pains, agranulocytosis, lupoid reactions, skin rash, optic neuritis, personality changes, Rheumatic syndromes, fever. Rifampicin It is a bactericidal agent, kills the semi-dormant bacilli which Isoniazid is unable to kill It acts by inhibiting DNA-dependent RNA polymerase As it is a fat soluble molecule, achieves excellent tissue penetration including CNS Drug interactions Rifampicin…. Rifampicin decreases the serum concentration of Warfarin, oral contraceptives, cyclosporine, Glucocorticoids, Itraconazole, Ketoconazole, Theophylline, Quinidine, Digitoxin, Verapamil, Nifedipine and Methadone. Counseling points Rifampicin…. • Ask the patient to take this medication on empty stomach • Inform the patient that this drug may cause orange discoloration of urine, sweat, tears and saliva • Counsel the patient to adopt alternate methods of contraception if they are on oral contraceptives as this drug may decrease the effect of oral contraceptives • Advice the patients on Rifampicin to avoid using contact lenses and encourage them to use spectacles Counseling points… Rifampicin…. About ADRs- Common- Anorexia, nausea, vomiting, abdominal pain, hepatitis, orange discoloration of urine, sweat, tears and saliva. Rare-Fever, rash, eosinophilia, thrombocytopenia, leucopenia, hemolytic anemia, acute renal failure. Pyrazinamide It is a bactericidal agent, kills bacilli in an acid environment inside cells (ex: macrophages) It is well absorbed from the gastrointestinal tract Widely distributed in body tissues and fluids including CSF Counseling points Pyrazinamide…. Ask the patient to take this medication on empty stomach About ADRs Common- joint pains, hepatitis Rare- skin rashes, sideroblastic anaemia Ethambutol It is a Bacteriostatic agent Acts by impairing incorporation of mycolic acids into the cell wall It also suppresses mycobacterial multiplication by interfering with RNA synthesis It has tissue penetration property including those of CNS especially when the meninges are inflamed Drug interactions Ethambutol…. Aluminium containing antacids decreases the absorption of Ethambutol Counseling points Ethambutol…. Patient must be told to avoid concurrent administration of aluminium containing antacids for at least 4 hours following Etambutol Drug may be taken with food as absorption is not affected Patient should be instructed to report any changes in visual acuity and seek medical attention immediately if changes do occur Counseling points…. Ethambutol…. About ADRs Retro bulbar neuritis (decreased visual acuity, loss of red-green color vision, central scotomata) Hypersensitivity reactions, neuritis, GI Intolerance, headache, hyperuricemia. Streptomycin It is an aminoglycoside bactericidal antibiotic It act by inhibiting protein synthesis by binding directly to the 30 S ribosomal subunit causing faulty peptide sequence to form in the protein chain. Drug interactions Streptomycin…. Use of Amphotericin B or loop diuretics along with streptomycin increases the risk of Nephrotoxicity Counseling points Streptomycin…. Patient should be informed to avoid high pitch sounds About ADRs- Ototoxicity, Nephrotoxicity, skin rashes, nausea, vomiting, headache, drowsiness, difficulty in breathing Contraindication: Pregnancy Treatment of Tuberculosis in Special Population Children Dosage in Children DRUGS THERAPY PER DOSE (THRICE A WEEK) Isoniazid 10-15 mg/kg Rifampicin 10 mg/kg Pyrazinamide 35 mg/kg Streptomycin 15 mg/kg Ethambutol 30 mg/kg Pregnancy pregnant women infected with TB should be treated with anti TB drugs similarly as that of a non-pregnant woman Use of streptomycin in pregnancy is contraindicated as it can cause permanent deafness in the baby Renal failure Based on creatinine clearance, Isoniazid, Pyrazinamide and streptomycin requires dosage adjustment Rifampicin found to be safe in renal impairment. Hepatic disease Most of the anti TB drugs can cause liver damage If the patient develops clinical signs of liver damage, all antitubercular drugs should be stopped as it is not possible to identify the agent responsible for liver damage The antitubercular drugs should then be reintroduced one at a time, each drug being given for about a week before another is added Hepatic disease . . . This should be accompanied by regular monitoring of LFTs and close clinical supervision, so that the drug responsible may be identified by a recurrence in symptoms The offending drug could be then omitted from the regimen or replaced by Streptomycin Jaundiced patients who develop TB should receive treatment with 2 SHE/ 6 HE Pyrazinamide should be avoided in patients with liver disease Elderly In elderly population as their renal and hepatic functions are compromised Anti TB drugs such as Isoniazid, Pyrazinamide and streptomycin requires dosage adjustment based on their individual creatinine clearance and extent of hepatic impairment HIV patients with TB HIV infected individual who do not require antiretroviral therapy can receive standard anti TB regimen If the individual with HIV who is co infected with TB and also receiving antiretroviral drugs the management of TB becomes complicated due to interactions between antiretroviral and anti TB drugs HIV patients with TB .... There are two options available In first, Rifabutin, Isoniazid, Pyrazinamide and Ethambutol are administered daily for either 2 weeks or 8 weeks to complete the induction phase and therapy is completed by administering Rifabutin and Isoniazid daily or twice a week for 4 months HIV patients with TB .... The usual Rifabutin dose of 300 mg should be reduced to 150 mg during daily therapy in patients who are also receiving Indinavir, Nelfinavir or amprenavir Dosage reduction for Rifabutin is not necessary during twice weekly Rifabutin therapy. HIV patients with TB . . . The second option is usually reserved for HIV patients who cannot receive Rifabutin It consists of Isoniazid, Streptomycin, Pyrazinamide and Ethambutol administered daily for either 2 weeks or 8 weeks and then twice a week for 6 weeks to complete the induction phase The therapy is completed by administration of Isoniazid, Streptomycin and Pyrazinamide two or three times a week for 7 months Drug resistant cases Multi-drug resistant tuberculosis (MDR-TB) is defined as “resistance to Isoniazid and Rifampicin whether there is resistance to other drugs or not” Extremely drug resistant TB (XDR-TB) is “The condition in which the bacilli show resistance to Isoniazid and Rifampicin plus resistance to any Fluroquinolones and any one of the second line injectable drug” Factors related to the development of drug resistance include Inadequate or inefficient administration of effective treatment Poor case handling Use of substandard drugs Inadequate or irregular drug supply Ignorance of health care workers in the treatment and control of TB Factors related to the development of drug resistance include... Interruption of chemotherapy due to side effects Non adherence of patients to the prescribed regimen Availability of anti TB drugs without prescription Illiteracy Factors related to the development of drug resistance include... Low socio economic status patients Massive bacillary load Laboratory delay in identification and susceptibility testing of Mycobacterium tuberculosis isolates Lack of use of uniform laboratory methodology and quality control measures Prevention of drug resistance Directly Observed Therapy (DOT) Monitoring the patient taking Anti-TB drugs by HCP WHO believes that personal monitoring will reduce the relapse and increases therapeutic outcome Treatment for MDR-TB Should be based on sensitivity testing Patient with suspected MDR-TB should be started on SHREZ Based on known sensitivities, five drugs should be choosen in the following order: An Aminoglycoside (Amikacin, Kanamycin) or polypeptide antibiotic (capreomycin) Pyrazinamide Ethambutol A Fluroquinolone (Moxifloxacin, Ofloxacin) Treatment for MDR-TB.... Rifabutin Cycloserine A Thioamide (Prothionamide or Ethionamide) Paraamino salicylic acid A Macrolide (Clarithromycin) Linezolid High dose INH (if low level resistance) Interferon alpha Thioridazine In XDR-TB, surgery is the last choice ADRs of essential anti-TB drugs Drug Isoniazid Rifampicin Pyrazinamide Ethambutol Common effects Peripheral neuropathy Skin rash Hepatitis Sleepiness and lethargy Abdominal pain Nausea, vomiting, Hepatitis, Generalized cutaneous reactions, Thrombocytopenic purpura Rare effects Convulsions Psychosis Arthralgia Anemia Osteomalacia Pseudomembranous colitis Pseudo adrenal crisis Acute renal failure Hemolytic anemia Arthralgia, Hepatitis, abdominal pain, nausea and Cutaneous reactions Sideroblastic anemia vomiting Generalized cutaneous reactions Retro bulbar neuritis Arthralgia Peripheral neuropathy Hepatitis (very rare) Streptomycin Vestibular and auditory nerve damage Nephrotoxicity Injection site cutaneous hypersensitivity Thiacetazone Skin rash, sometimes with mucosal involvement pain, rash, induration and numbness around the mouth and tingling soon after the injection ADRs of reserve anti-TB drugs Drug Common effects Rare effects Aminoglycosides Vestibular (vertigo) and Auditory nerve Cutaneous hypersensitivity Clinical renal failure damage Nephrotoxicity Ethionamide Anorexia, nausea, diarrhoea, abdominal pain, hepatotoxicity Convulsions, Mental symptoms Impotence, Gynaecomastia Fluroquinolones Anorexia, nausea, Vomiting Dizziness, headache, convulsions, Rupture of Achilles tendon Cycloserine Dizziness, Headache, Depression, Hepatitis, Psychosis, Convulsion Suicide Generalized hypersensitivity Hepatitis Para amino salicylic acid Anorexia, nausea, vomiting Hypersensitivity reactions like fever, rash, pruritus Hypothyroidism Hematological reactions Grading and Management of Adverse Drug Reactions Grade Adverse reaction Management Abnormal but requiring no immediate intervention Reassurance, occasionally symptomatic therapy, continue ATT Sufficiently abnormal requires evaluation to assess the causality and requires mild therapeutic intervention but may not require immediate changes in drug Symptomatic treatment and continuation of ATT III Sufficiently severe to require evaluation and treatment, including at least temporary suspension of the responsible drug Symptomatic treatment. If needed to reduce the dosage of drug responsible or temporary with-holding of the drug IV Life threatening severity, require an immediate evaluation, treatment and hospitalization. Study drug must be stopped immediately and drug should not be restarted until the abnormality is clearly felt to be caused by some other mechanism than the study drug Termination of the drug responsible/ change of treatment regimen I II