tuberculosis

Management of Tuberculosis : 

Management of Tuberculosis

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Presented By Jyoti Prakash

A Global Emergency: 

A Global Emergency The Tuberculosis in the beginning of the 21 st Century - declared as Global Emergency (WHO)

Table of Content : 

Table of Content Introduction Historical discovery MTB Etiology of TB Pathophysiology Diagnosis & Treatment Management of TB Epidemiology of TB Market research Conclusion

Introduction : 

Introduction Tuberculosis , MTB or TB (short for tubercle bacillus ) is lethal infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis . Tuberculosis usually attacks the lungs but can also affect other parts of the body. It is spread through the air when people who have an active MTB infection cough, sneeze, or otherwise transmit their saliva through the air.

Why Tuberculosis is an Important Disease: 

Why Tuberculosis is an Important Disease An Important communicable disease. A leading cause of morbidity and mortality in Developing world. Most common in Bangladesh, India, China , Indonesia, Africa, and Pakistan . “But it is Curable Disease”

Historical Background: 

Historical Background Neolithic Time 2400 BC - Egyptian mummies spinal columns 460 BC Hippocrates, Greece First clinical description: Phthisis / Consumption 500-1500 AD Roman occupation of Europe it spread to Britain 1650-1900 AD White plague of Europe, causing one in five deaths 24 th March 1882 (Robert Koch) TB Day Discovery of staining technique that identified Tuberculosis bacillus Definite diagnosis made possible and thus treatment could begin 1890 (Robert Koch) Tuberculin discovered Diagnostic use when injected into skin 1895 (Roentgen) Discovery of X-rays Early diagnosis of pulmonary disease

ETIOLOGY : 

ETIOLOGY

Causes of MTB : 

Causes of MTB Cause of TB, Mycobacterium tuberculosis (MTB)- Is a small aerobic non-motile bacillus. High lipid content It divides every 16 to 20 hours, MTB has a cell wall but lacks a phospholipid outer membrane. It is classified as a Gram-positive bacterium . if a Gram stain is performed, MTB either stains very weakly Gram-positive or does not retain dye as a result of the high lipid & mycolic acid content of its cell wall. MTB can withstand weak disinfectants and survive in a dry state for weeks. In nature, the bacterium can grow only within the cells of a host organism, but M. tuberculosis can be cultured in vitro .

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The M. tuberculosis complex includes four other TB-causing mycobacteria: M. bovis , M. africanum , M. canetti M. microti . M. africanum - not widespread, but in parts of Africa it is a significant cause of tuberculosis. M. bovis - a common cause of tuberculosis. M. canetti - rare and seems to be limited to Africa. M. microti - mostly seen in immunodeficient people. Other known pathogenic mycobacteria include M. leprae M. avium M. kansasii . The latter two are part of the nontuberculous mycobacteria (NTM) group. Nontuberculous mycobacteria cause neither TB nor leprosy , but they do cause pulmonary diseases resembling TB

When to suspect Tuberculosis: 

When to suspect Tuberculosis Cough longer than 2 weeks, Fever for 1 month, or Both . Blood stained sputum, Night sweats, weight loss.

PATHOPHYSIOLOGY: 

PATHOPHYSIOLOGY

Transmission: 

Transmission Incubation period 4-12 weeks Transmitted through droplet spread Undiagnosed / confirmed infected persons Breathing, coughing, sneezing, talking, or singing

Signs and symptoms: 

Signs and symptoms Early symptoms Common cold symptoms. Fatigue , fever . Minimally productive cough of yellow or green sputum. Later symptoms Night sweats, fever, cough with purulent secretions Haemoptysis, chest pain.

Pathophysiology of tuberculosis: 

Pathophysiology of tuberculosis First line of defense Second line of defense Third line of defense Fourth line of defense

First line of defense: 

First line of defense Majority of inhaled bacteria are trapped in the upper tracts of the airways where the mucous secreting goblet cells exist. The mucous produced catches foreign substances and the cilia one the surface of the cells constantly beat the mucous and its entrapped particles for removal. This mechanism prevents infection in most of the persons exposed to tuberculosis

Second line of defense: 

Second line of defense Bacteria that bypass the muco ciliary system and reach the alveoli are quickly surrounded and engulfed by alveolar macrophages. Macrophages are readily available phagocytic cells that combat many pathogens without previous exposure to the pathogens. The mycobacterial lipoarabinomanan is a key ligand for the macrophage receptor.

Third line of defense: 

Third line of defense If the macrophage alone could not engulf the bacteria it produces proteolytic enzymes and cytokines. The released cytokines attract T-lymphocytes to the site. Macrophages then present mycobacterial antigens on their surface to the T- cells.

Fourth line of defense: 

Fourth line of defense The defense mechanism involves the formation of granulomas around the m.tuberculosis organisms. Granulomas are accumulation of T lymphocytes and macrophages, which creates a micro environment that limits replication and the spread of the mycobacteria.

Epidemiology : 

Epidemiology

Aims of Epidemiology? : 

Aims of Epidemiology? To describe natural history of tuberculosis Describe Distribution of TB Measure frequency To define risk groups To predict future trends and changes in disease presentation.

TB rates increasing : 

TB rates increasing TB infection rate is increasing due to Aging population Increasing travel and migration Increasing drug resistance Increasing HIV prevalence

Other High Risk Groups: 

Other High Risk Groups Populations in war / civil unrest Refugees and migrants Slum dwellers Homeless people/Foot path dwellers Smoking Prisoners

TB Rates in Countries of Birth 2010: 

TB Rates in Countries of Birth 2010 Per 100,000 Source: World Health Organization

Who Should Be Tested: 

Who Should Be Tested Know the TB status of your at risk patients. Who is considered at risk? What countries are considered TB endemic? Foreign born patients from TB endemic countries, where prior TB exposure is almost certain All of Asia except Japan All of Central and South America All of Africa All of Eastern Europe (Yes, that is practically the whole world)

TB Case Rates by Age Group and Sex, United States, 2010: 

TB Case Rates by Age Group and Sex, United States, 2010 Highest Incidence is in 65+

Countries of Birth of Foreign-born Persons Reported with TB United States, 2008-10: 

Countries of Birth of Foreign-born Persons Reported with TB United States, 2008-10 Other Countries (38%) Guatemala (3%) Haiti (3%) China (5%) India (7%) Viet Nam (8%) Philippines (11%) Mexico (25%)

Management of TB: 

Management of TB

Diagnosis : 

Diagnosis Sputum X-ray chest Sputum culture

Diagnosis: 

Diagnosis Physical examination Microbiological studies Sputum Alternate sampling Radiography Chest x-ray Tuberculin skin test Mantoux skin test Heaf test

ANTI TUBERCULAR DRUGS: 

ANTI TUBERCULAR DRUGS FIRST LINE ESSENTIAL DRUGS Isoniazid Rifampicin Ethambutol Pyrazinamide FIRST LINE SUPPLEMENTARY DRUGS Streptomycin SECOND LINE ESSENTIAL DRUGS Category Drugs Aminoglycosides amikacin Thioamides ethionamide Polypeptide capreomycin Fluoroquinolones ofloxacin , ciprofloxacin PAS PAS

First line drug- INH (Isoniazide) H: 

First line drug- INH (Isoniazide) H Most active anti TB drug Important assets are Potency infrequent toxicity low cost Bactericidal for rapid multipliers B acterostatic for dormants Effective for both extra cellular & intracellular TB If combined with other drug it has good resistance preventing action

Mechanism of Action: 

Mechanism of Action ISONIAZID Kat G ( catalase peroxidase in mycobacteria ) Active INH AcpM & Kas A AcpM - Acyl Carrier protein KasA ( ß keto Acyl Carrier protein synthetase ) Block Mycolic Acid Synthesis

Pharmacokinetics: 

Pharmacokinetics Absorption Complete, Oral dose = Parenteral dose Distribution Penetrate all body tissues Placenta Meninges Caseous TB lesion Metabolism Liver INH N acetyl transferase (NAT 2 ) N-Acetyl Isoniazid Isonicotinic Acid Acetyl hydrazine 1 st ACETYLATION (Phase II ), then HYDROLYSIS (Phase I)

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Excretion: 75-95 % excreted in urine Dose adjustment is not required in Renal Failure INH & Acetyl Hydrazine are not bound

Drug interaction: 

Drug interaction Inhibits metabolism of 5HT, Inhibits parahydroxylation of 5HT Signs , Symptoms, Toxicity—27% plasma conc. to be monitered Inhibit metabolism of Warfarin , Diazepam, Disulfiram Absorption impaired by Al(OH) 3 PAS inhibits the metabolism of INH

Adverse Effect: 

Adverse Effect Rash Peripheral Neuropathy Hepatitis Transient loss of Memory Seizure Pleural effusion Toxicity Hepatotoxicity Acetyl Hydrazine cause the damage ↑in Serum Transaminase Clinical Hepatitis Can be fatal if not withdrawn promptly

Tuberculosis in the era of HIV / AIDS: 

Tuberculosis in the era of HIV / AIDS HIV / AIDS epidemic led to large increase of Smear negative pulmonary tuberculosis which in turn has led to poor treatment out comes, and early mortality

IMPACT OF HIV ON TB: 

IMPACT OF HIV ON TB Nearly 8 % of the global TB is attributable to HIV One third increase in TB in last five years is attributable to HIV Health services struggle to cope with the large and rising numbers of TB patients. TB accelerates the progression to AIDS TB shortens the survival of patients with HIV infection TB is the cause of death for one out of three people with AIDS worldwide

What is MDR TB / XDR TB?: 

What is MDR TB / XDR TB? MDR-TB ( Multidrug Resistant TB) describes strains of tuberculosis that are resistant to at least the two main first-line TB drugs - isoniazid and rifampicin . XDR-TB, or Extensive Drug Resistant TB (also referred to as Extreme Drug Resistance) is MDR-TB that is also resistant to three or more of the six classes of second-line drugs.

Mechanisms of Drug Resistance in Tuberculosis: 

Mechanisms of Drug Resistance in Tuberculosis

When to suspect MDR TB: 

When to suspect MDR TB Re-treatment patients who’s sputum smear remains positive after three months’ of intensive therapy Treatment failure and interruption cases Positive diagnoses with; TB culture and susceptibility testing

TREATMENT OF MDR/XDR TB: 

TREATMENT OF MDR/XDR TB 4 months of intensive phase (5 drugs) Kanamycins Ethionamide Pyrazinamide Ofloxacin Cycloserine or Ethambutol 18 months of continuation phase (3 drugs) Ethionamide Ofloxacin Cycloserine or Ethambutol

DOTS-Plus: 

DOTS - Plus A comprehensive strategy of the WHO Stop TB Partnership, developed for the diagnosis and management of MDR-TB and other forms of drug resistant TB.

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1. Sustained Political commitment 5. Recording and reporting system designed for DOTS-Plus programs. 4. Uninterrupted supply of quality assured second-line anti-tuberculosis drugs. 3. Appropriate treatment strategies that utilize second line drugs under proper management conditions . 2. Diagnosis of MDR-TB through quality-assured culture and drug susceptibility testing (DST ). THE DOTS-Plus Framework

Monitoring Schedule for MDR-TB Treatment Response : 

Monitoring Schedule for MDR-TB Treatment Response Daily symptom check during DOT for signs of disease activity Monthly clinical evaluation by MD: symptoms, weight, disease site-specific exam Monthly bacteriological evaluation until sustained conversion then bimonthly Chest x-rays: end of continuation phase, end of treatment

A WORLD FREE OF TB : 

A WORLD FREE OF TB WHO is working to dramatically reduce the burden of TB, and halve TB deaths and prevalence by 2015, through its Stop TB Strategy and supporting the Global Plan to Stop TB.

Market research: 

Market research Drug Market India Market USA Market Australia Other Isoniazid 29% 31% 19% 5% Amicacin 12% 28% 16% 9% Ethionamide 16% 21% 11% 6% Rifampin 23% 12% 10% 3%

Conclusion : 

Conclusion TB is the most prevalent disease in india Now a days TB is easily treatable As it affects the lungs the oxygen carring capacity is less

World Tuberculosis Day (March 24) : 

World Tuberculosis Day (March 24)

Any: 

Any