Tuberculosis (TB) is caused by the bacterium Mycobacterium tuberculosis. It typically affects the lungs and can cause symptoms like cough, fever, weight loss, and night sweats. Risk factors include HIV/AIDS, drug use, and other conditions that weaken the immune system. Diagnosis involves tests of sputum, chest x-rays, and tuberculin skin tests. Treatment requires multiple antibiotic drugs taken for 6-9 months. Drug-resistant TB requires specialized treatment with second-line drugs.

1. TUBERCULOSIS
Submitted To :
Dr. KANCHAN VOHRA
Assistant Professor
Submitted By :
Mohd. Rafi Bhat
Department of pharmaceutical science & Drug
Research

2. Introduction
Tuberculosis (TB) is a disease caused by bacteria called Mycobacterium
tuberculosis. The bacteria usually attack the lungs, but they can also
damage other parts of the body.

3. • Airborne

4. Aetiology
TB is caused by tubercle bacilli,
which belong to the genus
Mycobacterium.
These form a large group but
only three relatives
(Mycobacterium tuberculosis
complex) are obligate parasites that
can cause TB disease.
M. tuberculosis complex: M.
tuberculosis, M. bovis, M.
africanum
Discovered in 1882 by Robert Koch.

5. Examples of factors that increase risk of
developing TB
HIV positive
Injecting drug users
Solid organ transplantation, jejunoileal bypass or gastrectomy
Haematological malignancy, for example leukaemia and lymphomas
Chronic renal failure or receiving haemodialysis

6. Symptoms
The symptoms and signs of TB include:
Cough for 3 weeks or more/productive cough
Sputum usually mucopurulent or purulent
Haemoptysis not always a feature
Fever may be associated with night sweats
Tiredness
Weight loss variable
Anorexia variable
Severe Symptoms
 Persistent cough
 Chest pain
 Coughing with bloody sputum
 Shortness of breath
 Urine discoloration
 Cloudy & reddish urine
 Fever with chills.
 Fatigue

7. Pathogenesis

10. Clinical diagnosis
The clinical diagnosis of TB disease is based on the symptoms and signs in
the patient together with chest radiography, microscopy of sputum
followed by culture and tuberculin skin testing.
Blood-based immunological tests, introduced in the last few years, will
play an increasingly important role in TB diagnosis.
These tests can distinguish between TB infection and previous BCG
vaccination.

11. Microbiological
Microbiological investigations are undertaken to assess the infectious state (mycobacteria
causing TB and other mycobacteria).
Determine the drug-susceptibility patterns of the infecting organisms, to ensure that the
drugs .
Investigations comprise microscopy, culture, drug-susceptibility testing and strain
typing.
Direct microscopy of sputum is the simplest and quickest method of detecting the
infectious patient, by looking for acid-fast bacilli.
A minimum of three sputum samples, one of which should be early morning, should be
collected from patients with suspected respiratoryTB.

12. Cultures
Direct microscopy is not as useful in non-pulmonary disease, any specimens taken should
be sent for culture.
Lowenstein–Jensen medium, growth may take up to 6 weeks.
Polymerase chain reaction (PCR)-based tests can also detect M. tuberculosis complex in
clinical specimens.
A rapid test is available for assessing rifampicin resistance in individuals thought tohave
drug-resistant TB.
A positive result indicates the need to assess susceptibility to other first line anti-TBdrugs.
DNA fingerprinting, or strain typing, is useful in the public health management ofTB.
New method, mycobacterial (MIRU/VNTR) 24-loci strain typing, became available in
UK

13. Tuberculin testing

14. Tuberculin test interpretation

15. Chest radiography
The chest radiograph is a non-specific diagnostic tool, as TB may present as
virtually any abnormality on chest radiography.
This is why microbiological evidence of confirmation should be sought.
Pulmonary TB may appear as bronchopneumonia with confluent shadowing,
without cavitation.
Cavitation may be seen, the incidence can vary between 10% and 30%.
Uncharacteristic radiological patterns may occur in the presence of HIV infection.

16. Diagnosis in people with HIV
TB can occur early in the course of HIV infection and may therefore be diagnosed before
the patient is known to be HIV positive.
The possibility of HIV infection in people with TB should therefore be considered, and
testing for the virus is appropriate in those with risk factors for HIV.
Early in the course of HIV infection, before serious immunodeficiency occurs, TB is more
likely to present with typical clinical features, and a positive tuberculin skin test, with
cavitation and/or pleural disease on chest radiography.
In the late stages of HIV infection show chest findings and extra pulmonary disease.

17. Treatment
In treating TB, a number of factors are important:
• Choice of drugs
• Length of treatment
• Co-morbidity especially HIV infection, liver and renal diseases
• Adherence to treatment by the patient.
It is important to tailor the management of the patient according to his
or her situation, rather than just focus on the drug treatment of TB, as
other factors in the patient's life may affect adherence.
Bacille Calmette Guerin (BCG).
First used in 1921.
Only vaccine available today for protection against
tuberculosis.
It is most effective in protecting children from the disease.

18. Management

19. Drug treatment
 Treatment with anti-TB drugs has two main purposes:
• to cure people with TB, provided the bacilli are drug sensitive
• to control TB, by either preventing the development of infectious forms
 With the advent of effective anti-TB chemotherapy, patients no longer needed treatment in a sanatorium.
 Results with regimens containing isoniazid together with p-aminosalicylate (PAS) or ethambutol, and sometimes
streptomycin, gave excellent results.
 Treatment was required for 18–24 months if relapse was to be prevented.
 The availability of pyrazinamide and, more importantly, rifampicin made shorter courses of treatment a possibility.
 Most regimens in the developed world now contain isoniazid and rifampicin, which are the two most important drugs
together with pyrazinamide and possibly with another agent, such as ethambutol.

20. Treatment
The recommended standard treatment regimen for respiratory and most other forms
of TB
•rifampicin, isoniazid, pyrazinamide and ethambutol for the initial 2 months
(initial phase)
• a further 4 months of rifampicin and isoniazid (continuation phase).
A longer period of treatment than the standard 6 months is needed for meningealTB
and where there is direct spinal cord involvement.
Patients should be started on the standard treatment Regimen on clinical diagnosis.

21. The purpose of the concurrent use of four drugs in the initial phase is to reduce
the bacterial population as rapidly as possible and prevent the emergence of
drug-resistant bacteria.
It is important, however, to ensure the combination product contains the required
dose of the constituent drugs.
Patients with suspected drug reactions or drug-resistant TB should always be
referred back to the specialist physician and the healthcare team supervisingtheir
treatment.

22. DOTS
DOTS - Directly observed treatment, short-course
DOT means that a trained health care worker or other designated individual
provides the prescribed TB drugs and watches the patient swallow every dose.

24. Drugs MOA Diagram
Isoniazid Inhibits mycolic acid synthesis.
RIFAMPICIN Blocks RNAsynthesis by blocking DNA
dependent RNApolymerase
PYRAZINAMIDE •Bactericidal-slowly metabolizing organism
within acidic environment of Phagocyte or
caseous granuloma.

25. Drugs MOA Diagram
ETHAMBUTOL •Bacteriostatic
•Inhibition of Arabinosyl
Transferase
STREPTOMYCIN •Inhibition of Protein synthesis
by disruption of ribosomal
function

26. ADRs and its Management

27. Drug-resistant TB
MDR-TB is caused by bacteria that are resistant to at least isoniazid and rifampicin,the
most effective anti-TB drugs.
MDR-TB results from either primary infection with resistant bacteria.
XDR-TB is a form of TB caused by bacteria that are resistant to isoniazid and
rifampicin, fluoroquinolone and any of the second-line anti-TB injectable drugs
including amikacin, kanamycin or capreomycin

28. Drugs used in MDR-TB
 Bedaquiline ----- trade name – sirturo
 Works by blocking an enzyme inside the M. tuberculosis bacteria called ATP
synthase.This enzyme is used by the bacteria to generate energy. Without the
ability to generate energy , the TB bacteria die and the patient’s condition can
start to improve.
 Used in combination with other TB drugs. If resistant to main TB drugs –
isoniazid and rifampicin.
 DOSE- 400mg a day for four weeks and then 200 mg taken three times a
week.

29. delamanid
 Trade name– Deltyba
 Class- Nitroimidazoles.
 Dose- 50 mg tab. Two tabs. Twice a day with food.for six
months.
 Inhibiting the synthesis of mycobacterial cell wall components
, methoxy mycolic acid and ketomycolic acid.

30. Pretomanid
Another nitroimidazole-oxazole currently being developed
by the TB Alliance.
It also can potentially be used for the treatment of both
drug sensitive and drug resistant TB, and it has also shown
activity against both latent and active TB.