Tuberculosis is an infectious lung disease caused by bacteria that spreads through the air through coughing, sneezing, or spitting. In this presentation "Treatment of Tuberculsois (TB)" has been described including their causes, therapy, Principles, diagnosis, symptoms, management, etc. For more information, please contact us: 9779030507.

1. Treatment
of TB

2. Historical landmarks
 Magical and supernatural treatments
 Tubercle bacillus (Mycobacterium tuberculosis): Discovered on March 24, 1882 by
Robert Koch (Awarded Nobel Prize in 1905)
 Air, Diet, Fish-oils, Minerals etc
 Sanatoria treatment
 Chemotherapy: Streptomycin (1944),
P.A.S., Isoniazid (1952)
Ethambutal, Rifampicin (1960s-70s)
Other new drugs (1980s onwards)
Regimens and Strategies (SCC, Intermittent, DOTS)

3. Treatment: Issues
 Principles of therapy
 Goals
 Scientific Rationale – Bacterial Populations
 Drugs and Regimens: Efficacy, toxicity, costs
 Strategies: Efficacy, compliance
 Surgical Options
 Relapses and sequelae
 Specific situations: Comorbidities
 Multi and Extreme Drug Resistance (MDR/XDR)
 TB & HIV infection

4. Objectives of TB treatment
 To decrease mortality and long term morbidity by
 Ensuring care
 Minimizing relapses
 Preventing development of drug resistance
 To decrease and break the chain of transmission of infection
 To achieve the above whilst minimizing side effects due to drugs

5. Treatment Principles
 Most effective therapy to achieve early negative status
 Adequate period of time to ensure complete sterilization
 Most effective utilization of available resources
 Ensuring compliance
 Looking after social aspects

6. Why is the TB Therapy Long?
1. Nature of the disease pathology
• High Load
• Poor drug penetration
2. Phenotypic resistance in persisters
 Non-growing mycobacteria
a. Stationary phase bacteria
b. Residual survivors or persisters not killed during antibiotic exposure
c. Dormant bacilli
3. Poor host immune system for residual bacteria (not killed by drugs)

7. Bacterial Populations and Chemotherapy
A. Active growing
T.b. INH
Metabolic B. Bacilli with spurts
Activity of metabolism RIF
C. Bacilli in acid pH PZA
D. Persisters

8. Classification of Anti-TB drugs
Bacteristatic Ist line vs
Vs bactericidal Second line
Anti TB Drugs
TB specific drugs vs
Broad spectrum antibiotics

9. Anti TB drugs (Stop TB Deptt., WHO)
Group Drugs
I Oral H,R,Z,E
New generation rifamycin-rifabutin and
rifapentine
(For HIV-TB)
II Injectables Kana, Amika, Capreo, Strepto
III Fluoroquinolones Moxi, Gati, Levo, Ofloxacin
IV Oral bacteriostatic, 2nd line drugs – thioamides, cycloserine, RAS,
Terizidone
V Unclear efficacy Clofazimine, Linezolid, High dose H; antibiotics

10. Drug side-effects/ Toxicities (Ist line drugs)
 INH: Neuropathy, skin reactions, hepatitis, fever
 RIF: Hepatitis, Flu like syndrome, Nephritis
 ETM: Retrobulbar/ Optic neuritis, Skin rashes
 PZN: Hyperuricaemia, hepatotoxicity, skin rashes
 STM: Ototoxicity, vestibular toxicity, skin rashes
 PAS: GI upset, hypersensitivity, fever, rashes
Allergic reactions, skin rashes and GI intolerance can occur with almost any drug

11. Hepatotoxic anti-tuberculous agents
Hepatotoxic Non-hepatotoxic*
Isoniazid Ethambutol
Rifampicin Streptomycin
Pyrazinamide Kanamycin
Ethionamide Amikacin
Para-aminosalicylic acid Cycloserine
Capreomycin
Fluoroquinolones
*Rare hepatotoxic reactions may occur

12. Treatment strategies
(Short Course Chemotherapy
1. Use of multiple drugs
2. Most effective drugs
3. Intensive followed by maintenance
phase
4. Ensuring compliance and
completion
4 (Intensive phase)
2-3 (Maintenance)
R, H, Z
2 + 4 months
DOTS

13. Drugs and Regimens
1. Daily
 Intensive Phase:
RHZE (2 mths)
 Maintenance:
RH (4 mths)
RHE (HIV +ve Pts)
2. Intermittent (Always supervised)
RNTCP Regimen: Category I
2 R3 H3 Z3 E3 (24 doses)
4 R3 H3 (54 doses)

14. Tmt for EPTB
Duration (Mth)
Lymph node 6
Bone & joint 6-9
Pleural disease 6
Pericarditis 6
CNS 9-12
Disseminated 6
Genitourinary 6
Peritoneal 6

15. Paradoxical Reactions
Worsening during ATT (e.g. LN, Pl. effusion)
 ? Ongoing inflammation/fibrosis
 ? Immune reconstitution (esp. HIV)
 ? Release of toxins
Treatment
 Anti-inflammatory drugs
 ? Corticosteroids
 No need for ATT prolongation / 2nd line

16. Revised National TB Control
Programme (RNTCP)

17. WHY “REVISED” ?
 National Tuberculosis Programme
 Started in 1962
 Domiciliary treatment at District TB centers
 Over dependence on chest X-ray for diagnosis
 Self administered drug regimens
 Poor funding
 Poor treatment completion rates
 RNTCP
 Started in 1997
 Presently covers the entire country

18. Directly Observed Treatment, Short course
(DOTS)
 Principle strategy of RNTCP
 Components
 Sustained political commitment
 Access to quality-assured TB sputum microscopy
 Standardized short-course chemotherapy
 Uninterrupted supply of quality assured drugs
 Recording and reporting system enabling outcome assessment

19. Diagnosis of pulmonary tuberculosis
 Patients with TB feel ill and seek care promptly
 Active case finding is unnecessary and unproductive
 Microscopy is appropriate technology, indicating infectiousness, risk of
death, and priority for treatment
 X-ray is non-specific for TB diagnosis
 Serological and amplification technologies (PCR, etc.) currently of no
proven value in TB control

20. Diagnosis of Pulmonary Tuberculosis
Two specimens optimal
 Spot specimen on first visit; sputum container given to
patient
 Early morning collection by patient on next day
 Spot specimen during second visit

21. Patient categorization
1. New patients (Cat. I and III merged)
2. Previously treated / Retreatment cases/ Defaulters (Cat.
II)
3. Other specific categories
Multi-drug resistant TB (Cat IV)
TB and HIV

22. What is DOTS ?
A strategy (Directly Observed Therapy, Short Course) to ensure treatment
completion in which
 Treatment observer (DOT provider) must be accessible and acceptable to the
patient and accountable to the health system
 DOT provider administers the drugs in intensive phase.
 Ensures that the patient takes medicines correctly in continuation phase.
 Provides the necessary information and encouragement for completion of
treatment.
Direct observation ensures treatment for the entire course with the right drugs in
the right doses at the right intervals

23. Why DOTS?
1. To ensure compliance
2. To render early non-infectiousness
3. To standardize treatment regimen and avoid drug resistance
4. Provide free and affordable treatment
5. Control TB – nationally and globally

24. Treatment schedules (RNTCP)
New cases 2 H3R3Z3E3 /
4 H3R3
Previously treated 2 H3R3Z3E3S3/
1 H3R3Z3E3 /
5 H3R3E3
Treatment under Direct Supervision (DOTS)

25. RNTCP: What should be the duration?
New patients should receive a 6 month regimen
2HRZE/ 4HR (Thrice weekly)
Intensive Phase 2 months
Maintenance Phase 4 months

26. Can steroids help early resolution?
No. Steroids have proven benefit in only
TB Meninigitis
TB Pericarditis
Other uses of steroids in TB.
 (Tuberculous) Addison’s disease
 Acute hypersensitivity reaction to ATT
 Severe, unresolving IRS (Immune Reconstitution Syndrome)

27. Do anti TB drugs have interactions with other
drugs?
Yes. Rifampicin induces pathways that metabolize other drugs.
It reduces the concentrations and effects of following drugs:
1. Anti infective (macrolides, doxicycline, azole antifungals, mefloquine,
antiretroviral)
2. Hormones (tamoxifen, levothyroxine, ethinylestradiol, norethindrone)
3. Cardiovascular agents – digoxin, nifedipine, diltiazem, propranolol, hypo
lipidaemics, etc.
4. Others: Methadone, warfarin, cyclosporin, corticosteroids, anti
convulsants, theophylline, sulphoxylurla

28. Can ATT be used safely during pregnancy?
Yes, except streptomycin (Ototoxic to the fetus)
 Breast feeding should continue on ATT
 Treatment / Chemoprophylaxis for the babies of mothers with active TB

29. ATT in patients with liver disease?
1. No chronic liver disease; Hepatitis virus carriers; Past H/o hepatitis; Excessive alcohol use
 Usual TB regimens
 More common hepatotoxic reactions
2. Unstable / Advanced liver disease
 LFT before starting tmt. (ALT > 3 times)
i. Two hepatotoxic drugs
 9 RHE
 2 RHES 6 HR
 6-9 RZE
ii. One hepatotoxic drug – 2HES 10 HE
iii. No hepatotoxic drug – 18-24 SE Flouro

30. Latent MTB Infection
A. Diagnosis
• Positive tuberculin test
• Exclude active disease
B. Regimens
1. INH for 12 mths : For both
HIV – and + cases
2. R + Z for 2 mths : For HIV +ve
3. H + R for 3 mths: HIV –ve
4. R for 4 mths : HIV –ve

31. TB and HIV
Co-infection

32. Mechanisms of Coinfection
 Impairment of immune response
 Progressive depletion & dysfunction of CD4 lymphocytes
 Impaired macrophage function
 Invasion of inflamed bronchial walls – the breeding sites

33. Augmented Effects
HIV on TB
 Rapid progression
 Active disease (40%)
 Higher morbidity
 Mortality: 4 times higher (than HIV –ve), 20-35%
 Increased ADRs to ATT
 Increased drug resistance (MDR and XDR)
TB on HIV
 Increased viral replication, load, immune suppression, infections,
morbidity and mortality

34. How does TB occur?
1. Endogenous reactivation
• HIV is most potent risk factor
2. Exogenous (Re) infection
• Increased chances of TB exposure in hospitals

35. Clinical Features
Early stage (CD4 > 200/mm3)
• Typical reactivation TB
• (Upper lobes infiltrates/cavities)
Advanced stage (CD4 < 200/mm3)
• Atypical disease
• Disseminated/extrapulmonary TB

36. Clinical Presentation, Symptoms
 Fever, cough, chest pain, weight loss
 Chronic diarrhoea
 Generalized lymphadenopathy
 Organ specific symptoms and signs

37. Atypical Manifestations (Pulmonary)
 Lower lobe/diffuse involvement
 Absence of cavity formation
 Endobronchial involvement
 Prominent hilar/mediastinal
 Pleural effusion – common
 Miliary TB
 Chest wall abscess/cutaneous sinuses

38. Extra Pulmonary TB
 LYMPH NODE
- Commonest EP site
- Peripheral
- Intrathoracic
-Intra-abdominal
(accompanying visceral involvement)
 DISSEMINATED
- Miliary or more than
- one XP site
- Mycobacteremia
 SKIN
- May co-exist with pulmonary TB
- Erythematous papules, purpura,
subcutaneous nodules, pustules
- Biopsy- little granuloma, AFB+
 HEPATOSPLENIC
Round, hypoechoic, multiple lesions <1 cm
 TB MENINGITIS
CSF findings may be normal
 LARYNGEAL

39. Tuberculin skin testing
 Tuberculin reactivity four fold less in HIV infection
 Reactivity declines with increasing immune suppression
early HIV 40-70 %
advanced HIV 10-30%
 Annual tuberculin testing for HIV infection to detect latent infection
 Tuberculin anergy assoc. with risk of active TB is controversial

40. Treatment of HIV-TB dual infection
 Both ATT and ART (Anti retroviral treatment)
 HAART (Highly Active Anti-Retroviral Therapy)
At least 3 drugs from amongst:
- Protease inhibitors
- Reverse transcriptase inhibitors
- Viral integrase enzyme inhibitors
- Viral entry inhibitors
Combined ATT and ATT is more toxic; drug-drug interaction (Rif causes decrease in conc. of
ARV),
Rifabutin is an alternate choice.

41. Tuberculosis and ARV Therapy
Status When to Start ARV Therapy
CD4 less than 200/mm3 Start TB Therapy
Start ARV as soon as TB therapy
can be tolerated
CD4 between 200 and 350/mm3 Start TB therapy
Start ARV therapy after 2 mo. Of TB
therapy with EFV
CD4 greater than 350/mm3 Treat TB, start ARV therapy
according to general indications

42. Why MDR/ XDR TB in HIV?
 Poor immune response leads to increased rapidly dividing bacilli and
spontaneous mutations
 Noncompliance due to frequent ADR
 Large pill burden
 Malabsorption of ATT

43. Adverse drug reactions
 More frequently in HIV infected, 20-25%
 Related to level of immune activation and immune suppression
 Thiacetazone induced exfoliative dermatitis, TEN, Steven Johnson
syndrome can be fatal (contraindicated with HIV)
 ATT induced hepatitis four fold higher than in seronegative patient
 Risk factors- anergy , lymphopenia, Elevated Neopterin levels

44. Do anti TB drugs have interactions with
other drugs?
Yes. Rifampicin induces pathways that metabolize other drugs.
It reduces the concentrations and effects of following drugs:
1. Anti infective (macrolides, doxicycline, azole antifungals, mefloquine,
antiretroviral)
2. Hormones (tamoxifen, levothyroxine, ethinylestradiol, norethindrone)
3. Cardiovascular agents – digoxin, nifedipine, diltiazem, propranolol, hypo
lipidaemics, etc.
4. Others: Methadone, warfarin, cyclosporin, corticosteroids, anti
convulsants, theophylline, sulphoxylurla

45. Paradoxical reaction
 Defined as temporary worsening of clinical condition, appearance of
new radiologic manifestations after initiation of Tt ,and are not due to
Tt failure or a second process
 Due to recovery of immunological Th 1 response to mycobacterial
antigen
 Heightened granulomatous response may clear the organism but itself
may cause tissue damage

46. THANK YOU