Tuberculosis (TB) is a contagious infectious disease caused by the bacterium Mycobacterium tuberculosis. It primarily affects the lungs but can also affect other parts of the body, such as the brain, kidneys, or spine. Here's a four-step explanation of tuberculosis: Cause and Transmission: Tuberculosis is caused by the bacterium Mycobacterium tuberculosis. When an infected person with active TB coughs, sneezes, or talks, they release droplets containing the bacteria into the air. Another person can become infected by inhaling these droplets. TB is primarily transmitted through the air, making close and prolonged contact with an infected individual the main risk factor for transmission. Symptoms: TB can manifest differently depending on whether it's active or latent. Latent TB infection occurs when the bacteria are present in the body but are not causing symptoms or spreading to others. Active TB disease occurs when the bacteria are actively multiplying and causing symptoms. Common symptoms of active TB include a persistent cough, chest pain, coughing up blood, fatigue, weight loss, fever, and night sweats. Diagnosis: Diagnosis of TB involves several steps. Firstly, a medical history and physical examination are conducted to assess symptoms and risk factors. Following this, diagnostic tests such as the tuberculin skin test (TST) or interferon-gamma release assays (IGRAs) are used to determine if a person has been infected with TB bacteria. If these tests are positive, further tests such as chest X-rays, sputum tests, or cultures may be performed to confirm active TB disease and determine the most effective treatment. Treatment and Prevention: Treatment for TB usually involves a combination of antibiotics taken for several months. Commonly used antibiotics include isoniazid, rifampin, ethambutol, and pyrazinamide. It's essential to complete the full course of treatment to prevent the development of drug-resistant strains of TB. Additionally, preventive measures such as vaccination with the Bacillus Calmette-Guérin (BCG) vaccine, good ventilation in living and working spaces, and early identification and treatment of active cases can help control the spread of TB.

1. Tuberculosis
BY
SRIRAM THIRUNAVUKKARASU,
PHARM.D,

2. Introduction:
 Tuberculosis is a chronic granulomatous disease caused by
‘Mycobacterium Tuberculosis’
 It usually involves the lungs but may also affect any organ or tissue in the
body
 Primary tuberculosis is a form of disease that develops in a previously
unexposed & unsensitized persons
Secondary Tuberculosis:
 It arises in a previously sensitised host
 Reactivation may be due to exogenous re-infection or endogenous
 5% of the persons with primary tuberculosis get secondary tuberculosis
 Secondary tuberculosis is classically localized to the apex of one or both
upper lobes
 Most cases are the result of reactivation of prior infection, and persons at
highest risk include those with HIV infection, silicosis, diabetes mellitus,
chronic renal insufficiency, malignancy, malnutrition, and other forms of
immunosuppression, especially therapy with tumor necrosis factor (TNF)
antagonists like infliximab and etanercept.

3. Pathophysiology of tuberculosis:
 Earliest Phase: (< 3 weeks)
Virulent strains of mycobacteria
[Macrophage Mannose
Receptor recognise
mannose capped
glycolipid of tubercular enter
cell wall]
Alveolar macrophage endososmes
NRMP 1 (Natural
Resistance associated
Macrophage Protein)
cause
Endososmal manipulation
 maturation arrest
 lack of acid pH
 ineffective phagolysome formation
cause
Microbial proliferation (bacterimia)
 Despite the bacterimia, most patient at this stage are
asymptomatic or have a mild flu like illness

4. Later Phase: (> 3 weeks)
1. Microbial antigen Monocytes
undergo activation
reach & differentiation
MHC – class II Granulomatous response
(Major Histocompatibility [defence mechanism]
Complex) 2. IF – γ + TNF
to activate
CD4
+
, TH 0 cells Inducible Nitric Oxide
(with α β – T cell receptor) Synthase (iNOS) gene
mature under
influence of results
IL – 12 secreted ↑ NO2 levels
by macrophages
CD4
+
, TH 1 sub cells cause
↑ nitrogen intermediate
secrete &free radicals
Interferon γ (IF – γ)
oxidative
cause destruction
Activation of macrophages several micobacterial
constituents
secrete (cell wall, DNA, etc.)
Tumour Necrotic Factor [defence mechanism]
(TNF)
recruit

5. Risk factors for tuberculosis
The risk may be approximately three times greater (as with diabetes) to more than 100 times greater (as with HIV
infection) for people who have these conditions
 1. HIV infection
 2. Substance abuse (especially drug injection)
 3. Recent infection with M. tuberculosis (within the past 2 years)
 4. Chest radiograph findings suggestive of previous tuberculosis
 5. Diabetes mellitus
 6. Silicosis
 7. Prolonged corticosteroid therapy
 8. Other immunosuppressive therapy
 9. Cancer of the head and neck
 10. Hematologic and reticuloendothelial diseases (e.g., leukemia and Hodgkin's disease)
 11. End-stage renal disease
 12. Intestinal bypass or gastrectomy
 13. Chronic malabsorption syndromes
 14. Low body weight (10% or more below the ideal)
 15. Foreign-born, low socioeconomic class

6. Diagnosis:
1. Clinical manifestations: many patients are asymptomatic at the time of diagnosis;
others may report dry, nonproductive cough, night sweats, fever, anorexia, fatigue,
dyspnea, pleurisy chest pain, and hemoptysis.
2. Physical examination may reveal rales near the lung apices.
3. Tuberculin skin testing (TST) is commonly used in diagnosing latent tuberculosis
infection (LTBI) and includes measurement of the delayed type hypersensitivity
response 48 to 72 hours after intradermal injection of tuberculin purified protein
derivative (PPD). (Five tuberculin units of PPD in 0.1 mL of solution is injected
intracutaneously. )
 a. Sensitized individuals demonstrate a dermal reaction of redness, swelling, and
induration; only induration is considered in determining a positive reaction.
 b. If TST is used for baseline testing in health care workers, two-step testing is
recommended. For those whose initial TST tests are negative. The second-step TST
should be administered 1 to 3 weeks after the first TST was read. If the second-step
TST is positive, active tuberculous disease should be excluded, and if it is excluded,
the health care worker should be evaluated for treatment of LTBI.

7. 4. The QuantiFERON-TB Gold is a new test that may eventually replace
the PPD test. It measures the release of two unique proteins associated with
M. tuberculosis infection (early secretory antigenic target 6 [ESAT-6] and
culture filtrate protein 10 [cfp-10]) in whole blood.
5. Acid-fast stain for 3 days and cultures of sputum. Any positive
specimens should be held for sensitivity testing because of the increasing
incidence of drug-resistant tuberculosis.
6. Chest x-ray
 a. Initial film may show a variety of patterns; rarely, it may be
completely normal if the patient has endobronchial tuberculosis.
 b. Parenchymal infiltrates most commonly involve the upper lobes
(apical and posterior segments).
 c. Hilar and paratracheal adenopathy, unilateral pleural effusion, and
cavitary lesions may also be present.

8. Treatment
Objectives:
1- Detecting at least 70% of sputum positive tuberculosis patients in the
community.
2- Curing at least 85% of the newly detected sputum positive cases.
Components of DOTS (Directly observed treatment strategy)
1- Political and administrative commitment at all levels.
2- Diagnosis through sputum microscopy
3- Uninterrupted supply of short course chemotherapy drugs.
4- Direct observation of drug intake ( DOTS)
5- Systematic monitoring, evaluation and supervision at all levels.
Treatment schedule
Category-1:
*Newly diagnosed sputum positive pulmonary tuberculosis
*Sputum negative pulmonary tuberculosis with extensive
parenchymal involvement.
*Severe form of extrapulmonary tuberculosis
Category-2
*Treatment failure cases
* Relapse cases
* Return after interruption

9. Category-3
* sputum negative pulmonary tuberculosis with minimal involvement
* Less severe form of extrapulmonary tuberculosis
Category-4
 RNTCP will be using a Standardised Treatment Regimen (Cat IV) for the
treatment of MDR-TB cases (and those with rifampicin resistance) under the
programme.
 Cat IV regimen comprises of 6 drugs- kanamycin, ofloxacin (levofloxacin)†,
ethionamide, pyrazinamide, ethambutol and cycloserine during 6-9 months of
the Intensive Phase and 4 drugs- ofloxacin (levofloxacin), ethionamide,
ethambutol and cycloserine during the 18 months of the Continuation Phase.
 p-aminosalicylic acid (PAS) is included in the regimen as a substitute drug if
any bactericidal drug (K, Ofl, Z and Eto) or 2 bacteriostatic (E and Cs) drugs
are not tolerated.
RNTCP CATEGORY IV REGIMEN: 6 (9) Km Ofx (Lvx) Eto Cs Z E / 18
Ofx (Lvx)Eto CsE

10. S.No
CAT-IV
Drugs
16-25 kgs 26-45 kgs >45 kgs
1
2
3
4
5
6
7
8
Kanamycin
Ofloxacin
(Levofloxaci)
Ethionamide
Ethambutol
Pyrazinamide
Cycloserine
PAS (80%
Bioavailability) ‡
Pyridoxine
500 mg
400 mg
(200 mg)
375 mg
400 mg
500 mg
250 mg
5 gm
50 mg
500 mg
600 mg
(500 mg)
500 mg
800 mg
1250 mg
500 mg
10 gm
100mg
750 mg
800 mg
(750 mg)
750 mg
1000 mg
1500 mg
750 mg
12 gm
100mg

11. H= INH Isoniazid 600mg, R= Rifampicin 450mg, Z= Pyrazinamide
1500mg, E= Ethambutol 1200mg, S= Streptomycin 750 mg
The drugs are available in patient wise boxes containing the full course of
treatment for the individual patient. Each box contains two pouches – one for
intensive phase and the other for continuation phase.
 Drugs are packed in a blister pack; one blister pack for intensive phase
contains drugs for a single day whereas for continuation phase, each
blister pack contains drugs for one week.
All the drugs are to be taken on alternate days. During the intensive phase
all the doses are to be swallowed under direct observation (DOTS)
whereas in continuation phase the patient takes the first weekly dose under
direct observation and the remaining drugs for the week are to be
consumed at home.
 Follow Up Sputum Examination is done at the end of the intensive phase
to decide on the further course of treatment. If the sputum remains positive
for AFB, the intensive phase drugs are continued for another one month
before starting the continuation phase.Duration

12. Initial Phase
 Initial Phase The initial phase of treatment is crucial for preventing the
emergence of drug resistance and determining the ultimate outcome of
the regimen.
 Four drugs—INH, RIF, PZA, and EMB—should be included in the initial
treatment regimen until the results of drug-susceptibility tests are available.
 Each of the drugs in the initial regimen plays an important role. INH and RIF
allow for short-course regimens with high cure rates.
 PZA has potent sterilizing activity, which allows further shortening of the
regimen from 9 to 6 months.
 EMB helps to prevent the emergence of RIF resistance when primary INH
resistance is present.
 If drug-susceptibility test results are known and the organisms are fully
susceptible, EMB need not be included.
 For children whose clarity or sharpness of vision cannot be monitored, EMB is
usually not recommended except when the risk of drug resistance is high or
for children who have “adult-type” (upper lobe infiltration, cavity formation)
TB disease.

13. Continuation Phase
 The continuation phase of treatment is given for either 4 or 7
months.
 The 4-month continuation phase should be used in patients with
uncomplicated, noncavitary, drug-susceptible TB, if there is
documented sputum conversion within the first 2 months.
 The 7-month continuation phase is recommended only for
Patients with cavitary or extensive pulmonary TB disease
caused by drug-susceptible organisms and whose sputum culture
obtained at the time of completion of 2 months of treatment is
positive.
 Patients whose initial phase of treatment did not include PZA; or
Patients being treated with once-weekly INH and RPT and
whose sputum culture at the time of completion of the initial
phase (i.e., after 2 months) is positive.

14. Types of cases
New case: A patient who has never had treatment for TB or has taken anti-tuberculosis drugs for less than one
month.
Relapse case: A patient declared cured of TB by a physician but who reports back to the health service and is
found to be bacteriologically positive.
Transferred in case: A patient who has been received into a Tuberculosis Unit/District after starting treatment in
another unit where he has been recorded.
Treatment after default case: A patient who has received anti-tuberculosis treatment for one month or more
from any source and who has interrupted treatment for more than two months.
Failure case: An initial smear positive patient who remains smear positive at five months or more after starting
treatment OR an initial smear negative patient who becomes smear positive during the course of treatment.
Chronic case: A patient who remains smear positive after completing a re-treatment regimen
Other: A patient who does not fit into any of the above categories. e.g., a relapse patient may be smear negative
or an extra-pulmonary TB patient who has not responded to treatment. Such patients are categorized as others and
receive category two treatment.

15. Severity of illness
Seriously ill Smear negative pulmonary TB cases should be clinically
ascertained for the severity of illness.
Seriously ill extra-pulmonary TB includes:
Meningitis, disseminated TB, tuberculosis pericarditis, peritonitis, bilateral or
extensive pleurisy, spinal disease with neurological complications, intestinal
and genitourinary TB.
Depending on the classification of TB, type of TB, severity of illness, history
of treatment in the past, history of interruption in treatment, the patient will
receive category one, category two or category three treatment.
The drugs are to be taken on alternate days under direct observation (DOTS-
Directly Observed Treatment, Short-course)

16. Treatment
Category of
treatment
Type of patient Regimen
Category I
New sputum smear positive
2(HRZE)3 4(HR)3
Seriously ill smear negative
Seriously ill extra pulmonary
Category II
Sputum smear
positive positive relapse
2(HRZES)3/1(HRZE)3/5(HRE)
3
Sputum smear positive failure
Sputum smear positive treatment
after default
Category III
Sputum smear negative not
seriously ill
2(HRZ)3/4(HR)3

17. Categorywise sputum examination results and actions to be taken
Category of
treatment
Pretreatm
ent
sputum
Test at
month
IF result
is:
THEN
Category I
+ 2
-
Start continuation phase,test sputum again at 4
and 6 months
+ Continue intensive phase for one more month
- 2
-
Start continuation phase,test sputum again at 6
months
+
Continue intensive phase for one more month,test
sputum again at 3,4, and 7 months
Category II + 3
-
Start continuation phase,test sputum again at 5
and 6 months
+
Continue intensive phase for one more month,test
sputum again at 4,6 and 9 months
Category III - 2
-
Start continuation phase,test sputum again 1t 6
months
+
Reregister the patient and begin Category II
treatment

18. Phases and duration of treatment
Category
Duration(Number of doses)
Total
Intensive
phase
Continuation
phase
CAT I
8 weeks(24
doses)
18 weeks(54
doses)
26 weeks(78 doses)
CAT II
12 weeks(36
doses)
22 weeks(66
doses)
34 weeks(102 doses)
CAT III
8 weeks(24
doses)
18 weeks(54
doses)
26 weeks(78 doses)

19. Special situations:
Tuberculosis Meningitis:
● Patients should be referred to the hospital and treated under category
I treatment, with continu- ation phase lasting 6 - 7 months.
● Steroids should be given initially to reduce me- ningeal
inflammation and tapered over a period of 6 - 8 weeks.
During pregnancy:
● All anti tuberculosis drugs used in RNTCP except streptomycin are
safe during pregnancy.
● Breast feeding should be continued regardless of mother’s
Tuberculosis infective status.

21.  If the duration of pregnancy is <20 weeks, the patient should be advised to
opt for a Medical Termination of Pregnancy (MTP) .
 If the patient is willing, she should be referred to Gynaecologist/Obstetrician for
MTP following which Cat IV treatment can be initiated.
 For patients who are unwilling for MTP or have pregnancy of >20 weeks, modified
Cat IV should be started as detailed below:
 For patients in the first trimester (≤ 12 weeks), kanamycin and ethionamide are
omitted from the Cat IV regimen and PAS is added.
 For patients who have completed the first trimester (>12 weeks), kanamycin is
replaced with PAS. Post partum, PAS may be replaced with kanamycin and
continued until the end of the Intensive Phase.
 Pregnant MDR-TB patients need to be monitored carefully both in relation to the Cat
IV treatment and the progress of the pregnancy. This approach should lead to good
results, since the patient should be smear- negative at the time of parturition, and
mother and infant do not need to be separated. Breast-feeding should be
encouraged as long as the patient is sputum negative.

22. Child contacts - < 6 years of age with sputum smear positive case:
 If the child has symptoms of tuberculosis and if it is confirmed by the
treating physician – a full course of ATT (CAT III) should be given.
 If the child does not have symptoms:
 Tuberculin test: Not available – chemothera- phy for 6 months Isoniazid 5
mg/kg.
 Tuberculin test: Available – child should be given INH chemotherapy for 3
months and Tuberculin test should be done, then treat as per the notes given
below.
(If induration to tuberculin test < 6mm, stop preventive chemotherapy and
vaccinate with B.C.G (if not vaccinated previously).
If induration is >6mm, continue INH preventive chemotherapy for another
3 months.)
Vaccination:
 BCG vaccination does not protect an individual from developing adult type
pulmonary tuberculosis. But, several studies indicate that BCG prevents
serious forms of Tuberculosis in children.

23. MDR-TB with HIV co-infection
 The treatment of HIV positive individual with MDR-TB is the same as for HIV
negative patients. However treatment is more difficult and adverse events more
common.
 Deaths during treatment, partly due to TB itself and partly due to other HIV-related
diseases, are more frequent in HIV-infected patients, particularly in the advanced
stages of immunodeficiency.
 The use of ART in HIV infected patients with TB improves survival for both drug
resistant and susceptible disease.
 However HIV infected MDR patients without the benefit of ART may experience
mortality rates exceeding 90%.
 For severe paradoxical reactions prednisone (1-2 mg/kg for 1-2 weeks, then
gradually decreasing doses) may be used.
CD 4 Cell count ART
Recommendation
Timing of ART in relation to
treatment for MDR TB
≤ 350 cells/mm3 Recommend ART After 2 weeks, as soon as the
treatment for MDR TB is tolerated.
> 350 cells/mm3 Defer ART Re-evaluate patient monthly for
consideration of ART. CD4 testing is recommended every 3 months during
treatment for MDR TB
Not available Recommend ART After 2 weeks, as soon as the
treatment for MDR TB is tolerated.

24. MDR-TB in patients with renal impairment
 Renal insufficiency due to longstanding TB disease itself, previous use of
aminoglycosides or concurrent renal disease.
 Consideration needs to be taken that MDR-TB patients require aminoglycosides for 6
months or more.
 Other drugs, which also might require dose or interval adjustment in presence of
mild to moderate renal impairment, are: ethambutol, quinolones, cycloserine and PAS.
 After treatment initiation and then every three months whilst injection Kanamycin is
being administered..
Drug Method
of
modific
ation
Glomerular filtration rate, ml/min
>
50
10-50 <
1
0
Kanamycin D, I 7.5-15mg /Kg /24 hr 4-7.5mg/Kg/24 hr 3mg /Kg /48 hr
Ethambutol I 20mg /Kg /24 hr 20mg/Kg/24–36 hr 20mg /Kg /48 hr
Pyrazinamide D 30mg /Kg /24 hr 30 mg/Kg/24 hr 15-30 mg/Kg/ 24 hr
Ofloxacin D 100% * 50 – 75% * 50% *
Ethionamide D 100% * 100% * 50% *
Cycloserine D 100% * 50-100% * 50% *

26. Information for patients
 What is TB?
 How is TB spread?
 How does TB affect the body?
 What are the symptoms and signs of TB?
 What will happen if you have TB?
 What should you do to get better?
 Why is it important to complete the full drugs course?
 What about HIV and TB?
 Stop TB Progams

27. Thank you