• Tuberculosis

• 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.
• Pathophysiology of tuberculosis:
• 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
• 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.
•
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.
• 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
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
•
H= INH 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
• 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.
• 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)
• Treatment
• Categorywise sputum examination results and actions to be taken
• Phases and duration of treatment
• 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.
• 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.
• 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.
• 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.
• 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..
• 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