Tuberculosis is an infectious disease caused predominantly by Mycobacterium tuberculosis. It is most commonly transmitted by inhalation of infected droplet nuclei which are discharged in the air when a patient with untreated pulmonary TB coughs or sneezes. A smear positive pulmonary TB can infect 10-15 persons in a year, and remain infectious for 2-3 years if left untreated. The chances of getting infected depend on the duration, frequency of exposure and the immune status of an individual. All those who get infected do not necessarily develop TB disease. The lifetime risk of breaking down to disease among those infected with TB is 10-15%, which gets increased to 10% per year among those PLHIV. Other determinants like Diabetes Mellitus, smoking, alcohol abuse and malnutrition also increase the risk of progression from infection to disease.

Burden of TB in India:

 India accounts for one fourth of the global TB burden i.e 2.8 million out of

10.4 million new cases annually with the mortality rate of 36 per lakh population (source WHO Global TB Report 2016). In India, more than 40% of population is infected with Mycobacterium tuberculosis. It is estimated that there are approximately 5.1 million prevalent cases of all forms of TB disease.

India has the highest burden of both TB and MDRTB (1.3lakhs out of 5.8 lakhs globally). Based on sub-national drug resistant survey ~3% among new TB cases and 12-17% among previously treated TB cases have MDRTB

Symptoms of Tuberculosis

 1.  Pulmonary Tuberculosis (PTB)

 The most common symptoms of PTB are cough with or without expectoration, chest pain, hemoptysis and shortness of breath. It may be accompanied by constitutional symptoms like fever, weight loss, night sweats, tiredness, loss of appetite etc.

2.  Extrapulmonary TB (EPTB)

A person with EPTB may have symptoms related to the organs affected along with constitutional symptoms stated above.

Diagnosis: All efforts should be undertaken for microbiologically confirming the diagnosis in presumptive TB patients. The following are acceptable methods for diagnosis under NTEP and are available at free of cost-

1.      Sputum smear microscopy (for AFB) – Zeihl-Neelson staining and fluorescence staining.

2.      Culture- Solid and Liquid.

3.      Line Probe Assay (LPA).

4.      Nucleic Acid Amplification Test (CB-NAAT).

Other Diagnostic Tools:

1.      Radiography.

2.      Bio chemical.

3.      Histopathological.

4.      Tuberculin Skin Test (Only for supporting diagnosis as it indicates infection only NOT disease).

5.      USG.

Treatment:

 NTEP is now introducing for treatment of drug sensitive TB based on the principle of administering daily fixed dose combinations of 1st Line Anti TB drugs in appropriate weight bands.

Guidelines for treatment initiation:

1.      Counseling of the patient and close family member about the disease, mode of infection, cough hygiene, treatment, side effect and importance of regular treatment.

2.      Record of weight and height.

3.      Look for co-morbidities (HIV, Diabetes, liver/Renal/neurological disorders) and substance abuse (Tobacco, drugs, alcohol).

4.      Identify Treatment Supporter (erstwhile DOT provider).

The standard 6-month course of treatment consists of two phases-

H- Isoniazid       R- Rifampicin         Z-Pyrazinamide         E-Ethambutol                      S- Streptomycin

Extension of Continuation Phase: Extend CP by 3 to 6 months in special situations like Bone & Joint TB, Spinal TB with neurological involvement and neuro-tuberculosis.

Daily Dose Schedule for Adults (As per weight bands)

Drug dosage for paediatric TB

A=Adult FDC (HRZE = 75/150/400/275; HRE = 75/150/275)

Follow up:

1.      Clinical follow up: should be done monthly.

–         Improvement on chest symptoms, increase in weight etc. may indicate good prognosis

–         Control of co-morbid conditions like HIV and diabetes

–         Symptoms and signs of adverse reactions to drugs should be specifically asked .

2.      Laboratory:

–         In case of pulmonary tuberculosis, sputum smear microscopy/ Culture should be done at the end of IP and end of treatment. A negative sputum smear microscopy result at the end of IP may indicate good prognosis

–         However, in the presence of clinical deterioration, the medical officer may consider repeating sputum smear microscopy even during CP. This will provide the patient an early opportunity to undergo drug susceptibility testing if s/he is found to be sputum smear positive

–         Chest x-ray to be offered to drug sensitive pulmonary TB patients whenever required and available.

–         Response to treatment in extra-pulmonary TB may be best assessed clinically. Help of radiological and other relevant investigations may be taken.

3.      Long term follow up: After completion of treatment, the patients should be followed up at the end of 6, 12, 18 & 24 months.

Contact tracing: The following contacts of TB patients must be screened for TB.

1.      All close contacts like family members.

2.      Reverse contact tracing in case of paediatric TB patients.

3.      Children under 6 years.

4.      Contacts with immune-compromised condition, diabetes, pregnancy, alcoholics etc.

5.      Contacts with patient of DRTB.

Isoniazid Preventive Therapy (IPT)

1.      IPT should be given to PLHIV and children under 6 years who are close contact of TB patient after ruling out active disease irrespective of BCG/Nutritional status. The dose of Isoniazid is 10 mg/ kg body weight in pediatric and 300 mg in PLHIV (with pyridoxine 50 mg) daily for 6 months.

2.      A child born to mother who was diagnosed to have TB in pregnancy should receive prophylaxis for 6 months, provided congenital TB has been ruled out. BCG vaccination can be given at birth even if INH preventive therapy is planned.

Programmatic management drug resistant TB (PMDT)

The term Programmatic management of drug resistant TB refers to programme based drug resistant diagnosis, management, and treatment.

Definitions:

•            Mono-resistance (MR): A TB patient, whose biological specimen is resistant to one first-line anti-TB drug only.

•            Poly-Drug Resistance (PDR): A TB patient, whose biological specimen is resistant to more than one first-line anti-TB drug, other than both INH and Rifampicin.

•            Multi Drug Resistance (MDR): A TB patient, whose biological specimen is resistant to both isoniazid and rifampicin with or without resistance to other first line drugs, based on the results from a quality assured laboratory.

–   Rifampicin Resistance (RR): resistance to rifampicin detected using phenotypic or genotypic methods, with or without resistance to other anti-TB drugs excluding INH. Patients, who have any Rifampicin resistance, should also be managed as MDR TB case.

•            Extensive Drug Resistance (XDR): A MDR TB case whose biological specimen is additionally resistant to a fluoroquinolone (ofloxacin, levofloxacin, or moxifloxacin) and a second-line injectable anti TB drug (kanamycin, amikacin, or capreomycin) from a quality assured laboratory.

MDRTB suspect criteria:

1.      Criteria A:

·       All failures of New TB cases

·       Smear positive previously treated cases who remain smear positive at 4th month

·       All pulmonary TB cases who are contacts of known MDRTB case

2.      Criteria B: in addition to criteria A,

·         All smear positive previously treated pulmonary TB cases at diagnosis

·         Any follow up smear positive

3.      Criteria C: In addition to criteria B,

·       Smear negative previously treated pulmonary TB case at diagnosis

·       TBHIV co infected cases.

Diagnostic Technology: Molecular Drug Susceptibility Testing (DST) by LPA and CBNAAT, Liquid culture, Solid culture for diagnosis. For follow up cultures, liquid culture is preferred over solid.

Sputum collection and transport: For diagnosis, two fresh samples early morning & spot or spot & spot (taken at least 1 hr apart) collected in Falcon tubes are transported to NTEP certified lab in cold chain within 72hrs. For follow up cultures one sample is sufficient.

Pre-treatment evaluation:

1.      Detail history (including screening for mental illness, seizer disorder, drug/alcohol abuse etc.) Weight

2.      Height

3.      Complete Blood Count with platelets count

4.      Blood sugar to screen for Diabetes Mellitus

5.      Liver Function Tests

6.      Blood Urea and S. Creatinine to assess the Kidney function

7.      TSH levels to assess the thyroid function (TSH levels alone are usually sufficient to assess the thyroid function of the patient)

8.      Urine examination – Routine and Microscopic

9.      Pregnancy test (for all women in the child bearing age group)

10.  Chest X-Ray

11.  ECG (if Moxifloxacin is to be used)

12.  Serum electrolytes (if Capreomycin is to be used)

13.  All DRTB cases will be offered HIV counseling and testing.

The results of pretreatment evaluation are communicated to DRTB centre committee and, if approved appropriate treatment regimen is initiated at DRTB centre or at the district level by the District TB Officer.

All services under PMDT are offered free of cost including patient and one attendant transportation cost.

Treatment Regimen:

*For Isoniazid resistance, decision on use of Isoniazid in the regimen depends on following:

•            If High level resistance detected by Liquid culture - omit INH.

•            If low level resistance detected by Liquid culture - add high dose INH.

•            If LPA reports INH resistance by Kat G mutation- Omit INH If LPA reports INH resistance by INH A mutation- Use High dose INH. Ethionamide in the treatment regimen will be replaced with PAS.

Drug dosage for DRTB

*For mono-H resistant TB; $For Rifampicin Resistant TB In case of PAS with 60% weight/volume the dose will be increased to 10 gm (16-25 Kg); 14 gm (26-45

Kg); 16 gm (46-70 Kg) and 22 gm (>70 Kg)

Drug dosage for paediatric MDRTB

Drug dosage for paediatric XDTB

Follow up:

1.     Clinical- monthly during intensive phase and every three months during Continuation phase. It includes recording of weight and management of adverse drug reaction.

2.     Laboratory-

a.         S.Creatine: every month for the first three months, then every three month during injectable phase.

b.        Liver Function Test is to be done monthly during intensive phase and three monthly during continuation phase.

c.         ECG once a month in intensive phase if Moxifloxacin is used.

d.        Complete blood count with Platelets count weekly in the first month then monthly to rule out bone marrow suppression and anaemia as a side effect of Linezolid

e.         X-ray: End of intensive phase, end of treatment and whenever clinically indicated.

f.           Culture: MDRTB- every month (30days apart) from the 3rd month onwards during intensive phase, then every three months during Continuation phase. Mono resistant-2nd and 3rd month culture followed by 3 monthly culture till completion of treatment.

3.     Long term follow up- After completion of treatment patient shloud be followed up with clinical and/or sputum examination at 6,12,18 and 24 months.