|Year : 2017 | Volume
| Issue : 1 | Page : 1-9
Recent changes in technical and operational guidelines for tuberculosis control programme in India - 2016: A paradigm shift in tuberculosis control
Arunabha D Chaudhuri
Department of Pulmonary Medicine, R.G. Kar Medical College, Kolkata, West Bengal, India
|Date of Web Publication||29-Dec-2016|
Dr. Arunabha D Chaudhuri
Professor R.G. Kar Medical College, BF-130, Sector-I, Salt Lake City, Kolkata - 700 064, West Bengal
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Chaudhuri AD. Recent changes in technical and operational guidelines for tuberculosis control programme in India - 2016: A paradigm shift in tuberculosis control. J Assoc Chest Physicians 2017;5:1-9
|How to cite this URL:|
Chaudhuri AD. Recent changes in technical and operational guidelines for tuberculosis control programme in India - 2016: A paradigm shift in tuberculosis control. J Assoc Chest Physicians [serial online] 2017 [cited 2019 Dec 10];5:1-9. Available from: http://www.jacpjournal.org/text.asp?2017/5/1/1/196644
The national tuberculosis programme of India (NTP) was initiated in 1962 and was originally designed for domiciliary treatment, using self-administered standard drug regimen. In 1992, the Government of India with World Health Organization (WHO) and Swedish International Development Corporation Agency (SIDA) reviewed the tuberculosis (TB) situation and the performance of NTP which revealed that the NTP, though technically sound, suffered from managerial weakness, inadequate funding, over-reliance on X-ray for diagnosis, frequent interrupted supplies of drugs and low rate of treatment completion. In 1997, Revised TB Control Programme (RNTCP) was launched which formulated and adopted the internationally recommended Directly Observed Short Course (DOTS) strategy as the most systemic and cost-effective approach to revitalize the TB control programme in India.
The objectives of RNTPCP were to achieve at least 85% cure rate among the new smear-positive cases initiated on treatment and thereafter a case detection rate of at least 70% of such cases. The major addition of RNTCP was the establishment of a sub-district supervisory unit known as TB Unit, with RNTCP supervisor and decentralization of diagnostic and treatment services with treatment given under the support of DOT provider (DP).
The first technical and operational guidelines for RNTCP were developed during the initial years of implementation of the programme and were updated in 2005. The current document outlines the guidelines on TB care in line with RNTCP national strategic plan for TB control 2012–2017. Experts from National Institute, National and Intermediate Laboratories, Medical Colleges and Partners were involved in the process of preparing it. The documents covered strategies and guidelines for diagnosis and treatment for all forms of TB including pulmonary TB, extra-pulmonary TB, drug-resistant TB (DRTB), TB with comorbidity and paediatric TB. The programme management aspect covering patients support system, human resource management, partnership for TB control, advocacy, communications and social mobilization, infection control measures, planning and finance are also incorporated.
The goal of the national strategic plan is to achieve universal access of quality of TB diagnosis and treatment of all TB patients in the community. The objectives of the national strategic plan are:
- To achieve 90% notification rate for all cases
- To achieve 90% success rate for all new and 85% for re-treatment cases
- To significantly improve the successful outcome of treatment for DRTB cases
- To achieve decreased morbidity and mortality for HIV-associated TB cases
- To improve the outcome of TB care in the private sectors.
A government order issued by the Government of India in May 2012 mandates all health care providers to notify every TB case and/or treated to the local authorities. To support TB notification and strengthen TB surveillance in general, a case-based, web-based TB notification system NIKSHAY was established to provide platform for notification from both public and private sectors.
The major change in the organization structure of RNTCP is the formation of one TB Unit per block/1.5–2.5 lakh population in urban areas in contrast to previous RNTCP guidelines, where there was one TB Unit per 5 lakh population/1 per 2.5 lakh in tribal, hilly and difficult areas.
| Presumptive TB cases|| |
As per the previous guidelines, a pulmonary TB suspect was defined as:
- An individual having cough for 2 weeks or more
- Contacts of smear-positive TB patients having cough for any duration
- Suspected/confirmed extra-pulmonary TB having cough for any duration
- HIV-positive patient having cough for any duration.
But according to the new guidelines –
Presumptive pulmonary TB refers to a person with any of the symptoms or signs suggestive of TB:
- cough >2 weeks,
- fever >2 weeks,
- significant weight loss,
- any abnormalities in chest radiography.
In addition, contact of microbiologically confirmed TB patients, PL HIV, diabetics, malnourished, cancer patients, patients on immunosuppressive therapy or steroid should be regularly screened for signs and symptoms of TB.
There is no change in the definition of presumptive extra-pulmonary TB cases.
There are few additions in the definition of presumptive TB cases in paediatric patients, where loss of body weight is defined that loss of >5% body weight as compared to highest weight recorded in the last 3 months. The history of unexplained or no weight gain in the past 3 months and symptomatic child contact with any form of active TB in the last 2 years may be significant.
There have been changes in the definition of presumptive DRTB cases as follows:
- TB patients who have failed treatment with first-line anti-tubercular drugs (ATD)
- Paediatric TB non-responder
- TB patients who are contacts of DRTB
- TB patients who are found positive on any follow-up sputum smear examination during treatment with first-line ATD
- Previously treated TB cases
- TB patients with HIV co-infection.
Diagnostic algorithm of pulmonary TB has been completely changed from the previous guidelines
[Additional file 1]
- All presumptive TB will undergo sputum smear examination (spot–early morning or spot–spot). If the first sputum is positive and not at risk for DRTB, it is categorized as microbiologically confirmed TB
- Smear-positive and presumptive multi-drug resistance TB (MDR TB): A Cartridge-Based Nucleic Acid Amplification Test (CBNAAT) will be performed to rule out Rifampicin resistance and categorized as microbiologically confirmed drug-sensitive TB or RIF-resistant TB
- If the first smear is negative and chest X-ray (CXR) is suggestive of TB, 2nd sample will be subjected to smear and CBNAAT simultaneously
- On the basis of the CBNAAT result, patients will be categorized as microbiologically confirmed drug-sensitive TB or RIF-resistant TB
- A RIF indeterminate result will get an additional CBNAAT to get a valid result and in case of indeterminate on second occasion, the specimen will be sent to the Intermediate Reference Laboratory (IRL) or Culture and Drug Sensitivity Test (C and DST) centre for Line Probe Assay (LPA) or Liquid Culture and Drug Sensitivity Test (LC and DST)
- Whenever facilities are available, effort should be made to obtain DST results of all drugs
- If both the sputum smear and CXR are negative, the patient should be referred to a pulmonologist
- All key population (PLHIV, children, EPTB, etc.) will preferentially get a CBNAAT
- All diagnostic health care facilities should have TB lab that are quality assured by competent authority.
Diagnostic algorithm of extra-pulmonary TB has been completely changed:
[Additional file 2]
Diagnostic algorithm of paediatric TB has also been completely changed from the previous guidelines:
[Additional file 3]
Case definition: There are significant changes in the definition of cases as per New Guidelines:
- Microbiologically confirmed TB case refers to a presumptive TB patient with biological specimen positive for acid-fast bacilli, or positive for mycobacterium TB on culture, or positive for TB through Quality Assured Rapid Diagnostic molecular test.
- Clinically diagnosed TB case refers to a presumptive TB patient who is not microbiologically confirmed, but has been diagnosed with active TB by a clinician on the basis of X-ray abnormalities, histopathology or clinical signs with a decision to treat the patient with a full course of anti-TB treatment.
Microbiologically confirmed or clinically diagnosed cases of TB are classified according to
- Anatomical site of disease
- History of previous TB
- Drug resistance.
There are significant changes in the definition while the classification is done on the basis of history of the previous treatment.
- New case – A TB patient who has never had treatment for TB or has taken ATD for <1 month. (No change in new guidelines.)
- Previously treated patients have received one month or more ATD in the past. This may be:
- Recurrent TB case – A TB patient previously declared as successfully treated (cured/treatment completed) and who is subsequently found to be microbiologically confirmed TB case is a recurrent TB case. (Previously called relapse.)
- Treatment after failure – Patients are those who have previously been treated for TB and whose treatment failed at the end of their most recent course of treatment.
Previously, it was called failure where a TB patient is sputum-positive at 5 months or more after initiation of treatment.
- Treatment after loss to follow-up – A TB patient previously treated for TB for one month or more and who was declared lost to follow-up in their most recent course of treatment and subsequently found microbiologically confirmed TB cases.
Previously called treatment after default – a patient who has received treatment for TB for a month or more from any source and return for treatment after having defaulted, that is, not taking ATD consecutively for 2 months or more and found to have smear-positive.
There are significant additions in the definition while classification was done on the basis of drug resistance.
- Mono resistance (MR) – A TB patient whose biological specimen is resistant to one first-line anti-TB drug only.
- Poly 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 INH and Rifampicin with or without resistance other first-line ATD, based on results from a Quality Assured Laboratory. (No changes.)
- Rifampicin resistance (RR) – Resistance to Rifampicin detected by phenotypic or genotypic methods with or without resistant to other ATD excluding INH. Patient with RR should be managed as if they are in MDR TB case.
- Extensive drug resistance (XDR) – MDR TB case whose biological specimen was resistant to a Fluroquinolone (FQ) and a second-line injectable ATD from a Quality Assured Laboratory. (No changes.)
According to the previous guidelines, drug regimen for drug-sensitive TB was as follows:
- Standard intermittent regimen with 2 categories of treatment
- Treatment under direct observation of DP
- Category decided by MO (category I/II)
- Drugs to be taken three times a week under direct observation of the DP
- Intensive phase (IP) for 2–3 months – all doses given under supervision
- Continuation phase (CP) for 4–5 months – first dose of the week given under supervision.
But there are significant changes in the drug regimen in the new guidelines:
- Principle of treatment of TB has been shifted towards daily regimen with administration of daily fixed dose combination of first-line ATD as per appropriate weight bands.
For new TB cases
- Treatment in IP will consist of 8 weeks of INH, Rifampicin, Pyrazinamide and Ethambutol in daily dosages as per four weight bands categories
- There will be no need for extension of IP
- Only Pyrazinamide will be stopped in CP while the other three drugs will be continued for another 16 weeks as daily dosages.
For previously treated cases:
- IP will be of 12 weeks, where injection Streptomycin will be stopped after 8 weeks and the remaining four drugs in daily dosages as per weight band for another 4 weeks
- No need of extension of IP
- At the start of CP, Pyrazinamide will be stopped while rest of the drugs will be continued for another 20 weeks as daily dosages.
[Additional file 4]
Management of extra-pulmonary TB (new guidelines) – There is only one change as follows:
- The CP in both new and previously treated cases may be extended 3–6 months in certain TB such as CNS, skeletal, disseminated TB, and so on based on clinical decision of the treating physicians
- Extension beyond 3 months will only be on recommendation of experts of concerned field.(In the previous guidelines, extension of ATD in case of CNS and skeletal TB was maximum 3 months).
According to the new guidelines, ATD are to be given in fixed dose combination as daily doses; drug doses for adult TB is as follows:
Drug Dosage for Adult TB
[Additional file 5]
In patients above 50 years of age, maximum dose of Streptomycin should be 0.75 g.
Drug Dosage for Pediatric TB
[Additional file 6]
Follow-up of treatment: There are some changes in the new guidelines:
Clinical follow-up – (new addition)
Should be at least monthly – the patient may visit the clinical facility, or the medical officer may conduct the review when she/he visits the house of the patient to observe improvement of chest symptoms, weight gain, control the co-morbid conditions such as HIV and diabetes and to monitor any adverse reaction to ATD.
Follow-up laboratory investigation
For PTB cases – sputum smear examination at the end of IP and at the end of treatment. (In the previous guidelines, follow-up sputum smear to be done at 2, 4 and 6 months for new cases and 3, 5 and 8 months in previously treated cases.)
- In case of clinical deterioration, the Medical Office may consider repeat sputum smear even during CP. (New addition.)
- At the completion of treatment, sputum smear and culture should be done for every patient
- CXR – to be offered whenever required and available.
After completion of treatment, the patient should be followed up at the end of 6, 12, 18 and 24 months. Any clinical symptoms and/or cough, sputum microscopy and/or culture should be considered. (New addition) However, there was no provision of long-term follow-up in the previous guidelines.
Difference of RNTCP regimen between new and previous guidelines
[Additional file 7]
A microbiologically confirmed TB at the beginning of the treatment who was smear- or culture-negative at the end of complete treatment. (Changed).
TB patients either cured or treatment completed are accounted in the treatment success. (New addition).
A TB patient whose biological specimen is positive by smear or culture at the end of the treatment. (Changed).
Failure to respond
For paediatric TB patients. (New addition).
Lost to follow-up
A TB patient whose treatment was interrupted for one consecutive month or more. (New addition).
A TB patient for whom no treatment outcome is assigned. (Former transfer out).
Treatment regimen changed
Previously, it was called as switched over to MDR treatment.
There are some additions of chapter in the new guidelines like
Management of TB patients with liver disorder
If the serum alanine amino transferase level is more than three times normal before initiation of treatment, the regime should be:
- Containing two hepatotoxic drugs: INH + Rifampicin + Ethambutol for 9 months or
- INH + Rifampicin + Ethambutol + Streptomycin for 2 months followed by INH and Rifampicin for 7 months or
- Rifampicin + Ethambutol + Pyrazinamide for 6–9 months.
- Containing one hepatotoxic drug:
INH + Ethambutol + Streptomycin for 2 months followed by INH + Ethambutol for 10 months.
- Containing no hepatotoxic drugs:
Streptomycin + Ethambutol + FQ for 18–24 months.
Initiation of first-line ART in relation to ATD
[Additional file 8]
Isoniazid Preventive Therapy (IPT) for PLHIVs
- Adult and adolescents living with HIV should be screened for TB and those who are unlikely to have active TB should be offered IPT
- Children with HIV who have no TB symptoms and who are unlikely to have active TB on symptom-based screening should be offered IPT regardless of their age
- All children with HIV who have successfully completed treatment for TB disease should receive IPT.
Dosage of INH preventive therapy:
- Adult and adolescent: INH 300 mg + Pyridoxine 50 mg per day for 6 months.
- Children above 12 months: INH 10 mg/kg + Pyridoxine 25 mg per day for 6 months.
Changes in the DRTB (DRTB guidelines):
Introduction of new ATD under RNTCP
- Bedaquiline (BDQ):
- New class of drug, diarylquinoline that targets mycobacterial ATP synthase, and enzyme essential for supply of energy to mycobacterium TB
- Strong bactericidal and sterilizing activities against MTB
- It has no cross-resistance with first- and second-line ATD
- Significant benefit in improving the time to culture conversion in MDR TB patients
- RNTCP introducing BDQ at six sites in the country initially
- Basic criterion – Adult aged ≥18 years having pulmonary MDR TB
- Female should not be pregnant.
[Additional file 9]
MDR/RR TB cases (without additional resistance)
Treatment regimen for MDR TB contains 6–9 months of IP with Kanamycin, Levofoxacin, Ethambutol, Pyrazinamide, Ethionamide and Cycloserine and 18 months of CP with Levofoxacin, Ethambutol, Ethionamide and Cycloserine (no change).
But if INH resistance is not known or DST result shows sensitivity to INH, then addition of INH in the above-mentioned regimen of ATD is to be done. (New addition)
[Additional file 10]
All MDR TB cases would be subjected to LC and DST at baseline for Kanamycin and Levofloxacin. Appropriate modification of the treatment regimen can be done in case of additional resistance.
If isoniazid resistance is found, the use of isoniazid depends on:
- If high-level resistance detected by liquid culture – omit INH.
- If low-level resistance detected by LC – add high dose INH.
- If LPA reports INH resistance by Kat G mutation – omit INH.
- If LPA reports INH resistance by INH A mutation – add high dose INH.
There are some new additions
- If RR by CBNAAT, then add INH in the standard dose till result of LPA or LC and DST.
- For new patients diagnosed as TB and RR by CBNAAT – repeat CBNAAT and send the sample for liquid culture
- If second CBNAAT shows RR then start standard MDR till result for culture DST available. Perform DST to INH and SLDST on liquid culture.
- If second CBNAAT shows R sensitiveness, continue regimen for new TB cases and wait for LC and DST. As soon as LC result is available, modify the regimen as follows:
- If LC shows R sensitiveness – continue regimen for new TB cases
- If LC shows R resistance – refer the patients to DRTB centre for decision regarding starting MDR or continuing regimen for new TB cases depending on the response to treatment given so far.
- For mixed resistance pattern, consider oral drug in the sequence of preference – Pyrazanamide, Ethambutol, Ethionamide, Cycloserine, PAS, Clofazimine, Linezolide, Coamoxyclave, high dose INH, Clarythromycin
- Regimen designing or modification will be prerogative of the DRTB centre committee only.
Treatment of mono/poly drug resistance TB
- On receiving reports showing mono/poly DRTB from the quality assured C and DST laboratory, the patients and the family members are counselled
- Pre-treatment evaluation by the DRTB centre committee
- Mono drugs resistance TB.
- Injectable second-line drug (SLD) + FQ + Rifampicin + two out of the first-line drugs (from H, E, Z) to which the patient is sensitive to make a total five effective drugs given daily.
- In case of reported baseline additional resistance to other first-line drugs (FLD) the regime is – injection SLD + FQ + Rifampicin + any FLD to which the patient is sensitive + one of the remaining group four drugs (Ethionamide, Cycloserine, PAS)
- In addition, high dose INH is to be added if LPA shows inhA mutation or culture shows low-level INH resistance
- Total duration of treatment will be 9–12 months
- IP for 3 months with extension to a maximum 6 months and CP for 6 months depending on follow-up sputum reports
- Treatment initiated at DRTB centre.
[Additional file 11]
(1) For MDR TB patients –
Schedule for sputum culture examination for MDR TB (no change):
[Additional file 12]
(2) For mono DR and poly DRTB patients –
Schedule for sputum culture examination:
Microbiological: Sputum smear and culture at second and third months and then culture examination at three monthly interval till completion of the treatment.
- For mono/poly DRTB patients –
- IP should given for at least 3 months
- After this, the patient will be reviewed
- If after the 3 months the smear result remains positive, the sputum sample is sent for genotypic DST to Rifampicin for CBNAAT or LPA and liquid/solid culture and DST to see for resistance amplification
- Shifting from IP to CP will be based on the result of culture
- The IP can be extended maximum 3 months
- Duration of CP is 6 months
(3) MDR TB patients with additional drugs resistance including XDR TB patients
- Change from IP to CP will be done after achievement of culture conversion, that is, two consecutive negative cultures taken at least one month apart
- In case of delay in culture conversion, IP can be extended from 6 months to maximum 12 months.
Outcome for RR/MDR and/or XDR TB patients (new guidelines)
- Cure – Treatment completed as recommended by the National Policy without evidence of failure and three or more consecutive cultures taken at least 30 days apart are negative after IP
- Treatment completed – Treatment completed as recommended by the National Policy without evidence of failure but no record that three or more consecutive cultures taken at least 30 days apart are negative after IP
- Treatment success – The sum of cured and treatment completed
- Treatment failed – Treatment terminated or need for permanent regimen change of at least two or more ATD in CP because of lack of microbiological conversion by the end of IP or microbiological reversion in the CP after conversion to negative or evidence of additional acquired resistance FQ or second-line injectable drugs, or adverse drug reaction.
Outcomes for mono/poly drug-resistant TB patients
- Cure – A microbiologically confirmed TB at the beginning of treatment who was culture-negative in the last month of treatment and on at least one previous occasion
- Treatment completed – A patient who has completed treatment according to the guidelines but does not meet the definition for cure or treatment failure due to lack of microbiological results
- Failure – Treatment terminated or need for permanent regimen change of at least two or more anti-TB drugs in CP because of:
- Evidence of additional acquired resistance to Rifampicin, Rluroquinolone or second-line injectable during treatment
- Severe ADR
- Culture-positive during CP or at end of treatment
- Died – A patient who dies for any reason during the course of M/X DRTB treatment
- Loss to follow-up – A patient whose treatment was interrupted for one month or more for any reasons
- Not evaluated – A DRTB patient for whom no treatment outcome is assigned, and this included former ‘transfer out’.
Therefore, there are mammoth and comprehensive changes in the new RNTCP guidelines for both drug-sensitive and DRTB in regard to:
- The objectives, organizational structure, definition of presumptive TB cases, case definition, drug regimen, follow-up, treatment outcome and also in the management of DRTB cases
- Introduction of daily regimen – the Government of India has taken a decision to introduce daily regimen for treatment of drug-sensitive TB patients under Revised National TB Control Programme in a phased manner. Initially, it is going to be introduced for all TB patients in five states, that is, Bihar, Maharashtra, Sikkim, Himachal Pradesh and Kerala. In addition, all HIV-infected TB patients and paediatric TB cases in entire country will be provided daily regimen under the programme
- Modification of ART regimen in TB-HIV co-infected patients
- There are additions of some new chapters on diabetes and TB, nutrition, smoking, IPT in TB HIV and TB silicosis
- Clear-cut guidelines regarding absolute contraindication of ATD, reintroduction of ATD following adverse drug reactions, algorithm on liver Disease with TB and kidney disease with TB.
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