|Year : 2022 | Volume
| Issue : 2 | Page : 55-66
National TB Elimination Program (NTEP): at a glance
Susmita Kundu, Rahul Ghosh
Department of Pulmonary Medicine, RG Kar Medical College, Kolkata, West Bengal, India
|Date of Submission||06-May-2022|
|Date of Acceptance||09-May-2022|
|Date of Web Publication||19-Dec-2022|
Department of Pulmonary Medicine, RG Kar Medical College, Flat no. 101, Monomohini Apartment, 71, Shyamnagar Road, Kolkata 700 055, West Bengal
Source of Support: None, Conflict of Interest: None
India has the highest burden of tuberculosis worldwide. Over the last six decades there was evolution of national programs on tuberculosis. The present national program on tuberculosis emphasized on elimination and prevention of tuberculosis.
Keywords: Pulmonary tuberculosis, Extra-pulmonary tuberculosis, paediatric tuberculosis
|How to cite this article:|
Kundu S, Ghosh R. National TB Elimination Program (NTEP): at a glance. J Assoc Chest Physicians 2022;10:55-66
| Global Burden of Tuberculosis − 2018|| |
Disease wise tuberculosis (TB) is the single most common infective cause of global morbidity and mortality. India has the highest burden of both drug-sensitive as well as drug-resistant TB and second highest burden of HIV-associated TB based on the estimates published in the Global TB Report 2015. An estimated 71,000 cases of MDR-TB emerge annually from the notified cases of pulmonary TB in India. About 3% of new TB cases and 12% to 17% of the previously treated TB cases have MDR-TB. An estimated 1.1 lakh HIV-associated TB occurred in 2014 and 31,000 patients died among them. As a single disease, TB kills more adults in India than any other infectious disease.
In India every day:
- More than 6000 people develop TB disease.
- More than 600 people die of TB (two deaths every 5 minutes).
Evolution of TB control strategies in India
1950s to 1960s − Important TB research at TRC and NTI.
1962–National TB program.
1992–Program review ([Figure 1],[Figure 2],[Figure 3],[Figure 4],[Figure 5]).
|Figure 4 Algorithm for the management for hepatic impairment: before initiation.|
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|Figure 5 Algorithm for management of hepatic impairment: after initiation.|
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Only 30% patients diagnosed; of these only 30% treated successfully.
1992–Revised National TB Control Program (RNTCP) pilot began ([Table 1],[Table 2],[Table 3],[Table 4],[Table 5]).
1997–RNTCP launched as a National program (DOTS strategy adopted).
1998–RNTCP scale-up ([Table 6],[Table 7],[Table 8],[Table 9],[Table 10]).
|Table 6 Current management guideline for new and previously treated TB cases|
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|Table 8 Current recommended revised weight band for standard first-line regimen for TB in adults|
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2001–About 450 million population covered.
2004–More than 80% of the country covered.
2006–Entire country covered by RNTCP.
| Stop TB Strategy, 2006|| |
- Vision: A world free of TB.
- Goal: To dramatically reduce the global burden of TB by 2015 in line with the Millennium Development Goals and Stop TB Partnership targets.
Stop TB partnership targets:
- By 2005–At least 70% of the sputum-positive TB will be diagnosed and at least 85% cured.
- By 2015–Global burden of TB (prevalence and death rates) will be reduced by 50% relative to 1990 levels.
- Reduce prevalence <150/lakh population.
- Reduce deaths to <15/lakh population.
- Number of people dying from TB in 2015 should be <1 million, including those coinfected by HIV.
- By 2035–Global incidence of TB disease will be ≤1 case per million population per year.
National Tuberculosis Elimination Program
Revised National TB Control Program (RNTCP) nomenclature has been changed to National Tuberculosis Elimination Program (NTEP) from January 2020.
Objectives of NTEP
- To achieve 90% notification rate for all the cases.
- To achieve 90% success rate for all new and 85% success rate for all re-treatment cases.
- To significantly improve the successful outcomes of treatment of DR-TB patients.
- To decrease the morbidity and mortality of HIV-associated TB.
- To improve the outcomes of TB care in private sector.
| Presumptive TB|| |
- Presumptive pulmonary TB:
- Cough >2 weeks.
- Fever >2 weeks.
- Significant weight loss.
- Any abnormality on chest radiograph.
- (Note: Contacts of microbiologically confirmed pulmonary TB cases, PLHIV, diabetes, malnourished, cancer patients, and patients on immune suppressants or steroids should be regularly screened for the signs and symptoms of TB).
- Presumptive extrapulmonary TB:
- Organ specific symptoms, for example, swelling of joints, lymph nodes, neck stiffness, disorientation.
- Constitutional symptoms such as, weight loss, night sweats.
- Presumptive pediatric TB:
- Persistent fever >2 weeks.
- Cough >2 weeks.
- Loss of weight/no weight gain.
- History of contact with infective TB cases.
- (Loss of weight is defined as loss of >5% body weight as compared to highest weight recorded in last 3 months).
- Presumptive DR-TB (As per TOG 2016):
- Patients who are found to be positive on any follow-up sputum smear examination during treatment with first-line drugs.
- Previously treated TB cases.
- TB patients with HIV coinfection.
- TB patients who failed treatment with FLD.
- Pediatric TB nonresponders.
- TB patients who are contact of DR-TB (or RIF resistance).
| Case Definitions|| |
- Microbiologically confirmed TB case: Biological specimen positive for AFB or positive for Mycobacterium tuberculosis on culture or positive for M. tuberculosis through quality assured rapid diagnostic molecular test.
- Clinically diagnosed TB case: A presumptive TB patient who is not microbiologically confirmed but 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 ATD.
- New case: A TB patient who has never had been treated for TB or has taken anti-TB drugs for <1 month (definition is same as the old one).
- Previously treated case: All the patients who have received anti-TB drugs >1 month in the past.
- Recurrent TB case: A TB patient previously declared as successfully treated (cured/treatment completed) and is subsequently found to be microbiologically confirmed TB case is called a recurrent TB case (previously called relapse).
- Treatment after failure: These 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 called only “failure”).
- Treatment after lost to follow-up: A TB patient previously treated for TB for ≥1 month and was declared “lost to follow-up” in their most recent course of treatment and subsequently found to be a case of microbiologically confirmed TB case.
Tools for microbiological confirmation of TB
All efforts should be undertaken for microbiological confirmation of the diagnosis in presumptive TB patients under NTEP. Acceptable methods for microbiological diagnosis of TB are:
- Sputum smear microscopy (for AFB):
- Ziehl-Neelsen staining.
- Fluorescent staining.
- Solid culture on LJ media.
- Liquid culture system.
- Rapid molecular diagnostic testing:
- Line probe assay.
- Cartridge-based nucleic acid assay (CBNAAT)/TrueNat (MolBio Diagnostics Pvt Ltd, Goa, India)/UltraNAAT.
- Drug sensitivity testing:
- Modified PST for MGIT 960 system (for both first and second-line drugs).
- Economic variant of proportion sensitivity testing (1%) using LJ media (as a backup when indicated).
- Chest radiograph: Diagnosis on the basis of chest X-ray will be termed as clinically diagnosed.
- Tuberculin skin test and interferon gamma release assay (IGRA): Can be used as an ancillary test in children with other diagnostic modalities. Role of IGRA in high burden countries like India is not clear.
- Serological tests: Government of India has banned the use of serological tests for the diagnosis of TB currently.
Role of smear for acid-fast bacilli
Smear is the cheapest, simple, point of care confirmatory test ([Table 11],[Table 12],[Table 13],[Table 14]).
|Table 11 Drug dosage for anti-TB drugs in adult and pediatric population|
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Smear is less preferred as a single test for diagnosis due to several issues, such as:
- High level of agreement, more with increased number of bacilli on smear.
- Problems in getting the specimen.
- Young children do not bring up and cough sputum.
- Poor sensitivity in paucibacillary primary disease.
- No significant increase with fluorescent microscopy (LED FM).
- Extrapulmonary – a significant problem in children-less often AFB positive.
- Does not differentiate drug-sensitive from drug-resistant forms.
- Increased risk of amplification of resistance with standard regimens.
Smear is used in the laboratory before setting up for LPA (direct testing, only in smear-positive cases).
Ziehl-Neelsen staining procedure:
- New unscratched slide is selected and labeled with laboratory serial number.
- A smear is made from yellow purulent portion of the sputum using a broom stick. A good smear is spread evenly; 2 cm × 3 cm in size, neither too thick nor too thin. An ideal thickness of the smear should be such that if the smeared slide is kept on a printed paper the writing should be clearly readable through the smear.
- Smear is prepared near a flame, this is required as 6 inches from the flame is considered to be a sterile zone which coagulates aerosol during smear preparation.
- The slide is allowed to dry for 15 to 30 minutes.
- The slide is fixed by passing over the flame three to five times for 3 to 4 seconds each time.
- Then 1% filtered carbolfuchsin is poured all over the slide.
- The slide is heated with the carbolfuchsin on it until vapors start to rise; do not boil it.
- Carbolfuchsin is left on the slide for 5 minutes.
- The slide is gently rinsed with tap water until all free carbolfuchsin stain is washed away. At this point, smear on the slide looks red in color.
- After that, 25% sulfuric acid is poured onto the slide and allowed to stand for 2 to 4 minutes.
- The slide is gently rinsed with tap water and tilted to drain off the water.
- A properly decolorized slide looks pink in color.
- Then 0.1% methylene blue is poured onto the slide and left for 30 seconds. The slide is gently rinsed with tap water and allowed to dry.
- The slide is examined under binocular microscope using ×40 lens to select the suitable area; then the selected area is examined with ×100 lens with a drop of immersion oil.
- The results are documented in the laboratory form and laboratory register.
- The slides are inverted on a tissue paper till the immersion oil is completely absorbed.
- All positive and negative slides are stored serially in the same slidebox until instructed by the supervisor.
- All contaminated materials are disinfected as per guidelines before discarding.
- Based on the CBNAAT result patient will be categorized as microbiologically confirmed drug-sensitive TB or RIF-resistant TB.
- In case of RIF indeterminate result, an additional CBNAAT will be done to get a valid result. If indeterminate on second occasion, an additional specimen will be sent to nearest IRL or C & DST center for LPA or liquid culture and DST, as appropriate.
Changes in Diagnostic Algorithms
In a patient with presumptive pulmonary TB, smear examination and chest radiograph both have been given importance now. All these patients undergo two sputum smear examinations. If the first smear is positive for AFB, the patient is labelled as microbiologically confirmed TB. If the first smear is negative, the second sample is simultaneously subjected to smear and CBNAAT. On the basis of CBNAAT, the patient is diagnosed either as drug-sensitive TB or rifampicin-resistant TB. An indeterminate result calls for an additional CBNAAT for a valid result, and in case of a second indeterminate result, the specimen is to be sent to an accredited laboratory for culture and drug-sensitivity testing.
In a patient with presumptive extrapulmonary TB, appropriate specimen from the involved site should be collected and subjected directly to CBNAAT (except for urine, stool, and blood). Based on a positive CBNAAT or a positive culture (where CBNAAT is negative), the patient is classified as microbiologically confirmed extrapulmonary TB. If the patient is diagnosed as having extrapulmonary TB, based on clinical suspicion or other diagnostic tools, he/she can be classified as clinically diagnosed TB.
Similarly, for a presumptive pediatric pulmonary TB patient, CBNAAT should be straightaway performed on sputum sample or on gastric lavage if sputum is negative but chest radiograph is suggestive. If both these arms are not clinically relevant, further course of action should be decided.
Drug regimen for drug-sensitive TB
The principle of treatment of TB (other than drug-resistant TB) is with daily regimen with fixed-dose combination (FDC) of first-line anti-tubercular drugs in appropriate weight bands.
Main changes are in the following aspects:
- Daily regimen.
- Weight band.
- Ethambutol in CAT-I continuation phase (CP).
- No extension of intensive phase (IP).
- No CAT-II in the new guideline.
The rationale of each of the changes are as follows:
- Why daily regimen?
- When long-term relapse rates are studied in Thiruvallur district in southern India among new smear-positive pulmonary TB cases (NSP cases), which is not routinely done under RNTCP, it was found that relapse occurs in about 12.9% of the patients with history of treatment interruption, whereas it is only 8.8% in patients with no interruption. Comparison yielded an odds of 1.54. It means patients with treatment interruptions had 1.54 times more chances of TB relapse.
- Summary of evidences:
- Relapse rates are high with thrice weekly regime, more than many high-burden countries, over a period of time in all states.
- Relapse rates are high with treatment interruption, but not significantly different in patients without treatment interruption.
- Relapse rates are high among NSP TB patients in the areas with no private sector presence.
- Relapse rates are higher with intermittent regimen.
- Why FDC?
- The potential advantages of FDCs are as follows:
- Simplicity of treatment.
- Increased patient acceptance as: fewer tablets to swallow and prevents concealed irregularity.
- Increased health worker compliance.
- Fewer tablets to handle, hence quicker supervision of DOT.
- Easier drug management.
- Reduced use of monotherapy.
- Lower risk of misuse of single drug.
- Lower risk of emergence of drug resistance.
- Easier to adjust dosages by body weight.
- Why weight band?
- In RNTCP regimens for adults:
- <30 kg
- 30 to 60 kg
- 60 kg
- The dose of INH is inappropriately high for those in the weight band of 30 to 40 kg (almost 45% in our cohort).
- Drug toxicity related to INH in underweight patients is possibly one of the reasons of adverse effects and default.
- Why there are drugs (ethambutol) in CAT-I CP?
- Pretreatment INH resistance is high (>10%).
- Pretreatment INH resistance leads to amplification of resistance (acquired rifampicin resistance) loading to development of MDR-TB.
- Pretreatment INH resistance: HIV-positive patients with pulmonary TB are at higher risk of acquired rifampicin resistance, when failing a three times weekly short-course intermittent regimen, irrespective of length of treatment (6 month or 9 month duration).
- The fact is supported by the following findings:
- Out of 227 TB patients, there were a total of 19 (8.4%) bacteriological failures during treatment (eight patients in 6 months regime and 11 were in 9 months regimen).
- All of them had acquired rifampicin resistance.
- Also, 9 (47%) of these patients had isolates with initial isoniazid resistance.
- Ethambutol in CP can protect rifampicin and can prevent emergence of MDR in patients with pretreatment isoniazid resistance.
- Why no extension of IP?
- For new TB cases, the treatment in the IP will be of 8 weeks.
- There will be no extension of IP.
- Only pyrazinamide will be stopped in the CP.
- Other three drugs will be continued for another 16 weeks as daily dosages.
- CP of both new and previously treated cases may be extended by 12 to 24 weeks in certain forms of TB like: CNS TB, skeletal TB, disseminated TB, based on the clinical decision of the treating physician. Extension beyond 12 weeks should only be done on the basis of recommendation of the experts of the concerned field. Loose drugs will be needed as substitutions in case of adverse drug reaction or with comorbid conditions.
| Pediatric Formulation and Weight Bands|| |
Children up to 39 kg would be managed as per various weight bands available for children.
Children ≥40 kg of weight, would be managed same as per various weight bands available for adults ≥40 kg.
- At least monthly. Patient visits the clinical facility or the MO reviews during home visit.
- Improvement of the chest symptoms, increase in weight, etc., may indicate good prognosis.
- Control of comorbid conditions like HIV and diabetes.
- Symptoms and signs of adverse reactions to drugs should be specifically asked.
- Chest X-ray to be offered to drug-sensitive pulmonary TB patients whenever required and available.
- Response to treatment in extrapulmonary TB may be best assessed clinically. Help of radiological and other relevant investigations may be taken.
- Response to treatment in children may be assessed clinically who are unable to produce sputum. Help of relevant investigations may be taken.
In case of pulmonary TB, smear microscopy examination on one sputum specimen to be done at the end of IP and one at the end of the treatment. If becomes smear positive at the end of IP, no further extension of IP should be done.
At the end of the treatment, a sputum smear and/or culture should be done for every patient. At the end of the treatment if found to be smear/culture positive − treatment failure.
After the completion of treatment, the patient should follow-up at the end of 6, 12, 18, and 24 months. It will help to detect the recurrence at the earliest.
Rationale of adding pyridoxine in TB regimen
Tablet pyridoxine is not required for all TB patients. It is required to prevent INH-related neuropathy in persons at high risk of vitamin B6 deficiency, such as:
- Pregnant and lactating women.
- Patients with conditions such as: chronic renal failure, diabetes, HIV infection.
HIV and TB
Ideally all presumptive TB patients have to undergo HIV screening.
This is important to ensure all HIV-positive TB patients receive ART irrespective of CD4 count and chemoprophylaxis.
First-line ART for HIV-TB:
Tenofovir 300 mg + lamivudine 300 mg + efavirenz 600 mg (FDC)
Second-line ART for HIV-TB:
Tenofovir + lamivudine + PI (atazanavir/ritonavir or lopinavir/ritonavir)
Zidovudine + lamivudine + PI (atazanavir/ritonavir or lopinavir/ritonavir)
Stavudine + lamivudine + PI (atazanavir/ritonavir or lopinavir/ritonavir)
Abacavir + lamivudine + PI (atazanavir/ritonavir or lopinavir/ritonavir)
Rifampicin alters the metabolism of protease inhibitors, including atazanavir and ritonavir and reduces their effectiveness in standard doses.
HIV-TB collaboration − single window
Delivery of HIV-TB care at ART centers:
This single-window care comprises of the following components:
- Rapid molecular diagnosis CBNAAT.
- Daily FDC for HIV and TB.
- Information communication technology (ICT)-based adherence support (99DOTS).
- Pharmacovigilance (AMC).
- Isoniazid preventive therapy.
Progress so far:
- Training completed by NACO and CTD.
- Drugs supplied in October to November 2016.
- About 10,031 HIV-TB patients initiated on treatment.
Definitions of different treatment outcomes
Cured: Microbiologically confirmed TB patients at the beginning of the treatment who became smear or culture negative at the end of the complete treatment.
Treatment completed: A TB patient who completed the treatment without evidence of failure or clinical deterioration BUT with no records to show that the smear results of biological specimen in the last month were negative, either the test was not done or because result is unavailable.
Treatment success: TB patients either cured or treatment completed are accounted in treatment success.
Failure: A TB patient whose biological specimen is positive by smear or culture at the end of the treatment.
Failure to respond: A case of pediatric TB who fails to have microbiological conversion to negative status or fails to respond clinically or deterioration after 8 weeks of compliant IP shall be deemed to have failed response − provided alternate diagnosis/reasons for nonresponse have been ruled out.
Lost to follow-up: A TB patient whose treatment was interrupted for ≥1 consecutive month.
Not evaluated: A TB patient for whom no treatment outcome is being assigned; this includes former transfer out.
Treatment regimen changed: A TB patient who is on the first-line regimen and has been diagnosed as having DR-TB and switched to drug-resistant TB regimen prior to being declared as failed.
Died: A patient who has died during the course of the treatment with anti-TB drugs.
| 99DOTS|| |
- Patient workflow to monitor 99DOTS adherence:
- Step 1: Adult patient visits center with symptoms of TB (cough, fever, night sweats, weight loss).
- Step 2: Patients sputum sent for testing.
- Step 3: Medical evaluation for evidence of TB.
- Step 4: Patient identified positive for TB.
- Step 5: Patient counseled on 99DOTS adherence and then they are registered to Nikshay.
- Step 6: Patient takes medicines (based on weight bands) and calls a toll-free number.
- Step 7: Patient receives reminder, continuous follow-up on the adherence calendar.
- How the patient data will be accessed:
- Different ways of accessing the patient data are:
- Web dashboard (
- Every center will be given their own login ID and password to access their patients.
- Different logins for ART center, DTC, and field staff (with limited permissions).
- SMS alerts for staff and treatment supporters to take immediate actions in case of default.
- Benefits of 99DOTS:
- For patients:
- Less travel
- Increased convenience
- For field staffs/supervisors:
- Focused and more efficient care
- Program officers:
- Easy monitoring
- Accurate reports.
| Nikshay|| |
- What is Nikshay:
- Nikshay is an integrated ICT system for TB patient management and care in India.
- It is a real-time, web-based surveillance tool.
- Unified interface for public and private health-care provider.
- Nikshay webpage −
- Android mobile application available from Google Play Store.
- Demo site:
- Modalities of notification in Nikshay:
- Reporting via Nikshay Sampark (180011).
- Reporting into the Nikshay web portal or mobile application.
- Submission of hardcopies to DTO.
- Incentives to patients for social protection: These cover −
- Cost of treatment.
- Cost of diagnosis.
- Cost of travel.
- Nutritional support.
- Wage loss.
- Nikshay Poshan Yojana (launched on April 1, 2018) components are as follows:
- Nutritional support to direct benefit transfer of 500 INR per month.
- For patients on TB treatment throughout the duration of treatment.
- Patient to be registered to the Nikshay portal.
- Tribal patient incentive.
- Incentives to the treatment providers:
- Private provider incentive: There is incentive of 500 INR at the time of reporting and 500 INR on reporting the treatment outcome.
- Informant incentive: Incentive of 500 INR to informant for notification of patients in public sector.
- Incentive for treatment support:
- New case: 1000 INR at the completion of treatment.
- Drug-resistant case: 2000 INR at completion of IP and 3000 INR at completion of treatment.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11], [Table 12], [Table 13], [Table 14]