DR-TB HIV Coordinator: TB Case Finding in NTEP

Persons with cough of more than 2 weeks, with or without other symptoms suggestive of TB, should be promptly identified as presumptive pulmonary TB patients.

Under NTEP, they are to be referred to the designated microscopy centre (DMC) for sputum examination using the Request form for examination of biological specimen.

Patients belonging to the key population EPTB, HIV and Paediatrics groups (after X-ray screening in case of children) can be directly referred for NAAT.

All presumptive TB patients in the public and private sector must be evaluated for TB based on the diagnostic algorithm for pulmonary and extra-pulmonary TB (EPTB) and the following points must be considered:

• All presumptive pulmonary TB patients must be subjected to sputum smear examination. In places where TB diagnostic laboratories are upgraded to NAAT testing, NAAT can be offered for all presumptive TB patients upfront
• If both the chest X-ray and sputum smear (NAAT in integrated places) results are negative, but the physician considers the patient as presumptive TB, the patient needs to be referred to a chest physician for further evaluation
• NAAT testing will be performed to rule out Rif. resistance before treatment initiation (In places where transition has not yet been happened to NAAT for diagnosis)
• NAAT results will decide if the patient is MTB detected with either Rif. Resistance or Rif. Sensitive
• Upfront NAAT is offered for key populations like PLHIV/children/EPTB
• M.TB detected on NAAT will be further subjected for FL–LPA, SL-LPA, LC DST and based on the results DR-TB regimen may be initiated

Resources

• Technical and Operational Guidelines for TB Control in India 2016
• Revised PMDT Guidelines in India 2021

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It is crucial to make an effort for microbiological confirmation in presumptive Extrapulmonary Tuberculosis (EPTB) cases. Appropriate specimens from the Extrapulmonary (EP) site are collected and, depending on the specimen type and availability of facilities, the specimens are sent for:

• Cartridge-based Nucleic Acid Amplification Testing (CBNAAT)
• Culture and Drug Susceptibility Testing (C&DST) for M. tuberculosis 
• Histopathological examination

The diagnostic algorithm (see the figure below) to be followed for EPTB cases depends on 2 main factors:

1. Availability of appropriate specimens from the EP site
2. Availability of CBNAAT (preferred test)

Figure: Diagnostic Algorithm of EPTB

• If an appropriate specimen from the EP site is available, specimens from the presumed sites of involvement must be tested with CBNAAT.
• CBNAAT detects MTB and RIF status and helps to identify microbiologically confirmed EPTB cases.
• If CBNAAT is not available, the specimen is sent for Liquid Culture (LC) at the C&DST lab. If the LC is positive, it is identified as a microbiologically confirmed EPTB case.
• If there is high clinical suspicion of TB even after a negative culture result, other diagnostic tools are used to clinically diagnose EPTB (usually with a specialist). If these tests indicate TB, they may be treated as clinically diagnosed EPTB or else arrive at an alternate diagnosis.

Clinical Diagnosis of EP-TB

If an appropriate specimen from the EP site is not available, in the presence of high clinical suspicion of TB, other modalities of diagnosis are used in consultation with a specialist. If with other diagnostic modalities, TB diagnosis still cannot be established, the specialist may explore an alternate diagnosis. 

A clinical diagnosis of EPTB is made if a consultative decision is made to treat with a full course of anti-TB drugs in spite of the situations listed above. Chest X-ray (CXR), ultrasonography, Computerised Tomography (CT) scan, Magnetic Resonance Imaging (MRI) and biochemical examinations are supporting tests that can be used to help arrive at a diagnosis.

Resources

• Training Modules (1-4) for Programme Managers and Medical Officers, 2020.
• Technical Operational Guidelines, Chapter 3: Case Finding and Diagnosis Strategy, NTEP.

Assessment

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All children with persistent fever with/without cough for two or more weeks; close contact with TB patients in the last 2 years; unexplained sudden weight loss or signs of malnutrition despite good nutrition, should be subjected to Chest X-ray (CXR).

1) If the CXR is normal, the child should be checked for signs of Extrapulmonary TB (EPTB) and referred for detailed investigations to higher centres in case of any symptoms.

2) If the CXR is suggestive of TB, the child should be subjected to a sputum test/ gastric aspiration / induced sputum for Mycobacterium tb (MTB) testing.

               - If the report is MTB positive, the child is microbiologically confirmed for TB and should be further tested for Rifampicin (Rif)-resistance and treated accordingly for Drug-sensitive (DS)/ Drug-resistant (DR) TB, based on Rif results.

               - If the report is MTB negative, look for significantly enlarged peripheral lymph nodes and also repeat the sputum test with a good sample and refer to a higher centre if required.

3) If the CXR displays non-specific shadows prescribe antibiotics (amoxiclav/ amoxicillin) if not already taken. Do not prescribe quinolones or linezolid and review the shadow and symptoms.

4) If CXR displays pleural effusion send the pleural fluid for examination at Nucleic Acid Amplification Testing (NAAT) lab as well for cytology and biochemical examinations.

              - If pleural fluid turns out MTB positive at the NAAT, treat as per guidelines

              - If the pleural fluid is MTB negative, but is a straw-coloured exudative effusion, treat the child as clinically diagnosed probable TB.

Image

Figure: Diagnostic Algorithm for Paediatric TB; Source: Standard Treatment Workflows of India: Special Edition on Paediatric and Extrapulmonary Tuberculosis, 2022.

Resources

• Standard Treatment Workflows of India: Special Edition on Paediatric and Extrapulmonary Tuberculosis, ICMR, MoHFW, GoI, CTD, 2022.
• Guidelines on Programmatic Management of Drug Resistant TB (PMDT) in India, CTD, MoHFW, GoI, 2021.

Assessment

Drug-resistant TB (DR-TB) diagnosis is predominantly based on laboratory diagnosis. Presumptive-TB/ DR-TB is identified by the health facility doctor during passive screening or by health staff/ community volunteers during Active Case Finding (ACF). 

The vision of National TB Elimination Programme (NTEP) is to provide early diagnosis to all persons with any form of DR-TB through Universal Drug Susceptibility Testing (UDST).

All diagnosed TB patients are eligible for a NAAT test to know their Rifampicin sensitivity status. The integrated diagnostic algorithm for diagnosis of TB offers upfront Nucliec Acid Amplification Test (NAAT) for diagnosis of TB to vulnerable population. Among other eligible groups for NAAT are: non-responders to treatment and contacts of DR-TB patients are also offered upfront NAAT.

Rapid identification of DR-TB is achieved by using a combination of NAAT (CBNAAT/ Truenat) followed by sequential testing by first- and second-line Line Probe Assay (LPA) and Liquid Culture (LC) and Drug Susceptibility Testing (DST) for specific drugs as described below:

• When Rifampicin resistance is not detected by NAAT, the patient is offered First-line (FL) LPA.FL-LPA provides information on Isoniazid resistance.
• For Rif resistance/Inh resistance cases, SL-LPA  is done and it provides information on resistance to Levofloxacin, Moxifloxacin and Amikacin.
• For all Rif resistance cases, LC and DST is done for Pyrazinamid, Moxifloxacin (if resistance detected by LPA), Linezolid, Clofazimine*, Bedaquiline* and Delamanid*.

(* when available)

Resources

• Guidelines for PMDT in India, 2021.

Assessment

Check

Presumptive Drug-resistant TB (DR-TB) in Children

It occurs mostly in children who:

• Are contacts of adults with Multidrug-resistant (MDR)/ DR-TB
• Are lost to follow-up after initiating treatment
• Present with recurrence of disease after previous treatment
• Do not respond to treatment with first-line drugs
• Are Children Living with HIV (CLHIV).

All efforts must be taken to ensure microbiological confirmation of DR-TB diagnosis among children through getting an appropriate body fluid sample for both pulmonary or extrapulmonary-TB cases.

Sputum (or other relevant samples, e.g., gastric aspirate, induced sputum, bronchoscopic lavage, lymph node aspiration, Cerebro Spinal Fluid (CSF), tissue biopsies) needs to be collected in all children with presumed DR-TB for diagnosis.

The diagnosis of DR-TB in children is done based on Nucleic Acid Amplification Test (NAAT) or Line Probe Assay (LPA) results. If these are invalid, Culture and Drug Susceptibility Testing (C&DST) will be carried out to establish the diagnosis.

In a presumptive DR-TB patient, if there is no bacteriological confirmation, bacteriologically negative clinically diagnosed probable DR-TB can be considered after ruling out alternative diagnosis.

Resources

• Guidelines for Programmatic Management of Drug-resistant Tuberculosis in India, 2021.

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All childhood TB patients’ sputum and other relevant samples (e.g. gastric aspirate, induced sputum, bronchoscopic lavage, lymph node aspiration, CSF, tissue biopsies etc.) should be subjected to genotypic or the phenotypic Drug Susceptibility Tests (DSTs). Based on the bacteriological confirmation, the child should be treated for DS/DR TB as required.

But in cases where the child’s DST is unknown, the source patient’s DST should be considered.

If the source is a known DS TB, treat the child for DS TB. If the child responds poorly to the DS TB treatment consult the pediatrician and re attempt the necessary investigations.

If the source patient is a known DR TB patient, consult with the pediatrician and re-attempt DST on an appropriate specimen from the child and treat as per the child’s DST (if the report is conclusive), if not then treat the child as DR TB after the source patient.

If the source patient’s DST status is not known perform DST on the child’s and the source patient’s specimen and treat the child as per the DST of the child or the source patient, whichever report is conclusive.

Pediatric TB patients should be presented to and discussed with a DR-TBC Committee (including the pediatrician) to decide the treatment.

Image

Figure:  Diagnostic Algorithm for Paediatric DR-TB; Source: Guidelines on Programmatic Management of Drug-resistant TB (PMDT) in India,2021, CTD, MoHFW, India, p39. 

Abbr: DR-TB: Drug-resistant TB; DS-TB: Drug-sensitive TB; NAAT: Nucleic Acid Amplification Test; MGIT: Mycobacterium Growth Indicator Tube; DST: Drug Susceptibility Testing; DRT: Drug Resistance Testing; BAL: Bronchoalveolar Lavage.

Resources

• Standard Treatment Workflows of India: Special Edition on Paediatric and Extrapulmonary Tuberculosis.

• Guidelines on Programmatic Management of Drug Resistant TB (PMDT) in India, 2021, CTD, MoHFW, India.

Assessment

Based on the site of disease, Tuberculosis can be classified as-

1. Pulmonary tuberculosis (PTB) refers to any microbiologically confirmed or clinically diagnosed TB involving the lung parenchyma or the tracheo-bronchial tree.
2. Extra Pulmonary tuberculosis (EPTB) refers to any microbiologically confirmed or clinically diagnosed TB involving organs other than the lungs such as pleura, lymph nodes, intestine, genitourinary tract, joint and bones, meninges of the brain etc. 

Note: Miliary TB is classified as PTB because there are lesions in the lungs. A patient with both pulmonary and extra-pulmonary TB should be classied as a case of Pulmonary TB.

• New case - A TB patient who has never had treatment for TB or has taken anti-TB drugs for less than one month is considered as a new case. 
• Previously treated patients have received 1 month or more of anti-TB drugs in the past. They could be further classified as:
• 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 a recurrent TB case. 
• 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.  
• Treatment after loss to follow-up A TB patient previously treated for TB for 1 month or more and was declared lost to follow-up in their most recent course of treatment and subsequently found microbiologically confirmed TB case 
• Other previously treated patients are those who have previously been treated for TB but whose outcome after their most recent course of treatment is unknown or undocumented. 
• Transferred In: A TB patient who is received for treatment in a Tuberculosis Unit, after registered for treatment in another TB unit is considered as a case of transfer in.
• Transferred Out : A patient who has been transferred to another recording and reporting unit and whose treatment outcome is unknown.

Resources:

• Guidelines for Programmatic Management of Drug Resistant Tuberculosis in India, March 2021 
• WHO Consolidated Guidelines on Tuberculosis: Module 4-Treatment: Drug resistant TB Treatment, 2020

On the basis of diagnosis, Tuberculosis (TB) can be classified into 2 main types:

1. Microbiologically confirmed TB
2. Clinically diagnosed TB

Microbiologically Confirmed TB

• Microbiologically confirmed TB refers to a presumptive TB case from which a biological specimen is positive for acid-fast bacilli/ Mycobacterium tuberculosis on smear microscopy, culture, or on a rapid diagnostic molecular test (such as Cartridge-based Nucleic Acid Amplification Test (CBNAAT)/ Truenat).
• All such diagnosed cases should be notified at the source, regardless of whether TB treatment has started.

Clinically Diagnosed TB

• Clinically diagnosed TB refers to a presumptive TB case that is not microbiologically confirmed but has been diagnosed with active TB by a clinician who has decided to give the patient a full course of anti-TB treatment.
• This definition includes cases diagnosed on the basis of X-ray abnormalities or suggestive histology or extrapulmonary cases without laboratory confirmation.
• Clinically diagnosed cases subsequently found to be microbiologically positive (before or after starting treatment) should be reclassified as microbiologically confirmed.

Resources

• Training Modules (1-4) for Programme Managers and Medical Officers, 2020.
• Definitions and Reporting Framework for Tuberculosis, WHO, 2013.

Assessment