M-2: PHI Pharmacist: TB Treatment

The goals of tuberculosis treatment are:

• Rendering the patient non-infectious, breaking the chain of transmission and decreasing the infection​ pool

• Decreasing case fatality and morbidity by ensuring relapse-free cure

• Minimising and preventing the development of drug resistance.  ​

To meet the goals of treatment, the regimens should be:

• Safe, easy to administer and aid treatment adherence
• Long enough to achieve the long-term cure of the disease, and short enough to increase patient compliance.

Any treatment regimen which reduces the pill count but increases the overall treatment success is an ideal regimen to meet the goals of tuberculosis treatment.  

Resources

• Training Modules (1-4) for Programme Managers and Medical Officers, 2020.

Assessment

​

Under the National TB Elimination Programme (NTEP), strategies adopted in the treatment of TB are based on the available scientific and operational researches. These strategies are combined to ensure better treatment outcomes for the TB patients. The main strategies include:

Domiciliary Treatment

• This is a strategy that allows for the treatment of TB in a patient’s home.
• Domiciliary chemotherapy proved to be as effective as sanatoria treatment (which was the historical way of treating TB) and achieved higher cure rates.
• The patients having the social benefits of being at home. 

Short Course Chemotherapy (SCC)

• Chemotherapy of TB underwent revolutionary changes in the 70s owing to the availability of two well-tolerated and highly effective drugs – rifampicin and pyrazinamide.
• These drugs allowed for SCC and made it possible to simplify treatment and reduce its duration without reducing the therapeutic effect.
• Now with SCC regimens, it is possible to treat and cure TB patients in 6 months.
• When given daily, these regimens are effective, achieve high cure rates, prevent the emergence of drug resistance and minimize relapses.
• The shorter duration also contributes to improvement in treatment adherence.

Directly Observed Treatment (DOT)

DOT is a method whereby a trained healthcare worker or another trained designated person (treatment supporter) watches a patient swallow each dose of anti-TB drugs and document it.

• DOT can reduce the development of drug resistance, treatment failure, or relapse after the end of treatment.
• Many patients who do not receive directly observed treatment stop taking drugs once they feel better.
• Hence, by providing DOT, the NTEP ensures that patients receive the right drugs, in the right doses, at the right intervals and for the right duration.

The modern treatment strategy is based on standardized short-course chemotherapy regimens largely administered on a domiciliary basis, utilising the DOTS strategy and proper case management to ensure completion of treatment and cure.

Resources

• Training Modules (1-4) for Programme Managers and Medical Officers, 2020.
• Treatment of Tuberculosis Disease, CDC, 2006.
• Guide on Tuberculosis Control for Primary Health Care Providers, WHO, 2015.
• Treatment of Tuberculosis: Guidelines for National Programmes, WHO, 2003.

Assessment

Tuberculosis treatment and its different regimens have scientific backgrounds for their formulations. To understand this, we need to know about the mode of action of each anti-TB drug first.

Mode of Action of Anti-TB Drugs

Anti-TB drugs have the following three actions:

1. Early bactericidal activity: Killing of actively growing bacilli (in the phase of rapid multiplication and uninhibited metabolic activity).
2. Sterilizing activity of persisting bacilli, i.e., metabolically inhibited organisms in a quasi-dormant state.
3. Ability to prevent the emergence of drug resistance.

The ranking of first-line drugs with respect to their type of activity is indicated in Table 1 below.

Table 1: Ranking of first-line anti-TB drugs used in the treatment of drug-sensitive TB, based on the mode of action and activity

Thus, each drug has unique characteristics and drug combinations will make the regimen more effective.

Need for Long Duration of Treatment of TB

• Anti-TB drugs mostly kill actively multiplying tubercle bacilli.
• When bacilli have low metabolic activity, i.e., when bacterial growth has almost come to a standstill and the organisms are “dormant”, they are not killed by otherwise bactericidal drugs. Such organisms are referred to as persisters*.
• Though they may survive in the presence of drugs, behaving as if they were drug-resistant, they are in fact susceptible to the drugs.
• Thus, if for some reason these organisms regain their ability to multiply freely, they would be killed by the very drugs that had not harmed them before.
• When dormant bacilli again become metabolically active and start multiplying during effective chemotherapy, they are soon killed.
• Once chemotherapy has been completed, the revived bacilli may continue to multiply and thus cause relapse.
• This explains why conventional chemotherapy needs to be of long duration.

Resources

• Training Modules (1-4) for Programme Managers and Medical Officers, 2020.
• Tuberculosis Case-finding and Chemotherapy: Questions and Answers, K. Toman.

 Assessment

Standard TB Treatment is divided into two phases

• Intensive Phase(IP): In this phase,
  • Kills most of the TB bacteria during the first 8 weeks of treatment, but some bacteria can survive longer
  • Therefore, more drugs are administered to kill the bacteria and reduce the severity of disease.
  • Treatment in this phase usually is of short duration(2 to 6 Months or more) in comparison to Continuation Phase(CP)

• Continuation Phase(CP): In this phase,
  • All the remaining TB bacteria are in the dormant stage i.e., stage when growth and development of bacteria are temporarily stopped.
  • Therefore, fewer but powerful antibiotics are administered to kill those bacteria. 
  • Treatment in this phase usually lasts longer than Intensive Phase(IP)(4 to 18 Months or more)

Kindly provide your valuable feedback on the page to the link provided HERE

Fixed-dose combinations (FDCs) are drug formulations where two or more drugs are combined physically into one formulation such as a tablet or pill.

This is more convenient to the patients taking medicines and it also simplifies the supply chain.

Resources:

• Technical and Operational Guidelines for TB Control in India 2016

Kindly provide your valuable feedback on the page to the link provided HERE

Fixed-Dose Combination(FDC) provides a simple approach to deliver the correct number of drugs at the right dosage as all the necessary drugs are combined in a single tablet. By altering the number of pills according to the patient’s body weight, complete treatment is delivered without the need for calculation of dose

Figure: Advantages of Fixed Dose Combination(FDC)

A regimen means a prescribed systematic form of treatment for a course of drug(s). For TB treatment, Multi drug combination of regimen is followed. 

All TB drug regimens have an initial intensive phase(IP) followed by a continuation phase(CP). 

Following are some of the main TB drug regimens used based on the drug resistance pattern detected for TB patients.

• First-Line Anti TB Drugs(Prescribed for Drug Sensitive TB DS-TB)
  • Daily weight band wise FDC

• Second-Line Anti TB Drugs (Prescribed for Drug Resistance TB - DR-TB)
  • H Mono Poly Regimen
  • Shorter oral Bedaquiline containing MDR-TB regimen
  • Longer oral Bedaquiline containing regimen
  • Shorter injectable containing MDR-TB regimen

To know the TB treatment response and to determine that if patient is cured, TB patients are clinically evaluated at the end of every four weeks of treatment, and they are also followed up by performing sputum test at end of each treatment phase (i.e. Intensive phase and Continuation phase)

TB patients during clinical evaluations are assessed to

• Identify possible adverse reactions to medications;
• Check for any comorbid conditions;
• Weight change;
• monitor adherence; and determine treatment efficacy by observing their symptoms

Although each patient responds to treatment at a different pace, all TB symptoms should gradually improve and eventually go away.

Patients whose symptoms do not improve during the first 2 months of treatment, or whose symptoms worsen after improving initially, should be re-evaluated for adherence issues and development of drug resistance.

After completion of TB treatment, all patients should be followed up at the end of

• 6 months,
• 12 months,
• 18 months &
• 24 months

TB patients at the follow up should be screened for any clinical symptoms and/or cough. If found positive on screening, then sputum microscopy and/or culture should be considered. This is important in detecting the recurrence of TB at the earliest.

After completion of TB treatment, if the patient has not developed any clinical symptoms and/or cough and also if the microscopy remains negative during their follow up, then the patient is considered as “Relapse Free Cure from TB.”

When a TB patient consumes all the doses under the prescribed regimen, then Treatment Outcome is declared for a Patient.

Treatment success is considered when a TB patient either Cured or Treatment completed is accounted in treatment success

Adverse Drug Reactions(ADR) are unwanted or harmful reactions experienced following the use of a drug or combination of drugs and are suspected to be related to a drug. Severity of adverse effects varies from tolerable and mild ADRs to serious and life threatening ADRs.

Figure: Various Adverse Drug Reactions

Common ADR Symptoms:

• Pain in upper abdominal area, with loss of appetite
• Nausea – Uneasy feeling with inclination to vomit, after having the drugs
• Gastritis – Burning sensation in lower chest region, bloating sensation, sourness in mouth
• Diarrhoea - Loose stool(2-3 in a day)

Adverse Drug Reactions(ADR) are classified into serious and non-serious ADR depending upon the intensity of symptoms experienced by the patient. Below is the brief overview

1. Counsel and reassure the patient as the common occurring adverse effects usually resolve with time.
2. Advise the patient to take all the drugs together.
3. Advise patient to take light meal (biscuits, bread, rice etc.) before taking drugs.
4. Inform patients that they may take drugs embedded in banana or at the bedtime to reduce their associated side effects.
5. Encourage patients to keep themselves hydrated by increasing fluid intake.
6. Provide ORS (Oral Rehydration Solution) to counter dehydration due to loose motion and vomiting.

Figure: Referral to PHI for ADR

Resources:

• Training Guide for Peripheral Health Workers on Adverse Drug Reactions

Kindly provide your valuable feedback on the page to the link provided HERE

The Tuberculosis Treatment Card is a paper-based recording form that is kept in the institution treating the TB patient under the National TB Elimination Programme (NTEP). It is a pre-requisite documentation related to treatment services offered to TB patients under NTEP.

Uses of the TB Treatment Card

The TB treatment card is primarily used for:

1. Documenting administered drugs with their dosages
2. Documenting follow-up investigation results
3. Monitoring adherence to treatment
4. Recording adverse events
5. Recording treatment outcomes

There are two pages in the TB treatment card and details in each page is delineated in the table below.

Important Points to Note

• The TB treatment card is filled at the Peripheral Health Institution (PHI) when a patient is initiated on treatment.
• The original TB treatment card is kept at the PHI and updated fortnightly.
• A duplicate treatment card is to be given to the treatment supporter for documentation of daily events. 
• The treatment supporter should be trained on how to record the treatment card. 
• Details on the patient’s HIV status are not included in the treatment supporter’s copy to maintain confidentiality.

The figure below shows the 1^st page of the TB treatment card. Click here to access the full form in the NTEP Training Modules 1-4 for Programme Managers & Medical Officers, p. 223.

Figure: First Page of the TB Treatment Card; Source: NTEP Training Modules 1-4 for Programme Managers & Medical Officers, p. 223

Resources

• NTEP Training Modules 1-4 for Programme Managers & Medical Officers, 2020.

Kindly provide your valuable feedback on the page to the link provided HERE

In the National TB Elimination Programme (NTEP), the ‘NTEP TB identity card’ is provided for their identification and record of clinical follow-ups.

The identity card is completed for each patient who has a Tuberculosis (TB) Treatment Card, and it is kept with the patient. Information from the TB Treatment Card is used to complete the identity card.

There are 3 parts in the NTEP TB identity card and details in each part is delineated in Table 1.

The information contained in this card will help to continue treatment in case the patient is transferred or admitted to any other health facility any time during the treatment period. The TB identity card is shown in Figure 1.

Figure 1: NTEP TB Identity Card; Source: NTEP Training Modules 1-4 for Programme Managers & Medical Officers, 2020

Resources

• NTEP Training Modules 1-4 for Programme Managers & Medical Officers, 2020

Kindly provide your valuable feedback on the page to the link provided HERE

TB patients may not stay in one place throughout the treatment duration. When they move from one place to other, there should be a mechanism to hand over the responsibility of continuing the patient's treatment in a facility near the new place of the patient. This is the concept of patient transfer and can be easily managed in Nikshay portal.

• The transfer module in Nikshay enables transfer requests of patients between Health Facilities (HFs) across the country.
• Provision of shifting of patient from one HF to another is possible if the patient changes his/her residence for the purpose of treatment.
• The requests are of two types: “Transfer In” and “Transfer Out”.
• All transfer requests needs to be accepted by the “District/ TB Unit (TU)/ Peripheral Health Institute (PHI)” where the transfer request is made in order for it to take effect.
• Transfer requests can be made to even the District/ TU level. However, it can be completed only once the “Transferred to PHI” has been assigned.

Figure: Transfer Management in Nikshay; Source: Nikshay Zendesk, Nikshay Knowledge Base, Advanced Transfer in Web.

Steps in Transfer of TB Patient

1. In Nikshay, the referring HF updates details from the current HF of patient to the HF where patient is being transferred.

2. The receiving HF gets the intimation about the transfer.

The patient transfer module also provides the provision to pull the patient belonging to another HF to the recipient HF. The accountability of the transferred patients is now with the receiving HF and the treatment initiating facility.

A separate transfer register is also available to get details about various transfers from and to a given district, which can be downloaded from Nikshay reports.

Resources

• Nikshay Zendesk, Nikshay Knowledge Base, Advanced Transfer in Web.
• Guidelines for PMDT in India, 2021.

Assessment

​The management principles of Extrapulmonary Tuberculosis (EPTB) are shown in the figure below.

Figure: Ten principles about what every EPTB patient in India needs as a basic standard of care

Abbr: CBNAAT:Cartridge-based Nucleic Acid AMplification Test; PTB: Pulmonary TB; NTEP: National TB Elimination Programme

Diagnosis of EP-TB

• All efforts need to be made to get a microbiological confirmation whenever a sample is available. 
• Clinical diagnosis can be made by treating physician based on the clinical features, lab investigations, imaging studies and by ruling out other causes

Treatment Regimen and Duration for EPTB

The treatment regimen and schedule for EPTB cases will remain the same as for pulmonary TB (2HRZE/ 4HRE). However, the duration of the continuation phase in EPTB may be extended in special situations such as TB Meningitis, bone and spine TB etc.

Role of Surgery in EPTB Cases

• Surgery is sometimes required for the diagnosis of EPTB. It is reserved for management of late complications of the disease.

Monitoring Treatment Response

• Response to treatment in EPTB may be best assessed clinically. Clinical follow-up is the most important criterion for the follow-up of EPTB patients. The clinician can assess the patient’s condition by checking weight gain and a decrease/ increase in presenting clinical symptoms.
• Investigations such as Acid-fast Bacilli (AFB) microscopy, chest X-ray, liver function tests, serum creatinine, and USG-abdomen can be used to monitor the treatment status.

The treatment support and other monitoring activities remain the same as for pulmonary TB.

Resources

• Training Modules (1-4) for Programme Managers and Medical Officers, 2020.
• Index TB Guidelines on Extra-pulmonary Tuberculosis for India, Central TB Division, 2016.

Assessment

Treatment interruption is defined as a patient-initiated episode in which the patient discontinues TB treatment. All efforts must be made to ensure that TB patients do not interrupt treatment or are not lost to follow-up. Action should be taken to promptly retrieve patients who fail to come for their daily dose by the treatment supporter

The management of treatment interruptions is made based on the following criteria:

i. Type of case: Whether new, relapse or failure

ii. Duration of treatment taken: Less than one month/ more than one month. This helps in assessing the risk of the presence of drug resistance.

iii. Duration of Interruption: Less than one month/ more than a month.

If treatment interruption is more than one month, the outcome is declared as ‘lost to follow up’.

If a patient returns to the health facility after interrupting treatment for more than one month, the patient sample needs to be subjected to Drug Susceptibility Testing (DST) to determine resistance/ sensitivity status to anti-TB drugs.

In case the interruption is for less than one month, the same treatment regimen is completed to complete all doses.

Modes of Retrieval

TB treatment is supervised by a trained treatment supporter (a health worker, family member or community volunteer). The residential address is verified for all TB patients by home visits. However, in case of treatment interruption, patient retrieval action is required.

Retrieval can be done by the following modes:

1. Retrieval of patients interrupting treatment within 24 hours of discontinuation is done by the Treatment Supporter (TS) or Accredited Social Health Activist (ASHA)/ Auxilliary Nurse Midwife (ANM)/ Multipurpose Worker (MPW). The reason for interruptions should be reviewed carefully and efforts made to counsel and bring the patient back for treatment.

2. If the TS is not successful in retrieving such patients, it should be reported to the next higher level of supervisors, like Senior Treatment Supervisor (STS), and they should take all efforts to counsel and retrieve the patient.

3. If the patient interrupts treatment on more than one occasion, the Medical Officer of the Peripheral Health Institute (MO-PHI) should visit the patient’s home. The MO-PHI should give intensive counselling to the patient and may provide additional support to continue the treatment without interruption.

4. Innovative use of information and communication technologies for treatment adherence monitoring through 99 DOTS, Medication Event Reminder Monitor (MERM), etc. are also beneficial in finding missed doses and initiating retrieval action by the health staff.

Resources

1. Training Modules (1-4) for Programme Managers and Medical Officers.

2. Guidelines for PMDT in India, 2021.

Assessment

There are five principal ways to prevent Drug-resistant Tuberculosis (DR-TB), as given in the figure below.

Image

 Figure: Five Principal Ways to Prevent DR-TB; Source: Guideline for PMDT in India, 2021.

• Drug resistance cannot be prevented by mere diagnosis and treatment of DR-TB.
• Basic TB diagnostic and treatment services should receive priority for the prevention of drug resistance.
• Systems for early detection and treatment of DR-TB should be integrated into the existing TB services and the general health system.
• Healthcare facilities and congregate settings should be provided with proper infection control measures.
• Transmission should be prevented by addressing non-specific determinants like access to care, comorbidities and awareness.

Resources

• Guidelines for PMDT in India, 2021.
• Companion Handbook to the WHO Guidelines for the Programmatic Management of Drug-resistant Tuberculosis.

Kindly provide your valuable feedback on the page to the link provided HERE

The suggested treatment regimen covering maximum non-Mycobacterium Tuberculosis (NTM) mainly Mycobacterium Avium Complex (MAC) is as follows: 

• Rifampicin (R) 450-600 mg OD
• Ethambutol (E) 800-1200 mg OD
• Clarithromycin (Clr) 1 gm OD (split into two doses)
• Add injection Amikacin (Am) 750 mg – 1 gm thrice weekly for the first 2-3 months

Intensive Phase (IP) is for 3 months and can be extended to a maximum of 6 months with all four drugs. 

Continuation Phase (CP) of treatment will be with the same drugs except for injectable. This should be continued for 12 months after sputum culture conversion. Drugs will be given as per the standard weight bands.

If the patient does not culture convert by end of 3 months, then species identification and Drug Susceptibility Testing (DST) are required for further management. 

Management of complicated/ invasive TB disease:

• Recommended initial regimen for most patients with nodular/ bronchiectatic MAC lung disease:
  • Thrice-weekly regimen including Clarithromycin 1000 mg or Azithromycin 500 mg, Ethambutol 25 mg/kg, and Rifampicin 600 mg administered three times per week.
• Recommended initial regimen for fibro-cavitary or severe nodular/ bronchiectatic MAC lung disease: 
• Clarithromycin 500-1000 mg/day or Azithromycin 250 mg/day, Ethambutol 15 mg/kg/day, and Rifampicin 10 mg/kg/day (maximum, 600 mg). 

Points to Note

• Intermittent drug therapy is not recommended for patients who have a cavitary disease, patients who have been previously treated, or patients who have moderate or severe disease.
• The primary microbiologic goal of therapy is 12 months of negative sputum cultures while on therapy; therefore, sputum must be collected from patients for Acid-fast Bacilli (AFB) examination throughout treatment on monthly basis in IP and quarterly basis in CP after culture conversion is achieved.
• Given these complexities, the treatment of NTM will be the prerogative of the Nodal Drug-resistant TB Centres (NDR-TBCs).

Resources

• Training Modules (1-4) for Programme Managers & Medical Officers (NTEP), 2020.
• British Thoracic Society Guidelines for the Management of Nontuberculous Mycobacterial Pulmonary Disease, 2017.
• Guidelines for Programmatic Management of Drug-resistant Tuberculosis in India, March 2021.

Kindly provide your valuable feedback on the page to the link provided HERE

Daily Regimen is prescribed for Drug Sensitive TB patients (DSTB), where the patient needs to consume the FDC formulation daily.

Daily Regimen comprises the first line Anti TB drugs based on

• Age: Adult/ Pediatric
• Weight of the patient: Weight Bands

Age: Based on age, patients are categorized into

• Adults: The patient's age should be greater than 19 years
• Paediatrics: Patient's age up to 19 years and weight less than 39 Kgs

Weight Bands: 

• Treatment dosages are based on TB patients’ weight.
• A weight band category is defined for Adults and Pediatric patients separately, and FDC are issued based on that weight category.

Intensive Phase(IP): Consists of eight weeks (56 doses) of HRZE in daily dosages as per weight of patient.

Continuation Phase(CP): Consists of 16 weeks (112 doses) of HRE in daily dosages as per weight of patient.

For adults, there are five weight bands, as shown in the table below. The table also indicates the number of FDC tablets that have to be consumed in each weight band

Regular monthly follow up of the patient needs to be done and if patient loses or gains approx. 5 kg weight and if weight band changes during the treatment, then the dose of the patient needs to be recalculated.
 

Intensive Phase (IP)

Consists of eight weeks (56 doses) of HRZ in daily dosages as per weight of patient.

Ethambutol (E) is given separately for children to monitor ophthalmic side effects.

Continuous Phase (CP)

Consists of 16 weeks (112 doses) of HRE in daily dosages as per the weight of the patient.

In Pediatric, there are six weight bands’s as shown in the table below. The table also indicates the number of FDC tablets  that has to be consumed in each weight band

Regular monthly follow-up of the paediatric patient needs to be done and if the patient weight crosses the range of the weight band during the treatment, then the weight band of the patient should be changed immediately.

Children above 39 kg shall usually be adolescents, the drug dosage requirement for them would be similar to adults

Resources:

• Technical and Operational Guidelines for TB Control in India 2016

Kindly provide your valuable feedback on the page to the link provided HERE

Community Health Volunteers(CHVs) have to refer the presumptive cases identified based on the r symptom screening to the nearest NTEP health facility for further investigation. Once Diagnosed with TB, the TB patients are initiated on the first-line TB treatment. Patients are also offered NAAT within a maximum of 15 days to rule out any drug resistance. If no drug resistance is detected, then the patient continues on the first-line TB treatment. TB patients are then clinically evaluated every month to check the progress of TB treatment. 

The treatment duration of TB is divided into two phases - The Intensive Phase(IP) and the Continuation Phase(CP). Post-treatment completion, patients are then evaluated at intervals of 6,12,18 and 24 Months to ensure a relapse-free TB cure for the patient.

Figure: DSTB Treatment Flow

What is Drug-Resistant Tuberculosis?

• Drug-Resistant TB occurs when bacteria become resistant to the drugs used to treat TB. This means that the drug can no longer kill the TB bacteria.

• Multidrug-resistant TB (MDR TB) is a type of DR-TB where TB bacteria is resistant to both Isoniazid and Rifampicin, the two most potent anti-TB drugs.

                               Figure: High Risk for Drug-Resistant Tuberculosis (DRTB)

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

Goals of Drug-resistant Tuberculosis (DR-TB) treatment under the National Tuberculosis Elimination Program (NTEP) are as follows:

Image

Figure: Goals of DR-TB Treatment; Source: Guidelines for PMDT in India, March 2021, p41.

Resources

• Guidelines for Programmatic Management of Drug-resistant Tuberculosis in India, March 2021.
• Technical and Operational Guidelines for TB in India, 2016. 

Kindly provide your valuable feedback on the page to the link provided HERE

All patients diagnosed with TB should have universal access to rapid DST for at least Rifampicin and further DST for at least Fluoroquinolones among all TB patients with rifampicin resistance, i.e. UDST. 

UDST tests are offered preferably before treatment initiation to a maximum within 15 days from diagnosis. Based on the UDST test result, if Rifampicin resistance is detected, the patient is shifted to DR-TB Treatment Regimen. If Rifampicin resistance is not detected, then first-line anti TB treatment is continued, and the patient is screened further on their follow-ups. If tested positive in sputum examination during any patient follow up, then sputum is sent for further drug resistance testing, and the patient is referred to PHI for follow-up.

Figure: Screening of patient for initiating DRTB Treatment from DSTB Treatment

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

Depending upon type of drug resistance, there are four broad DRTB Treatment regimen.

1. H Mono/Poly Treatment Regimen(6-9 months)
2. Shorter oral Bedaquiline containing MDR/RR-TB regimen(9-11 months)
3. Shorter injectable containing regimen(9-11 months)
4. Longer oral M/XDR-TB regimen(18-20 months)

Drugs administered for DRTB Regimen:

• Drugs are decided based on the drug resistance detected for a patient and will be informed by the medical officer.
• Injections might also be administered to the admitted patient.
• H Mono/Poly Regimen can be initiated at any health facility, while the other two regimen need to be initiated at N/DDR-TB Centre

Figure: Patient wise boxes(PWB) for DRTB Treatment

PTE Objective

Drugs used for the treatment of drug-resistant TB have significant adverse effects. Hence, there is a need for PTE to rule out any underlying condition at the baseline, like co-morbid conditions, radiological abnormalities, Electrocardiogram (ECG) changes, or biochemical derangements. 

PTE is essential to identify:

• The patient's eligibility for initiation of a particular regimen
• Patients who require special attention during treatment
• Regimen modifications from the beginning of treatment

Important Points 

• In the majority of Multidrug-resistant (MDR)/ Rifampicin-resistant Tuberculosis (RR-TB) patients, PTE can be done on an outpatient basis.
• The District TB Officer (DTO) and Medical Officer of the TB Unit (MO-TU) can arrange for PTE at the Nodal and District DR-TB Centre (N/DDR-TBC) or at the sub-district level health facility, wherever feasible.
• No additional investigations are required for H Mono/ Poly DR-TB patients unless clinically indicated.
• The PTE carried out at the time of treatment initiation can be considered valid for 1 month from the date of the test result and the patient can be re-initiated on a subsequent regimen considering the previously conducted PTEs.
• Active Drug Safety Management and Monitoring (aDSM) treatment initiation forms are required to be completed for all DR-TB patients at the time of initiation of each new episode of treatment.
• PTE should include a thorough clinical evaluation by a physician and expert consultation as per the need. 
• Laboratory-based tests should be performed based on the drugs used in the treatment regimen.
• Pre-treatment evaluation should be made available free of charge to the patient.​

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.

The anti-TB drugs recommended for treatment of Multi- and Extensively Drug-resistant (M/XDR) TB patients are grouped into three groups –  A, B and C (Figure below).

Figure: Groups A, B and C of Anti-TB Drugs used in Treatment of M/XDR-TB Patients

Grouping of drugs is done based on their efficacy, experience of use and drug class. This grouping is intended to guide the design of individualized, longer M/XDR-TB regimens (the composition of the recommended shorter MDR/RR-TB regimen is largely standardized).

Resources

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

Kindly provide your valuable feedback on the page to the link provided HERE

Figure: Sirturo 100 mg Bedaquiline Tablets

Newer anti-TB drugs are needed to improve the treatment outcomes of DR-TB, shorten the duration of treatment, address the problem of drug resistance, and have less toxic drugs. Five decades after the discovery of Rifampicin, two newer drugs with anti-TB effects were approved for the treatment of multidrug-resistant tuberculosis (MDR-TB) by the Central Drugs Standard Control Organization (CDSCO). These are: Bedaquiline (Bdq) Delamanid (Dlm) In July 2020, the Drug Controller General of India (DCGI) also approved a third newer drug - Pretomanid (Pa) to use under the Conditional Access Programme (CAP) under the National Tuberculosis Elimination Program (NTEP).

Resources

• The Use of Bedaquiline in the Treatment of Multidrug-resistant Tuberculosis, Interim Policy Guidance, WHO, 2013.
• The Use of Delamanid in the Treatment of Multidrug-resistant Tuberculosis in Children and Adolescents, Interim Policy Guidance, WHO, 2016.
• WHO Consolidated Guidelines on Tuberculosis, Module 4: Treatment- Drug-resistant TB Treatment.  
• Guidelines for Programmatic Management of Drug-resistant Tuberculosis in India, March 2021.

Kindly provide your valuable feedback on the page to the link provided HERE

The dosage for Drug-resistant TB (DR-TB) drugs used in the regimen by weight bands for adults are enumerated in the table below.

Resources

• Guidelines for Programmatic Management of Drug-resistant Tuberculosis in India, March 2021.
• Companion Handbook to the WHO Guidelines for the Programmatic Management of Drug-resistant Tuberculosis, 2014.

Kindly provide your valuable feedback on the page to the link provided HERE

The principles of designing Drug-resistant TB (DR-TB) treatment regimens (Shorter or longer oral Multi (M)/ Extensively Drug-resistant TB (XDR-TB), and H mono/ poly DR-TB regimens in children are similar to adults:

• Children, aged 5 years to less than 18 years of age and weighing at least 15 kg, are eligible for both longer oral and shorter oral Bedaquiline-containing Multidrug-resistant (MDR)/ Rifampicin-resistant TB (RR-TB) regimens.​
• Management of H mono/ poly DR-TB in children will be the same as in adults and child-friendly formulations can be used.
• The drug doses should be used as per paediatric weight bands.
• Bedaquiline (Bdq) tablets suspended in water have been shown to have the same bioavailability as tablets swallowed whole and therefore, should be used to treat DR-TB in children until a child-friendly formulation becomes available.​
• Delamanid (Dlm) is already approved for treating M/XDR-TB under the National TB Elimination Programme (NTEP) for children from 6 years onwards.​
• As in adults, the extension of Bdq beyond 6 months and concomitant use of Bdq and Dlm in special situations will apply to children as well. ​
• Treatment can be directly extended to 9 months in certain conditions like extensive disease, extrapulmonary TB, uncontrolled comorbidity, smear-positive cases at the end of the 4th month and when the regimen is modified.
• Shortening the total treatment duration to less than 18 months may be considered in children without the extensive disease.​
• For children under 5 years of age, where neither Bdq nor Dlm is approved yet, the longer oral M/XDR-TB regimen should be suitably modified as per the replacement drug. A suitable regimen can be designed considering child-friendly formulations where Bdq can be replaced with Amikacin (Am), Pyrazinamide (Z) or Ethionamide (Eto) in the initial phase.​
• Children below 5 years are not excluded from short-course regimens, instead receive short course injectables till further evidence on the use of Bdq is available.
• The use of injectable agents in children should be exceptional and limited to salvage treatment and be monitored for early detection of ototoxicity. 
• Meropenem is the preferred drug over imipenem in TB meningitis considering the risk of seizures in children due to Imipenem.

Additional Information

• Achieving an appropriate dose in children aged 3-5 years will be easier when the special formulation dispersible 25 mg tablet used in trials in these age groups becomes available.​
• The recent data review for the World Health Organization (WHO) guidelines suggested that there are no additional safety concerns for concurrent use of Dlm with Bdq.​
• For treatment and management of adverse drug reactions in children, there should be provision for treatment in consultation with a specialist. 

Resources

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

Kindly provide your valuable feedback on the page to the link provided HERE

Common Adverse events to second line treatment are as below

Figure: Adverse Drug Reaction to Second line drugs

Adverse events should be identified, monitored and be referred to

• Nearest treating doctor for minor symptoms or
• District DR-TB Centres for major symptoms

If required, hospitalization can be done at the District DR-TB Centers where inpatient facility is available or referred to a Nodal DRTB Centre for admission

Resources

• Guidelines for Programmatic Management of Drug Resistant Tuberculosis in India, March 2021
• Ready reckoner for Medical Officer -Adverse Drug Reactions Associated with Anti-TB Drugs identification and Management, 2019

Based on the World Health Organization (WHO) treatment guidelines, 2020 recommendations, the National TB Elimination Programme (NTEP) have decided to transition from the current shorter injectable-containing Multi-drug Resistant (MDR)/ Rifampicin-resistant TB (RR-TB) regimen to the shorter oral bedaquiline-containing MDR/RR-TB regimen in the year 2021.​

Salient Features of the Shorter Oral Bedaquiline-containing MDR/RR-TB Regimen

• This regimen will be used in patients >5 years of age weighing 15 kg or more.​
• The regimen will be expanded in a phased manner starting with selected states to gain programmatic experience to guide future expansion within 2021.​
• The regimen consists of an initial phase of 4 months that may be extended up to 6 months and a continuation phase of 5 months, giving a total duration of 9-11 months. Bdq is used for a duration of 6 months.​

​

Figure 1: Regimen and duration of shorter oral Bdq-containing MDR/RR-TB regimen

Abbr: Bdq - Bedaquiline, Lfx- Levofloxacin, Cfz- Clofazamine, Z- Pyrazinamide, E- Ethambutol, H^h- High-dose Isoniazid, Eto- Ethionamide​

Points to Note

• From the start to the end of 4 months these drugs are used: Bedaquiline, Levofloxacine, Clofazamine, Pyrazinamide, Ethambutol, high-dose Isoniazid, Ethionamide
• From the start of 5 months to the end of 6 months (If IP not extended): Bdq, Lfx, Cfz, Z, E
• From the start of 7 months to the end of 9 months: Lfx, Cfz, Z, E

If the IP is extended up to 6 months, then all 3 drugs Bdq, Hh and Eto are stopped together

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. 

Kindly provide your valuable feedback on the page to the link provided HERE

The total duration of treatment in this regimen is 9-11 months with Intensive Phase (IP) at least 4 months and Continuation Phase (CP) for 5 months. Treatment extension of IP is done up to 2 months based on follow-up results and is indicated in the algorithm presented in the figure below.

Figure: Treatment Extension/ Regimen Change Based on Follow up Smear/ Culture/ DST Results

Abbr: FL & SL- LPA- First Line & Second Line- Line Probe Assay, C&DST- Culture and Drug Susceptibility Test, Z- Pyrazinamide,  Cfz- Clofazimine, FQ- Fluoroquinolone, N/DDR-TBC- Nodal/ District DR-TB Centre

Resources

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

Drug dose administration for shorter/ longer oral Bedaquiline (Bdq)-containing Multidrug-resistant (MDR)/ Rifampicin-resistant (RR)-TB regimen depends on the factors described below.

• The dosage of second-line anti-TB drugs would vary as per the weight of the Drug-resistant TB (DR-TB) patients.​ There are five weight bands in adult patients (≥ 18 years): <16 kg, 16-29 kg, 30-45 kg, 46-70 kg and >70 kg. The weight bands of adult patients for Drug-sensitive TB (DS-TB) patients are different compared to DR-TB patients.
• All morning doses should be supervised by the treatment supporter via Directly Observed Treatment, Short-course (DOTS).​
• In patients with drug intolerance, Cycloserine (Cs), Ethionamide (Eto) and Sodium (Na) Para Aminosalicylic Acid (PAS), can be given in two divided doses.​ Pyridoxine should be provided as part of the regimen till the end of treatment for all patients. ​​

Change in Weight Bands during Treatment​

• For adult DR-TB patients whose weight increases or decreases by 5 kg or more compared to baseline weight and crosses the current weight band during the course of the treatment, the weight band must be changed at the time of issuing next month's box to the treatment supporter of the patient.
• For paediatric patients, the drug dosage should be adjusted immediately once the weight of the patient crosses the range of the weight band. Counsel the patient about the change in dose.

​Key Considerations for Newer Drugs ​

• Avoid milk-containing products with drugs: The calcium in the milk can decrease the absorption of Fluoroquinolones (FQs)​.
• Avoid large fatty meals: Fat impairs the absorption of anti-TB drugs (Cs, Isoniazid (H), etc.).​

Resources

• Guidelines for Programmatic Management of Tuberculosis in India, 2021.
• The Use of Bedaquiline in the Treatment of Multidrug-resistant Tuberculosis: Interim Policy Guidance, 2013

In adults, the dosage of drugs for a shorter oral Bedaquiline (Bdq) - containing Multi-drug Resistant (MDR)/ Rifampicin-resistant Tuberculosis (RR-TB) regimen, varies according to their weight. 

The table below provides drug dosages for adult patients, according to their weight bands, in a shorter oral Bedaquiline-containing MDR/RR-TB regimen.

Resources​

• Guidelines for Programmatic Management of Drug-resistant Tuberculosis in India, March 2021.
• The Use of Bedaquiline in the Treatment of Multidrug-resistant Tuberculosis: Interim Policy Guidance, 2013.

Kindly provide your valuable feedback on the page to the link provided HERE

Drugs that are part of the shorter Bedaquiline (Bdq)-containing regimen have some typical side effects which need close monitoring of Drug Resistant-TB (DR-TB) patients while providing the treatment.

Resources​

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

Kindly provide your valuable feedback on the page to the link provided HERE

Longer oral Multi (M)/ Extensive Drug-resistant (XDR) -TB treatment is specified with a definite regime and duration.

Regimen: (18-20) Levofloxacin (Lfx), Bedaquiline (Bdq) (6 months or longer), Linezolid^# (Lzd), Clofazimine (Cfz), Cycloserine (Cs)​​ (^# dose of Lzd will be tapered to 300 mg after the initial 6–8 months of treatment)​

• Duration: 18-20 months
• No separate Intensive Phase (IP) and Continuation Phase (CP).
• Bdq will be given for 6 months and extended beyond 6 months as an exception.
• Pyridoxine should be given to all Drug-resistant TB (DR-TB) patients as per the weight bands.
• For Extensively Drug-resistant TB (XDR-TB) patients, the duration of a longer oral XDR-TB regimen would be for 20 months.

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.

Kindly provide your valuable feedback on the page to the link provided HERE

The total duration of a longer oral Multidrug/ Extensively drug-resistant TB (M/XDR-TB) regimen is 18–20 months. ​

Image

Figure: Protocol for Treatment Extension in Longer Oral M/XDR-TB Treatment Regimen

Extension of Bedaquiline (Bdq) beyond 6 months is to be considered in patients in whom an effective regimen cannot otherwise be designed.

• If any additional resistance to Group A, B or C drugs in use is detected, the patient needs to be reassessed at the Nodal/ District Drug-resistant Tuberculosis Centre (N/DDR-TBC) for modification of a longer oral M/XDR-TB regimen immediately on receiving the report.
• A treatment duration of 15–17 months after culture conversion is suggested for most patients. The duration may be modified according to the patient’s response to treatment.

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. 

Kindly provide your valuable feedback on the page to the link provided HERE

The table below showcases the adverse drug events that may be caused by drugs used for longer oral Multi (M)/ Extensively Drug-resistant TB (XDR-TB) regimen. In these situations, replacement drugs are used instead of these drugs.

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.

Kindly provide your valuable feedback on the page to the link provided HERE

It is important to know the dosages of Multi (M)/ Extensively Drug-resistant TB (XDR-TB) drugs for adults on a longer oral M/XDR-TB regimen.​

The table below shows the M/XDR-TB regimen drugs for adults weight band-wise, used in longer oral M/XDR-TB regimen customized for India by national experts.

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.

Kindly provide your valuable feedback on the page to the link provided HERE

Isoniazid (H) mono/ poly Drug-resistant TB (DR-TB) regimen has the following regimen, duration and dosage of drugs.

Regimen: (6 or 9) Lfx R E Z

Dosage

• The dosage of drugs would vary as per the weight of the patients.
• Adult patients (≥ 18 years) would be classified in weight bands of <16 kg, 16-29 kg, 30-45 kg, 46-70 kg and 70 kg. The drug dosages by these weight bands are shown in the table below.
• All drugs in the regimen are to be given on a daily basis under observation.

Duration

• H mono/ poly DR-TB regimen is for 6 or 9 months with no separate Intensive Phase (IP)/ Continuation Phase (CP).
• In exceptional situations of unavailability of loose drug R or E or Z, the use of 4 FDC (HREZ) with Levofloxacin (Lfx) loose tablets may be considered as an option rather than not starting the H mono/ poly DR-TB patients on treatment.

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.

Kindly provide your valuable feedback on the page to the link provided HERE

he potential adverse drug events that can occur when using drugs in the H mono/ poly DR-TB regimen are tabulated below:

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.
• Technical and Operational Guidelines for TB in India, 2016.

Kindly provide your valuable feedback on the page to the link provided HERE

• TB Infection (or previously known as Latent TB infection) is a stage in between uninfected and having active TB. In this stage the person has no symptoms and can only be identified using laboratory tests.

• The vast majority of infected people may never develop TB disease. However, to achieve TB elimination, it is important to treat TB infection in people at risk of developing active TB disease.

• It is a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens with no evidence of clinically manifested active TB.

• There is no single acceptable/reliable test for direct identification of Mycobacterium tuberculosis infection in humans. Tuberculin Skin Test (TST) and Interferon-gamma release assay (IGRA) are commonly used tests for identifying TB infection.

Resources:

• Latent Tuberculosis Infection Guideline

• Guideline for Programmatic Management of Tuberculosis Preventive Treatment in India

For TB infection, there are two recommended tests which can be used to identify such patients.

Tuberculin Skin Test (TST)

The skin test is done by injecting a small amount (0.5 ml) of TB antigens into the top layer of skin on your inner forearm. If one has ever been exposed to TB bacteria (Mycobacterium tuberculosis), there will be a reaction indicated by the development of a firm red bump (induration) >= 10 mm at the site within 2 days.

Image

Figure: Tuberculin Skin Test

Interferon-gamma release assay (IGRA)

IGRA is a Blood test. If one has been exposed to TB bacteria, the white blood cell in the blood will release a substance called gamma interferon when the cells are exposed to specific TB antigens.

Image

Figure: Interferon-gamma release assay (IGRA)

Resources:

• Latent Tuberculosis Infection Guideline
• Guideline for Programmatic Management of Tuberculosis Preventive Treatment in India

Kindly provide your valuable feedback on the page to the link provided HERE

TPT treatment options recommended under NTEP include:

• 3-month weekly Isoniazid and Rifapentine (3HP)
• 6-months daily isoniazid (6H)

Table 1: TPT Options for Target Population; Source: (Guidelines for Programmatic Management of Tuberculosis Preventive Treatment)

Table 2: TPT dosage based on age and weight band recommended by NTEP; Source: Guidelines for Programmatic Management of Tuberculosis Preventive Treatment

Resources

• Guidelines for Programmatic Management of Tuberculosis Preventive Treatment
• National Strategic Plan for TB Elimination

Assessment

The NTEP has prioritized the target population for TPT based on elevated risk of progression from infection to TB disease or increased likelihood of exposure to TB disease. 

The target populations have been divided into two groups:

1. Household contacts of bacteriologically confirmed pulmonary TB patients notified in Nikshay from public and private sector.

#Chest X Ray (CXR) and TBI testing would be offered wherever available, but TPT must not be deferred in their absence

*Bacteriologically confirmed pulmonary TB patients to be prioritized for enumeration of the target population for TPT

2. Expanded to other risk groups

Several medical conditions are risk factors for TB and poor TB treatment outcomes. Similarly, TB can complicate the course of some diseases. Therefore, it is important to identify these comorbidities in people diagnosed with TB to ensure early diagnosis and improved outcomes. When these conditions are highly prevalent in the general population, they can significantly contribute to the TB burden. Consequently, reducing the prevalence of these conditions can help prevent TB.

TB shares underlying social determinants with many of these conditions. Addressing the social determinants of health is a shared responsibility across disease programmes and other stakeholders within and beyond the health sector. 

Figure: Various comorbid and special situation related with tuberculosis

The primary impact of HIV on TB is that the risk of developing TB becomes higher in patients with HIV. Overall, HIV-infected persons have an approximately 8-times greater risk of TB than persons without HIV infection. 

Screen TB PLHIV patients for symptoms of TB and HIV

Figure: Screening steps for TB - HIV patients

Treatment for TB HIV Patients​

• All TB patients who have been diagnosed and registered under NTEP should be referred for screening for HIV.
• Referral of TB patients for screening for HIV and its recording & reporting is the responsibility of the Peripheral Health Institutions(PHI) where TB treatment is initiated.
• TB patients diagnosed with HIV will receive the same duration of TB treatment with daily regimen as non-HIV TB patients.
• TB patients must be referred to the nearest ART(Anti - Retroviral Treatment) centre for management of HIV.

As a consequence of urbanization as well as social and economic development, there has been a rapidly growing epidemic of Diabetes Mellitus(DM). India has the second largest number of diabetic people in the world.

Screen TB patients for symptoms of diabetes

Figure: Screening steps for TB - Diabetic Patients

Treatment for TB Diabetes Patients​

• All TB patients who have been diagnosed and registered under NTEP will be referred for screening for Diabetes.
• Referral of TB patients for screening for DM and its recording & reporting is the responsibility of the Peripheral Health Institutions(PHI) where TB treatment is initiated.
• TB patients diagnosed with diabetes will receive the same duration of TB treatment with daily regimen as non-diabetic TB patients.
• TB patients must be referred to the nearest healthcare facility for management of DM.
• Regular monitoring of blood sugar levels is advised.

Malnutrition refers to deficiencies, excesses or imbalances in a person’s intake of energy and/or nutrients. The term malnutrition covers 2 broad groups of conditions.

• One is ‘undernutrition’—which includes stunting(low height for age), wasting(low weight for height), underweight(low weight for age) and micronutrient deficiencies or insufficiencies(a lack of important vitamins and minerals).
• The other is overweight, obesity and diet-related non communicable diseases (such as heart disease, stroke, diabetes, and cancer).

Screen TB Malnutrition patients for nutritional needs

Figure: Screening Steps for TB - Malnutrition patients

Treatment for TB Malnutrition Patients

Cases of TB with SAM and moderate undernutrition should be referred to the nearest health facility of NTEP for further management. Special focus should be given to the following categories:

• Children below five years
• School-age children and adolescents(Up to age 18 years)
• Adults, including pregnant and lactating women, with active TB and SAM

About 10% TB deaths globally have been attributed to alcohol as a risk factor(WHO, Global TB Report 2017). Alcohol abuse is associated with threefold increase in risk of contracting tuberculosis.

Side effects of anti TB drugs in this situation might get aggravated.

Figure: Impact of Alcoholism on TB patients

Treatment for Alcoholic TB Patients:

• Patients with TB and a history of alcohol use should be referred to the nearest health facility of NTEP to manage TB and alcoholism.
• While registering as a TB case, the status of alcohol use should be recorded in the patient records. If the TB patient is an alcohol user, he/she should be counselled to quit it. If the patient doesn't quit alcohol, s/he may be referred to the nearest alcohol de-addiction facility.
• The patient should be assessed at every follow-up visit for TB and the status of use of alcohol.
• At the end of treatment, his/her status of alcohol use should be recorded on the treatment card. If the patient has not quit alcohol, he/she should be referred to the nearest alcohol de-addiction facility and Alcohol Anonymous wherever available.

Almost 38% of TB deaths are associated with the use of tobacco. The prevalence of TB is three times higher among ever-smokers as compared to that of never-smokers. Mortality from TB is three to four times higher among ever-smokers as compared to never-smokers. Smoking contributes to 50% of male deaths in the 25-69 age group from TB in India.

Figure: Impact of Tobacco on TB patients

Treatment for TB - Tobacco Patients:

• While registering as a TB case, the status of tobacco use is recorded on the TB treatment card.
• If the TB patient is a smoker or tobacco user, he/she is counselled to quit tobacco use. The patient is assessed at every visit for follow up for TB and the status of tobacco use.
• At the end of treatment, his/her status of tobacco use is recorded in the treatment card. If the patient has not quit tobacco use, he/she will be referred to the nearest Tobacco Cessation Clinic(TCC) or Quit Line or M-Cessation Initiative.

Silicosis is a progressive and disabling interstitial lung disease caused by inhalation and deposition in the lungs of particles of free silica.

Mutual Risk of TB and Silicosis

• TB is a clinical complication of silicosis, called silico-tuberculosis. Silica-exposed workers with or without silicosis are at increased risk for TB. There is also an increased risk of extrapulmonary TB in individuals exposed to silica.
• The risk of a patient with silicosis developing TB is 2.8 – 3.9 times higher than a healthy individual.
• The risk of TB relapse in patients with silicosis is approximately 1.5 times higher than in patients without silicosis.

The presence of silica particles in the lung and silicosis may:

• Facilitate initiation of TB infection and progression to active TB
• Exacerbate the course and outcome of TB, including prognosis and survival

Diagnosis

The diagnosis of silicosis is made based on a history of exposure to silica accompanied by a clinical and radiological profile consistent with the disease.

Under the Integrated Management Algorithm for TB disease and TB infection released by the National TB Elimination Programme (NTEP), patients with silicosis are first screened according to the four-symptom complex to rule out/in active TB and tested for TB accordingly. 

If active TB is ruled out >> Refer for Tuberculin Skin Test (TST)/ Interferon Gamma Release Assay (IGRA) >> Positive test >> Evaluate with Chest X-ray (CXR) >> Commence TB Preventive Therapy (TPT) irrespective of CXR results.

CXR often indicates TB in silicosis patients earlier than the clinical symptoms, and regular radiographic screening is required for early TB detection. Radiographic comparison of serial films is done with particular attention to:

• Rapid appearance of new opacities, symmetric nodules or consolidation and the finding of pleural effusion or excavations.
• Cavitation is the strongest indicator of probable silico-tuberculosis.

Other diagnostic tools that can help in diagnosis are:

• Chest Computed Tomography (CT) scan
• Bronchoscopy with bronchoalveolar lavage in conjunction with transbronchial biopsy
• Spirometry

Treatment and Follow-up

To keep the disease from getting worse, all silicosis patients need to eliminate any more exposure to silica. Supportive measures include the use of cough medicines, bronchodilators, oxygen therapy and pulmonary rehabilitation.

TB treatment in patients with silicosis is challenging, perhaps due to impairment of macrophage function by free silica and/or poor drug penetration into fibrotic nodules. Usual anti-TB drugs with directly observed therapy are recommended but for an extended duration of at least 8 months, to reduce the chances of relapse.

Follow-up of patients with silicosis and TB follow the same schedule as is in prevailing guidelines.

Prevention

TB prevention in silicosis patients is essential and includes:

• Active surveillance of vulnerable groups including workers
• Adoption of measures to reduce exposure to silica dust
• Patients with silicosis are eligible for TPT after ruling out active TB

NTEP is in the process of engaging with the Ministry of Labour and Mining to identify high priority districts with stone crushing units/ mining industry. Specific guidelines will be developed to support persons with an occupational risk for TB and provide access, diagnosis and treatment services from the programme.

Resources

• NTEP at a Glance; Comprehensive Clinical Management Protocol of Tuberculosis, 2022.
• Training Modules (1-4) for Programme Managers and Medical Officers, 2020.
• Silico-tuberculosis, Silicosis and Other Respiratory Morbidities Among Sandstone Mine-workers in Rajasthan - A Cross-sectional Study, Saranya Rajavel et al., 2020.
• Mini-review: Silico-tuberculosis; Massimiliano Lanzafame et al, 2021.
• Immunity to the Dual Threat of Silica Exposure and Mycobacterium tuberculosis, Petr Konečný et al., 2019.

Assessment

​

Relationship between Cancer and Tuberculosis (TB)

TB and malignancy may be related in the following four ways:

1. TB as a marker for occult cancer: Occult cancer may lead to locally-reduced infection barriers and/or generalised immunosuppression, rendering a cancer patient susceptible to TB infection/ reactivation.
2. TB as a risk factor for cancer: TB may increase the risk of cancer locally and systemically through chronic inflammation, fibrosis and production of carcinogenic molecules.
3. Shared risk factors for TB and some cancers: Shared risk factors such as smoking, alcoholism, Chronic Obstructive Pulmonary Disease (COPD) and immunosuppression, including HIV, may lead to both TB and cancer, affecting both prevalent and subsequent cancer risk.
4. Treatment of cancer-fueling TB: Many cancers are treated with immunosuppressants or steroids. These drugs might induce immunosuppression in the patients undergoing treatment for cancer and hence, a flare-up of TB.

Mutual Risk of Cancer and TB

• TB patients are 2-11 times more likely than non-TB patients to develop lung cancer, according to studies.
• After cancer diagnosis, the incidence of TB also increases, both in the short term and long-term.
• All types of cancer increase the risk of the development of active TB, but with varying degrees. Haematologic cancer patients had the highest rates of active TB, followed by head and neck cancers, lung cancer and breast cancer patients.

There is intrinsic immunosuppression due to the cancer itself, immunosuppressive effects of chemotherapy, or other host factors (e.g., smoking, malnutrition) that may increase the susceptibility to both cancer and TB. Thus, there is increased incidence of TB in cancer patients, and vice-versa.

Diagnosis of TB in Cancer Patients: Under the Integrated Management Algorithm for TB disease and TB infection released by the National TB Elimination Programme (NTEP), cancer patients are first screened according to the four-symptom complex to rule out/in active TB and all presumptive TB cases need to undergo testing for TB.

Co-existence of TB and cancer poses a diagnostic challenge since clinical and radiological presentations between TB and cancers are similar, hence the need for bidirectional screening. E.g., if biopsy specimens reveal infiltration by malignant cells, still send sample for microbiological confirmation of M. tuberculosis. Thus, allowing for accurate diagnosis and initiation of anti-TB treatment instead of attributing clinical deterioration to chemotherapy complications and progression of underlying malignancy.

Diagnosis of lung cancer in TB patients is usually done in consultation with a clinical specialist and can include examination of induced sputum specimens for malignant cells, as well as use of other diagnostic tools such as Computed Tomography (CT) scans, bronchoscopy, Positron Emission Tomography (PET) scans, Magnetic Resonance Imaging (MRI), histopathology and the use of biological markers.

Treatment

TB treatment in cancer patients uses the standard DS-TB/DR-TB regimens and course, except that the treating physician should assess the drug interactions between anti-TB and anti-cancer drugs. For cancer treatment, drugs may have to be modified to accommodate anti-TB treatment and to aid better prognosis of the TB outcome. However, all decisions must be taken by a competent specialist after examining the individual case.

Curative resection, chemotherapy and radiation therapy are the mainstay treatment options for cancer in TB patients. Co-existence of TB in cancer patients necessitates anti-TB treatment with extended duration, if required. Follow-up during and after treatment also follows prevailing guidelines.

Prevention

Under the NTEP, TB prevention in cancer patients is essential and includes:

• Regular screening for signs and symptoms of TB infection among all patients on immunosuppressive therapy and anti-Tumour Necrosis Factor (TNF) medicines.
• Education and referral of patients who do not have TB symptoms for TB infection testing/assessment of their eligibility for TPT.

Resources

• NTEP at a Glance; Comprehensive Clinical Management Protocol of Tuberculosis, 2022.
• Training Modules (1-4) for Programme Managers and Medical Officers, 2020.
• Tuberculosis and Risk of Cancer: A Danish Nationwide Cohort Study, D. F. Simonsen et al., International Journal of Tuberculosis and Lung Diseases, The Union, 2014.
• Increased Risk of Active Tuberculosis after Cancer Diagnosis, Dennis F. Simonsen et al., Journal of Infection, 2017.
• Pulmonary Tuberculosis as Differential Diagnosis of Lung Cancer; MLB Bhatt et al., South Asian Journal of Cancer, 2012.

Assessment

The presence of tuberculosis disease during pregnancy, delivery, and postpartum is known to result in unfavourable outcomes for both pregnant women and their infants. These outcomes include a roughly two-fold increased risk of preterm birth, low birth weight, intrauterine growth restriction, and a six-fold increase in perinatal death.

Screen TB patients in Pregnancy & Lactating Patients

Figure: Screening Steps in special situation - Pregnancy and Lactating TB Patients

Treatment for TB - Pregnant & Lactating Patients

• Cases of pregnant/lactating women with active TB should be referred to the nearest health facility of NTEP for further management.
• They should be continued on iron and folic acid and other vitamins and minerals to complement their maternal micronutrient needs.
• In situations when calcium intake is low, calcium supplementation is recommended as part of antenatal care.

Tuberculosis and COVID-19 are infectious diseases which primarily attack the lungs. They present with similar symptoms of cough, fever and difficulty in breathing, although TB disease has a longer incubation period and a slower onset of disease.

Screen patients for symptoms of TB and COVID-19

Figure: Screening steps for TB - COVID 19 Patients

Management of TB & COVID-19 Patients

People with TB are likely to be at increased risk of COVID-19 infection, illness and death. So, TB patients should take precautions as advised by health authorities to be protected from COVID-19 and continue their TB treatment as prescribed.

Prevention: While both TB and COVID-19 are spread by close contact between people, the exact mode of transmission differs. Thus, the patient should be explained the following measures to control disease spread.

• Apart from that keeping rooms well ventilated, avoiding crowds and Respiratory precautions are thus important in the control of COVID-19 and TB Disease

Tuberculosis(TB) is curable if patients are treated with effective, uninterrupted anti-tuberculous treatment. Treatment adherence is critical for curing individual patients, controlling the spread of infection in the community, and minimizing the development of drug resistance.

Adherence to treatment means that a patient follows the recommended course of treatment by taking all the prescribed medications for the entire length of time, as necessary. In other words, “right dose for the right duration”.

In Drug Sensitive Tuberculosis(DSTB), a TB patient completes 168 doses of TB treatment and adheres to TB treatment.

Adherence to tuberculosis(TB) treatment is important for promoting individual and public health. Poor adherence to TB treatment results in:

• More individual suffering and death,
• Costly treatment as treatment regimens lengthen and
• Increases the risk for Drug Resistant Tuberculosis

Proper treatment of all forms of TB is critical to reducing individual morbidity and mortality and to interrupting transmission among family and community members.

Recording of Treatment Adherence can be done as

• Manually by DOT/Health Care Provider in TB Treatment Card of a patient.
• Self-reported by Patient using digital tools for reporting adherence using 99 DOTS and MERM technologies.

Monitoring Treatment Adherence:

All TB patients should be monitored to assess their response to TB treatment. Nikshay Adherence calendar has a colour legend for various doses taken by a patient

Figure: Sample Nikshay Adherence Calendar in web and Mobile App

Image

Figure: DSTB Treatment Card (Paper)
 

99DOTS is a low-cost digital adherence technology built-in Nikshay that uses inexpensive packaging(envelopes or stickers) with medication that enables people taking medication to engage with their treatment daily. This packaging, distributed to TB patients taking medications, has a hidden number behind perforated flaps on the external envelope; in some cases, the number may be fixed outside the medication blister or pill bottle. This number can be a toll-free number that can be called to register daily adherence or a code sent by SMS, USSD, or other communication channels. Calling or messaging the number is free!

Figure: 99 DOTS Envelope

MERM: The Medication Event Reminder Monitor(MERM) is a digital pillbox that provides daily pill-taking reminders and facilitates remote monitoring of medication adherence. This system provides visual and audible reminders for both daily dosing and refill,.transmits this data to a server so that healthcare providers can remotely visualize patients’ dosing histories to support enhanced adherence counselling. 

Figure: MERM Box

Manual recording of Adherence in Nikshay:

in Nikshay, Adherence can only be recorded only if there is corresponding dispensation being issued to a Patient 

Figure: Steps to record manual dose in Nikshay

Recording in Patient Treatment Card:

Figure: Filled Treatment card for TB Patient

Missed Dose recording in Nikshay:

For recording missed doses in Nikshay, following steps should be followed:

A person affected by TB requires support throughout the course of treatment and beyond that. The support to a TB patient is essential to ensure that s/he completes the treatment without affecting her/his quality of life (QoL). Keeping the patient as the central figure in the continuum of care, and ensuring social and personal circumstances are supportive (not only meeting immediate requirements of medical treatment) is the key to treatment support.

Figure: Key Components of Treatment Support

Resources

National Strategic Plan for Tuberculosis Elimination 2017–2025, RNTCP, 2017.

A Patient-centred Approach to TB Care, WHO, 2018.

Assessment

A Treatment Supporter can be any person such as a Medical Officer, MPWs, community volunteers working with the program etc. Even a patient’s relative or family member can be a Treatment Supporter.

As per NTEP guidelines, salaried NTEP/General Health System staff may also be assigned as treatment supporters for a patient.  However, they will not be eligible for any honorarium.

A patient can only be linked to one treatment supporter at a time in Nikshay.