STLS: Concepts in 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

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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)

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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

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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

It is extremely important for any type of TB patient to be initiated on the right treatment at the earliest in order to have better treatment outcomes. Therefore as soon as the patient is diagnosed, s/he should immediately be traced with the help of the Community Health Officer (CHO) of the Health and Wellness Centres (HWC), TB Health Visitors (TBHV) / Senior Treatment Supervisor(STS) and the health facility doctors and initiated on the appropriate treatment regimen.

Steps in TB Treatment Initiation

Image

Figure: Flowchart-Treatment Initiation

Resources

• Guidelines on Programmatic Management of Drug-resistant TB (PMDT) in India, CTD, MoHFW, India, 2021.
• Training Modules (1-4) for Programme Managers and Medical Officers, CTD, MoHFW, India.

Assessment

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.

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

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.

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