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TB Treatment – Curing TB, failure, relapse & recurrence

TB treatment

Archbishop Desmond Tutu was treated and cured of TB as a child

Archbishop Desmond Tutu was treated and cured of TB as a child

The aims of TB treatment are:

  • To cure the patient of TB and restore their quality of life and productivity;
  • to prevent relapse of TB;
  • to reduce the transmission of TB to others;
  • to prevent the development and transmission of drug resistant TB.1“Treatment of Tuberculosis guidelines”, WHO, Geneva, 2011, 29 www.who.int/tb/en/

Curing TB

TB treatment can cure most people who have TB, using a combination of the different drugs available for TB treatment. Surgery is not often now used for TB treatment.

TB treatment, the drugs

There are more than twenty drugs available for TB treatment. They are used in differing combinations in different circumstances. So for example, some TB drugs are only used for the treatment of new patients when there is no suggestion of any drug resistance. Others are only used for the treatment of drug resistant TB.2“Guidelines for treatment of Tuberculosis”, WHO, Geneva, 2010, 85 www.who.int/tb/publications/2010/9789241547833/en/ The new TB drug bedaquiline, is available to be used for the treatment of MDR-TB when there aren’t any other drugs available. More than 90% of people with drug susceptible TB (that is TB which is not drug resistant) can be cured in six months using a combination of “first line” TB drugs.3“The Global Plan to Stop TB”, WHO, Geneva, 2011, vi www.stoptb.org/global/plan/

Killing the TB bacteria

The TB drugs that are taken for the treatment of TB, have the aim of killing all the TB bacteria in the person’s body. This means that the person is cured of TB. However, TB bacteria die very slowly, and so the drugs have to be taken for quite a few months. Even when a patient starts to feel better they can still have bacteria alive in their body. So the person needs to keep taking the TB treatment until all the bacteria are dead.

All the drugs must be taken for the entire period of TB treatment. If only one or two TB drugs are taken then the bacteria may not all be killed. They may then become resistant to the TB drugs which then don’t work. If the person becomes sick again then different TB drugs may be needed.

General principles of drug treatment of pulmonary TB

Some general principles of pulmonary TB drug treatment (sometimes referred to as TB chemotherapy) are:

  • Drug treatment is the only effective treatment for TB;
  • Single drug treatment for active TB is associated with a substantial relapse rate. A patient is said to have a relapse if they improve whilst taking TB treatment but become ill again after they have finished their treatment. Single drug treatment is also associated with the development of bacteria that are resistant to the drug;
  • Patients with active TB disease should receive at least three drugs as their initial TB drug treatment. Fewer than three drugs can result in the development of resistance;
  • Never add a single TB drug to a failing regimen, a regimen simply means the course of treatment, in this instance the combination of TB drugs;
  • Compliance with TB treatment is the responsibility of the treating physician as well as the patient.

TB drug treatment is sometimes referred to as antitubercular treatment or ATT.

First line drugs for TB treatment

TB drug treatment &#169 CDC

TB treatment, first line drugs © CDC

The first line drugs:

  • Isoniazid
  • Rifampicin
  • Pyrazinamide
  • Ethambutol
  • and Streptomycin

are those TB drugs that generally have the greatest bactericidal activity when used for TB treatment. The amount of drug that a TB patient needs to take depends on the patient’s weight.

TB treatment for new patients

New patients are those who have not had TB treatment before, or they have received less than one month of anti TB drugs. New patients are presumed to have drug susceptible TB (i.e. TB which is not drug resistant) unless:

  1. There is a high level of isoniazid resistance locally in new TB patients, or
  2. the patient has developed active TB disease after known contact with a patient who is documented as having drug resistant TB.

For new patients with presumed drug susceptible pulmonary TB, the World Health Organisation (WHO) recommends that they should have six months of TB treatment. This consists of a two month intensive TB treatment phase followed by a four month continuation phase.

For the two month intensive TB treatment phase they should receive:

  • Isoniazid
  • plus rifampicin
  • plus pyrazinamide
  • plus ethambutol

followed by

  • Isoniazid
  • plus rifampicin

for the continuation TB treatment phase.

Taking tb drug treatment

Taking TB drug treatment

It is recommended that patients take the TB drugs every day for the six months. Although taking the drugs three times a week is possible in some circumstances, it is essential that all the recommended TB drugs are taken. If only one or two drugs are taken, then the TB treatment probably won’t work, because the TB bacteria that the patient has develops resistance to the drugs. Not only is the patient then still ill, but to be cured they then have to take drugs for the treatment of drug resistant TB. These drugs are more expensive and have more side effects.

TB treatment for other patients

A patient may not qualify for treatment as a new patient, for example because they have had TB treatment before. Then they probably need to take a different and longer course of drug treatment. If they just have the same course of TB drug treatment again, they will probably not be cured. The drug regimen or plan will need to be worked out in the same way as a TB treatment regimen or plan is worked out for a patient who needs treatment for drug resistant TB.

TB treatment failure

It is often suggested that TB treatment fails because a patient doesn’t take their TB drugs correctly. However there can be a number of different reasons for TB treatment failure. It is certainly true that if a patient doesn’t take their TB drug treatment properly that this can lead to the development of drug resistant TB. However the patient may already have drug resistant TB. If they already have drug resistant TB, then treatment that someone is provided with may result in treatment failure even if the treatment is taken correctly.

The three main causes of TB treatment failing, relate to the actions of doctors in prescribing incorrect regimes, the fact that there may be problems with the drugs being delivered (either when they are delivered or the quality), and that patients for a number of reasons may not have a sufficient intake of the drugs.4Based on Lambregts-van Weezenbeck, C. S. “Control of drug-resistant tuberculosis” Tubercle and Lung Disease, (1995) 76, 455

Doctors – as a cause of TB drug treatment failure:
Inappropriate guidelines,
Non compliance with guidelines,
Absence of guidelines.
Drugs – as a cause of inadequate TB treatment:
Poor quality,
Irregular supply,
Wrong delivery (dose/combination),
Drugs are unsuitable due to drug resistance.
Patients – as a cause of TB drug treatment failure:
Lack of information,
Lack of money for treatment and/or transport,
Actual or presumed side effects,
Lack of commitment to a long course of drugs,
Malabsorption,
Social barriers.

Patients who experience only a short improvement whilst on TB treatment, or who never respond to treatment, are said to have failed their TB treatment. Treatment failure is also sometimes defined as the continued presence of positive sputum or culture (positive result to a culture test) or positive sputum or culture appears again, during the course of a patient’s anti tuberculosis drug treatment (att).5“Monitoring of relapse, treatment failure and drug resistance”, British HIV Association www.bhiva.org/

After three months of multi drug treatment for pulmonary TB caused by drug susceptible bacteria, 90-95% of patients will have negative sputum or culture and show clinical improvement. Normally it is considered that if a patient still has a positive culture  after three months of treatment, the patient must be carefully evaluated to identify why their positive culture hasn’t changed to negative. Patients whose sputum culture remain positive after four months of drug treatment should be classified as treatment failures. If drug treatment failure occurs then a sample should be sent to a reference laboratory for drug susceptibility testing for both first and second line drugs.

TB treatment relapse & recurrence

A patient is said to relapse if they become and remain culture negative (or they become well) whilst on TB treatment, but become culture positive (or become ill) again after finishing their TB treatment.

Recurrence of active TB is usually used to refer to the situation when a person’s first TB treatment appears to have been successful. There has then been a significant time interval before active TB develops again. This may either be because of reactivation of the person’s previously latent TB or because they have been reinfected. In any of these situations occur it must be considered a real possibility that the person has drug resistant TB. Their new TB treatment programme must be decided taking this into account.

TB treatment monitoring

Patients collecting more drugs for their TB drug treatment by presenting the empty packages from the last week.&#169WHO/TBP/Ger Steenbergen

Patients collecting more drugs for their TB treatment by presenting the empty packages from the last week.©WHO/TBP/Ger Steenbergen

All patients receiving TB treatment should be monitored during their treatment to assess their response to the drug treatment. Regular monitoring also helps to ensure that patients complete their treatment. It can also help to identify and manage adverse drug reactions. Patients need to have their weight checked every month, and if the patient’s weight changes the drug dosages may need to be adjusted.6“Guidelines for treatment of Tuberculosis”, WHO, Geneva, 2010, 85 www.who.int/tb/publications/2010/9789241547833/en/

When patients have pulmonary TB the patients response to TB treatment should be monitored using sputum smear microscopy. The recommendation from the World Health Organisation (WHO) is that for smear positive TB patients treated with first line drugs, the patients should have smear microscopy performed at the end of the two month intensive phase of treatment. Sputum should be collected when the patient is given the last dose of the intensive phase of treatment.

If the patient has a positive sputum smear at the end of the intensive phase, then there should be a patient assessment carried out. This is because the positive smear could indicate a number of different situations. An example is that the patient might have drug resistant TB, and a change in the TB drugs they are taking might be needed. Alternatively, patient adherence might have been poor, and they might not have been taking their drugs correctly. So the assessment might result in changes needing to be made to the patient’s treatment, or to their support and supervision. Different action may need to be taken in a variety of other circumstances, such as the patient having received treatment before.

New molecular tests, such as the GeneXpert TB test, cannot be used for TB treatment monitoring as they detect both live and dead bacteria, and cannot distinguish between them.7“Early tuberculosis treatment monitoring by Xpert MTB/RIF”, European Respiratory Journal, May 1 2012 //erj.ersjournals.com/content/39/5/1269.extract#

References

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1. “Treatment of Tuberculosis guidelines”, WHO, Geneva, 2011, 29 www.who.int/tb/en/
2. “Guidelines for treatment of Tuberculosis”, WHO, Geneva, 2010, 85 www.who.int/tb/publications/2010/9789241547833/en/
3. “The Global Plan to Stop TB”, WHO, Geneva, 2011, vi www.stoptb.org/global/plan/
4. Based on Lambregts-van Weezenbeck, C. S. “Control of drug-resistant tuberculosis” Tubercle and Lung Disease, (1995) 76, 455
5. “Monitoring of relapse, treatment failure and drug resistance”, British HIV Association www.bhiva.org/
6. “Guidelines for treatment of Tuberculosis”, WHO, Geneva, 2010, 85 www.who.int/tb/publications/2010/9789241547833/en/
7. “Early tuberculosis treatment monitoring by Xpert MTB/RIF”, European Respiratory Journal, May 1 2012 //erj.ersjournals.com/content/39/5/1269.extract#