Treatment of tuberculosis

Croften (1997) gave the following as the general information on treatment of tuberculosis; tuberculosis treatment must not be started until a firm diagnosis has been made, treatment should be started as soon as sputum result are positive or if patient is severely ill and clinical suspicion of tuberculosis is high. A medical officer should decide on treatment for those with only one sputum results or those with sputum negative results.

Croften (1997) opined that the basis of tuberculosis treatment is adequate chemotherapy. This is the most important measure in tuberculosis control, because when applied correctly can produce a rapid reduction in the magnitude of the tuberculosis problems in the community priority is given to smear-positive cases.

  • Prescribed and given in the correct dosage.
  • Taken regularly by patients
  • For the require length of time prevent relapse of the disease.
  • Treatment must be given to every patient confirmed as having tuberculosis and must be given free of charge.

Treatment regimen          

Treatment of smear positive cases are given in two phase. An initial intensive phase lasting for two months for new cases and continued until they become smear negative but for not more than three months or three months for previously treated cases. The main aim of this phase is to reduce rapidly and if possible eliminate the activity of multiplying mycobacteria, without allowing the development of acquire resistance the applied drugs. This is a vital stage of the treatment and it should be absolutely certain that the patient completes correctly, through directly observation treatment short course (DOTS).

The continuation phase for five months for previously treated patients, six month for new cases and ten months in standard treatment. This phase ensure that patient is permanently cured and does not relapse.

Before treatment is commenced, it is necessary to question all patients closely and carefully to determine whether or not they have previously taken treatment for Tuberculosis sputum smear positive patients who have been treated previously for up to one month should be one suspected of having multi-drug resisting to one or more drugs. Such patients should be placed on re-treatment regimen and should be closely monitored.

Supervision of treatment

Unfortunately many patients do not persist with their treatment. They stop because they are feeling better. It has been shown that patients can be cured without having to be admitted to hospital. But this is only possible if the supervision of treatment is of a very high standard. To get this success, patients must be helped not to default (Default is stopping treatment before time). WHO recommend that national programmed adopt the use of “DOTS” strategy. DOTS are directly observed treatment short course. Each dose of treatment is supervised by a health worker, other trained worker or trained volunteer. This is essential in the initial intensive phase of treatment. The advantage of this method is that you can be sure that the patients get every dose if he fails to come for this dose you can immediately take steps to get him back, this prevents relapse and saves him from starting all over again.

 Management of non-compliance (defaulters)

According to Croften (1997) it is very important that the patient does not interrupt treatment because if he does the tuberculosis may start to multiply again. It is particularly important that it does not interrupt treatment in the initial phase of treatment. If a patient is defaults of this stage you must make every effort to get him back on treatment.

During the intensive phase when every dose is supervised if he misses more than one dose take action to get him back. During the continuation phase if he fails to attend clinic on the due date get him back.

Action to get patient back

It is important to get patient correct address. Always visit patient home to persuade him to come persuading personality is important.

Preventing default/non-compliance

There are many aspects of this problem everything possible must be done to make sure that patients take their fill treatment, if not, they will relapse. Coftton and Norman (1999) stated before starting patient on treatment sufficient time must be taken to talk to the patient and explain everything about the disease to him in simple terms (Health Education).

If patient can read give him a leaflet which set out the important details of treatment. If he cannot read, someone in his family or village can read it for him. Explain what tuberculosis is and what it is not and how it is spread. Reassure him that the disease is curable if follow all advice given to him and complete his treatment, if not the disease will come back.

Show him the kind of pill he is expected to take and how he will take it them, make sure he understands. He should not stop his medication even when he begins to feel better. Explain the reaction he is likely to get from the drugs which are fever, itching of the skin, rash and if on streptomycin, giddiness. If he is to have ethambatol he should report at once any difficulty with vision. Once very important reason why patient should not return to clinic is during his working hours because he might lose his job

Clinic distance should not be far from patients’ home or working place, because it will mean patient trekking long distance or spending money on transport, this will discourage patient. Clinic should be centralized or as near to the patient home or working place as possible. It is useful to have tuberculosis treatment centre at the same place where people come for other medical purpose e.g. Maternity or immunization clinics health posts to eliminate stigmatization, clinic should be timed so that patient does not miss work and patient should be kept waiting for long time, when patient come to the clinic or when he visited at home carry out urine test for the presence of drugs sure that he takes his drugs correctly.

Get patient’s relatives and family to help and encourage patients to take his drugs correctly and regularly, advice patient not to take any medication for the treatment of tuberculosis from any other source other than one given to him in the clinic. Other factors which many interfere with compliance in treatment are personal problem, e.g. loss of job and fear about what friends and neighbours will say when they know about his disease, render any help to make sure that patient take his treatment.

Where the patient should be treated

Hospitalization itself has little or no effect on the outcome of treatment, if the patient takes appropriate drugs he/she will do equally well with treatment in or out of hospital. The arguments in favour of hospitals treatment are that compliance is better; drug toxicity is detected earlier, education of patients better and the isolation means that spread of disease to families and other contacts is less. In fact well organised clinic can achieve all the benefits which are claimed for hospitalization.

However, the excellent results have mostly been under ideal conditions where there has been plenty of well trained staff. In-patient treatment is necessary often only for a few weeks for severely ill patients, those with tuberculosis complications or other serious disease requiring hospitalization. Hospitalization also ensure that the patient during the intensive phase of ensures that the patient during the intensive phase of therapy complete treatment as prescribe and may be used in cases where DOTS cannot be guaranteed.

Isolation

Since good chemotherapy has been started isolation is much less important, there is no increase risk of infection for the family whether patient is treated at home or in hospital. The greatest risk of infection is before treatment begins. However these groups of patients may need isolation

  1. Short-term isolation for teacher and others in contact with young children.
  2. Isolation until smear negative; where there is contact with people receiving immunosuppressive drugs e.g. anticancer drugs, patients who have drug resistance Tuberculosis.
  3. In hospital HIV-positive patients who do not have tuberculosis and HIV positive, staffs who are still working must be protected from contact with infectious tuberculosis patients.

 Drugs Resistance

This is important because treatment will not be succeeds if tubercle bacilli are resistance to the drugs used; there are three types of resistance.

  1. Natural drug resistance strain is a wild strain resistance to a particular drug without ever having been in contact with it. The probability that drug resistance bacilli (Mutants) are present depends mainly on the total number of pulmonary tuberculosis; resistance mutants are always present, since there are millions of tubercle bacilli inside on average cavity. Mutants resistant to two drugs are rare, if only ones drug is given the sensitive tubercle bacilli are destroyed but the resistant one multiply, never give a single drug (monotherapy).
  2. Acquired or secondary resistance is due to incorrect chemotherapy: for instance, treatment with a single potent drug in patient with smear-positive tuberculosis or administration of potent drugs to a patient harbouring tubercle bacilli to all but one of the drug or the patient failing to take his drugs properly.
  3. If a person with acquired resistance infects a health individual this individual will present with the resistance strain from the onset of the disease, this is called primary resistance. Micro-organisms with resistance to at least the two most important medications, insoniazid and rifampicin are termed multidrug-resistant.

 Use of chemotherapy in the treatment of tuberculosis

There are only a limited number of medications currently available for the treatment of tuberculosis, this caution in order not to create resistance on them; the presence of resistance makes the treatment much less likely to be successful, the most important medication use for the treatment of tuberculosis are;

  • Isoniazid (H).
  • Rifampicin (R).
  • Pyraziamide (Z).
  • Ethambutol (E).
  • Streptomycin (S).
  • Thioacetazone (T).

Some medications are available in combined preparations, ripampicin with isoniazid (RH) thioacetazone with isoniazid (EH). The duration of time after the manufacturing date that medications may be used safely (The shelf life of the medications) provided they are kept in a proper storage conditions is as follows;

5 years: Isonazide, ethambutol and thwacetazone.

3 years: Rifampicin, pyrazinamide and streptomycin.

The use of rifampici and streptomycin for diseases other than mycobacterial diseases should be limited to very carefully considered indications, those medication used for treatment of tuberculosis should only be available to the community through the National Tuberculosis Programme, they should not be available freely in the market.

The dosage of all drugs is related to the weight of the patient at the start of treatment (Pre-treatment weight) and should remain the same throughout the treatment period even with the change in weight of patient during treatment.

Short-course chemotherapy of new cases of smear positive pulmonary tuberculosis

All smear positive cases of pulmonary tuberculosis who were never previously treated for as much as one month for tuberculosis will receive this regimen. This regimen may be used for patients with other forms of tuberculosis never previously treated if they are seriously ill according to the diagnosis of a medical officer experienced in tuberculosis.

The full regimen is Refampilin/Isoniazid (Combined Tablet), Pyrazinamide and Ethambutol daily for 2 months followed by Thiazina (Isoniazid with Thiacetazone) or Ethambutol with Isoniazid (combined) daily for 6 months.

In children 0-6 years old Ethambutol should be replaced with Streptomycin injection, Thiacetazone is associated with high risk of severe and sometimes fatal, skin reaction in HIV-infected individuals, use Ethambutol instead of Thiacetazone.

Chemotherapy for previously treated patients (re-treatment) 

Smear positive patient who have taken medications for treatment of tuberculosis for as much as one month in the past must be given a retirement regimen, they include;

Relapses:      These are patients who have become smear positive again after having been tested for tuberculosis and declared “cured’’ after the completion of treatment.

Failure case: These are patient who on initial treatment for smear positive pulmonary tuberculosis, remained or become again smear positive at 5 months or 7th months during the course of treatment.

Return after default: Positive case-patients who are smear positive while returning to treatment after having defaulted more than two months after the start of treatment.

Chronic excretors of tubercle bacilli: Chronic cases are defined here as those who continue to be smear positive after the completion of a fully observed re-treatment regimen (Failures of re-treatment). Every dose taken must be observed, the tablets should be given single dose on an empty stomach before the injection of streptomycin.

 Use of twelve month chemotherapy for newly diagnosed cases

While Direct Observed Treatment Short-Course (DOTS) should be used as much possible to treat Tuberculosis in all patients, for patients whom we cannot ensure regularity and supervision give the 12 months standard treatment (ST).

For twelve- month chemotherapy Isoniazid plus Thioacetazone (in a combined tablet) is used daily for 12 months for smear positive patients this combination must always be supplemented by Streptomycin or Ethambutol daily for the first two months of Chemotherapy.

 Adverse effects of anti-tuberculosis drugs isoniazid

Adverse effects of isoniazid are uncommon generalized skin rashes rarely occur;

  • Peripheral neuropathy (tingling and numbness of the hands and feet) is the main adverse effect, it is common in malnourished patient and in higher doses; it can be treated by giving 100-200 mg pyridoxine daily and can be prevented by giving 10 mg pyridoxine daily.
  • Hepatitis may occur especially in patients more than 35 years old, other rare adverse effects includes giddiness, convulsions, optic neuritis etc.

 Refampicin

The main side effect includes;

  • Gastro intestinal: Nausea, anorexia and mild abdominal pain, diarrhoea occurring less frequently.
  • Cutaneous reaction in form of mild flushing, itching of the skin and occasionally rash.
  • Hepatitis is extremely uncommon unless the patient has history of liver disease or alcoholism.
  • Respiratory and shock syndrome: Short of breath, wheeziness, fall in blood pressure, collapse.
  • Acute haemolytic anaemia and renal failure. Rifampicin should not be given if shock syndrome, acute haemolytic anaemia or acute renal failure occurred.

 Streptomycin

The main adverse effects are coetaneous hypersensitivity and ototoxicity (Damage to Eight Cranial Nerve).

  • Skin reaction- rash and fever.
  • Damage to the vestibular (balancing) apparatus.
  • Anaphylaxis: Infection may be followed by tingling around the mouth, nausea and occasionally by sudden collapse. Streptomycin should be avoided in pregnancy because it may cause deafness in the child.

 Ethambutol

The main and very serious side effect is progressive loss of sight (vision) caused by retrobular neuritis. Hepatitis, cutaneous hypersensitivity, peripheral neupathy are rare.

 Pyrazinamide

The most common side effects are liver damage (hepatoxicity) and joints pain (arthralgia). Anorexia, mild fever, tender enlargement of liver and spleen may follow with jaundice; if severe hepatitis occurs stop the drugs.

 Thioacetazone (Thi)

The main adverse effects are generalized coetaneous reaction and gastrointestinal symptoms, there are common in HIV infection and may be very severe.

 Complication of tuberculosis

According to NTBLCP worker manual complications are;

A         Pulmonary tuberculosis

  • Haemoptysis (Coughing blood).
  • Spontaneous Pneumothorax (Collapse of lung).
  • Pleural effusion.
  • Cor Pulmonale.
  • Destructive Lung Disease.

B          Extra-pulmonar tuberculosis

Complications depend upon site of the disease for example; Tuberculosis of the spine may be present with Paraplegia.

References

Crofton, J. (1997). Guideline of the management if Drug resistance Managing these difficult cases. BMJ 1:13-14.

Crofton, J. & Norman M. (1999). Clinical Tuberculosis (2nd ed.). London: Macmillan.

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