Introduction

Aims of anti-TB drug treatment

1. To cure the patient of TB.

2. To prevent death from active TB or its late effects.

3. To prevent TB relapse or recurrent disease.

4. To prevent the development of drug resistance.

5. To decrease TB transmission to others.

Properly applied anti-TB drug treatment will achieve these aims.

Effective anti-TB drug treatment = properly applied short-course chemotherapy

We have known for over 100 years that M. tuberculosis causes TB.We have had effective anti-TB drugs for nearly 50 years.Yet the world's TB problem is now bigger than ever. Why? The problem is not the lack of an effective treatment. Properly applied short-course chemotherapy (SCC) fulfils the above aims of anti-TB drug treatment. The problem is organizational: how to apply SCC properly? The answer is a well managed TB control programme. Chapter 2 describes the organizational framework of an effective national TB programme (NTP).

Standardized TB treatment regimens

There are many different possible anti-TB treatment regimens. WHO and the IUATLD recommend standardized TB treatment regimens.The NTP in your country will recommend which regimens to use. When properly applied, these standardized regimens fulfil the above aims of anti-TB drug treatment. The regimens are affordable. The World Bank recognises SCC as one of the most cost-effective of all health interventions.The Global Drug Facility (GDF) is a mechanism to ensure uninterrupted access to quality anti-TB drugs at low cost (http://stoptb.org/GDF).

The first-line anti-TB drugs

The table below shows the first-line anti-TB drugs and their mode of action, potency, and recommended dose. The doses are the same for adults and children.

First-line

Mode of

Potency

Recommended dose

anti-TB drugs

action

(mg/kg of body weight)

(abbreviation)

daily

intermittent (3 times a week)

isoniazid (H)

bactericidal

high

S

iG

rifampicin (R)

bactericidal

high

iG

iG

pyrazinamide (Z)

bactericidal

low

2S

3S

streptomycin (S)

bactericidal

low

iS

iS

ethambutol (E)

bacteriostatic

low

iS

(3G)

thioacetazone (T)

bacteriostatic

low

2.S

not applicable

The available formulations and combinations of these drugs vary from country to country. Follow the recommendations in your NTP manual.

Intermittent use

Thioacetazone is the only essential anti-TB drug not effective when given intermittently. In any case, patients known or suspected to be HIVpositive should not receive thioacetazone. The efficacy of intermittent ethambutol is not proven.

Thioacetazone

Some countries still use thioacetazone (usually in combination with isoniazid in the continuation phase). WHO discourages the use of thioacetazone because of the risk of severe toxicity, especially in HIV-infected individuals. Ethambutol should replace thioacetazone, especially in areas where HIV is common. It is becoming easier to mobilize the resources to replace it with ethambutol.The price of rifampicin is falling. Also, the GDF is now making low-cost, quality-assured anti-TB drugs available to more countries.

Where thioacetazone is still in use, it is essential to warn patients about the risk of severe skin reactions. Advise the patient to stop thioacetazone at once and report to a health unit if itching or a skin reaction occurs.

T^H MODES OF ACTION OF ANTI-TB DRUGS

A population of TB bacilli in a TB patient consists of the following groups:

a) metabolically active, continuously growing bacilli inside cavities;

b) bacilli inside cells, e.g. macrophages;

c) semidormant bacilli (persisters), which undergo occasional spurts of metabolic activity;

d) dormant bacilli, which fade away and die on their own.

Different anti-TB drugs act against different groups of bacilli.

Anti-TB drug treatment takes a long time because it is difficult to kill the semidormant TB bacilli.

Bactericidal drugs

Isoniazid kills 90% of the total population of bacilli during the first few days of treatment. It is most effective against the metabolically active, continuously growing bacilli.

Rifampicin can kill the semidormant bacilli that isoniazid cannot.

Pyrazinamide kills bacilli in an acid environment inside cells, e.g. macrophages.

Sterilizing action

This means killing all the bacilli.The persisters are hardest to kill.The aim of killing all the bacilli is to prevent relapse. Rifampicin is the most effective sterilizing drug. Its effectiveness makes short-course chemotherapy possible. Pyrazinamide is also a good sterilizing drug, since it kills the bacilli protected inside cells.

Preventing drug resistance

A population of TB bacilli never previously exposed to anti-TB drugs will include a few naturally occurring drug-resistant mutant bacilli. Faced with anti-TB drugs, these drug-resistant mutant bacilli will grow and replace the drug-sensitive bacilli under the following circumstances:

a) inadequate anti-TB drug combinations;

b) inadequate application of anti-TB drug treatment.

Isoniazid and rifampicin are most effective in preventing resistance to other drugs. Streptomycin and ethambutol are slightly less effective.

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