INTRODUCTION

Tuberculosis continues to be a major public health problem throughout the world,

particularly in the developing countries. Nearly one-third of the global population (i.e.
two billion people) is infected with M.tuberculosis and is at risk of developing the
disease. More than eight million people develop active tuberculosis every year and about
two million die of the disease. It is the leading cause of death due to a single infectious
agent among adults. The highest burden of the disease is in the most economically
productive age group of our society (15-54 years). The rapid increase in the incidence of
tuberculosis in the developing countries and its resurgence in the developed countries led
the World Health Organization (WHO) to declare Tuberculosis a Global Emergency in
1993.

The aims of the fight against Tuberculosis are:

For individual patients - to cure their disease, quickly restore their capacity for activities
of daily living and allow them to be within the family and community and thereby
maintain their socio-economic status.
For the community - to decrease the spread of tuberculosis infection through early case
finding and by appropriate management and cure.

Much concerted efforts are needed to control the tuberculosis epidemic. The first priority
of tuberculosis control is the appropriate management and cure of tuberculosis patients,
especially the infectious cases who are the source of transmission of infection in the
community. It is the only way to break the chain of transmission of the disease.

The fight against Tuberculosis is best conducted within the setting of a National
Tuberculosis Programme (NTP) integrated with the general health services of the country.
For effective control of tuberculosis and to prevent emergence of drug resistance, it is
important to have a uniform treatment policy for all patients. Close co-operation of all
health care providers with the NTP is essential at all levels, for successful implementation
of the control programme. Participation of community health workers, religious groups,
political leaders, and voluntary organizations is essential to achieve success in
tuberculosis control. It is important that the community is made aware of the nature and
extent of the problem of tuberculosis as well as its prevention and cure. It must be
1

stressed that the disease is curable and preventable and there is no reason for
discrimination or stigma.

The key in controlling tuberculosis is to ensure that patients take their medicines regularly
until they are cured. Non-compliance of patients to treatment is one of the major
problems faced by all national tuberculosis programmes. To overcome this, the strategy
of Directly Observed Treatment, Short-course (DOTS) has been recommended by the
WHO and accepted internationally. DOTS has been recognised as the only proven costeffective method which can ensure cure. Under the DOTS strategy, a trained health
worker actually watches the patient swallow his/her medicines, and ensure cure. This is
the key to stopping tuberculosis at the source.

Community participation will encourage people with symptoms of tuberculosis to seek

medical advice for early case detection and improve patients compliance to treatment.
Case finding followed by proper treatment reduces suffering, disability and death from
tuberculosis and transmission of the disease in the community.

PART I
BASIC INFORMATION ON TUBERCULOSIS
AND
TECHNICAL GUIDELINES
FOR
TUBERCULOSIS CONTROL

TUBERCULOSIS

What is tuberculosis (TB)?

Tuberculosis is an infectious disease caused by the bacillus- Mycobacterium tuberculosis
and occasionally by Mycobacterium bovis and Mycobacterium africanum. Tuberculosis
commonly affects the lungs, but it can affect any other organ in the body.

How does tuberculosis spread?

The bacteria that cause tuberculosis usually spread through air. When a patient with
infectious pulmonary tuberculosis coughs, sneezes or laughs, bacilli are expelled into the
air in the form of tiny droplets. These droplets dry up rapidly to form droplet nuclei and
may remain suspended in the air for several hours. Adequate through and through
ventilation removes and dilutes these droplet nuclei, and direct sunlight quickly kills the
bacilli, but they can survive in the dark for several days. When a healthy person inhales
these droplet nuclei containing the tubercle bacilli, he/she may become infected.

Risk of infection
An individuals risk of infection depends on the extent of exposure to an infectious source
and susceptibility of the individual to infection. The risk of infection is therefore high in a
person who has close, prolonged exposure to a person with sputum smear positive
pulmonary TB. The risk of transmission of infection from sputum smear-negative
pulmonary TB is low and with extrapulmonary TB, still lower.

How does TB develop?

Tuberculosis develops in two stages. The first stage occurs when the tubercle bacilli from
an infectious source enter the body of an individual but remain dormant without causing
disease and is called tuberculous infection. The second stage is when the infected
individual actually develops the disease and is called tuberculosis or tuberculous disease.

Risk of progression of infection to disease

Once infected with M.tuberculosis, a person probably remains infected for life.
Approximately 10% of people infected will develop active disease during their lifetime.
The majority (90%) of people will not develop the disease and the only evidence of
infection in these individuals, may be a positive tuberculin skin test. However the
organisms may remain dormant within the body and the disease can develop at any time.
The chance of developing the disease is greatest shortly after infection (within the first
two years) and lessens as time goes by, but the risk probably remains for life. Any
weakening of the immune system will lead to progression of infection to disease e.g. HIV
infection, diabetes, malnutrition, prolonged steroid therapy, chronic alcoholism,
malignancies etc.

Pathogenesis
Primary infection
Primary infection occurs on first exposure of a person to tubercle bacilli. Once the
tubercle bacilli enter the respiratory tract through inhalation, the organisms reach the
alveoli of the lungs and start multiplying to form the Ghons focus. The bacilli spread
through the lymphatics to the hilar lymph nodes causing enlargement of the nodes. The
Ghons focus and the hilar lymphadenopathy form the Primary Complex. Bacilli from the
primary complex may spread via the blood stream and lymphatics to other parts of the
body .The immune response (delayed hypersensitivity and cellular immunity) develops
about 4-6 weeks after the primary infection. In most cases the immune response is
sufficient to stop the multiplication of bacilli and prevent development of disease. The
primary lesion may heal by fibrosis or by calcification. A positive tuberculin skin test
may be the only evidence of infection.
In few cases (e.g. the newborn, malnutrition, HIV) the immune response may not be
sufficient to prevent the multiplication of bacilli and the tuberculous infection may
progress to tuberculous disease within a few months.

Post-primary tuberculosis
Post primary tuberculosis occurs after a latent period of months or years after the primary
infection. It may occur either by endogenous reactivation of the latent primary infection
or by exogenous re-infection with TB bacilli.

Natural history of untreated PTB

Without treatment, after 5 years,

50% of pulmonary TB patients die

25% remain asymptomatic (good immune response)

25% remain ill with chronic infectious TB

Who is a TB suspect?
A TB suspect is a person who presents with symptoms or signs suggestive of TB,
particularly cough of three weeks or more.

Who is considered a Case of tuberculosis?

A case of tuberculosis is a patient in whom TB has been bacteriologically confirmed or
diagnosed by a clinician.

Definite case of TB
A definite case of TB is a patient with positive culture for the Mycobacterium
tuberculosis complex. (In countries where culture is not routinely available, a patient with
two sputum smears positive for acid-fast bacilli (AFB) is considered a definite case)

Common symptoms of pulmonary tuberculosis

Respiratory symptoms:
Cough usually more than three weeks
Haemoptysis (blood stained sputum)
Shortness of breath
Chest pain

Constitutional symptoms:
Fever and night sweats
Loss of appetite
Loss of weight
Tiredness (fatigue)

Symptoms of Extrapulmonary TB
The symptoms depend on the organ involved. Patients may present with constitutional
features of the disease fever, night sweats, loss of weight, and loss of appetite or local
symptoms related to the site of the disease.

CLASSIFICATION OF TUBERCULOSIS

It is important to classify the cases of TB in order to determine the correct treatment

regimen and the duration of treatment and for recording and reporting purposes, which
will facilitate cohort analysis of treatment outcome.
Classification of tuberculosis is based on:

Site of TB disease

Results of sputum smear

History of previous TB treatment

Classification by Site of disease and Result of sputum smear

Pulmonary tuberculosis (PTB)
Pulmonary tuberculosis refers to disease involving the lung parenchyma.

Smear-positive pulmonary tuberculosis

A patient with at least two sputum smears positive for AFB by direct
smear microscopy
OR

A patient with at least one sputum smear positive for AFB by microscopy
and chest X-ray abnormalities consistent with active pulmonary TB as
determined by a clinician
OR

A patient with at least one sputum smear positive for AFB by microscopy
and sputum culture positive for M. tuberculosis.

Smear-negative pulmonary tuberculosis

A patient with at least three sputum smears negative for AFB by

microscopy and chest X-ray abnormalities consistent with active
pulmonary tuberculosis and no response to a course of broad-spectrum
antibiotics and a decision by a clinician to treat the patient with a full
course of anti-tuberculosis therapy (Any patient given anti-TB treatment

should be recorded as a case. Incomplete trials of anti-tuberculosis

treatment should not be considered a method of diagnosis).
OR

A patient whose initial sputum smears were negative for AFB, but whose
sputum culture is positive for M. tuberculosis.

This group also includes cases without smear result, which should be
exceptional in adults but are relatively more frequent in children, because
children rarely produce a positive sputum smear.

Extrapulmonary tuberculosis (EPTB)

This refers to tuberculosis of any organ of the body other than the lung parenchyma.
Diagnosis should be based on one smear/culture-positive specimen, or histological or
strong clinical evidence consistent with active extrapulmonary tuberculosis, followed by a
decision by a clinician to treat with a full course of anti-tuberculosis chemotherapy.
A patient with both pulmonary and extrapulmonary tuberculosis should be classified as a
case of pulmonary TB.
Cases of pleural effusion and intra-thoracic lymphadenopathy (mediastinal and hilar)
without X-ray abnormalities in the lung parenchyma are also classified as extrapulmonary
TB.

Classification by previous treatment

In order to identify those patients at increased risk of acquired drug resistance and to
prescribe appropriate treatment, a case should be defined according to whether or not the
patient has previously received TB treatment.
The following definitions are used:

New
A patient who has never taken treatment for TB
OR
Who has taken anti-tuberculosis drugs for less than one month

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Relapse
A patient previously treated for TB who has been declared cured or treatment
completed, and is diagnosed with bacteriologically positive (smear or culture)
tuberculosis

Treatment after failure

A patient on treatment with category 1 who remains smear-positive at the end of
5 months or later during the course of treatment

Treatment after default

A patient who returns to treatment, with positive bacteriology, following
interruption of treatment for two months or more

Transfer in
A patient already registered in one district and transferred to another district for
continuation of treatment

Other
A patient who does not fit into anyone of the above definitions: e.g.
- A patient who has been taking treatment for TB for more than four weeks
without being registered with the NTP.
- A patient with smear-negative pulmonary TB or extrapulmonary TB who may
have relapsed (but without any bacteriological evidence) although this may be
rare.

Chronic
Patient remaining sputum smear positive after completing a fully supervised
re-treatment regimen

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Figure I

CLASSIFICATION OF TUBERCULOSIS

BACTERIOLOGY

SITE OF
DISEASE

PREVIOUS
TREATMENT

NO

SMEAR
POSITIVE

NEW CASE

PULMONARY
RELAPSE

SMEAR
NEGATIVE

TB CASES

EXTRA
PULMONARY

YES

TREATMENT
AFTER
FAILURE
TREATMENT
AFTER
DEFAULT
OTHERS
CHRONIC

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DIAGNOSIS OF TUBERCULOSIS

The highest priority for tuberculosis control is the identification and cure of the infectious
cases of tuberculosis. Therefore any person with symptoms suggestive of tuberculosis,
particularly cough for more than three weeks should be investigated.

Investigations
Sputum Smear microscopy
Sputum smear microscopy is the most reliable and cost effective method of diagnosing
infectious cases of pulmonary tuberculosis cases. Whenever tuberculosis is suspected in a
patient who has had a cough of three weeks or more, three sputum samples should be
collected and examined by microscopy for Acid-Fast Bacilli (AFB).

Collection of sputum samples

A PTB suspect should submit three sputum samples for microscopy. Three early morning
samples are preferable. Patient should be advised to collect sputum after coughing
following a deep inspiration and it should not be saliva.
Outpatients may provide sputum specimens as follows:

First spot specimen

- Supervised spot specimen at the first visit

Early morning specimen - Patient is given a sputum container to collect early morning
specimen on the following day.
Second spot specimen - Second supervised spot specimen is collected when the patient
returns with the early morning specimen, on the following day.

Chest X-ray
The chest X-ray has a limited role in confirming the diagnosis of pulmonary tuberculosis.
Diagnosis of tuberculosis by means of X-ray alone is unreliable. Abnormalities seen on a
chest X-ray may be mimicked by a variety of other conditions. However chest X-ray is
helpful particularly in the following instances:

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Diagnosis of PTB in children

Diagnosis of PTB in a suspect, whose sputum smears are negative for AFB

The decision to start on anti-TB treatment on patients should not be based solely on
abnormal chest X-ray findings and all efforts should be made to perform sputum
microscopy.

Sputum Culture for AFB

Culture examination of sputum for AFB is more sensitive and specific than direct smear
microscopy and may be useful in detecting cases where the number of organisms are
fewer than can be detected by direct smear microscopy. But this is more expensive and
takes at least 6-8 weeks to get the results.
Under ideal circumstances pre-treatment sputum cultures for AFB should be performed
on all PTB patients.
However due to limited facilities available, sputum cultures are recommended only in the
following situations: a) Pre-treatment cultures in Category 1 patients (Ref. page no. 21) who have a high
risk of drug resistance like health care workers, prisoners, HIV positive patients,
drug addicts and contacts of known drug resistant TB patients.
b) Pre- treatment cultures in all Category 2 patients. (Ref. page no. 22)
c) Pre treatment cultures in sputum smear-negative PTB patients
d) patients who fail to convert at the end of two months of Category 1 treatment

If there is likely to be a delay of more than 3 days in transporting the specimen, add a
preservative (cetyl pyridinium chloride) to the bottle. The central laboratory will provide
universal containers with CPC to the District Chest Clinics.

Tuberculin Skin Test

Tuberculin is a purified protein derived from tubercle bacilli. Following infection with M.
tuberculosis, a person develops hypersensitivity to tuberculin. When tuberculin is injected
into the skin of an infected person, a delayed local reaction occurs at the site of injection
after 24-48 hours.

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The Tuberculin skin test is of limited value in clinical work, especially in countries with
a high prevalence of TB

A positive test only indicates infection and not the presence or extent of
tuberculous disease.

A negative test does not necessarily exclude active TB.

There are several methods of doing the Tuberculin skin test- Mantoux, Heaf and Tine
methods. In Sri-Lanka, the Mantoux test is the method used.

Technique of Mantoux test

Several preparations of Tuberculin are available.
The tuberculin that is used in NTP in Sri Lanka is PPD-RT-23+ Tween 80 (2 TU).
The test is done by injecting 0.1 ml of tuberculin intra-dermally to the anterior aspect of
the left forearm. The transverse diameter of the induration is measured after 72 hours.
The results are recorded and interpreted as follows:
0 - 9 mm - Negative
> 10 mm - Positive
> 15 mm - Strongly positive

Interpretation of Tuberculin test

A Positive Tuberculin skin test

Only indicates past infection with Mycobacterium tuberculosis or with

mycobacteria other than M. tuberculosis
o May be due to previous BCG vaccination. This reaction is usually a
weaker reaction less than 10 mm.

A strongly positive test (>15 mm in BCG vaccinated individuals) favours a

diagnosis of tuberculosis.

However this should be interpreted in the context of clinical picture and other
investigations.
A positive tuberculin test is only one piece of evidence in favour of a diagnosis of
tuberculosis
A Tuberculin test has no value in diagnosis of re-activation. Repeat Mantoux testing is
not recommended in the diagnosis of TB because repeat test is known to have a booster
effect and may give a false positive result.

15

A Negative Tuberculin skin test

A diameter of skin induration less than 10 mm is considered as negative. However this
does not exclude a diagnosis of tuberculosis.
The following conditions may suppress the tuberculin skin test

HIV infection

Malnutrition

Severe bacterial infections including TB

Viral infections e.g. measles. chickenpox, glandular fever

Cancer

Immuno-suppressive drugs e.g. steroids

Diagnosis of Tuberculosis in children

Diagnosis of TB in children is often difficult
Only a small proportion of children have tuberculosis, which is sputum smear positive,
and many children cannot produce sputum for examination.
Since most young children swallow the sputum, gastric lavage or induced sputum may be
obtained early morning and sent for culture for M. tuberculosis. However since this is
very distressing to the child and the yield is low, it should be done only if it is essential
e.g. when the diagnosis is particularly difficult or when the child is ill.
Diagnosis of TB in children should be considered in the following situations.

Respiratory symptoms more than three weeks not responding to broad-spectrum

antibiotics

Undiagnosed illness continuing for more than 2- 4 weeks

Unexplained fever

History of contact with an infectious pulmonary TB case, particularly in the same

household

An abnormal chest X ray

A positive Tuberculin test

Unexplained weight loss or failure to gain weight in spite of adequate nutrition

Failure to thrive in an infant

Focal lesions such as enlarged lymph nodes, abdominal mass, ascites, CNS signs.

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TREATMENT OF TUBERCULOSIS

Treatment of tuberculosis is the cornerstone of any NTP. The modern treatment strategy
is based on standardized short course chemotherapy regimens and proper case
management to ensure completion of treatment and cure.

Aims of treatment of TB are:

To cure the patient of TB

To prevent death from active TB or its late effects

To prevent relapse of TB

To decrease transmission of TB in the community

To prevent the emergence of drug resistant TB

Short Course Chemotherapy (SCC) is now the recommended treatment for tuberculosis
and when properly applied, fulfills the above aims of anti-TB drug treatment.

Requirements for adequate chemotherapy

An appropriate combination of anti-tuberculosis drugs

Prescribed in correct dosage

Taken regularly by the patient

For the prescribed period of time

It is essential for the patients to receive and to adhere to the recommended course of
treatment (usually 6-8 months) in order to be cured. If patients fail to take their
combination of drugs regularly, the bacilli may become resistant to the drugs. The best
way to ensure patient adherence to treatment is Direct Observation of Treatment (DOT).
This means that the patient swallows the tablets under the direct observation of a health
worker or a trained person. The strategy of DOTS has been recommended by the WHO
and now internationally accepted as the standard method for TB control.

17

Essential (First-Line) Anti-tuberculosis Drugs

The five essential anti-TB drugs are:
Isoniazid (H)
Rifampicin (R)
Pyrazinamide (Z)
Ethambutol (E)
Streptomycin (S)

Mode of action of anti-TB drugs

A population of TB bacilli in a TB patient consists of the following groups.
1. Metabolically active, continuously growing bacilli inside cavities
2. Intra cellular dormant forms - bacilli inside macrophages
3. Extra cellular dormant forms
a) Bacilli which undergo occasional spurts of metabolism (semi dormant)
b) Dormant bacilli, which gradually die on their own.

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

Isoniazid, rifampicin, ethambutol, PAS are active against metabolically active bacilli.
Rifampicin has a special action against the semi dormant forms.
Pyrazinamide acts in an acid environment inside cells e.g. macrophages.
So far there is no drug, which can act on dormant bacilli

TB treatment regimens
Treatment regimens consist of two phases:
1.

Initial intensive phase

2.

Continuation phase

Intensive phase
During the initial intensive phase, there is rapid killing of TB bacilli. Infectious patients
quickly become non-infectious (within about two weeks) and symptoms improve. Most
patients with sputum smear-positive pulmonary TB becomes smear negative within two
months. Directly Observed Therapy (DOT) is essential in the initial phase to ensure that
the patient takes every single dose. This prevents development of drug resistance. The

18

risk of development of drug resistance is higher during the early stages of anti-TB
treatment, when there are more bacilli.

Continuation Phase
During the continuation phase, fewer drugs are necessary, but for a longer period. The
sterilizing effect of the drugs eliminates the remaining bacilli, thus preventing subsequent
relapses.
Patients who have taken anti-tuberculosis drugs previously are much more likely to
develop drug resistance, which may have been acquired through inadequate prior
chemotherapy. Such patients require a stronger regimen consisting of more drugs and for
a longer period.

Therefore before starting treatment, it is essential to question all patients closely and
carefully to determine whether or not they have previously taken treatment for
tuberculosis, so that they can be given the proper treatment regimen.

Standard code for TB treatment regimens

There is a standard code for TB treatment regimens and each anti-tuberculosis drug has
an abbreviation.
H Isoniazid
R - Rifampicin
Z - Pyrazinamide
E - Ethambutol
S Streptomycin

A TB treatment regimen consists of two phases, the intensive phase and the continuation
phase. The number before a phase is the duration of that phase in months. A subscript
number (e.g. 3) after a letter indicates the number of doses of that drug per week. No
subscript number after a letter indicates that the treatment is daily.
E.g.: 4 HR means 4 months of Isoniazid and Rifampicin daily.
5 H3 R3 E3 means 5 months of Isoniazid, Rifampicin and Ethambutol three times a week.

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Categories and Treatment Regimens

The treatment regimen recommended depends on the treatment category for each patient.
Two treatment categories and standardized regimens are used in Sri Lanka.

Table 1 Case definitions, Treatment Categories and Recommended Regimens

Case Definition

Treatment
Category

Treatment Regimen
Intensive Phase

Continuation
Phase

2 HRZE

4 HR

New cases
- PTB smear-positive
- PTB smear-negative
- Extrapulmonary TB

CAT 1

Re-treatment cases
- Relapses
-Treatment after failure
-Treatment after default
(smear-positive)

Category 1 (CAT 1) -

CAT 2

2HRZES / 1 HRZE

5 HRE

(Refer Flow Chart I)

This is given to all new patients:

-

New sputum smear-positive PTB

New sputum smear-negative PTB

New Extrapulmonary TB

Recommended Treatment Regimen

2 HRZE / 4 HR
Intensive Phase

Isoniazid
Rifampicin

daily for two months

Pyrazinamide
Ethambutol

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In patients who cannot be given Ethambutol as in the case of small children who are
unable to communicate visual symptoms, Streptomycin may be given instead of
Ethambutol.

In pulmonary TB cases, at the end of two months of intensive phase, do the

sputum smear examination.
-

If the smear is negative, start on the continuation phase of treatment.

- If the smear is positive at the end of two months, continue the intensive
phase of four drugs for another one month.

Repeat the sputum smear examination at the end of the 3rd month.

If the smear is positive at the end of the 3rd month, stop drugs for three days; send
sputum for TB culture and ABST.

Start on the continuation phase of treatment, regardless of the sputum result.

Continuation Phase

Isoniazid
Rifampicin

Daily for four months

Do follow up sputum smear examination at the end of 5 months and end of

treatment.
- If sputum smear is negative at the end of the 5th month and at the end of 6
months of treatment, chest X- ray is taken (optional) and anti-TB drugs
stopped.
- If the sputum is positive at the end of the 5th month or more, re-register
the patient as a Treatment Failure and start on Category 2 treatment.

For patients with tuberculous meningitis, miliary TB, or spinal tuberculosis with
neurological complications, continuation phase can be extended up to 7 months.

Category 2 (CAT 2) - (Refer Flow Chart II)

This is given to all Re-treatment cases:
-

Relapses

Treatment after failure

21

Treatment after default (sputum smear-positive)

Recommended Treatment Regimen

2 HRZES/ 1 HRZE / 5HRE

Intensive phase

Isoniazid
Rifampicin
Pyrazinamide

Daily for two months

Ethambtol
Streptomycin

Isoniazid
Rifampicin

Daily for one month

Pyrazinamide
Ethambutol

Do the sputum smear examination at the end of the 3rd month.

-

If the sputum smear is negative, start on the continuation phase of

treatment

- If the sputum is positive, the four oral drugs are continued for another
month

Repeat the sputum smear, at the end of the 4th month (If found positive at the end
of the 3rd month).
-

If the sputum is negative, start on the continuation phase of treatment.

If the sputum is still positive, further treatment will depend on the results
of pre-treatment culture and sensitivity test.

If the results are suggestive of multidrug-resistant TB, such patients should

be referred to Chest Physician for further management.

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Continuation Phase

Isoniazid

Daily for five months

Rifampicin
Ethambutol

Do the follow up sputum smear examinations at the end of the 5th month and end
of treatment.
- If the sputum is negative, do the chest X-ray (optional) and anti-TB drugs
are stopped.
- If the patient remains smear positive after the completion of a fully
supervised re-treatment regimen, he should be referred to the Chest
Physician for management. Such patients are defined as Chronic cases.

Fixed-dose combination tablets (FDCs)

Tablets of fixed-dose drug combinations have been recommended. There are several
advantages as well as disadvantages of using fixed drug combination tablets over
individual drugs. Sri Lanka has introduced FDCs for TB treatment regimens in 2005.

Advantages

Prescription errors are likely to be less frequent because dosage recommendations

are more straightforward and adjustment of dosage according to patient weight is
easier.

The number of tablets to ingest is smaller and may thus encourage patient
adherence to treatment.

If treatment is not observed, patient cannot be selective in the choice of drugs to

ingest.

Disadvantages

If prescription errors do occur, excess dosage (risk of toxicity) or sub-inhibitory

concentrations of all drugs (favouring development of drug resistance) may result

Health care workers may be tempted to evade Directly Observed Therapy,

erroneously believing that adherence is automatically guaranteed.

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Poor rifampicin bioavailability has been found for some FDCs, particularly in 3 or
4 drug combinations. Quality assurance is therefore essential.

Using FDCs does not obviate the need for separate drugs for a minority of patients
who develop drug toxicity.

Table 2 WHO recommended formulations of FDC

Drug

Dose form

Strength for daily use

Strength

for

thrice- weekly
use
Isoniazid+ rifampicin

Tablet

75mg +150mg

150mg+ i50mg

150mg + 300mg

Tablet or pack 30mg + 60mg

60mg + 60mg

of granules
Isoniazid+ethambutol

Tablet

150mg + 400mg

--

Isoniazid+thioacetazone

Tablet

100mg + 50 mg

--

300mg + 150mg
Isoniazid + rifampicin +

Tablet

75mg + 150mg + 400mg

pyrazinamide

150mg + 150mg+
500mg

Tablet or pack 30mg+60mg+150mg

--

of granules
Isoniazid+rifampicin+
pyrazinamide+ethambutol

Tablet

75mg+150mg+400mg+

---

275mg

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Flow chart I

Treatment and follow up of new smear-positive PTB cases - (CAT 1)

2 HRZE (S) *
Examine sputum (end of 2nd month)

Positive

Negative

Continue 1 HRZE (S)*

Start continuation phase

4 HR

Examine sputum
(end of the 3rd month)

Positive
Stop ATT for 3 days
Send sputum for culture
and ABST

Examine sputum
(end of the 5th month and
end of treatment)

Negative

Positive

Negative

Start continuation phase

4 HR

Examine sputum
(end of the 5th month and end of treatment)
Do a CXR**
and stop ATT
(Cured)
Positive

Negative

Do a CXR** and stop ATT

(Cured)
Treatment failure
Re-register and start on CAT 2
* Streptomycin is used where Ethambutol cannot be given as in young children
** Optional

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