Management of Tubeculosis

8/14/2019 Management of Tubeculosis

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MANAGEMENT OF

TUBERCULOSIS

A Guide ForLow Income Countries

Fifth edition2000

Donald A Enarson, Hans L Rieder, Thuridur Arnadottir, Arnaud Trbucq

International Union Against Tuberculosisand Lung Disease

68 boulevard Saint-Michel, 75006 Paris, France

The publication of this Guide was made possible thanks to the support ofMISEREOR, Postfach 1450, Mozartstrasse 9, 5100 Aachen, Germany


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Editor:

International Union Against Tuberculosis and Lung Disease (IUATLD)

68 boulevard Saint-Michel, 75006 Paris, France

Authors: D.A. Enarson, H.L. Rieder, T. Arnadottir, A. Trbucq

International Union Against Tuberculosis

and Lung Disease (IUATLD)

June 2000

All rights reserved.

No part in this publication may be reproduced without the prior permission

of the authors, the publisher, and the publishing house.

ISBN: 2-914365-00-4


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While tuberculosis has declined considerably in industrialised countries,the disease still poses a serious and even increasing problem in many low

income countries, affecting the health and social welfare of millions of

people. Fighting tuberculosis is a challenge to all who are concerned about

health and development. Thanks to modern antituberculosis medications,

it has become possible to cure practically all patients suffering from this

potentially fatal disease. Successful treatment, however, presupposes ade-

quate medication, close supervision of staff, direct observation of med-

ication swallowing and monitoring of treatment results by bacteriological

examination. Our project partners, including religious and other non-gov-

ernmental organisations, have repeatedly expressed their need for a con-

cise description of how to recognise, cure and combat tuberculosis today

in low income countries.

We have joined together with the International Union Against

Tuberculosis and Lung Disease in offering this Guide. The first edition of

10,000 copies, in English and French, was out of print in four years. The

second edition of 18,000 copies in English, French and Spanish, was out

of print in three years. It has also been translated into Chinese andMongolian. The third completely revised edition, in English, French and

Spanish, was published in 1994; 10,000 copies were out of print within

eighteen months. It was slightly edited in a fourth edition of which

10,000 copies were distributed, and which was out of print within two years.

The Guide contains a description of tuberculosis and its identification.

The treatment of tuberculosis and the organisation and management of tuber-

culosis services and the structure within which such services can be deliv-

ered, even under the most stringent socio-economic conditions, is outlined.

The tuberculosis situation is evaluated, and the interventions designed to

bring it under control are discussed. This fifth edition has been thoroughly

edited. The order of presentation has been revised to provide a more log-

ical flow of ideas. The new edition addresses issues that previously lacked

explanation, most notably the resistance of Mycobacterium tuberculosis to

medications and its impact on the management of tuberculosis.

We hope this will be a useful guide for tuberculosis control for those

who are valiantly shouldering the seemingly overwhelming task in remote

rural areas and in overcrowded urban slums. It will also be of interest to

PREFACE


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I. INTRODUCTION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

II. TUBERCULOSIS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

A. What do we know about this disease? . . . . . . . . . . . . . . . . . . . . . . . . . 3

1. What is tuberculosis? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

2. How does tuberculosis develop?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

3. How does HIV affect tuberculosis? . . . . . . . . . . . . . . . . . . . . . . . . . 4

4. What is drug resistance and how does it develop?. . . . . . . . . . 5

B. How is tuberculosis diagnosed?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

1. When is tuberculosis likely to be present? . . . . . . . . . . . . . . . . . . 6

2. Where is tuberculosis most likely to be found? . . . . . . . . . . . . . 6

3. How is a diagnosis of tuberculosis confirmed?. . . . . . . . . . . . . . 7

4. Who should be considered a case of tuberculosis?. . . . . . . . 9

5. How does HIV infection influence the diagnosis? . . . . . . . . . . 10

6. How do we know if a patient has drug resistance? . . . . . . . . . 10

III. TREATING THE DISEASE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

A. How is tuberculosis treated?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

1. What are the principles of treatment of tuberculosis? . . . . . . . 11

2. What if the patient has previously been treated?. . . . . . . . . . . . 12

3. What is directly observed treatment and how is it used? . . . 12

4. What do we use for treating tuberculosis? . . . . . . . . . . . . . . . . . . 13

B. What factors might affect treatment? . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

1. How does HIV affect treatment? . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

2. How does drug resistance affect treatment? . . . . . . . . . . . . . . . . . 22

3. What if the patient is pregnant or breast feeding? . . . . . . . . . . 23

C. What about those exposed to tuberculosis? . . . . . . . . . . . . . . . . . . . . . 23

1. What is preventive therapy and its role? . . . . . . . . . . . . . . . . . . . . 23

2. Can a patient on treatment infect you?. . . . . . . . . . . . . . . . . . . . . . 24

IV. CARING FOR THE PATIENTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

A. How should the patients be followed?. . . . . . . . . . . . . . . . . . . . . . . . . . 25

1. Are all the patients on treatment? . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

TABLE OF CONTENTS


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2. How can we encourage full participation of the patient? . . . 25

3. How do we monitor progress during treatment? . . . . . . . . . . . . 26

B. What is the most efficient way to deliver tuberculosis services? . 27

1. What is the proper structure of tuberculosis services? . . . . . . 27

2. How should the services be organised? . . . . . . . . . . . . . . . . . . . . . 28C. How is the laboratory service organised?. . . . . . . . . . . . . . . . . . . . . . . 31

1. What is the basis of the laboratory examination? . . . . . . . . . . . 31

2. What are the aims of the laboratory service? . . . . . . . . . . . . . . . 32

D. How do we monitor care? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

1. What records are necessary? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

2. How are the results reported? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

E. What supplies are needed and how are they managed? . . . . . . . . 42

1. How are supplies of medications managed?. . . . . . . . . . . . . . . . . 42

2. How are laboratory supplies managed?. . . . . . . . . . . . . . . . . . . . . . 443. What other supplies are needed? . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

V. PROTECTING THE COMMUNITY .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

A. What is the rationale for a tuberculosis programme?. . . . . . . . . . . 46

1. Why do we believe tuberculosis can be controlled? . . . . . . . . 46

2. Can tuberculosis be prevented by vaccination?. . . . . . . . . . . . . . 48

B. What should be done if there is no programme?. . . . . . . . . . . . . . . 481. Why is a programme important? . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48

2. How can care be given safely?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49

C. How can we ensure that activities achieve good results?. . . . . . . 50

1. How do we evaluate control measures? . . . . . . . . . . . . . . . . . . . . . 50

2. What is the size of the tuberculosis problem? . . . . . . . . . . . . . . 51

3. How will HIV affect the situation? . . . . . . . . . . . . . . . . . . . . . . . . . 52

4. Will patients respond to treatment?. . . . . . . . . . . . . . . . . . . . . . . . . . 53

VI. APPENDIX 1

Technical Guide for Smear Microscopy. . . . . . . . . . . . . . . . . . . . . . . . . . . . 55

VII. APPENDIX 2

Forms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91


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Tuberculosis is a great problem in most low income countries; it is the sin-gle most frequent cause of death in individuals aged fifteen to forty-nine

years. For this reason, activities directed against tuberculosis as a public

health problem are the direct responsibility of government health authorities.

The International Union Against Tuberculosis and Lung Disease is the

oldest international non-governmental organisation dealing with health. It

has gained immense experience in collaborating with partners in providing

care for more than one million tuberculosis patients in some of the poor-

est countries in the world, through the vehicle of the National TuberculosisProgramme. This Guide summarises that experience.

In setting out to combat a problem like tuberculosis, it is essential to

have a clear concept of aims and priorities. The aims of the fight against

tuberculosis are:

for a community: to reduce the spread of tuberculous infection, and

by this means to hasten the disappearance of this disease from society.

for individual patients: to cure their disease, to quickly restore theircapacity for activities of daily living and to preserve their position in

their family and community.

Of the priorities of tuberculosis activities, the first is the treatment and

cure of tuberculosis patients, especially those patients who are the source

of transmission of infection with tuberculosis micro-organisms. Because

tuberculosis is so frequent and is such a serious disease, it must be a high

priority for all who provide health care in low income countries, and tuber-

culosis services must be included in all health services provided.

Tuberculosis can be controlled successfully only in the context of a

National Tuberculosis Programme (NTP). Such a programme must operate

within the routine health service of each country. Paramedical personnel as

part of the many activities of the general health services usually perform

the everyday tuberculosis activities (case finding and treatment). It is essen-

tial that such personnel be properly trained, motivated and supervised.

The general population must be mobilised to participate, including

community organisations as well as groups of health professionals. It is

I. INTRODUCTION


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important to make clear to the population that tuberculosis is curable and

that there is no basis for discrimination or stigma. Community participa-

tion is essential to encourage individuals with symptoms suggestive of tuber-

culosis to present themselves to the health services for diagnostic exami-

nation and to ensure that tuberculosis patients continue to take their treatmentuntil they are cured.

In many countries, non-governmental organisations provide tuberculo-

sis services. They often work under difficult conditions in remote areas

where they provide the only medical services available. Their activities

should, nevertheless, always be undertaken in co-ordination with govern-

ment offices and must follow the guidelines of the National Tuberculosis

Programme.


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A. What do we know about this disease?

1. What is tuberculosis?

Tuberculosis is an infectious disease, caused in most cases by micro-

organisms calledMycobacterium tuberculosis. The micro-organisms usually

enter the body by inhalation through the lungs. They spread from the ini-

tial location in the lungs to other parts of the body via the blood stream,

the lymphatic system, via the airways or by direct extension to other organs.

Pulmonary tuberculosis is the most frequent form of the disease, occur-

ring in over 80% of cases. This is the form of tuberculosis which may

be infectious.

Extra-pulmonary tuberculosis is tuberculosis affecting organs other than

the lungs, most frequently pleura, lymph nodes, spine, joints, genito-

urinary tract, nervous system or abdomen. Tuberculosis may affect any

part of the body.

2. How does tuberculosis develop?

Tuberculosis develops in the human body in two stages. The first stage

occurs when an individual who is exposed to micro-organisms from an

infectious case of tuberculosis becomes infected (tuberculous infection), and

the second is when the infected individual develops the disease (tubercu-

losis).

2.1 How are tuberculosis micro-organisms spread?

How likely it is that a patient with tuberculosis may infect another person

is determined by the concentration of micro-organisms within the lungs and

their spread into the surrounding air. Patients with pulmonary tuberculosis

in whom the micro-organisms are so numerous as to be seen on micro-

scopic examination of sputum specimens (smear positive cases) are the most

infectious cases. Those in whom micro-organisms cannot be seen directly

II. TUBERCULOSIS


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under the microscope (smear negative cases) are very much less infectious

and the severity of their disease is usually less than that of the smear pos-

itive cases. Extra-pulmonary cases are almost never infectious, unless they

have pulmonary tuberculosis as well.

The infectious tuberculosis patient expels micro-organisms into the airin tiny droplets when coughing, laughing or sneezing. These small droplets

dry rapidly, become droplet nuclei carrying the micro-organisms, and may

remain suspended in the air for several hours. Any person entering the room

may inhale these droplet nuclei. If the micro-organisms establish themselves

in the lungs of the person who inhaled them, and begin to multiply, infec-

tion has occurred. Exposure to the micro-organisms is greatest among those

in close and prolonged contact with an infectious case (i.e., those living in

the same household).

The micro-organisms are rapidly destroyed by exposure to sunlight and

their concentration in the air is reduced by good ventilation. Except in the

event of close and prolonged contact with an infectious case of tuberculo-

sis, the chance of becoming infected from a single contact with a tubercu-

losis patient is very small. Most individuals who become infected have no

symptoms or evidence of illness in association with this infection.

2.2 What happens after infection

Among those who do become infected, most (possibly 80-90%) will never

become ill with tuberculosis unless their immunity is seriously compro-

mised. The micro-organisms remain dormant within the body and their pres-

ence is indicated only by a significant size of induration in reaction to a

tuberculin skin test. Some individuals who have become infected subse-

quently develop disease from this infection (termed tuberculosis). They are

most likely to develop disease in the period immediately following infec-

tion, but continue to experience a risk of tuberculosis throughout the remain-

der of their lives.

3. How does HIV affect tuberculosis?

Infection with the human immunodeficiency virus (HIV) leads to extensive

destruction of the immune defence mechanisms of the body. As a result,

those infected with HIV become ill with severe and often deadly diseases

to which persons without HIV infection would not usually be susceptible.

The development of tuberculosis following infection with tuberculosis micro-


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organisms is usually prevented by the actions of the immune system; this

explains why only a relatively small proportion of those individuals who

have been infected with tuberculosis go on to become ill with the disease.

When the protection provided by the immune system is reduced by HIV

infection, the tuberculosis micro-organisms that are dormant within the bodyof an individual who has been infected begin to multiply, causing tuber-

culosis.

4. What is drug resistance and how does it develop?

Clinically important resistance to medications is always a man-made prob-

lem. Because large populations of tuberculosis micro-organisms always con-

tain some mutants naturally resistant to medications, a substantial popula-

tion of resistant micro-organisms is always selected when a single medicationis used to treat a patient with a large population of micro-organisms. This

occurs because only the micro-organisms susceptible to the medications are

killed, leaving the resistant micro-organisms to multiply. When the micro-

organisms in a patient are resistant to all but one of the medications given

to that patient, the treatment has the same result as when a single medica-

tion is given alone.

There are two important types of resistance to medications in tuber-

culosis micro-organisms:

acquired or secondary resistance is due to incorrect treatment; for

instance, treatment with a single powerful medication in patients with

smear positive pulmonary tuberculosis (this is sometimes referred to

as monotherapy), or administration of powerful medications to a

patient harbouring tuberculosis micro-organisms resistant to all but one

of the medications which the patient is given (this phenomenon is

sometimes referred to as effective monotherapy);

primary resistance occurs when a patient develops tuberculosis after

being infected by another patient who has resistant micro-organisms.

Micro-organisms with resistance to at least the two most important med-

ications, isoniazid and rifampicin, are termed multidrug-resistant.


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B. How is tuberculosis diagnosed?

1. When is tuberculosis likely to be present?

The most frequent symptoms of pulmonary tuberculosis are:

persistent cough for 3 weeks or more; every patient presenting to a

health facility with this symptom should be designated a tuberculo-

sis suspect;

sputum production which may be blood-stained (termed haemoptysis),

shortness of breath and chest pain;

loss of appetite and loss of weight, a general feeling of illness (malaise)and tiredness (fatigue), night sweats and fever.

A patient presenting with these symptoms who is, or was, in contact with

a person with infectious tuberculosis is all the more likely to be suffering

from tuberculosis.

Symptoms of extra-pulmonary tuberculosis depend on the organ

involved. Chest pain from tuberculous pleurisy, enlarged lymph nodes and

sharp angular deformity of the spine are the most frequent signs of extra-

pulmonary tuberculosis.

2. Where is tuberculosis most likely to be found?

Tuberculosis cases are most frequently found in the following circumstances:

among patients who present themselves on their own initiative at a

health facility, with symptoms suggesting tuberculosis;

among those (especially children and young adults) living in the same

household with smear positive patients;

in those with an abnormality on a chest radiograph which has the

appearance of tuberculosis.

Tuberculosis will be detected most efficiently where health care providers

and community members are highly conscious of the symptoms suggestive

of tuberculosis.


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3. How is a diagnosis of tuberculosis confirmed?

3.1. What is the value of bacteriology?

Every individual suspected of having tuberculosis must have an examina-tion of sputum to determine whether or not they have infectious tubercu-

losis. This must be done prior to the commencement of their treatment. The

examination consists of microscopic examination of a specimen of sputum

that has been spread on a slide and stained by the Ziehl-Neelsen method

(smear microscopy). If micro-organisms (frequently referred to as acid-fast

bacilli, or AFB) are detected by this method, the patient is said to have

smear positive tuberculosis. Smear microscopy is the only means by which

the diagnosis of tuberculosis can be confirmed in most low income coun-

tries. It is important to carry out because it efficiently identifies the casesthat are most infectious and therefore have the highest priority for care. In

many low income countries, a different form of treatment is given to infec-

tious cases than is given to those cases who are not infectious.

Whenever tuberculosis is suspected, three specimens must be collected

for examination by microscopy. Whenever possible, they should be obtained

within twenty-four hours, as follows:

First specimen At the first interview with the patient a spot specimen iscollected; this specimen is obtained on the spot, after coughing and

clearing the back of the throat, under the supervision of a staff mem-

ber, in a well ventilated area, preferably in the open air.

Second specimen The patient is then given a sputum container for col-

lection of an early morning specimen (early morning specimen) before

the second interview, which should be on the next working day.

Third specimen On the second interview with the patient, another spot

specimen is collected.

Should the first spot specimen be positive and should the patient not return

for the second interview, an immediate search must be made to find the

patient in order to prevent transmission of micro-organisms in the commu-

nity and deterioration of the patients condition. A diagnosis should always

be confirmed by a second positive sputum specimen. A Medical Officer

should review any patient who is positive on only a single specimen.


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With three consecutive early morning specimens, it has been repeat-

edly found that of those patients who are eventually demonstrated to be

positive, approximately 80% are positive on the first examination, an addi-

tional 15% are first demonstrated to be positive on the second and an addi-

tional 5% on the third examination. An early morning specimen is morelikely to be positive than a spot specimen. Thus, the yield from a third,

spot, specimen might be expected to be lower. Consequently, when the

workload of the laboratory is excessive, it might be reasonable to routinely

examine only two specimens, rather than three. In this case, should a patient

be judged to require treatment, even though the two specimens are nega-

tive, a third specimen should be examined.

Prior to commencing treatment, a Medical Officer should review all

those thought to have tuberculosis but in whom the sputum smears are neg-

ative. The Medical Officer may wish to proceed in the following manner inorder to determine whether or not the patient actually has tuberculosis. If

chest radiography is available, it may be performed. If the chest radiograph

demonstrates shadows in the lung fields consistent with a pulmonary infec-

tion, a course of broad spectrum antibiotics may be given. If the patient

continues to show symptoms after completion of the antibiotics, a second

series of 3 sputum smear examinations may be performed and, if still neg-

ative, the Medical Officer may choose to treat the patient for tuberculosis

and record the patient as a case of pulmonary tuberculosis, smear negative.

3.2 Is radiology useful?

Diagnosis by means of radiographic examination in patients suspected of

tuberculosis is unreliable. Abnormalities identified on a chest radiograph

may be due to tuberculosis or to a variety of other conditions, and the

appearance on the radiograph is not specific for tuberculosis. Some indi-

viduals who have previously had tuberculosis that is now healed (and there-

fore does not require treatment) may have a chest radiograph that resem-bles tuberculosis requiring treatment. Chest radiographs may be helpful in

those patients who are not sputum smear positive, but they can be read

reliably only by a competent Medical Officer.

3.3 What about the tuberculin test?

A tuberculin skin test is sometimes used to help in the diagnosis of tuber-

culosis. The interpretation of a test result is often very difficult, as a pos-

itive test may not be caused by tuberculosis and a negative test does not


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always rule it out. Furthermore, tuberculin is not routinely available in many

peripheral health institutions, it is expensive, has a very short expiry date,

must be kept protected from light and heat and requires some technical

skills in administration and reading. Thus in most instances health care

workers are forced to work without this test.

3.4 How is tuberculosis diagnosed in children?

Diagnosis of tuberculosis in children is quite difficult. It should be remem-

bered that, in the majority of instances (with the exception of disseminated

tuberculosis, tuberculous meningitis, spinal tuberculosis and tuberculosis in

immunosuppressed children), childhood tuberculosis is a mild disease that

heals on its own, even with minimal or no treatment. Nevertheless, chil-

dren with tuberculosis should be treated to prevent complications and to

ensure that they do not subsequently develop tuberculosis from reactivation

of their infection. Only a very small proportion of children have tubercu-

losis that is smear positive, and many children cannot produce sputum for

examination. Points of most importance in determining a diagnosis in chil-

dren, in order of priority, are:

a history of contact with a case of infectious tuberculosis, particularly

in the same household;

an abnormal chest radiograph showing unilateral lymphadenopathyand/or shadows in the lung field indicating infiltration;

a positive tuberculin skin test, where such a test is available.

In the absence of all of the above, it is highly unlikely that the child has

tuberculosis. Any child whose tuberculin skin test remains consistently neg-

ative over some months of observation, while the clinical condition is good

or shows improvement, does not have tuberculosis.

Any child under 5 years of age, in contact with a smear positive caseand with signs or symptoms suggesting tuberculosis, should be regarded as

having active tuberculosis and should be given a full course of treatment.

Those without signs or symptoms of disease should be considered for pre-

ventive chemotherapy.

4. Who should be considered a case of tuberculosis?

Any person given treatment for tuberculosis should be recorded as a case.

Those who have tuberculosis micro-organisms visible on two microscopic


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examinations of sputum should be recorded as smear positive. All other

cases should be recorded in such a way as to distinguish them from smear

positive cases (as smear negative or as extra-pulmonary cases).

5. How does HIV infection influence the diagnosis?

Tuberculosis cases associated with HIV infection are, in the majority of

instances, indistinguishable from other cases. Smear positive cases are equally

identifiable whether or not they are infected with HIV. Some cases of tuber-

culosis associated with HIV infection may show unusual clinical features

and there may be an increase in the overall proportion of cases that are

smear negative and/or extra-pulmonary. Nevertheless, sputum smear exam-

ination remains an essential component in the diagnosis of tuberculosis in

those countries where HIV infection is frequent, because of its ability toidentify the infectious cases, and because the majority of patients with pul-

monary tuberculosis and HIV infection are found to be smear positive.

6. How do we know if a patient has drug resistance?

The confirmation of the diagnosis of tuberculosis in most low income coun-

tries is based on sputum smear microscopy. To detect resistance, it is nec-

essary to culture the micro-organisms and subsequently perform tests to

determine their susceptibility to medications. These methods are complex

and expensive, and are not routinely available in most low income coun-

tries. Treatment is given without knowledge of the susceptibility of the

micro-organisms to the medications.

If drug resistance is already present, there is a possibility that the treat-

ment might create more resistance. The recommendations put forward in

this Guide were developed specifically in order to prevent this from occur-

ring. Changes to the recommendations may compromise the balance nec-

essary to prevent resistance. On the other hand, when the recommendationsare strictly followed, tuberculosis can be successfully treated in the vast

majority of cases, without knowledge of the susceptibility patterns of indi-

vidual patients, and without promoting drug resistance.


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A. How is tuberculosis treated?

If the diagnosis of tuberculosis is made at an early stage of the disease and

the patient is not seriously ill (either from tuberculosis or from other dis-

ease), it is possible to cure virtually any case of tuberculosis. This is achieved

if they are treated properly and the micro-organisms causing their disease

are not resistant to the medications frequently used for treatment of tubercu-

losis. Patients with multidrug-resistant tuberculosis (caused by micro-

organisms that are resistant to both isoniazid and rifampicin) are difficult,if not impossible, to cure.

1. What are the principles of treatment of tuberculosis?

1.1 What is the basis of treatment?

The basis of the treatment of tuberculosis is chemotherapy. It is also one

of the most efficient means of preventing the spread of tuberculosis micro-

organisms. The requirements for adequate chemotherapy are:

an appropriate combination of antituberculosis medications to prevent

the development of resistance to those medications;

prescribed in the correct dosage;

taken regularly by the patient;

for a sufficient period to prevent relapse of the disease after comple-tion of treatment.

Treatment must be given to every patient confirmed as having tuberculo-

sis, and must be given free of charge to the patients.

1.2 When should treatment be started?

Treatment should not be commenced until a firm diagnosis is made.

Treatment should always be started as soon as possible after two labora-

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tory reports are received indicating smear positive examinations, or if the

patient is severely ill and the clinical suspicion of tuberculosis is high. A

Medical Officer should determine treatment for those with only a single

positive report or with negative reports.

1.3 What are the phases of treatment?

Treatment of smear positive cases should always include an initial inten-

sive phase. An initial course of the combination of medications recom-

mended in this Guide is effective in eliminating micro-organisms and in

minimising the influence of micro-organisms that are resistant to medica-

tions. The intensive phase in those patients who are initially smear posi-

tive should be given for a minimum of 2 months and continued until they

become smear negative, but for no longer than a total of 3 months (themajority of cases will already be negative at 2 months). The intensive phase

is a very important part of the chemotherapy.

The continuation phase is important to ensure that the patient is per-

manently cured and does not relapse after completion of treatment. The

continuation phase does not require as many medications, but does require

a sufficient duration to ensure success.

2. What if the patient has previously been treated?

Before treatment is started, it is essential to question all patients closely

and carefully to determine whether or not they have previously taken treat-

ment for tuberculosis. Sputum smear positive patients who have been pre-

viously treated for as much as one month should be suspected of having

micro-organisms resistant to one or more medications. Such patients require

a different form of treatment from those who have never been previously

treated. A Medical Officer should carefully supervise their care.

3. What is directly observed treatment and how is it used?

The regimens proposed in this Guide will cure most newly diagnosed cases

of tuberculosis. To achieve this, it is vital that the patient takes the total

quantity of medication prescribed. To ensure that this occurs, frequent and

careful supervision is necessary. Whenever rifampicin is given to a patient,

a health worker must directly observe that the patient swallows every dose

of the combination of medications given. This will require the patient to

be present for direct administration on a daily basis for the total period


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during which rifampicin is given. This is usually accomplished on an

ambulatory basis if the patient can attend the treatment centre daily.

Occasionally it will require that the patient has accommodation arranged

at the treatment centre, in a hostel or in some other location. When the

patient is very ill, it may be necessary for the patient to be admitted tohospital.

The continuation phase does not contain rifampicin and is usually given

in monthly supplies for daily, self-administered intake (except in the case

of retreatment, where rifampicin is given). This limits the duration of time

required for the patient to attend the health service daily, freeing the patient

to return to normal daily activities after the initial intensive phase, when

the patient is usually strong enough to do so.

When the patient has completed the prescribed duration of treatment,

the medications should be stopped. Additional chemotherapy is unneces-

sary if all the medications prescribed have been taken. Although it is dis-

tinctly unusual for tuberculosis to relapse after adequate treatment, patients

should be told to report for re-examination if symptoms suggesting tuber-

culosis recur.

4. What do we use for treating tuberculosis?

There are only a limited number of medications currently available for thetreatment of tuberculosis. For this reason they must be used with great care

in order not to create resistance to these medications. The presence of resis-

tance, and particularly of multidrug resistance, makes the treatment much

less likely to be successful.

4.1 Which medications are most effective?

The most important medications for the treatment of tuberculosis are iso-

niazid (H), rifampicin (R), pyrazinamide (Z), ethambutol (E), streptomycin(S) and thioacetazone (T). Some medications are available in combined

preparations: rifampicin with isoniazid {RH}, thioacetazone with isoniazid

{TH}, and ethambutol 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 proper storage conditions, is as

follows:

5 years: isoniazid, ethambutol, thioacetazone

3 years: rifampicin, pyrazinamide, streptomycin


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The use of rifampicin and streptomycin for diseases other than mycobac-

terial diseases should be limited to very carefully considered indications.

Those medications used for treatment of tuberculosis should only be avail-

able to the community through the National Tuberculosis Programme; they

should not be available freely from the private market.

4.2 What do they contain?

There is international agreement on the recommended dosage of each

antituberculosis medication, which is calculated per kilogram body weight

(Table 1).

MedicationDaily dosein mg/kg

Intermittent dose3 times/wk in mg/kg

Isoniazid5

(4-6)10

(8-12)

Rifampicin 10(8-12)

10(8-12)

Pyrazinamide25

(20-30)35

(30-40)

Ethambutol15

(15-20)30

(25-35)

Streptomycin15

(12-18)15

(12-18)

Thioacetazone2

(2.5)

Table 1. Optimal dosages for essential antituberculosis medications

(the range is given in parentheses).

This guide proposes that a limited variety of preparations be available

for each drug. This will simplify the management of the supply of med-


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ications. It will enhance safety in prescription, and will allow the correct

dosage to be given. The preparation with the lowest content is usually rec-

ommended for treatment of adults: {RH} 150 mg/75 mg; H 100 mg;

Z 400 mg; E 400 mg; {EH} 400 mg/150 mg; S 1 g. The exception is {TH},

for which the larger, single-tablet dosage of {TH} 150 mg/300 mg is moresimple to use for adults > 40 kg.

4.3 How are they used?

For both the patient and the community it is essential to prevent the devel-

opment of drug-resistant tuberculosis. A patient who fails on a first course

of treatment is more likely to have resistant micro-organisms. Resistance

to one medication may lead to the development of resistance to any other

medication when that medication is given as a sole companion to one towhich the micro-organism is already resistant.

A retreatment regimen must be available that is likely to cure any

patient who fails on the first course of treatment. This regimen must use

the best available medications to which the patient is likely to respond,

because it is the patients last chance for cure. The retreatment regimen

recommended by this Guide includes rifampicin plus isoniazid throughout,

supplemented with ethambutol. Patients who fail on the first-line treatment

regimen should not be taking rifampicin as a sole companion to isoniazid

at the point at which they are identified as failing the treatment, as thismay lead to development of multidrug resistance. It is for this reason that

the Guide strongly discourages the use of rifampicin in the continuation

phase of treatment for patients never previously treated for tuberculosis for

as much as one month.

A patient who is identified as failing treatment when taking isoniazid

plus thioacetazone still has a high probability of cure. In such a case, two

effective medications (rifampicin and ethambutol) are given in the continu-

ation phase of the retreatment regimen. These medications will never havebeen previously used alone with isoniazid, to which the micro-organisms

may have been resistant at the outset. If the patient has been given isoni-

azid plus ethambutol in the continuation phase of the first-line regimen, the

retreatment regimen should contain pyrazinamide throughout the course,

again to ensure that the patient at all times receives at least two medica-

tions in the retreatment regimen which are likely to be effective.


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Eight-month chemotherapy for newly diagnosed casesof tuberculosis

Eight-month chemotherapy should be given to all smear positive cases of

pulmonary tuberculosis who were never previously treated for as much as

one month for tuberculosis, provided arrangements can be made to ensurethat every dose of medication in the intensive phase of treatment is directly

observed to be swallowed. This regimen may also be used for patients with

other forms of tuberculosis that have never been previously treated, if they

are seriously ill. Such treatment should be given under the direction of a

Medical Officer and directly observed swallowing should be used in the

intensive phase. The directions for administration of medications according

to the weight of the patient are given in Table 2.

Table 2. Number of tablets to be taken daily for adults on treatment

according to weight and content of the tablets.

Monthof treatment

Medication

Weight in kg

25-39 40-55 > 55

1-2Intensive

phase

{RH}

(R 150 mgH 75 mg)

Combined tablets

2 3 4

3-8Continuation

phase

{TH}(T 50 mgH 100 mg)

Combined tablets

2

{TH}(T 150 mgH 300 mg)

Combined tablets

1 1

Z (400 mg) 2 3 4

E (400 mg) 1.5 2 3

R = rifampicin; H = isoniazid; Z = pyrazinamide; E = ethambutol; T = thioacetazone.


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Eight-month chemotherapy of previously treated patients

Smear positive patients who have taken medications for treatment of tuber-

culosis for as much as one month in the past must be given a retreatment

regimen (Table 3). They include:

Relapses: these are patients who become smear positive again after having

been treated for tuberculosis and declared cured after the comple-

tion of their treatment.

Treatment after failure: these are patients who, on initial treatment for smear

positive pulmonary tuberculosis, remained or became again smear pos-

itive at 5 months or later during the course of treatment.

Treatment after default: these are patients who return to treatment smear

positive after having left their treatment for more than 2 months. Those

who on return to treatment are smear negative should not be newly

recorded, but should continue their original treatment until the com-

pletion of the total quantity prescribed.

Chronic cases are defined here as those who continue to be smear

positive after the completion of a fully observed retreatment regimen

(failures of retreatment). Their micro-organisms are likely to be resistantto both isoniazid and rifampicin, and such patients are virtually incurable

in most low income countries. Such patients should be registered

separately.

Twelve-month chemotherapy for newly diagnosed cases

of tuberculosis

For twelve-month chemotherapy the following regimen is used: isoniazid

plus thioacetazone (in a combined tablet) daily for 12 months. For smear

positive patients this combination must always be supplemented by

streptomycin or ethambutol daily for the first 2 months of chemotherapy

(Table 4).

This regimen is used for all cases of tuberculosis other than those that

are smear positive. It may be given to new cases of smear positive tuber-

culosis (supplemented with streptomycin in the intensive phase) if the

8-month regimen is not available or if it is impossible to directly observe

all doses of medication in the intensive phase.


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Table 3. Number of tablets to be taken for adults on retreatment according to

the weight and content of the tablets.

R = rifampicin; H = isoniazid; Z = pyrazinamide; E = ethambutol; S = streptomycin* Patients aged 45 years and over should receive 0.75 g; streptomycin should not be given to pregnant

women.** When E is used routinely in new cases in the continuation phase, Z (400 mg) must be continued

during months 4-8 in the retreatment phase, 3 tablets for those < 40 kg, 3 tablets for those 40-55 kg

and 4 tablets for those > 55 kg.

432E (400 mg)

211H (100 mg)

432

{RH}(R 150 mgH 75 mg)

Combined tablets4-8

Continuation

phase(three timesweekly)**

321.5E (400 mg)

432Z (400 mg)

432

{RH}(R 150 mgH 75 mg)

Combined tablets3

Intensivephase(daily)

321.5E (400 mg)

1.0 g*0.75 g0.5 gS

432Z (400 mg)

432

{RH}(R 150 mgH 75 mg)

Combined tablets1-2

Intensive

phase(daily)

Monthof treatment

Medication

Weight in kg

25-39 40-55 > 55


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Table 4. Dosage of medications to be taken for patients on twelve-month treat-

ment according to weight.

1

{TH}(T 50 mg

H 100 mg)Combined tablets

Weight in kg

10-24

2

25-39

40-55

{TH}(T 150 mgH 300 mg)

Combined tablets

1 1

0.25 gS 0.50 g 0.75 g 1.00 g

1E (400 mg) 1.5 2 3

>55Medication

4.4 What adverse effects can they have?

Adequate treatment of each case for the full duration of the prescribed reg-imen is very important if success in treatment is to be achieved. Any change

to the treatment regimen due to what appear to be side effects must be

made only after careful consideration.

Treatment of tuberculosis is prolonged over a number of months. During

such a period of time in anyones life, some events might occur which, if

they occur in someone taking medications, may be thought to have been

caused by these medications. Particularly frequent events of this type include

skin rashes and abdominal complaints. In studies of the use of isoniazid,

in which the comparison group was given no active medication, it wasnoted that of episodes that doctors considered were caused by reactions to

medications, approximately half were caused by something else. How, then,

do we know if a reaction is due to the medications?

When to stop medications without further consideration

These are very infrequent reactions that require the medications to be

stopped, and frequently that the patient be hospitalised for management.

They include the following:

T = thioacetazone; H = isoniazid; S = streptomycin; E = ethambutol


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Skin irritation or rash in any patient on thioacetazone. The med-

ication must be stopped immediately and never given again (it should

be replaced with ethambutol).

Generalised reactions including shock, purpura and fever. This is very

rare but may be caused by rifampicin, pyrazinamide or streptomycin.

The medication thought to be responsible for the reaction should never

be given again.

Impairment of vision in a patient on ethambutol. Patients develop-

ing impaired vision should report immediately for examination. If

ethambutol is thought to be responsible, it should never be given again.

Patients who are pregnant must neverbe given streptomycin due to

risk of vestibulo-cochlear damage to the foetus.

What to do when you think there may be an adverse effect

Dizziness may be caused by vestibular damage due to streptomycin.

This is most frequent in older individuals. Correct dosage and dura-

tion of treatment is important to prevent occurrence of these side effects.

If a patient develops the following symptoms, medications may need to be

stopped while the cause is investigated.

Jaundice or severe abdominal discomfort may be caused by hepati-

tis. It is most frequently due to isoniazid, but may also be caused by

rifampicin and pyrazinamide. Any patient with these symptoms should

be referred to the Medical Officer for further consideration.

Skin rash in a patient not on thioacetazone. This is most frequently

due to isoniazid, streptomycin or pyrazinamide. If the patient is clin-

ically well (does not suffer from advanced tuberculosis or serious formssuch as meningitis or disseminated disease), it is best to stop all med-

ications and recommence them when the reaction has subsided. If the

symptoms recur, the patient should be referred to the Medical Officer.

Reactions not requiring interruption of treatment

Numbness or tingling may be caused by isoniazid. When it occurs,

it can be treated by supplementing the isoniazid with vitamin B6 at a

dose of 5 mg daily.


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Joint symptoms may be caused by pyrazinamide. Check the dosage

by weight; it is usually caused by overdosage. It may be easily alle-

viated with acetyl salicylic acid.

All patients on rifampicin: inform each patient to expect a red/orangecolour to body fluids (tears, saliva, sputum, urine and sweat) which is

not dangerous.

Determine if the patient is taking birth control medications, anti-epileptic

medications, corticosteroids, oral treatment for diabetes, or oral anticoagu-

lants. These may require adjustment of dosage, or the use of alternative

methods in the case of birth control.

B. What factors might affect treatment?

1. How does HIV affect treatment?

Patients infected with HIV usually have a response to treatment similar to

that of patients who are not infected with HIV, with a few exceptions:

they are more likely to die during the course of treatment, usually fromcauses other than tuberculosis;

they may be more likely to experience toxic reactions to medications

(and particularly to thioacetazone) than those who are not HIV

infected, and their treatment must be adjusted for this reason;

they are more likely to relapse if treated with the twelve-month

regimen.

HIV infection is spread most frequently by sexual intercourse, through

exchange of blood or blood products and from mother to child. Because

of the association between tuberculosis and HIV infection, great care must

be taken in tuberculosis programmes and in health services in general to

prevent the spread of both of these infections. The highest standards of

hygiene must be observed, particularly when there is a risk of exposure

to blood or blood products, when caring for tuberculosis patients. The use

of injections should be limited as much as possible. Where they cannot


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be avoided, every health care worker should strictly adhere to the princi-

ple: a sterilised needle and syringe for each injection in each individual

patient.

A health care worker who is HIV seropositive should avoid exposure

to tuberculosis patients because of the greatly increased risk of developingtuberculosis if infected. Any patient who is infected with HIV should be

carefully protected from exposure to other patients with tuberculosis.

Moreover, wherever HIV positive patients come together (in hospital wards,

hospices and community support groups), a great deal of attention should

be paid to any possibility of the occurrence of tuberculosis in these patients

and every effort should be made to quickly diagnose and treat tuberculo-

sis which may occur.

Patients known or suspected of having HIV infection should neverbegiven thioacetazone. The best alternative is to provide them with treatment

consisting of appropriate doses of ethambutol and isoniazid, according to

their weight, given in the form of combined tablets containing 400 mg

ethambutol plus 150 mg isoniazid {EH}: 3 tablets for those > 55 kg,

2 tablets for those 40-55 kg, and 1.5 tablet for those 25-39 kg.

2. How does drug resistance affect treatment?

Large populations of tuberculosis micro-organisms, such as those in patients

who are sputum smear positive, always contain some mutants naturally

resistant to medications. If a correct combination of medications is pre-

scribed and is taken by the patient, this resistance is overcome and does

not pose a problem. This is the reason for using a greater number of med-

ications during the intensive phase of treatment until the population of

micro-organisms has been rapidly reduced. This important principle must

be respected in order to prevent development or extension of clinically

important resistance to medications.

Once developed, resistance to antituberculosis medications can have

an influence on the impact of treatment of tuberculosis cases, by causing

the emergence of further resistance (where an insufficient combination of

medications is used) or by rendering the patients incurable (where resis-

tance to isoniazid and rifampicin coincide in an individual patient). The

recommendations put forward in this Guide propose the steps most likely

to be successful in preventing multidrug-resistant tuberculosis and thus pre-

venting the development and spread of incurable tuberculosis.


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3. What if the patient is pregnant or breast feeding?

Pregnant women with tuberculosis should start or continue their treatment

for tuberculosis in the same way as other patients. However, streptomycin

should not be used because of the risk of toxicity to the unborn child. Whenthe patient has a nursing infant, it is of particular importance to continue

breast feeding, as its discontinuation poses a serious risk for the develop-

ment of the infant.

C. What about those exposed to tuberculosis?

Those who live in the same household with any patient who is smear pos-

itive have a higher risk of having tuberculosis themselves. If they have anysymptoms, they should be requested to attend for a medical examination.

Any child in the household under 5 years of age who has symptoms that

suggest tuberculosis should be given treatment as a case of tuberculosis.

All of the other children under 5 years of age should be given preventive

chemotherapy, even if they have previously been vaccinated.

1. What is preventive therapy and its role?

Preventive therapy is the treatment of those infected with Mycobacterium

tuberculosis (tuberculous infection) who do not have the disease (tubercu-

losis). The infection can be identified with a tuberculin skin test. The risk

of developing tuberculosis in those who are tuberculin skin test positive is

relatively low unless the infection has been acquired relatively recently or

the person is also HIV positive. Preventive therapy in such persons can

prevent the development of tuberculosis to an important extent.

This Guide recommends preventive treatment with isoniazid daily for

a period of 6 months at a dose of 5 mg/kg body weight.

Often tuberculin is not available. The most important group that can

be identified as needing preventive therapy are children under the age of

5 years who are living in the same household as a newly discovered smear

positive tuberculosis patient. The chance that the child has been infected is

high, as is the chance of the development of tuberculosis. New smear pos-

itive patients must be questioned carefully to determine if there are chil-

dren in their household. These children must then be examined and treated

as outlined above.


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2. Can a patient on treatment infect you?

Treatment is effective in rapidly diminishing the infectiousness of any patient

with susceptible micro-organisms. This is because the medications rapidly

reduce the number of micro-organisms, and the patients cough rapidly sub-

sides, resulting in fewer micro-organisms expelled into the air. In most set-

tings, no special precautions for preventing the spread of infection need be

taken once the patient is on treatment; the best prevention is to ensure that

the medication is being taken regularly.

This is not true, however, if the micro-organisms are multidrug-

resistant, in which case great care must be taken to avoid transmission to

those around the patient. Where multidrug-resistant tuberculosis is frequent,

great care must be taken to avoid contact, as much as possible, between

those who have (or are likely to have) tuberculosis and any personlikely to have HIV infection. Good ventilation must be provided wherever

tuberculosis patients (or those likely to have tuberculosis) gather. Institution-

alisation of tuberculosis patients should be avoided, whenever possible, and

where they are institutionalised, the best ventilation possible for the area

should be provided. Moreover, tuberculosis patients (and those likely to

have tuberculosis) should be given accommodation in an area away from

other patients.


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The quality of the care given to patients and the thoroughness with whichit is followed are important determinants of successful treatment and of

reduction in the risk of becoming infected. Poor treatment increases the

number of infectious cases in a community.

A. How should the patients be followed?

Because tuberculosis treatment is prolonged, great care must be taken to

ensure that the treatment is taken as prescribed.

1. Are all the patients on treatment?

A periodic review, usually once a week, should be performed to compare

the names of the patients identified as smear positive in the laboratory with

the list of patients commenced on treatment, to ensure that no patients iden-

tified in the laboratory go without treatment. Moreover, the laboratory results

of all those patients who have been commenced on treatment who are notsmear positive should be confirmed in the laboratory to ensure that their

examinations have been performed and are negative.

2. How can we encourage full participation of the patient?

The successful treatment of the patient requires that the patient understand

what is happening. When the patient understands the nature of the disease

and its treatment, the patient is more likely to follow the treatment required

to achieve cure. The relationship developed between the patient and the

care giver is key to achieving success in treatment, and requires investment

of time and energy.

The patient and, if possible, at least one member of the patients fam-

ily, should clearly understand the answers to the following questions:

What is tuberculosis?

How is the disease spread?

What measures can be taken to limit its spread?

IV. CARING FOR THE PATIENTS


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How is it treated?

Can the disease be cured?

Can I get treatment free of charge?

What medications are used and for how long?

How is the treatment followed? What are the possible side effects of the medications?

If the patient understands the disease and its treatment, this information

will be passed on to the community and, as a result, other individuals with

tuberculosis will be encouraged to come forward to seek diagnosis and

treatment.

3. How do we monitor progress during treatment?The results of sputum smear examination should be recorded for all adult

patients prior to the commencement of treatment. Priority is given to treat-

ment of smear positive patients, as these are the most potent sources of

infection in the community.

Bacteriological follow-up examinations in smear positive patients are

the most important means of assessing progress. After 2 months of inten-

sive phase treatment the sputum in these patients must be examined. Those

patients found to have no tuberculosis micro-organisms on sputum exami-nation should start the continuation phase. If the examination is positive,

the intensive phase should be prolonged, but only up to a total of 3 months.

At this time the continuation phase is started without additional microscopic

examination. This is a safe practice where regimens using {TH} in the con-

tinuation phase are used. Should other medications (R or E) be given alone

with H in the continuation phase, this practice may carry the risk of extend-

ing drug resistance in a patient with micro-organisms that are already resis-

tant to H.

In all smear positive patients, a microscopic examination is done at

5 months. If the result is negative, treatment should be continued. If

any micro-organisms are identified (whatever the grade of the positive

result see Appendix 1, Technical Guide for Smear Microscopy), the

result should be confirmed by a second positive result before declaring

the patient a treatment failure who must be given the re-treatment

regimen.

Sputum microscopy examination is repeated on the final visit, one

month prior to completing the treatment course. If negative, the patient is


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given the last one-month supply of medications and declared cured. Patients

with positive smears on this examination, confirmed by a second exam-

ination, are declared treatment failures and must be given the re-treatment

regimen.

The total duration of treatment is always 8 months or 12 months,depending on the regimen, unless the patients are treatment failures. Patients

who do occasionally miss an appointment during the continuation phase

should have the time of treatment missed added to the originally planned

duration. If irregular treatment lasts longer than 15 months, the outcome of

treatment of the patient is recorded as defaulted.

B. What is the most efficient way to delivertuberculosis services?

Because tuberculosis is a widespread disease and its prevention is depen-

dent on good quality medical care of individual patients, the organisation

and system through which this care is given is an important element in

achieving success in tuberculosis services.

1. What is the proper structure of tuberculosis services?

The responsibility for activities directed at controlling tuberculosis rests

with the government. These activities must be organised in the form of a

National Tuberculosis Programme. The aims of a National Tuberculosis

Programme are as follows:

to quickly diagnose and cure as many of the infectious cases of tuber-

culosis as possible, and in this way, to rapidly and greatly reduce the

rate of spread of tuberculosis micro-organisms;

to maintain vigilance in the detection of all new infectious cases which

will continue to arise during the entire lifetime of that group in the

population which has already been infected prior to the application of

control measures;

to limit the excess transmission of tuberculosis micro-organisms result-

ing from the presence of HIV infection in the community.


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To achieve these aims, a National Tuberculosis Programme must be:

country-wide, with a focus on areas where the greatest proportion

of the population lives. It requires a strong urban component (urban-

isation is increasing rapidly and tuberculosis is a particularly serious

problem in overcrowded urban areas);

permanent, ensuring that the cases continuously arising from those

already infected with tuberculosis micro-organisms will be rapidly iden-

tified and rendered non-infectious (a process that must continue through

the lifespan of the last heavily infected group in the population);

adapted to the realities of each community within which it operates,

taking note of the characteristics of the population, the accessibility

of health facilities, and the attitudes of health care personnel;

integrated within the general health services of the community, as

tuberculosis is one of the most important causes of ill health in low

income countries and patients present with their symptoms at every

level of the health service.

The modern National Tuberculosis Programme is based on the DOTS strat-

egy (Directly Observed Treatment, Short-course), promoted by the World

Health Organization. This strategy has been based on the experience of the

IUATLD and its partners, which is described in this Guide. The elements

of the DOTS Strategy are:

political commitmenton the part of the government;

a secure supply of essential medications and diagnostic materials;

diagnosis and follow up based on sputum smear microscopy;

treatment using short-course chemotherapy for at least smear positive

cases, and directly observed treatment (DOT) when rifampicin is used;

monitoring through proper recording and reporting of activities.

2. How should the services be organised?

The structure of the tuberculosis service should be based upon the unit of

management serving, on average, a population of 50,000 to 150,000.


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2.1 At the unit of management

Each unit of management should have a Unit Co-ordinator. This person,

usually a paramedical, is responsible for ensuring that tuberculosis activi-

ties (case-finding and treatment) are correctly applied within the unit of

management, along with the other responsibilities normally carried out

by the health workers. This level should be the most peripheral site of

sputum microscopy, as services that are more peripheral than this cannot

be sure of maintaining proficiency in carrying out their activities, and the

organisation of supplies and supervision becomes impossible. The Unit

Co-ordinator is responsible for:

ensuring that the correct treatment regimen is applied to all patients

(in particular, ensuring that those patients eligible for the retreatment

regimen are correctly identified and treated);

ensuring that all rifampicin-containing treatment is given directly

observed by a health worker;

determining that all patients commenced on treatment have had a spu-

tum smear examination performed;

comparing the Tuberculosis and Laboratory Registers (see Appendix 2,

Forms 2 and 4) to make sure that all patients are enrolled on treatment;

ensuring action aimed at preventing defaulting (such as patient edu-

cation and communication) and initiating early action to trace all

patients who do not appear at regular appointment times;

keeping the Tuberculosis Register in order and up-to-date;

reporting the results of tuberculosis activities in the unit;

maintaining supplies of materials (including treatment supplies such as

medications, and diagnostic supplies such as reagents) within the unit.

2.2 At the intermediate level

In order to maintain a good quality of service, a system of training and

supervision must be in place to support the Tuberculosis Co-ordinator in

the management unit. For this reason, each group of 5-10 districts should

have an individual (the Provincial/Regional Co-ordinator) responsible for


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ensuring that this occurs. In most instances, this individual is a physician

or medical assistant who acts as an expert in the area to determine what

is to be done when problems arise. This individual carries out the tuber-

culosis activities in addition to other responsibilities (often providing spe-

cialist services for chest diseases or other communicable diseases). TheProvincial/Regional Tuberculosis Co-ordinator is responsible for:

nominating health workers to manage the care of tuberculosis patients;

supporting and supervising the activities of the Co-ordinator in the

management unit, who must be visited at least quarterly (or more fre-

quently in the case of poor performance);

providing training for all new personnel and refresher training of thosewho require special attention in the light of their performance;

maintaining a continuous supply of materials and a system of quality

control of sputum smear microscopy;

organising the treatment of patients, including living arrangements for

patients who must remain away from home to receive treatment;

reviewing the reports of tuberculosis activities and discussing themwith the Co-ordinators of the management units each quarter;

co-ordinating with officials at the central level to ensure regular super-

vision, training, supply and reporting, and with colleagues respon-

sible for other programmes such as AIDS, Leprosy and Laboratory

Services.

2.3 At the central level

Within the Ministry of Health, there must be a Central Tuberculosis Unit

with a full time director and support staff to ensure that the National

Tuberculosis Programme functions appropriately. The Director must have

responsibility for all activities in the country. The functions of the Central

Tuberculosis Unit include the following:

planning, implementing, monitoring and evaluating the National

Tuberculosis Programme, including work plans, budgets, reports and

administration;


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co-ordinating with the Division of Laboratories to ensure that the net-

work of laboratories is properly supervised, that quality control activ-

ities are carried out correctly and that training is appropriate;

ensuring, in collaboration with those responsible for logistics and sup-

ply, the regular supply of materials throughout the country, including

monitoring consumption based on reports of case-finding results, co-

ordination with the supply system in the Ministry of Health, estima-

tion of requirements for supplies of materials and medications;

regularly supervising and supporting the Provincial/Regional Co-

ordinators;

collaborating with the AIDS Programme to ensure that patients who

are affected by both tuberculosis and HIV are properly cared for and

that exposure of HIV infected individuals to tuberculosis micro-

organisms is avoided;

ensuring that authorities are fully aware of the priority that should be

given to tuberculosis programme activities, including allocation of mate-

rial and human resources.

2.4 External evaluation

Periodic external evaluation by recognised experts in tuberculosis control

should be undertaken in all countries for review of technical aspects of the

programme and their implementation. Such reviews provide an independent

critique of the programme and give support to programme personnel in their

attempts to gain a hearing from decision makers in order to make neces-

sary changes.

C. How is the laboratory service organised?

A well-functioning laboratory is the first requirement for successful man-

agement of tuberculosis. If the diagnosis is not made reliably and if fol-

low-up of treatment is not trustworthy, all other activities will be affected.

1. What is the basis of the laboratory examination?

Every patient requires sputum smear examination to correctly determine the

treatment that the individual needs. Because of this, it is necessary to have


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laboratory services that reach the entire population served by the health ser-

vice. Such laboratory services should be provided within the context of the

already existing health service structure, and the duties of sputum smear

examination should be included among the other duties of the laboratory

technicians already present within the health service. There is no need forspecialised personnel for performance of sputum smear microscopy within

the general health service. Because tuberculosis contributes to such an extent

to the health problems of most countries, every general laboratory techni-

cian within the health service should have the skills to perform this diag-

nostic procedure.

The recommended method for routine confirmation of a diagnosis of

tuberculosis is the microscopic examination of smears of sputum specimens

stained using the Ziehl-Neelsen method. For this purpose, a good quality

binocular microscope with an electrical light source (or a mirror where elec-

tricity is unavailable) is essential. The microscope must be equipped with

an oil immersion objective (x 100) in order to carry out the examination,

and should have a movable stage.

The technical aspects of sputum smear examination are provided in

the Technical Guide for Sputum Examination for Tuberculosis by Direct

Microscopy (Appendix 1).

2. What are the aims of the laboratory service?

The aims of the laboratory service with respect to tuberculosis are:

the confirmation of tuberculosis diagnosis (including the correct clas-

sification of cases upon which the treatment regimen is determined);

the monitoring of the treatment of sputum smear positive cases; and

the surveillance of the tuberculosis situation in the community.

2.1 The network of microscopy centres

Diagnosis must be made as close as possible to the residence of the patients,

while maintaining the proficiency of the testing procedures. To accomplish

the first two of the above aims, a network of laboratory centres carrying out

sputum smear microscopy at a high technical level must be maintained.


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The laboratory technicians in the general health services must be com-

petent to carry out sputum smear microscopy; this requires that they be

trained, motivated and properly supervised.

It is important to plan services in such a way that they are accessible

to the population and yet maintain an adequate degree of technical profi-ciency. To accomplish this, it is generally recommended that one microscopy

centre should be developed for each unit of population containing between

50,000 and 150,000 inhabitants, according to the incidence of tuberculosis

and the geographic distribution of the population. Great care should be

taken not to extend the network to a more peripheral level, as this results

in deterioration of technical proficiency and an inability to properly super-

vise the activities. In principle, the microscopy centre should be located at

the same site as the treatment centre (which should serve a similar sized

population).

2.2 Assuring quality of smear microscopy

Quality assurance of all laboratory investigations (including sputum smear

microscopy) is essential if the tests are to be meaningful and useful in the

care of the patient. Because the network of sputum smear microscopy cen-

tres is so important in the care of the patients, quality assurance is an indis-

pensable component of any tuberculosis programme. Quality assurance ofsmear microscopy is the responsibility of the National Public Health Service

Tuberculosis Reference Laboratory. A regular system of quality assurance

must be part of the supervision process, and retraining of technicians who

perform their duties in a deficient manner must be undertaken.

Quality assurance consists of three components. Internal quality con-

trol includes all means by which the laboratory itself controls its operation.

Proficiency testing (often called external quality control) is undertaken by

selecting a sample of slides for rereading outside the laboratory by a dif-

ferent individual than the one who performed the original examination, with-out the second individual knowing the result of the first examination.

Improvement in the quality of work results from identification, through

internal quality control and proficiency testing, of weaknesses or errors.

Quality assurance of sputum smear microscopy is more than a laboratory

exercise: it is a method of ensuring the quality of diagnosis and classifi-

cation of the tuberculosis patients within the health service.

Various methods may be chosen for proficiency testing. Immediately

following training of a laboratory technician, slides of known content may


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be given to the trainee for re-examination. This allows the capabilities of the

newly trained individual to be assessed. To ascertain the routine performance

of a laboratory, slides might be randomly selected following identification

in the Laboratory Register. To determine the quality of patient classifica-

tion, slides from patients registered in the Tuberculosis Register, comprisinga representative sample of all patients cared for in the health service, may

be examined. With each approach, the sample should include negative slides

(or slides from patients classified as sputum smear negative) and positive

slides (or slides from patients classified as sputum smear positive).

Detailed information on establishing and carrying out these activities

is included in the publication The Public Health Service National

Tuberculosis Reference Laboratory and the National Laboratory Network,

available from the IUATLD.

2.3 Culture and susceptibility testing

Sputum smear microscopy must have the highest priority in the care of

tuberculosis patients. More sophisticated tests (such as culture and suscep-

tibility testing) should not be undertaken until an adequate network of lab-

oratories for smear microscopy has been developed which serves the whole

community and which has a good system of quality control. It is usually

not possible to provide a diagnostic service based upon culture and sus-

ceptibility testing. The role of culture and susceptibility testing is to accom-plish another aim of the laboratory service, the surveillance of the tuber-

culosis situation in the community.

The determination and surveillance of resistance ofM. tuberculosis to

medications is useful as a means of monitoring the adequacy of a tuber-

culosis programme. Clinically important resistance of micro-organisms to

medications is always a man-made problem and is frequently a reflection

of individual or programmatic malpractice (the prescription or provision of

inappropriate or inadequate treatment regimens, resulting in effective

monotherapy). The development and/or promotion of resistance to medica-

tions reflects such malpractice. When it is detected using a system of sur-

veillance, prompt action must be taken to prevent further occurrence. The

development of resistance to medications (and particularly to isoniazid and

rifampicin) severely compromises the ability of the health services to cure

the individual patient and to bring the tuberculosis problem under control.

Technical guidelines for the determination and surveillance of resis-

tance to medications in National Tuberculosis Programmes are available

upon request from the IUATLD.


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D. How do we monitor care?

The adequate care of tuberculosis cases requires that records be kept on

each individual patient, with periodic reporting of the results of case-find-

ing and of treatment. This is essential to ensure that the patient is correctlytreated and that adequate supplies of essential materials are provided. In

addition, the information that is routinely collected and reviewed allows

problems that may arise with the management of the patients and of the

system to be identified. The documents used to record and report the care

of the patients should be simple, clear and kept to the absolute minimum

that is required for adequate care. The following description provides a

guide for the recording of patients as they appear to the health facility, and

comprises the minimum number of records and reports necessary to ensure

the proper care of the patients.

1. What records are necessary?

1.1 Records of diagnostic examinations

All individuals who present themselves to the general health service who

are likely to have tuberculosis are required to have a sputum smear exam-

ination. The initial sputum sample is obtained during the first consultation

with the health care worker, at which time a Request for Sputum Examination

(Appendix 2, Form 1) is completed. When the sputum sample is received

in the laboratory, the information on the individual patient is entered in the

Tuberculosis Laboratory Register (Appendix 2, Form 2). As indicated in

the sample form, each patient examined for diagnosis will have at least

two sputum examinations that are entered on a single line in the laboratory

register.

1.2 Records of cases of tuberculosis

If the patient is designated a tuberculosis case, a Patient Identity Cardwill

be completed which will be kept by the patient. This card contains the

name, age, sex and address of the patient. It identifies the health service

identification number (where this is routinely used), the tuberculosis regis-

ter number and the name of the health service. The type of tuberculosis as

well as the date and results of bacteriological examination at the time of

diagnosis, the date the treatment was commenced, the regimen prescribed


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and spaces for the dates of follow-up appointments and results of follow-

up sputum examinations are recorded. At the same time a Tuberculosis

Treatment Card (Appendix 2, Form 3) is completed, which is kept at the

health service where the patient receives treatment. The information from

this card is entered into the Tuberculosis Register (Appendix 2, Form 4)within the unit where the patients care is managed. If the patient is diag-

nosed in a referral facility (such as a hospital or other institution), the loca-

tion in which the patients care will be managed after leaving the institu-

tion should be determined, and the patient should be entered into that

register.

In completing the Tuberculosis Register, great care should be taken to

ensure that the information is correctly recorded and regularly updated.

When a patient is newly detected, precise information should be entered.

Patients should be recorded in numerical order as they become known tothe health worker responsible for the Tuberculosis Register. Numbering

commences with number one at the beginning of each calendar year, regard-

less of when the patient was diagnosed or commenced treatment. Particular

attention should be taken to ensure that the patient is correctly recorded

and treated. This includes identification of the correct disease site:

Pulmonary cases are those with tuberculosis of the lungs including

those who are sputum smear positive and those who are sputum smear

negative (provided a minimum of three sputum examinations have beenperformed).

Extra-pulmonary cases are all other patients, including those with tuber-

culous pleurisy and miliary tuberculosis (the specific site should be

recorded).

The correct category of patient necessary to determine the proper treat-

ment is one of the following:

A new case is one who has never previously been treated for as much

as one month.

A relapse case is one who, having previously been treated, was declared

cured prior to becoming once again sputum smear positive.

Treatment after failure is a patient who, while on treatment, remained

or became again smear positive at 5 months or later during the course

of treatment.


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A patient is recorded as treatment after default on returning to the

health service sputum positive after having interrupted treatment for

more than 2 months.

A patient who is a transfer in is any patient who has been registered

for treatment in another tuberculosis register and has been transferred

to the unit to continue treatment. The results of treatment of all such

patients should be reported to the location in which the patient was

initially registered, for inclusion in the regular reports of treatment

results. The results of such patients should never be reported to the

central authorities from the location to which the patient has been trans-

ferred to continue treatment.

All other patients are entered under the column other.

It is extremely important to determine correctly, for all patients with smear

positive pulmonary tuberculosis, whether or not they have previously been

treated for as much as one month. The incorrect designation of such patients

will result in incorrect treatment of the patient. The correct assignment of

patients to the three categories relapse, treatment after failure, and treat-

ment after default, allows precision

Documents

Management of Tubeculosis