GENERAL MANNUAL

FOR TUBERCULOSIS CONTROL

National programme for Tuberculosis Control and Chest Diseases

Ministry of Health

Sri Lanka January 2005

GENERAL MANUAL

FOR

TUBERCULOSIS CONTROL

Second Edition - 2005

National Programme for Tuberculosis Control and Chest Diseases

Ministry of Health

Sri Lanka January 2005

i

NPTCCD-2005

International Consultant – Dr. Shantha Devi Thottikkamath National Consultant – Dr. Vessamitta R. Weeraratna

First Edition 1997

ii

CONTENTS

Foreword vi

Preface vii

Abbreviations and acronyms viii

Introduction 1

PART I – BASIC INFORMATION ON TUBERCULOSIS AND

TECHNICAL GUIDELINES FOR TUBERCULOSIS CONTROL 3

1. Tuberculosis 5

2. Classification of Tuberculosis 9

3. Diagnosis of Tuberculosis 13

4. Treatment of Tuberculosis 17

5. Essential (First line) anti-TB drugs 32

6. Monitoring of treatment 44

7. Tuberculosis and HIV 47

8. Pregnancy and Tuberculosis 50

9. Role of BCG vaccination 52

10. Prevention of Tuberculosis 54

11. Multidrug-resistant TB 56

PART II – OPERATIONAL GUIDELINES FOR TUBERCULOSIS CONTROL 63

1. Objectives and strategy of National Tuberculosis Programme 65

2. National Tuberculosis Programme 67

3. Tuberculosis case finding 73

4. Treatment and follow up of TB patients 80

5. Recording and Reporting 85

6. Supervision 90

7. Evaluation 92

8. Training 95

9. Management of drugs and supplies 96

iii

10. Intersectoral co-ordination 97

PART III – ADMINISTRATION OF A CHEST CLINIC 99

1. District Chest Clinic 101

2. Drug supplies 103

3. Issue of medical certificates 106

LIST OF FLOW CHARTS Flow Chart I Treatment and follow up of new smear-positive PTB cases (CAT 1) 25

Flow Chart II Treatment and follow up of Re-treatment cases (CAT 2) 26

Flow Chart III Treatment and follow up of smear-negative PTB cases 27

Flow Chart IV Management of TB suspects at Peripheral Health Institutions 76

Flow Chart V Management of TB suspects at District Chest Clinics 79

LIST OF FIGURES

Figure I Classification of Tuberculosis 12

Figure II Anti-TB drug management cycle 96

LIST OF TABLES

Table 1 Case definition, Treatment Categories and Recommended Regimens 20

Table 2 WHO recommended formulations of FDC 24

Table 3 Actions in interruption of TB treatment 31

Table 4 Number of tablets of FDC used in CAT 1 and CAT 2 37

Table 5 Adverse effects of first line anti-TB drugs 38

Table 6 Symptom based management of side-effects of Anti-TB drugs 39

Table 7 Re introduction of anti-TB drugs following drug induced hepatitis

after LFTs return to normal 41

Table 8 Re-introduction of anti- TB drugs following drug reaction 43

Table 9 Schedule for follow up sputum examination 45

iv

Table 10 How PTB differs in early and late HIV infection 48

Table 11 Dosages and mode of action of reserve anti-tuberculosis drugs 59

Table 12 Suggested treatment regimen for MDR-TB (WHO) 60

Table 13 Training schedule for operational staff of the NTP 95

ANNEXES

Annex 1 Organization of the NPTCCD 111

Annex 2 Tuberculosis Treatment Card 113

Annex 3 Tuberculosis Follow up Card 115

Annex 4 District Tuberculosis Register 117

Annex 5 Tuberculosis Laboratory Register 119

Annex 6 Request for Sputum Examination form 121

Annex 7 Request for Tuberculosis Culture and Drug Susceptibility Test form 123

Annex 8 Transfer/Referral Form for Tuberculosis Patients 125

Annex 9 Quarterly Report on Case Finding 127

Annex 10 Quarterly Report on Sputum Conversion of smear-positive

patients at the end of intensive phase 129

Annex 11 Quarterly Report on the Results of Treatment of patients 131

registered 12-15 months earlier

Annex 12 Quarterly Report on Microscopy activities and Logistics 133

Annex 13 Quarterly Report of Programme Management (District level) 135

Annex 14 Quarterly Report – TB & non TB wards 143

Annex 15 Quarterly Report – Chest Hospital, Welisara 147

Annex 16 Quarterly Report – National TB Reference Laboratory 153

Annex 17 Register of TB suspects 157

v

FOREWORD

Tuberculosis (TB) remains a major & growing public health problem throughout the

world. Tuberculosis can affect all sections of society and all countries and communities

are vulnerable to this infectious disease. In Sri Lanka about 9,000 cases are detected each

year.

Tuberculosis can be cured completely through directly observed treatment, short-course

(DOTS) which is also the most cost-effective way of controlling the disease. Inadequate

treatment of patients, in particular the sputum smear-positive cases can lead to the

emergence of Multidrug-resistant tuberculosis in the country.

Therefore, it is essential that all tuberculosis patients should be managed according to the

national guidelines provided in this manual. This is the second edition of the manual

which has been updated giving the information on HIV-related TB, Multidrug-resistant

TB (MDR-TB) and the use of Fixed-dose combinations of anti-tuberculosis drugs. The

manual will help all health personnel to update their knowledge on tuberculosis and its

control.

I request all health personnel in the country to adhere to the national guidelines provided

in this manual and join hands in addressing the challenge of tuberculosis control.

Dr. Athula Kahandaliyanage

Director General of Health Services

vi

PREFACE

The National Programme for Tuberculosis control and Chest Diseases has prepared this second

edition of “General Manual for Tuberculosis Control” with the aim to give practical guidance to

all those who manage tuberculosis patients. In addition to updating the information already

published in the first edition, the information on HIV-related TB, Multidrug-resistant TB (MDR-

TB) and the Fixed-dose Combinations of anti-tuberculosis drugs has been included.

The identification and cure of infectious TB cases i.e. the patients with smear-positive pulmonary

TB is the only way to interrupt the transmission of the disease in the community. These guidelines

cover the identification of patients in a very cost-effective manner, the treatment of patients, both

adults and children, with smear-positive pulmonary TB, smear-negative pulmonary TB and

extrapulmonary TB. The treatment regimens based on standardized short-course chemotherapy

and proper case management ensure cure. Standardized treatment is a component of the

internationally recommended strategy for TB control known as “DOTS”. The revised guidelines

focus on this strategy.

The guidelines given here closely follow the “Guidelines for National Tuberculosis Programmes”

published by WHO. The revision and updating of the manual and the guidelines was done by

Dr.(Mrs.) S. D. Thottikkamath and Dr.(Mrs.) V.R. Weeraratna in consultation with the consultant

chest physicians and the medical officers of the NPTCCD. Several workshops were held to

discuss different aspects of this work and to finalize the chapters. The contents have been perused

by the SLMA Committee on Communicable Diseases and their comments were discussed and

included. The development and the printing of the manual has been funded by the IDA assisted

National HIV/AIDS Prevention Project.

This edition is intended for the use by all the medical officers both in the public and private sector

in the management of TB patients and I trust that they will adhere to the guidelines laid down here

to diagnose the TB patients early in the disease, to ensure cure of the diagnosed patients and to

prevent the emergence of Multidrug-resistant TB.

I express my sincere thanks to all those who worked hard in developing the second edition.

Dr. Chandra Sarukkali

Director

National Programme for Tubercuosis Control and Chest Diseases

vii

ABBREVIATIONS AND ACRONYMS

ABST - Antibiotic Sensitivity Test AFB - Acid Fast Bacilli AIDS - Acquired Immuno Deficiency Syndrome AMO - Assistant Medical Officer ATT - Anti-tuberculosis Therapy BCG - Bacillus Calmette Guerin BHT - Bed Head Ticket CAT 1 - Category 1 CAT 2 - Category 2 CXR - Chest X-ray CNS - Central Nervous system DDG/PHS - Deputy Director General, Public Health Services DOTS - Directly Observed Treatment Short course DTCD - Diploma in Tuberculosis and Chest Diseases DTCO - District Tuberculosis Control Officer EPI - Expanded Programme of Immunisation EPTB - Extra Pulmonary Tuberculosis FDCs - Fixed Dose Combinations FEFO - First Expired First Out HIV - Human Immuno-deficiency Virus IV - Intravenous LFT - Liver Function Test MDR-TB - Multi Drug-resistant Tuberculosis MLT - Medical Laboratory Technologist MO - Medical Officer MOH - Medical Officer of Health MRO - Medical Records Officer NGO - Non Governmental Organisation NPTCCD - National Programme for Tuberculosis and Chest Diseases NTP - National Tuberculosis Programme PHI - Public Health Inspector PTB - Pulmonary Tuberculosis RMO - Registered Medical Officer RMSD - Regional Medical Supplies Division SCC - Short Course Chemotherapy TB - Tuberculosis VCT - Voluntary Counseling and Testing WHO - World Health Organisation

viii

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 cost-

effective 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.

2

PART I

BASIC INFORMATION ON TUBERCULOSIS

AND

TECHNICAL GUIDELINES

FOR

TUBERCULOSIS CONTROL

3

4

1 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 individual’s 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.

5

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 Ghon’s focus. The bacilli spread

through the lymphatics to the hilar lymph nodes causing enlargement of the nodes. The

Ghon’s 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.

6

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

7

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.

8

2 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

9

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

11

Figure I CLASSIFICATION OF TUBERCULOSIS

BACTERIOLOGY SITE OF DISEASE

NO NEW CASE

YES

SMEAR POSITIVE

SMEAR NEGATIVE

PULMONARY

EXTRA PULMONARY

TB CASES

PREVIOUS TREATMENT

TREATMENT AFTER FAILURE

RELAPSE

CHRONIC

OTHERS

TREATMENTAFTER DEFAULT

12

DIAGNOSIS OF TUBERCULOSIS

3 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:

13

• 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.

14

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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4 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.

19

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

Treatment Regimen Case Definition Treatment Category

Intensive Phase Continuation Phase

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

CAT 1

2 HRZE

4 HR

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

CAT 2

2HRZES / 1 HRZE

5 HRE

Category 1 (CAT 1) - (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

20

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.

22

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.

23

• 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

Tablet or pack

of granules

75mg +150mg

150mg + 300mg

30mg + 60mg

150mg+ i50mg

60mg + 60mg

Isoniazid+ethambutol Tablet 150mg + 400mg --

Isoniazid+thioacetazone Tablet 100mg + 50 mg

300mg + 150mg

--

Isoniazid + rifampicin +

pyrazinamide

Tablet

Tablet or pack

of granules

75mg + 150mg + 400mg

30mg+60mg+150mg

150mg + 150mg+

500mg

--

Isoniazid+rifampicin+

pyrazinamide+ethambutol

Tablet 75mg+150mg+400mg+

275mg

---

24

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 Examine sputum (end of the 3rd month) (end of the 5th month and

end of treatment)

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

25

Flow chart II

Treatment and follow up of Re-treatment cases (CAT 2) (Send sputum for pre-treatment culture and ABST)

2 HRZES

1 HRZE

Examine sputum (end of the 3rd month)

Positive Negative Continue 1 HRZE Start continuation phase 5 HRE Examine sputum (end of the 4th month) Examine sputum end of the 5th month and end of treatment) Positive Negative Further treatment determined by result Start continuation phase of pre-treatment 5 HRE Positive Negative culture & ABST

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)

‘Chronic Case’ Refer to a Chest Physician ** Optional

26

Flow chart III

Treatment and follow up of smear-negative PTB cases

Smear-negative PTB

(Send sputum for pre-treatment culture)

2 HRZE(S)

CXR after 1 month

Examine sputum (end of the 2nd month). Negative Positive Start Continuation Phase Treatment Failure 4 HR Examine sputum Stop ATT * Do a CXR Re-register Stop ATT Start CAT 2 (Completed Rx)

* If no improvement in the abnormality found in the original CXR, refer the patient to a

Chest Physician.

27

Directly Observed Treatment Directly Observed Treatment (DOT) is one of the important elements of the

internationally recommended strategy for TB control. Directly Observed Treatment

means that an observer watches the patient swallow their tablets. This ensures that a TB

patient takes the right anti-tuberculosis drugs, in the right doses at the right intervals

without interruption and ensures that the patient completes the full course of treatment.

Why is Directly Observed Treatment necessary?

Patient compliance is a key factor in treatment success. Many patients who receive self-

administered treatment often take drugs irregularly and a significant proportion of

patients stop treatment before completion due to various reasons. It is impossible to

predict who will or will not comply. Therefore directly observed treatment is required to

ensure treatment adherence and it also helps to motivate the patient to continue treatment.

It is recommended in the intensive phase of treatment at least for all sputum positive

cases. A patient who misses one attendance for DOT can be traced immediately,

counseled and returned to treatment.

Patient compliance should be promoted through a patient centered approach by:

- Facilitating easy access to treatment, by organizing directly observed

treatment as close to patient’s home (or the work place) as possible

- Providing anti-tuberculosis drugs free of charge

- Providing polite and rapid attention.

28

National policy for the implementation of Directly Observed Treatment (DOT)

Patients who will be given DOT –

• New Pulmonary TB (sputum positive and negative) cases

Intensive phase:

All new Pulmonary TB (sputum positive and negative) patients should be given

directly observed treatment daily during the intensive phase. This should be

arranged as far as possible community based, or hospital based wherever

necessary as in the case of very ill patients or those patients who are unable to

come daily for supervised treatment

Continuation phase:

Since the continuation phase also contains Rifampicin, every effort should be

made to give each dose under observation. Wherever this is not possible patients

will be advised to attend the chest clinic once a week, and the first dose will be

given under direct observation and the remaining six doses will be supplied for

self-administration at home. DTCO will make arrangements for supervisory visits

to check drug intake (including pill counts).

• Extra pulmonary TB

Intensive Phase:

Drugs will be given under direct observation

Continuation phase:

Since the continuation phase also contains Rifampicin, every effort should be

made to give each dose under observation. Wherever this is not possible patients

will be advised to attend the chest clinic once a week and the first dose will be

given under direct observation and the remaining six doses will be supplied for

self-administration at home. The DTCO will make arrangements for supervisory

visits to check drug intake (including pill counts).

• All Re-treatment cases

Directly Observed treatment should be given throughout the entire period of

treatment daily, both in the intensive and continuation phase of treatment.

Admission to hospital is recommended whenever possible.

29

DOT Providers –

The following categories will provide Direct Observation of Treatment.

• Health workers at state health care facilities

• Field health care workers

• General practitioners

• Trained volunteers

• Community leaders

Trained community volunteers or community leaders need regular support, motivation

and supervision by the NTP staff to ensure that quality is maintained.

Provision of drugs for the DOT Centres -

Drugs for each patient will be delivered to the DOT centres from the District Chest Clinic

by the PHI or any other staff assigned by the DTCO.

Interruption of treatment (default) Directly Observed Treatment adapted to the needs of the patient is the best method of

avoiding treatment interruption. However, even with directly observed treatment and

during the continuation phase of treatment, which may be self-administered, there may be

treatment interruption.

Measures to minimize treatment interruption

At the time of registration of a TB patient, the staff must educate the patient and the

family regarding the duration of treatment and the importance of adherence to treatment.

It is vital to record the patient’s address and other relevant addresses e.g. parents or work

place etc. in order to help locate the patients who interrupt treatment. As far as possible,

the address should be verified at the beginning of treatment.

Management of patients who interrupt treatment

It is important to take action on defaulters immediately. Patients should be contacted the

day after missing a dose during the intensive phase and as soon as possible during the

continuation phase. It is important to find out the reason for the patient’s absence in order

to take appropriate action and continue treatment.

30

Table 3 Actions in interruption of TB treatment

Interruption for less than 1 month

• Trace patient

• Solve the cause of interruption

• Continue treatment and prolong it to compensate for missed doses

Interruption for 1-2 months Action 1 Action 2

Continue treatment and prolong it to

compensate for missed doses

Treatment Continue treatment and

received: prolong it to compensate

for

< 5 months missed doses

• Trace the patient

Solve the cause of

interruption

• Do 3 sputum smears.

Continue treatment

while waiting

If smears negative

or EPTB

If one or more

smears positive

do culture &

ABST

> 5 months Category 1: Start Cat 2

Category 2: refer for advice

(may evolve to Chronic)

Interruption for 2 months or more (defaulter) Action 1 Action 2 • Do 3 sputum smears

Solve the cause of

interruption, if possible

No treatment while

waiting for results

• Send culture & ABST

Negative smears

or EPTB

One or more

smears positive

Clinical decision on individual basis

whether to restart or continue treatment,

or no further treatment

If on Category 1 Start Category 2

If on Category2 Refer for advice (may

evolve to Chronic)

31

ESSENTIAL (FIRST LINE) ANTI-TB DRUGS 5

Isoniazid (INAH) Isoniazid is highly bactericidal against replicating tubercle bacilli. It is rapidly absorbed

and diffuses readily into all fluids and tissues. The plasma half-life, which is genetically

determined, varies from less than one hour in fast acetylators to more than three hours in

slow acetylators. It is largely excreted in the urine within 24 hours, mostly as inactive

metabolites.

Uses

• Isoniazid is a component of all TB chemotherapeutic regimens currently

recommended by WHO.

• Isoniazid alone is occasionally used in chemoprophylaxis

Administration

Isoniazid is normally given orally.

Dosages

For treatment-

Adults and children: 5mg/kg (4-6mg/kg) daily, maximum 300mg.

10 mg/kg 3 times weekly

Preventive therapy:

Adults: 300mg daily for at least 6 months

Children: 5mg/kg daily (maximum 300mg) for at least 6 months

Side-effects

Isoniazid is generally well tolerated at recommended doses.

• Systemic or cutaneous hypersensitivity reactions occasionally occur during the first

weeks of treatment.

• Peripheral neuropathy may occur in persons with malnutrition, chronic alcoholics, and

pregnant women or in diabetics. This can be prevented or minimized by giving,

supplementary pyridoxine 10 mg daily to those at risk.

• Other less common forms of neurological disturbances including optic neuritis, toxic

psychosis, and generalized convulsions can develop in susceptible individuals,

32

particularly in the later stages of treatment, which occasionally may necessitate

withdrawal of Isoniazid.

• Hepatitis is an uncommon but potentially serious reaction that can usually be averted

by prompt withdrawal of the treatment. Monitoring of hepatic transaminases should

be done in patients with pre-existing chronic liver disease.

• Isoniazid tends to raise plasma concentrations of phenytoin and carbamazapine by

inhibiting their metabolism in the liver. Therefore it may be necessary to reduce the

dosages of these drugs during treatment with Isoniazid.

• Patients on treatment with Isoniazid should be cautioned against eating ‘Red fish’

such as skipjack and tuna, which contain high concentrations of histamine. Isoniazid

is an inhibitor of histaminase, which is normally present in the tissues and is

responsible for the inactivation of ingested histamine. As a result, the histamine level

in the tissues of the patient tends to rise shortly after a meal containing these varieties

of fish, and the patient may experience symptoms of histamine intoxication like

erythema, severe headache, red eyes, palpitation, diarrohoea, vomiting and wheezing.

Isoniazid is not teratogenic and can be used during pregnancy.

Rifampicin Rifampicin has a potent bactericidal and sterilizing effect against tubercle bacilli in both

cellular and extra-cellular locations. Following oral administration, it is rapidly absorbed

and distributed throughout the cellular tissues and body fluids.

Since resistance develops rapidly, Rifampicin must always be administered in

combination with other effective anti-mycobacterial agents.

Uses

It is a component of all 6 months and 8 months TB chemotherapeutic regimens currently

recommended by WHO.

Administration and dosage:

Rifampicin is administered orally and should preferably be given at least 30 minutes

before meals, since absorption is reduced when it is taken with food.

This however may not be clinically significant and food can reduce intolerance to the

drugs.

33

Adults and children: 10 mg/kg (8-12 mg/kg) daily, maximum 600mg daily.

10mg/kg 3 times weekly

Side-effects

Rifampicin is well tolerated by most patients at currently recommended doses

Side-effects include:

• Gastro-intestinal - nausea, anorexia, vomiting and abdominal pain

• Hepatitis is a major side effect although it is rare. Alcoholics and pre existing liver

disease may increase the risk and it may be advisable to monitor the liver function

tests in these high-risk groups.

The following reactions are more likely to occur with intermittent therapy:

• ‘Flu’ syndrome - consisting of attacks of fever, chills, malaise headache, bone

pain

• Cutaneous reaction – consisting of flushing, and pruritus with or without a rash

• *Thrombocytopenia and purpura

• *Heamolytic aneamia and acute renal failure may occur

• *Respiratory shock syndrome consisting of shortness of breath and rarely

associated with collapse and shock. may occur

* If these reactions occur Rifampicin must be stopped immediately and admitted to

hospital for management. It should not be given again.

Drug interactions

Rifampicin induces hepatic enzymes and may accelerate clearance of drugs metabolized

by the liver, and patients may need higher dosages of these drugs. These include

corticosteroids, oral contraceptives, oral hypoglyceamic agents, oral anticoagualants,

anticonvulsants, and cimetidine, cyclosporin and digitalis glycosides.

Since Rifampicin reduces the effectiveness of oral contraceptives, women should be

advised to use an alternative method of contraception.

Rifampicin is excreted in urine, tears, sweat and other body fluids and may colour them

red or orange. Patients should be warned of discoloration of urine and other body fluids.

Rifampicin may be used safely in pregnancy. Vitamin K should be administered at birth

to an infant of a mother taking Rifampicin because of the risk of postnatal haemorrhage.

34

Pyrazinamide Pyrazinamide is bactericidal and particularly effective against bacilli in an acid

environment inside macrophages. It is highly effective during the first two months of

treatment by destroying the intracellular bacilli and reduces the risk of relapse.

Uses:

It is a component of all 6 month and 8 month TB chemotherapeutic regimens currently

recommended by WHO. Administration and dosage:

It is administered orally and is rapidly absorbed from the gastro-intestinal tract and

rapidly distributed throughout all tissues and fluids.

Adults and children: (for the first 2 or 3 months)

25mg/kg daily (20-30 mg/kg)

35 mg/kg (30-40mg/kg) 3 times weekly

Side-effects

• Gastro intestinal symptoms- nausea, anorexia

• Hypersensitivity reactions are rare, but some patients may complain of flushing of

the skin

• Hepatitis is the most important adverse effect, though it is rare.

• Hyperuriceamia may occur due to diminished excretion of uric acid in urine, but

this is often asymptomatic. Arthralgia may occur and treatment with simple

analgesics is often sufficient. Attacks of acute gout are uncommon.

Ethambutol Ethambutol has a bacteriostatic effect. It is used in combination with other ant-TB drugs

to prevent the emergence of drug resistant strains.

It is given orally and absorbed readily from the gastro intestinal tract.

Administration and dosage:

Ethambutol is given orally

Adults: 15mg/kg (15-20 mg/kg) daily

30mg/kg (25-35mg/kg) 3 times weekly.

Children: Maximum 15mg/kg daily

35

Ethambutol is not recommended in children who are too young for assessment of visual

acuity and red- green colour discrimination (generally under 6 years of age). Side-effects

Dose dependant optic neuritis is the most important side effect and can result in

impairment of visual acuity and colour vision. Early changes are usually reversible, but

blindness can occur if treatment is not discontinued promptly. Therefore patients should

be advised to report immediately to a clinician if their vision deteriorates.

Streptomycin Streptomycin is bactericidal in action. It is not absorbed from the gastrointestinal tract and

must be given by intra-muscular injection

Streptomycin is excreted entirely through the kidneys and therefore drug should be used

in reduced dosage and with extreme caution in patients with renal insufficiency and in the

elderly. Administration and dosage:

Streptomycin must be administered by deep intra-muscular injection. Syringes and

needles should be sterilized properly. Whenever possible use disposable syringes and

needles.

Adults and children: 15mg/kg (12-18mg/kg) daily or 3 times weekly.

Patients over the age of 60 years may not be able to tolerate more than 500mg daily.

Side-effects

• Hypersensitivity reactions are rare. If they do occur (usually during the first few

weeks of treatment), streptomycin should be withdrawn immediately. Once fever

and skin rash have resolved, desensitization may be attempted.

• Auditory nerve damage can occur resulting in deafness and is more common in

elderly and in patients with renal impairment.

• Vestibular damage is uncommon, with the recommended doses, but if headache,

vomiting, vertigo, dizziness and nystagmus occur, doses should be reduced.

• Nephrotoxicity can occur

Streptomycin should not be used in pregnancy. It crosses the placenta and can cause

auditory nerve impairment and nephrotoxicity in the foetus.

36

Fixed Dose Combination (FDC) tablets

Tablets containing a combination of four drugs (RHZE), three drugs (RHE) and two

drugs (RH) will be used in identified districts in Sri- Lanka from 2005.

Table 4 Number of tablets of FDC used in CAT 1 and CAT 2

Weight (Kg)

Category

<35 35-54 55-70 >70

CATEGORY 1

Duration of treatment

Intensive phase-daily

RHZE (tab)

150+75+400+275mg

2 3 4 5 2 months

Continuation phase-daily

RH (tab)

150+75

2 3 4 5 4 months

CATEGORY 2

Intensive phase-daily

RHZE (tab)

150+75+400+275mg

&

Streptomycin

2

0.5g

3

0.75g

4

1g

5

1g

2 months

RHZE (tab)

150+75+400+275mg

2 3 4 5

1 month

Continuation phase-daily

RHE (tab)

150+75+275mg

2 3 4 5 5 months

*Patients over 60 years, the dose of streptomycin 0.5g, irrespective of the weight

37

Management of Side-effects of First-line Anti-TB drugs Side-effects of anti-tuberculosis drugs are of two types.

Major side-effects are those, which causes serious health hazards. In this case, the anti-

tuberculosis drugs should be stopped and the patient referred to hospital for management.

Minor side-effects cause only relatively little discomfort. They often respond to

symptomatic treatment. In general, a patient who develops minor side-effects should

continue the anti-TB treatment.

Table 5 Adverse effects of first-line anti-TB drugs

Drug

Common side-effects

Rare side-effects

Isoniazid

• Peripheral neuropathy • Hepatitis • Histamine Reaction after

ingestion of red fish e.g., bala, kelawalla

Convulsions, pellagra. Joint pains, Agranulocytosis, lupoid reaction, skin rash

Rifampicin

• Gastro-intestinal-nausea,

anorexia, abdominal pain • Hepatitis • Reduced effect of oral

contraceptives, antiepileptic drugs, oral hypoglyceamic drugs and theophyllines

Acute renal failure, shock, thrombocytopenia, skin rash, ‘Flu syndrome’ (with intermittent doses) pseudo membranous colitis, pseudo adrenal crisis.

Pyrazinamide

• Joint pains • Hepatitis

Gastrointestinal symptoms, skin rashes, sideroblastic aneamia.

Streptomycin

• Auditory and vestibular

damage (also to the foetus) • Renal damage

Skin rash

Ethambutol

• Optic neuritis

Skin rash, joint pains, peripheral neuropathy.

38

Table 6 Symptom based management of side-effects of Anti-TB drugs

Side-effects

Drug(s) responsible Management

MINOR CONTINUE DRUGS 1.Anorexia, nausea, abdominal pain 2.Joint pain 3.Burning sensation in feet 4.Orange/red urine 5.Histamine reaction

Rifampicin or bulk of the drugs Pyrazinamide Isoniazid Rifampicin Isoniazid

Give drugs with small meals or last thing at night Give Asprin/NSAIDs Pyridoxine 100 mg daily Reassurance Advice not to eat ‘Red ‘ fish

MAJOR STOP DRUGS RESPONSIBLE REFER FOR EVALUATION 1. Itching of skin, skin rash 2. Deafness 3. Dizziness, vertigo, nystagmus 4. Jaundice (other causes excluded) 5. Vomiting and confusion 6. Visual impairment 7. Shock, purpura, acute renal failure, haemolytic anaemia

Streptomycin Streptomycin Streptomycin Most anti-TB drugs especially INAH, Rifampicin and Pyrazinamide Most anti-TB drugs Ethambutol Rifampicin

Stop anti-TB drugs (See page 40) Stop Streptomycin Stop Streptomycin Stop anti-TB drugs (see page 39) Stop anti-TB drugs Stop Ethambutol Stop Rifampicin (Never give again)

39

Management of severe drug reactions

Hepatitis

• Most anti-TB drugs can damage the liver. Isoniazid, pyrazinamide and rifampicin

are the drugs most commonly responsible and ethambutol rarely.

• When a patient develops hepatitis during anti-TB treatment, it is important to rule

out other possible causes of hepatitis before deciding that the hepatitis is drug-

induced.

• Mild transient increases in serum transaminases may occur during the initial

treatment. This rise is not more than 2-3 folds of the normal. This subsequently

falls to normal despite continuation of anti-TB drugs. This is not an indication to

stop anti-TB drugs provided serum bilirubin level remains normal.

• Ideally, pre-treatment base-line Liver Function Tests (LFTs) should be done in all

patients. Since this may not be practical, it should be done at least on those who

are at a higher risk of developing drug-induced hepatitis e.g. known chronic

alcoholics, pre-existing liver disease, pregnant mothers and the elderly.

• Liver function tests should be performed when patient is having symptoms &

signs suggestive of hepatitis. i.e. nausea, vomiting with or without icterus or

hepatomegaly.

• If drug-induced hepatitis is diagnosed, all anti-TB drugs should be stopped and

patient may need admission to hospital.

• Repeat the Liver Function Tests after 1-2 weeks.

• Sometimes tuberculous disease is so severe that all anti TB drugs cannot be

withdrawn. In such situations, patient should be treated with two of the least

hepatotoxic drugs streptomycin and ethambutol (provided the patient is not

allergic to the latter two drugs) until the LFTs come back to normal.

• Once LFTs return to normal, challenge doses of original drugs can be

reintroduced sequentially in the order of isoniazid, rifampicin and pyrazinamide

with daily monitoring of the patient’s clinical condition and at least weekly

monitoring of LFTs. If symptoms recur early, LFTs should be repeated before one

week. Isoniazid should be introduced initially at 50 mg/day increasing

sequentially to 300 mg/day after 2-3 days if no reaction occurs, and then

continued. After a further 2-3 days without reaction, rifampicin should be added at

40

a dose of 75 mg/day increasing sequentially to full dose after 2-3 days and then

continued. The final drug to add is pyrazinamide starting with a dose of

250mg/day increasing to the full dose after 2-3 days.

• If there is no further reaction, standard chemotherapy can be continued, and any

alternative drugs introduced temporarily can then be withdrawn.

• During this procedure if the patient complains of a recurrence of symptoms

suggestive of hepatitis, LFTs should be repeated, and if found abnormal the drug

added last should be withdrawn and attempts should not be made to reintroduce it.

A suitable alternative drug regimen should be used on the advice of and under the

supervision of a chest physician e.g. 2 SHE / 10 HE,

2 HRE / 7 HR,

2 H3R3Z3E3 / 4 H3R3.

• Generally, all previously used first-line anti TB drugs can be recommenced on

most patients who develop anti-TB drug induced hepatitis, without a recurrence of

the liver impairment.

N.B. Ideally it is better to get advice from a chest physician for the management

of drug induced hepatitis

Table 7 Re introduction of anti- TB drugs following drug induced hepatitis after

LFTs return to normal

Isoniazid 50mg, increase to full dose over 2-3 days and continue at full dose for

another 2-3 days

No symptoms

LFTs normal

Rifampicin 75mg, increase to full dose over 2-3 days and continue at full dose for

another 2-3 days

No symptoms

LFTs normal

Pyrazinamide 250mg, increase to full dose over 2-3 days and continue at full dose for

another 2-3 days

41

Severe cutaneous reactions

• If the reaction is only pruritus and no rash, (and there is no obvious cause e.g.

scabies) give symptomatic treatment with anti-histamines, reassure and continue

anti-TB treatment and observe the patient closely.

• However, if a skin rash develops, stop all anti-TB drugs.

• Wait till the rash resolves. Sometimes the patient may need steroids.

• Once the reaction has resolved, the anti-TB drugs should be re-introduced. The

drug, which was responsible for the reaction, should be identified.

• The idea of drug challenging is to identify the drug responsible for the reaction.

Drug challenge starts with the anti-TB drug least likely to be responsible for the

reaction (i.e. isoniazid). The idea of starting with a small challenge dose (e.g. 50

mg of isoniazid) is that if a reaction occurs to a small challenge dose, it will be

less severe than the reaction to a full dose. The dose is gradually increased to the

full dose over a period of three days. The procedure is repeated, adding in one

drug at a time. A reaction after adding in a particular drug identifies that drug as

the one responsible for the reaction. There is no evidence that this challenge

process gives rise to drug resistance.

• If the drug responsible for the reaction is pyrazinamide, ethambutol or

streptomycin, anti-TB treatment should be resumed without the offending drug. If

possible, the offending drug should be replaced with another drug. It may be

necessary to extend the duration of the treatment regimen. This prolongs the total

time of TB treatment, but decreases the risk of relapse.

• Rarely, the patients develop hypersensitivity reactions to the two most powerful

anti-TB drugs- isoniazid and rifampicin. These drugs form the cornerstone of

Short Course Chemotherapy.

42

Table 8 Re introduction of anti-TB drugs following sever cutaneous drug

reaction

Likelihood of

causing a reaction

Challenge doses

Drug Day 1 Day 2 Day 3

Isoniazid 50 mg 300 mg 300mg

Rifampicin 75 mg 300 mg Full dose

Pyrazinamide 250 mg 1 gm Full dose

Ethambutol 100 mg 500 mg Full dose

Streptomycin

Least Likely

Most Likely 125 mg 500 mg Full dose

Adverse reactions to FDCs Adverse reactions to drugs are not more common if FDCs are used. Nevertheless,

whenever side-effects to one or more components in a FDC are suspected, there will be a

need to switch to single-drug formulations. Reactions to FDCs which warrant withdrawal

of drugs generally occur in only 3-6% of patients on TB treatment.

Role of steroids

Indications for treatment with steroids:

• TB meningitis with altered level of consciousness and focal neurological signs

• TB pericarditis

• TB pleural effusion- when large and with severe symptoms and not responding

satisfactorily with anti-TB drugs alone.

• TB peritonitis

• Hypo-adrenalism

• TB laryngitis (with life threatening airway obstruction)

• Severe hypersensitivity reactions to anti-TB drugs

• Renal tract TB (to prevent ureteric scarring)

• Massive lymph gland enlargement with pressure effects

• Spinal TB with neurological involvement (e.g. paraplegia).

43

MONITORING OF TREATMENT

Monitoring of treatment There are two ways to monitor tuberculosis patients on treatment.

6

• Bacteriological monitoring is done for sputum smear positive pulmonary TB cases

by examination of sputum smears at regular intervals during treatment.

• Monitoring the drug intake during intensive phase and drug collection

during the continuation phase by reviewing the treatment cards.

Monitoring of sputum smear-positive pulmonary TB patients

Response to treatment should be monitored by sputum smear examination. Generally two

sputum samples should be collected for smear examination at each follow up sputum

check.

Sputum smear examinations should be performed at the end of the intensive phase of

treatment, during the fifth month and at the end of treatment. Negative sputum smears

indicate good treatment progress.

The best way to monitor the sputum smear-positive patients is to check for sputum

conversion from smear positive to negative. Conversion from smear positive to negative

is the best indicator that the intensive phase of chemotherapy has been regular and is

effective.

After two months of chemotherapy, more than 80% of new smear positive PTB cases

should be smear negative and after 3 months, the rate should be more than 90%.

Pulmonary smear positive relapse cases should have approximately the same rates of

sputum conversion as new pulmonary smear positive cases. Other smear positive re-

treatment cases such as treatment failures may have sputum conversion rates of more than

75% after three months of receiving the re-treatment regimen

Sputum smears are again checked at the end of the 5th month and at the end of treatment.

In a new smear-positive PTB case if the sputum smear is positive at the end of 5 months

or later, these cases are considered as treatment failures, re-registered and given CAT 2

regimen

44

Sputum smear-negative PTB patients

Sputum smear negative patients should be monitored clinically. It is important to check

the sputum smear at the end of two months. If the sputum is positive, there are two

possibilities:

- An error at the time of initial diagnosis- i.e., a true smear positive patient

incorrectly diagnosed as smear negative at the beginning of treatment

- Progress of the disease due to non- adherence to treatment

In such a situation the intensive phase with all four drugs should be continued for a

further one month under direct observation.

Extrapulmonary TB patients

These patients are monitored by assessing the clinical response to treatment.

Table 9 Schedule for follow up sputum examination

Category of patients

When to do sputum smear

CAT 1 (smear-positive PTB)

• End of the 2nd month

(End of the3rd month if smear- positive at the end of the 2nd month)

• End of the 5th month • End of treatment

CAT 1 (smear-negative PTB)

• End of the 2nd month • End of treatment

CAT 2

Relapse Treatment after failure Treatment after default (smear-positive)

• End of the 3rd month

(End of the 4th month if smear-positive at the end of the 3rd month)

• End of the 5th month • End of treatment

45

Treatment Outcome At the end of treatment course for each patient, the treatment outcome is recorded in the

District Tuberculosis Register.

There are six possible treatment outcomes.

1. Cured

A patient who was initially sputum smear-positive and has completed treatment

and is sputum smear-negative in the last month of treatment and on at least one

previous occasion.

2. Treatment completed

A smear-positive patient who has completed treatment, but who does not meet the

criteria to be classified as cure or failure (e.g. follow up sputum examination not

done or results not available).

OR

A smear-negative PTB or Extrapulmonary TB Patient who has completed

treatment.

3. Treatment Failure

A patient who is sputum smear-positive at 5 months or later during treatment

4. Died

A patient who dies for any reason during the course of treatment.

5. Default

Patient whose treatment was interrupted for two consecutive months or more

before the completion of treatment.

6. Transfer out

Patient who has been transferred to another district for continuation of treatment

and whose treatment outcome is not known at the initial treatment unit

46

TUBERCULOSIS AND HIV

The Human Immunodeficiency Virus (HIV) destroys the immune system of an individual

and increases his susceptibility to many infections including TB.

HIV is the most potent factor known to increase the risk of progression of latent

tuberculous infection to tuberculous disease. In a HIV negative patient who is infected

with M. tuberculosis, the lifetime risk of developing tuberculosis is only 10%, whereas in

person dually infected with TB and HIV, it is 50%

Tuberculosis is the most important life threatening opportunistic infection associated with

HIV infection. It is the leading cause of death among people who are HIV positive and

accounts for more than one third of AIDS deaths worldwide.

Features of HIV related TB

TB usually occurs earlier in the course of HIV infection than other opportunistic

infections seen in HIV, but it may occur at any stage of HIV infection as a result of rapid

progression of a recently acquired new or re-infection. As a result of TB infection in a

HIV infected person there is a transient drop in CD4 count and progression of the HIV

infection.

As HIV infection progresses the CD4 lymphocyte count declines and the immune system

is less efficient in preventing the growth and spread of M. tuberculosis, As a result,

disseminated and extrapulmonary disease is more common in HIV positive patients than

in HIV negative patients. Nevertheless, pulmonary TB is still the most common form of

TB seen, in HIV infected patients, with or without concomitant extrapulmonary TB.

Pulmonary TB

The presentation of pulmonary TB in HIV infected individuals depends on the stage of

the degree of immunosuppression. The clinical picture, sputum result, and chest X-ray

appearance often differ in early and late HIV infection. (Table 9)

Diagnosis

The diagnosis of TB in HIV infected patients is often difficult because:

7

47

- The sputum smear examinations tend to be more frequently negative,

particularly in the late stages of HIV infection

- X-ray abnormalities are often atypical

- The Tuberculin skin test is often negative due to immunosuppression.

Table 10 How PTB differs in early and late HIV infection

Features of PTB Stages of HIV infection

Early Late

Clinical picture Often resembles post primary PTB

Often resembles primary TB

Sputum smear result Often positive

Often negative

Chest X-ray - Often cavities - Lymphadenopathy usually absent - Pleural effusions rare

- Often infiltrates, - No cavities - Lymphadenopathy and pleural effusions often present

Treatment of HIV associated TB

• Generally anti-TB treatment in HIV positive patients is the same as for HIV

negative TB patients.

• It is important that these patients should receive Directly Observed Treatment.

(DOT). Effective treatment using DOTS can cure TB, prevent the spread of the

disease and prolong the life of HIV patients.

• Adverse reactions to anti-TB drugs are more common in HIV positive patients.

• The rate of recurrence of TB after completion of treatment is higher in HIV

positive patients than in HIV negative TB patients. For patients known to have

HIV co-infection, secondary prophylaxis with isoniazid 300mg daily may be

given for 9 months after cessation of anti-TB treatment.

• The Case Fatality Rate is higher in HIV +ve TB patients than in HIV –ve TB

patients. The excess deaths in TB/HIV patients are partly due to the tuberculosis

itself and partly due to other HIV related problems.

48

Primary prophylaxis

HIV positive patients with a positive Mantoux test above 5 mm should be screened for

active TB. If there is no active disease they should be given INAH prophylaxis for 9

months.

Screening of TB patients for HIV

TB patients in the high-risk group (IV drug users, commercial sex workers, homosexuals,

people having multiple sexual partners, institutionalized individuals) need Voluntary

Counseling and Testing (VCT). Patients with atypical presentations and disseminated TB

also need VCT.

TB treatment and anti-retroviral therapy

Rifampicin stimulates the activity of cytochrome P450 that metabolizes protease

inhibitors (PIs e.g. saquinavir, ritonavir, indinavir, nelfinavir, amprenavir) and

nonnucleoside reverse transcriptase inhibitors (NNRTIs, e.g. nevirapine, delavirdine). PIs

and NNRTIs also enhance or inhibit the same enzyme system and this may result in

decreased blood levels of rifampicin and the anti-retrovirals resulting in ineffectiveness of

both.

In patients with HIV and TB, the priority is to treat TB, especially the smear positive TB

patients.

Possible options for antiretroviral therapy in TB patients include:

• Defer antiretroviral therapy until TB treatment is completed

• Defer antiretrovirals until the end of intensive phase and use ethambutol and

isoniazid for 6 months in the continuation phase

• Treat TB with a rifampicin containing regimen and use efavirenz + 2 nucleoside

reverse transriptase inhibitors (NRTIs).

• Treat TB with rifampicin containing regimen and use 2 NRTIs; then change to

maximally suppressive highly active antiretroviral therapy (HAART) regimen on

completion of TB treatment.

49

PREGNANCY AND TUBERCULOSIS

Diagnosis In pregnancy, chest X-rays should be avoided as far as possible, especially during the first

trimester, because of the adverse effects of x-rays on the foetus.

Therefore, diagnosis will depend more on sputum examination when a pregnant mother

presents with symptoms suggestive of tuberculosis. However, if an X-ray is absolutely

necessary, this may be done with the abdomen covered with a lead apron.

Treatment during Pregnancy Anti-TB treatment should be started as soon as the diagnosis is made, and the full course

of treatment given.

The basic principles of treatment are the same in pregnancy. Most anti-TB drugs are safe

for use during pregnancy except streptomycin.

Streptomycin should not be given because it can cause oto-toxicity in the foetus.

Pregnant mothers should be given pyridoxine 10mg daily along with INAH.

Vitamin K should be administered at birth to the infant of a mother taking rifampicin

because of the risk of post-natal haemorrhage.

Treatment during breast-feeding A patient who has TB and is breast-feeding should receive the full course of anti-TB

treatment. Properly taken treatment is the best way of preventing transmission of TB to

her baby. All anti-TB drugs are compatible with breast-feeding. A patient taking anti-TB

treatment can continue to breastfeed her baby in the normal way.

Breastfeeding should be avoided only in cases where the mother has dual TB/HIV

infection.

Management of a newborn child of a mother with active TB

8

• Do not separate the child from the mother unless she is acutely ill.

• If the mother is sputum smear negative, and if the infant has no evidence of

congenital TB, BCG is given to the infant.

50

• If the mother is sputum smear-positive at the time of delivery, infant should be

carefully examined for evidence of active disease.

- If the infant is ill at birth and congenital TB is suspected, a full course of

anti-TB treatment should be given.

- If the child is well, give prophylactic treatment with INAH 5mg/ kg body

weight, daily for three months. BCG is withheld.

• The Mantoux skin test is done after three months.

- If the Mantoux test is negative and the child is well, prophylactic treatment

with INAH is stopped and child is given BCG.

- If the Mantoux test is positive, careful examination of the child for active

TB is done including a chest X-ray.

- If active disease is diagnosed, a full course of anti-TB treatment should be

commenced.

- If the physical examination and the chest X-ray are normal, INAH

chemoprophylaxis is continued up to six months and BCG is given.

51

ROLE OF BCG VACCINATION

BCG (Bacillus Calmette Guerin) is a live attenuated vaccine derived from M. bovis. It is a

freeze-dried vaccine. It can be stored at room temperature up to one month and in a

refrigerator at 4°C up to one year.

It is easily killed by direct sunlight. Once reconstituted, it should be used within four

hours and any remaining solution should be discarded.

Dose- 0.05 ml of vaccine is administered to newborn infants aged less than one year

and 0.1 ml for children aged over one year. It should be administered intradermally to

the upper lateral aspect of the left arm.

The National Policy of Sri Lanka is to give BCG vaccination to all newborn babies

immediately after birth. BCG vaccination is carried out under the Expanded Programme

of Immunisation (EPI)

BCG protects the young children against serious disseminated forms of TB, like TB

meningitis and military TB.

It does not decrease the spread of TB in the community

Complications of BCG vaccination

Complications after BCG vaccination are uncommon. It includes the following:

9

• Subcutaneous abscess at the site of injection due to secondary infection

• Ulceration at the site of injection

• Swelling with or without abscess formation of the regional lymph glands(BCG

adenitis)

• Disseminated TB (which is extremely rare and occurs only in severely

immunosuppressed patients).

Some of the complications are due to faulty immunization technique.

Most complications resolve on their own. In the case of suppurative lymphadenitis or

progressive adenitis surgical removal of affected nodes may be required. INAH may be

given for 3- 6-months for non healing ulcers or sinuses.

52

Contraindications for BCG vaccination

Contraindications for vaccination are extremely uncommon. The only two known

conditions where children should not be vaccinated are:

• Congenital or acquired immunodeficiency

• Children with clinical signs of AIDS

BCG should be withheld in the presence of skin sepsis, and systemic infections until these

conditions resolve.

If the mother is sputum smear positive at the time of delivery, the baby is commenced on

chemoprophylaxis and BCG administered at the end of the period of chemoprophylaxis.

(Refer page 49- 50).

BCG in HIV positive infants

The WHO recommended policy is to give BCG vaccination to HIV positive babies who

do not have any evidence of HIV disease. But it should not be given to children with

symptoms of HIV/AIDS.

Absent BCG scar

This is a common occurrence. If the mother is certain that there was no reaction to BCG

vaccination, or if there is no BCG scar, revaccination may be done. In children under 5

years revaccination may be done without Mantoux test.

53

PREVENTION OF TUBERCULOSIS

From the public health point of view, the best way to prevent TB is to identify the

infectious cases as early as possible and provide effective treatment to cure them. This

interrupts the chain of transmission.

BCG vaccination This protects young children against serious disseminated forms of TB, but does not have

an impact on the spread of the disease in the community, and does not protect the child

from developing post-primary tuberculosis in later life.

Contact screening Household contacts of infectious TB patients (adults and children >5 years) should be

screened for symptoms of TB. Those who have symptoms suggestive of TB should be

investigated with sputum smears irrespective of the duration of the symptoms.

Children under the age of 5 years should be screened with chest X-ray and Mantoux test.

Preventive treatment The aim of preventive treatment is to prevent progression of M. tuberculosis infection to

disease.

Primary chemoprophylaxis

When a person is exposed to TB bacilli, but not yet infected eg. newborn breastfed baby

of a sputum smear-positive mother

Secondary chemoprophylaxis

A person who is infected, but not yet developed clinical disease e.g. tuberculin positive

close contacts of sputum smear-positive patients.

In Sri Lanka, chemoprophylaxis is given for the following groups:

10

• Breast fed infants of sputum smear-positive mothers.

• Household contacts below 5 years of age of sputum smear-positive patients, who

do not have evidence of active disease.

Prophylactic treatment in Sri Lanka is – INAH 5mg/ kg body weight for 6 months.

54

Health Education Health education is a critical component of tuberculosis control. The target groups, which

need to be addressed, are the patients and their families, health personnel, and the

community.

The health staff should educate the patients and their families regarding the disease, how

it is spread, and the duration of treatment. It must be emphasized that TB is curable if the

treatment is taken fully and to stress the importance of directly observed treatment.

Patients should be made aware of the risks of irregular and incomplete treatment. Health

workers should also teach them simple ways of decreasing the risk of transmitting the

disease, like covering the mouth with the hand when coughing and to use a sputum pot

with a lid and disposing of the sputum by burning.

The general public should be educated regarding the disease and the symptoms and the

importance of seeking medical advice early if they have any symptoms suggestive of TB.

They should be made aware of the locations and the facilities available for the

management of TB. Also, education should be aimed at removing the social stigma

attached to TB, so that symptomatic patients will seek treatment early.

Health personnel should also be made aware of the importance of identifying TB suspects

early and referring them for investigation.

55

MULTI DRUG RESISTANT TB (MDR-TB) 11

Drug resistance means that certain strains or types of bacteria are not killed by the anti-

tuberculosis drugs given during treatment. Some strains may be resistant to one or more

drugs. Multidrug-resistant tuberculosis (MDR-TB) refers to tuberculosis, which is

resistant to INAH and Rifampicin, the two most powerful anti-tuberculosis drugs. The

diagnosis of MDR-TB should be confirmed by drug susceptibility testing.

There are two types of drug resistance:

Drug resistance among previously treated cases (Acquired resistance) is that found in

a patient who has previously received at least one month of anti-TB therapy. This

resistance develops as a result of inadequate treatment. Use of a single drug (directly or

indirectly) is the most important cause. This is because some bacilli are naturally resastant

to anti-TB drugs. If a single drug is used to treat a patient who is infected with a large

number of TB bacilli, only those which are sensitive to that drug, are killed allowing the

resistant bacilli to multiply. This is the reason for using several drugs during the initial

intensive phase of treatment, until the number of bacilli has been greatly reduced.

Drug resistance among new cases (Primary resistance) is the presence of resistant

strains of M. tuberculosis in a newly diagnosed TB patient who has never received TB

drugs or has received the drugs for less than one month of treatment.

MDR-TB is entirely a man made phenomenon and is an indicator of poor management of

TB patients by the entire health system.

Common causes of MDR-TB are:

Service factors

• Prescribing incorrect chemotherapy (wrong combination of drugs, dosages and

duration)

• Failure to ensure a regular and uninterrupted drug supply

• Poor case management – incomplete and irregular treatment, where patients are

not directly observed taking their drugs

• Use of drugs of unproven bioavailability.

• Adding one new drug at a time to a failing (or failed) anti-TB drug regimen

56

• Prescribing CAT 1 regimen to a patient who needs CAT 2 regimen.

• Not referring TB patients to the state health sector for treatment and patients being

forced to purchase drugs which they cannot afford.

Patient factors

• Not taking the full prescribed number of drugs

• Taking lesser than the prescribed dose

• Taking drugs irregularly

MDR-TB is a significant threat to tuberculosis control, because:

• Commonly used first-line anti-tuberculosis drugs are no longer effective

• MDR-TB is more difficult to treat and it requires treatment with ‘Reserve’ or

Second-line anti-tuberculosis drugs for at least two years.

• These drugs are very toxic to the patients and have severe adverse reactions

• The reserve drugs are at least 100 times more expensive than the standard First-

line drugs

• The results of treatment are poor and the mortality rate is high.

• Reserve second-line drugs are not as potent as the first-line drugs, though they

have more side-effects than the first-line drugs.

When to suspect MDR-TB? Chronic cases and MDR-TB are not synonymous. Chronic patients probably have MDR-

TB because they have received at least two full courses of treatment with essential anti-

tuberculosis drugs. However, MDR-TB has to be confirmed with mycobacterial

susceptibility results.

MDR TB should be suspected in the following groups of patients:

• Treatment failures

• Defaulters

• Contacts of known MDR-TB patients

• Health care workers

• HIV infected persons

57

Management of MDR-TB The best way to control MDR-TB is to prevent the development of MDR-TB. Strict

adherence to first line treatment is imperative in the prevention of development of drug

resistance.

Effective implementation of DOTS is the only proven way to prevent emergence of

MDR-TB.

Basic Principles of management of MDR-TB

• Forming a specialized unit for managing MDR-TB patients.

• Assuring the availability of specific laboratory services [including reliable

drug-susceptibility testing at least for essential drugs].

• Designing an appropriate treatment strategy that utilizes reserve anti-TB

drugs.

• Establishing a reliable supply of high-quality reserve anti-TB drugs.

• Instituting measures to promote patient adherence to treatment.

• Implementing an information system to allow proper management of data,

monitoring of performance, and evaluation of intervention.

• Establishing strong pharmaceutical regulations to limit the use of second line

reserve drugs in order to prevent the emergence of incurable tuberculosis.

Principles of Treatment of MDR-TB

• The treatment should include in the initial phase three drugs to which the

patient has not been exposed to earlier. This should include an injectable drug

(Aminoglycoside) and a fluoroquinolone.

• Treatment should be given daily and directly observed throughout the whole

duration.

• Sputum culture and drug susceptibility should be done at least once in 2

months.

• Once the culture is negative continue at least 3 of the most active and best-

tolerated drugs for a further 18 – 24 months.

• In case of localized disease a better prognosis could be achieved by surgery.

58

• Never add a single drug to a failing regime.

Reserve anti-tuberculosis drugs Aminoglycosides

• Kanamycin

• Amikacin

• Capreomycin Thiomides

• Ethionamide

• Prothionamide

Fluoroquinolone

• Ofloxacin

• Ciprofloxacin Cycloserine

P-aminosaycilic acid

Table 11 Dosages and mode of action of reserve anti-tuberculosis drugs

Recommended daily dosage Reserve drug (abbreviation)

Mode of action Average

(mg/kg) Minimum (mg )

Maximum (mg)

Amikacin (Am) Capreomycin (Cm) Ciprofloxacin (Cx) Cycloserine (Cs) Ethionamide (Et) Kanamycin (Km) Ofloxacin (O) P-aminosalycilic Acid (PAS) Prothionamide (Pt)

Bactericidal Bactericidal Bactericidal Bacteriostatic Bactericidal Bactericidal Bactericidal Bacteriostatic Bactericidal

15 15 10-20 10-20 10-20 15 7.5-15 150 10-20

750 750 1000 500 500 750 600 8 g 500

1000 1000 1500 750 750 1000 800 12 g 750

59

Table 12 Suggested treatment regimen for MDR-TB (WHO)

Initial phase Continuation phase Susceptibility testing to essential drugs

Drugs Rhythm & duration

Drugs Rhythm & duration

Not available Km*+Et+Q**+Z+E

Daily for 6-months

Et+Q**+Z+E Daily for 12-18months

Available Resistant to H+R Resistant to all essential drugs

S*+Et+Q**+ Z+E I injectable+1 fluroquinolone + 2 of the oral drugs from PAS, Et, Cs

Daily for 6-months Daily for 6-months

Et+Q**+Z+E Same oral drugs

Daily for 12-18months Daily for 18months

* If resistant to S, Km to be used, if resistant to Km, amikacin or capreomycin can be

used

** Ofloxacin or ciprofloxacin

MDR-TB and chronic cases will be categorized as Category 4

60

Side-effects of Reserve drugs

Kanamycin and Amikacin

Bactericidal agents of the aminoglycoside class.

Administration: deep intra-muscular injection

Side-effects:

Similar to those associated with streptomycin and capreomycin.

• Oto-toxicity. - deafness and vertigo

• Reversible nephrotoxicity

Daily dosage should be reduced in patients with renal impairment.

Should not be used in pregnancy.

Capreomycin

Bactericidal in action.

No cross-resistance with other aminoglycosides.

Administration: Deep intra-muscular injection

Side-effects:

Similar to those of streptomycin

• Mainly tinnitus and vertigo with a lesser risk of deafness

• Renal damage may occur

• General cutaneous reactions and hepatitis may occur rarely.

Should be avoided in patients with impaired renal functions or impaired hearing.

Contraindicated in pregnancy.

Ethionamide (or Prothionamide)

These are bactericidal agents

Administration:

They are administered orally. They may be given with orange juice or milk or at bedtime

to avoid nausea.

Side-effects:

• Epigastric discomfort, anorexia. nausea, metallic taste, and sulphurous

belching

• Vomiting and excessive salivation can occur

61

• Psychotic reactions including hallucination and depression may occur.

• Hypoglyceamia may occur but is rare

• Hepatitis may occur in 10% of cases.

• Prolonged administration in large doses may produce hypothyroidism and

goitre. These will reverse when the drug is withdrawn.

• Other rare side-effects include gynaecomastia, menstrual disturbances,

impotence, acne, headache, and peripheral neuropathy.

They are contra-indicated in pregnancy.

Ofloxacin and Ciprofloxacin

These are weakly bactericidal agents

Administration: Given orally

Side-effects: Uncommon

• Gastro-intestinal disturbances – anorexia, nausea, vomiting

• Central nervous system symptoms – dizziness, headache, mood changes and

rarely convulsions.

• May cause tendon rupture

• May impair cartilage growth and hence should not be given for children below 18

years of age

Not used in pregnancy and children below 18 years of age

Cycloserine

Bacteriostatic in action

Administration: Given orally

Side-effects:

• Dizziness, slurred speech, convulsions, headache tremor, insomnia, confusion

depression an altered behaviour.

• Suicidal tendency

• Generalized hypersensitivity reactions and hepatitis occur rarely

Para-amino salicylic acid (PAS)

Bacteriostatic in action

Administration: Given orally.

62

Bulky and unpleasant

Side-effects:

• Gastro-intestinal disturbances - anorexia, nausea, vomiting, abdominal discomfort

• Skin or other hypersensitivity reactions

• Hepatic dysfunction

• Prolonged administration may produce hypothyroidism and goitre, which will

reverse when the drug is withdrawn.

PART II

OPERATIONAL GUIDELINES

FOR

63

TUBERCULOSIS CONTROL

64

1 OBJECTIVES AND STRATEGY OF

NATIONAL TUBERCULOSIS PROGRAMME

Epidemiology of tuberculosis in Sri Lanka

Tuberculosis is still a significant public health problem in Sri Lanka. About 8000 new

cases of tuberculosis are notified every year, of which around 60% are smear positive

pulmonary TB cases. There has been a gradual increase in the number of cases notified

during the last four years. This may be due to improved case detection and also due to

more referrals and better case notifications from the general health institutions.

Objectives of the National Tuberculosis Programme The overall objectives of the National Tuberculosis Programme are:

• To reduce the mortality, morbidity and transmission of tuberculosis in the

community until it is no longer a public health problem.

• To prevent the development of drug resistant TB.

65

Strategy for TB control The basic strategy is to identify and treat all tuberculosis patients until they are cured.

The priority is to provide all diagnosed sputum smear positive pulmonary tuberculosis

cases with short course chemotherapy under direct observation, until they are cured, since

they are the main source of infection in the community. The most effective step to control

tuberculosis is to cure the infectious cases in order to break the chain of transmission. Sri

Lanka has adopted the WHO recommended strategy of ‘DOTS’ for the control of

tuberculosis.

DOTS strategy ‘DOTS’ stands for Directly Observed Treatment, Short-course

This strategy has five components:

• Government commitment to sustained TB control

• Detection of TB cases through sputum smear microscopy of symptomatic patients

presenting at health facilities

• Regular and uninterrupted supply of good quality anti-TB drugs

• Short-course chemotherapy given under direct observation of a health worker or a

trained person

• Recording and reporting system to monitor treatment progress and evaluate the

outcome of every patient treated and the overall performance of the programme.

Targets for TB control Our aim is to achieve the following targets by the year 2005:

• To cure at least 85% of the detected sputum smear-positive pulmonary

tuberculosis cases.

66

• To detect 70 % of existing sputum smear-positive tuberculosis cases

Priority should be given to achieve a high cure rate before increasing the case detection.

NATIONAL TUBERCULOSIS PROGRAMME 2

The National Tuberculosis Programme (NTP) is a part of the national health services

which functions under the Deputy Director General, Public Health Services (DDGPHS)

within the Ministry of Health. The programme is headed by the Director /National

Programme for Tuberculosis Control and Chest Diseases (NPTCCD), and is responsible

for the tuberculosis control activities of the entire country. The NTP functions through a

network of district chest clinics, branch chest clinics, chest hospitals, and chest wards in

close co-ordination with the general health services.

The structure of the NTP The organizational setup of the NPTCCD is shown in Annex 1.

The Central Unit At the national level is the Central Unit of the NPTCCD and the Director is in charge of

tuberculosis control activities in the country. The Central Unit acts as the technical nodal

point covering all aspects of the NTP.

67

Main responsibilities of the Central Unit

• Plan, supervise, monitor and evaluate the tuberculosis control activities

throughout the country.

• Co-ordinate the National Tuberculosis Programme at the intermediate level and

with other sections of the Ministry of Health.

• Provide printed forms, documents (e.g. manuals, training modules) and other

materials needed for the programme

• Train personnel involved in the National Tuberculosis Programme.

• Provide a Reference Laboratory for tuberculosis

District Level The District Chest Clinic is the nodal point for the tuberculosis control activities in the

district. At this level, the District TB Control Officer (DTCO) is responsible for carrying

out the tuberculosis control activities in the district. S/he is responsible administratively to

the Provincial/Deputy Provincial Director of Health and technically follows the

instructions of the Central Unit of the NTP. Financial allocations for the chest clinic

activities are provided by the Provincial Director.

Main responsibilities at District Level

• To implement the national TB control programme through the staff of the chest

clinic and other health institutions.

• Maintain a map of the district with details of all health facilities and the staff

responsible for the TB control activities.

• To assist in case finding in all health institutions in the district and to make sure

that health staff properly identify the suspects and refer them for diagnosis.

• Ensure that a Register of TB Suspects is maintained in all health institutions and

the names and complete addresses of TB suspects referred are entered in this

register.

• Ensure that all TB suspects have three sputum specimens examined for diagnosis

• To take measures to implement directly observed treatment throughout the district

68

• Identify the microscopy centres, the treatment centres for DOT, and the staff

responsible for DOT in consultation with the officers in charge of these health

institutions.

• To supervise and ensure proper treatment of tuberculosis patients throughout the

district and particularly ensure that:

- The correct regimens of treatment are provided

- The patients are receiving the drugs under direct observation of a health

worker during the intensive phase of treatment.

- Patients are collecting the drugs regularly during the continuation phase of

treatment

- Patients and their family members are individually advised regarding the

disease and the importance of adhering to treatment schedules

- Two sputum examinations for tubercle bacilli are done at the stipulated

time intervals

- Treatment regimens are given for the required period and cured patients

are discharged from treatment

- Treatment outcomes are determined and recorded in the District

Tuberculosis Register

- Tuberculosis follow up card is completed and given to the patient to be

kept as a diagnosis card.

• To notify all cases of tuberculosis including the re-treatment cases to the Central

Unit.

• Maintain a regular supply of drugs, laboratory material needed for sputum

examination, and forms and registers for recording and reporting for the entire

district and distribution of these to the treatment centres and microscopy centres.

• Ensure that the District TB Register is updated and accurate.

• To supervise the chest clinic laboratory and the microscopy centres regularly and

monitor the maintenance of the TB Laboratory Register and documentation

related to microscopy examination.

• To establish quality control of sputum microscopy at the district chest clinic

laboratory.

• To conduct supervisory visits to all health institutions (DOTS centres, case finding

centres, microscopy centres) in the district, at least once a month.

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• To complete the quarterly reports on case finding, sputum conversion and

treatment outcome and forward it to the Central Unit on due dates.

• To carry out training of medical and paramedical staff on a continuous basis

• To organize health education programmes for the public

• To establish liaison with the general practitioners and the non-governmental

organizations (NGOs) to improve TB control in the district

• To carry out administration and financial activities of the Chest Clinic.

• To issue medical certificates to TB patients if they require.

• To issue certificates for obtaining financial assistance for the needy TB patients

PHI/Nurse/ any staff assigned by the DTCO

• Update the treatment card

• Maintain and update District TB register

• To trace a smear positive patient not started on treatment

• Maintain adequate drug supply to the DOT centres

• Prepare quarterly reports

• Take defaulter action to retrieve defaulters

• Impart health education to the patient and their family

Branch Chest Clinics

In every district, one or two branch chest clinics are held in selected general health

institutions in the district. These are conducted once or twice a month by the DTCO.

At these branch chest clinics, diagnosis, treatment and follow up of diagnosed TB patients

are carried out.

Health Institutional Level All general health institutions including teaching hospitals, provincial /general hospitals,

base hospitals, district hospitals, peripheral units, rural hospitals and central dispensaries

take part in TB control activities. Medical Officers of Health and their staff also play an

active role in TB control at this level.

Main responsibilities at the health institutional level

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A Medical Officer/Registered or Assistant Medical officer at the health institution will be

responsible for the TB control activities

The main functions are:

• To identify tuberculosis suspects and refer to the chest clinic or identified

microscopy centres for sputum examination.

• Maintain a Register of TB suspects and the names and complete addresses of all

TB suspects referred are entered in this register. Also ensure that when the results

of sputum examinations are received from the laboratory, they are entered in the

appropriate column.

• Cases diagnosed as tuberculosis should be referred to the DTCO/Chest Clinic for

registration, notification and commencement of treatment

• A treatment supervisor (DOT provider) should be identified at these institutions

for implementing DOTS. (This may be a MO/RMO/AMO/ Nurse/ Pharmacist/

Dispenser/ PHI/ Family Health Worker). They should be trained by the NTP.

• DOTS should be strictly implemented for the patients referred back from the

District Chest Clinic after registration and commencement of treatment.

• To ensure that patients complete the full course of treatment and the patients who

default treatment are traced immediately and treatment continued.

Duties of the Treatment supervisor (DOT provider)

• Observe the patient taking the drugs daily during the intensive phase of treatment

• Mark the Treatment Card daily, when the patient swallows the drugs

• Give health education to the patient and explain to him the importance of taking

the drugs regularly without interruption. This should be done on a continuous

basis

• Refer the patients at correct intervals for follow up sputum examination

• If the patient develops any side-effects due to the drugs, or any other complication

refer the patient to the medical officer of the health institution or to the District

Chest Clinic

• If the patient defaults treatment even for one day, take action to trace him and

continue treatment-

- Inform PHI of the area through Medical Officer of Health (MOH)

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- Get the help of another patient or any other person who lives close to the

patient’s residence

- If the patient cannot be traced inform DTCO

• All TB Treatment Cards should be kept in a separate file and numbered serially

• Keep the Treatment Cards updated for inspection by the DTCO on

his supervisory visits

• Once the patient has completed the intensive phase of treatment, refer back patient

to the District Chest Clinic for the continuation of treatment. This is better done

when 3 doses of the Intensive Phase are remaining so that results will be available

at 2 months to decide on Continuation Phase or extension of Intensive Phase.

Microscopy Centres

Microscopy centres are established in identified health institutions

Functions of the microscopy centres are:

• To examine the sputum specimens of all new patients referred from the same

institution or other health institutions in the area or by the General Practitioners.

• To examine the sputum of follow up TB patients referred to the centre.

• Ensure that three sputa are examined for diagnosis and two for follow up.

• Positive results are entered in RED.

• To maintain an accurate and updated TB Laboratory Register.

• To preserve all positive slides and the negative slides for quality control at the

district Chest Clinic Laboratory.

Functions of TB wards

• When patients are too ill for outdoor treatment or unable to come for daily DOTS

treatment, they may be admitted for indoor treatment and the nursing staff should

directly observe the patient taking the drugs.

• Patients should be given health education regarding the disease and the treatment

• At the end of intensive phase of treatment, the sputum should be examined before

discharge from the ward.

• On discharge, the TB Referral form should be filled in duplicate and the patient

referred to the appropriate District Chest Clinic with the original. The copy of the

Referral form should be posted to the referring chest clinic.

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3 TUBERCULOSIS CASE FINDING

The highest priority in tuberculosis control is to identify the infectious cases of

tuberculosis in the community as early as possible and treat them fully until they are

cured.

Patients with chest symptoms or any other symptoms usually seek treatment at the nearest

health facility, which may be governmental or private. If the medical officer suspects

tuberculosis, he should examine three specimens of sputum for Acid Fast Bacilli.

This could be done at the same institution if the microscopy facilities are available or the

patient referred to the closest health institution with microscopy facilities or to the District

Chest Clinic.

Three samples of sputum should be collected as follows:

• Supervised spot specimen

• Early morning sample on the next day

• Supervised second spot specimen when the patient returns with the early morning

sample.

Patients suspected of tuberculosis may be referred by general practitioners to the

government health institutions for diagnosis and treatment.

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Sputum examination should be provided free of charge for all patients. Referring medical

practitioners should be informed of the patient’s diagnosis.

Register of TB suspects

A Register of TB suspects should be maintained at all health institutions. This is a record

of all the patients identified as TB suspects at the health centre and referred for sputum

examination.

The register is useful:

• To monitor whether the results of smear examinations have been returned for all

sputum samples sent / TB suspects referred to the laboratory.

• To review the case finding activity of the health institution.

Whenever you identify a TB suspect, this should be recorded in the register. Make sure

that the full name and complete address of patient is written, so that the TB suspect could

be located if he does not return for the results and the sputum smear is positive.

Sample of a Register of TB suspects is shown in Annex XVII.

Management Plan of TB suspects Management of suspects attending general health institutions (Refer Flow Chart 1V) The ‘Results’ section of the Laboratory Request Form for Sputum examination should be

completed by the laboratory technician and returned to the referring medical officer who

should review the form. The results and the date of receiving it should be entered in the

Register of TB suspects in the appropriate columns.

Depending on the results of sputum smear examination:

• If two or more sputum smears are positive for AFB, the patient will be referred to

the District Chest Clinic, where a chest X-ray is done and the patient is registered

and notified as a case of sputum smear-positive PTB and appropriate treatment

commenced. A copy of the referral form is also sent to the DTCO by post. If the

patient is missing, the medical officer at the health institution should ensure that

s/he is traced.

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• If only two sputum specimens were examined and one specimen is smear positive

for AFB, another specimen should be collected and examined. If the third

specimen is positive, s/he will be referred to the chest clinic and managed as

above.

• If three specimens were examined and one smear is positive for AFB, refer the

patient to the District Chest Clinic, where a chest X-ray will be done. If the X-ray

is consistent with TB, the patient is registered and notified as a case of sputum

smear-positive PTB and appropriate treatment commenced.

In a well functioning laboratory, patients with only one out of three sputum

samples positive are exceptionally rare.

• If all sputum smears are negative for AFB, give the patient treatment that the

medical officer thinks is appropriate. If antibiotics are used, it is advisable to use a

broad-spectrum antibiotic like amoxicillin, co-trimoxazole, or erythromycin,

which does not have anti-tuberculosis activity, for a period of 1-2 weeks. The

patient should be reviewed after the course of treatment. If the patient has

improved, it is unlikely to be TB. Ask the patient to come back for review if the

symptoms recur.

• If the symptoms persist, the patient should be referred to the Chest Clinic for chest

X-ray and further management.

• Extra-pulmonary TB cases will be diagnosed by the physicians of various

specialties and referred to a District Chest Clinic for initiating treatment.

• When a patient is referred to the District Chest Clinic, a copy of the referral form

should be sent to the DTCO by post.

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Flow Chart IV

Management of TB suspects at Peripheral Health Institutions

Cough 3 weeks or more

Sputum smear x 3

Refer Chest Clinic

Symptoms persist Patient improves

1 smear positive 3 smears negative 2 or 3 smears positive

Appropriate treatment / Antibiotics

Refer Chest Clinic Refer Chest Clinic

`

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TB unlikely Treat symptomatically Review if symptoms recur

Management of suspects attending chest clinics (Refer Flow chart V)

For all chest symptomatics, a chest X-ray and three sputum smear examinations are done.

Depending on the results of the smear examination and X-ray findings, the patients will

be managed as follows:

• If two or three sputum smears are positive, patient is registered and notified as a

case of sputum smear-positive PTB irrespective of X-ray findings and Anti-TB

treatment commenced.

• If only two sputum specimens were examined and one smear is positive for AFB,

another specimen is collected and examined. If the third specimen is positive, he

will be managed as above.

• If one smear is positive out of the three smears examined and X-ray is suggestive

of TB, the patient is registered as a case of sputum smear-positive PTB and

Anti-TB treatment commenced.

• If one smear is positive out of the three smears examined and X-ray does not show

any abnormality, sputum examination should be repeated

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If sputum smear is again positive, he should be registered as a case of sputum

smear-positive PTB and Anti-TB treatment commenced.

If the repeat sputum smear is negative, give a course of antibiotics such as

amoxycillin, co-trimoxozole or erythromycin for 1-2 weeks. (Drugs such as

Fluoroquinolones which do have anti-TB activity should be avoided). Repeat the

sputum smear examination and chest X-ray after the course of antibiotics.

If the repeat CXR shows changes suggestive of TB, the patient is registered as a

case of smear-positive PTB and anti-TB treatment commenced.

If repeat CXR is still normal, then send a sample of sputum for TB culture and

review the patient in six weeks.

• If all three sputum smears are negative and the chest X-ray is normal, it is unlikely

to be TB, and symptomatic treatment given. Ask the patient to come back if the

symptoms recur.

• If all three sputum smears are negative, but chest X-ray shows abnormality, give a

course of antibiotics such as amoxycillin, co-trimoxazole, or erythromycin for 1-2

weeks. Repeat the chest X-ray two weeks after the course of antibiotics.

- If the patient has improved clinically and the X-ray has improved, it is

unlikely to be TB. However patient should be followed up.

- If the symptoms persist and X-ray shows no improvement, re-check the

sputum for AFB.

• If the sputum is negative and the DTCO is of the opinion that it is TB,

- Then send the sputum for culture for AFB

- Register and notify the patient as a case of sputum smear-negative PTB

- Start anti-TB treatment

- Repeat chest X-ray after one month of anti-TB therapy

• If the DTCO is of the opinion that it is not TB, then other diagnoses should be

considered and the patient referred to the chest physician for further investigation

and management.

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Flow Chart V

Management of TB Suspects at District Chest Clinics

Cough 3 weeks or more

Sputum smears x 3 Chest X-ray

` Re-check sputum Smear +ve Smear -ve

CXR consistent with TB

Repeat CXR after 2 weeks

Symptoms persist CXR no improvement

Patient improves CXR improves

1 smear positive 3 smears negative2 or 3 smears positive

CXR abnormal CXR normal

Antibiotics 1- 2 weeksRe-check sputum

Smear +ve Smear -ve

Antibiotics for 1-2 weeks

Repeat CXR and sputum after 2 weeks

CXR normal

CXR consistent with TB

CXR Normal

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MO’s decision

Yes TB No TB

Send sputum for culture

Review in 6 weeks

TB unlikely Treat symptomatically Review if symptoms recur

Register & Notify as smear +ve PTB Start ATT

Send sputum for culture Register & notify as smear –ve PTB Start ATT Repeat CXR after one month

Consider other diagnosis Refer chest physician

4 TREATMENT AND FOLLOW UP OF TB PATIENTS

When a patient is diagnosed as a case of tuberculosis, the following steps should be

adhered to –

1. Registration

- Register the patient in the District TB Register (TB 03) and allot him a

District TB Number

- Classify the patient depending on the site, sputum smear result and history

of previous treatment for TB

- Identify the correct category of treatment.

CAT 1 - All new cases

CAT 2 - Re-treatment cases (Relapse, Treatment after failure,

and Treatment after default).

2. Fill in the TB Treatment Card (TB 01) in duplicate.

3. Prepare the Patient Follow-up Card (TB 02).

4. Notification -

Fill up the TB Notification Form (H 816) with two carbonized copies and send the

relevant copies as indicated in the Notification form to the relevant units. When the

relevant copy reaches the Central Unit, patient is registered and a Central TB Register

Number is given.

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5. Health education -

The patient and the family should be given health education:

- Regarding the disease and how it is spread

- Treatment, duration, dosages, number of tablets, colour of tablets etc.

- Stress the importance of directly observed treatment and regular,

uninterrupted treatment for the entire duration.

- The need for sputum examination at regular intervals for monitoring

- Possible common side-effects

- Examination of close contacts

6. Treatment

Sputum smear-positive PTB cases

Intensive phase of treatment

• During the intensive phase of treatment, each and every dose of medicine should

be given under the direct observation of the identified treatment observer.

• Explain to the patient, that the treatment during the intensive phase is very

important and should be directly observed.

• If the patient is too ill for outdoor treatment or if s/he is unable to come for daily-

observed treatment, s/he may be admitted to hospital for indoor treatment. The

nursing staff should directly observe the patient swallowing the drugs.

• Identify the DOTS centre, which is most easily accessible and convenient to the

patient after discussing with him, and arrange for his treatment there. This could

be the Chest Clinic itself or an identified DOT centre close to his home or work

place

• One copy of the Treatment Card and the drugs are dispatched to the appropriate

treatment centre through a staff of the chest clinic.

At the treatment centre -

• The treatment supervisor should receive the Treatment Card and the drugs sent by

the Chest Clinic

• He should receive the patient, talk to him and establish a good rapport with the

patient.

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• Explain to him the importance of taking the drugs daily for the entire period

without interruption

• The treatment supervisor should allocate a time convenient for DOT and advise

the patient to adhere to the time schedule as far as possible.

• He should make arrangements to give the drugs to the patient with no or minimum

delay.

• He should hand over the drugs and observe the patient swallowing the drugs.

• Tick off the Treatment Card daily each time the patient takes the drugs.

• If the patient develops any minor side-effects, he may be referred to the medical

officer of the health institution. If he develops any major side effect or any

complications, he should be referred to the Chest Clinic.

• If the patient does not come for treatment even for one day, prompt action should

be taken to trace the patient

- Inform the PHI of the area or the Public Health Midwife

- Send a message through a volunteer or any other patient or staff

member who lives close to the patient’s residence

- Inform the DTCO/MO of the Chest Clinic if necessary.

- Record the action taken

- At the end of the intensive phase of treatment, the patient should be

referred back to the Chest Clinic with the Treatment Card and advise

patient to take an early morning sample of sputum for examination

Continuation Phase of Treatment

• The patient will come to the Chest Clinic with an early morning sample of

sputum.

• Collect another spot sample.

• If the sputum smear is positive, the patient will be directed to the treatment

centre with the Treatment Card for DOT for another one month.

• After one month, the patient has to be referred back to the clinic with the

treatment card and another early morning sputum sample.

• When the sputum smear is negative at the end of intensive phase, the

patient is given the continuation phase of treatment.

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Since the continuation phase also contains Rifampicin, every effort should

be made to give each dose under observation. Wherever this is not possible

patients will be advised to attend the DOT centre/chest clinic once a week,

and the first dose will be given under direct observation and the remaining

six doses will be supplied for self-administration at home. The DTCO

should ensure that a household member observes the patient taking the

drugs daily and will make arrangements for supervisory visits to check

drug intake (including pill counts).

• Sputum is examined at the required intervals and treatment continued till

the end.

• At the end of treatment, the treatment outcome is entered in the TB Follow

up Card (TB 02) the patient is advised to keep it as a diagnosis card.

Sputum smear-negative PTB cases

Intensive phase

• For the sputum smear negative patients too, DOT should be given during the

intensive phase of treatment as in the case of sputum smear positive patients.

Continuation phase

• Since the continuation phase also contains Rifampicin, every effort should be

made to give each dose under observation. Wherever this is not possible patients

will be advised to attend the DOT centre/chest clinic once a week, and the first

dose will be given under direct observation and the remaining six doses will be

supplied for self-administration at home. The DTCO should ensure that a

household member observes the patient taking the drugs daily and will make

arrangements for supervisory visits to check drug intake (including pill counts).

Extra-pulmonary TB cases

Intensive phase

• Treatment will be given under direct observation during the initial intensive phase

of 2 months.

Continuation phase

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• Since the continuation phase also contains Rifampicin, every effort should be

made to give each dose under observation. Wherever this is not possible patients

will be advised to attend the DOT centre/chest clinic once a week, and the first

dose will be given under direct observation and the remaining six doses will be

supplied for self-administration at home. The DTCO should ensure that a

household member observes the patient taking the drugs daily and will make

arrangements for supervisory visits to check drug intake (including pill counts).

Re-treatment cases

• All Re-treatment cases should be given DOT throughout the entire period of

treatment. Admission to hospital is recommended whenever possible.

Intensive phase - Daily, directly observed treatment

Continuation phase - Daily, directly observed treatment

• For streptomycin injections, disposable syringes and needles should be used. If

glass syringes and needles are used, they should be properly sterilized.

Transfer of patients The district initiating treatment is responsible for reporting treatment outcome for the

transferred cases

If the patient is transferred to another district after starting treatment -

• Fill up the Referral /Transfer Form (TB 09) in triplicate

- One copy of the form is given to the patient

- One copy is sent by post to the Chest Clinic of the district where the

patient proposes to take treatment

- Third copy is retained at the original clinic.

• At the receiving Chest Clinic, the patient is registered in the District TB Register

as ‘Transfer in’ and a new District TB Number is given.

• The lower portion of the Transfer form, which the patient brings, is sent back to

the clinic from where he was transferred out.

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• At the end of treatment, inform the treatment outcome to the referring unit in the

copy sent by post.

RECORDING AND REPORTING 5

Recording and Reporting is an essential part of the National Tuberculosis Programme.

• Careful recording of information on each patient helps to keep track of their

treatment and progress

• Periodic reporting on NTP activities helps to evaluate the performance of the

control programme and plan and calculate the resources needed.

Following Records and Reports are used in the NTP:

Records 1. TUBERCULOSIS TREATMENT CARD (TB 01) As soon as the diagnosis is made, this card should be filled for each patient started on

treatment. If the patient is given DOTS at another treatment centre, TB treatment Card

should be written in duplicate. The original card is retained in the clinic and the duplicate

sent to the DOTS treatment centre. This contains spaces for the health worker to mark

when the patient takes the treatment each time.

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The information on the duplicate treatment card should be transferred to the original

Treatment Card during supervisory visits or when the PHI / Health worker takes the drugs

to the DOTS centre next time.

The relevant information, particularly the sputum results should be transferred from the

Treatment Card to the District TB Register kept at the District Chest Clinic.

If the patient is transferred to another district, the original is kept at the clinic and the

duplicate Treatment Card with entries updated will be given to the patient to be taken to

the new district.

2. TUBERCULOSIS FOLLOW-UP CARD (TB 02) This should be filled as soon as a patient is diagnosed. This is kept by the patient

This contains information similar to the treatment card. It also includes spaces for the

dates of follow up appointments and health messages.

At the end of treatment, outcome of treatment is written on this card in the space

provided and is given to the patient. This can be used as the diagnosis card.

3. DISTRICT TUBERCULOSIS REGISTER (TB 03) This is maintained at the District Chest Clinic. All tuberculosis patients diagnosed and

receiving treatment in the district are entered in this register and it contains all the details

of the patient.

It helps to keep track of all patients receiving treatment in the district. The relevant

information from the TB treatment Card, particularly the sputum results should be

transferred to the register regularly.

The DTCO uses the information in this register to prepare the Quarterly Reports on Case

Finding, Sputum conversion and the Treatment Outcome

4. TUBERCULOSIS LABORATORY REGISTER (TB 04) This is kept at all Laboratories and microscopy centres carrying out sputum smear

examinations. This is maintained by the laboratory technician and he should enter all the

details in the relevant columns and keep the register updated

5. REQUEST FOR SPUTUM EXAMINATION (TB 05) This is kept at all health institutions. This should be filled by the medical officer for every

patient referred for sputum examination. Only one form need to be filled for all three

sputum specimens collected from each patient.

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After examining the smears, the Laboratory technician should enter the ‘Results’ in the

relevant section of the form and send it back to the referring medical officer as soon as

possible.

6. REQUEST FOR TB CULTURE AND DRUG SUSCEPTIBILITY

TEST (TB 06) This is kept at the District Chest Clinics and Chest Hospital. This is sent to the Central

Tuberculosis Laboratory when sputum culture and sensitivity is requested.

7. TRANSFER / REFERRAL FORM FOR TB PATIENTS (TB 07) When a patient is transferred to another district, this form should be filled in triplicate.

- Original form is given to the patient to be taken to the new district

- One copy sent directly to the new district by post.

- One copy is retained in the clinic.

The receiving Chest Clinic will fill the bottom part of the copy brought by the patient and

return it to the referring clinic as soon as the patient has been registered in the new district

as a ‘Transfer in’. At the end of treatment, the bottom part of the copy sent by post

should be completed and returned to the referred unit informing the treatment outcome of

the patient.

8. REGISTER OF TUBERCULOSIS SUSPECTS (TB 16) This is maintained at all Health Institutions in the district which are involved in detecting

TB suspects. This register helps/allows to find out whether the health institutions are

correctly identifying the TB suspects and subjecting them for sputum examinations.

Reports The quarterly reports on cases are made so as to permit cohort analysis. The reports are

prepared using the information in the District TB register. Accurate and timely reports

can only be produced if the register is kept up to date.

The DTCO should submit the following quarterly reports to the Central Unit within the

first week of each quarter. The reports should be completed in duplicate. The original

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should be sent to the Central Unit and the duplicate retained at the clinic for record

purposes.

1. QUARTERLY REPORT ON CASE FINDING (TB 08) This report contains information on New and Re-treatment cases of TB registered during

the quarter and age and sex breakdown.

This report is useful in programme planning and monitoring of trends.

The dates for submitting the report is as follows:

Quarter Date of completion

1st Quarter (January - March) 1st week of April

2nd Quarter (April –June) 1st week of July

3rd Quarter (July – September) 1st week of October

4th Quarter (October – December) 1st week of January

2. QUARTERLY REPORT ON SPUTUM CONVERSION (TB 09) This report gives the proportion of sputum positive cases registered in the quarter ended

three months ago, who became smear negative at two and three months of treatment

The sputum conversion rate is a critical indicator of the effectiveness of the programme

implementation during the intensive phase of treatment.

The reports should be submitted as follows:

Quarter Date of completion

1st Quarter (January - March) 1st week of July

2nd Quarter (April – June) 1st week of August

3rd Quarter (July – September) 1st week of January

4th Quarter (October – December) 1st week of April

3. QUARTERLY REPORT ON TREATMENT OUTCOME (TB 10) This report gives the treatment outcome of patients registered 12-15 months earlier.

The report provides information needed to analyze the treatment indicators of the NTP.

Regular monitoring of treatment results will enable to assess the adequacy of treatment

regimens as well as quality of case management.

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The dates for submitting the Report on treatment outcome of patients who started

treatment for e.g. 1997 will be as follows:

Quarter Date of completion

1st January - 31st March 1997 1st week of April 1998

1st April - 30th June 1997 1st week of July 1998

1st July - 30th September 1997 1st week of Oct. 1998

1st October - 31st December 1997 1st week of Jan. 1999

4. QUARTERLY REPORT ON MICROSCOPY ACTIVITIES AND

LOGISTICS (DISTRIC LEVEL) (TB 11) This report has two parts. Part A gives information regarding the case finding activities

and has to be filled by all Health Institutions in the district. Part B has to be filled by the

health Institutions where microscopy Centers are located.

5. QUARTERLY REPORT ON PROGRAMME MANAGEMENT

(DISTRICT LEVEL) (TB12) This should be completed by the DTCO and sent to the Central Unit during the first week

of each quarter. This report gives information regarding the case finding and microscopy

activities, supervisory activities, availability and training of health staff, involvement of

other stakeholders for TB control and advocacy programmes in the district. It also

provides information on drug consumption and other supplies.

6. QUARTERLY REPORT - TB & NON TB WARDS (TB 13) This report gives information regarding admissions and discharges in TB and non-TB

wards in the district and the microscopy services in these institutions.

7. QUARTERLY REPORT - CHEST HOSPITAL, WELISARSA (TB

14) This form gives information on outpatient and inpatient services and the laboratory

services in the Chest Hospital, Welisara.

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8. QUARTERLY REPORT - NATIONAL TUBERCULOSIS

REFERENCE LABORATORY (TB 15) This report provides information on culture examinations, susceptibility patterns and the

number of MDR-TB cases for a quarter.

Compilation and analysis The quarterly reports are compiled at the district level on the first week of each quarter

and sent to the central level. The DTCO should initiate remedial actions if the technical

and managerial indicators have not been met and send the proposed remedial actions to

the central unit. The central unit compiles and analyses reports from all the districts and

gives feed back to the DTCO within 6 weeks of receipt of the reports.

SUPERVISION 6

Supervision is an essential part of the National Tuberculosis Programme. The success of

the NTP depends on whether staff at all levels performs their work well. Supervision is a

process of helping the staff to improve their work performance.

Supervisory visits give an opportunity to assess their performance and provide technical

advice and guidance so that the staff can correctly perform their activities as stipulated in

the programme. The crux of the supervisory visits should be on education and guidance to

perform as per guidelines.

Supervisory visits should be carried out on a regular basis at all levels.

• Director of the National Programme should do regular supervisory visits to the

District Chest Clinics.

• The District Tuberculosis Control Officer should visit the health institutions,

treatment centres, and the microscopy centres in the district

• Staff from the Central Tuberculosis Laboratory should visit the district chest clinic

laboratories.

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The supervisory visits and the frequency of visits should be planned out. Some districts or

health units may need more supervision than others based on performance indicators.

For the supervisory visit to be productive and effective –

• Plan and prepare for the visit

• A supervisory check list should be prepared. Check list should include activities in

relation to case finding, treatment, microscopy, drugs, patient awareness, and

logistics.

• You should inform the staff concerned in advance of your visit so that they should

be there during your visit. Sometimes you may do occasional surprise visits.

Some ways to collect information during supervisory visits are:

• Review of tuberculosis treatment card

• Review of the laboratory register

• Observing the health workers

• Talking with the health workers

• Talking with the TB patients

• Checking the stock position of drugs and other consumables

• Checking of defaulter retrieval actions

During supervisory visits, check whether a TB suspect register is properly maintained at

the peripheral health institutions and whether all patients referred have attended the

microscopy centers and returned with results. Ensure that all patients diagnosed with

smear positive TB are on directly observed treatment during the intensive phase of

treatment. All patients found to be smear positive should be accounted for in the

laboratory register and all smear positive patients found in the laboratory register are

started on treatment and registered in the TB register. Also review laboratory register and

ensure that all patients have follow up smear examination as detailed in the NTP. This

will be facilitated if the TB number is recorded in the remarks column of the laboratory

register.

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7 EVALUATION

Evaluation should be an integral component of any National Tuberculosis Programme.

Evaluation of the programme will assess the degree of success that has been achieved in

reaching the objectives.

Collecting information quarterly allows for cohort analysis of data for a given district. It

is mandatory to collect information regularly on case finding and on the results of

chemotherapy. The most important method for the evaluation of control measures is by

review and analysis of the following reports:

• Quarterly Report of Case Finding

• Quarterly Report of Sputum Conversion of smear-positive cases

• Quarterly Report on Treatment Results

Using indicators is a way to measure the achievement of activities of the programme.

There are certain indicators, which should be examined regularly by the NTP.

Indicators of Case Finding

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• Case detection rate of new smear-positive PTB cases

The case detection rate is the number of new pulmonary smear-positive cases

detected, expressed as a percentage of the estimate of new smear-positive cases. It

provides a measure of case finding coverage.

• Proportion of pulmonary smear-positive cases out of all pulmonary cases

registered in a quarter.

Approximately 65% of all the pulmonary cases registered in a quarter should be

smear-positive. If the percentage of smear positive cases is significantly lower, the

quality of diagnosis of pulmonary tuberculosis may be poor.

• Ratio of new smear-positive case to new smear-negative and extra pulmonary

cases

There should be approximately a 1:1 ratio between the number of new smear-

positive and the number of smear-negative cases and extra pulmonary cases

combined.

• Proportion of smear-positive cases among TB suspects

This is the number of smear-positive cases detected divided by the total number of

suspects examined. This is usually around 10%. This rate will decrease as the

prevalence of TB decrease in the community.

• Reported case notification rate for new smear-positive cases (per 100,000

population)

This is the number of newly detected smear-positive cases per 100,000

population. The reported case notification rate is important for observing trends in

case notification over several years. This is usually calculated once a year.

This should also be done by age and sex. The reported case notification rate of

new smear positive cases by age and sex is the number of new smear-positive

cases detected in specific age and sex groups per population of 100,000. It

provides information on the trend of TB.

As the transmission of TB decreases, the disease in young people falls. The

incidence in older people does not fall so rapidly, because many of them were

infected years earlier. In a successful TB control Programme, the peak gradually

moves from young people to older people.

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Indicators of case holding

• Sputum Conversion rate at 2 (3) months of treatment for new smear-positive

cases and at 3(4) months of treatment for relapses and re-treatment cases.

Conversion rate is the number of smear positive cases, which convert from smear

positive to smear-negative at the end of intensive phase of treatment, out of all

smear-positive cases registered during a quarter. The conversion rate for new

smear-positive cases and relapses should be at least 85%. It should be at least 80%

for other re-treatment cases.

• Treatment outcomes for new smear-positive cases, relapses and other re-

treatment cases - Cure rate, Completion rate, Default rate, Failure rate,

Death rate, Transfer rate.

Cure rate of new pulmonary smear-positive cases is the proportion of new

pulmonary smear-positive cases cured out of all new smear-positive cases

registered during a given quarter. It should be at least 85%. This is the most

important outcome indicator.

Completion rate of new smear-positive cases is the proportion of new pulmonary

smear-positive cases who completed treatment (but did not have a bacteriological

examination of smears at the end of treatment) out of all registered new smear-

positive cases during a given quarter.

Default rate of new smear-positive cases is the proportion of new smear-positive

cases who do not collect drugs for two or more months out of all registered new

smear-positive cases for a given quarter. This should be less than 5%.

Failure rate of new smear-positive cases is the proportion of failures of new

smear-positive cases out of all registered new smear-positive cases for a given

quarter. If there is no drug resistance, this should be less than 4%.

Death rate - Proportion of deaths of new smear-positive cases out of all registered

new smear-positive cases during a given quarter.

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Transfer rate - Proportion of new smear-positive cases who were transferred to

another district, out of all registered new smear-positive cases during a given

quarter.

Success Rate – % Cure rate + %Completion rate

Cohort analysis of re-treatment cases, smear-negative cases and extra pulmonary

cases also should be done in the same way.

The central unit will give feed back to the DTCO regarding the performance of

their district for the quarter and suggest corrective actions, if any.

TRAINING

Training activities

Training of all the staff involved in the programme as per the DOTS strategy is an

important component of the programme. They need to be trained as per the revised

technical, operational and laboratory manuals. The district tuberculosis control officers

will be trained at the central level using the 10 modules prepared. Training will be for 10

days. The DTCO in turn will train the medical officers in the district using modules1-4

for 5-days, and arrange for the training of the paramedical staff. The LT and the PHI of

the district chest clinic also will be trained at the central level and they in turn will impart

training to the other LTs, microscopists and other staff involved in drug delivery of the

district. Separate training modules will be made available for LTs and paramedical staff

involved in the NTP activities. Training should include field and practical exercise.

Table 13 Training schedule for operational staff of the NTP

Officials to be trained

Duration Methodology Place of training

DTCOs/Chest 10 days Work shop using training Central unit

8

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physicians modules, and field visits

Nurses/PHIs of

District Chest Clinic

6 days Training modules, practical

exercise

Central unit

LTs of District

Chest Clinic

8 days Training modules and

practical exercise

Central unit

Other MOs of the

district

3 days Training modules and

exercise

District chest clinic

Other LTs and

microscopists

5 days Training modules and

practical exercise

District chest clinic

DOT providers 2 days Training modules and

practical exercise

District chest

clinic/DOT centers

Community workers ½-1 day Training Guidelines DOT centre

9 MANAGEMENT OF DRUGS AND SUPPLIES

Activities for management of drugs and supplies must be designed to support tuberculosis

control activities, providing supplies to carry out activities as spelt out in the programme.

Procurement and supply are recurring process. Various components of the management

cycle are:

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Figure II Anti-TB drug management cycle

Management support is an integral part of each of these components. A viable

management information system (MIS) must be in place to provide specific programme

data required to ensure adequate supply. In NTP, the quarterly reporting system helps to

identify requirements of each item and to procure based on these requirements.

INTER-SECTORAL COORDINATION

Tuberculosis is being managed by all health institutions, be it private or public. If the

disease is to be controlled, there is a need that all these agencies work together. In

addition to the preventive side, the curative side of medicine and the teaching institutions

play a major role in TB control. Patients diagnosed at these institutions should be referred

to the programme for further management.

Procurement

Selection

Quality assurance

Use Management

support

Distribution

10

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Health institutions attached to other ministries also manage tuberculosis e.g. Police,

defence ministry etc. They also should come under the frame work of TB control so that a

complete tracking system of TB patients is available.

In addition, there is a large private sector in the country, diagnosing and treating

tuberculosis. There is a need to involve them also in the fight against tuberculosis. Only

when all sectors managing tuberculosis come together, the country will have a clear

picture on the control of the disease.

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PART III

ADMINISTRATION

OF

A CHEST CLINIC

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DISTRICT CHEST CLINIC 1

The District Chest Clinic is the key organizational unit of the National Tuberculosis

programme at district level.

The Chest Physician / District Tuberculosis Control Officer (DTCO) is in charge of the

administration of the chest clinic and functions under his guidance.

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Staff The staff of the District Chest Clinic consists of the following categories:

• Chest Physician /DTCO (preferably with DTCD qualification)

• Medical Officer

• Nursing Officer

• Radiographer

• MLT/ Microscopist

• PHI

• Pharmacist / Dispenser

• Clerk

• Laboratory orderly

• Labourers

• Driver

The number of each category of personnel will depend on the size of the clinic and the

population it serves.

Structure Basically the Chest Clinic consists of the following sections:

• Registration section

• Clinical section

• Laboratory

• X-ray department

• Pharmacy

• Health Education section

• Statistical section

• General Office / Administrative section

• Stores

Duties and Responsibilities of the DTCO

• Tuberculosis Control Activities

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The activities related to Tuberculosis control have been described in detail in the

previous sections.

In addition to these the Medical officer in charge of the District Chest Clinic

(Chest Physician / DTCO) has the following responsibilities:

• General administration of the chest clinic – smooth functioning of the clinic,

supervision of staff, etc.

• Financial Responsibilities

- Maintenance of the Remittance Register and the Petty cash Register

- Payment of salaries for the staff

• Estimation of requirements of drugs, treatment related materials, laboratory

materials, stores items, and equipment for the following year.

• Periodical checking of drug stores and general stores

• Issue of medical certificates to patients when required

• Issue of medical certificates for needy TB patients for obtaining TB assistance

from the Social Services Department.

• To ensure the safety of staff and proper disposal of sputum – (This is described in

detail in the Laboratory Manual for TB Control).

DRUGS AND SUPPLIES 2

One of the most important tasks of the DTCO is to ensure a continuous regular supply of

drugs and other supplies required for the diagnosis and management of tuberculosis and

other respiratory diseases.

The drugs and supplies include the following:

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• The anti-tuberculosis drugs required to treat new and re-treatment TB cases

• Treatment-related supplies -syringes, needles, sterilizers, etc.

• Laboratory supplies for diagnosis – sputum containers, slides. reagents, etc.

• Tuberculin and BCG vaccine vials

• Recording and Reporting Forms and Registers

• Drugs required for other respiratory diseases.

The District TB control Officer should calculate the requirement of the anti-TB drugs for

the following year and send to the Central Unit of the NTP along with the requirements of

sputum containers, tuberculin vials and Tuberculosis forms and registers. These will be

issued quarterly from the NTP.

The drugs required for other respiratory diseases, treatment related supplies, slides,

reagents and other laboratory materials needed for the district for the entire year is

calculated separately and the estimates are send to the Deputy Provincial Director of

Health. The requirements will be issued to the District Chest Clinic quarterly from the

Regional Medical Supplies Division (RMSD).

The DTCO must work closely with the treatment units and the Microscopy centres to

make sure they receive drug supplies and other materials regularly. It is essential that

patients receive the drugs promptly after diagnosis. Keeping large stocks of drug supplies

is not always practical for peripheral health units because they may only have a limited

number of patients in a year. Arrangements should be made to deliver the drugs to the

treatment centres immediately, when a patient is referred to a health centre for DOTS.

Maintain an adequate supply of drugs It is very important to make sure that the district has an adequate supply of anti-TB drugs.

There should be a reserve stock of drugs for a three-month period at the Regional Medical

Supplies Division (RMSD) and the District Chest Clinic should have another reserve

stock of drugs for a three-month period.

Estimation of anti-TB drug requirements.

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Calculate the amount of drugs needed for the year based on the number of cases

discovered during the previous year.

Calculate as follows:

1) Determine the number of patients registered in the last quarter for each

treatment regimen (CAT 1 and 2).

2) Determine the amount of tablets/or grams of each drug needed for one patient per

treatment regimen.

3) Determine the total amount of tablets or grams of each drug needed to treat all

patients during the quarter.

4) Calculate the total number of tablets or grams of each drug needed for the entire

year, by multiplying the amount of each tablet by 4 (for the four quarters of the

year).

5) To allow for the reserve stock, add the amount of tablets or grams of each drug

needed for a quarter (3 months) (i.e. the numbers obtained in step 3) to the amount

calculated for the year (numbers obtained in step 4).

6) Check the stocks available in the stores. Subtract the amount of tablets in the drug

store from the total amount of each drug needed (the numbers obtained in step 5).

Calculate the Number of syringes and needles required for administering streptomycin

Injections for the year.

After calculating the amount of drugs and other supplies needed, send your annual

requirement to the Director, NPTCCD / Deputy Provincial Director of Health.

Storage of drugs

• Drugs should be stored in a secured stockroom and protected from unauthorized

access

• Should be protected from heat, light. moisture/rain, dust, pests and fire

• Store the drugs according to their expiry dates with each drug clearly marked.

• Use the FEFO (First –Expired –First-Out) rule: First drugs to expire are the first

drugs out (i.e., issue the oldest drug s first).

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3 ISSUE OF MEDICAL CERTIFICATES

Medical certificates for Leave • Rules and regulations governing the issue of medical certificates to patients are

embodied in the following government circulars:

- General Circular 1006 / 20.06.79

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- General Circular 1086 / 07.05.80

- General Circular 1481 / 21.10.86

• Public servants bounded by Public Service Commission rules and government

funds are issued medical certificates in form ‘medical 170’ (major staff) and in

form ‘medical 331’ (minor staff) free of charge.

• Private individuals, corporation and board employees and private sector

employees are issued medical certificates in form ‘H 307’.on payment. The fee

charged for the issue of private medical certificates will be according to the

prevailing hospital charges circular issued by the government.

• The quantum of leave to be recommended for public servants and private sector,

in each medical certificate is as follows:

1st instance - Not exceeding one month

2nd instance - Not exceeding one month

3rd instance - two weeks

4th instance - two weeks

• After a period of leave for three months, the patient concerned should be

examined by a Medical Board. The medical board will decide whether the patient

is fit for work or whether he needs further leave from work.

• For TB patients who may need more than three months leave, a medical board

may be recommended in the first medical itself so that the employer can take

necessary steps to arrange for a Medical Board without delay.

• The Medical Officer who treated the patient cannot sit on the Medical Board for

that particular patient (vide General Circular No 2951).

• Past absence from duty can be covered retrospectively up to five days from the

day of issuing the medical certificate, and in the case of indoor patients, the period

of stay in the hospital can be covered.

• Special TB leave granted to TB patients is governed by Establishment Code

chapter (XX111) and as amended by Public Administration circulars 30/89 of

03.05. 89 and 32/93 of 20.12. 93.

- A TB patient who is in public service is entitled to four months of full pay

special leave in the first instance.

- In the event of a relapse, he is entitled again to four months of fully paid

leave only after a period of 04 years.

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- This special TB leave of four months can be recommended only by a

medical board as mentioned.

• TB patients who want to get their EPF money back before retirement age should

be advised to apply for a Medical Board.

• Any patient referred regardless of his employment status (private or public sector)

should be screened for TB free of charge at any government health institution. The

report in such a case should state only “no evidence of TB’ or ‘evidence of TB’

and issued free of charge.

• Any individual referred by a private practitioner for any specific investigation

other than the sputum for AFB should be charged the fee as mentioned in the

prevailing hospital charges circular.

Medical certificates for Financial Assistance • An unemployed TB patient is entitled to seek financial assistance if he wishes to.

• Financial assistance is provided by the Social Services Department and the

DTCO/MO of the chest clinic or chest hospital has to issue a medical certificate

on Form SS/TB/M1.

• The necessary investigations as to whether the patient’s economic status deserves

such assistance and the amount to be given depending on the number of

dependents will be the responsibility of the Social Services Department.

• The assistance will be given only during the period of anti-tuberculosis treatment.

Conditions of eligibility for financial assistance

• The applicant should be examined and certified to be suffering from tuberculosis

by a Medical Officer of a Chest Clinic or Chest Hospital.

• The applicant should accept and continue to follow regular treatment prescribed

by the Medical officer

Administrative procedure for the TB Assistance scheme

The following steps should be followed regarding TB assistance for TB patients (in-

patients and outpatients) of chest clinics and chest hospitals.

• The Medical Officer of the Chest Clinic /Chest Hospital will issue a medical

certificate on the prescribed form (SS/TB/M1) at the request of the patient for him

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to obtain the financial assistance. This form will be posted to the relevant

Divisional secretary, who will make suitable arrangements for the payment of TB

assistance to the patient or his dependants.

• The Divisional Secretary will inform the patient / medical officer of the decision

taken, after evaluation by the social service officer (S.S.O) in his office.

• The MO will issue a medical certificate on the prescribed form in the first instance

for three months and thereafter a renewed medical certificate will be sent on the

same form for every three months for renewal of the allowance.

• This will be issued only for the duration of anti-TB treatment.

• When the patient completes treatment, or defaults or dies, the Medical Officer will

inform the Assistant Director/Social Services of the change.

Procedure for issue of Medical Certificates on Form SS/TB/M1

• The Medical Officer should note in the BHT or patient’s clinic file, the

recommended period of TB assistance and should verify this period is correctly

entered in the medical certificate before placing his signature.

• The relevant medical certificate number should be noted on the BHT or clinic file

with the above entry before dispatch

• The medical officer should enter the relevant details in the counterfoil of the

certificate issued.

• A register on the issue of medical certificates for financial assistance should be

maintained. This should be maintained in serial order and the relevant date of

posting the medical certificate should be entered in the register.

• All letters received from the Provincial Secretary regarding the payment

/nonpayment of TB assistance to TB patients should be kept filed in the relevant

BHT/or clinic file.

• The specimen signature of medical officers authorized to sign the medical

certificates should be sent to the Provincial Secretary in advance.

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