WHO/HTM/TB/2004.329

second edition

A CLINICAL MANUAL

TB HIV

WORLD HEALTH ORGANIZATION

TB/HIV

A CLINICAL MANUAL

Second edition

Stop TB Department

Department of HIV/AIDS

Department of Child and Adolescent Health and Development

World Health Organization

Geneva

Writing team:

Anthony Harries

Adviser to National Tuberculosis Control Programme,Lilongwe, Malawi

Dermot Maher

Stop TB Department,World Health Organization,Geneva, Switzerland

Stephen Graham

Wellcome Trust Research Laboratories,Blantyre, Malawi and

Liverpool School of Tropical Medicine,Liverpool, England

With contributions from:

Mario Raviglione andPaul Nunn

Stop TB Department

Charles Gilks

Department of HIV/AIDS

Shamim Qazi and Martin Weber

Department of Child and Adolescent Health and Development

World Health Organization

Eric van Praag

Family Health International,Washington DC,USA

And forewords by:

Dr JW Lee (2

edition)

Sir John Crofton(1

edition)

Acknowledgments:

We gratefully acknowledge the helpful comments and suggestions of

Drs Kevin de Cock,Robert Colebunders, Peter Donald,

Malgosia Grzemska,Fabio Scano, Robert Scherpbier,Jeffrey Starke and

Mukund Uplekar who reviewed the manuscript.

WHO/HTM/TB/2004.329

WHO Library Cataloguing-in-Publication Data

TB/HIV:a clinical manual / writing team:

Anthony Harries,Dermot Maher and Stephen Graham. - 2nd ed.

1.Tuberculosis,Pulmonary 2.Tuberculosis 3.HIV infections 4.AIDS-related

opportunistic infections 5.Antitubercular agents 6.Anti-retroviral agents

7.Delivery of health care,Integrated 8.Manuals I. Harries,Anthony

II.Maher,Dermot. III.Graham,Stephen.

ISBN 92 4 154634 4 (NLM classification:WF 200)

obtained from Marketing and Dissemination,World Health Organization,20

Avenue Appia,1211 Geneva 27, Switzerland (tel:+41 22 791 2476; fax: +41

22 791 4857; email: book

orders@who.int). Requests for permission to

reproduce or translate WHO publications – whether for sale or for

noncommercial distribution – should be addressed to Publications,at the

above address (fax:+41 22 791 4806; email:permissions@who.int).

The designations employed and the presentation of the material in this

publication do not imply the expression of any opinion whatsoever on the

part of the World Health Organization concerning the legal status of any

country, territory, city or area or of its authorities, or concerning the

delimitation of its frontiers or boundaries.Dotted lines on maps represent

approximate border lines for which there may not yet be full agreement.

The mention of specific companies or of certain manufacturers’ products

does not imply that they are endorsed or recommended by the World

Health Organization in preference to others of a similar nature that are not

mentioned. Errors and omissions excepted, the names of proprietary

products are distinguished by initial capital letters.

The World Health Organization does not warrant that the information

contained in this publication is complete and correct and shall not be liable

for any damages incurred as a result of its use.

The named authors alone are responsible for the views expressed in this

publication.

Printed in China

CONTENTS

Forewordto second edition. . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Forewordto first edition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Preface to second edition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Glossary and abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

1 Background information on tuberculosis

and human immunodeficiency virus . . . . . . . . . . . . 23

1.1 Tuberculosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

1.1.1 Basic facts about TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

1.1.2 Pathogenesis of TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

1.2 Human immunodeficiency virus. . . . . . . . . . . . . . . . . . . . 27

1.2.1 Introduction:HIV and AIDS . . . . . . . . . . . . . . . . . . . . . . . 27

1.2.2 HIV/AIDS epidemiology. . . . . . . . . . . . . . . . . . . . . . . . . . 28

1.2.3 HIV transmission. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

1.2.4 Prevention of HIV transmission in health units . . . . . . . . 29

1.2.5 Immunopathogenesis of HIV infection . . . . . . . . . . . . . . 30

1.2.6 Natural history of HIV infection . . . . . . . . . . . . . . . . . . . 31

1.2.7 Clinical staging. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

1.2.8 Epidemiological surveillance of AIDS . . . . . . . . . . . . . . . . 35

1.3 HIV-related TB. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36

1.3.1 Epidemiology of coinfection of HIV and M tuberculosis. . . 36

1.3.2 HIV infection and risk of TB. . . . . . . . . . . . . . . . . . . . . . . 37

1.3.3 TB in the course of HIV progression. . . . . . . . . . . . . . . . 37

1.3.4 Consequence of HIV/M tuberculosis coinfection. . . . . . . . 37

1.3.5 Impact of HIV on TB control. . . . . . . . . . . . . . . . . . . . . . 37

1.3.6 Patterns of HIV-related TB. . . . . . . . . . . . . . . . . . . . . . . . 38

1.3.7 Impact of TB on HIV . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

2 An expanded framework for effective

tuberculosis control. . . . . . . . . . . . . . . . . . . . . . . . . . . 41

2.1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41

2.2 Components of expanded TB control framework. . . . . . 41

2.2.1 Goals of TB control. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42

2.2.2 Targets for TB control (cure and case detection). . . . . . . 42

2.2.3 TB control policy package (the DOTS strategy). . . . . . . 43

TB/HIV:A CLINICAL MANUAL

2.2.4 Key operations for DOTS implementation. . . . . . . . . . . . 44

2.2.5 Indicators to measure NTP progress in TB control. . . . . 45

2.3 Directly observed treatment . . . . . . . . . . . . . . . . . . . . . 45

2.4 TB/HIV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

2.5 DOTS-Plus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47

3 Diagnosis of pulmonary tuberculosis in adults. . . . 49

3.1 Diagnostic approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49

3.2 Clinical features. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50

3.3 Diagnostic sputum smear microscopy . . . . . . . . . . . . . . . 51

3.4 Differential diagnosis of pulmonary TB. . . . . . . . . . . . . . . 54

3.5 Chest X-ray in diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . 55

3.6 Radiographic abnormalities seen in pulmonary TB. . . . . . 55

3.7 Differential diagnosis of chest X-ray findings . . . . . . . . . . 56

3.8 The place of mycobacterial culture in the diagnosis of TB57

3.9 Sepsis and concomitant TB . . . . . . . . . . . . . . . . . . . . . . . 57

3.10 Distinguishing other HIV-related pulmonary diseases

from pulmonary TB. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58

4 Diagnosis of pulmonary tuberculosis in children. . 61

4.1 Epidemiology of childhood TB. . . . . . . . . . . . . . . . . . . . . 61

4.2 How does TB in children differ from TB in adults? . . . . . 62

4.3 Approach to diagnosis of TB. . . . . . . . . . . . . . . . . . . . . . 63

4.4 Score system for diagnosis of TB in children. . . . . . . . . . 66

4.5 Tuberculin skin test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67

4.6 The decision to start TB treatment in children . . . . . . . . 68

4.7 Impact of HIV on the diagnosis of TB in children. . . . . . . 69

4.8 Differential diagnosis of pulmonary TB in

HIV-infected children. . . . . . . . . . . . . . . . . . . . . . . . . . . . 70

4.9 Management of child contacts of infectious adults. . . . . . 71

5 Diagnosis of extrapulmonary tuberculosis in

adults and children . . . . . . . . . . . . . . . . . . . . . . . . . . . 75

5.1 Diagnostic approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75

5.2 Tuberculous lymphadenopathy. . . . . . . . . . . . . . . . . . . . . 75

5.3 Miliary (disseminated) TB. . . . . . . . . . . . . . . . . . . . . . . . . 78

5.4 Tuberculous serous effusions (pleural,pericardial,ascites) 79

5.5 Tuberculous meningitis. . . . . . . . . . . . . . . . . . . . . . . . . . . 84

5.6 Other forms of extrapulmonary TB. . . . . . . . . . . . . . . . . 87

5.7 Further information on spinal,gastrointestinal

and hepatic TB. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88

CONTENTS

6 Diagnosis of HIV infection in adults

with tuberculosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91

6.1 Clinical recognition of HIV infection in TB patients. . . . . 91

6.2 HIV testing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92

6.2.1 HIV antibody tests. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92

6.2.2 Tests to detect the virus itself. . . . . . . . . . . . . . . . . . . . . 93

6.2.3 Objectives of HIV antibody testing in TB patients. . . . . . 94

6.2.4 Strategy for HIV antibody testing in TB patients . . . . . . . 94

6.2.5 Diagnosis of HIV infection in individual TB patients. . . . . 95

6.3 HIV counselling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95

7 Diagnosis of HIV infection in children with

tuberculosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99

7.1 Clinical recognition of HIV infection in children with TB. 99

7.2 HIV testing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100

7.3 Counselling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101

8 Standardized tuberculosis case definitions

and treatment categories. . . . . . . . . . . . . . . . . . . . . 105

8.1 Standardized case definitions. . . . . . . . . . . . . . . . . . . . . 105

8.1.1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105

8.1.2 Questions and answers about case definitions. . . . . . . . 105

8.1.3 Case definitions by site and result of sputum smear . . . 106

8.1.4 Category of TB patient for registration on diagnosis. . . 107

8.2 Standardized dignostic categories. . . . . . . . . . . . . . . . . . 108

9 Management of patients with tuberculosis. . . . . . 111

9.1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111

9.2 Modes of action of anti-TB drugs. . . . . . . . . . . . . . . . . . 112

9.3 TB treatment regimens . . . . . . . . . . . . . . . . . . . . . . . . . 113

9.3.1 New cases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114

9.3.2 Re-treatment cases . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114

9.3.3 Standard code for TB treatment regimens. . . . . . . . . . . 114

9.3.4 Recommended treatment regimens. . . . . . . . . . . . . . . . 115

9.3.5 Use of streptomycin in areas of high HIV prevalence. . . 117

9.3.6 Use of TB drugs in children. . . . . . . . . . . . . . . . . . . . . . 117

TB/HIV:A CLINICAL MANUAL

9.4 TB treatment regimens:questions and answers . . . . . . . 118

9.5 Use of anti-TB drugs in special situations . . . . . . . . . . . 120

9.6 The role of adjuvant steroid treatment:questions

and answers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121

9.7 Monitoring of TB patients during treatment. . . . . . . . . . 122

9.7.1 Monitoring of patients with sputum

smear-positive PTB

. 122

9.7.2 Recording treatment outcome . . . . . . . . . . . . . . . . . . . 123

9.7.3 Cohort analysis:questions and answers . . . . . . . . . . . . . 124

9.8 Response of HIV-positive TB patients to

anti-TB treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124

10 Side-effects of anti-tuberculosis drugs . . . . . . . . . . 129

10.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129

10.2 Prevention of side-effects . . . . . . . . . . . . . . . . . . . . . . . 129

10.3 Where to manage drug reactions . . . . . . . . . . . . . . . . . 129

10.4 When to stop anti-TB drugs . . . . . . . . . . . . . . . . . . . . . 129

10.5 Side-effects of anti-TB drugs . . . . . . . . . . . . . . . . . . . . . 130

10.5.1 Side-effects of anti-TB drugs in HIV-positive TB patients131

10.6 Symptom-based approach to management of

drug side-effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132

10.7 Management of skin itching and rash . . . . . . . . . . . . . . 132

10.7.1 Treatment regimen includes thioacetazone . . . . . . . . . . 133

10.7.2 Treatment regimen does not include thioacetazone. . . . 133

10.8 Desensitization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134

10.9 Management of hepatitis . . . . . . . . . . . . . . . . . . . . . . . . 135

11 Antiretroviral therapy for the treatment of

HIV infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137

11.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137

11.2 Antiretroviral drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138

11.3 Principles of ART . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138

CONTENTS

11.4 Principles of a public health approach to ART . . . . . . . . 139

11.5 Initiation of ART. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139

11.5.1 Adults and adolescents with documented HIV infection 140

11.5.2 Infants and children. . . . . . . . . . . . . . . . . . . . . . . . . . . . 140

11.6 Recommended doses of ARV drugs . . . . . . . . . . . . . . . . 141

11.6.1 Adults and adolescents . . . . . . . . . . . . . . . . . . . . . . . . . 141

11.6.2 Children. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142

11.7 Choice of ART regimen . . . . . . . . . . . . . . . . . . . . . . . . . 149

11.7.1 Adults. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149

11.7.2 Children. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150

11.8 Monitoring the efficacy of ART. . . . . . . . . . . . . . . . . . . . 151

11.9 Adverse effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151

11.10 Interactions between ARV drugs and drugs used to

prevent or treat opportunistic infections. . . . . . . . . . . . 153

11.11 Antiretroviral drugs and TB treatment . . . . . . . . . . . . . 153

11.11.1 Drug interactions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153

11.11.2 Treating TB and HIV together . . . . . . . . . . . . . . . . . . . . 153

11.11.3 Immune reconstitution syndrome . . . . . . . . . . . . . . . . . 154

11.11.4 Options for ART in patients with TB . . . . . . . . . . . . . . . 154

12 Treatment and prevention of other HIV-related

diseases in TB/HIV patients. . . . . . . . . . . . . . . . . . . 157

12.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157

12.2 Clinical spectrum of HIV-related disease . . . . . . . . . . . . 157

12.3 Sexually transmitted infections . . . . . . . . . . . . . . . . . . . . 158

12.3.1 Syndromic management. . . . . . . . . . . . . . . . . . . . . . . . . 158

12.3.2 Treatment regimens for common STIs. . . . . . . . . . . . . . 159

12.4 Skin and mouth problems . . . . . . . . . . . . . . . . . . . . . . . 161

12.5 Respiratory problems . . . . . . . . . . . . . . . . . . . . . . . . . . 165

12.5.1 Respiratory problems in adults . . . . . . . . . . . . . . . . . . . 165

12.5.2 Respiratory problems in children. . . . . . . . . . . . . . . . . . 167

12.6 Gastrointestinal problems . . . . . . . . . . . . . . . . . . . . . . . 167

12.6.1 Dysphagia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167

12.6.2 Diarrhoea in adults . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168

12.6.3 Diarrhoea in children. . . . . . . . . . . . . . . . . . . . . . . . . . . 170

TB/HIV:A CLINICAL MANUAL

12.7 Neurological problems in adults. . . . . . . . . . . . . . . . . . . 171

12.7.1 Acute confusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171

12.7.2 Chronic behaviour change. . . . . . . . . . . . . . . . . . . . . . . 172

12.7.3 Persistent headache. . . . . . . . . . . . . . . . . . . . . . . . . . . . 172

12.7.4 Difficulty in walking. . . . . . . . . . . . . . . . . . . . . . . . . . . . 174

12.7.5 Poor vision. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175

12.7.6 Burning sensation in the feet. . . . . . . . . . . . . . . . . . . . . 175

12.8 Neurological problems common in children . . . . . . . . . 175

12.9 Fever . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176

12.9.1 Approach to management. . . . . . . . . . . . . . . . . . . . . . . 176

12.9.2 Disseminated infection. . . . . . . . . . . . . . . . . . . . . . . . . . 176

12.10 Other HIV-related problems . . . . . . . . . . . . . . . . . . . . . 177

12.11 Prevention of HIV-related opportunistic infections. . . . . 179

12.11.1 General measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179

12.11.2 Immunizations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179

12.11.3 Primary chemoprophylaxis in adults. . . . . . . . . . . . . . . . 180

12.11.4 Primary chemoprophylaxis in children. . . . . . . . . . . . . . 181

12.11.5 Secondary chemoprophylaxis in adults. . . . . . . . . . . . . . 181

13 Coordinated care in different settings. . . . . . . . . . 185

13.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185

13.2 The expanded scope of a new approach to decrease

the burden of TB/HIV . . . . . . . . . . . . . . . . . . . . . . . . . . 185

13.3 Referral to local HIV/AIDS care services . . . . . . . . . . . . 186

13.4 Benefits of support from local HIV/AIDS care services . 186

13.5 A framework for HIV/AIDS care that incorporates

interventions to address TB. . . . . . . . . . . . . . . . . . . . . . 187

13.5.1 Home and community care. . . . . . . . . . . . . . . . . . . . . . 187

13.5.2 Primary care. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 188

13.5.3 Secondary care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189

13.5.4 Tertiary care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189

13.6 The private sector . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191

13.6.1 Private medical practitioners. . . . . . . . . . . . . . . . . . . . . 191

13.6.2 Traditional practitioners. . . . . . . . . . . . . . . . . . . . . . . . . 191

13.7 Operational research aimed at improving integrated

TB and HIV/AIDS prevention and care . . . . . . . . . . . . . 192

CONTENTS

13.7.1 Promoting voluntary counselling and testing (VCT)

for HIV as an entry point to better TB care . . . . . . . . . 192

13.7.2 The Practical Approach to Lung Health (PAL). . . . . . . . 192

14 Prevention of tuberculosis in HIV-infected

individuals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195

14.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195

14.2 Protection of HIV-positive persons against exposure

to TB. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195

14.2.1 Environmental control . . . . . . . . . . . . . . . . . . . . . . . . . . 195

14.2.2 Face-masks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196

14.2.3 Patient education . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196

14.2.4 Pulmonary TB suspects . . . . . . . . . . . . . . . . . . . . . . . . . 196

14.2.5 Patients with sputum smear-positive pulmonary TB. . . . 197

14.2.6 Patients with multidrug-resistant TB (MDR-TB). . . . . . . 197

14.3 Role of BCG in preventing TB in HIV-infected individuals. 197

14.3.1 Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197

14.3.2 BCG protection against TB in HIV-infected children. . . . 198

14.3.3 BCG safety in HIV-infected children. . . . . . . . . . . . . . . . 198

14.3.4 WHO recommended policy on BCG and HIV. . . . . . . . 198

14.4 The role of the Expanded Programme on

Immunization (EPI). . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199

14.5 Preventive treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . 199

14.5.1 Target groups for preventive treatment. . . . . . . . . . . . . 200

14.5.2 Role of isoniazid preventive treatment in HIV-positive

individuals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201

14.5.3 WHO/UNAIDS recommendations on preventive

therapy against TB in HIV-positive persons. . . . . . . . . . . 201

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205

TB/HIV:A CLINICAL MANUAL

FOREWORD TO SECOND EDITION

WHO is committed to achieving major progress in global public health.

Goals for tuberculosis include a worldwide cure rate of 85% and a case

detection rate of 70% by 2005.Goals for human immunodeciciency virus

include treating 3 million people with HIV infection in developing

countries with antiretroviral drugs by 2005. The Millennium

Development Goals include targets for improved child health and

survival and for improved control of priority communicable diseases

(including TB and HIV) by 2015.Progress in improving TB/HIV clinical

care will contribute to achieving these goals. Clinicians have a vital

contribution to make,not only to the clinical care of patients, but also

to public health.

The public health foundation of TB control is good clinical care,through

identification and effective treatment of TB patients.A cornerstone of

public health activities for HIV prevention is to increase the proportion

of HIV-infected people who choose to know their HIV status.One of

the benefits of testing positive for HIV should be access to good clinical

care.This is crucial in promoting community confidence in HIV/AIDS

care,and therefore encouraging the uptake of HIV testing. This manual

provides practical guidance on the clinical care of patients of all ages

with HIV infection, including the treatment of HIV infection with

antiretroviral drugs and of HIV-related diseases,including TB.

TB and HIV are overlapping epidemics.For clinicians,the patient is at the

centre of public health activities to tackle TB/HIV.For example, clinicians

are usually in a good position to offer TB patients voluntary counselling

and testing for HIV.When patients with TB find out they are HIV-

positive,clinicians are well placed to ensure directly or by referral that

they receive lifelong care.Lifelong care should comprise the following:

treatment of HIV infection; prevention and treatment of HIV-related

diseases; support to decrease risk of HIV transmission;and social and

psychological support.

This manual provides valuable guidance for clinicians caring for patients

with TB/HIV.Their efforts are crucial to the collective achievement of

global public health goals.

Dr JW Lee

Director-General,World Health Organization

Geneva,Switzerland

FOREWORD TO FIRST EDITION

Doctors and other health professionals working in sub-Saharan Africa

will be only too aware of the many patients they encounter with TB.

They will also be all too well aware of the epidemic of HIV infection and

the effect this has had on dramatically increasing the TB burden.They will

know that in many patients development of clinical TB is the first sign of

underlying HIV infection.This excellent book is designed for the busy

clinician.It summarizes the characteristics of both diseases and of their

interactions. It concentrates particularly on the clinical problems of

diagnosis and management, both in adults and children.It summarizes

the other HIV-related diseases which the clinician may encounter in

TB/HIV patients.It provides a most useful review to those new to the

problems and a handy reference for the experienced clinician when

faced with some particular difficulty.It is well set out and easy to use.

The modern treatment of TB in HIV-infected patients is highly successful.

This not only benefits the patient but reduces the spread of TB to

families and the community.Other treatments can help to improve or

control many HIV-related diseases.This book well summarizes the range

of treatments available.It also provides useful guides on counselling and

on interagency cooperation, both essential components of TB/HIV

management.

The enormous problems of HIV and TB in sub-Saharan Africa are now

also increasing in Asia and South America,where the book should prove

equally useful.

I congratulate WHO on deciding to produce this valuable book and the

authors on the imaginative and practical way they have presented the

problems and their management.

Sir John Crofton

Professor Emeritus of Respiratory Diseases and Tuberculosis

University of Edinburgh,Scotland

PREFACE TO SECOND EDITION

Recognition of the impact of HIV on the clinical management of TB

prompted WHO to publish the first edition of this manual in 1996.In

response to popular demand, the manual was adapted for different

regions and translated into many languages.The total number of copies

distributed has run to well over 100000.Recognition of the strengths

and weaknesses of the first edition and developments in the TB/HIV field

have now prompted a second edition.

There is increasing attention to the need to ensure high quality care of

children with TB within National TB Programmes.Therefore this second

edition provides improved guidance on dealing with TB in children.

HIV fuels the TB epidemic in populations where there is overlap

between those infected with HIV and those infected with Mycobacterium

tuberculosis.Intense transmission of M. tuberculosis increases the pool of

HIV-infected people exposed to, and subsequently infected with, M.

tuberculosis. In populations with high HIV prevalence, many people

infected with HIV develop TB,and many TB patients are coinfected with

HIV.Unfor tunately, at present a very small proportion of all people

infected with HIV have access to antiretroviral treatment.However,this

proportion is sure to increase and clinicians involved in managing TB

patients need to know about antiretroviral treatment.For these reasons

this edition includes a new chapter on antiretroviral drugs in the

treatment of HIV infection.

The new expanded framework for TB control and the strategic

framework to control TB/HIV reflect the development of TB control

policies since 1996.Chapter 2 incorporates these new policies.

With the above changes, the manual provides up-to-date guidance on

clinical management of patients with TB and HIV.

This manual is mainly for doctors and other health professionals

working in district hospitals and health centres in high HIV and TB

prevalence countries.It deals mainly with sub-Saharan Africa, since this

is the region most badly affected by HIV and HIV-related TB.However,

we hope it will also be helpful in other parts of the world facing similar

problems.

Facilities vary from hospital to hospital and from health centre to health

centre. In this manual we assume your hospital has a small laboratory

and X-ray service. Even if you do not have these facilities,the manual

should still be useful.Health professionals who care for TB patients now

need to know how to diagnose and treat TB,the principles of diagnosis

and treatment of HIV and other HIV-related diseases.This manual will

help you in this task.

The manual fits into a white coat pocket so you can use it on the ward,

in the clinic and at home.There is not enough room in a pocket manual

for all the possible information you may want to know about TB among

HIV-infected people.So,at the end of each chapter there are suggestions

for further reading. These suggestions include relevant books,

background material,reviews and recent articles in journals.

Since English is not the first language of many of the people using this

manual,the writing style is deliberately simple.You are welcome to send

any comments on the manual to WHO.We will use your comments to

help improve future editions.Many of the references in the manual are

to WHO publications.To order copies of WHO publications,you should

contact Marketing and Dissemination,World Health Organization,1211

Geneva 27,Switzerland.

PREFACE TO SECOND EDITION

TB/HIV:A CLINICAL MANUAL

GLOSSARY AND ABBREVIATIONS

This glossary explains the abbreviations and acronyms and some of the

terms used in this book.

ambulatory able to walk

acquired resistance resistance of Mycobacterium tuberculosis to anti-TB

drugs in a TB patient who has previously received

anti-TB treatment

adherence to treatment

the patient taking the medicines as directed

adjuvant treatment an addition to other treatment

AFB Acid-Fast Bacilli

agranulocytosis absence of polymorph white blood cells

AIDS Acquired ImmunoDeficiency Syndrome

anorexia loss of appetite for food

ARC AIDS-Related Complex

ART AntiRetroviral Therapy

ARV AntiRetroViral (drug)

atypical mycobacterianontuberculous mycobacteria

bactericidal kills bacteria

bacteriostatic stops bacteria from growing

BCG Bacille Calmette-Guerin

bronchiectasis irreversibly dilated bronchi with persistently

infected sputum

bubo swollen,pus-containing lymph node

caseation tissue breakdown by TB bacilli,forming yellow-

white,cheese-like material

chemotherapy treatment with drugs, e.g. anti-TB chemotherapy

means treatment with anti-TB drugs

CAT or CT (scan) Computerized Axial Tomography

CD4 cells subgroup of T-lymphocytes carrying CD4 antigens

CDC Centers for Disease Control and Prevention (USA)

CMV CytoMegaloVirus

CNS Central Nervous System

coinfection infection with different pathogens at the same

time,e.g. Mycobacterium tuberculosis and HIV

contacts people (often family members) close to a TB

patient and at risk of infection

cotrimoxazole trimethoprim/sulfamethoxazole (TMP/SMX)

counselling face-to-face communication in which one person

(counsellor) helps another (patient/client) to

make decisions and act on them

CSF CerebroSpinal Fluid

CXR chest X-ray

dactylitis inflammation of the fingers

default patient stopping treatment before completion

desensitization way of overcoming hypersensitivity to a drug in a

patient by gradual re-exposure to the drug

disseminated spread throughout the body to many different

organs

dormant sleeping or inactive

DOT Directly Observed Treatment (supporter watches

patient to ensure the patient takes the tablets)

dyspnoea shortness of breath

DTO District TB Officer

EDL Essential Drugs List

EIA Enzyme ImmunoAssay

erythema nodosum painful, tender,red nodules over the front of the legs

empirical treatment treatment for a certain condition without exact

diagnostic confirmation by tests

EPI Expanded Programme on Immunization

EPTB extrapulmonary TB;TB outside the lungs

exudate fluid with a high protein content and inflammatory

cells in an area of disease

false-negative a negative test result,when the true result is in

test result fact positive

false-positive a positive test result, when the true result is in

test result fact negative

FBC Full Blood Count

FDC Fixed-Dose Combination

fluorochrome stain stain shines brightly under ultraviolet light

GDF Global Drug Facility

gibbus an acute angle in the spine due to vertebral

collapse from TB

HAART Highly Active AntiRetroviral Therapy

haemoptysis coughing up of blood-stained sputum

HEPA High Efficiency Particulate Air (filter mask)

hilar at the root of the lung

hilum the root of the lung

HIV Human Immunodeficiency Virus

GLOSSARY

TB/HIV:A CLINICAL MANUAL

HIV-negative absence of (antibodies against) HIV

HIV-positive presence of (antibodies against) HIV

HIV-related TB TB occurring in somebody infected with HIV

HIV status presence or absence of HIV

HIV test blood test for antibodies against HIV

home care care for a patient at home rather than in hospital

hypersensitivity immunological reaction to even a small amount of

reaction a drug or other antigen, e.g. tuberculin

IEC Information, Education and Communication

IMCI Integrated Management of Childhood Illness

i.m.injection intramuscular injection

immunosuppressant drugs that suppress normal immunity

drugs

incidence the number of new cases of a disease in a

population in a given time (usually one year)

induration thickening,e.g.of the skin in a tuberculin test

infant child less than 12 months of age

initial resistance resistance of Mycobacterium tuberculosis to anti-TB

drugs in a TB patient who has never before

received anti-TB drugs

IPT Isoniazid Preventive Treatment

IUATLD International Union Against Tuberculosis and Lung

Disease

JVP Jugular Venous Pressure

KS Kaposi Sarcoma

latent something that is there but not obvious (it can

become obvious later)

lesion an area of damage or injury to a tissue or organ

LIP Lymphocytic (lymphoid) Interstitial Pneumonitis

LFTs Liver Function Tests

MAC Mycobacter ium Avium intraCellulare(one of the

atypical mycobacteria)

MCV Mean Corpuscular Volume

MDR-TB Multidrug-resistant TB

meningism presence of clinical features suggestive of

meningitis, e.g. headache, neck-stiffness, positive

Kernig's sign

monotherapy treatment with one drug

mutant bacilli bacilli that suddenly change genetically and

become different from the rest of the population

mutation a sudden genetic change,e.g. a bacillus becoming

drug-resistant

NGO NonGovernmental Organization

NNRTI non-nucleoside reverse transcriptase inhibitor

NsRTI nucleoside reverse transcriptase inhibitor

NtRTI nucleotide reverse transcriptase inhibitor

NSAID Non-Steroidal Anti-Inflammatory Drug

NTP National TB Programme

opportunistic infection an infection that "takes the opportunity" to cause

disease when a person's immune defence is weak

PAL Practical Approach to Lung Health

passive case-finding detection of TB cases by active testing (sputum

smear) of TB suspects

pathogenesis how a disease arises

PCP Pneumocystis Carinii Pneumonia (now known as

Pneumocystis jiroveci)

pericardial effusion accumulation of fluid in the pericardial cavity

phlyctenular painful hypersensitivity reaction of the conjunctiva

conjunctivitis to primary TB infection,with inflammation and

small red spots where the cornea meets the

sclera

PGL Persistent Generalized Lymphadenopathy

PHC Primary Health Care

PI Protease inhibitor

pleural effusion accumulation of fluid in the pleural space

PLWH People Living With HIV

PML Progressive multifocal lenkoencephalopathy

pneumothorax accumulation of air in the pleural space

PPD Purified Protein Derivative (tuberculin)

preventive treatment treatment aimed at preventing disease, e.g.

isoniazid for the prevention of TB in certain

circumstances

PTB Pulmonary TuBerculosis

PTB suspect patient presenting with features that make the

health worker think the patient may have PTB,

most importantly cough of more than 3 weeks'

duration

regimen a drug, or several drugs, given in certain doses for

a stated duration

relapse disease starting again after a patient was declared

cured

GLOSSARY

TB/HIV:A CLINICAL MANUAL

RNA Ribonucleic acid

RTI Reverse transcriptase inhibitor

SCC Shor t-Course Chemotherapy

scrofula tuberculous lymph nodes in the neck

sensitivity test test of TB bacilli for sensitivity or resistance to

anti-TB drugs

seroconversion the first appearance of HIV antobodies in the

blood,usually about 3 months after HIV infection

seroprevalence the proportion of people testing seropositive (e.g.

for HIV) in a population at any one time

slim disease HIV-related chronic diarrhoea and weight loss

spinal block obstruction to normal flow of CSF around the

spinal cord

sputum smear absence of AFBs on sputum microscopy

negative

sputum smear presence of AFBs on sputum microscopy

positive

STI Sexually Transmitted Infection

Stevens-Johnson a characteristic rash with "target lesions" and

syndrome inflammation of the mucous membranes

syndrome a group of symptoms and signs

TB TuBerculosis

TB suspect patient with symptoms suggestive of TB

TB/HIV TB and HIV coinfection

TB/HIV patient HIV-infected TB patient

TEN Toxic Epidermal Necrolysis

thrombocytopenia low platelet count

T-lymphocytes type of lymphocyte providing cellular immunity

TMP-SMX TriMethoPrim-SulfaMethoXazole

tubercles small rounded areas of TB disease

tuberculin protein extracted from TB bacilli (PPD)

tuberculoma rounded area of TB disease, usually 1cm or more

wide

UNICEF United Nations Children's Fund

VCT Voluntary Counselling and Testing (for HIV)

WHO World Health Organization

window period the gap of about 3 months between the time

when a person becomes infected with HIV and

the time when antibodies first appear in the blood

ZN stain Ziehl-Neelsen stain

INTRODUCTION

Untreated HIV infection leads to progressive immunodeficiency and

increased susceptibility to infections,including TB. HIV is driving the TB

epidemic in many countries, especially in sub-Saharan Africa and,

increasingly,in Asia and South America.TB in populations with high HIV

prevalence is a leading cause of morbidity and mortality.TB programmes

and HIV/AIDS programmes therefore share mutual concerns.

Prevention of HIV should be a priority for TB control;TB care and

prevention should be priority concerns of HIV/AIDS programmes.TB

and HIV programmes provide support to general health service

providers.Previously TB programmes and HIV/AIDS programmes have

largely pursued separate courses. However, a new approach to TB

control in populations with high HIV prevalence requires collaboration

between these programmes.

HIV infection increases the demands on TB programmes,which are

struggling to cope with the increased TB case load.The impact of HIV

exposes any weaknesses in TB control programmes.The rise in TB

suspects is putting a strain on diagnostic services. Extrapulmonary and

smear-negative pulmonary TB cases, which are more difficult to

diagnose,account for an increased proportion of total cases. There are

more adverse drug reactions.There is a higher morbidity and mortality,

partly due to other, curable, HIV-related infections.The risk of TB

recurrence is higher.The diagnosis of TB in young children has always

been difficult and is even more so with HIV.

The objectives of a TB control programme are to decrease morbidity,

mortality and transmission of TB,while avoiding the emergence of drug

resistance. Up to now, the efforts to tackle TB among HIV-infected

people have mainly focused on implementing the DOTS strategy for TB

control.At the heart of this strategy is the identification and cure of

infectious TB cases (among patients presenting to general health

services).This targets the final step in the sequence of events by which

HIV fuels TB, namely the transmission of Mycobacterium tuberculosis

infection by infectious TB cases.The expanded scope of the new

approach to TB control in populations with high HIV prevalence

comprises interventions against TB and interventions against HIV (and

therefore indirectly against TB).Implementing this approach depends on

TB and HIV programmes continuing their core activities and,in addition,

collaborating in joint activities.These activities address areas of mutual

interest,e .g.staff training, public education, drug supply,case detection

and management,and surveillance.

TB/HIV:A CLINICAL MANUAL

BACKGROUND INFORMATION ON

TUBERCULOSIS AND HIV

This chapter provides background information on tuberculosis (TB),

human immunodeficiency virus and acquired immunodeficiency

syndrome,and the interaction between them.

1.1 TUBERCULOSIS

1.1.1 Basic facts about TB

Mycobacterium tuberculosis

TB is a bacterial disease caused by Mycobacterium tuberculosis (and

occasionally by Mycobacterium bovisand Mycobacter ium africanum).These

organisms are also known as tubercle bacilli (because they cause lesions

called tubercles) or as acid-fast bacilli (AFB).When sputum containing

tubercle bacilli is stained with certain dyes and examined under the

microscope,the bacilli look red. This is because they are acid-fast (they

have kept the dye even after being washed with acid and alcohol).

Tubercle bacilli can remain dormant in tissues and persist for many years.

Tuberculous infection and tuberculosis

Tuberculous infection occurs when a person carries the tubercle bacilli

inside the body,but the bacteria are in small numbers and are dormant.

These dormant bacteria are kept under control by the body’s defences

and do not cause disease. Many people have tuberculous infection and

are well.Tuberculosis is a state in which one or more organs of the body

become diseased as shown by clinical symptoms and signs. This is

because the tubercle bacilli in the body have started to multiply and

become numerous enough to overcome the body’s defences.

Sources of infection

The most important source of infection is the patient with TB of the

lung,or pulmonary TB (PTB),and who is coughing. This person is usually

sputum smear-positive (see Chapter 3). Coughing produces tiny

infectious droplet nuclei (infectious particles of respiratory secretions

usually less than 5 µm in diameter and containing tubercle bacilli).A

single cough can produce 3000 droplet nuclei.Droplet nuclei can also be

spread into the air by talking, sneezing,spitting and singing, and can

remain suspended in the air for long periods. Direct sunlight kills

tubercle bacilli in 5 minutes,but they can survive in the dark for long

periods.Transmission therefore generally occurs indoors.Droplet nuclei

are so small that they avoid the defences of the bronchi and penetrate

into the terminal alveoli of the lungs,where multiplication and infection

begin. Two factors determine an individual's risk of exposure: the

concentration of droplet nuclei in contaminated air and the length of

time he or she breathes that air.

TB of cattle (bovine TB) occurs in some countries.Milk-borne M. bovis

may infect the tonsils presenting as scrofula (cervical lymphadenitis),or

the intestinal tract,causing abdominal TB.

Routes by which TB is not transmitted

TB is not transmitted through food and water or by sexual intercourse,

blood transfusion,or mosquitoes.

Risk of infection

An individual's risk of infection depends on the extent of exposure to

droplet nuclei and his or her susceptibility to infection.The risk of

infection of a susceptible individual is high with close,prolonged, indoor

exposure to a person with sputum smear-positive PTB.The risk of

transmission of infection from a person with sputum smear-negative PTB

is low,and even lower from someone with extrapulmonary TB (EPTB).

Risk of progression of infection to disease

Infection with M.tuberculosis can occur at any age. Once infected with M.

tuberculosis,a person can stay infected for many years, probably for life.

The vast majority (90%) of people without HIV infection who are

infected with M.tuberculosis do not develop TB. In these,asymptomatic

but infected individuals,the only evidence of infection may be a positive

tuberculin skin test.

Infected persons can develop TB at any time.The disease can affect most

tissues and organs, but especially the lungs.The chance of developing

disease is greatest shortly after infection and steadily lessens as time

goes by. Infected infants and young children are at greater risk of

developing disease than older people because they have an immature

immune system.TB is also more likely to spread from the lungs to other

parts of the body in this age group.Children who develop disease usually

do so within two years following exposure and infection.Most do not

develop disease in childhood but may do so later in life.Various physical

or emotional stresses may trigger progression of infection to disease.

The most important trigger is weakening of immune resistance,

especially by HIV infection.

Natural history of untreated TB

Without treatment,by the end of 5 years 50% of PTB patients will be

BACKGROUND INFORMATION ON TB AND HIV

dead,25% will be healthy (self-cured by a strong immune defence) and

25% will remain ill with chronic infectious TB.

Epidemiology

M. tuberculosis infects a third of the world's population. In 2000 there

were an estimated 8.3 million new cases of TB worldwide.95% of TB

cases and 98% of TB deaths are in developing countries.75% of TB cases

in developing countries are in the economically productive age group

(15–50 years).In 2000, Sub-Saharan Africa had the highest TB incidence

rate (290/100000 per year) and the highest annual rate of increase of

cases (6%).There were 1.8 million deaths from TB in 2000,with 226000

attributable to HIV (12%).TB deaths comprise 25% of all avoidable adult

deaths in developing countries.

A direct consequence of increasing numbers of adults with TB is an

increase in childhood TB.Neonatal BCG immunization has had limited

effect in preventing childhood TB in developing countries.Infants and

young children (less than 5 years) are at particular risk for infection and

disease.Accurate definition of the burden of childhood TB is difficult

because of difficulties with diagnosis, particularly in regions where

childhood HIV infection is common.Chapter 4 deals with these issues

in more detail.

1.1.2 Pathogenesis of TB

Primary infection

Primary infection occurs in people who have not had any previous

exposure to tubercle bacilli.Droplet nuclei, which are inhaled into the

lungs, are so small that they avoid the mucociliary defences of the

bronchi and lodge in the terminal alveoli of the lungs.Infection begins

with multiplication of tubercle bacilli in the lungs.The resulting lesion is

the Ghon focus.Lymphatics drain the bacilli to the hilar lymph nodes.

The Ghon focus and related hilar lymphadenopathy form the primary

complex. Bacilli may spread in the blood from the primary complex

throughout the body.The immune response (delayed hypersensitivity

and cellular immunity) develops about 4–6 weeks after the primary

infection.The size of the infecting dose of bacilli and the strength of the

immune response determine what happens next. In most cases,the

immune response stops the multiplication of bacilli. However, a few

dormant bacilli may persist.A positive tuberculin skin test would be the

only evidence of infection.In a few cases the immune response is not

strong enough to prevent multiplication of bacilli,and disease occurs

within a few months.

TB/HIV:A CLINICAL MANUAL

Post-primary TB

Post-primary TB occurs after a latent period of months or years

following primary infection. It may occur either by reactivation of the

dormant tubercle bacilli acquired from a primary infection or by

reinfection.Reactivation means that dormant bacilli persisting in tissues

for months or years after primary infection start to multiply.This may be

in response to a trigger,such as weakening of the immune system by HIV

infection. Reinfection means a repeat infection in a person who has

previously had a primary infection.

The immune response of the patient results in a pathological lesion that

is characteristically localized,often with extensive tissue destruction and

cavitation.Post-primary TB usually affects the lungs but can involve any

part of the body.The characteristic features of post-primary PTB are the

following: extensive lung destruction with cavitation; positive sputum

BACKGROUND INFORMATION ON TB AND HIV

PRACTICAL POINT

Following primary infection,rapid progression to intra-thoracic

disease is more common in children less than 5 years of age.

Chest X-Ray (CXR) may show intrathoracic

lymphadenopathy

and lung infiltrates.

no clinical disease

positive tuberculin skin test

(usual outcome:90% of cases)

hypersensitivity reactions

e.g. erythema nodosum

phlyctenular conjunctivitis

dactylitis

primary pulmonar y and pleural complications

complex e.g. tuberculous pneumonia

hyperinflation and collapse/consolidation

pleural effusion

disseminated disease

lymphadenopathy (usually cervical)

meningitis

pericarditis

miliary disease

Outcomes of primary infection

smear; upper lobe involvement; usually no intrathoracic

lymphadenopathy.Patients with these lesions are the main transmitters

of infection in the commmunity.

Post-primary TB

1.2 HUMAN IMMUNODEFICIENCY VIRUS

1.2.1 Introduction:HIV and AIDS

Since the first description of AIDS in 1981,researchers have identified

two types of HIV,the cause of AIDS. HIV-1 is the predominant type

worldwide.HIV-2 occurs most commonly in West Africa,and occasional

TB/HIV:A CLINICAL MANUAL

Pulmonary TB

e.g. cavities

upper lobe infiltrates

fibrosis

progressive pneumonia

endobronchial

Extrapulmonary TB

Common Less common

Pleural effusion Empyema

Lymphadenopathy Male genital tract

(usually cervical) (epididymitis, orchitis)

Central nervous system Female genital tract

(meningitis,cerebral tuberculoma) (tubo-ovarian,endometrium)

Pericarditis Kidney

(effusion/constrictive)

Adrenal gland

Gastrointestinal

(ileocaecal,peritoneal) Skin

(lupus vulgaris,tuberculids, miliary)

Spine,other bone and joint

PRACTICAL POINT

Post-primary infection with pulmonary disease usually occurs

in adults and leads to microscopy-positive sputum smears.

infections have occurred in East Africa,Europe,Asia and Latin America.

Both types cause AIDS and the routes of transmission are the same.

However,HIV-2 transmission is slightly less easy and the progression of

HIV-2 infection to AIDS may be slower.

1.2.2 HIV/AIDS epidemiology

By the end of 2002, there were an estimated 42 million adults and

children living with HIV or AIDS.Of these,28.5 million (68%) were living

in sub-Saharan Africa,and 6 million (14%) in South and South-East Asia.

In 2002,an estimated 5 million adults and children became infected with

HIV, and an estimated 3.1 million adults and children died from

HIV/AIDS. 2.4 million (77%) of these deaths occurred in sub-Saharan

Africa. Sub-Saharan Africa is the region with the highest overall HIV

seroprevalence rate in the general adult (15–49 years) population (9% as

of end 2002).

Of 25 countries with an adult HIV seroprevalence rate above 5% in 2001,

24 are in sub-Saharan Africa.The only other country with an adult HIV

seroprevalence greater than 5% is Haiti.In 9 countries (all in Southern

Africa),the adult HIV seroprevalence rate is 15% or above. Sub-Saharan

Africa thus bears the largest burden of the HIV/AIDS epidemic.However,

certain countries in other regions are also badly affected by HIV,with an

adult HIV seroprevalence of 1–5%,e.g. Cambodia, Myanmar and Thailand

(South-East Asia) and Belize,Guatemala,Guyana, Haiti,Honduras, Panama,

and Suriname (the Americas).HIV seroprevalence appears to be stabilizing

in sub-Saharan Africa but is still increasing in some other large populations,

e.g.in the Russian Federation.

1.2.3 HIV transmission

Worldwide the most common route of HIV transmission is through

sexual intercourse. Other sexually transmitted infections (especially

those that cause genital ulcers) increase the risk of HIV transmission.

The main routes of HIV transmission vary between regions.The main

routes of transmission of HIV in sub-Saharan Africa are through sexual

intercourse, blood and from mother to infant. In most low-income

countries roughly equal numbers of men and women are HIV-infected.

Bloodborne HIV transmission occurs through contaminated blood

transfusion,injections with contaminated needles and syringes, and the

use of non-sterile skin-piercing instruments.The commonest route of

HIV transmission in the fast-growing HIV epidemics in the Russian

Federation and Ukraine is through injecting drug use.

BACKGROUND INFORMATION ON TB AND HIV

TB/HIV:A CLINICAL MANUAL

About one-third of children born to HIV-infected mothers are also HIV-

infected,with infection occurring mainly around the time of birth.There

is a smaller risk of HIV transmission through breastfeeding.However,in

many low-income countries breastfeeding is still safer than bottle feeding.

There is no evidence that HIV transmission occurs through everyday

contact,hugging or kissing, food or drink, or the bites of mosquitoes or

other insects.

1.2.4 Prevention of HIV transmission in health units

Transmission to patients

Patients may potentially be at risk of HIV infection from HIV-positive

staff and HIV-positive patients. Known HIV-positive staff should not

perform surgery or invasive diagnostic or therapeutic procedures on

patients.Cross-infection between patients can occur from contaminated

medical,surgical or dental equipment. It is vital to follow recommended

sterilization procedures.When and where possible, reducing injections

helps to decrease the risk of cross-infection.

Transmission to staff

Most HIV-positive health workers acquire HIV infection outside the

workplace, by sexual transmission from an HIV-positive partner or

spouse.The risk of HIV transmission from patients to staff is small if staff

observe standard infection control procedures.The risk is less than that

of hepatitis B transmission.Less than 0.5% of health workers exposed by

a needle-stick injury to the blood of an HIV-positive patient have

acquired HIV infection. Contaminated “sharps” pose a risk of HIV

transmission to health staff.Therefore handle all “sharps” carefully and

follow local guidelines for their disposal.If you have a needle-stick injury,

squeeze the wound to encourage blood flow and wash well with soap

and water.In areas of high HIV prevalence, assume that all blood and

body fluids are potentially infectious.The table on page 30 indicates

measures to prevent transmission of HIV to health workers.Where

available, start postexposure prophylaxis with antiretroviral drugs as

soon as possible (within 24 hours) after a needle-stick injury.

1.2.5 Immunopathogenesis of HIV infection

How HIV infects cells

HIV infects cells that have the CD4 antigen molecules on their surface.

These cells are principally the helper subset of T-lymphocytes,which are

central to cell-mediated immunity.They are called CD4+ T-lymphocytes.In

recent years it has also been discovered that HIV needs other molecules,

called chemokines,on the cell surface to gain entry into the cell. Patients

who do not have some of these specific chemokines (for example,CCR5)

are more resistant to HIV infection.Others, who have molecular changes

in these chemokine receptors,progress more slowly to AIDS.

How HIV destroys the immune system

The critical abnormality resulting from HIV infection is a progressive

decline in the number of CD4+ T-lymphocytes.These cells are the most

BACKGROUND INFORMATION ON TB AND HIV

Exposure to risk Precautions for prevention

of transmission of HIV

venepuncture wear gloves

use a closed vacuum system if available

discard needle and syringe into “sharps” box

discard gloves and swabs into leakproof

plastic bag for incineration

label blood bottle and request form

"inoculation risk"

invasive procedure, wear gloves and apron

surgery,delivery protect your eyes (glasses or protective goggles)

of a baby discard sharps into “sharps” box

spilled blood or clear up as soon as possible using available

other body fluids disinfectant (e.g.glutaraldehyde, phenol,

sodium hypochlorite)

resuscitation avoid mouth-to-mouth resuscitation

(use bag and mask)

laundry disposal wear gloves and apron

dispose into leakproof plastic bags

wash laundry at high temperatures or with

appropriate chemical disinfectant

important cells in the cell-mediated immune response. In addition the

surviving CD4+ T-lymphocytes do not perform their functions as well as

they did before infection. Progressive HIV infection therefore causes

progressive decline in immunity.

1.2.6 Natural history of HIV infection

Acute HIV infection

Acute HIV infection is also called “primary HIV infection” or “acute

seroconversion syndrome”. Between 40% and 90% of new HIV

infections are associated with symptomatic illness. The time from

exposure to onset of symptoms is usually 2–4 weeks. Some people

present with a glandular-fever -like illness (fever, rash,ar thralgia and

lymphadenopathy). Occasionally acute neurological syndromes may

occur, which are often self-limiting.These include aseptic meningitis,

peripheral neuropathy,encephalitis and myelitis. A severe illness may

predict a worse long-term outcome. Most symptomatic patients seek

medical help. However, the diagnosis is infrequently made,for several

possible reasons. First, the clinician may not consider HIV infection.

Secondly,the nonspecific clinical features may be mistaken for another

cause, e.g. malaria.Thirdly, standard serological tests at this stage are

usually negative. Serological tests first become positive about 4–12

weeks after infection,with over 95% of patients “seroconverting” within

6 months of HIV transmission.The diagnosis of acute HIV infection is

best established by demonstration of HIV RNA in plasma.

Asymptomatic HIV infection

In adults,there is a long, variable,latent period from HIV infection to the

onset of HIV-related disease and AIDS.A person infected with HIV may

be asymptomatic for 10 years or more.The vast majority of HIV-infected

children are infected in the perinatal period.The period of asymptomatic

infection is shorter in children than in adults.A few infants become ill in

the first few weeks of life.Most children start to become ill before 2

years of age.A few children remain well for several years.

Persistent generalized lymphadenopathy (PGL)

PGL is defined as enlarged lymph nodes involving at least two sites other

than inguinal nodes.At this time, the lymph tissue serves as the major

reservoir for HIV.PGL occurs in about one-third of otherwise healthy

HIV-infected people. The enlarged lymph nodes are persistent,

generalized, symmetrical, and non-tender. PGL has no particular

prognostic significance.

TB/HIV:A CLINICAL MANUAL

Progression from HIV infection to HIV-related disease and AIDS

Almost all (if not all) HIV-infected people,if untreated, will ultimately

develop HIV-related disease and AIDS.Some HIV-infected individuals

progress more quickly than others to HIV-related disease and AIDS.The

rate of progression depends on virus and host characteristics.Virus

characteristics include type and subtype: HIV-1 and certain HIV-1

subtypes may cause faster progression.Host characteristics that may

cause faster progression include:age less than 5 years; age more than 40

years;concurrent infections; and genetic factors.

Advancing immunosuppression

As HIV infection progresses and immunity declines, patients become

more susceptible to infections.These include TB,pneumonia, recurrent

fungal infections of the skin and oropharynx, and herpes zoster.These

infections can occur at any stage of progression of HIV infection and

immunosuppression. Some patients may develop constitutional

symptoms (unexplained fever and weight loss), previously known as

"AIDS-related complex" (ARC). Some patients develop chronic

diarrhoea with weight loss,often known as "slim disease".

Certain specific HIV-related diseases occur predominantly with severe

immunosuppression.These include certain opportunistic infections (e.g.

cryptococcal meningitis) and certain tumours (e.g. Kaposi sarcoma).At

this late stage,unless patients receive specific therapy for HIV infection,

they usually die in less than 2 years.This late stage is sometimes known

as "full-blown AIDS".

1.2.7 Clinical staging

WHO clinical staging system for HIV infection and HIV-related

disease.

WHO has developed a clinical staging system (originally for prognosis),

based on clinical criteria.The definition of symptoms, signs and diseases

is according to clinical judgement. Clinical condition or performance

score,whichever is the higher,determines whether a patient is at clinical

stage 1,2, 3 or 4 (see table on page 33). Clinical stage is important as a

criterion for starting antiretroviral (ARV) therapy.

BACKGROUND INFORMATION ON TB AND HIV

PRACTICAL POINT

TB can occur at any point in the course of progression of HIV

infection.

TB/HIV:A CLINICAL MANUAL

Adults

WHO clinical staging system for HIV infection and related

disease in adults (13 years or older)

Stage 1:

Asymptomatic

Persistent generalized lymphadenopathy

Performance scale 1:asymptomatic, normal activity

Stage 2:

Weight loss < 10% of body weight

Minor mucocutaneous manifestations

(e.g.oral ulcerations, fungal nail infections)

Herpes zoster within the last 5 years

Recurrent upper respiratory tract infections

(e.g.bacterial sinusitis)

and/or Performance scale 2:symptomatic, normal activity

Stage 3:

Weight loss > 10% of body weight

Unexplained chronic diarrhoea for more than 1 month

Unexplained prolonged fever for more than 1 month

Oral candidiasis (thrush)

Oral hairy leukoplakia

Pulmonary TB

Severe bacterial infections (pneumonia,pyomyositis)

and/or Performance scale 3:bedridden < 50% of the day

during the last month

Stage 4:

HIV wasting syndrome,as defined by CDC

Pneumocystis carinii pneumonia

Toxoplasmosis of the brain

Cryptosporidiosis with diarrhoea,for more than 1 month

Cryptococcosis,extrapulmonary

Cytomegalovirus (CMV) disease of an organ other than

liver,spleen, lymph nodes

Herpesvirus infection,mucocutaneous for more than 1

month,or visceral any duration

Progressive multifocal leukoencephalopathy (PML)

Any disseminated endemic fungal infection

(e.g.histoplasmosis)

Candidiasis of the oesophagus,trachea, bronchi or lungs

Atypical mycobacteriosis,disseminated

Non-typhoid salmonella septicaemia

Extrapulmonary TB

Lymphoma

Kaposi sarcoma

HIV encephalopathy,defined by CDC

and/or Performance scale 4:bedridden > 50% of the day during the last

month

(Note:both definitive and presumptive diagnoses are acceptable)

Children

WHO clinical staging system for HIV infection and related

disease in children

Stage 1:

Asymptomatic

Persistent generalised lymphadenopathy

Stage 2:

Unexplained chronic diarrhoea

Severe persistent or recurrent candidiasis outside the

neonatal period

Weight loss or failure to thrive

Persistent fever

Recurrent severe bacterial infections

Stage 3:

AIDS-defining opportunistic infections

Severe failure to thrive

Progressive encephalopathy

Malignancy

Recurrent septicaemia or meningitis

BACKGROUND INFORMATION ON TB AND HIV

HIV wasting syndrome = weight loss > 10% of body weight, plus either unexplained

diarrhoea for more than one month or chronic weakness and unexplained fever for more

than one month.

HIV encephalopathy = clinical findings of disabling mental or motor dysfunction,interfering

with activities of daily living, progressing over weeks and months,in the absence of a

concurrent illness or condition other than HIV infection which could explain the findings.

TB/HIV:A CLINICAL MANUAL

1.2.8 Epidemiological surveillance of AIDS

AIDS is a term with an official definition used for epidemiological

surveillance.This means that systematic reporting of AIDS cases is useful

in helping to monitor the HIV pandemic and to plan public health

responses.The term AIDS is not useful in the clinical care of individual

patients. In managing patients with HIV-related disease,the aim is to

identify and treat whichever HIV-related diseases are present.WHO has

recommended case definitions for AIDS surveillance in adults and

children where HIV testing facilities are not available.

WHO case definitions for AIDS surveillance in adults and children

where HIV testing facilities are not available

Adults

The case definition for AIDS is fulfilled if at least 2 major signs and at

least 1 minor sign are present.

Major signs

weight loss > 10% of body weight

chronic diarrhoea for more than 1 month

prolonged fever for more than 1 month

Minor signs

persistent cough for more than 1 month

generalized pruritic dermatitis

history of herpes zoster

oropharyngeal candidiasis

chronic progressive or disseminated herpes simplex infection

generalized lymphadenopathy

The presence of either generalized Kaposi sarcoma or cryptococcal

meningitis is sufficient for the case definition of AIDS.

The advantages of this case definition are that it is simple to use and

inexpensive. The disadvantages are its relatively low sensitivity and

specificity.For example,HIV-negative TB cases could be counted as AIDS

cases because of their similarity in clinical presentation.

PRACTICAL POINT

The term AIDS is used for epidemiological surveillance,not

for clinical care.

For patients with TB,persistent cough for more than 1 month should not be considered as a minor sign.

Children

The case definition for AIDS is fulfilled if at least 2 major signs and 2

minor signs are present (if there is no other known cause of

immunosuppression).

Major signs

weight loss or abnormally slow growth

chronic diarrhoea for more than 1 month

prolonged fever for more than 1 month

Minor signs

generalized lymph node enlargement

oropharyngeal candidiasis

recurrent common infections,e.g. ear infection,phar yngitis

persistent cough

generalized rash

Confirmed HIV infection in the mother counts as a minor criterion.

The definition for children is not very specific, particularly in poor

regions where childhood malnutrition and TB are common.Further,

many children present with acute HIV-related illness such as PCP

without any clinical evidence of AIDS.

1.3 HIV-RELATED TB

1.3.1 Epidemiology of coinfection of HIV and M.tuberculosis

By the end of 2000,about 11.5 million HIV-infected people worldwide

were coinfected with M.tuberculosis. 70% of coinfected people were in

sub-Saharan Africa,20% in South-East Asia and 4% in Latin America and

the Caribbean.

Numbers of coinfected adults (15–49 years) in WHO regions by

end 2000

BACKGROUND INFORMATION ON TB AND HIV

WHO Region Number of people coinfected % of global

with TB & HIV (thousands) total

Africa 7979 70

Americas 468 4

Eastern Mediterranean

163 1

Europe 133 1

South-East Asia 2269 20

Western Pacific 427 4

Total 11440 100

TB/HIV:A CLINICAL MANUAL

1.3.2 HIV infection and risk of TB

HIV probably increases susceptibility to infection with M. tuberculosis.

HIV increases the risk of progression of M.tuberculosis infection to TB

disease. This risk increases with increasing immunosuppression. HIV

increases not only the risk but also the rate of progression of recent or

latent M. tuberculosis infection to disease. The table below shows the

effect of HIV infection on lifetime risk of an M. tuberculosis-infected

individual developing TB.

HIV

STATUS LIFETIME RISK OF DEVELOPING TB

negative 5–10%

positive 50%

1.3.3 TB in the course of HIV progression

TB can occur at any point in the course of progression of HIV infection.

The risk of developing TB rises sharply with worsening immune status.

1.3.4 Consequence of HIV/M.tuberculosis coinfection

Compared with an individual who is not infected with HIV,a person

infected with HIV has a 10 times increased risk of developing TB.TB

notifications have increased in populations where both HIV infection and

M.tuberculosis infection are common. For example,some parts of sub-

Saharan Africa have seen a 3–5 fold increase in the number of TB case

notifications over the past decade. HIV seroprevalence in these TB

patients is up to 75%.In sub-Saharan Africa, one-third or more of HIV-

infected people may develop TB.

1.3.5 Impact of HIV on TB control

The principles of TB control are the same even when there are many

HIV/TB patients. However,in populations where HIV/TB is common,

health services struggle to cope with the large and rising numbers of TB

patients.

PRACTICAL POINT

HIV is the most powerful factor known to increase the risk

of TB.

The consequences include the following:

overdiagnosis of sputum smear-negative PTB (due to difficulties in

diagnosis);

underdiagnosis of sputum smear-positive PTB (due to excess

laboratory workload);

inadequate supervision of anti-TB chemotherapy;

low cure rates;

high morbidity during treatment;

high mortality rates during treatment;

high default rates because of adverse drug reactions;

high rates of TB recurrence;

increased transmission of drug-resistant strains among HIV-infected

patients in congregate settings.

1.3.6 Patterns of HIV-related TB

As HIV infection progresses, CD4+ T-lymphocytes decline in number

and function.These cells play an important role in the body’s defence

against tubercle bacilli.Thus, the immune system becomes less able to

prevent the growth and local spread of M.tuberculosis. Disseminated and

extrapulmonary disease is more common.

Pulmonary TB

Even in HIV-infected patients,PTB is still the commonest form of TB.The

presentation depends on the degree of immunosuppression.The table

below shows how the clinical picture, sputum smear result and CXR

appearance often differ in early and late HIV infection.

How PTB differs in early and late HIV infection

Extrapulmonary TB

The commonest forms extrapulmonary TB are: pleural effusion,

lymphadenopathy, pericardial disease, miliary disease, meningitis,

disseminated TB (with mycobacteraemia).

BACKGROUND INFORMATION ON TB AND HIV

Features of PTB Stage of HIV infection

Early Late

Clinical picture Often resembles Often resembles

post-primary PTB primar y PTB

Sputum smear result Often positive Often negative

CXR appearance Often cavities Often infiltrates

with no cavities

TB/HIV:A CLINICAL MANUAL

HIV-related TB in children

As in adults, the natural history of TB in a child infected with HIV

depends on the stage of HIV disease. Early in HIV infection, when

immunity is good,the signs of TB are similar to those in a child without

HIV infection. As HIV infection progresses and immunity declines,

dissemination of TB becomes more common.Tuberculous meningitis,

miliary TB,and widespread tuberculous lymphadenopathy occur.

1.3.7 Impact of TB on HIV

In an individual infected with HIV,the presence of other infections,

including TB,may allow HIV to multiply more quickly.This may result in

more rapid progression of HIV disease.

SUGGESTIONS FOR FURTHER READING

TUBERCULOSIS

Crofton J, Horne N, Miller F.Clinical tuberculosis. Second edition. London,

MacMillan Press Limited,1999.

Schlossberg D, ed: Tuberculosis and nontuberculous mycobacterial infections.

Fourth edition. Philadelphia,WB Saunders, 1998.

International Union Against Tuberculosis and Lung Disease. Tuberculosis guide

for low income countries. Fifth edition.Paris, 2000.

Reider HL.Epidemiologic basis of tuberculosis control. Paris, International Union

Against Tuberculosis and Lung Disease,1999.

World Health Organization. Tuberculosis handbook. Geneva, 1998

(WHO/TB/98.253).

World Health Organization. Global tuberculosis control: surveillance, planning,

financing.WHO report 2003. Geneva, 2003 (WHO/CDS/TB/2003.316).

HIV/AIDS

Fauci AS.The AIDS epidemic.Considerations for the 21st centur y.

New England Journal of Medicine,1999, 341: 1046–1050.

Royce RA,Sena A, Cates Jr, W Cohen, MS.Sexual transmission of HIV.

New England Journal of Medicine, 1997,336: 1072–1078.

World AIDS series.Lancet, 2000, 355:WA1–WA40.

Joint United Nations Programme on HIV/AIDS (UNAIDS).Report on the global

HIV/AIDS epidemic:July 2002. Geneva, (contains country-specific estimates).

Joint United Nations Programme on HIV/AIDS (UNAIDS). AIDS epidemic

update:December 2002. Geneva, 2002.

CLINICAL STAGING SYSTEM FOR HIV AND HIV-RELATED

DISEASE

World Health Organization. Scaling up antiretroviral therapy in resource-limited

settings.Guidelines for a public health approach. Geneva, 2002.

AIDS CASE DEFINITIONS FOR SURVEILLANCE

Acquired immunodeficiency syndrome (AIDS).WHO/CDC case definition for

AIDS. Weekly epidemiological record, 1986, 61: 69–73. (WHO clinical case

definitions for AIDS in children where HIV testing is not available).

Centers for Disease Control and Prevention.1994 revised classification system

for human immunodeficiency virus infection in children less than 13 years of

age. Morbidity and mortality weekly report, 1994;43 (No. RR-12): 1-10. (Case

definition for AIDS in children where HIV testing is available).

WHO case definitions for AIDS surveillance in adults and adolescents.Weekly

epidemiological record 1994,69: 273-275.

HIV-RELATED TUBERCULOSIS

Corbett EL,Watt CJ,Walker N, Maher D,Williams BG, Raviglione MC, Dye C.

The growing burden of tuberculosis: global trends and interactions with the

HIV epidemic.Archives of internal medicine , 2003,163: 1009–1021.

Raviglione MC, Harries AD,Msiska R, Wilkinson D,Nunn P. Tuberculosis and

HIV:current status in Africa. AIDS, 1997, 11 (suppl B):S115 - S123.

Ya Diul M,Maher D, Harries A. Tuberculosis case fatality rates in high HIV

prevalence populations in sub-Saharan Africa.AIDS, 2001, 15: 143-152.

World Health Organization. A strategic framework to decrease the burden of

TB/HIV.Geneva, 2002 (WHO/CDS/TB/2002.296;WHO/HIV_AIDS/2002.2).

World Health Organization.Guidelines for collaborative TB and HIV programme

activities. Geneva,2003, (WHO/CDS/TB/2003.319;WHO/HIV/2003.01).

BACKGROUND INFORMATION ON TB AND HIV

TB/HIV:A CLINICAL MANUAL

AN EXPANDED FRAMEWORK FOR EFFECTIVE

TUBERCULOSIS CONTROL

2.1 INTRODUCTION

WHO has declared that TB is a global emergency,because TB is out of

control in many parts of the world.The following are the main reasons

why TB is out of control:

a) governments in many parts of the world have neglected the disease;

b) inadequate TB control programmes have led to an increased burden of

disease (inadequately treated TB patients live longer with chronic disease

and infect other people) and the emergence of drug-resistant TB;

c) high rates of population growth have contributed to an increased

number of TB cases;

d) the HIV epidemic has led to an enormous increase in the number of

TB cases,in places where HIV and TB are both common.

WHO has expanded the framework for TB control in order to reflect

experience gained since the development of the original framework in

1994.The expanded framework is relevant in all settings,including where

HIV is common.Successful TB control depends on health care workers

treating TB patients within this framework in a national TB programme

(NTP).Full implementation of the DOTS strategy remains the priority.

This means ensuring the accurate diagnosis and effective treatment of all

TB patients.

In addition TB and HIV/AIDS programmes must collaborate to

counteract the impact of HIV on TB.This depends on implementation of

the DOTS strategy and other interventions.In addition to effective TB

case-finding and cure,these interventions include: measures to decrease

HIV transmission (e.g. promotion of condoms, treatment of sexually

transmitted infections);highly active antiretroviral therapy (HAART);TB

preventive treatment; and antibiotic prophylaxis against HIV-related

bacterial infections.

2.2 COMPONENTS OF EXPANDED TB CONTROL

FRAMEWORK

The expanded framework consists of the following:

1. Goals of TB control.

2. Targets for TB control.

3. TB control policy package.

4. Key operations for DOTS implemantation.

5. Indicators to measure NTP progress in TB control.

2.2.1 Goals of TB control

The goals of TB control are to reduce mortality,morbidity and disease

transmission (while preventing drug resistance) until TB no longer poses

a threat to public health.The aim is also to reduce human suffering and

the social and economic burden on families and communities as a

consequence of TB.In order to achieve this, it is necessary to ensure

access to diagnosis,treatment and cure for each patient.

2.2.2 Targets for TB control (cure and case detection)

a) To cure 85% of the sputum smear-positive PTB cases detected.

A national TB programme that achieves at least an 85% cure rate in

patients with sputum smear-positive PTB has the following impact on TB:

i) TB prevalence,TB mortality and rate of TB transmission decrease

rapidly;

ii) TB incidence decreases gradually;

iii)there is less drug resistance (which makes future treatment of TB

easier and more affordable).

Achieving high cure rates is the highest priority.TB programmes with

high cure rates rapidly reduce disease transmission.They are likely to

attract the majority of existing cases in the community.

b) To detect 70% of existing cases of sputum smear-positive PTB.

It is important to expand case-finding only when the national TB

programme has achieved a high cure rate.A national TB programme that

has a low cure rate makes the TB problem worse:

i) there are more cases of sputum smear-positive PTB treatment failure;

ii) transmission of drug resistance increases.

A treatable epidemic becomes an untreatable epidemic.

An effective NTP has a high cure rate and a low level of drug resistance.

Provided that a high cure rate is achieved,increased case detection of

sputum smear-positive PTB cases will decrease TB transmission.

AN EXPANDED FRAMEWORK FOR EFFECTIVE TB CONTROL

2.2.3 TB control policy package (the DOTS strategy)

NTPs face new challenges.They need significant strengthening in order

to achieve the targets for TB control.

General public health services need to increase their capacity to

sustain and expand DOTS implementation.At the same time they

must maintain the quality of case detection and treatment.

Promoting a patient-centred approach and community involvement in

TB care can improve both access to and utilization of health services.

Collaboration is essential between the public, private,and voluntary

sectors to ensure accessible and quality-assured TB diagnosis and

treatment.

The increasing impact of HIV on the incidence of TB requires new

approaches and partnerships.

A high prevalence of drug-resistant TB requires two complementary

approaches:NTPs need to cure existing multidrug-resistant (MDR) TB

cases as well as prevent new cases (through the DOTS strategy).

The expanded DOTS framework reinforces the five essential elements

of the DOTS strategy:

a. Sustained political commitment to increase human and

financial resources and make TB control a nationwide activity

integral to the national health system.

b. Access to quality-assured TB sputum microscopy for case

detection among persons presenting with, or found through

screening to have,symptoms of TB (most importantly prolonged

cough). Special attention to case detection is necessary among

HIV-infected people and other high-risk groups, e.g.people in

institutions.

c. Standardized short-course chemotherapy (SCC) for all

cases of TB under proper case-management conditions

including direct observation of treatment. Proper case

management conditions imply technically sound and socially

supportive treatment services.

TB/HIV:A CLINICAL MANUAL

d. Uninterrupted supply of quality-assured drugs with reliable

drug procurement and distribution systems.

e. Recording and reporting system enabling outcome

assessment of every patient and assessment of the overall

programme performance.

2.2.4 Key operations for DOTS implementation

Establish a national TB programme (NTP) with a central unit.

Prepare a programme development plan.

Prepare the NTP manualand make it available at district level.

Establish a recording and reporting system using standardized

material allowing categorizaton of cases registered and cohort analysis

for treatment outcomes.

Plan and initiate a training programme covering all aspects of the

policy package.

Establish a microscopy services network in close contact with

primary health care (PHC) services and subject to regular quality control.

Establish treatment services within the PHC system where

directly observed short-course chemotherapy is given priority and

patient education is provided.Treatment services should achieve total

geographical and patient coverage.

Secure a regular supply of drugs and diagnostic materialbased

on previous case notification data.

Design a plan of supervision of the key operations at the

intermediate and district level to be implemented from the start of

the programme.

Undertake social mobilization through information, education

and communication activities, in order to mobilize and sustain

support for TB control.

Involve all health care providers,e.g. private and voluntary health

care providers, nongovernmental organizations (NGOs), religious

organizations and employers.

AN EXPANDED FRAMEWORK FOR EFFECTIVE TB CONTROL

TB/HIV:A CLINICAL MANUAL

Undertake economic analysis and financial planning to ensure

that the NTP is on a sound financial footing.

Undertake operational research as an integral component of

DOTS implementation to improve NTP performance.

2.2.5 Indicators to measure NTP progress in TB control

National TB control policies,as set out in the NTP manual,consistent

with the DOTS strategy.

The number of administrative areas in the country that are

implementing the DOTS strategy.

The cure rate in new smear-positive cases.

The case detection rate.

The WHO document, “An expanded DOTS framework for effective

tuberculosis control” (WHO/CDS/TB/2002.297),provides a full list of

indicators.

2.3 DIRECTLY OBSERVED TREATMENT

What is directly observed treatment?

Patient adherence to treatment is necessary to ensure that the

treatment cures the patient. Patient adherence to SCC means the

patient takes every dose of the recommended treatment regimen.It may

be difficult for a patient to adhere to anti-TB treatment for 6 to 8

months. It is difficult to predict which TB patients will adhere to self-

administered treatment.One certain way to ensure patient adherence

to treatment is direct observation of treatment. This means that

someone supports the patient during the course of treatment and

watches the patient swallow the tablets. The NTP coordinates the

training of patient supporters and monitors their effectiveness in

ensuring treatment adherence.

Directly observed treatment as close to the patient's home as

possible

TB patients are unlikely to adhere to treatment if they have far to go for

treatment. One of the aims of a TB programme is to organize TB

services so that patients have treatment as close to home as possible.A

TB programme brings treatment to patients wherever they live.Many TB

patients live close to a health facility (e.g.health centre, district hospital).

For these patients, the treatment supporter who directly observes

treatment could be one of the health staff in the health facility.Some TB

patients live far away from a health facility.For these patients, the

supervisor may be a trained local community member or a health

outreach worker.Family members who provide health care support can

also be trained as TB treatment supporters.Some areas have HIV/AIDS

community care schemes.With suitable training and supervision, the

HIV/AIDS home care providers can support TB patients, including

directly observing treatment.

Integration of TB treatment services with general health services

In the past,some TB programmes have relied on special TB hospitals and

clinics,separate from the general health service. The problem with that

system is that many TB patients live far from a TB hospital or clinic.One

reason why TB is out of control in many countries is that TB patients do

not have access to TB diagnosis and treatment services.A successful

NTP brings TB diagnosis and treatment services to the TB patients.This

is why TB treatment services are integrated with existing general health

services.

2.4 TB/HIV

TB and HIV are closely interlinked.TB is a leading cause of HIV-related

morbidity and mortality.HIV is the most important factor fuelling the TB

epidemic in populations with a high HIV prevalence.The WHO global

strategic framework to control TB/HIV represents a coordinated

response to the joint epidemics of TB and HIV.Collaboration between

TB and HIV/AIDS programmes is crucial in supporting general health

service providers.These providers need support in delivering the full

range of HIV and TB prevention and care interventions.To counteract

the impact of HIV on TB,other interventions are required apart from

effective TB case-finding and cure.These interventions include

measures to decrease HIV transmission (e.g. promotion of condoms,

treatment of sexually transmitted infections,voluntary counselling and

HIV testing, safe intravenous drug use,reduction in the number of

sexual partners, prevention of mother-to-child HIV transmission,HIV

screening of blood for transfusion, and application of universal HIV

precautions by health care workers);

antiretroviral therapy (ART) (to improve or maintain immune function

in people living with HIV infection);

care for people living with HIV infection (e.g.treatment of HIV-related

diseases,prevention of HIV-related infections,TB prevention,palliative

care and nutritional support).

AN EXPANDED FRAMEWORK FOR EFFECTIVE TB CONTROL

TB/HIV:A CLINICAL MANUAL

2.5 DOTS-PLUS

High levels of multidrug-resistant TB (MDR-TB) in some areas threaten

TB control efforts.MDR-TB is TB that is resistant to at least isoniazid

and rifampicin.DOTS-Plus for MDR-TB is a comprehensive management

initiative,built upon the five elements of the DOTS strategy. However,

DOTS-Plus also takes into account specific issues,such as the use of

second-line anti-TB drugs.The goal of DOTS-Plus is to prevent further

development and spread of MDR-TB. DOTS-Plus is not intended for

universal application, and is not required in all settings.The aim of

implementation of DOTS-Plus in selected areas with significant levels of

MDR-TB is to combat an emerging epidemic.The underlying principle is

that the first step in controlling MDR-TB is prevention by full

implementation of DOTS. An effective DOTS-based TB control

programme is a prerequisite for implementation of DOTS-Plus.

SUGGESTIONS FOR FURTHER READING

International Union Against Tuberculosis and Lung Disease. Tuberculosis guide

for low income countries.Fifth edition. Paris, 2000.

Maher D,van Gorkom JLC, Gondrie P,Raviglione MC. Community contribution

to tuberculosis care in countries with high tuberculosis prevalence: past,

present and future. International journal of tuberculosis and lung disease, 1999,

3: 762–768.

World Health Organization. Guidelines for the management of drug-resistant

Tuberculosis.Geneva, 1997,(WHO/TB/96.210 - Rev.1).

World Health Organization.What is DOTS? A guide to understanding the

WHO-recommended TB control strategy known as DOTS.Geneva, 1999,

(WHO/CDS/CPC/TB/99.270).

World Health Organization.Anti-tuberculosis drug resistance in the world. Report

No.2.Prevalence and trends. Geneva, 2000 (WHO/CDS/TB/2000.278).

World Health Organization.The WHO/IUATLD Global Project on anti-tuberculosis

drug resistance surveillance. Geneva, 2000.

World Health Organization. Guidelines for establishing DOTS-Plus pilot projects

for the management of multidrug-resistant TB. Geneva, 2000

(WHO/CDS/TB/2000.279).

World Health Organisation. An expanded DOTS framework for effective

tuberculosis control. Geneva,2002, (WHO/CDS/TB/2002.297).

World Health Organization. A strategic framework to decrease the burden of

TB/HIV.Geneva, 2002,(WHO/CDS/TB/2002.296).

World Health Organisation. Treatment of tuberculosis:guidelines for national

programmes.Third edition. Geneva, 2003, (WHO/CDS/TB/2003.313).

World Health Organization. Community contribution to TB care:practice and

policy.Geneva, 2003,(WHO/CDS/TB/2003.312).

World Health Organization.Guidelines for collaborative TB and HIV programme

activities. Geneva,2003, (WHO/CDS/TB/2003.319,WHO/HIV/2003.01).

AN EXPANDED FRAMEWORK FOR EFFECTIVE TB CONTROL

TB/HIV:A CLINICAL MANUAL

DIAGNOSIS OF PULMONARY TUBERCULOSIS

IN ADULTS

3.1 DIAGNOSTIC APPROACH

The highest priority for TB control is the identification and cure of

infectious cases,i.e. patients with sputum smear-positive PTB.Therefore

all patients (regardless of HIV status) with clinical features suggestive of

PTB must submit sputum for diagnostic sputum smear microscopy.

Most TB suspects (people with symptoms or signs suggestive of TB) are

ambulatory. The diagnosis of PTB is therefore usually done on an

outpatient basis.Some TB suspects are severely ill and/or bed-bound and

therefore need investigation as inpatients.

Clinical screening by assessment of symptoms identifies PTB suspects

among patients attending health facilities. The most cost-effective

method of detecting TB cases among PTB suspects in high-prevalence

countries is by sputum smear microscopy.A suspect who has a positive

sputum smear has sputum smear-positive PTB.The district TB officer

(DTO) registers the TB patient,and treatment is started.In most cases

of smear-positive PTB,a chest X-ray is unnecessary.

Sometimes a patient may be negative on sputum smear microscopy but

may not improve on a broad-spectrum antibiotic.If you still suspect TB,

reassess the patient and do a CXR.If the CXR is typical of PTB, register

the patient with the DTO and start TB treatment.If doubtful about the

CXR diagnosis of TB, e.g.if the CXR shows nonspecific pulmonary

infiltrates, give the patient another course of antibiotics.If there is no

clinical improvement,or if the cough disappears only to return shortly

afterwards,repeat sputum smear microscopy.If you still think the patient

may have TB despite,further negative sputum smears,again reassess the

patient and repeat the CXR.Then decide whether the diagnosis is TB or

not. In cases where diagnostic doubt persists, sputum culture may be

useful if suitable facilities are available.

In populations with a high TB prevalence,the tuberculin skin test is of

little value in the diagnosis of TB in adults.A positive tuberculin skin test

does not by itself distinguish M. tuberculosis infection from TB disease.

Previous exposure to environmental mycobacteria may also result in a

false-positive test result.Conversely, the tuberculin skin test result may

be negative,even when the patient has TB. Conditions often associated

with a false-negative tuberculin skin test include HIV infection,severe

malnutrition and miliary TB.

3.2 CLINICAL FEATURES

Symptoms

The most important symptoms in the diagnosis of PTB are the following:

cough for more than 2 or 3 weeks;

sputum production;

weight loss.

Over 90% of patients with sputum smear-positive PTB develop a cough

soon after disease onset.However, cough is not specific to PTB.Cough

is common in smokers and in patients with acute upper or lower

respiratory tract infection. Most acute respiratory infections resolve

within 3 weeks.Therefore a patient with a cough for more than 2 or 3

weeks is a PTB suspect and must submit sputum samples for diagnostic

microscopy.

Patients with PTB may also have other symptoms. These may be

respiratory or constitutional (general or systemic).

Respiratory: chest pain,haemoptysis, breathlessness.

Constitutional: fever, night sweats, tiredness, loss of appetite,

secondary amenorrhoea.

Weight loss and fever are more common in HIV-positive PTB patients

than in those who are HIV-negative.Conversely,cough and haemoptysis

are less common in HIV-positive PTB patients than in those who are

HIV-negative. This is probably because there is less cavitation,

inflammation and endobronchial irritation in HIV-positive patients.

Physical signs

The physical signs in patients with PTB are nonspecific.They do not help

to distinguish PTB from other chest diseases.There may be general signs,

such as fever,tachycardia (fast pulse rate) and finger clubbing.Chest signs

(heard through a stethoscope) may include crackles,wheezes, bronchial

breathing and amphoric breathing.There are often no abnormal signs in

the chest.

DIAGNOSIS OF PULMONARY TB IN ADULTS

PRACTICAL POINT

All PTB suspects must provide sputum samples for smear

microscopy for TB case-detection.

3.3 DIAGNOSTIC SPUTUM SMEAR MICROSCOPY

Collection of sputum samples

A PTB suspect should submit three sputum samples for microscopy.The

chances of finding TB bacilli are greater with three samples than with

two samples or one sample.Secretions build up in the airways overnight.

So an early morning sputum sample is more likely to contain TB bacilli

than one taken later in the day.It may be difficult for an outpatient to

provide three early morning sputum samples.Therefore in practice an

out-patient usually provides sputum samples as follows:

day 1 sample 1 Patient provides an "on-the-spot" sample under

supervision when presenting to the health facility.

Give the patient a sputum container to take home

for an early morning sample the following morning.

day 2 sample 2 Patient brings an early morning sample.

sample 3 Patient provides another "on-the-spot" sample

under supervision.

Some patients cannot produce a sputum sample. A nurse or

physiotherapist may help them to give a good cough and bring up some

sputum.Inpatients can follow the same method as outpatients.

Terminology

Mycobacteria are "acid- and alcohol-fast bacilli" (AAFB),often shortened

to "acid-fast bacilli" (AFB).The waxy coat of mycobacteria retains an

aniline dye (e.g.carbol fuchsin) even after decolorization with acid and

alcohol.

Ziehl-Neelsen (Z-N) stain

This simple stain detects AFB.This is how to perform the Z-N stain:

Fix the smear on the slide.

Cover the fixed smear with carbol fuchsin for 3 minutes.

Heat,rinse with tapwater, and decolorize with acid-

alcohol for 3–5 seconds.

Counterstain with methylene blue for 30 seconds.

Rinse again with tapwater.

Observe under the microscope (use the x100 oil immersion lens

and x10 eyepiece lens).

The bacilli appear as red, beaded rods,2–4 µm long and 0.2–0.5 µm

wide.

TB/HIV:A CLINICAL MANUAL

Fluorochrome stain

Use of this stain to detect TB bacilli requires a special fluorescence

microscope.The fluorochrome stain is phenolic auramine or auramine-

rhodamine. After acid-alcohol decolorization and a methylene blue

counterstain, the bacilli fluoresce bright yellow against a dark

background.The advantage of this method is that smears can be scanned

quickly under low magnification.It is important to check fluorochrome

stain-positive smears using the Z-N stain.

Slide reporting

The number of bacilli seen in a smear reflects disease severity and

patient infectivity.Therefore it is important to record the number of

bacilli seen on each smear.The table below shows the standard method

of reporting using 1000 x magnification.

Number of bacilli Result reported

no AFB per 100 oil immersion fields 0

1–9 AFB per 100 oil immersion fields scanty (or number AFB seen)

10–99 AFB per 100 oil immersion fields + (1+)

1–10 AFB per oil immersion field ++ (2+)

> 10 AFB per oil immersion field +++ (3+)

Laboratory technicians should examine all three sputum samples from

each TB suspect.They must record the result of each sputum sample

with the laboratory reference number in the laboratory register and on

the sputum request form. Results as indicated above are made available

to the clinician who can then categorize the patient. Categorizing

patients as smear-positive or negative requires results from more than

one smear. A guide to classification of patients with pulmonary

symptoms is given below.

DIAGNOSIS OF PULMONARY TB IN ADULTS

Smear-positive Indeterminate Smear negative

At least 2 smears Several possibilities,e.g. At least two smears

examined and both

only one smear examined reported 0

positive,i.e. reported (whatever the grading) (negative)

1–9 per 100 fields

3 smears examined but

(scanty) or greater only one reported positive

In either of these

situations,either further

sputum smears or a CXR

are required before a

patient can be classified.

Sensitivity of sputum smear microscopy

Sputum smear microscopy for tubercle bacilli is positive when there are

at least 10000 organisms present per ml of sputum.

Sputum microscopy in HIV infection

Sputum smear positivity rates in TB/HIV patients depend on the degree

of immunocompromise,as shown below.

Degree of Likelihood of positive sputum smear

immunocompromise

mild similar to HIV-negative patient

severe decreased(decreased inflammation in lungs)

False-positive results of sputum smear microscopy

A false-positive result means that the sputum smear result is positive

even though the patient does not really have sputum smear-positive

PTB. This may arise because of the following:red stain retained by

scratches on the slide;accidental transfer of AFBs from a positive slide

to a negative one;contamination of the slide or smear by environmental

mycobacteria;presence of various particles that are acid-fast (e.g. food

particles,precipitates, other microorganisms).

False-negative results of sputum smear microscopy

A false-negative result means that the sputum smear result is negative

even though the patient really does havesputum smear-positive PTB.

This may arise because of problems in collecting, processing, or

interpreting sputum smears,or because of administrative errors.

Causes of false negative results of sputum smear microscopy

Type of problem Example

sputum collection patient provides inadequate sample

inappropriate sputum container used

sputum stored too long before smear microscopy

sputum processing faulty sampling of sputum for smear

faulty smear preparation and staining

sputum smear inadequate time spent examining smear

interpretation inadequate attention to smear (poor motivation)

TB/HIV:A CLINICAL MANUAL

PRACTICAL POINT

A sputum smear result may be unexpectedly negative (e.g.

in a patient with upper lobe cavities on CXR).Think of the

possibility of a false-negative result and repeat the sputum

microscopy.

administrative errors misidentification of patient

incorrect labelling of sample

mistakes in documentation

3.4 DIFFERENTIAL DIAGNOSIS OF PULMONARY TB

The table shows possible alternative diagnoses.

DIAGNOSIS OF PULMONARY TB IN ADULTS

PRACTICAL POINT

A PTB suspect with 3 negative sputum smears may not have

PTB. Reassess the patient for conditions that may be

mistaken for PTB.

Diagnosis Pointers to the correct diagnosis

bronchiectasis coughing large amounts of purulent

sputum

bronchial carcinoma risk factor (smoking, older age,

(lung cancer) previous mine-work)

other infections,e.g.

bacterial pneumonia usually shorter history,febrile, response

to antibiotic

lung abscess cough with large amounts of purulent

sputum

abscess with fluid level on CXR

Pneumocystis carinii often dry,non-productive cough with

prominent dyspnoea

congestive cardiac failure symptoms of heart failure

left ventricular failure (dyspnoea, orthopnoea, paroxysmal

nocturnal dyspnoea,haemoptysis, oedema,

epigastric discomfort from hepatic

congestion)

signs of heart failure

asthma intermittent symptoms, generalized

expiratory wheeze;

symptoms wake the patient at night

chronic obstructive risk factor (smoking), chronic symptoms,

airways disease prominent dyspnoea,generalized wheeze,

signs of right heart failure (e.g.ankle oedema)

TB/HIV:A CLINICAL MANUAL

3.5 CHEST X-RAY IN DIAGNOSIS

Indications for CXR

Positive sputum smear

The first screening test for PTB suspects is sputum smear microscopy.

In most cases of sputum smear-positive PTB a CXR is not necessary.In

a few cases,a CXR may be necessary; the indications are as follows:

(a) suspected complications in a breathless patient, needing specific

treatment,e.g. pneumothorax,pericardial effusion or pleural effusion

(note that a positive sputum smear is rare in pericardial effusion and

pleural effusion);

(b) frequent or severe haemoptysis (to exclude bronchiectasis or

aspergilloma);

CXR is a necessary additional criterion for the diagnosis of sputum

smear-positive PTB).

Negative sputum smear

Reassess patients who continue to cough despite a course of broad-

spectrum antibiotic, and who have had at least two (and preferably

three) negative sputum smears. If you still suspect TB despite negative

sputum smears,the patient needs a CXR.

3.6 RADIOGRAPHIC ABNORMALITIES SEEN IN

PULMONARY TB

The table below shows so-called "classical" and "atypical" CXR patterns.

The classical pattern is more common in HIV-negative patients,and the

atypical pattern in HIV-positive patients.

PRACTICAL POINT

If the patient is breathless,has continuing haemoptysis, and

has negative sputum smears, listen carefully for a low-

pitched, rumbling, mid-diastolic murmur, indicating mitral

stenosis with pulmonary oedema.

PRACTICAL POINT

No CXR pattern is absolutely typical of PTB,especially with

underlying HIV infection.

3.7 DIFFERENTIAL DIAGNOSIS OF CHEST X-RAY

FINDINGS

The CXR findings associated with PTB may be nonspecific. Diseases

other than PTB can cause both the "classical" and the "atypical" CXR

findings.

The table shows the differential diagnosis of CXR findings often

associated with PTB.

DIAGNOSIS OF PULMONARY TB IN ADULTS

CXR finding Differential diagnosis

cavitation infections

some bacterial pneumonias

nocardiosis

melioidosis

paragonimiasis (lung fluke)

lung abscess

some fungal infections

PRACTICAL POINT

The vast majority of patients with cavitary PTB (over 90%)

are sputum smear-positive.Therefore,a patient with cavities

on CXR and repeated negative sputum smears probably has

a disease other than PTB.

CLASSICAL PATTERN ATYPICALPATTERN

upper lobe infiltrates interstitial infiltrates (especially

bilateral infiltrates lower zones)

cavitation intrathoracic lymphadenopathy

pulmonary fibrosis and shrinkage no cavitation

no abnormalities

PRACTICAL POINT

CXR changes in TB/HIV patients reflect the degree of

immunocompromise. In mild immunocompromise, the

appearance is often classical (with cavitation and upper lobe

infiltrates). In severe immunocompromise,the appearance

is often atypical.

3.8 THE PLACE OF MYCOBACTERIAL CULTURE IN

THE DIAGNOSIS OF TB

Laboratory culture of M tuberculosis

When M. tuberculosis is cultured from clinical specimens (e.g. sputum,

lymph node aspirate,cerebrospinal fluid) this provides the gold standard

for the definitive diagnosis of TB.Tubercle bacilli that have grown in

culture can also be tested in vitro for sensitivity to anti-TB drugs.The

usual culture medium is Löwenstein Jensen, although liquid culture

media and automated systems (e.g. Bactec) can also be used in more

sophisticated laboratories.

Limitations of mycobacterial culture for diagnosis

M.tuberculosis is a slow-growing organism, and it often takes between 6

and 8 weeks before cultures become positive. Culture results may

therefore not be helpful in making a rapid individual diagnosis,although

they can be helpful retrospectively. There is also the need for

considerable laboratory infrastructure and laboratory skills in order to

sustain a mycobacterial culture facility. Most developing countries have

one or two mycobacterial reference centres where cultures and drug

sensitivity analysis can be performed.However, most hospitals will not

have TB culture facilities readily available.

3.9 SEPSIS AND CONCOMITANT TB

Sepsis can occur as a coinfection with TB. An inadequate clinical

response after treatment of sepsis,e.g. pneumonia, may be due to the

presence of concomitant HIV-related TB.

TB/HIV:A CLINICAL MANUAL

cavitation non-infectious disease

bronchial carcinoma

connective tissue disease

occupational lung disease

unilateral infiltration pneumonia

bronchial carcinoma

bilateral infiltration pneumonia

connective tissue disease

occupational lung disease

sarcoidosis

mediastinal lymphadenopathy lymphoma

bronchial carcinoma

sarcoidosis

3.10 DISTINGUISHING OTHER HIV-RELATED

PULMONARY DISEASES FROM PULMONARY TB

This is a common, and often difficult, diagnostic problem. Several

diseases in HIV-positive individuals may present in a similar way, with

cough,fever, sometimes chest signs,and CXR shadowing. Pneumonia is

the most frequent and important differential diagnosis.Pneumonia can

also occur as a coinfection with TB. In each case,a careful clinical

assessment is needed.Send sputum samples for AFBs if the patient has

had cough for 3 weeks or more.

Acute bacterial pneumonia

This is common in HIV-positive patients.The shorter history usually

differentiates pneumonia from PTB.The most common pathogen is

Streptococcus pneumoniae. Regardless of HIV status, acute bacterial

pneumonia usually responds well to standard treatment with penicillin,

cotrimoxazole or ampicillin.

Kaposi sarcoma (KS)

The clinical recognition of KS is straightforward when there are typical

lesions on the skin and mucous membranes.The diagnosis of pulmonary

or pleural KS is more difficult.The patient usually presents with cough,

fever,haemoptysis and dyspnoea, and usually has KS lesions elsewhere.

CXR shows a diffuse nodular infiltrate (with infiltrates spreading out

from the hilar regions) or pleural effusion.The pleural fluid is usually

blood-stained.Cytology may provide the diagnosis. It can be difficult to

rule out concurrent PTB.

Pneumocystis carinii pneumonia (PCP)

Adult PCP is less commonly seen in patients with AIDS in sub-Saharan

Africa than in developed countries.The patient usually presents with dry

cough and progressive dyspnoea.The table below shows the clinical and

CXR features that help to distinguish PCP from PTB.

DIAGNOSIS OF PULMONARY TB IN ADULTS

PRACTICAL POINT

If a patient with presumed pneumonia fails to respond to a

full course of standard antibiotics,consider other pathogens,

e.g.M. tuberculosis.

TB/HIV:A CLINICAL MANUAL

Clinical and CXR features of PCP and TB

Typical of PCP Typical of TB

symptoms dr y cough productive cough

sputum mucoid (if any) purulent sputum

dyspnoea pleuritic chest pain

haemoptysis

signs may be normal signs of consolidation

fine inspiratory crackles signs of pleural effusion

CXR bilateral diffuse lobar consolidation

interstitial shadowing cavitation

may be normal pleural effusion

intrathoracic

lymphadenopathy

The definitive diagnosis of PCP rests on finding the cysts in induced

sputum, broncho-alveolar lavage or biopsy specimens. These

investigations are often not possible in district hospitals.The diagnosis

therefore depends on the clinical and CXR features,exclusion of TB and

response to a trial of high-dose cotrimoxazole, combined with

corticosteroids if there is severe dyspnoea.

Other conditions

Other uncommon conditions are cryptococcosis and nocardiosis.They

may present in a similar way to TB.The diagnosis of pulmonary

cryptococcosis rests on finding the fungal spores in sputum smears.

Nocardiosis may be particularly difficult to differentiate from TB.The

CXR often shows upper lobe,cavitary infiltrates.The organism may also

be weakly positive on acid-fast staining.Associated soft-tissue and brain

abscesses raise clinical suspicion.The diagnosis rests on finding beaded

and branching Gram-positive rods on sputum smear.In South-East Asia,

penicilliosis (due to a fungus called Penicillium marneffei) and melioidosis

can present in a similar way to PTB and may be HIV-related.The same is

true for common fungal infections (paracoccidioidomycosis and

histoplasmosis) in the Americas.

SUGGESTIONS FOR FURTHER READING

Crofton J,Horne N, Miller F. Clinical tuberculosis,second edition.

London,MacMillan Press Limited, 1999.

Harries AD,Maher D,Nunn P. An approach to the problems of diagnosing and

treating adult smear-negative pulmonary tuberculosis in high-HIV-prevalence

settings in sub-Saharan Africa.Bulletin of the World Health Organization, 1998,

76:651–662.

International Union Against Tubertculosis and Lung Disease. Technical guide.

Sputum examination for tuberculosis by direct microscopy in low-income countries.

Fifth edition.Paris, 2000.

Toman K.Tuberculosis.Case finding and chemotherapy. Geneva, WHO,1979.

World Health Organization. Tuberculosis handbook. Geneva, 1998,

(WHO/TB/98.253).

DIAGNOSIS OF PULMONARY TB IN ADULTS

TB/HIV:A CLINICAL MANUAL

DIAGNOSIS OF PULMONARY TUBERCULOSIS

IN CHILDREN

4.1 EPIDEMIOLOGY OF CHILDHOOD TB

The source of transmission of TB to a child is usually an adult (often a

family member) with sputum smear-positive PTB.Cases of TB in children

usually represent between 10% and 20% of all TB cases.The frequency

of childhood TB in a given population depends on the following:the

number of infectious cases,the closeness of contact with an infectious

case,the age of children when exposed to TB, and the age structure of

the population.Children rarely have sputum smear-positive TB and so it

is unlikely they are a powerful source of transmission.TB in children is

mainly due to failure of TB control in adults.Failure of TB control in

adults means failure to cure infectious cases (patients with sputum

smear-positive PTB).The highest priority in TB control is to cure the

infectious cases.However, it is still important to cure children with TB!

Good treatment of TB in childhood will result in the following:

a) improved well-being through decreased morbidity and mortality;

b) improved credibility and reputation of the NTP;and c) less chance for

children to have TB reactivation with cavitation in later life.

Immunization

In many countries, newborns receive BCG immunization, and yet

childhood PTB still occurs.This shows that BCG is not fully effective in

protecting against PTB. BCG seems to give better protection against

disseminated disease, such as miliary TB or TB meningitis,than it does

against PTB.The effectiveness of BCG against PTB is variable between

regions,and the reasons for this are not completely understood. One

problem is likely to be the timing of the vaccination. In developing

countries where TB is common,children will often be exposed to TB

early in life and so immunization needs to be given as early as possible,

i.e.soon after birth. However,the immune system of a newborn may be

too immature to be able to produce an effective immune reaction to the

BCG.BCG has been more effective when given to school-aged children.

However,in communities where TB is common,this would be too late

to protect against most disease. Other factors that reduce the

PRACTICAL POINT

A good TB control programme is the best way to prevent TB

in children.

effectiveness of BCG immunization are malnutrition and severe

infections such as HIV or measles.

Risk of infection

Risk of infection depends on extent of exposure to infectious droplet

nuclei. An infant whose mother has sputum smear-positive PTB,for

instance, has a high chance of becoming infected.Being in very close

contact with the mother,he or she is likely to inhale a larger number of

infectious droplets from the air than other household contacts.The

greater the exposure to infection,the greater the likelihood of disease.

Risk of progression of infection to disease

The chance of developing disease is greatest shortly after infection,and

steadily decreases as time goes by.Infants and young children under 5

years of age have less-developed immune systems than school-aged

children.They are therefore at particular risk (up to 20%) of developing

disease following infection. Many will present with disease within one

year following infection,most within 2 years. For infants particularly,the

time-span between infection and disease may be quite short and the

presentation of PTB is as an acute rather than chronic pneumonia.Almost

always in those cases,the contact is the mother. The majority of HIV-

negative children infected with M.tuberculosis do not develop TB disease

in childhood.In these healthy,asymptomatic, but TB-infected children,the

only evidence of infection may be a positive tuberculin skin test.

An infected child can develop TB disease at any time.Various illnesses or

stresses may trigger progression of infection to disease.The most

important trigger is weakening of immune resistance.This occurs with

HIV infection,other infections (especially measles and whooping cough)

and malnutrition.These conditions are also most common in infancy and

early childhood.

4.2 HOW DOES TB IN CHILDREN DIFFER FROM TB

IN ADULTS?

The commonest age of presentation of childhood TB disease is between

1 and 4 years.As already emphasized, young age is a risk factor for

infection, for progression from infection to disease,and for spread of

DIAGNOSIS OF PULMONARY TB IN CHILDREN

PRACTICAL POINT

The suspicion of TB in an infant should lead to investigation

of the mother for PTB.If there is no definite history of TB in

the mother,ask also about a history of chronic cough.

disease to other parts of the body,i.e. dissemination.Most children with

TB are not infectious to others.

The commonest type of TB in children is smear-negative PTB.This is

because cavitating TB is infrequent in children.The majority of children

with PTB are too young to provide a sputum specimen for smear

microscopy.Therefore an alternative method of obtaining sputum,such

as gastric aspiration,is required.If alternative diagnostic methods are not

available or routinely practised, the children are registered as having

“smear-negative PTB”,even though a smear has not been done.The next

commonest type is extrapulmonary TB. Common forms of EPTB in

children include: miliary TB and TB meningitis (usually in children less

than 3 years of age);TB lymphadenopathy (all ages);TB effusions (pleural,

pericardial and peritoneal); and spinal TB (often school-aged children)

(see Chapter 5). Smear-positive PTB is usually diagnosed in children

older than 6 years.The prevalence of PTB is normally low between 5 and

12 years and then increases in adolescents. In adolescents, PTB is

generally like adult PTB,e.g. often with cavitation.

Pathogenesis

TB disease in children is usually primary TB.Post-primary TB may occur

in adults following reactivation of dormant TB bacilli acquired in

childhood.The age when a child is infected determines the pattern of

primary disease.Pulmonary disease in young children is closely linked to

pathology of the mediastinal nodes.This is lymphobronchial TB, which

results in a wide spectrum of segmental lesions.These lesions may also

be found in adults, but are unusual.Adults usually develop TB in the

apices of the upper or lower lobes.Young children (i.e.less than 5 years

of age) are particularly susceptible to severe forms of disseminated

disease following primary infection.These severe forms include miliary

TB and extrapulmonary forms of TB,e.g. meningitis.

4.3 APPROACH TO DIAGNOSIS OF TB

The diagnosis of PTB in children is difficult.If you find the diagnosis of

PTB in children easy, you are probably overdiagnosing. It is easy to

overdiagnose PTB,but also easy to miss the diagnosis and presume the

TB/HIV:A CLINICAL MANUAL

PRACTICAL POINT

Malnourished and HIV-infected children may develop severe

PTB at any age.

clinical presentation is due to malnutrition or AIDS.Carefully assess all

the evidence before making the diagnosis.

The diagnosis of PTB is particularly difficult in children because,under

the age of 6–8 years, children with PTB rarely cough up sputum.The

readily available usual test for adults and older children with PTB is

sputum smear microscopy.However, there is no such “gold standard”

test for the majority of children with TB.Young children usually swallow

their sputum. Gastric suction and laryngeal swabs are generally not

useful unless facilities are available for M.tuberculosis culture.This means

that bacteriological confirmation is usually not possible.The diagnosis of

PTB in children is therefore nearly always presumptive.

The approach to diagnosis of extrapulmonary TB in children is similar to

that described for adults and is outlined in Chapter 5.In some hospitals,

helpful special diagnostic investigations may be available.These may

include microscopy of fluid (e.g.pleural fluid, cerebrospinal fluid, ascitic

fluid) and TB culture,specialized X-rays,biopsy and histology.

Clinical assessment

There are no specific features on clinical examination that can confirm

that the presenting illness is due to PTB. Respiratory symptoms and

disease are extremely common in childhood,particularly before 5 years

of age.In most cases of suspected PTB, the child has been treated with

a broad-spectrum antibiotic,with no clinical response. Always look for

three important clues to TB in children:

(1) Contact with an adult or older child with smear-positive PTB.

It is usually possible to identify the source of infection.This is most

often the child’s mother or another female carer,such as an aunt,

grandmother or older sister.They are the ones who spend most

time with young children.Make sure you ask for a specific history of

illness in each household contact.For example, do not just ask “does

anyone in the home have TB?” but also “is anyone at home ill and

what are the symptoms?” Remember that the contact may have

occurred 6 months to 2 years ago.This is the usual time lapse

between infection and developing symptoms of disease.Adult cases

of PTB are occasionally diagnosed when a child presents with

suspected TB.

(2) Failure to thrive or weight loss (growth faltering).

This is a good indicator of chronic disease in children and TB may be

the cause. It is not specific and may also be due to poor nutrition,

persistent or recurrent diarrhoea or HIV infection.

DIAGNOSIS OF PULMONARY TB IN CHILDREN

TB/HIV:A CLINICAL MANUAL

(3) Respiratory symptoms such as cough lasting for more than three

weeks in a child who has received a course of broad-spectrum

antibiotics.

In the absence of these clues,TB is less likely. However,always take a

clear history and examine the child carefully.There may be clues to

other diagnoses, such as asthma or an inhaled foreign body.Note the

nutritional state of the child and look for signs of HIV infection (see

Chapter 7).Examine the chest. There may be unexpected findings,such

as consolidation or pleural effusion.A child with these abnormalities

who does not look acutely unwell (e.g.no signs of respiratory distress

such as tachypnoea) and has not recently had antibiotics is more likely

to have TB rather than the more common bacterial pneumonias.Finally,

do not forget to examine the heart. Otherwise children with cardiac

failure due to congenital heart disease, rheumatic heart disease or

cardiomyopathy may be misdiagnosed as having PTB.

Investigations

If available, a tuberculin skin test should be done,as it may provide

supportive evidence. A negative tuberculin test does not exclude TB.

The tuberculin test is discussed in Section 4.5.

CXR is a common investigation in suspected PTB or miliary TB.The

most consistent specific feature on CXR is nodal enlargement and this

will be present in many children with PTB.Cavitation may be seen in

older children and adolescents, who will often be sputum smear-

positive.A normal CXR can be useful to exclude PTB or miliary TB in a

child with suggestive symptoms, such as persistent fever, night sweats

and failure to thrive.A single CXR at the time of presentation of illness

has limited value.A child presenting with persistent cough should receive

a course of broad-spectrum antibiotics,with a follow-up CXR at least

one month later.As for clinical examination, marked abnormalities are

occasionally found on CXR in a child who does not look acutely unwell.

This is suggestive of PTB.

The usefulness of the tuberculin test and CXR are further reduced in

malnourished or HIV-infected children (see Section 4.5). This is

PRACTICAL POINT

Ask the mother of a child with suspected TB for the child's

"road to health" card (growth card).If the card is available,

look for growth faltering or weight loss.

unfortunate as these are common conditions that the health worker

often needs to differentiate from TB.To add to the confusion, both

groups are at particular risk for TB disease.

Differential diagnosis of chronic respiratory symptoms

Other conditions that present with chronic respiratory symptoms

include:

pertussis (whooping cough)

asthma

HIV infection (see section 4.8)

aspirated foreign body

bronchiectasis

cystic fibrosis

cardiac disease

severe gastro-oesophageal reflux

severe cerebral palsy

4.4 SCORE SYSTEM FOR DIAGNOSIS OF TB IN

CHILDREN

There are a number of diagnostic score charts to improve diagnosis of

TB in children.These score charts have rarely been evaluated.The basis

of a score system is the careful and systematic collection of diagnostic

information.A score system is, in fact, not diagnostic but is rather a

useful screening test that helps guide your clinical judgement.A score

above a certain threshold indicates a high likelihood of TB.Examples can

be found in Clinical tuberculosis(Crofton, Horne & Miller) or in the article

by van Beekhuizen in Tropical doctor (see “Suggestions for further

reading” at the end of the chapter).

Characteristic clinical features (e.g.spinal deformity, scrofula or painless

ascites) supported by simple investigations often point to the diagnosis

of various forms of extrapulmonary TB.These permit a confident

diagnosis of TB,even if rarely confirmed microbiologically.However,the

commonest type is PTB and this is the most difficult to diagnose.Score

charts are least useful for PTB because they are so nonspecific in regions

where malnutrition and HIV are common.Features suggestive of TB (and

commonly used in score charts) include:

duration of illness greater than 4 weeks,particularly if the illness has

not responded to other treatments, e.g.broad-spectrum antibiotics

for persistent cough;

DIAGNOSIS OF PULMONARY TB IN CHILDREN

evidence of wasting (i.e. under 60% of median weight-for-age),

especially if there is a lack of weight gain in response to intensive

nutritional support;

family history of sputum-positive PTB (this is very important

information);

significant or “positive” tuberculin test.

Some score charts use response to TB treatment as a factor supporting

a diagnosis of TB.This does not mean that a TB treatment trial should be

used for diagnostic purposes!

4.5 TUBERCULIN SKIN TEST

Tuberculin is a purified protein derived from tubercle bacilli.Another

name for tuberculin is PPD (purified protein derivative). Following

infection with M. tuberculosis, a person develops hypersensitivity to

tuberculin. Tuberculin injected into the skin of an infected person

produces a delayed local reaction after 24–48 hours.This reaction is

quantified by measuring the diameter of skin induration (thickening) at

the site of the reaction.Various conditions can suppress this reaction.

The reaction indicates hypersensitivity.In other words, the reaction

only shows that the person has at some time be infected with M.

tuberculosis.

The technical details about tuberculins and how to administer and read

a tuberculin test are beyond the scope of this book.Clinical tuberculosis

(Crofton,Horne & Miller) gives a good account.The standard amount of

tuberculin used is 5 units,injected as 0.1 ml into the anterior surface of

the forearm at the junction of the middle and upper thirds.It is very

important that the tuberculin is injected intradermally so that it is well

localized.If correctly given, the injection should raise a small bump of 5

mm or more in diameter,which disappears within 1–2 hours.This is not

easy in a vigorous and protesting child. Poor injection technique can

cause a false-negative reaction.

TB/HIV:A CLINICAL MANUAL

PRACTICAL POINT

A tuberculin test does not measure immunity.By itself, it

does not indicate the presence or extent of TB disease;it

only indicates infection.

Value of a negative tuberculin test

A tuberculin test is not significant,or “negative”, when the diameter of

skin induration is less than 10 mm (or less than 5 mm in an HIV-infected

child).This is regardless of whether the child has had BCG.A negative

tuberculin skin test does not exclude TB.Thus,it is of no help in deciding

that someone does not have TB.The table below shows the conditions

that can suppress a tuberculin skin test in a person with active TB.

Conditions that may suppress the tuberculin skin test

HIV infection

malnutrition

severe bacterial infections,including TB itself

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

cancer

immunosuppressive drugs,e.g. steroids

incorrect injection of PPD

Value of a positive tuberculin skin test

The criterion for a significant or “positive” tuberculin test depends on

whether a child has previously had BCG vaccination or not.This is

because a reaction to tuberculin is usual after a previous BCG,at least

for several years.The reaction is usually weaker (diameter often less than

10 mm) than the reaction to natural infection with M. tuberculosis.A

tuberculin test is considered significant or positive when the diameter of

skin induration is 10 mm or more.However, if the child is HIV-infected,

the tuberculin test is considered positive if the induration is 5 mm or

more.A positive tuberculin test is only one piece of evidence in favour

of the diagnosis of TB.The younger the child and the greater the

diameter of induration,the stronger is that one piece of evidence.

4.6 THE DECISION TO START TB TREATMENT IN

CHILDREN

The decision to start TB treatment in a child is an active process,which

involves weighing up the clinical evidence and investigation findings,

careful thought, and often a period of observation.For children with

confirmed TB or for whom there is a high likelihood of TB,there is no

need to hesitate about starting treatment.If the diagnostic evidence is

weak and the child is older and not acutely ill, there is no need for

anxiety or urgency about starting treatment.Wait and see! If, however,

the child is very young and acutely ill it may be necessary to start

treatment on the basis of less robust evidence.

DIAGNOSIS OF PULMONARY TB IN CHILDREN

TB/HIV:A CLINICAL MANUAL

In the past,some doctors have advocated a “treatment trial” with anti-

TB drugs for purposes of diagnosis.The idea is that if the child responds

to the treatment,then the diagnosis is TB.There are some problems with

this approach:

a) some anti-TB drugs, such as rifampicin, kill other bacteria, so

response to anti-TB drugs may be because the child has another

(bacterial) infection;

b) compliance with a "treatment trial" is often poor,because of the lack

of certainty surrounding the decision to treat;

c) there may be a tendency to jump too quickly to a "treatment trial"

without the necessary careful and thoughtful approach to diagnosis;

d) a hasty “treatment trial” may not leave enough time to give

treatment for other more common infections,such as bacterial or

atypical pneumonia;

e) once TB treatment is started,it should be completed.

4.7 IMPACT OF HIV ON THE DIAGNOSIS OF TB

IN CHILDREN

HIV makes the diagnosis and management of TB in children even more

difficult than usual,for the following reasons:

a) Several HIV-related diseases, including TB,may present in a similar

way (see section 4.8 for differential diagnosis).

b) The interpretation of tuberculin skin testing is less reliable. An

immunocompromised child may have a negative tuberculin skin test

despite having TB.

c) In some countries HIV infection is very common in adults with TB.

If there is a history of contact with an adult with smear-positive PTB

and that adult is the child’s parent,then the child has an increased

chance of being HIV infected as well.In addition, the child with TB,

even if not HIV-infected,may come from a household where one or

both parents have died. This situation makes compliance and

completion of treatment more difficult.

For these reasons and those mentioned above, many of the clinical

features that are used to suggest a diagnosis of childhood TB are less

useful in the presence of HIV infection.

Impact of HIV infection on the usefulness of features used to

diagnose PTB in children

4.8 DIFFERENTIAL DIAGNOSIS OF PULMONARY TB

IN HIV-INFECTED CHILDREN

Bacterial pneumonia

Bacterial pneumonia is very common in all HIV-infected children and

recurrent bacterial pneumonia is a feature of children with AIDS.The

commonest cause is Streptococcus pneumoniae and response to

treatment is usually satisfactory. Other causes include Haemophilus

influenzae, Salmonella, Staphylococcus aureus, Klebsiella pneumoniae and

Escherichia coli.The presentation of PTB in infants can be acute, so PTB

should be considered when there is a poor clinical response to standard

antibiotics and the mother has TB.Pneumonia due to Staphylococcus or

Klebsiella may be a problem in HIV-infected children with chronic lung

disease.These bacteria can cause cystic changes and cavitation.

Lymphocytic interstitial pneumonitis (LIP)

LIP is a very common cause of lung disease in HIV-infected children over

2 years of age.LIP may be difficult to differentiate from PTB or miliary

TB. Clinical features that are commonly associated with LIP include

symmetrical, generalized lymphadenopathy (painless and mobile),

bilateral chronic non-tender parotid enlargement, and finger clubbing.

Diagnosis is clinical as it can only be confirmed by lung biopsy.Typical

CXR findings are bilateral diffuse reticulonodular pattern and enlarged

mediastinal/hilar lymph nodes. Note that the CXR abnormalities are

often unilateral with PTB.However,LIP presents with a broad spectrum

of clinical and radiological features. Bacterial pneumonia is a common

complication and further confuses the CXR findings.

Bronchiectasis

This is usually a complication of LIP but may also complicate TB.A cough

DIAGNOSIS OF PULMONARY TB IN CHILDREN

Diagnostic feature Impact of HIV

Chronic symptoms less specific

Smear-positive contact (if parent) less specific

Malnutrition or failure to thrive less specific

Positive tuberculin test less sensitive

“Characteristic” CXR abnormalities less specific

Satisfactory response to TB treatment less sensitive

productive of copious purulent and sometimes blood-stained sputum,

finger clubbing,and halitosis are typical features.

Pulmonary Kaposi sarcoma

KS can involve the lungs and causes diffuse lung infiltration and lymph

node enlargement. Patients may present with a large pleural effusion

which is bloody on aspiration.Look for the typical KS lesions elsewhere:

on the skin,palate or conjunctiva.

Pneumocystis carinii pneumonia

PCP is a common problem in HIV-infected children and usually presents

as an acute, severe pneumonia in infants less than 6 months of age.

Compared with TB in infants,PCP is characterized by severe hypoxia.

The commonest CXR abnormalities are diffuse interstitial infiltration

and hyperinflation. In developing countries, PCP is a very unlikely

diagnosis of persistent respiratory disease in children after infancy.In

countries where there is antenatal HIV screening and routine

cotrimoxazole prophylaxis in HIV-infected infants,PCP is now unusual .

Others

Other conditions to be considered in the differential diagnosis include:

fungal pneumonia,e.g. due to Candida or cryptococcus, nocardiosis and

pulmonary lymphoma.

4.9 MANAGEMENT OF CHILD CONTACTS OF

INFECTIOUS ADULTS

Children with TB may present to health units when they are ill.However,

most national TB control programmes also recommend active contact

tracing of children who are household contacts of infectious adults.In

order to be effective,this screening must be systematic. If you do not

have a systematic,organized process for child contact screening where

you work,could you start one?

The scheme below shows how to manage child contacts of infectious

adults (with sputum smear-positive PTB).Suspicion that a child contact

is HIV-infected may arise because of the following:the child has clinical

TB/HIV:A CLINICAL MANUAL

PRACTICAL POINT

The commonest HIV-related lung disease in children that

may be confused with TB is LIP.

evidence of HIV infection; the parent (the infectious TB patient) is

known,or suspected, to be HIV-positive.If you suspect a child contact is

HIV-infected,it is important to counsel the parents before HIV-testing

the child.

How to identify and manage child contacts of infectious adults

A child under 5 years of age living with a sputum smear-positive PTB

patient is at high risk of TB infection and developing TB disease,especially

if HIV-positive. Tuberculin skin testing is not a reliable way of

DIAGNOSIS OF PULMONARY TB IN CHILDREN

target group of adults with sputum

infectious adults smear-positive PTB

identify all household child

children at risk contacts

select children all children < 5 years

for screening children of any age with cough > 3 weeks

screening histor y and examination

process tuberculin skin test and CXR (where

resources permit)

outcome of TB TB TB

screening unlikely possible highly likely

treat for confirm

action other possibilities diagnosis

and re-evaluate

isoniazid register and

prophylaxis treat for TB

for all

children

< 5 years

TB/HIV:A CLINICAL MANUAL

distinguishing TB-infected from non-TB-infected children and is often

not available.The IUATLD therefore recommends isoniazid preventive

treatment for all child household contacts (under 5 years of age) of

sputum smear-positive PTB patients.The preventive treatment should be

based on the drug sensitivity profile of the likely source of infection,

whenever this profile is available.

SUGGESTIONS FOR FURTHER READING

Chaulet P et al.Childhood tuberculosis, still with us. Paris, International Children’s

Centre,1992.

Crofton J, Horne N, Miller F. Clinical tuberculosis, second edition. London,

MacMillan Press Limited,1999.

Donald PR, Fourie PB, Grange JM. Tuberculosis in childhood.Pretoria, JL van

Schaik,1999.

Graham SM, Coulter JBS,Gilks CF. Pulmonary disease in HIV-infected African

children.International journal of tuberculosis and lung disease, 2001, 5: 12-23.

Hesseling AC, Schaaf HS, Gie RP, Starke JR,Beyer s N.A critical review of

diagnostic approaches used in the diagnosis of childhood tuberculosis.

International journal of tuberculosis and lung disease, 2002, 6:1038-1045.

International Union Against Tuberculosis and Lung Disease. Tuberculosis guide

for low income countries. 5

edition,Frankfur t,pmi Verlagsgruppe, 2000.

Miller FJW.Tuberculosis in children. New Delhi,Churchill-Livingstone, 1986.

Mukadi YD,Wiktor SZ, Coulibaly I-M, et al. Impact of HIV infection on the

development, clinical presentation, and outcome of tuberculosis among

children in Abidjan,Cote d’Ivoire. AIDS, 1997, 11:1151-1158.

Osborne CM. The challenge of diagnosing childhood tuberculosis in a

developing country.Archives of diseases in childhood, 1995, 72: 369-74.

Palme IB, Gudetta B, Bruchfeld J, Muhe L, Giesecke J. Impact of human

immunodeficiency virus 1 infection on clinical presentation,treatment outcome

and survival in a cohort of Ethiopian children with tuberculosis. The pediatric

infectious disease journal, 2002,21: 1053-1061.

Reider HL.Epidemiologic basis of tuberculosis control. Paris, International Union

Against Tuberculosis and Lung Disease,1999.

Schaaf HS, Beyers N,Gie RP, et al.Respirator y tuberculosis in childhood:the

diagnostic value of clinical features and special investigations. The pediatric

infectious disease journal, 1995,14: 189-194.

Van Beekhuizen HJ.Tuberculosis score chart in children in Aitape,Papua New

Guinea.Tropical doctor, 1998, 28:155-160.

DIAGNOSIS OF PULMONARY TB IN CHILDREN

TB/HIV:A CLINICAL MANUAL

DIAGNOSIS OF EXTRAPULMONARY

TUBERCULOSIS IN ADULTS AND CHILDREN

Extrapulmonary TB (EPTB) can occur at any age.Young children and HIV-

positive adults are particularly susceptible.Up to 25% of TB cases may

present with EPTB.Children of less than 2 years of age are at risk of

disseminated disease causing miliary TB or TB meningitis.The common

forms of extrapulmonary TB associated with HIV are the following:

lymphadenopathy,pleural effusion, pericardial disease, miliary TB, and

meningitis. Many patients with extrapulmonary TB also have coexistent

pulmonary TB.

5.1 DIAGNOSTIC APPROACH

Definitive diagnosis of extrapulmonary TB is often difficult.Diagnosis

may be presumptive, provided you can exclude other conditions.

Patients usually present with constitutional features (fever,night sweats,

weight loss) and local features related to the site of disease.These local

features are similar in adults and children.The degree of certainty of

diagnosis depends on the availability of diagnostic tools,e.g. specialized

X-rays,ultrasound, biopsy.

5.2 TUBERCULOUS LYMPHADENOPATHY

Regardless of HIV status,the lymph nodes most commonly involved are

the cervical nodes.The usual course of lymph node disease is as follows:

firm,discrete fluctuant nodes skin breakdown, healing with

nodes

→matted together → abscesses, → scarring

chronic sinuses

PRACTICAL POINT

If a patient has extrapulmonary TB,look for pulmonary TB.

If the patient has had a productive cough for more than 2 or

3 weeks,send sputum samples for AFB. If testing AFBs the

test is negative,do a CXR.

PRACTICAL POINT

In severely immunocompromised patients,tuberculous

lymphadenopathy may be acute and resemble acute

pyogenic lymphadenitis.

In adults, the differential diagnosis of tuberculous lymphadenopathy

includes the following: persistent generalized lymphadenopathy (PGL),

lymphoma,Kaposi sarcoma, carcinomatous metastases,sarcoid, and drug

reactions (e.g.phenytoin).

Lymphoid interstitial pneumonitis (LIP) is often associated with PGL in

HIV-infected children. LIP may be confused with TB as chronic

respiratory symptoms are very common.The lymphadenopathy with LIP

is characteristically generalized, symmetrical, mobile,non-tender, firm

and non-fluctuant. Differential diagnoses of focal lymphadenopathy in

children include bacterial or pyogenic adenitis and lymphoma (e.g.

Burkitt lymphoma).

Persistent generalized lymphadenopathy (PGL)

PGL is a feature of HIV infection which develops in up to 50% of HIV-

infected individuals.It is of no prognostic significance.There is no specific

treatment.The diagnostic criteria for PGL are as follows: lymph nodes

larger than

1 cm in diameter

in 2 or more extra-inguinal sites

for 3 or more months.

The nodes are non-tender,symmetrical, and often involve the posterior

cervical and epitrochlear nodes. PGL may slowly regress during the

course of HIV infection and may disappear before the onset of AIDS.In

populations with a high HIV prevalence,PGL is the commonest cause of

lymphadenopathy.In HIV-positive individuals PGL is a clinical diagnosis.

Only investigate further if there are features of another disease.The

features of lymph nodes that indicate a need for further investigation,

including biopsy,are:

large (> 4 cm diameter) or rapidly growing lymph nodes

asymmetrical lymphadenopathy

tender/painful lymph nodes not associated with local infection

matted/fluctuant lymph nodes

obvious constitutional features (e.g.fever,night sweats, weight loss)

hilar or mediastinal lymphadenopathy on CXR.

DIAGNOSIS OF EPTB IN ADULTS AND CHILDREN

Practical approach to investigation of lymphadenopathy

(if clinical features suggest a cause of lymphadenopathy other than PGL).

Diagnosis of tuberculous lymphadenopathy is possible even without

laboratory facilities for histology or TB culture.Diagnostic sensitivity of

tuberculous lymphadenopathy by aspirate and smear for AFB is 70%.

Diagnostic sensitivity increases to 80% if you excise a lymph node,look

at the cut surface,and do a smear for AFB.

The histological appearance of tuberculous lymph nodes from HIV-

positive patients depends on the degree of immunocompromise, as

shown below.

TB/HIV:A CLINICAL MANUAL

Procedure Test Result Diagnosis

look at material

➝ caseation ➝ TB

aspirated

needle smear for

➝ AFB present ➝ TB

aspirate AFB

of lymph

node smear for

➝ malignant ➝ malignancy

cytology cells seen e .g.KS,

lymphoma,

carcinoma

if no diagnosis after aspirate

look at cut

➝ caseation ➝ TB

surface

smear from cut

➝ AFB seen ➝ TB

surface for AFB

lymph

node fresh node

➝ positive ➝ TB

biopsy sent for TB culture

TB culture

node in

➝ granuloma ➝ TB

formalin and AFB

for histology

malignant

➝ malignancy

cells

➝

Degree of Histological appearance of

immunocompromise lymph nodes

mild caseating lesions with few or no AFB

severe little cellular reaction with many AFB

5.3 MILIARY (DISSEMINATED) TB

Miliary TB results from widespread bloodborne dissemination of TB

bacilli.This results from either a recent primary infection or the erosion

of a tuberculous lesion into a blood vessel.

Clinical features

Patients present with constitutional features rather than respiratory

symptoms.They may have hepatosplenomegaly and choroidal tubercles

(fundoscopy). Often the presentation is associated with fever of

unknown origin and wasting may be marked. Miliary TB is an

underdiagnosed cause of end-stage wasting in HIV-positive individuals.A

high index of suspicion is necessary.

Diagnosis

CXR shows diffuse, uniformly distributed, small miliary shadows.

"Miliary" means "like small millet seeds".The CXR can appear normal in

advanced cases because of severe immunosuppression and therefore

inability to mount an inflammatory response.Full blood count may show

pancytopenia. Liver function tests may be abnormal. Bacteriological

confirmation (smears or mycobacterial culture) is sometimes possible

from sputum,cerebrospinal fluid, bone marrow,liver or blood.

Differential diagnosis

The differential diagnosis includes the following:the syndrome of HIV

wasting disease (sometimes referred to as “slim disease”),bacteraemia

(including typhoid fever),disseminated carcinoma,disseminated infection

with "atypical" mycobacteria,trypanosomiasis (in endemic regions) and

connective tissue diseases.

The typical diffuse CXR abnormalities can be confused with those of LIP

in children. The table below lists features that help to differentiate

miliary TB from LIP.However, there is clinical overlap as LIP presents

with a broad range of clinical and radiographic features, which vary

depending on the stage of HIV disease.

DIAGNOSIS OF EPTB IN ADULTS AND CHILDREN

TB/HIV:A CLINICAL MANUAL

Clinical differentiation of miliary TB from LIP in children

5.4 TUBERCULOUS SEROUS EFFUSIONS (PLEURAL,

PERICARDIAL,ASCITES)

Inflammatory tuberculous effusions may occur in any of the serous

cavities of the body,i.e.pleural, pericardial or peritoneal cavities.They are

more common in HIV-positive than in HIV-negative adults,and also

occur in school-aged children with or without HIV infection. Serous

effusions are often indicative of primary disease or reinfection.

Approach to diagnosis

The presentation is usually with constitutional and local features.

Microscopy of the aspirate from tuberculous serous effusions rarely

shows AFB because the fluid forms as an inflammatory reaction to TB

lesions in the serous membrane.TB culture, even if available, is of no

immediate help.A culture result usually takes 4-6 weeks.The white cell

content is variable,usually with predominant lymphocytes and monocytes.

The aspirate is an exudate (i.e.protein content is more than 30 g/l).

Miliary TB LIP

Clinical features:

Respiratory symptoms -/+ +++

Persistent fever ++ ++

Wasting +++ -/+

Generalized lymphadenopathy -/+ +++

Parotid enlargement - ++

Clubbing - +

Hepatomegaly ++ ++

CXR features:

Diffuse micronodular ++ +

Diffuse reticular - ++

Lymphadenopathy -/+ ++

PRACTICAL POINT

A biochemistry laboratory is not essential to diagnose an

exudate.Simply leave the aspirate standing: if “spider clots”

develop in the specimen,it is an exudate.

In populations in sub-Saharan Africa with high HIVprevalence,TB is the

commonest cause of an exudative serous effusion.The diagnosis is

usually presumptive (i.e. without microbiological or histological

confirmation).It is important to exclude other causes of an exudate.

Tuberculous pleural effusion

The clinical and CXR diagnosis of a pleural effusion is straightforward.

The typical clinical features are constitutional and local (chest pain;

breathlessness;tracheal and mediastinal shift away from the side of the

effusion;decreased chest movement,dull percussion note and decreased

breath sounds on the side of the effusion). CXR shows unilateral,

uniform white opacity,often with a concave upper border. If available,

ultrasound can confirm the presence of fluid in the pleural space in case

of doubt.

Always perform diagnostic pleural aspiration if a patient has a pleural

effusion. The fluid is usually straw-coloured.The white cell count is

usually high (about 1000–2500 per mm

) with predominant

lymphocytes.Occasionally the fluid is blood-stained.The presence of pus

on aspiration indicates an empyema (purulent effusion).

If facilities are available,closed pleural biopsy using an Abrams needle is

useful for histological diagnosis.Since the distribution of TB lesions in the

pleura is patchy,the diagnostic yield of closed pleural biopsy is about

75%.Multiple biopsies increase the diagnostic yield. A small open pleural

biopsy increases the yield even further but is not usually necessary.

Differential diagnosis

The differential diagnosis of an exudative pleural effusion includes

DIAGNOSIS OF EPTB IN ADULTS AND CHILDREN

PRACTICAL POINT

Interpret with caution the laboratory result of protein

concentration in any aspirated fluid. If there has been a

delay in laboratory analysis,a protein clot may have formed

in the sample.The laboratory result may then be falsely low.

PRACTICAL POINT

In a hospital with limited facilities serving a population with

high TB prevalence, patients with a unilateral exudative

pleural effusion that has not responded to a full course of

antibiotics should be treated with anti-TB drugs.

TB/HIV:A CLINICAL MANUAL

malignancy,post-pneumonic effusion, pulmonary embolism and amoebic

liver abscess (extending on the right).

Tuberculous empyema

This usually arises when a tuberculous cavity in the lung ruptures into

the pleural space.The physical signs are those of a pleural effusion, but

aspiration reveals thick white or yellow pus.If the pus is too thick to

remove using a needle and syringe,use an intercostal drain.Send the pus

to the laboratory for examination for TB and also for Gram stain and

bacterial culture.If facilities are available, closed pleural biopsy is useful

for histological diagnosis.

The main differential diagnosis is bacterial empyema,when the patient is

usually more acutely ill and toxic.It may be possible to confirm bacterial

empyema by Gram stain or culture of the aspirated pus.

A succussion splash is a splashing sound heard with the stethoscope

while shaking the patient's chest. A succussion splash indicates a

pyopneumothorax (pus and air in the pleural space). After CXR

confirmation,insert a chest drain with underwater seal.

Tuberculous pericardial effusion

Diagnosis

The diagnosis usually rests on suggestive constitutional and

cardiovascular features and investigation findings (ECG, CXR and

echocardiography). It is important to exclude uraemia and Kaposi

sarcoma.

Cardiovascular symptoms

chest pain

shortness of breath

cough

dizziness and weakness (low cardiac output)

leg swelling

right hypochondrial pain (liver congestion)

abdominal swelling (ascites)

PRACTICAL POINT

Always test a patient with signs of a pleural effusion for a

succussion splash.

Cardiovascular signs

tachycardia

low blood pressure

pulsus paradoxus

raised jugular venous pressure (JVP) with small amplitude "a" and "v"

waves

impalpable apex beat

quiet heart sounds

pericardial friction rub

signs of right-sided heart failure (e.g.hepatomegaly, ascites,oedema)

CXR

large globular heart

clear lung fields

pleural fluid

ECG

tachycardia

ST and T wave changes

low voltage QRS complexes

sometimes electrical alternans (alternating positive and negative R

waves, reflecting a heart that moves with each beat within the

pericardial fluid)

Echocardiography

pericardial fluid

strands crossing between visceral and parietal pericardium

Pitfalls in diagnosis of pericardial effusion

Clinicians have misdiagnosed pericardial effusion as the following:

congestive cardiac failure;

hepatoma or amoebic liver abscess (enlarged liver);

bilateral pleural effusions.

Pericardiocentesis

This is only safe under the following conditions:

a) echocardiography has confirmed a moderate to large pericardial

effusion;

b) the operator is experienced.

DIAGNOSIS OF EPTB IN ADULTS AND CHILDREN

PRACTICAL POINT

The signs may be subtle.Assess carefully any patient with

oedema or ascites with the possibility of pericardial effusion

in mind.

TB/HIV:A CLINICAL MANUAL

Therapeutic pericardiocentesis is necessary if there is cardiac

tamponade (acute life-threatening cardiac impairment).

Treatment with steroids and anti-TB drugs,without pericardiocentesis,

usually results in satisfactory resolution of tuberculous pericardial

effusion.

Outcome

A possible complication despite TB cure is the development of

pericardial constriction. Medical management of heart failure due to

pericardial constriction helps in some cases. A surgeon may weigh up

the possible benefit to the patient of pericardiectomy,set against the

operative risks.

Differential diagnosis

Apart from TB,the differential diagnosis of pericardial effusion includes

the following:

transudates: uraemia,heart failure, liver failure, hypothyroidism;

exudates: malignancy, bacterial pericardial empyema, inflammatory

diseases.

Tuberculous ascites

Ascites results from peritoneal TB.Routes of spread of TB to the

peritoneum include the following:

a) from tuberculous mesenteric lymph nodes;

b) from intestinal TB (pulmonary TB patients may develop intestinal

ulcers and fistulae as a result of swallowing infected sputum);

c) bloodborne.

Clinical features

Patients present with constitutional features and ascites.Marked wasting

is common in children.Signs of other causes of ascites such as nephrotic

syndrome (peripheral and periorbital oedema) or portal hypertension

(marked splenomegaly) are usually absent. There may be palpable

abdominal masses (mesenteric lymph nodes). Adhesion of nodes to

PRACTICAL POINT

In populations with high TB/HIV prevalence,TB is the most

likely treatable cause of pericardial effusion.It may be safer

for the patient to start presumptive anti-TB treatment than

to undergo diagnostic pericardiocentesis.

bowel may cause bowel obstruction. Fistulae may develop between

bowel,bladder and abdominal wall.

Investigations

Do a CXR to look for associated PTB.Always do a diagnostic ascitic tap.

The aspirated fluid is usually straw-coloured,but occasionally turbid or

blood-stained.The fluid is an exudate, usually with more than 300 white

cells per mm

and predominantly lymphocytes.Ultrasound, if available,

may show features consistent with TB,including enlarged mesenteric or

retroperitoneal lymph nodes.

Diagnosis

The diagnosis is usually presumptive. Definitive diagnosis rests on a

peritoneal biopsy,available in some hospitals.Blind percutaneous needle

biopsy of the peritoneum has a low pick-up rate and a high complication

rate. In experienced hands, laparoscopy under local anaesthetic has a

high pick-up rate.Laparoscopy enables direct visualization and biopsy of

peritoneal TB lesions. Laparotomy will confirm the diagnosis in nearly

every case but is too invasive for routine use.

Differential diagnosis

Apart from TB,the differential diagnosis of ascites includes the following:

transudates: heart failure, renal failure, nephrotic syndrome, chronic

liver disease due to cirrhosis, hepatosplenic schistosomiasis,

hypoproteinaemia;

exudates: malignancy,other infections causing peritonitis.

5.5 TUBERCULOUS MENINGITIS

Routes of spread of TB to the meninges include the following:

a) from rupture of a cerebral tuberculoma into the subarachnoid space;

b) bloodborne.

DIAGNOSIS OF EPTB IN ADULTS AND CHILDREN

PRACTICAL POINT

An ill,wasted patient with TB ascites may have a low serum

albumin concentration. In this case,the usual threshold of

30 g/l albumin concentration for diagnosing an exudate is

too high. Instead, calculate the difference between the

albumin concentrations in serum and ascites. A

serum–ascites albumin difference of less than 11 g/l means

that the ascites is an exudate.

TB/HIV:A CLINICAL MANUAL

Clinical features

The patient may present with constitutional features and chronic

meningitis. There is gradual onset and progression of headache and

decreased consciousness.Examination often reveals neck stiffness and a

positive Kernig's sign.Cranial nerve palsies result from exudate around

the base of the brain.Tuberculomas and vascular occlusion may cause

focal neurological deficits and seizures.Obstructive hydrocephalus may

develop. Spinal meningeal involvement causes paraplegia (spastic or

flaccid).

Diagnosis

The diagnosis usually rests on clinical grounds and cerebrospinal fluid

(CSF) examination. In most cases of clinically suspected TB meningitis,

lumbar puncture is safe.

The CSF opening pressure is high. The CSF may look clear or

occasionally cloudy.The white cell count is usually less than 500 per mm

with predominantly lymphocytes (or early in the course of infection,

predominantly polymorphs). Usually the protein level is high and the

glucose low.CSF microscopy shows AFBs in a minority of cases. It is

possible to increase the diagnostic pick-up rate by the following:

a) examine the deposit on centrifugation of a 10 ml CSF sample;

b) examine the deposit for at least half an hour before reporting it as

negative;

c) examine several CSF samples obtained over a few days.

PRACTICAL POINT

Lumbar puncture is hazardous if the patient has a focal

neurological deficit (cerebral space-occupying lesion) or if

fundoscopy shows papilloedema (raised intracranial

pressure).In these circumstances,a CT brain scan is helpful,

if available.Otherwise, it may be safer to start presumptive

treatment with anti-TB drugs rather than risk lumbar

puncture.

PRACTICAL POINT

Lumbar puncture is important for differentiating purulent

from TB meningitis.Always exclude cryptococcal meningitis

by CSF microscopy (India ink stain) and,if available, fungal

culture.

Difficulties in interpreting CSF findings

Some of the CSF findings may be normal, especially in HIV-positive

patients.The percentages of HIV-positive TB meningitis patients with

normal CSF findings are as follows:glucose 15%, protein 40%,white cell

count 10%.

Differential diagnosis

The table below shows the differential diagnosis of TB meningitis,with

typical CSF abnormalities.

Differential diagnosis of tuberculous meningitis

PMN = polymorphonuclear leukocytes;L = lymphocytes

* common differential diagnosis

CSF abnormalities

Disease White Protein Glucose Microscopy

cells

tuberculous Elevated Increased Decreased AFB

meningitis L > PMN (in some cases)

cryptococcal Elevated Increased Decreased Positive India

meningitis* L > PMN ink staining

partially Elevated Increased Decreased

Bacteria on Gram

treated stain (rarely)

bacterial

meningitis*

viral Elevated Increased Normal

meningitis L > PMN

(low in mumps

or H.simplex)

acute Elevated Increased Normal

syphilis L > PMN

late stage Elevated Increased Decreased Motile

trypanosomiasis L > PMN trypanosomes

tumour Elevated Increased Decreased Cytology shows

(carcinoma/ L > PMN malignant cells

lymphoma)

leptospirosis Elevated Increased Decreased Leptospires

L > PMN

amoebic Elevated Increased Decreased Amoebae

meningitis L > PMN

DIAGNOSIS OF EPTB IN ADULTS AND CHILDREN

TB/HIV:A CLINICAL MANUAL

5.6 OTHER FORMS OF EXTRAPULMONARY TB

Other forms of extrapulmonary TB are less common.There is no

information as to whether they occur any more frequently in HIV-

positive than in HIV-negative individuals.The table below shows the

usual clinical features and diagnostic tests.

Site of disease Clinical features Diagnosis

Spine Back pain Plain X-ray

Gibbus Tissue biopsy

Psoas abscess

Radicular pain

Spinal cord compression

Bone Chronic osteomyelitis Tissue biopsy

Peripheral joints Usually monoarthritis Plain X-ray

especially hip or knee Synovial biopsy

Gastrointestinal Abdominal mass Barium X-ray

Diarrhoea

Liver Right upper quadrant Ultrasound and

pain and mass biopsy

Renal and urinary Urinar y frequency Sterile pyuria

tract Dysuria Urine culture

Haematuria Intravenous

Loin pain/swelling pyelogram

Ultrasound

Adrenal gland Features of Plain X-ray

hypoadrenalism (calcification)

(hypotension, Ultrasound

low serum sodium,

normal/high potassium,

raised urea,low glucose)

Upper respiratory Hoarseness and stridor Usually complication

tract Pain in ear of pulmonary disease

Pain on swallowing

Female genital tract Infertility Pelvic examination

Pelvic inflammatory X-ray genital tract

disease Ultrasound pelvis

Ectopic pregnancy Tissue biopsy

Male genital tract Epididymitis Often evidence of

renal/urinary tract TB

DIAGNOSIS OF EPTB IN ADULTS AND CHILDREN

5.7 FURTHER INFORMATION ON SPINAL,

GASTROINTESTINAL AND HEPATIC TB

Spinal TB

TB of the spine is important.The disastrous consequence for the patient

of a missed diagnosis of thoracic or cervical spinal TB is paralysis.TB

starts in an intervertebral disc and spreads along the anterior and

longitudinal ligaments, before involving the adjacent vertebral bodies.

Where TB is common,plain X-ray of the spine is usually diagnostic.The

typical appearance is erosion of the anterior edges of the superior and

inferior borders of adjacent vertebral bodies. The disc space is

narrowed.The sites most commonly involved are the lower thoracic,

lumbar and lumbosacral areas.

The main differential diagnoses are malignancy and pyogenic spinal

infections.Malignant deposits in the spine tend to erode the pedicles and

spinal bodies,leaving the disc intact. Pyogenic infection tends to be more

acute than TB,with more severe pain.

Gastrointestinal TB

Ileocaecal TB may present with constitutional features, chronic

diarrhoea, subacute obstruction, or a right iliac fossa mass.Diagnosis

rests on barium examination of the small and large bowel, or on

colonoscopy, if available.The differential diagnosis includes ileocaecal

Crohn disease,carcinoma of the caecum, appendix abscess, lymphoma,

amoeboma and tubo-ovarian abscess.

Hepatic TB

Miliary TB may involve the liver. Hepatic TB can cause diagnostic

confusion. Solitary or multiple TB abscess formation can mimic amoebic

liver abscess. Nodular hepatic TB can mimic hepatoma. In these

situations, ultrasound examination is useful.Liver biopsy, available in

some hospitals,is diagnostic.

TB/HIV:A CLINICAL MANUAL

SUGGESTIONS FOR FURTHER READING

Crofton J, Horne N, Miller F.Clinical tuberculosis. second edition. London,

MacMillan Press Limited,1999.

Donald PR, Fourie PB, Grange JM. Tuberculosis in childhood.Pretoria, JL van

Schaik,1999.

Harries AD,Maher D,Nunn P.An approach to the problems of diagnosing and

treating adult smear-negative pulmonary tuberculosis in high HIV prevalence

settings in sub-Saharan Africa.Bulletin of the World Health Organization, 1998,

76, (6):651-662.

Maher D, Harries AD.Tuberculous pericardial effusion:a prospective clinical

study in a low-resource setting – Blantyre, Malawi. International Journal of

Tuberculosis lung Disease,1997, 1 (4): 358-364.

Miller FJW.Tuberculosis in children. New Delhi,Churchill-Livingstone ,1986.

Toman’s tuberculosis case detection, treatment and monitoring:questions and

answers.Edited by T Frieden, second edition. World Health Organization,

Geneva,2004. ISBN 92 4 154603 4.(WHO/HTM/TB/2004.334).

TB/HIV:A CLINICAL MANUAL

DIAGNOSIS OF HIV INFECTION IN ADULTS

WITH TUBERCULOSIS

6.1 CLINICAL RECOGNITION OF HIV INFECTION IN

TB PATIENTS

In many TB/HIV patients in sub-Saharan Africa,the only HIV-related

illness present is TB. However, certain clinical features are more

common in HIV-positive TB patients than in HIV-negative TB patients.

The table below shows the clinical features that suggest possible HIV

infection.

Clinical features suggestive of HIV coinfection in TB patients

Past

sexually transmitted infection (STI)

history

herpes zoster (shingles),which often leaves a scar

recent or recurrent pneumonia

severe bacterial infections

(sinusitis,bacteraemia, pyomyositis)

recent treated TB

Symptoms

weight loss (> 10 kg or > 20% of original weight)

diarrhoea (> 1 month)

retrosternal pain on swallowing

(suggests oesophageal candidiasis)

burning sensation of feet

(peripheral sensory neuropathy)

Signs

scar of herpes zoster

pruritic (itchy) papular skin rash

Kaposi sarcoma

symmetrical generalized lymphadenopathy

oral candidiasis

angular cheilitis

oral hairy leukoplakia

necrotizing gingivitis

giant aphthous ulceration

persistent painful genital ulceration

PRACTICAL POINT

Always look in the mouth of any patient. Many mouth

lesions are highly suggestive of HIV infection,and others are

pathognomonic.

The definitive diagnosis of HIV infection rests on a positive HIV test.

6.2 HIV TESTING

HIV infection is usually diagnosed through detection of antibodies to the

virus. Production of these antibodies usually begins 3–8 weeks after

infection.The period following infection but before antibodies become

detectable is known as the “window period”.Diagnosis of HIV infection

is also possible through detection of the virus (p24 antigen,nucleic-acid

based tests or culture).

6.2.1 HIV antibody tests

The most widely available way of identifying HIV-infected individuals is

the detection of HIV antibodies in serum or plasma samples.The table

below shows the two main methods of testing for HIV antibodies.

Serological tests are available that test for both HIV-1 and HIV-2.The

technical details of these tests are beyond the scope of this manual.HIV

diagnostic tests are extremely reliable, and are highly sensitive and

specific. The reliability of test results depends on proper sample

collection and testing. The staff taking the sample must label the

specimen bottle and the form accurately.High quality performance of

tests by laboratory staff is crucial.

Advantages and disadvantages of HIV antibody tests

DIAGNOSIS OF HIV IN ADULTS WITH TB

PRACTICAL POINT

Full blood count (FBC) findings suggestive of HIV infection

are unexplained anaemia,leukopenia or thrombocytopenia.

HIV testing Advantages Disadvantages

method

EIA

less expensive than

some specialized

(formerly known immunoblot laboratory equipment

as ELISA)

large numbers of sera necessary

can be tested daily

skilled technical staff

sensitive and specific

steady power supply

a whole kit

(90–100 samples)

has to be used

TB/HIV:A CLINICAL MANUAL

EIA

The usual type of test for HIV antibodies is the enzyme immunoassay

(EIA). EIAs are probably the most efficient tests for testing large

numbers of samples per day,as in large blood banks or for surveillance

studies.The cost per individual EIA is about US$ 0.75–1.75.

Simple/rapid tests

Several antibody tests can equal the performance of EIA and do not

need special equipment or highly trained staff. These tests are

considered rapid if they take less than 10 minutes and simple if they take

longer.There are four types of assay:agglutination, comb/dipstick, flow-

through membrane and lateral flow membrane. In most formats,the

appearance of a clearly visible dot or line indicates a positive result.Many

of the tests have an internal control sample,which validates each test

run.Test kits are relatively expensive at US$ 1–2 per test.

Tests not using plasma or serum

Tests are available that can use whole blood,dried blood spots,saliva or

urine. They are much more user-friendly than those that require

traditional blood sampling by venepuncture.The level of antibodies in

these specimens is much lower than in serum or plasma.While useful for

surveillance, a positive result needs to be confirmed for an individual

diagnosis.

6.2.2 Tests to detect the virus itself

The first assays capable of detecting free circulating HIV particles were

the HIV p24 antigen EIAs. Quantitative measurement of plasma HIV

RNA (viral load) have now superseded these EIAs.Measurement of viral

load is based on amplification of viral nucleic acids or of the probe-

binding signal (e.g.branched DNA tests). Results are reported as copies

of virus per ml,and the new generation tests can detect 20–50 copies

per ml. Measurement of viral load is now standard in industrialized

Simple/rapid

simple,rapid

(e.g.rapid

less expensive than

immunobinding immunoblot

assay)

no specialized

equipment necessary

supplied as single-use

tests so individual

specimens can be tested

countries for staging and monitoring response to antiretroviral therapy.

However,several factors have limited their use so far in developing

countries. These include the expense of the complex equipment

necessary and the need for rigorous laboratory conditions, quality

control and highly trained staff.

6.2.3 Objectives of HIV antibody testing in TB patients

There are three possible main objectives in performing HIV antibody

tests in TB patients:

a) individual patient management (HIV testing in individual TB patients);

b) surveillance (anonymous testing to monitor epidemiological trends);

c) research (voluntary testing for epidemiological, clinical,or virological

studies).

6.2.4 Strategy for HIV antibody testing in TB patients

(which tests to use and when to use them)

In general, WHO recommends different HIV testing strategies,

depending on the objective of testing.The aim is to maximize accuracy

and minimize cost.The table below shows the strategy appropriate for

each objective of testing.

Objectives,strategies and interpretation of HIV tests

DIAGNOSIS OF HIV IN ADULTS WITH TB

Objective Testing strategy Interpretation of

result

Individual Test sample with EIA 1st assay negative =

patient or simple/rapid assay patient HIV negative

management or test to be repeated

1st assay positive +

2nd assay positive =

patient HIV-positive

1st assay positive and

2nd assay negative ➝

repeat both assays

Results remain

discordant ➝

repeat sample and testing

Surveillance Test sample with EIA Assay negative =

(in population or simple/rapid assay patient HIV-negative

with HIV

prevalence Assay positive =

> 10%) patient HIV-positive

TB/HIV:A CLINICAL MANUAL

6.2.5 Diagnosis of HIV infection in individual TB patients

The link between HIV and TB is well known to many members of the

public.Patients with TB may therefore be well aware of the possibility of

HIV coinfection.It is impor tant to offer counselling and voluntary HIV

testing,if available, to TB patients.Possible benefits include:

a) patients may want the chance to know their HIV status;

b) better diagnosis and management of other HIV-related illnesses;

c) avoidance of drugs associated with a high risk of side-effects;

d) increased condom use and decreased HIV transmission;

e) possible use of chemoprophylaxis with cotrimoxazole to prevent

opportunistic infections and reduce mortality;

f) possible use of ART for HIV;

g) the opportunity to counsel patients and relatives about HIV

infection and about the prognosis;

h) the opportunity to advise patients and relatives about measures to

prevent further HIV transmission.

It is preferable to have same-day HIV testing using rapid test kits as this

minimizes the number of visits to counselling and testing centres.The

other important issue for clients is confidentiality.

A policy of compulsory HIV testing of TB patients (even if this were

legal) would be counterproductive.This type of policy would have the

following results:

a) patients would be deterred from seeking care;

b) there would be decreased case-finding in at-risk groups;

c) the credibility of health services would be reduced.

6.3 HIV COUNSELLING

HIV voluntary counselling and testing (VCT) starts with counselling of

individuals to enable them to make an informed choice about HIV

testing.This decision is entirely the choice of the individual,who must be

assured that the process will be confidential.Confidential counselling is

essential before and after HIV antibody testing.Individuals give explicit

informed consent to have the test.This means that they understand

what the test involves and the implications of testing.The counsellor

PRACTICAL POINT

Anti-TB drug treatment is the same for HIV-positive and

HIV-negative TB patients,with one exception: do not give

thioacetazone to HIV-positive TB patients (increased risk of

severe and sometimes fatal skin reactions).

provides support.Counselling is a dialogue between the individual and

the counsellor.

Counsellors

With suitable training,anyone who works with patients and families can

be a counsellor.Counsellors may be members of the community or

health workers. For sustainability of VCT services, counsellors need

support and supervision. Many health workers have had counselling

training. In the course of their duties they have the opportunity to

counsel patients for HIV testing.Doctors and other clinicians are often

in a good position to counsel patients for HIV testing.This is because

clinicians have already established a relationship with the patient,who

usually trusts the clinician.

Pretest counselling

The aim is to enable people to make an informed decision to have the

test or not.People need to know what the test involves and what are

the implications of the result.Together the counsellor and the person

considering being tested assess the person’s: a) likelihood of having

acquired HIV infection,b) knowledge about HIV, and c) ability to cope

with a positive result.

a) Assessment of risk

multiple sex partners

of having acquired

sex with commercial sex workers

HIV infection

for men,sex with other men

nonsterile skin piercing,e.g. scarification,

tattooing

previous blood transfusion

intravenous drug use

sexual partner/spouse of person at risk

b)Assessment of

what does the test involve and mean?

knowledge about HIV

how does HIV transmission occur?

what is high-risk behaviour?

c) Assessment of

person's expected reaction to result

ability to cope with

who will provide emotional support?

result

impact of a positive result on

- relationships

- social issues,e.g. employment

- future health

PRACTICAL POINT

In high HIV-prevalence regions,anyone with TB is in a high-

risk group for HIV.

DIAGNOSIS OF HIV IN ADULTS WITH TB

TB/HIV:A CLINICAL MANUAL

Post-test counselling

The content of post-test counselling depends on the HIV test result.The

aims are to discuss the result,share information, provide support, and

encourage future safe sexual behaviour.Always ensure confidentiality.

Break the news openly and sympathetically.When someone has a

positive HIV test result, common reactions at different times may

include shock, anger, guilt, grief and depression. People will need

continuing support.

Issues for discussion when the HIV test result is negative

If the person has recently indulged in high-risk behaviours,then he or

she could still be incubating HIV (i.e.the test could be in the "window

period").

Avoidance of unsafe sexual behaviour.

Promotion of healthy behaviour.

Issues for discussion when the HIV test result is positive

General health (good diet, balance of rest and exercise, avoiding

infections,when to seek advice about symptoms of other HIV-related

illnesses).

Avoidance of preganancy.

Awareness of possible anti-TB drug side-effects.

A positive result is an entry point to medical care of HIV-related

diseases, to chemoprophylaxis for opportunistic infections and

possibly to ART.

Safe sexual behaviour.

Avoidance of blood or organ donation.

The person's reaction to the test result.

Emotional and psychological support for the person.

How to tell friends,family and sexual partners.

Counselling of partner(s) if possible.

Referral to local community services and support groups,if available.

º Social implications, e.g. employment,life assurance.

DIAGNOSIS OF HIV IN ADULTS WITH TB

SUGGESTIONS FOR FURTHER READING

UNAIDS policy on HIV testing and counselling. Geneva,Joint UN Programme on

HIV/AIDS,1997.

UNAIDS Technical Update. HIV testing methods. Joint UN Programme on

HIV/AIDS,Geneva, 1997,UNAIDS Best Practice Collection.

Joint UN Programme on HIV/AIDS,World Health Organization. Operational

characteristics of commercially available assays to determine antibodies to HIV-1

and/or HIV-2 in human sera. Report 11. Geneva, 1999. WHO/BTS/99.1;

UNAIDS/99.5.

UNAIDS Technical Update.Voluntary counselling and testing (VCT).Geneva, 2000,

Joint UN Programme on HIV/AIDS,Best Practice Collection.

Volberding PA. HIV quantification:clinical applications. Lancet, 1996, 347:71-73.

World Health Organization. Revised recommendations for the selection and

use of HIV antibody tests.Weekly epidemiological record, 1997, 72: 81–83.

World Health Organization.The importance of simple and rapid tests in HIV

diagnostics:WHO recommendations. Weekly epidemiological record, 1998, 73:

321–328.

World Health Organization. Increasing access to knowledge of HIV status:

conclusions of a WHO consultation,3–4 December 2001,WHO/HIV/2002.09.

World Health Organization. Testing and counselling. Geneva, 2002

http://www.who.int/hiv/topics/vct/testing(accessed 8 May 2003).

TB/HIV:A CLINICAL MANUAL

DIAGNOSIS OF HIV INFECTION IN CHILDREN

WITH TUBERCULOSIS

7.1 CLINICAL RECOGNITION OF HIV INFECTION IN

CHILDREN WITH TB

HIV infection in children may show in many ways.The clinical signs are

often not specific for HIV infection.For example, weight loss, fever and

cough are common in TB,with or without HIV infection. The clinical

definition of HIV infection is therefore difficult.

WHO has developed a clinical staging system for HIV infection and HIV-

related disease (see Chapter 1).The main uses are for prognosis and for

deciding when to start antiretroviral therapy.The features of paediatric

HIV/AIDS are not very specific in developing countries where childhood

malnutrition is common and TB is endemic. Severe malnutrition or

wasting in a school-aged child or in a child from a well-nourished family

is unlikely to be due simply to poor intake. This should raise the

suspicion of underlying disease,e.g. HIV or TB or both.The table below

lists clinical signs suggestive of HIV infection. Many are more specific

than those in the WHO clinical staging system but are less sensitive.In

other words, the presence of a particular sign strongly suggests HIV

infection, but many children have HIV infection without that sign.The

interpretation of clinical signs also depends on local patterns of disease.

For example, splenomegaly is commonly caused by malaria in sub-

Saharan Africa,where its specificity as a sign of HIV-related disease is

therefore low.

Clinical signs suggestive of HIV infection in children

Common failure to thrive in a breastfed infant before 6 months

of age

recurrent bacterial infections

generalized symmetrical lymph node enlargement

extensive oropharyngeal candidiasis

suppurative otitis media in a breastfed infant

generalized rash e.g.itchy papular rash, extensive

molluscum contagiosum

PRACTICAL POINT

Parents provide important clues to possible HIV infection in

their children. Ask the parents about their health.

Sometimes parents may reveal their own HIV status.

100

DIAGNOSIS OF HIV IN CHILDREN WITH TB

extensive fungal skin,nail and scalp infections

bilateral non-tender parotid gland enlargement

finger clubbing

enlarged non-tender liver with no apparent cause

splenomegaly (in non-malarious areas)

persistent severe anaemia

Less recurrent abscesses or deep tissue necrosis

common recurrent herpes simplex

KS lesions

shingles in more than one dermatome

developmental regression

acquired rectovaginal fistula

Many of these signs are strongly suggestive of HIV. However, no

particular sign is diagnostic and confirmation is necessary by HIV testing.

7.2 HIV TESTING

The usual HIV test is one that detects antibodies to HIV in the blood.

Rarely,a single HIV test for an individual person may not be reliable.The

usual recommendation in diagnosing HIV infection is therefore to

perform two tests.Both tests should be positive for a diagnosis of HIV

infection.

A positive HIV antibody test is not a reliable indicator of HIV infection

in infants. During the pregnancy of a woman with HIV infection,

antibodies to HIV cross the placenta.Therefore almost all children born

to HIV-positive mothers have HIV antibodies in their blood at birth.

However,only about one-third of children born to HIV-infected mothers

are infected.Initially, therefore, HIV antibody testing cannot distinguish

uninfected from infected children.In uninfected children, these maternal

antibodies usually become undetectable by 9 months of age, but

occasionally they remain detectable until 15 months. Most infected

children make their own antibodies,so the HIV antibody test will still be

positive after 15 months.

PRACTICAL POINT

In children under 15 months of age, the diagnosis of HIV

infection rests on clinical features and a positive HIV test in

the mother.

101

TB/HIV:A CLINICAL MANUAL

7.3 COUNSELLING

A child with suspected HIV generally means a family with suspected HIV.

Counselling therefore has to take into consideration the mother and,if

possible,the father.Until recently there have been few specific treatment

options to offer the child and family when a child tests HIV-positive.This

has made raising the issue of testing difficult. However,the increasing

availability of antiretroviral treatment is likely to encourage HIV testing.

Also,parents often want to know the cause of their child’s illness. See

Chapter 6 for the issues for discussion with adults with suspected HIV.

Pretest counselling

It is important to counsel the mother before testing her child for HIV.

Her consent is necessary before testing her blood (if the child is under

18 months) or the child's blood (if the child is over 18 months) for HIV.

If her child tests HIV-positive,then it is extremely likely that she is the

source of infection and is HIV-positive.

Consider the implications for the mother when she hears that her child

may have HIV infection:

º her child may have an incurable and fatal disease;

º she herself may have HIV;

º her husband may have HIV;

º any future children may have HIV.

Her decision to have a test or not is difficult.She will need time and

support while she considers the advantages and disadvantages of a test.

If she knows she is HIV-positive,the main advantage is that she can plan

for the future.On the other hand, she may be fearful that her husband

will beat her or leave her if she tells him that she is HIV-positive.She may

also be concerned that if her child tests positive,the health workers will

no longer provide good care for her child.

Post-test counselling

Chapter 6 lists the issues for discussion relevant to anyone who tests

HIV-positive.There are other issues specific to a mother who tests HIV-

PRACTICAL POINT

The mother may like to bring her husband for joint pretest

counselling. It is usually easier for a woman to tell her

husband she may be HIV-positive than to tell him afterwards

that she is HIV-positive.

102

DIAGNOSIS OF HIV IN CHILDREN WITH TB

positive.These include the poor outlook for the child and the risk of

future babies being HIV-infected.About one-third of children born to

HIV-positive women are also HIV-infected (in the absence of

interventions to prevent mother-to-child transmission).

When counselling women who are breastfeeding or who have delivered

recently,it is impor tant to discuss breastfeeding.There is risk of HIV

transmission by breastfeeding.However, in many low-income countries,

breastfeeding is still a safer alternative to bottle-feeding.For example, a

child whose mother is HIV-positive and who lives in an environment

where there is no clean water is probably at higher risk of dying from

diarrhoea if bottle-fed than from AIDS if breastfed.

It is also important to consider PCP prophylaxis with cotrimoxazole for

infants born to an HIV-infected mother.PCP is a very common cause of

death in HIV-infected infants especially before 6 months of age.The

recommended cotrimoxazole dosage for PCP prophylaxis is 150 mg

TMP/750 mg SMX per m

/day given 3 times per week.Thus,appropriate

dosage for infants 2–6 months (usually 3–6 kg) would be 40 mg TMP/200

mg SMX once a day three times per week.If only cotrimoxazole tablets

are available,then give half a crushed tablet (80 mg TMP/400 mg SMX)

on Monday,Wednesday and Friday.

103

TB/HIV:A CLINICAL MANUAL

SUGGESTIONS FOR FURTHER READING

Lepage P,Spira R, Kalibala S, et al. Care of human immunodeficiency virus-

infected children in developing countries.The pediatric infectious disease journal,

1998,17: 581–586.

Marum LH,Tindyebwa D,Gibb D.Care of children with HIV infection and AIDS

in Africa.AIDS, 1997, 11 (Supplement B):S125-S134.

Joint UN Programme on HIV/AIDS. Provisional WHO/UNAIDS Secretariat

recommendations on the use of cotrimoxazole prophylaxis in adults and children

living with HIV/AIDS in Africa.Geneva, 2000.(Available at http://www.unaids.org).

Temmerman M,Ndinya-Achola J, Ambani J,Piot P.The right not to know HIV-

test results.Lancet, 1995, 345: 969–970.

Joint United Nations Programme on HIV/AIDS, AIDS epidemic update:

December 2002. Geneva.

World Health Organization, Counselling for HIV/AIDS:a key to caring. Geneva,

1995.

World Health Organization, Scaling up antiretroviral therapy in resource-limited

settings.Guidelines for a public health approach. Geneva, 2002 (includes a clinical

staging system for HIV and HIV-related disease).

105

TB/HIV:A CLINICAL MANUAL

STANDARDIZED TUBERCULOSIS CASE

DEFINITIONS AND TREATMENT CATEGORIES

8.1 STANDARDIZED CASE DEFINITIONS

8.1.1 Introduction

The diagnosis of TB means that a patient has symptomatic disease due

to lesions caused by M.tuberculosis. What type of TB? It is important to

answer this question before starting treatment.A case definition tells us

the type of TB.We define TB cases in a standardized way.This means that

when we talk about a certain type of TB,we are all talking about the

same thing.

A TB suspect is any person who presents with symptoms and signs

suggestive of TB,in particular cough of long duration.

A case of TB is a patient in whom TB has been bacteriologically

confirmed,or who has been diagnosed by a clinician.

Note:any person given treatment for TB should be recorded.

A definite TB case is a patient who is culture-positive for the M.

tuberculosis complex. (In countries where culture is not routinely

available, a patient with two sputum smears positive for AFB is also

considered a “definite case”.)

8.1.2 Questions and answers about case definitions

Why make case definitions?There are 2 purposes:

a) to determine treatment;

b) for recording and reporting (see Chapter 2).

Why do case definitions determine treatment? There are 3

reasons:

a) to identify priority cases;

b) to make the most cost-effective use of resources (by targeting

resources on priority cases);

c) to minimize side-effects for patients (by using the most intensive

regimens only for certain cases).

What determines a case definition? There are 4 determinants:

a) site of TB;

b) result of sputum smear;

c) previous TB treatment;

d) severity of TB.

The table below shows the determinants of the case definition and their

importance.

Determinant of case Importance

definition

site of TB recording and reporting

result of sputum smear

priority is to identify sputum smear-

for AFBs positive cases (since these are the

infectious cases)

in a good NTP,at least 50% of total cases

will be smear-positive PTB

recording and reporting (monitoring of

bacteriological cure is readily available

only in this group)

previous TB treatment previously treated patients who are still

sputum smear-positive have a high risk of

drug-resistant TB and so need a different

and more powerful regimen

severity of TB most authorities recommend a less

intensive regimen for patients with non-

cavitary,smear-negative PTB (who are

known to be HIV-negative)

8.1.3 Case definitions by site and result of sputum smear

Pulmonary TB – sputum smear-positive (PTB+)

Two or more initial sputum smear examinations positive for AFB

1 sputum smear positive for AFB,and CXR abnormalities consistent

with active pulmonary TB as determined by a clinician

1 sputum smear positive for AFB,which is also culture positive for M.

tuberculosis

106

STANDARDIZED TB CASE DEFINITIONS AND TREATMENT CATEGORIES

PRACTICAL POINT

Always ask "new" TB patients if they have ever had TB

treatment before.

107

TB/HIV:A CLINICAL MANUAL

Pulmonary TB – sputum smear-negative (PTB-)

A case of pulmonary TB that does not meet the above definition for

smear-positive TB.

In keeping with good clinical and public health practices, diagnostic

criteria should include:

at least three sputum smears negative for AFB

and

no response to a course of broad-spectrum antibiotics

and

CXR abnormalities consistent with active TB

and

decision by a clinician to treat with a full course of anti-TB treatment

Extrapulmonary TB

TB of organs other than the lungs: e.g.pleura, lymph nodes, abdomen,

genitourinary tract, skin,joints, bones, meninges.Diagnosis is based on

one culture-positive specimen,or histological or strong clinical evidence

consistent with active extrapulmonary TB,followed by a decision by a

clinician to treat with a full course of anti-TB treatment. A patient

diagnosed with both pulmonary and extrapulmonary TB should be

classified as a case of pulmonary TB.

8.1.4 Category of TB patient for registration on diagnosis

New

A patient who has definitely never taken anti-TB drugs or who has taken

anti-TB drugs for less than one month.

Relapse

A TB patient who:

a) previously received treatment and was declared cured or treatment

completed;

and

b) has once again developed bacteriologically positive (by smear or

culture) TB.

PRACTICAL POINT

The following are forms of extrapulmonary TB:

pleural effusion (the pleurae are outside the lungs);

miliary (TB is widespread throughout the body and not

limited to the lungs).

108

STANDARDIZED TB CASE DEFINITIONS AND TREATMENT CATEGORIES

Treatment after failure

A patient who is started on a re-treatment regimen after having failed

previous treatment.

Treatment after default

A TB patient who returns to treatment, bacteriologically positive,

following interruption of treatment for 2 months or more.

Transfer in

A TB patient who has been transferred from another TB register to

continue treatment.

Other

All TB patients who do not fit the above definitions.This group includes

chronic cases (TB patients who are sputum smear-positive at the end of

a re-treatment regimen).

8.2 STANDARDIZED DIAGNOSTIC CATEGORIES

Based on case definition,all TB patients (adults and children) fall into one

of four diagnostic categories for treatment.Patients are categorized in

order to match each diagnostic category with an effective treatment

regimen.The table below shows the patients belonging to each category.

TB diagnostic Patients