A clinical manual for South East Asia, A Harries, D Maher, M Uplekar

Tags: SOUTH EAST ASIA, TB/HIV patients, Differential diagnosis, DIAGNOSIS OF TUBERCULOSIS, chest X-ray, HIV infection, pleural effusion, HIV/AIDS care, tertiary referral hospital, primary health care, HIV-positive patients, AIDS Home Care Handbook, HIV/AIDS services, TB control, HIV/AIDS home care, HIV-negative, NTP, District Hospital, lymph nodes, clinical management, connective tissue disease, National AIDS Control Programme, health care, sputum smear, Global Tuberculosis, liver disease, Sir John Crofton, tuberculosis control, Pulmonary TB, tuberculosis, Clinical features, HIV-positive individuals, chest X-ray findings, WORLD HEALTH ORGANIZATION, PTB, pericardial effusion, EXTRAPULMONARY TB
Content: WHO/TB/96.200 (SEA)
WORLD HEALTH ORGANIZATION
TB
WHO/TB/96.200 (SEA) Distr.: GENERAL Original: ENGLISH
A CLINICAL MANUAL FOR SOUTH EAST ASIA
Authors: ANTHONY HARRIES University of Malawi College of Medicine Blantyre, Malawi Global Tuberculosis Programme World Health Organization Geneva, Switzerland DERMOT MAHER Global Tuberculosis Programme World Health Organization Geneva, Switzerland Adaptation for South East Asia of "TB/HIV: A Clinical Manual" by MUKUND UPLEKAR Foundation for Research in Community Health Bombay, India with contributions from: MARIO RAVIGLIONE, PIERRE CHAULET, PAUL NUNN, FABIO LUELMO Global Tuberculosis Programme and ERIC VAN PRAAG Office of HIV/AIDS and STDs World Health Organization Geneva, Switzerland and a foreword by SIR JOHN CROFTON Professor Emeritus of Respiratory Diseases and Tuberculosis University of Edinburgh
World Health Organization 1997
Preface to South East Asia Edition This manual is designed to meet the needs of clinicians in the countries of the WHO South East Asia region. The first version of this manual was published by WHO in 1996 as "TB/HIV: A Clinical Manual". The authors and contributors gratefully acknowledge the helpful comments and suggestions of Dr Kevin De Cock and Dr Robert Colebunders, who reviewed the original manuscript. Copyright © World Health Organization (1997) This document is not a formal publication of the World Health Organization (WHO) and all rights are reserved by the Organization. The document may, however, be freely reviewed, abstracted, reproduced, or translated in part, but not for sale or for use in conjunction with commercial purposes. It may also be reproduced in full by non-commercial entities for information or for educational purposes with prior permission from WHO. For authorization to translate the work in full, and for any use by commercial entities, applications and enquiries should be addressed to the Global Tuberculosis Programme, World Health Organization, Geneva, Switzerland, which will be glad to provide the latest information on any changes made to the text, plans for new editions, and the reprints, regional adaptations and translations that are already available. The views expressed herein by named authors are solely the responsibility of those authors. Printed in Italy Designer: Jotto Associati s.a.s. - Biella - Italy Printer: Stabilimento Tipografico Ferrero s.r.l. - Romano Canavese (TO) - Italy
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CONTENTS
Foreword by Sir John Crofton . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Ch.1. Background information on tuberculosis . . . . . . . . . . . . . . . 19
1.1 1.1.1 1.1.2
Tuberculosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 Basic facts about TB (M. tuberculosis, transmission, risk of progression to disease, natural history of untreated TB, epidemiology). . . . . . . . . . . . . . . . . . . . 19 Pathogenesis of TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Ch.2. Diagnosis of tuberculosis in adults . . . . . . . . . . . . . . . . . . . 25
2.1 2.1.1 2.1.2 2.1.3 2.1.4 2.1.5 2.1.6 2.1.7
Pulmonary TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Diagnostic approach. . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Clinical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Diagnostic sputum smear microscopy . . . . . . . . . . . . . . . 26 Differential diagnosis of pulmonary TB . . . . . . . . . . . . . . 29 Chest X-rays in diagnosis . . . . . . . . . . . . . . . . . . . . . . . . 30 Patterns of disease in pulmonary TB . . . . . . . . . . . . . . . . 31 Differential diagnosis of chest X-ray findings . . . . . . . . . . 31
2.2 2.2.1 2.2.2 2.2.3 2.2.4 2.2.5 2.2.6 2.2.7
Extrapulmonary TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 Diagnostic approach. . . . . . . . . . . . . . . . . . . . . . . . . . . 33 TB lymphadenopathy . . . . . . . . . . . . . . . . . . . . . . . . . . 33 Miliary TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 TB serous effusions (pleural, pericardial, ascites). . . . . . . . 35 TB meningitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 Other forms of extrapulmonary TB . . . . . . . . . . . . . . . . . 43 Further information on spinal, gastrointestinal and hepatic TB. 44
Ch.3. Diagnosis of tuberculosis in children . . . . . . . . . . . . . . . . . . 45
3.1 How does TB in children differ from TB in adults? . . . . . . 45
3.2 Approach to diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . 46
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3.3 Score system for the diagnosis of TB in children . . . . . . . . 47
3.4 "Treatment trial" . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
3.5 Tuberculin skin test . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
3.6 Management of child contacts of infectious adults. . . . . . . 50
Ch.4. Standardised TB case definitions and treatment categories . . 53
4.1 4.1.1 4.1.2 4.1.3 4.1.4
Standardised case definitions. . . . . . . . . . . . . . . . . . . . . 53 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 Questions and answers about case definitions . . . . . . . . . 53 Case definitions by site and result of sputum smear. . . . . . 54 Case definitions by previous treatment . . . . . . . . . . . . . . 55
4.2 Standardised treatment categories . . . . . . . . . . . . . . . . . 56
Ch.5. Treatment of TB patients . . . . . . . . . . . . . . . . . . . . . . . . . . 57
5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
5.2 Mode of action of anti-TB drugs . . . . . . . . . . . . . . . . . . . 58
5.3 5.3.1 5.3.2 5.3.3 5.3.4 5.3.5
TB treatment regimens . . . . . . . . . . . . . . . . . . . . . . . . . . 59 New cases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 Retreatment cases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 Standard code for TB treatment regimens . . . . . . . . . . . . 60 Recommended treatment regimens . . . . . . . . . . . . . . . . . 61 Use of streptomycin and thiacetazone in areas of high HIV prevalence . . . . . . . . . . . . . . . . . . . 62
5.4 TB treatment regimens: questions and answers . . . . . . . . . 62
5.5 Use of anti-TB drugs in special situations: pregnancy, renal failure, liver disease . . . . . . . . . . . . . . . 63
5.6 The role of steroid treatment: questions and answers . . . . . 64
5.7 Monitoring of TB patients during treatment. . . . . . . . . . . . 65 5.7.1 Monitoring of patients with sputum smear-positive PTB. . . . 65
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5.7.2 Recording treatment outcome in sputum smear-positive PTB patients . . . . . . . . . . . . . . . . . . . . . . 66
Ch.6. Side effects of anti-TB drugs . . . . . . . . . . . . . . . . . . . . . . . 69
6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
6.2 Prevention of side-effects . . . . . . . . . . . . . . . . . . . . . . . . 69
6.3 Where to manage drug reactions . . . . . . . . . . . . . . . . . . 69
6.4 When to stop anti-TB drugs . . . . . . . . . . . . . . . . . . . . . . 69
6.5 Side-effects of anti-TB drugs . . . . . . . . . . . . . . . . . . . . . . 70
6.6 Symptom-based approach to management of drug side-effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
6.7 Management of skin itching/rash . . . . . . . . . . . . . . . . . . 72 6.7.1 Treatment regimen includes thiacetazone. . . . . . . . . . . . . 72 6.7.2 Treatment regimen does not include thiacetazone . . . . . . . 72
6.8 Desensitisation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
6.9 Management of hepatitis . . . . . . . . . . . . . . . . . . . . . . . . 74
Ch.7. Framework for effective tuberculosis control . . . . . . . . . . . . 77
7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
7.2 7.2.1 7.2.2 7.2.3 7.2.4 7.2.5 7.2.6 7.2.7
Components of TB control framework . . . . . . . . . . . . . . . 77 Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 Strategy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 Targets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 Policy package. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 Key features of a national TB programme (NTP) . . . . . . . . 79 Indicators of NTP progress in TB control . . . . . . . . . . . . . 79 Cohort analysis: questions and answers . . . . . . . . . . . . . 79
7.3 Directly observed therapy . . . . . . . . . . . . . . . . . . . . . . . 80
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Ch.8. Background information on HIV/AIDS . . . . . . . . . . . . . . . . 83
8.1 8.1.1 8.1.2 8.1.3 8.1.4 8.1.5 8.1.6
HIV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 Introduction: HIV and AIDS . . . . . . . . . . . . . . . . . . . . . . 83 HIV/AIDS epidemiology . . . . . . . . . . . . . . . . . . . . . . . . 83 HIV transmission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 Prevention of HIV transmission in health units . . . . . . . . . . 84 Immunopathogenesis of HIV infection . . . . . . . . . . . . . . . 85 Natural history of HIV infection . . . . . . . . . . . . . . . . . . . 85
8.2 AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86 8.2.1 WHO case definitions for AIDS surveillance . . . . . . . . . . 87
Ch.9. HIV-related TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
9.1 9.1.1 9.1.2 9.1.3 9.1.4 9.1.5
Basic Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 Epidemiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 HIV infection and risk of TB . . . . . . . . . . . . . . . . . . . . . . 91 Consequence of HIV/M. tuberculosis co-infection . . . . . . . 91 Impact of HIV on TB control . . . . . . . . . . . . . . . . . . . . . . 92 Impact of TB on HIV . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
9.2 Patterns of HIV-related TB. . . . . . . . . . . . . . . . . . . . . . . . 92 9.2.1 Pulmonary TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 9.2.2 Extra-pulmonary TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
9.3 9.3.1 9.3.2 9.3.3
HIV-related TB in children. . . . . . . . . . . . . . . . . . . . . . . . 97 The impact of HIV on the diagnosis of TB in children . . . . . 97 Differential diagnosis of PTB in HIV-infected children . . . . . 97 Child contacts who may be HIV-infected . . . . . . . . . . . . . 97
9.4 Response of HIV-positive TB patients to anti-TB treatment . . 98 9.4.1 Side-effects of anti-TB drugs in TB/HIV patients . . . . . . . . . 99
Ch.10. Diagnosis of HIV infection in adults with tuberculosis . . . . 101
10.1 Clinical recognition of HIV infection in TB patients . . . . . 101
10.2 HIV testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 10.2.1 HIV tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 10.2.2 Objectives of HIV antibody testing in TB patients . . . . . . 103
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10.2.3 Strategy for HIV antibody testing in TB patients . . . . . . . 103 10.2.4 Diagnosis of HIV infection in individual TB patients . . . . . 104 10.3 HIV counselling Ch.11. Diagnosis of HIV infection in children with tuberculosis . . . 107 11.1 Clinical recognition of HIV infection in children with TB . . 107 11.2 HIV testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 11.3 Counselling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 Ch.12. Management of other HIV-related diseases in TB/HIV patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 12.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 12.2 Sexually transmitted diseases . . . . . . . . . . . . . . . . . . . . 111 12.2.1 Syndromic management . . . . . . . . . . . . . . . . . . . . . . . 111 12.2.2 Treatment regimens for common STDs . . . . . . . . . . . . . . 112 12.3 Skin and mouth problems . . . . . . . . . . . . . . . . . . . . . . 113 12.4 Gastrointestinal problems . . . . . . . . . . . . . . . . . . . . . . 115 12.4.1 Dysphagia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 12.4.2 Diarrhoea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116 12.5 Respiratory problems . . . . . . . . . . . . . . . . . . . . . . . . . 117 12.6 Neurological problems . . . . . . . . . . . . . . . . . . . . . . . . 119 12.6.1 Acute confusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 12.6.2 Chronic behaviour change . . . . . . . . . . . . . . . . . . . . . 119 12.6.3 Persistent headache . . . . . . . . . . . . . . . . . . . . . . . . . . 120 12.6.4 Difficulty in walking . . . . . . . . . . . . . . . . . . . . . . . . . . 121 12.6.5 Poor vision. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 12.6.6 Burning sensation in feet . . . . . . . . . . . . . . . . . . . . . . . 122 12.7 Fever. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 12.7.1 Approach to management . . . . . . . . . . . . . . . . . . . . . . 123 12.7.2 Disseminated infection. . . . . . . . . . . . . . . . . . . . . . . . . 123 7
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12.8 Other HIV-related problems which may occur in TB/HIV patients . . . . . . . . . . . . . . . 124 Ch.13. Coordinated care in different settings . . . . . . . . . . . . . . . 127 13.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127 13.2 Benefits of support from local HIV/AIDS care services. . . 127 13.3 Integrated system of HIV/AIDS and TB care . . . . . . . . . . 127 13.3.1 Referral to local HIV/AIDS care services . . . . . . . . . . . . 128 13.3.2 HIV counselling and voluntary testing centres . . . . . . . . . 129 13.3.3 Care in the community . . . . . . . . . . . . . . . . . . . . . . . . 130 13.3.4 Care at Primary Health Care level . . . . . . . . . . . . . . . . 130 13.3.5 Private sector . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130 13.3.6 Care at district level . . . . . . . . . . . . . . . . . . . . . . . . . . 131 13.3.7 Tertiary referral care . . . . . . . . . . . . . . . . . . . . . . . . . . 131 Ch.14. Prevention of TB. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 14.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 14.2 Protection against exposure to TB . . . . . . . . . . . . . . . . . 133 14.2.1 Environmental control . . . . . . . . . . . . . . . . . . . . . . . . . 133 14.2.2 Face-masks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134 14.2.3 Patient education . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134 14.2.4 PTB suspects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134 14.2.5 Patients with sputum smear-positive PTB . . . . . . . . . . . . . 134 14.3 Role of BCG in preventing TB. . . . . . . . . . . . . . . . . . . . 135 14.3.1 General. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 14.3.2 BCG protection against TB in HIV-infected children . . . . . 135 14.3.3 BCG safety in HIV-infected children. . . . . . . . . . . . . . . . 135 14.3.4 WHO recommended policy on BCG and HIV . . . . . . . . 135 14.4 The role of the Expanded Programme on Immunisation (EPI) . . . . . . . . . . . . . . . . . . . . . . . . . 136 14.5 Preventive treatment . . . . . . . . . . . . . . . . . . . . . . . . . . 136 14.5.1 Target groups for preventive treatment . . . . . . . . . . . . . . 136 14.5.2 Role of isoniazid preventive treatment in HIV-positive individuals . . . . . . . . . . . . . . . . . . . . . . 137 8
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FOREWORD Doctors and other health professionals working in most countries will be only too aware of the many patients they encounter with tuberculosis. This excellent book is designed for the busy clinician. It concentrates particularly on the clinical problems of diagnosis and management of tuberculosis, both in adults and children. 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. Clinicians will also be all too well aware of the epidemic of HIV infection and the effect this has had on dramatically increasing the tuberculosis burden, not only in sub-Saharan Africa, but also increasingly in Asia and Latin America. This book summarises the characteristics of tuberculosis and HIV/AIDS and of their interactions. It also summarises the other HIVrelated diseases which the clinician may encounter in TB/HIV patients. The modern treatment of tuberculosis, including in HIV-infected patients, is highly successful. This not only benefits the patient but reduces the spread of tuberculosis to families and the community. Other treatments can help to improve or control many other HIV-related diseases. This book well summarises the range of treatments available. It also provides useful guides on counselling and on inter-agency cooperation, both essential components of TB/HIV management. 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 9
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INTRODUCTION Many countries where tuberculosis is common have national tuberculosis control programmes. Following a review of the tuberculosis situation in several countries in the South East Asia Region, the National Tuberculosis Programmes have been recently revised. The emergence and rapid spread of HIV infection and HIV-related TB (TB/HIV) give a fresh impetus to the efforts of these programmes to control TB. The essential activities of tuberculosis control are the same even in populations where HIV infection is common. The objectives of a tuberculosis control programme are to decrease morbidity, mortality and transmission of tuberculosis, while avoiding the emergence of drug resistance. The WHO strategy is to provide shortcourse chemotherapy under direct observation to, at least, all identified smear-positive cases. The provision of short-course chemotherapy for tuberculosis patients is one of the most cost-effective of all health interventions. The aim is to achieve global targets of 85% cure rate and 70% case detection rate. Health professionals in the region may learn from the TB/HIV experiences in sub-Saharan Africa. Evidently, a rise in HIV-related tuberculosis increases demands on tuberculosis programmes. The rise in tuberculosis suspects puts a strain on diagnostic services. There is an increase in the proportion of extra-pulmonary and smear-negative pulmonary tuberculosis cases, which are more difficult to diagnose. Adverse drug reactions are more frequently seen. There is a higher morbidity and mortality, partly due to other, curable, HIV-related infections. The risk of tuberculosis recurrence is higher. This manual is mainly for doctors and other health professionals who work in public or private health centres and hospitals in high tuberculosis prevalence countries where the problem of TB/HIV is also increasing. Health care facilities vary from place to place. In this manual we assume your health care set-up has access to a small laboratory and X-ray service. Even if you do not have these facilities, we hope that the manual will still be useful. Health professionals who care for tuberculosis patients now need to know how to diagnose and treat tuberculosis and other HIV-related diseases. This manual will help you in this task. 11
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This pocket manual is so designed that 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 and TB/HIV. 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. You are welcome to send any comments on the manual to the WHO Global Tuberculosis Programme. 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 WHO Publications, Distribution and Sales, 1211 Geneva 27, Switzerland. 12
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GLOSSARY This glossary explains the abbreviations and some of the words used in this book. 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 adjuvant treatment. . . . . . . as an addition to other treatment AFBs . . . . . . . . . . . . . . . . Acid-Fast Bacilli agranulocytosis . . . . . . . . . absence of polymorph white blood cells AIDS . . . . . . . . . . . . . . . . Acquired Immuno Deficiency Syndrome anorexia . . . . . . . . . . . . . loss of appetite for food ARC . . . . . . . . . . . . . . . . AIDS-Related Complex atypical mycobacteria . . . . non-tuberculous mycobacteria bactericidal . . . . . . . . . . . kills bacteria bacteriostatic . . . . . . . . . . stops bacteria from growing BCG . . . . . . . . . . . . . . . . Bacille Calmette-Guerin bubo . . . . . . . . . . . . . . . . swollen, pus-containing lymph node caseation . . . . . . . . . . . . . tissue breakdown by TB bacilli, forming yellow-white, cheese-like material chemotherapy. . . . . . . . . . treatment with chemical drugs, e.g. anti-TB chemotherapy means treatment with anti-TB drugs CD4 cells . . . . . . . . . . . . . sub-group of T-lymphocytes carrying CD4 antigens CMV . . . . . . . . . . . . . . . . CytoMegaloVirus CNS . . . . . . . . . . . . . . . . Central nervous system co-infection. . . . . . . . . . . . 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 counselling . . . . . . . . . . . . face-to-face communication in which one person (counsellor) helps another (patient/ client) to make decisions and act on them CSF . . . . . . . . . . . . . . . . . CerebroSpinal Fluid dactylitis. . . . . . . . . . . . . . inflammation of the fingers 13
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default . . . . . . . . . . . . . . . patient stopping treatment before completion desensitisation . . . . . . . . . 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 Therapy (supervisor watches patient to ensure the patient takes the tablets) 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 Immunisation extrapulmonary tuberculosis. tuberculosis outside the lungs exudate . . . . . . . . . . . . . . fluid with a high protein content and inflammatory cells in an area of disease false negative test result . . . a test result which shows negative, when the true result is in fact positive FBC . . . . . . . . . . . . . . . . . Full Blood Count fluorochrome stain. . . . . . . shines brightly under ultraviolet light gibbus . . . . . . . . . . . . . . . an acute angle in the spine due to vertebral collapse from TB hilar . . . . . . . . . . . . . . . . at the root of the lung hilum . . . . . . . . . . . . . . . . the root of the lung HIV . . . . . . . . . . . . . . . . . Human Immunodeficiency Virus HIV-negative . . . . . . . . . . . blood test shows absence of antibodies against HIV HIV-positive . . . . . . . . . . . blood test shows presence of antibodies against HIV HIV-related TB . . . . . . . . . . TB occurring in somebody infected with HIV HIV status . . . . . . . . . . . . . whether a person is known to be HIV-positive or HIV-negative HIV test . . . . . . . . . . . . . . blood test for antibodies against HIV home care . . . . . . . . . . . . providing care for a patient in his home rather than in hospital hypersensitivity reaction . . . type of immunological reaction to even a small amount of a drug or other antigen, e.g. tuberculin 14
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i.m. injection. . . . . . . . . . . intramuscular injection immunosuppressant drugs . drugs which suppress normal immunity 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 initial resistance . . . . . . . . resistance of Mycobacterium tuberculosis to anti-TB drugs in a TB patient who has never before received anti-TB drugs IUATLD. . . . . . . . . . . . . . . International Union Against TB and Lung Disease JVP . . . . . . . . . . . . . . . . . Jugular Venous Pressure KS . . . . . . . . . . . . . . . . . . Kaposi's Sarcoma latent . . . . . . . . . . . . . . . . something that is there but not obvious (it can become obvious later) lesion. . . . . . . . . . . . . . . . an area of disease in the body LFTs . . . . . . . . . . . . . . . . . Liver Function Tests MAC . . . . . . . . . . . . . . . . Mycobacterium Avium intraCellulare (one of the atypical mycobacteria) MCV . . . . . . . . . . . . . . . . Mean Corpuscular Volume meningism . . . . . . . . . . . . presence of clinical features suggestive of meningitis, e.g. headache, neck-stiffness, positive Kernig's sign mutant bacilli . . . . . . . . . . bacilli which suddenly change genetically and become different from the rest of the population mutation. . . . . . . . . . . . . . a sudden genetic change, e.g. which results in a bacillus becoming drug-resistant NGO. . . . . . . . . . . . . . . . Non-Governmental Organisation NSAID . . . . . . . . . . . . . . . Non-Steroidal Anti-Inflammatory Drug NTP . . . . . . . . . . . . . . . . . National Tuberculosis Programme opportunistic infection . . . . an infection which "takes the opportunity" to cause disease when a person's immune defence is weak "passive" case finding . . . . detection of TB cases by active testing (sputum smear) of TB suspects attending health services pathogenesis . . . . . . . . . . how a disease arises PCP . . . . . . . . . . . . . . . . . Pneumocystis Carinii Pneumonia phlyctenular conjunctivitis . . painful hypersensitivity reaction of the conjunctiva to primary tuberculosis infection, 15
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with inflammation and small red spots where the cornea meets the sclera PGL . . . . . . . . . . . . . . . . . Persistent Generalised Lymphadenopathy 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 which 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 SCC . . . . . . . . . . . . . . . . Short-Course Chemotherapy scrofula . . . . . . . . . . . . . . tuberculous lymph nodes in the neck sensitivity tests. . . . . . . . . . tests of TB bacilli for sensitivity or resistance to anti-TB drugs seroconversion . . . . . . . . . when a blood test first shows that a person is HIV seropositive, usually about 3 months after HIV infection seroprevalence . . . . . . . . . the proportion of people testing sero-positive (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 negative. . . . absence of AFBs on sputum microscopy sputum smear positive . . . . presence of AFBs on sputum microscopy STD . . . . . . . . . . . . . . . . . Sexually Transmitted Disease Stevens-Johnson syndrome . a characteristic rash with "target lesions" and inflammation of the mucous membranes syndrome . . . . . . . . . . . . . a group of symptoms and signs TB . . . . . . . . . . . . . . . . . . TuBerculosis TB/HIV . . . . . . . . . . . . . . TB and HIV co-infection TB/HIV patient . . . . . . . . . HIV-infected TB patient TEN. . . . . . . . . . . . . . . . . Toxic Epidermal Necrolysis 16
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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 WHO . . . . . . . . . . . . . . . World Health Organisation window period . . . . . . . . . the gap of about 3 months between the time when a person becomes infected with HIV and the time when the blood test for HIV first shows positive ZN stain. . . . . . . . . . . . . . Ziehl-Neelsen stain 17
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B A C K G R O U N D I N F O R M AT I O N O N T U B E R C U L O S I S
CHAPTER 1 BACKGROUND INFORMATION ON TUBERCULOSIS 1 1 TUBERCULOSIS (TB) 1 1 1 Basic facts about TB Mycobacterium tuberculosis TB is a bacterial disease caused by Mycobacterium tuberculosis (and occasionally by Mycobacterium bovis and Mycobacterium africanum). These organisms are also known as tubercle bacilli (because they cause lesions called tubercles) or as acid-fast bacilli (AFB). When examining sputum containing tubercle bacilli stained with certain dyes under the microscope, the bacilli look red. This is because they are acid-fast (they have kept the dye even after washing with acid and alcohol). Tubercle bacilli can remain dormant in tissues and persist for many years. Transmission of infection Transmission occurs by airborne spread of infectious droplets. The source of infection is a person with TB of the lung who is coughing. TB of the lung is pulmonary TB (PTB). This person is usually sputum smear-positive (see Chapter 2). Coughing produces tiny infectious droplets (droplet nuclei). One cough can produce 3,000 droplet nuclei. Transmission generally occurs indoors, where droplet nuclei can stay in the air for a long time. Ventilation removes droplet nuclei. Direct sunlight quickly kills tubercle bacilli, but they can survive in the dark for several hours. Two factors determine an individual's risk of exposure: the concentration of droplet nuclei in contaminated air and the length of time breathing that air. Risk of infection An individual's risk of infection depends on the extent of exposure to droplet nuclei and susceptibility to infection. The risk of infection of a susceptible individual is therefore 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 with extra-pulmonary TB is even lower. Risk of progression of infection to disease. Once infected with M.tuberculosis, a person stays infected for many years, probably for life. The vast majority (90%) of people without HIV 19
TB: A CLINICAL MANUAL FOR SOUTH EAST ASIA
infection who are infected with M.tuberculosis do not develop tuberculosis disease. In these healthy, asymptomatic, but infected individuals, the only evidence of infection may be a positive tuberculin skin test. Infected persons can develop tuberculosis disease at any time. The chance of developing disease is greatest shortly after infection and then steadily lessens as time goes by. 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. Disease can affect most tissues and organs, but especially the lungs. Natural history of untreated TB Without treatment, after 5 years, 50% of pulmonary TB patients will be dead, 25% will be healthy (self-cured by strong immune defence) and 25% will remain ill with chronic, infectious TB. Epidemiology M. tuberculosis infects a third of the world's population. Worldwide in 1995 there were about 9 million new cases of TB with 3 million deaths. These deaths comprise 25% of all avoidable deaths in developing countries. 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). 1 1 2 Pathogenesis of TB Primary infection Primary infection occurs on first exposure to tubercle bacilli. Inhaled droplet nuclei are so small that they avoid the muco-ciliary defences of the bronchi and lodge in the terminal alveoli of the lungs. Infection begins with multiplication of tubercle bacilli in the lungs. This 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. The immune 20
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response in a few cases is not strong enough to prevent multiplication of bacilli, and disease occurs within a few months.
Outcome of primary infection
No clinical disease Positive tuberculin skin test (usual outcome in over 90% of cases)
Primary complex
Hypersensitivity reactions e.g. erythema nodosum phlyctenular conjunctivitis dactylitis Pulmonary and pleural complications e.g. tuberculous pneumonia lobar collapse (bronchial compression) pleural effusion
Disseminated disease e.g. lymphadenopathy (usually cervical) meningitis pericarditis miliary disease
PRACTICAL POINT Following primary infection, rapid progression to intra-thoracic disease is more common in children than in adults. Chest X-ray may show intrathoracic lymphadenopathy and lung infiltrates.
Post-primary TB Post-primary TB occurs after a latent period of months or years after primary infection. It may occur either by reactivation 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
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a primary infection. 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 smear; upper lobe involvement; usually no intrathoracic lymphadenopathy.
POST-PRIMARY TB
PULMONARY TB e.g. cavities upper lobe infiltrates fibrosis progressive pneumonia endobronchial
EXTRA-PULMONARY TB COMMON Pleural effusion Lymphadenopathy (usually cervical) Central nervous system (meningitis, cerebral tuberculoma) Pericarditis (effusion/constrictive) Gastro-intestinal (ileocaecal, peritoneal) Spine, other bone and joint
LESS COMMON Empyema Male genital tract (epididymitis, orchitis) Female genital tract (tubo-ovarian, endometrium) Kidney Adrenal gland Skin (lupus vulgaris, tuberculids, miliary)
PRACTICAL POINT Post-primary infection with pulmonary disease usually occurs in adults, with positive sputum smears.
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SUGGESTIONS FOR FURTHER READING Crofton J, Horne N and Miller F. Clinical Tuberculosis. The Macmillan Press Limited. 1992. Davies PDO. Clinical Tuberculosis. Chapman and Hall Medical. 1994. International Union Against Tuberculosis and Lung Disease. Tuberculosis Guide For Low Income Countries. pmi Verlagsgruppe. 3rd edition. Frankfurt, 1994. Raviglione MC, Snider D, Kochi A. Global epidemiology of tuberculosis. Morbidity and mortality of a worldwide epidemic. JAMA 1995; 273: 220-226. Dolin PJ, Raviglione MC, Kochi A. Global tuberculosis incidence and mortality during 1990-2000. Bull. World Health Organ. 1994; 72(2): 213-220. 23
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24
DIAGNOSIS OF TUBERCULOSIS IN ADULTS
CHAPTER 2 DIAGNOSIS OF TUBERCULOSIS IN ADULTS 2 1 PULMONARY TB 2 1 1 Diagnostic approach The highest priority for TB control is the identification and cure of the infectious cases, i.e. patients with sputum smear-positive PTB. Therefore all patients with clinical features suspicious of PTB must submit sputum for diagnostic sputum smear microscopy. Most TB suspects are ambulatory. The diagnosis of PTB is therefore usually on an out-patient basis. A few TB suspects are severely ill and/or bed-bound and therefore need investigation as in-patients. Clinical screening by assessment of symptoms identifies PTB suspects among patients attending health facilities. The most cost-effective method of screening PTB suspects in high-prevalence countries is by sputum smear microscopy. When a suspect has a positive sputum smear, the person has sputum smear-positive PTB. Register this person with the appropriate health authority and start treatment. In most cases, a chest X-ray is un-necessary. 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 tuberculosis 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 does have TB. Conditions often associated with a false-negative tuberculin skin test include HIV infection, severe malnutrition and miliary TB. 2 1 2 Clinical features Symptoms The most important symptoms in the diagnosis of PTB are the following: cough > 3 weeks sputum production weight loss 25
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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 3 weeks is a PTB suspect and must submit sputums for diagnostic microscopy. Patients with PTB may also have other symptoms. These may be respiratory or constitutional (general or systemic). Respiratory: haemoptysis, chest pain, breathlessness Constitutional: fever/night sweats, tiredness, loss of appetite Physical signs The physical signs in patients with PTB are non-specific. They do not help to distinguish PTB from other chest diseases. PRACTICAL POINT PTB suspects (patients with suggestive symptoms) must submit sputums for sputum smear microscopy. 2 1 3 Diagnostic sputum smear microscopy Collection of sputum samples A PTB suspect should submit 3 sputum samples for microscopy. The chances of finding tubercle bacilli are greater with 3 sputum samples than with 2 samples or 1 sample. Secretions build up in the airways overnight. So an early morning sputum sample is more likely than a sample later in the day to contain tubercle bacilli. It may be difficult for an out-patient to provide 3 early morning sputum samples. Therefore in practice an outpatient usually provides sputum samples as follows: day 1 . . . sample 1 . . Patient provides an "on the spot" sample under supervision at the time of presenting to the health facility. Give the patient a sputum container to take home for an early morning sample the following morning. 26
DIAGNOSIS OF TUBERCULOSIS IN ADULTS
day 2 . . . sample 2 . . Patient brings an early morning sample. sample 3 . . Patient provides another "on the spot" sample under supervision. If a patient can't produce a sputum sample, a nurse or physiotherapist may help the patient to give a good cough and bring up some sputum. An in-patient can provide 3 early morning sputum samples under supervision in hospital. 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 decolourisation 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 w · cover the fixed smear with carbol fuchsin for 3 minutes w · heat, rinse with tap water, and decolourise with acid-alcohol for 3-5 seconds w · counter-stain with methylene blue for 30 seconds w · rinse again with tap water w · observe under the microscope (use the oil immersion lens (x100) and x6 or x8 eye-piece lens) The bacilli appear as red, beaded rods, 2-4 µm long and 0.2-0.5 µm wide. Fluorochrome stain This is a different stain for tubercle bacilli. A special fluorescent microscope is necessary. The fluorochrome stain is phenolic auramine or auramine-rhodamine. After acid-alcohol decolourisation and a methylene blue counterstain, the bacilli fluoresce bright yellow against a dark background. The advantage of this method is that it is possible to scan 27
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smears quickly under low magnification. It is important to re-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.
NUMBER OF BACILLI SEEN IN A SMEAR
no
AFB per 100 oil immersion fields
1 -9 AFB per 100 oil immersion fields
10 - 99 AFB per 100 oil immersion fields
1 -10 AFB per oil immersion field
> 10 AFB per oil immersion field
RESULT REPORTED
0
scanty
+
(1+)
++ (2+)
+++ (3+)
The laboratory technician must examine all 3 sputum samples from each TB suspect. The technician must record the result of each sputum sample with the laboratory reference number in the laboratory register and on the sputum request form.
Sensitivity of sputum smear microscopy Sputum smear microscopy for tubercle bacilli is positive when there are at least 10,000 organisms present per 1 ml of sputum.
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; various particles that are acid-fast (e.g. food particles, precipitates, other micro-organisms).
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 have sputum smear-positive PTB. This may arise because of problems in collecting, processing, or interpreting sputum smears, or because of administrative errors.
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PRACTICAL POINT If a sputum smear result is unexpectedly negative (e.g. in a patient with upper lobe cavities on chest X-ray), think of the possibility of a false negative result and repeat the sputum microscopy.
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 sample for smear faulty smear preparation and staining
sputum smear interpretation . inadequate time spent examining smear inadequate attention to smear (poor motivation)
administrative errors . . . . . . mis-identification of patient incorrect labelling of sample mistakes in documentation
2 1 4 Differential diagnosis of pulmonary TB
PRACTICAL POINT A PTB suspect with 3 negative sputum smears may not have PTB at all. Reassess the patient in case he has a condition mistaken for PTB.
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The table shows the differential diagnosis of PTB.
DIFFERENTIAL DIAGNOSIS congestive cardiac failure left ventricular failure asthma chronic obstructive airways disease bronchiectasis bronchial carcinoma other infections, e.g. bacterial pneumonia lung abscess pneumocystis carinii
POINTERS TO THE CORRECT DIAGNOSIS symptoms of heart failure (dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea, haemoptysis, oedema, epigastric discomfort from hepatic congestion) signs of heart failure intermittent symptoms, generalised expiratory wheezes risk factor (smoking), chronic symptoms, prominent dyspnoea, generalised wheezes large amounts of purulent sputum risk factor (smoking) response to antibiotic abscess with fluid level on chest X-ray dyspnoea prominent
PRACTICAL POINT If a patient is breathless, has continuing haemoptyses, and has negative sputum smears, listen carefully for a low-pitched, rumbling, mid-diastolic murmur in case the diagnosis is mitral stenosis with pulmonary oedema.
2 1 5 Chest X-rays in diagnosis INDICATIONS FOR CHEST X-RAY Positive sputum smear The first screening test for PTB suspects is sputum smear microscopy. In most cases of sputum smear-positive PTB a chest X-ray is un-necessary. In those few cases of sputum smear-positive PTB when a chest X-ray is necessary, the indications are as follows:
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a) suspected complications in the breathless patient, needing specific treatment, e.g. pneumothorax, (pericardial effusion or pleural effusion positive sputum smear is rare); b) frequent or severe haemoptysis (to exclude bronchiectasis or aspergilloma); c) only 1 sputum smear positive out of 3 (in this case, an abnormal chest X-ray is a necessary additional criterion for the diagnosis of sputum smear-positive PTB). Negative sputum smears Re-assess the patient who continues to cough despite a course of broad-spectrum antibiotic, and who has had 3 negative sputum smears. It is often worthwhile repeating the sputum smears after 2 weeks. If you still suspect TB despite negative sputum smears, the patient needs a chest X-ray. 2 1 6 Patterns of disease in PTB PRACTICAL POINT No chest X-ray pattern is absolutely typical of PTB.
The table shows the so-called "classical" and "atypical" patterns. (The atypical pattern is more common in HIV positive patients).
CLASSICAL PATTERN upper lobe infiltrates bilateral infiltrates cavitation pulmonary fibrosis and shrinkage
ATYPICAL PATTERN interstitial infiltrates (especially lower zones) no cavitation no abnormalities
2 1 7 Differential diagnosis of chest X-ray findings
The chest X-ray findings associated with PTB are non-specific. Diseases other than PTB can cause both the "classical" and the "atypical" chest X-ray findings.
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PRACTICAL POINT The vast majority of patients (over 90%) with cavitary PTB are sputum smear-positive. Therefore, a patient with cavities on chest X-ray and repeated negative sputum smears probably has a disease other than PTB.
The table shows the differential diagnosis of chest X-ray findings often associated with PTB.
CHEST X-RAY FINDING
DIFFERENTIAL DIAGNOSIS
cavitation . . . . . . . . . . . . . . . . . . . infections some bacterial pneumonias lung abscess some fungal infections
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
2 2 EXTRAPULMONARY TB
Common forms of extrapulmonary TB include the following: lymphadenopathy, pleural effusion, pericardial disease, miliary, meningitis. Patients usually present with constitutional features (fever, night sweats, weight loss) and local features related to the site of disease. The local features related to the site of disease are similar in adults and children.
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w w w DIAGNOSIS OF TUBERCULOSIS IN ADULTS
2 2 1 Diagnostic approach Many patients with extrapulmonary TB also have co-existent pulmonary TB. PRACTICAL POINT If a patient has extrapulmonary TB, look for pulmonary TB. Send sputum samples for AFBs and, if sputum AFBs are negative, do a chest X-ray.
Definitive diagnosis of extrapulmonary TB is often difficult. Diagnosis may be presumptive, provided you can exclude other conditions. The degree of certainty of diagnosis depends on the availability of diagnostic tools, e.g. specialised X-rays, biopsy procedures.
2 2 2 Tuberculous lymphadenopathy
The lymph nodes most commonly involved are the cervical nodes. The usual course of lymph node disease is as follows:
firm, discrete nodes
fluctuant nodes matted together
skin breakdown, abscesses, chronic sinuses
healing with scarring
PRACTICAL POINT In severe immunocompromise, tuberculous lymphadenopathy may be acute and resemble acute pyogenic lymphadenitis.
The differential diagnosis of tuberculous lymphadenopathy includes the following: persistent generalised lymphadenopathy (PGL), lymphoma, Kaposi's sarcoma, carcinomatous metastases, sarcoid, drug reactions (e.g. phenytoin).
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Practical approach to investigation of lymphadenopathy
PROCEDURE needle aspirate of lymph node if no diagnosis after aspirate lymph node biopsy
TEST
RESULT
DIAGNOSIS
look at material aspirated . . . . . . . . caseation . . . . . . . . TB
smear for AFBs . . . . AFBs present . . . . . . TB
smear for cytology . . malignant cells seen . malignancy e.g. KS, lymphoma, carcinoma
look at cut surface . . caseation . . . . . . . . TB
smear from cut surface for AFBs . . . AFBs seen . . . . . . . . TB
fresh node sent for TB culture. . . . . . positive TB culture. . . TB
node in formalin for histology . . . . . . granuloma and AFBs . TB . . . . . . . . . . . . . . malignant cells. . . . . malignancy
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 AFBs is 70%. Diagnostic sensitivity increases to 80% if you excise a lymph node, look at the cut surface, and do a smear for AFBs. 2 2 3 Miliary TB Miliary TB results from widespread blood-borne dissemination of TB bacilli. This is either the consequence of a recent primary infection or the erosion of a tuberculous lesion into a blood vessel. Clinical features The patient presents with constitutional features. Hepatosplenomegaly and choroidal tubercles (fundoscopy) may be present. Diagnosis Chest X-ray shows diffuse, uniformly distributed, small miliary shadows. "Miliary" means "like small millet seeds". Full blood count may show pancytopenia. Liver function tests may be abnormal. Bacteriological confirmation is sometimes possible from sputum, C.S.F., or bone marrow.
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Differential diagnosis The differential diagnosis includes the following: slim disease, bacteraemia (including typhoid fever), disseminated carcinoma, disseminated infection with "atypical" mycobacteria. 2 2 4 Tuberculous serous effusions Inflammatory tuberculous effusions may occur in any of the serous cavities of the body, i.e. pleural, pericardial or peritoneal cavities. Approach to diagnosis The presentation is usually with constitutional and local features. Microscopy of the aspirate from tuberculous serous effusions rarely shows AFBs 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). PRACTICAL POINT A biochemistry laboratory is not essential to diagnose an exudate. Simply leave the aspirate standing: if it clots, it is an exudate. TB is a common 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. 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 be falsely low. 35
TB: A CLINICAL MANUAL FOR SOUTH EAST ASIA
TUBERCULOUS PLEURAL EFFUSION The clinical and chest X-ray 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, percussion note and breath sounds on the side of the effusion). Chest X-ray shows unilateral, uniform white opacity, often with a concave upper border. If available, ultrasound confirms 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 1000-2,500 per mm3) with predominant lymphocytes. Occasionally the fluid is blood-stained. The presence of pus on aspiration indicates an empyema (purulent effusion). PRACTICAL POINT In a high TB prevalence population, if there are no facilities for aspiration, you should treat a patient with a unilateral exudative pleural effusion with anti-TB drugs. 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 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/yellow pus. If the pus is too thick to remove using a needle and syringe, use an intercostal drain. Send the pus to the 36
DIAGNOSIS OF TUBERCULOSIS IN ADULTS
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 and/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 chest X-ray confirmation, insert a chest drain with underwater seal. PRACTICAL POINT Always test a patient with signs of a pleural effusion for a succussion splash. TUBERCULOUS PERICARDIAL EFFUSION Diagnosis The diagnosis usually rests on suggestive constitutional and cardiovascular features and investigation findings (ECG, chest X-ray and echocardiography). It is important to exclude uraemia and Kaposi's 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) Cardiovascular signs · tachycardia · low blood pressure · pulsus paradoxus 37
TB: A CLINICAL MANUAL FOR SOUTH EAST ASIA
· 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) PRACTICAL POINT The signs may be subtle. Assess carefully any patient with oedema and/or ascites with the possibility of pericardial effusion in mind. Chest X-ray · large globular heart · clear lung fields · pleural fluid ECG · tachycardia · ST and T wave changes · low voltage QRS complexes Echocardiography · pericardial fluid · strands crossing between visceral and parietal pericardium Pitfalls in diagnosis of pericardial effusion Clinicians have mis-diagnosed 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. 38
DIAGNOSIS OF TUBERCULOSIS IN ADULTS
Therapeutic pericardiocentesis is necessary if there is cardiac tamponade (acute life-threatening cardiac impairment). PRACTICAL POINT In high TB prevalence populations, TB is the most likely treatable cause of pericardial effusion. It may be safer for the patient to start presumptive anti-TB treatment rather than undergo diagnostic pericardiocentesis. 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 EXUDATES . . . . . . . . . malignancy, bacterial pericardial empyema, inflammatory diseases, hypothyroidism 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) blood-borne. Clinical features Patients present with constitutional features and ascites. There may be palpable abdominal masses (mesenteric lymph nodes). Adhesion of nodes 39
TB: A CLINICAL MANUAL FOR SOUTH EAST ASIA
to bowel may cause bowel obstruction. Fistulae may develop between bowel, bladder and abdominal wall. Investigations Do a chest X-ray 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 mm3 and predominantly lymphocytes. Ultrasound, if available, may show features consistent with TB, including enlarged mesenteric or retroperitoneal lymph nodes. 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. 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 visualisation 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 tuberculosis, the differential diagnosis of ascites includes the following: TRANSUDATES . . . . . . heart failure, renal failure, nephrotic syndrome, liver failure, hypoproteinaemia; EXUDATES . . . . . . . . . malignancy, other infections causing peritonitis. 40
DIAGNOSIS OF TUBERCULOSIS IN ADULTS
2 2 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) blood-borne. Clinical features The patient may present with constitutional features and a 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 (C.S.F.) examination. In most cases of clinically suspected TB meningitis, lumbar puncture is safe. PRACTICAL POINT Lumbar puncture is hazardous if the patient has a focal neurological deficit (cerebral space-occupying lesion) or if fundoscopy shows papilloedema (raised intra-cranial pressure). In these circumstances, a C.A.T. brain scan is helpful, if available. Otherwise, it may be safer to start presumptive treatment with anti-TB drugs rather than risk lumbar puncture. The C.S.F. opening pressure is high. The C.S.F. may look clear or cloudy. The white cell count is usually about 500 per mm3 with predominantly lymphocytes (or early in the course of infection, predominantly polymorphs). Usually the protein level is high and the glucose low. C.S.F 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 C.S.F. sample; b) examine the deposit for at least half an hour before reporting it as negative; c) examine several C.S.F samples obtained over a few days. 41
TB: A CLINICAL MANUAL FOR SOUTH EAST ASIA
PRACTICAL POINT Always exclude cryptococcal meningitis by C.S.F. microscopy (India ink stain) and, if available, fungal culture.
Differential diagnosis The table below shows the differential diagnosis of TB meningitis, with typical C.S.F. abnormal findings.
Differential diagnosis of tuberculous meningitis
CSF ABNORMALITIES
DISEASE
CSF WHITE CELLS
PROTEIN
GLUCOSE
MICROSCOPY
tuberculous. . . . . . . Elevated. . . . . . Increased . . . . . Decreased . . . . . AFB
meningitis
L > PMN
(in some cases)
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
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
cryptococcal . . . . . Elevated . . . . . Increased . . . . Decreased . . . . Positive India
meningitis
L > PMN
ink staining
PMN = polymorphonuclear leucocytes; L = lymphocytes * common differential diagnosis
42
DIAGNOSIS OF TUBERCULOSIS IN ADULTS
2 2 6 Other forms of extrapulmonary TB
Other forms of extrapulmonary tuberculosis are less common. The table below shows the usual clinical features and diagnostic tests.
Other forms of extrapulmonary TB
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 Synovial biopsy
Gastrointestinal . . . . . . . . Abdominal mass . . . . . . . . . . . Barium X-rays Diarrhoea
Liver . . . . . . . . . . . . . . . Right upper quadrant. . . . . . . . Ultrasound and
pain and mass
biopsy
Renal and urinary tract . . . Urinary frequency . . . . . . . . . . Sterile pyuria
Dysuria
Urine culture
Haematuria
Intravenous
Loin pain / swelling
pyelogram
Adrenal gland . . . . . . . . . Features of hypoadrenalism . . . Plain X-ray
(hypotension,
(calcification)
low serum sodium,
Ultrasound
normal/high potassium,
raised urea, low glucose
Upper respiratory tract . . . Hoarseness . . . . . . . . . . . . . . Usually complication
Pain in ear
of pulmonary disease
Pain on swallowing
Female genital tract . . . . . Infertility . . . . . . . . . . . . . . . . Pelvic examination
Pelvic inflammatory disease X-ray genital tract
Ectopic pregnancy
Tissue biopsy
Male genital tract . . . . . . . Epididymitis . . . . . . . . . . . . . . Often evidence of renal/ urinary tract TB
43
TB: A CLINICAL MANUAL FOR SOUTH EAST ASIA
2 2 7 Further information on spinal, gastrointestinal and hepatic TB Spinal TB Tuberculosis 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, spreads along the anterior and longitudinal ligaments, then involves the adjacent vertebral bodies. In areas of high TB prevalence, 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. 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 Ileo-caecal 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 ileo-caecal Crohn's 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. SUGGESTIONS FOR FURTHER READING Toman K. Tuberculosis. Case finding and chemotherapy. Geneva: WHO, 1979. Crofton J, Horne N and Miller F. Clinical Tuberculosis. The MacMillan Press Limited. 1992. Davies PDO. Clinical Tuberculosis. Chapman and Hall Medical. 1994. 44
DIAGNOSIS OF TUBERCULOSIS IN CHILDREN
CHAPTER 3 DIAGNOSIS OF TUBERCULOSIS IN CHILDREN 3 1 HOW DOES TB IN CHILDREN DIFFER FROM TB IN ADULTS? Transmission of TB to children The source of transmission of TB to a child is usually an adult (usually a family member) with sputum smear-positive PTB. Public health importance Cases of TB in children usually represent between 5-15% of all TB cases. The frequency of childhood TB in a given population depends on the following: the number of infectious cases, the intensity of transmission, and the age structure of the population. Children rarely have sputum smearpositive TB. So they are rarely infectious. TB in children is therefore due to failure of TB control in adults. Failure of TB control in adults means failure to cure the infectious cases (patients with sputum smear-positive PTB). PRACTICAL POINT A good TB control programme is the best way to prevent TB in children. The highest priority in TB control is to cure the infectious cases. Children are rarely infectious. However, it is still important to cure them! Good treatment of TB in childhood will result in the following: a) decreased morbidity and mortality; b) improved NTP credibility and reputation. Risk of infection Risk of infection depends on 2 factors: a) extent of exposure to infectious droplet nuclei, and b) susceptibility to infection. Consider an infant whose mother has sputum smear-positive PTB. The infant has a high risk of acquiring infection: mother and infant are in very close contact; immune defences are poor. An infant with HIV infection has an even greater susceptibility to infection with tubercle bacilli. Risk of progression of infection to disease. The vast majority of HIV-negative children infected with M. tuberculosis do not develop TB disease. In these healthy, asymptomatic, but TB-infected children, the only evidence of infection may be a positive tuberculin skin 45
TB: A CLINICAL MANUAL FOR SOUTH EAST ASIA
test. However, an infected child can develop TB disease at any time. The chance of developing disease is greatest shortly after infection and then steadily decreases as time goes by. 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. Other important triggers include the following: other infections (especially measles and whooping cough) and malnutrition. Pathogenesis The usual route of infection and early sequence of events in primary pulmonary infection are similar in adults and children. TB disease in children is usually primary TB. A child may have asymptomatic M. tuberculosis infection: the tubercle bacilli can lie dormant for many years. If the tubercle bacilli reactivate some years later, causing post-primary TB, the child has usually grown into an adult by then. The age when a child is infected determines the pattern of primary disease. Up to puberty, bloodborne spread is common. This results in disseminated (miliary and extrapulmonary) disease. After puberty, pulmonary spread is more common. PRACTICAL POINT Malnourished children may develop severe PTB at any age. 3 2 APPROACH TO DIAGNOSIS If you find the diagnosis of TB in children easy, you are probably overdiagnosing TB. If you find the diagnosis of TB in children difficult, you are not alone. It is easy to over-diagnose TB in children. It is also easy to miss TB in children. Carefully assess all the evidence before making the diagnosis. Adults with PTB usually present with cough and sputum. Although sputum culture is the definitive test, in practice the readily available usual "gold standard" test for adults with PTB is sputum smear microscopy. However, there is no such "gold standard" test in children. TB in children is a general disease which may appear in any part of the body. Also, under the age of 10 years, children with PTB rarely cough up sputum. They 46
DIAGNOSIS OF TUBERCULOSIS IN CHILDREN
usually swallow their sputum. Gastric suction and laryngeal swabs are generally not useful unless facilities are available for M. tuberculosis culture. The diagnosis of TB in children is therefore nearly always presumptive. This means that bacteriological confirmation is usually not possible. This situation in children is similar to that in adults with sputum smear-negative PTB or extrapulmonary TB. The clinical features are constitutional and local (depending on the part of the body affected). The local clinical features related to the site of disease are similar in children and adults (see Chapter 2 for details). The diagnosis rests on consistent clinical features and investigation findings. If available, a tuberculin skin test may be helpful. In most cases of suspected PTB, the child has usually received treatment with a broadspectrum antibiotic, with no clinical response. In some hospitals, helpful special diagnostic investigations may be available. These may include specialised X-rays, biopsy and histology, and TB culture. Always look for the following 2 important clues to TB in children: 1) it is usually possible to identify the adult source of infection; 2) failure to thrive or weight loss (growth faltering). In the absence of these 2 clues, TB is less likely. PRACTICAL POINT Ask the mother of a child with suspected TB for the child's "road to health" card (growth card). Look at the card for growth faltering or weight loss. 3 3 SCORE SYSTEM FOR THE DIAGNOSIS OF TB IN CHILDREN A score system is one way of trying to improve the diagnosis of childhood TB. The basis of a score system is the careful and systematic collection of diagnostic information. A score system helps guide your clinical judgment. A score above a certain threshold indicates a high likelihood of TB. The table shows a score chart (adapted from Crofton, Horne and Miller) for helping to diagnose childhood TB. A score of 7 or more indicates a high likelihood of TB. 47
TB: A CLINICAL MANUAL FOR SOUTH EAST ASIA
48
DIAGNOSIS OF TUBERCULOSIS IN CHILDREN
3 4 "TREATMENT TRIAL" This is a controversial topic. In the past, some doctors have advocated a treatment trial with anti-TB drugs as a diagnostic manoeuvre. The idea is that if the child responds to treatment with anti-TB drugs, then the diagnosis is TB. There are some problems with this approach: a) some anti-TB drugs also 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. On account of these problems, it is better to try to come to a decision: yes, the child has TB; or, no, the child does not have TB. The process of coming to a decision is an active process. The process involves weighing up the clinical evidence and investigation findings, careful thought, and often a period of observation. 3 5 TUBERCULIN SKIN TEST Tuberculin is a purified protein derived from tubercle bacilli. Thus, 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. We quantify this reaction by measuring the diameter of skin induration (thickening) at the site of the reaction. Various conditions may suppress this reaction. The reaction indicates hypersensitivity. In other words, the reaction only shows that the person has at some time had infection with M. tuberculosis. PRACTICAL POINT A tuberculin test does not measure immunity. By itself, it does not indicate the presence or extent of tuberculosis disease; it only indicates infection. 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 and Miller) gives a good account. 49
TB: A CLINICAL MANUAL FOR SOUTH EAST ASIA
Value of a negative tuberculin test A tuberculin test is negative when the diameter of skin induration is less than 10 mm. This is regardless of whether or not the person has had BCG. A negative tuberculin skin test does not exclude TB. In other words, a negative test is of no help in deciding that someone does not have TB. The table shows the conditions which may suppress a tuberculin skin test in a person with active TB. CONDITIONS WHICH 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 Value of a positive tuberculin skin test The criterion for a 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. This reaction is usually a weaker reaction (diameter often less than 10 mm) than the reaction to natural infection with M. tuberculosis. Therefore, in a child who has not had BCG, a tuberculin test is positive when the diameter of skin induration is 10 mm or more. In a child who has had BCG, a test is positive when the diameter of induration is 15 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 (above 10-15 mm), the stronger is that one piece of evidence. 3 6 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 don't have a systematic, organised 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). 50
DIAGNOSIS OF TUBERCULOSIS IN CHILDREN
Consider a child under 5 years of age living with a sputum smear-positive PTB patient. This child household contact is at high risk of TB infection and developing TB disease, especially if HIV-positive. Tuberculin skin testing is often not available. Also, tuberculin skin testing is not a reliable way of distinguishing TB-infected from non-TB-infected children. The IUATLD therefore recommends isoniazid preventive treatment for all child household contacts (under 5 years of age) of sputum smear-positive PTB patients. SUGGESTIONS FOR FURTHER READING Miller FJW. Tuberculosis in children. New Delhi: Churchill-Livingstone, 1986. Chaulet P and collaborators. Children in the Tropics. Childhood tuberculosis, still with us. International Children's Centre, Paris. Paris, 1992. Crofton J, Horne N and Miller F. Clinical Tuberculosis. The Macmillan Press Limited. 1992. International Union Against Tuberculosis and Lung Disease. Tuberculosis guide for low income countries. pmi Verlagsgruppe. 3rd edition. Frankfurt, 1994. Topley JM, Maher D, Mbewe LN. Transmission of tuberculosis to contacts of sputum positive adults in Malawi. Arch Dis Child 1996; 74: 140-143. 51
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52
STANDARDISED TB CASE DEFINITIONS AND TREATMENT CATEGORIES
CHAPTER 4 STANDARDISED TB CASE DEFINITIONS AND TREATMENT CATEGORIES 4 1 STANDARDISED CASE DEFINITIONS 4 1 1 Introduction The diagnosis of TB means that a patient has TB. But 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 standardised way. This means that when we talk about a certain type of TB, we are all talking about the same thing. PRACTICAL POINT On making the diagnosis of TB, you must also decide on the TB case definition. 4 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 7). 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 minimise 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 PRACTICAL POINT Always ask a "new" TB patient if he or she has ever had TB treatment before. 53
TB: A CLINICAL MANUAL FOR SOUTH EAST ASIA
The table below shows the determinants of case definition and their importance.
DETERMINANT OF CASE DEFINITION
IMPORTANCE
site of TB
some authorities recommend a more intensive regimen for certain sites (e.g. pulmonary compared to extrapulmonary) recording and reporting (in a good NTP, at least 50% of total cases will be pulmonary)
priority is to identify sputum smear-positive cases (since these are the infectious cases) result of sputum smear for AFBs recording and reporting (monitoring of bacteriological cure is readily available only in this group)
previous TB treatment severity of TB
the previously treated patient who is still sputum smear-positive has a high risk of drug-resistant TB and so needs a different and more powerful regimen most authorities recommend a more intensive regimen for smear-negative PTB patients with extensive disease rather than limited disease
4 1 3 Case definitions by site and result of sputum smear PTB Smear positive case: at least 2 sputum smears positive for AFBs OR 1 sputum smear positive for AFBs and chest X-ray abnormalities consistent with active TB. Smear negative case: at least 2 (and preferably 3) sputum smears negative for AFBs AND chest X-ray abnormalities consistent with active TB. In most cases, the patient will have had treatment with a broad-spectrum antibiotic, with no response.
54
STANDARDISED TB CASE DEFINITIONS AND TREATMENT CATEGORIES
Extrapulmonary TB Clinical and/or histological evidence consistent with active TB. PRACTICAL POINT The following are forms of extrapulmonary TB: pleural effusion (pleura are outside the lungs); hilar lymphadenopathy (hilar lymph nodes are outside the lungs); miliary (TB is widespread throughout the body and not limited to the lungs). 4 1 4 Case definitions by previous treatment New A patient who for sure has never taken anti-TB drugs for more than one month. Relapse A TB patient who a) previously received treatment and was declared cured AND b) has once again developed sputum smear-positive TB. Treatment failure A new TB patient who is still sputum smear-positive 5 months or more after starting treatment. Return after interruption of treatment (default) A new TB patient who a) completed at least one month of treatment AND b) returned after at least 2 months' interruption of treatment Transfer in A TB patient already registered for treatment in one district who transfers to another district and continues treatment. Other A TB patient who does not easily fit into one of the above case definitions. One example is a chronic case (a TB patient who remains sputum smearpositive after completing a supervised re-treatment regimen). 55
TB: A CLINICAL MANUAL FOR SOUTH EAST ASIA
4 2 STANDARDISED TREATMENT CATEGORIES
Based on case definition, a TB patient falls into 1 of 4 categories for treatment. The categories are in order of priority. The highest priority is to treat Category 1 patients. The lowest priority is to treat Category 4 patients. The table below shows the patients belonging to each category.
TB TREATMENT CATEGORY
PATIENTS
Category 1. . . . . . . . . . . . . . new sputum smear-positive PTB
newly diagnosed seriously ill patients
with severe forms of TB
Category 2. . . . . . . . . . . . . . relapse treatment failure return after default (interrupted treatment)
Category 3. . . . . . . . . . . . . . sputum smear-negative PTB with limited parenchymal involvement extrapulmonary TB (less severe forms)
Category 4. . . . . . . . . . . . . . chronic cases
The table below shows the severe and less severe forms of extrapulmonary TB.
SEVERE EXTRAPULMONARY TB
LESS SEVERE EXTRAPULMONARY TB
· meningitis · miliary · pericarditis · peritonitis · bilateral or extensive · pleural effusion · spinal · intestinal · genito-urinary
· lymph node · pleural effusion (unilateral) · bone (excluding spine) · peripheral joint · adrenal gland
Children Children and adolescents often fall into Category 3. PTB in children is almost always "smear-negative" (actually smear not done, since children rarely cough up sputum). Young people infected during adolescence may develop primary TB. This usually presents as pleural effusion or small parenchymal lesions in the lungs. In one series of adolescents with pleural effusion, without treatment about 25% went on to develop PTB.
SUGGESTED FURTHER READING WHO. Treatment of tuberculosis. Guidelines for national programmes. Geneva, 1993.
56
PAT I E N T S
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OF
CHAPTER 5 TREATMENT OF TB PATIENTS 5 1 INTRODUCTION Aims of anti-TB drug treatment · To cure the patient of TB. · To prevent death from active TB or its late effects. · To prevent TB relapse. · To decrease TB transmission to others. PRACTICAL POINT Properly applied anti-TB drug treatment will achieve these aims and prevent the emergence of drug resistant M. tuberculosis. Effective anti-TB drug treatment = properly applied ShortCourse Chemotherapy We have known for over 100 years that M. tuberculosis causes TB. We have had effective anti-TB drugs for nearly 50 years. Yet the world's TB problem is now bigger than ever. Why? The problem is not the lack of an effective treatment. Properly applied short-course chemotherapy (SCC) fulfills the above aims of anti-TB drug treatment. The problem is an organisational problem: how to apply SCC properly? The answer is a properly managed TB control programme. Chapter 7 describes the organisational framework of an effective TB control programme. Standardised TB treatment regimens There are many different possible anti-TB treatment regimens. The World Health Organisation (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD) recommend standardised TB treatment regimens. The national TB control programme (NTP) in your country recommends which regimens to use. When properly applied, these standardised regimens fulfill the above aims of anti-TB drug treatment. The regimens are affordable. The World Bank recognises shortcourse chemotherapy (SCC) as one of the most cost-effective of all health interventions. 57
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The essential anti-TB drugs The table shows the essential anti-TB drugs and their mode of action, potency, and recommended dose.
ESSENTIAL ANTI-TB DRUG (ABBREVIATION)
MODE OF ACTION POTENCY
isoniazid (H)
bactericidal
high
rifampicin (R)
bactericidal
high
pyrazinamide (Z) bactericidal
low
streptomycin (S) bactericidal
low
RECOMMENDED DOSE (MG/KG)
DAILY 5 10 25 15
INTERMITTENT
3X/WK 10 10 35 15
2X/WK 15 10 50 15
ethambutol (E) bacteriostatic low
15
(30)
(45)
thiacetazone (T) bacteriostatic low
3
not applicable
The available formulations and combinations of the marketed drugs vary from brand to brand. Check them before you prescribe.
Intermittent use Thiacetazone is the only anti-TB drug not effective when given intermittently (2 or 3 times a week). The efficacy of intermittent ethambutol is not proven.
5 2 MODES OF ACTION OF ANTI-TB DRUGS
Consider a population of TB bacilli in a TB patient. This population of bacilli consists of the following groups: a) metabolically active, continuously growing bacilli inside cavities; b) bacilli inside cells, e.g. macrophages; c) semi-dormant bacilli (persisters) which undergo occasional spurts of metabolism; d) dormant bacilli which fade away and die on their own. Different anti-TB drugs act against different groups of bacilli. PRACTICAL POINT Anti-TB drug treatment is so long because it is difficult to kill the semi-dormant TB bacilli.
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Bactericidal drugs ISONIAZID kills 90% of the total population of bacilli during the first few days of treatment. It is most effective against the metabolically active, continuously growing bacilli. RIFAMPICIN can kill the semi-dormant bacilli which isoniazid cannot. PYRAZINAMIDE kills bacilli in an acid environment inside cells, e.g. macrophages. Sterilising action This means killing all the bacilli. The persisters are hardest to kill. The aim of killing all the bacilli is to prevent relapse. Rifampicin is the most effective sterilising drug. Its effectiveness makes short-course chemotherapy possible. Pyrazinamide is also a good sterilising drug, since it kills the bacilli protected inside cells. Preventing drug resistance Consider a population of TB bacilli never previously exposed to anti-TB drugs. There will be a few naturally-occurring drug-resistant mutant bacilli. Faced with anti-TB drugs, these drug-resistant mutant bacilli will grow and replace the drug-sensitive bacilli under the following circumstances: a) inadequate anti-TB drug combinations; b) anti-TB drug treatment not properly applied. Isoniazid and rifampicin are most effective in preventing resistance to other drugs. Streptomycin and ethambutol are slightly less effective. 5 3 TB TREATMENT REGIMENS Treatment regimens have an initial (intensive) phase and a continuation phase. 5 3 1 New cases Initial phase (2 months) During the initial phase, there is rapid killing of TB bacilli. Infectious patients become non-infectious within about 2 weeks. Symptoms improve. The vast majority of patients with sputum smear-positive TB become sputum smear-negative within 2 months. Directly observed therapy (DOT) is essential in the initial phase to ensure that the patient takes every single 59
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dose. This protects rifampicin against the development of drug resistance. The risk of drug resistance is higher during the early stages of anti-TB drug treatment when there are more TB bacilli. Continuation phase (4-6 months) Fewer drugs are necessary, but for a longer time, in the continuation phase. The drugs eliminate the remaining TB bacilli. Killing the persisters prevents relapse after completion of treatment. Directly observed therapy is the ideal when the patient receives rifampicin in the continuation phase. If local conditions do not allow directly observed therapy, the next best is as close supervision as possible, for example weekly supervision. The risk of drug resistance is less during the continuation phase when there are fewer TB bacilli. The patient usually receives monthly drug supplies for self-administered treatment during a continuation phase which does not include rifampicin. 5 3 2 Retreatment cases The initial phase lasts 3 months, with directly observed therapy. The continuation phase lasts 5 months, with close supervision. 5 3 3 Standard code for TB treatment regimens There is a standard code for TB treatment regimens. Each anti-TB drug has an abbreviation (shown above). A regimen consists of 2 phases. The number before a phase is the duration of that phase in months. A number in subscript (e.g. 3) after a letter is the number of doses of that drug per week. If there is no number in subscript after a letter, then treatment with that drug is daily. An alternative drug (or drugs) appears as a letter (or letters) in brackets. Examples 2 SHRZ / 6 HE. This is a common regimen. The initial phase is 2 SHRZ. The duration of the phase is 2 months. Drug treatment is daily (no subscript number, e.g. 3 after the letters), with streptomycin (S), isoniazid (H), rifampicin (R) and pyrazinamide (Z). The continuation phase is 6 HE. The duration of the phase is 6 months. Drug treatment is daily, with isoniazid (H) and ethambutol (E). 2 SHRZ / 4 H3R3. In some countries, resources are available to provide rifampicin in the continuation phase as well as in the initial phase. 60
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The intensive phase (2 SHRZ) is the same as before. The continuation phase is 4 H3R3. The duration is 4 months, with isoniazid and rifampicin three times per week (subscript number 3 after the letters).
5 3 4 Recommended treatment regimens
There are several different possible regimens. The regimen recommended depends on the patient treatment category (see Chapter 4). The table shows possible alternative regimens for each treatment category. Follow the regimens recommended by the NTP in your country. Look in the NTP Manual.
ALTERNATIVE TREATMENT REGIMENS FOR EACH PATIENT TREATMENT CATEGORY
TB TREATMENT CATEGORY
TB PATIENTS
ALTERNATIVE TB TREATMENT REGIMENS
INITIAL PHASE
CONTINUATION PHASE
new smear-positive PTB 2 SHRZ (EHRZ) 6 HE
and seriously ill
2 SHRZ (EHRZ) 4 HR
1
extrapulmonary or smear- 2 SHRZ (EHRZ) 4 H3R3
negative pulmonary
2 E3H3R3Z3*
4 H3R3*
(severe TB)
sputum smear-positive: 2 SHRZE/1 HRZE 5 H3R3E3
2
relapse treatment failure, and
2 SHRZE/1 HRZE 5 HRE
2 S3H3R3Z3E3/
5 H3R3E3*
return after default
1 H3R3Z3E3*
smear-negative PTB and 2 HRZ or 2 H3R3Z3 6 HE
extrapulmonary TB
3
(less severe)
2 HRZ or 2 H3R3Z3 2 HR/4 H 2 HRZ or 2 H3R3Z3 2 H3R3/4H
2 H3R3Z3*
4 H3R3*
chronic case
NOT APPLICABLE
4
(still sputum-positive after
(Refer to special centre if
supervised re-treatment)
second-line drugs available)
* Directly observed treatment regimens applied in the Revised National Tuberculosis Programme in India. Some authorities recommend a 7 month continuation phase with daily isoniazid and rifampicin (7 HR) for Category 1 patients with the following forms of TB: TB meningitis, miliary TB, spinal TB with neurological signs.
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5 3 5 Use of streptomycin and thiacetazone in areas of high HIV prevalence Streptomycin · In high TB/HIV prevalence populations, overcrowding is common in TB wards. The high staff workload may result in inadequate sterilisation of needles and syringes used for streptomycin injections. There is a risk of transmission of HIV and other blood-born pathogens between patients. · Streptomycin injections are very painful in wasted HIV-infected TB patients. · Many NTPs now recommend the use of ethambutol in place of streptomycin. Thiacetazone · Thiacetazone is associated with a high risk of severe, and sometimes fatal, skin reaction in HIV-infected individuals. · Use ethambutol instead of thiacetazone in patients with known or suspected HIV infection. · At present some countries do not have the resources to substitute ethambutol for thiacetazone. The most effective treatment available in some countries may still include thiacetazone. Where it is not possible to avoid the use of thiacetazone, it is essential to warn patients about the risk of severe skin reactions. Advise the patient to stop thiacetazone at once and report to a health unit if itching or a skin reaction occurs. 5 4 TB TREATMENT REGIMENS: QUESTIONS AND ANSWERS Why use 4 drugs in the initial phase? · There is a high degree of initial resistance in some populations. · Use of a 3-drug regimen runs the risk of selecting out drug-resistant mutants. This may happen especially in patients with high bacillary loads, e.g. cavitary pulmonary TB. · A 4-drug regimen decreases the risks of drug resistance, treatment failure, and relapse. Why use pyrazinamide only in the initial phase? · Pyrazinamide has its maximum sterilising effect within the first 2 months. There is less benefit from longer use. Is a 4 month continuation phase possible? · A 4 month continuation phase is possible with rifampicin throughout (e.g. 2 SHRZ/ 4 HR). This is because isoniazid and rifampicin are 62
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both potent bactericidal drugs. In the usual 6 month continuation phase (6 HE or 6 HT), the only potent bactericidal drug is isoniazid. Why not always use regimens containing rifampicin throughout? · Rifampicin is too expensive for many countries to afford these regimens. Why is it so important to prevent rifampicin resistance? · Rifampicin is the most effective anti-TB drug. It is unlikely that a new anti- TB drug will become widely available in the near future. If rifampicin resistance becomes widespread, TB will be effectively untreatable. How do we prevent rifampicin resistance? · Bad TB control programmes, lack of supervision of anti-TB treatment, bad prescribing by clinicians, and the use of rifampicin alone generate acquired drug resistance. The best way to prevent rifampicin resistance is to strengthen NTPs and ensure directly observed therapy when and where possible. It is important to use methods of drug administration which avoid the danger of the use of rifampicin alone. These include the use whenever possible of fixed-dose combination tablets and of anti-TB drugs supplied in blister packs. What is the treatment for multi-drug resistant TB? · Multi-drug resistant TB arises from failure to deliver anti-TB drug treatment properly. Multi-drug resistance represents NTP failure. In many high TB prevalence countries, second-line drugs are prohibitively expensive and unavailable, e.g. ethionamide, cycloserine, kanamycin, capreomycin. Multi-drug resistant TB is therefore often untreatable. What should we do when faced with multi-drug resistant TB? · The cause of the problem is NTP failure. The answer is to devote time, effort and resources to improving the NTP. In some countries, one or two specialist centres may have the specialist expertise and second-line drugs available to treat patients with multi-drug resistant TB. 5 5 USE OF ANTI-TB DRUGS IN SPECIAL SITUATIONS Pregnancy · Streptomycin during pregnancy can cause permanent deafness in the baby. · Do not give streptomycin in pregnancy. Use ethambutol instead. 63
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Renal failure · Rifampicin, isoniazid and pyrazinamide are safe. · The excretion of streptomycin is renal. The excretion of ethambutol and thiacetazone is partly renal. · Avoid streptomycin and ethambutol if there are alternatives. Otherwise give in reduced doses at less frequent intervals. · Do not give thiacetazone. The margin is too narrow between the therapeutic and toxic dose. Liver disease · Most anti-TB drugs can cause liver damage. Jaundiced patients who develop TB should receive treatment with the following regimen: 2 SHE / 6 HE. · Do not give pyrazinamide to patients with liver disease. 5 6 THE ROLE OF STEROID TREATMENT: QUESTIONS AND ANSWERS What are the indications for treatment with steroids? · TB meningitis (decreased consciousness, neurological defects, or spinal block). · TB pericarditis (with effusion or constriction). · TB pleural effusion (when large with severe symptoms). · Hypo-adrenalism (TB of adrenal glands). · TB laryngitis (with life-threatening airway obstruction). · Severe hypersensitivity reactions to anti-TB drugs. · Renal tract TB (to prevent ureteric scarring). · Massive lymph node enlargement with pressure effects. What is adjuvant steroid treatment? Adjuvant steroid treatment is steroid treatment given in addition to anti-TB drug treatment. Prospective controlled clinical trials have confirmed the benefit of steroids in TB meningitis and pleural and pericardial TB. What are the recommended treatment doses of prednisolone? Rifampicin is a potent inducer of hepatic enzymes which metabolise steroids. The effective dose of prednisolone is therefore half the prescribed treatment dose given to the patient. The table below shows suggested treatment doses of prednisolone. 64
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INDICATION
PREDNISOLONE TREATMENT
TB meningitis . . . . . 60mg daily for weeks 1-4, then decrease over several weeks
TB pericarditis . . . . . 60mg daily for weeks 1-4 30mg daily for weeks 5-8 then decrease over several weeks
TB pleural effusion . . 40mg daily for 1-2 weeks
Is steroid treatment safe in TB/HIV patients? Steroids are immunosuppressants. The worry is that steroids may further depress immunity and increase risk of opportunistic infections in HIVpositive patients. However, on balance, TB/HIV patients are still likely to benefit from the use of steroids for the above indications.
5 7 MONITORING OF TB PATIENTS DURING TREATMENT
Bacteriological monitoring is readily available only for patients with sputum smear-positive pulmonary TB. Routine monitoring of treatment response by chest X-rays is un-necessary and wasteful of resources. For other TB patients, clinical monitoring is the usual guide to treatment response. PRACTICAL POINT Recording treatment results in sputum smearpositive pulmonary TB patients is vital to monitor patient cure and NTP effectiveness (see Chapter 7).
5 7 1 Monitoring of patients with sputum smear-positive PTB
WHEN TO MONITOR
8 MONTH TREATMENT REGIMEN 6 MONTH TREATMENT REGIMEN
At time of diagnosis SPUTUM SMEAR
SPUTUM SMEAR
At end of initial phase SPUTUM SMEAR
SPUTUM SMEAR
In continuation phase SPUTUM SMEAR (MONTH 5) SPUTUM SMEAR (MONTH 5)
On completion of treatment SPUTUM SMEAR (MONTH 8) SPUTUM SMEAR (MONTH 6)
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Sputum smear at end of initial phase The vast majority of patients have a negative sputum smear at the end of the initial phase. If the sputum smear is still positive at the end of the initial phase, continue initial phase treatment with the same 4 drugs for 4 more weeks. If you check the sputum smear again at this point, it is unlikely still to be positive. Go on to the continuation phase (even if the sputum smear after the extra 4 weeks of initial phase treatment is still positive).
Sputum smear in continuation phase In 8 month regimens, a positive sputum smear at 5 months (or any time after 5 months) means treatment failure. In 6 month regimens, a positive sputum smear at 5 months (or any time after 5 months) means treatment failure. A common cause of treatment failure is the failure of the programme to ensure patient adherence to treatment. The patient changes treatment category to Category 2 and starts the re-treatment regimen.
Sputum smear on completion of treatment In 8 month regimens, negative sputum smears at 5 and at 7 or 8 months mean bacteriological cure. In 6 month regimens, negative sputum smears at 5 and 6 months mean bacteriological cure.
5 7 2 Recording treatment outcome in sputum smear-positive PTB patients
At the end of the treatment course in each individual patient, the District TB Officer should record the treatment outcome as follows:
Cure
patient who is smear negative at (or one month prior to) the completion of treatment and on at least one previous occasion
Treatment patient who has completed treatment but in whom smear results are not completed available on at least two occasions prior to the completion of treatment
Treatment patient who remains or becomes again smear positive at failure 5 months or later, after starting treatment
Died patient who dies for any reason during the course of chemotherapy
Defaulted (treatment interrupted)
patient whose treatment has been interrupted for more than 2 consecutive months before the end of course of treatment
Transferred patient who has been transferred to another treatment
out
centre and whose treatment results are not known
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SUGGESTIONS FOR FURTHER READING WHO. Treatment of tuberculosis. Guidelines for national programmes. Geneva, 1993. Horne NW. Modern drug treatment of tuberculosis. Chest, Heart and Stroke Association. 7th edition. London, 1990. Dean P, Ebrahim GJ. The practical care of sick children. A manual for use in small tropical hospitals. London: Macmillan, 1986. WHO. Guidelines on the management of drug-resistant tuberculosis. WHO/TB/96.210. Geneva, 1996. 67
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CHAPTER 6 SIDE EFFECTS OF ANTI-TB DRUGS
6 1 INTRODUCTION
Most TB patients complete their treatment without any significant drug side effects. However, a few patients do develop side effects. So clinical monitoring of all TB patients for side effects is important during TB treatment. Routine laboratory monitoring is not necessary. How do health personnel monitor patients for drug side effects? a) by teaching patients how to recognise symptoms of common side effects and to report if they develop such symptoms. b) by asking specifically about these symptoms when they see all patients at least monthly during treatment.
6 2 PREVENTION OF SIDE EFFECTS
Health personnel should be aware of the special situations which influence the choice and dose of anti-TB drugs (see Chapter 5). It is possible to prevent the peripheral neuropathy caused by isoniazid. This neuropathy usually shows as a burning sensation of the feet. It occurs more commonly in HIV-positive individuals, in drinkers (alcohol), and in patients with diabetes. These patients should receive preventive treatment with pyridoxine 10 mg daily. Ideally, where possible, pyridoxine 10 mg daily should routinely accompany isoniazid.
6 3 WHERE TO MANAGE DRUG REACTIONS
REACTION minor, e.g. gastro-intestinal joint pains major, e.g.jaundice severe rash
WHERE TO MANAGE REACTION out-patient setting refer to district or central hospital
6 4 WHEN TO STOP ANTI-TB DRUGS When a patient has minor drug side-effects, explain the situation, offer symptomatic treatment, and encourage him/her to continue treatment.
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When a patient has a major reaction, stop the suspected drug(s) responsible at once. A patient who develops one of the following reactions must never receive that drug again:
REACTION
DRUG RESPONSIBLE
severe rash agranulocytosis . . . . . . . . . . . . . . . . . . . . . thiacetazone
hearing loss or disturbed balance . . . . . . . . . . . . . . . . streptomycin
visual disturbance (poor vision and colour perception). . . ethambutol
renal failure, shock, or thrombocytopenia . . . . . . . . . . . rifampicin
6 5 SIDE EFFECTS OF ANTI-TB DRUGS
DRUG
COMMON SIDE EFFECTS
isoniazid
· peripheral neuropathy · hepatitis
RARE SIDE EFFECTS convulsions, pellagra, joint pains, agranulocytosis, lupoid reactions, skin rash
rifampicin
· gastrointestinal: anorexia, nausea, vomiting, abdominal pain · hepatitis · reduced effectiveness of oral contraceptive pill
acute renal failure, shock, thrombocytopenia, skin rash, "flu syndrome" (intermittent doses), pseudomembranous colitis, pseudoadrenal crisis
pyrazinamide
· joint pains · hepatitis
gastrointestinal symptoms, skin rash, sideroblastic anaemia
· auditory and vestibular streptomycin nerve damage (also to foetus) skin rash · renal damage
ethambutol · optic neuritis
skin rash, joint pains, peripheral neuropathy
thiacetazone
· skin rash, often with mucous membrane involvement
hepatitis, agranulocytosis
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PRACTICAL POINT Rifampicin reduces the effectiveness of the oral contraceptive pill. Advise a woman to choose between the following two options. Following consultation with a physician, she could take an oral contraceptive pill containing a higher dose of oestrogen (50mcg). Alternatively, she could use another form of contraception.
6 6 SYMPTOM-BASED APPROACH TO MANAGEMENT OF DRUG SIDE EFFECTS
SIDE EFFECTS
DRUG(S) PROBABLY RESPONSIBLE
MANAGEMENT
minor
continue anti-TB drugs
anorexia, nausea, . . . . . . rifampicin . . . . . . . . give tablets last thing
abdominal pain
at night
joint pains . . . . . . . . . . . pyrazinamide . . . . . aspirin
burning sensation in feet. . isoniazid. . . . . . . . . pyridoxine 100 mg daily
orange/red urine . . . . . . rifampicin . . . . . . . . reassurance
major
stop drug(s) responsible
skin itching/ rash . . . . . . thiacetazone . . . . . . stop anti-TB drugs (see below) (streptomycin)
deafness . . . . . . . . . . . . streptomycin . . . . . . stop streptomycin, use
(no wax on auroscopy)
ethambutol instead
dizziness . . . . . . . . . . . . streptomycin . . . . . . stop streptomycin, use
(vertigo and nystagmus)
ethambutol instead
jaundice . . . . . . . . . . . . . most anti-TB drugs . . stop all anti-TB drugs until
(other causes excluded)
jaundice resolves (see below)
vomiting and confusion . . most anti-TB drugs . . stop anti-TB drugs, urgent
(suspected drug-induced
liver function tests
pre-icteric hepatitis)
visual impairment . . . . . . . ethambutol . . . . . . . stop ethambutol
generalised, including. . . . rifampicin . . . . . . . . stop rifampicin shock and purpura
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6 7 MANAGEMENT OF SKIN ITCHING/RASH The approach depends on whether or not the patient is receiving thiacetazone. In populations with a high TB/HIV prevalence, thiacetazone is the drug most likely to cause skin reactions. 6 7 1 Treatment regimen includes thiacetazone If a patient starts to itch, and there is no other obvious cause (e.g. scabies), stop the anti-TB drugs at once. The itching may be a warning sign of severe skin reaction. Stopping the thiacetazone at once may avert, or decrease the severity, of the skin reaction. Give the patient intravenous fluids if the skin reaction is severe: a) exfoliative dermatitis or toxic epidermal necrolysis b) mucous membrane involvement c) hypotension Many physicians give steroid treatment, although there is no firm evidence that this helps. A typical dose schedule consists of 60 mg daily of oral prednisolone until there is some improvement. A gradual reduction in dose over the next few days depends on the patient's response. Initially, if a patient is unable to swallow, give intravenous hydrocortisone 100-200 mg daily (instead of oral prednisolone). On recovery, restart anti-TB drugs, replacing thiacetazone with ethambutol. PRACTICAL POINT Never give a patient thiacetazone again after any thiacetazone reaction. A severe reaction may mean stopping anti-TB treatment for 3-4 weeks. A severely ill TB patient may die without anti-TB treatment. In this case, give 2 or more previously unused drugs until the reaction has resolved. Then reintroduce the initial regimen (with ethambutol instead of thiacetazone). 6 7 2 Treatment regimen does not include thiacetazone If a patient starts to itch, exclude other obvious causes. Try treatment with anti-histamines, continue anti-TB treatment and observe the patient closely. 72
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In some cases, the itching resolves. In other cases, a rash develops. In this case, stop the anti-TB drugs. Wait for the rash to resolve. If the reaction is severe, the patient may need supportive treatment as above.
The problem now is re-introducing TB treatment when we don't know which anti-TB drug was the drug responsible for the reaction. The table shows the standard approach to re-introducing anti-TB drugs one by one after a drug reaction.
RE-INTRODUCTION OF ANTI-TB DRUGS FOLLOWING DRUG REACTION
LIKELIHOOD OF CAUSING A REACTION
CHALLENGE DOSES
DRUG
DAY 1 DAY 2 DAY 3
Isoniazid
least likely
50mg 300mg 300mg
Rifampicin
75mg 300mg Full dose
Pyrazinamide
250mg 1 gram Full dose
Ethambutol
100mg 500mg Full dose
Streptomycin most likely
125mg 500mg Full dose
If possible, while the patient undergoes drug challenging, give 2 anti-TB drugs which the patient has not had before. The idea of drug challenging is to identify the drug responsible for the reaction. Drug challenge starts with the anti-TB drug least likely to be responsible for the reaction (i.e. isoniazid). Start with a small challenge dose. If a reaction occurs to a small challenge dose, it will not be such a bad reaction as to a full dose. Gradually increase the dose over 3 days. Repeat the procedure, adding in one drug at a time. A reaction after adding in a particular drug identifies that drug as the one responsible for the reaction. If the drug responsible for the reaction is pyrazinamide, ethambutol, or streptomycin, resume anti-TB treatment without the offending drug. If possible, replace the offending drug with another drug. It may be
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necessary to extend the treatment regimen. Consider the start of the resumed regimen as a new start of treatment. This prolongs the total time of TB treatment, but decreases the risk of recurrence. PRACTICAL POINT Refer patients with severe drug reactions to specialist centres. 6 8 DESENSITISATION Rarely, patients develop hypersensitivity reactions to the 2 most potent anti-TB drugs, isoniazid and rifampicin. These drugs form the corner-stone of SCC. If an HIV-negative patient has had a reaction (but not a severe reaction) to isoniazid or rifampicin, it may be possible to desensitise the patient to the drug. However, never attempt desensitisation in TB/HIV patients because of the high risk of serious toxicity. The following method for desensitisaion therefore does not apply to TB/HIV patients. Start desensitisation with a tenth of the normal dose. Then increase the dose by a tenth each day, until the patient has the full dose on the tenth day. Once drug sensitisation is over, give the drug as part of the usual treatment regimen. If possible, while carrying out desensitisation, give the patient 2 anti-TB drugs which the patient has not had before. This is to avoid the risk of drug resistance developing during desensitisation. PRACTICAL POINT Never attempt desensitisation in TB/HIV patients. 6 9 MANAGEMENT OF HEPATITIS Most anti-TB drugs can damage the liver. Isoniazid and pyrazinamide are most commonly responsible. Ethambutol is rarely responsible. When a patient develops hepatitis during anti-TB treatment, the cause may be the anti-TB treatment or another cause. It is often difficult to find out. Try to rule out other possible causes before deciding that the hepatitis is druginduced. Hepatitis presents with anorexia, jaundice and often liver enlargement. 74
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If you diagnose drug-induced hepatitis, stop the anti-TB drugs. Wait until the jaundice resolves. It is strange, but fortunate, that in most cases the patient can re-start the same anti-TB drugs without hepatitis returning. A severely ill TB patient may die without anti-TB drugs. In this case, treat the patient with 2 of the least hepatotoxic drugs, streptomycin and ethambutol. When the hepatitis resolves, re-start usual anti-TB treatment. SUGGESTIONS FOR FURTHER READING Crofton J, Horne N and Miller F. Clinical Tuberculosis. The Macmillan Press Limited. 1992. Horne NW. Modern Drug Treatment of Tuberculosis. The Chest, Heart and Stroke Association. Seventh edition. London, 1990. 75
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FRAMEWORK FOR EFFECTIVE TUBERCULOSIS CONTROL
CHAPTER 7 FRAMEWORK FOR EFFECTIVE TUBERCULOSIS CONTROL 7 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 developed a new framework of strategy and policy for TB control in response to this global emergency. This strategy and policy is unchanged in the face of the epidemic of TB/HIV co-infection. It is vital for successful TB control for health care workers to treat TB patients within this framework in a National TB Programme (NTP). 7 2 COMPONENTS OF TB CONTROL FRAMEWORK The framework consists of the following: 1. Overall objectives of TB control. 2. Strategy for TB control. 3. Targets for TB control. 4. TB control policy package. 5. Key operations of a national TB programme. 6. Indicators to measure progress in TB control. 7 2 1 Overall objectives of TB control To reduce mortality, morbidity and disease transmission (while avoiding the development of drug resistance). 77
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7 2 2 Strategy for TB control To provide short-course chemotherapy under direct observation to, at least, all identified smear-positive TB cases (the sources of infection). 7 2 3 Targets for TB control a) To cure 85% of new detected cases of sputum smear-positive PTB. A national TB programme which achieves at least an 85% cure rate in patients with sputum smear-positive PTB has the following impact on TB: i) TB prevalence and the rate of TB transmission both decrease immediately; ii) TB incidence decreases gradually; iii) there is less acquired drug resistance (which makes future treatment of TB easier and more affordable). b) To detect 70% of existing cases of sputum smear-positive PTB It is important to expand case-finding only when a national TB programme has achieved a high cure rate. A national TB programme which 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 acquired drug-resistance increases. A treatable epidemic becomes an untreatable epidemic. AN EFFECTIVE NTP HAS A HIGH CURE RATE AND A LOW LEVEL OF ACQUIRED DRUG RESISTANCE. In the presence of a high cure rate, increased case detection of sputum smear-positive PTB cases will decrease TB transmission. 7 2 4 TB control policy package The success of the WHO strategy depends on the implementation of a 5-point package: i) government commitment to a national TB programme; ii) case detection through "passive" case-finding (sputum smear microscopy for PTB suspects attending health services); iii) short-course chemotherapy for all smear-positive PTB cases (under direct observation for, at least, the initial phase of treatment); iv) regular, uninterrupted supply of all essential anti-TB drugs; v) monitoring system for programme supervision and evaluation. 78
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7 2 5 Key features of a national TB programme (NTP) i) NTP has a central unit. ii) NTP manual available in districts. iii) A recording and reporting system using standardised registers. iv) A training programme covering all aspects of the policy package. v) Microscopy services nationwide. vi) Treatment services integrated with existing health services, with priority for supervised short-course chemotherapy. vii) Regular supply of drugs and diagnostic materials. viii)Plan of supervision. ix) A project development plan, with details of budget, sources of funding and responsibilities. 7 2 6 Indicators of NTP progress in TB control. i) NTP manual available in districts (reflects government commitment). ii) The number of administrative areas in the country which are implementing the new TB control strategy. iii) The cure rate. iv) The case detection rate. 7 2 7 Cohort analysis: questions and answers What is cohort analysis? A cohort of TB patients consists of all those sputum smear-positive PTB patients registered during a certain time. The time period may be a quarter of a year or one year. New and previously treated patients form separate cohorts. For example, consider all those sputum smear-positive PTB patients registered from 1 January to 31 March in any year. They form the cohort for that quarter-year. Cohort analysis refers to the statistical breakdown of that cohort according to certain indicators. These indicators are the standardised case definitions and treatment categories (see Chapter 4) and the 6 treatment outcomes described in Chapter 5 (section 5.7.2). Who performs cohort analysis and how often? Cohort analysis is a continuous process. The District TB Officer performs cohort analysis on TB patients registered in his district every quarter-year and at the end of every year. The Regional TB Officer performs cohort analysis on all TB patients registered in the region. The NTP directorate performs cohort analysis on all TB patients registered nationally. 79
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What is cohort analysis for? Cohort analysis is the key management tool used to evaluate the effectiveness of TB control programme delivery. It enables regional NTP staff and the NTP directorate to identify districts with problems. Examples of problems identified include the following: low cure rate, high default rate, higher than expected proportions of sputum smear-negative PTB or extrapulmonary TB, lower than expected case detection rate. Identification of problems enables the NTP to overcome them and improve programme delivery. 7 3 DIRECTLY OBSERVED THERAPY What is directly observed therapy? To ensure the treatment cures the patient, we have to ensure patient adherence to the treatment. Patient adherence to short-course chemotherapy means the patient takes every dose of the recommended treatment regimen. It is difficult for a patient to adhere to anti-TB treatment for 8 months. It is difficult to predict which TB patients will adhere to selfadministered treatment. Therefore one certain way to ensure patient adherence to treatment is direct observation of therapy (DOT). This means that a supervisor watches the patient swallowing tablets. The NTP trains and monitors the supervisors. Directly observed therapy as close to the patient's home as possible A TB patient is unlikely to adhere to treatment if there is a long distance to go for treatment. One of the aims of a TB programme is to organise TB services so that the patient has TB treatment as close to home as possible. A TB programme brings TB treatment to TB patients wherever they live. Many TB patients live close to a health facility (e.g. health centre, district hospital). For these patients, the supervisor of directly observed therapy will therefore 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 will be a trained local community member or health outreach worker. Some areas have HIV/AIDS community care schemes. The HIV/AIDS home care providers with suitable training and supervision can administer directly observed therapy. 80
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Integration of TB treatment services with general health services In the past, some TB programmes have relied only on special TB hospitals and clinics, separate from the general health services. The big problem with that system is that many TB patients live far from TB hospitals and clinics. One reason why TB is out of control in many countries is because 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 health services. SUGGESTIONS FOR FURTHER READING World Health Organisation. TB - A Global Emergency. WHO report on the TB epidemic, 1994. Geneva: WHO, 1994. World Health Organisation. Stop TB at the source. WHO report on the TB epidemic, 1995. Geneva: WHO, 1995. World Health Organisation. Groups at risk. WHO report on the TB epidemic, 1996. Geneva: WHO, 1996. World Health Organisation. Framework for effective tuberculosis control. WHO Tuberculosis Programme, 1994. Geneva: WHO, 1994. World Health Organisation. Treatment of tuberculosis. Guidelines for national programmes. Geneva: WHO, 1993. International Union Against Tuberculosis and Lung Disease. Tuberculosis guide for low income countries. pmi Verlagsgruppe. 3rd edition. Frankfurt, 1994. 81
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CHAPTER 8 BACKGROUND INFORMATION ON HIV / AIDS 8 1 HUMAN IMMUNODEFICIENCY VIRUS (HIV) 8 1 1 Introduction: HIV and AIDS Since the first description of AIDS in 1981, researchers have identified 2 serotypes of HIV, the cause of AIDS. HIV-1 is the predominant serotype worldwide. HIV-2 occurs most commonly in West Africa. They both cause AIDS and the routes of transmission are the same. However, HIV-2 transmission is slightly less easy and HIV-2 may cause slower progression to AIDS. 8 1 2 HIV/AIDS epidemiology In 1995 worldwide there were about 17 million HIV-infected adults. An estimated 6 million adult and paediatric AIDS cases have occurred since the HIV pandemic began. Most of these cases of HIV and AIDS have been in sub-Saharan Africa and the Americas. There are now growing numbers in South East Asia. In some sub-Saharan African countries, HIV seroprevalence in the general population aged over 15 years is as high as 20%. 8 1 3 HIV transmission The main modes of transmission of HIV are through sexual intercourse, blood and from mother to infant. Worldwide the most important route of transmission is through sexual intercourse. In most low-income countries equal numbers of men and women are HIV-infected. Other sexually transmitted diseases (especially those causing genital ulcers) increase the risk of HIV transmission. Bloodborne HIV transmission occurs through contaminated blood transfusion, injections with contaminated needles and syringes, and the use of non-sterile skin-piercing instruments. About one third of children born to HIV-infected mothers are also HIV-infected. There is a small risk of HIV transmission through breast-feeding. However, in many low-income countries breast-feeding is still a safer alternative to bottle-feeding. There is no evidence that HIV transmission occurs through everyday contact, hugging or kissing, food or drink, or bites of mosquitoes or other insects. 83
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8 1 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 other patients. Known HIV-positive staff should not perform invasive procedures (surgery, 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 sterilisation 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/spouse. The risk of transmission of HIV from patients to staff is small if staff observe standard infection control procedures. In health units, HIV transmission is less common than 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. Handle all "sharps" carefully. If you have a needle-stick injury, squeeze the wound to encourage blood flow and wash well with soap and water. Assume that all blood and body fluids are potentially infectious. The table gives some guidance on prevention of transmission to health workers.
EXPOSURE TO RISK venepuncture
PRECAUTIONS FOR PREVENTION OF TRANSMISSION OF HIV wear gloves use a closed vacuum system if available discard needle and syringe into sharps box discard gloves and swabs into leak-proof 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 other body fluids
clear up as soon as possible using available disinfectant (e.g. glutaraldehyde, phenol, sodium hypochlorite)
resuscitation
avoid mouth-to-mouth resuscitation (use bag and mask)
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laundry disposal
wear gloves and apron dispose into leak-proof plastic bags wash laundry at high temperatures or with appropriate chemical disinfectant
8 1 5 Immunopathogenesis of HIV infection The helper subset of T-lymphocytes is central to cell-mediated immunity. These cells carry the CD4 antigen on their surface (CD4+ lymphocytes). HIV recognises the CD4 antigen, and enters and infects CD4+ lymphocytes. The result is killing of many CD4+ lymphocytes (progressive decrease in CD4+ lymphocyte count) and poor function of the survivors. Progressive HIV infection therefore causes progressive decline in immunity. 8 1 6 Natural history of HIV infection Acute HIV infection Most people infected with HIV do not know that they have become infected. HIV infected persons develop antibodies to HIV antigens usually 6 weeks, but upto 3 months, after infection. This "seroconversion" is when a person recently infected with HIV first tests sero-positive for HIV antibodies. Some people have a "glandular fever" - like illness (fever, rash, arthralgia and lymphadenopathy) at the time of seroconversion. Occasionally acute neurological syndromes may occur which are often self-limiting. These include aseptic meningitis, peripheral neuropathy, encephalitis and myelitis. A severe seroconversion illness may predict a worse long term outcome. 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 up to 10 years or more. The vast majority of HIV-infected children are infected in the peri-natal 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. Progression from HIV infection to HIV-related disease and AIDS Almost all (if not all) HIV-infected people will ultimately develop HIV-related
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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 serotype and strain: HIV-1 and certain HIV strains may cause faster progression. Host characteristics which may cause faster progression include age less than 5 years, age more than 40 years, concurrent infections, and possibly genetic factors. Persistent generalised lymphadenopathy (PGL) This occurs in about one third of otherwise healthy HIV-infected people. The enlarged lymph nodes are persistent, generalised, symmetrical, and non-tender. Early immunosuppression As HIV infection progresses and immunity declines, patients become more susceptible to infections. These include tuberculosis, septicaemia, pneumonia, and recurrent fungal infections of the skin and oropharynx. Patients may develop constitutional symptoms (unexplained fever and weight loss), sometimes known as "AIDS-related complex" (ARC). Some patients develop chronic diarrhoea with weight loss, often known as "slim disease". Late immunosuppression Any infection that can occur with early immunosuppression can also occur with late immunosuppression. In addition, 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's sarcoma). At this late stage, the patient usually dies in less than 1-2 years. This late stage is sometimes known as "full-blown AIDS". PRACTICAL POINT Tuberculosis can occur at any point in the course of progression of HIV infection. 8 2 AIDS AIDS is a term with an official definition used for epidemiological surveillance. This means that systematic reporting of AIDS cases is useful 86
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in helping to monitor the HIV pandemic and to plan public health responses. The term AIDS is not useful for 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. PRACTICAL POINT The term AIDS is used for epidemiological surveillance, not for clinical care. 8 2 1 WHO case definitions for AIDS surveillance ADULTS AND ADOLESCENTS WHO has recommended AIDS case definitions for use in adults and adolescents in countries with limited clinical and laboratory diagnostic facilities. The recommended case definition depends on whether HIV testing is available. One case definition is for use where HIV testing is not available. The other case definition is for use where HIV testing is available. WHO case definition for AIDS surveillance where HIV testing is not available. The case definition for AIDS is fulfilled in the presence of at least 2 major signs and at least 1 minor sign. 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 montha · generalised pruritic dermatitis · history of Herpes zoster · oropharyngeal candidiasis · chronic progressive or disseminated herpes simplex infection · generalised lymphadenopathy a For patients with tuberculosis, persistent cough for more than 1 month should not be considered as a minor sign. 87
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The presence of either generalised Kaposi's 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 tuberculosis cases could be counted as AIDS cases because of their similarity in clinical presentation. WHO case definition for AIDS surveillance where HIV testing is available The case definition for AIDS is fulfilled in the presence of a positive HIV test and 1 or more of the following conditions: · weight loss > 10% body weight, or cachexia, with diarrhoea or fever, or both, for at least 1 month, not known to be due to a condition unrelated to HIV infection · cryptococcal meningitis · tuberculosis (pulmonary or extrapulmonary) · Kaposi's sarcoma · neurological impairment which prevents independent daily activities, not known to be due to a condition unrelated to HIV infection · oesophageal candidiasis · life-threatening, or recurrent episodes of, pneumonia · invasive cervical cancer An advantage of this case definition is that it has a higher specificity. A disadvantage is that it requires the availability of HIV serological testing, which may be logistically difficult and costly. CHILDREN WHO case definition for AIDS surveillance where HIV testing is not available The case definition for AIDS is fulfilled in the presence of at least 2 major signs and 2 minor signs (if no other known cause of immunosuppression). Major signs · weight loss or abnormally slow growth · chronic diarrhoea (> 1 month) · prolonged fever (>1 month) 88
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Minor signs · generalised lymph node enlargement · oropharyngeal candidiasis · recurrent common infections, e.g. ear infections, pharyngitis · persistent cough · generalised rash Confirmed HIV infection in the mother counts as a minor criterion. This definition is not very specific. WHO case definition for AIDS surveillance where HIV testing is available This case definition is complex and depends on advanced clinical and laboratory diagnostic facilities. The applicability of this case definition is therefore limited and is beyond the scope of this manual. Those interested should see the suggestions for further reading at the end of the chapter. SUGGESTIONS FOR FURTHER READING HIV/AIDS WHO Global Programme on AIDS. AIDS in Africa: A manual for physicians. Geneva, 1992. WHO Global Programme on AIDS. Preventing HIV transmission in health facilities. Geneva 1995. WHO. AIDS: images of the epidemic. Geneva 1994. Mertens TE, Burton A, Stoneburner R, et al. Global estimates and epidemiology of HIV infections and AIDS. AIDS 1994, 8(suppl 1): S361-S372. AIDS case definitions for surveillance Acquired Immunodeficiency Syndrome (AIDS). WHO/CDC case definition for AIDS. Wkly Epidem Rec 1986; 61: 69-73. (WHO clinical case definitions for AIDS in children where HIV testing is not available). Acquired Immunodeficiency Syndrome (AIDS). 1987 revision of CDC/WHO case definition for AIDS. Wkly Epidem Rec 1988; 63: 1-7. (WHO case definition for AIDS in children where HIV testing is available). WHO case definitions for AIDS surveillance in adults and adolescents. Wkly Epidem Rec 1994; 69: 273-275. (WHO case definitions for AIDS in adults). 89
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9 1 BASIC INFORMATION
9 1 1 Epidemiology of co-infection of HIV and M. tuberculosis In 1995, about one third of the 15 million HIV-infected people worldwide were also co-infected with M. tuberculosis. 70% of co-infected people live in sub-Saharan Africa, 20% in Asia and 8% in Latin America and the Caribbean.
9 1 2 HIV infection and risk of TB
HIV increases a person's susceptibility to infection with M. tuberculosis. In a person infected with M. tuberculosis, HIV is a potent cause of progression of tuberculosis infection to disease.
Consider an individual infected with M. tuberculosis. The table shows the effect of HIV infection on the lifetime risk of developing TB.
HIV STATUS
LIFETIME RISK OF DEVELOPING TB
negative . . . . . . . . . . . . . . . . . . . . . . . 5-10%
positive . . . . . . . . . . . . . . . . . . . . . . . . 50 %
PRACTICAL POINT HIV is the most powerful factor known to increase the risk of TB.
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9 1 4 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. The consequences include the following: · over-diagnosis of sputum smear-negative PTB · under-diagnosis of sputum smear-positive PTB · inadequate supervision of anti-TB chemotherapy · low cure rates · high mortality rates during treatment · high default rates because of adverse drug reactions · high rates of TB recurrence · increased emergence of drug resistance 9 1 5 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 infection and AIDS. 9 2 PATTERNS OF HIV-RELATED TB As HIV infection progresses, CD4 lymphocytes decline in number and function. The immune system is less able to prevent the growth and local spread of M. tuberculosis. Disseminated and extra-pulmonary disease is more common. 9 2 1 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 chest X-ray appearance often differ in early and late HIV infection. 92
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HOW PTB DIFFERS IN EARLY AND LATE HIV INFECTION
features of PTB
Stage of HIV infection
early
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often resembles primary PTB
sputum smear result
often positive
often negative
chest X-ray appearance
often cavities
often infiltrates with no cavities
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 HIVnegative. This is probably because there is less cavitation, inflammation and endobronchial irritation in HIV positive patients. Sputum microscopy Sputum smear positivity rates in TB/HIV patients also depend on the degree of immunocompromise, as shown below. DEGREE OF IMMUNOCOMPROMISE LIKELIHOOD OF POSITIVE SPUTUM SMEAR mild . . . . . . . . . . . . . . . . . . . similar to HIV-negative patient severe . . . . . . . . . . . . . . . . . . decreased (decreased inflammation in lungs) Chest x-ray appearance The classical chest X-ray pattern is more common in HIV-negative patients. The atypical pattern is more common in HIV-positive patients. PRACTICAL POINT Chest X-ray 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.
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Distinguishing other HIV-related pulmonary diseases from PTB. 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 chest X-ray shadowing. In each case it is important to make a careful clinical assessment and 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, co-trimoxazole or ampicillin. PRACTICAL POINT If pneumonia fails to respond to standard antibiotics, consider other pathogens, e.g. M. tuberculosis. Kaposi 's 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 and dyspnoea, and usually has KS elsewhere. Chest X-ray shows a diffuse nodular infiltrate 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) The incidence of PCP in HIV-infected individuals shows a wide goegraphic variation. The patient usually presents with dry cough and progressive dyspnoea. The table below shows the clinical and chest X-ray features which help to distinguish PCP from PTB. 94
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Clinical and chest X-ray features of PCP in contrast with TB
TYPICAL OF PCP
TYPICAL OF TB
SYMPTOMS
dry cough sputum mucoid if any dyspnoea
productive cough purulent sputum pleuritic chest pain, haemoptysis
SIGNS
normal
signs of consolidation
fine inspiratory crackles signs of pleural effusion
CHEST X-RAY
bilateral diffuse interstitial shadowing normal
lobar consolidation cavitation 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 unavailable in district hospitals. The diagnosis therefore depends on the clinical and chest X-ray features, exclusion of TB and response to a trial of high-dose cotrimoxazole. Other conditions Two other rare 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 chest X-ray often shows upper lobe, cavitary infiltrates. The organism may also stain weakly acidfast. Associated soft-tissue and brain abscesses raise clinical suspicion. The diagnosis rests on finding beaded and branching Gram positive rods on sputum smear. 9 2 2 Extra-pulmonary TB Extrapulmonary TB is common in HIV-positive patients. The commonest forms are the following: lymphadenopathy, pleural effusion, pericardial disease, miliary disease, meningitis. Serous effusions are a more common form of TB in HIV-positive than in HIV-negative individuals. Miliary TB is an under-diagnosed cause of end-stage wasting in HIVpositive individuals.
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PRACTICAL POINT Some of the CSF findings may be normal in TB meningitis 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%.
Persistent generalised lymphadenopathy (PGL) PGL is a feature of HIV infection which develops in up to 50% of HIV-infected individuals. 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 duration
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 table below shows the features of lymph nodes which indicate further investigation, including biopsy.
Features of lymph nodes which indicate further investigation · 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 chest X-ray
The histological appearance of tuberculous lymph nodes from HIV positive patients depends on the degree of immunocompromise, as shown below.
DEGREE OF IMMUNOCOMPROMISE
HISTOLOGICAL APPEARANCE OF LYMPH NODES
mild . . . . . . . . . . . . . . . . . . . . . caseating lesions with few or no AFBs
severe. . . . . . . . . . . . . . . . . . . . little cellular reaction with many AFBs
Features of other forms of extrapulmonary TB are described in chapter 2, section 2.
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9 3 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 tuberculosis, and widespread tuberculous lymphadenopathy occur. 9 3 1 The impact of HIV on the diagnosis of TB in children HIV makes the diagnosis 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 9.3.2 for differential diagnosis). b) The interpretation of tuberculin skin testing is even more unreliable than usual. An immunocompromised child may have a negative tuberculin skin test despite having TB. c) A child with HIV infection usually comes from a household where the parents have HIV infection. One or both parents may have died from AIDS. It may be difficult for the child to attend a health facility. 9 3 2 Differential diagnosis of PTB in HIV-infected children · bacterial pneumonia · viral pneumonia, e.g. cytomegalovirus · fungal pneumonia, e.g. candida, cryptococcus · Pneumocystis carinii pneumonia · lymphocytic interstitial pneumonitis · pulmonary lymphoma 9 3 3 Child contacts who may be HIV-infected Refer to chapter 3 for the management of child contacts of infectious (sputum smear positive) adults. Suspicion that a child contact is HIV-infected may arise because of the following: the child has clinical 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. 97
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9 4 RESPONSE OF HIV-POSITIVE TB PATIENTS TO ANTI-TB TREATMENT Case fatality The case fatality of TB/HIV patients 1 year after starting TB treatment is about 20%. This case fatality is greater than in HIV-negative TB patients. The excess deaths in TB/HIV patients during and after treatment are partly due to TB itself and partly due to other HIV-related problems. These other HIV-related problems include the following: septicaemia, diarrhoea, pneumonia, anaemia, Kaposi's sarcoma, cryptococcal meningitis. Case fatality is less in TB/HIV patients treated with SCC than with the old standard regimen (1 SHT or SHE / 11 HT or HE). This is partly because SCC is a more effective anti-TB treatment. Also, rifampicin has broadspectrum antimicrobial activity as well as anti-TB activity. This may decrease case fatality due to HIV-related bacterial infections during anti-TB treatment. Response in survivors Several studies have assessed the clinical, radiological, and microbiological response to SCC in HIV-positive and HIV-negative TB patients. Excluding patients who died, response rates were similar in HIV-positive and HIVnegative TB patients. The only exception was that on average weight gain was less in HIV-positive than in HIV-negative TB patients. RECURRENCE OF TB AFTER COMPLETING ANTI-TB TREATMENT Old standard treatment The recurrence rate is higher in HIV-positive than in HIV-negative TB patients. In one study of TB/HIV patients there was an association between recurrence and cutaneous reaction to thiacetazone. A severe thiacetazone reaction necessitated interruption of treatment and a change to ethambutol. There are several possible explanations for the link between increased risk of recurrence and thiacetazone reaction. These include treatment interruption, subsequent poor compliance, more advanced immunocompromise, and change to the combination of isoniazid and ethambutol in the 11 months continuation phase. SCC The recurrence rate is similar in HIV-positive and HIV-negative TB patients who complete treatment. 98
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Recurrence: relapse or re-infection? When TB recurs after previous cure, there are 2 possibilities: a) true relapse (reactivation of persisters not killed by anti-TB drugs); b) re-infection (due to re-exposure to another source of infection). The proportions of recurrences due to these 2 possibilities are not known. 9 4 1 Side effects of anti-TB drugs in TB/HIV patients Adverse drug reactions are more common in HIV-positive than in HIVnegative TB patients. Risk of drug reaction increases with increased immunocompromise. Most reactions occur in the first 2 months of treatment. Skin rash This is the commonest reaction. Fever often precedes and accompanies the rash. Mucous membrane involvement is common. The usual drug responsible is thiacetazone. Streptomycin and rifampicin are sometimes to blame. Severe skin reactions, which may be fatal, include exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis. Other reactions The commonest reactions necessitating change in treatment include gastrointestinal disturbance and hepatitis. There may be an increased risk of rifampicin-associated anaphylactic shock and thrombocytopenia. PRACTICAL POINT Following a drug reaction, never attempt desensitisation in TB/HIV patients. SUGGESTIONS FOR FURTHER READING Narain JP, Raviglione MC, Kochi A. HIV-associated tuberculosis in developing countries: epidemiology and strategies for prevention. Tubercle and Lung Disease 1992; 73: 311-321. Dolin PJ, Raviglione MC, Kochi A. Global tuberculosis incidence and mortality during 1990-2000. Bull. World Health Organ. 1994; 72(2): 213-220. 99
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CHAPTER 10 DIAGNOSIS OF HIV IN ADULTS WITH TUBERCULOSIS
10 1 CLINICAL RECOGNITION OF HIV INFECTION IN TB PATIENTS
In areas where the prevalence of both TB and HIV are high, the only HIVrelated illness present in many TB/HIV patients is TB. However, certain clinical features are more common in HIV-positive TB patients than in HIVnegative TB patients. The table below shows these clinical features suspicious of HIV infection.
CLINICAL FEATURES SUSPICIOUS OF HIV CO-INFECTION IN TB PATIENTS
Past history
sexually transmitted disease (STD) herpes zoster (shingles) recurrent pneumonia bacteraemia (especially Salmonella typhimurium)
Symptoms
weight loss (> 10 kg or > 20% of original weight) diarrhoea (> 1 month) pain on swallowing (suggests oesophageal candida) burning sensation of feet (peripheral sensory neuropathy)
Signs
scar of herpes zoster pruritic papular rash Kaposi's sarcoma symmetrical generalised lymphadenopathy oral candidiasis oral hairy leukoplakia persistent painful genital ulceration
PRACTICAL POINT Full blood count (FBC) findings suspicious of HIV infection are unexplained anaemia, leucopenia or thrombocytopenia.
The definitive diagnosis of HIV infection rests on a positive HIV test.
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10 2 HIV TESTING
10 2 1 HIV tests
There are different ways of testing for HIV. 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 3 main methods of HIV-testing. The technical details of these tests are beyond the scope of this manual, but there is a good account in "AIDS in Africa: a manual for physicians".
HIV TESTING METHODS WITH ADVANTAGES AND DISADVANTAGES
HIV TESTING METHOD
ADVANTAGES
DISADVANTAGES
less expensive than immunoblot
some specialised laboratory equipment necessary
ELISA
large numbers of sera can be tested daily
sensitive and specific
simple/rapid (e.g. rapid immunobinding assay)
simple, rapid less expensive than immunoblot no specialised equipment necessary
older tests less sensitive and less specific but newer tests improved
immunoblot
most sensitive and specific
expensive specialised laboratory equipment necessary
The usual type of test for HIV antibodies is the ELISA (Enzyme-Linked ImmunoSorbent Assay). (The cost per individual ELISA test is about US $0.75-1.75). There are ELISA tests available which test for both HIV-1 and HIV-2.
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10 2 2 Objectives of HIV antibody testing in TB patients
There are 3 main possible objectives in performing HIV antibody tests in TB patients: a) diagnosis of HIV infection in individual TB patients; b) surveillance (anonymous testing to monitor epidemiological trends); c) research (voluntary testing for epidemiological, clinical, or virological studies). 10 2 3 Strategy for HIV antibody testing in TB patients (Which tests to use and when to use them)
HIV testing methods vary in accuracy and cost. In general, WHO recommends different HIV-testing strategies, depending on the objective of testing. The aim is to maximise accuracy and minimise cost. The table below shows the strategy appropriate for the objective of testing.
OBJECTIVES, STRATEGIES AND INTERPRETATION OF HIV TESTS
OBJECTIVE
TESTING STRATEGY
INTERPRETATION OF RESULT
Test sample with ELISA or simple/rapid assay
1st assay negative = patient HIV negative
Diagnosis of HIV infection in individual TB patients (a group with a high HIV seroprevalence)
If 1st assay positive, re-test using ELISA or simple/rapid assay based on a different antigen preparation or test
1st assay positive + 2nd assay positive = patient HIV positive 1st assay positive + 2nd assay negative -> repeat both assays Results remain discordant -> repeat sample and testing
Surveillance (in population with HIV prevalence > 10%)
Test sample with ELISA or simple/rapid assay
Assay negative = patient HIV negative Assay positive = patient HIV positive
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PRACTICAL POINT Many low-income countries cannot afford the cost of the strategy of 2 positive tests in order to diagnose HIV infection in an individual patient. In practice, a patient has 1 test only: test negative = patient HIV negative; test positive = patient HIV positive. 10 2 4 Diagnosis of HIV infection in individual TB patients The link between HIV and TB is well known to many members of the public. A patient with TB may therefore be well aware of the possibility also of HIV infection. It is important to offer counselling and voluntary HIV testing, if available, to TB patients on account of the following possible benefits: a) the patient may want the chance to know his/her 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. PRACTICAL POINT Anti-TB drug treatment is the same for HIV-positive and HIV-negative TB patients, with one exception: do not give thiacetazone to HIV-positive TB patients (increased risk of severe and sometimes fatal skin reactions). A policy of compulsory HIV testing (even if this were legal) of TB patients would be counter-productive. This type of policy would have the following results: a) patients deterred from seeking care; b) decreased case-finding in at-risk groups; c) reduced credibility of health services. 10 3 HIV COUNSELLING Confidential counselling is essential before and after HIV antibody testing. The patient gives explicit informed consent to have the test. The patient must understand what the test involves and the implications of testing. The counsellor provides support. Counselling is a dialogue between patient and counsellor. 104
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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. 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. Pre-test counselling The aim is to enable the patient to make an informed decision to have the test or not. The patient needs to know what the test involves and what are the implications of the result. The main issues for discussion are assessments of the following: a) the patient's likelihood of having acquired HIV infection, b) knowledge about HIV, and c) ability to cope with a positive result.
a) Assessment of risk of having acquired HIV infection
· multiple sex partners · sex with commercial sex workers · for men, sex with other men · non-sterile skin piercing, e.g. scarification, tattooing · previous blood transfusion · intravenous drug use · sexual partner/spouse of person at risk
b) Assessment of knowledge about HIV
· what does the test involve and mean? · how does HIV transmission occur? · what is high risk behaviour?
c) Assessment of ability to cope with result
· patient's expected reaction to result · who will provide emotional support? · impact of a positive result on - relationships - social issues, e.g. employment - future health
PRACTICAL POINT The HIV test does not become positive until usually 6 weeks, and up to about 3 months, after infection (the "window period").
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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. Patients will need continuing support. Issues for discussion when the HIV test result is negative · A negative result does not mean that the patient definitely does not have HIV infection (the test could be in the seroconversion "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). · Awareness of possible anti-TB drug side-effects. · Safe sexual behaviour. · Avoidance of blood or organ donation. · The patient's reaction to the test result. · Emotional and psychological support for the patient. · How to tell friends, family and lovers. · Counselling partner(s) if possible. · Referral to local community services and support groups, if available. · Social implications, e.g. employment, life insurance. SUGGESTIONS FOR FURTHER READING WHO. AIDS in Africa: a manual for physicians. Geneva 1992. WHO. Weekly Epidemiological Record. 1992; 67: 145-149. WHO. Guidelines for HIV Surveillance Among Tuberculosis Patients. Geneva 1994. WHO. AIDS Series 8. Guidelines For Counselling About HIV Infection And Disease. Geneva 1990. WHO Global Programme on AIDS. Counselling for HIV/AIDS: a key to caring. Geneva 1995 WHO Global Programme on AIDS. Living with AIDS in the community. Geneva 1992. 106
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CHAPTER 11 DIAGNOSIS OF HIV IN CHILDREN WITH TUBERCULOSIS 11 1 CLINICAL RECOGNITION OF HIV INFECTION IN CHILDREN 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. 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. The table below shows clinical signs suspicious of HIV infection in children. CLINICAL SIGNS SUSPICIOUS OF HIV INFECTION IN CHILDREN weight loss or abnormally slow growth chronic diarrhoea (> 1 month) prolonged fever (>1 month) generalised lymph node enlargement oropharyngeal candidiasis recurrent common infections, e.g. ear infections, pharyngitis persistent cough generalised rash neurological problems delay in development bilateral parotid gland enlargement enlarged spleen enlarged liver recurrent abscesses meningitis recurrent herpes simplex 107
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11 2 HIV TESTING Positive and negative HIV tests are not always reliable. Rarely, a baby with HIV infection has a negative HIV antibody test. The reason for this is not known. The definitive diagnosis of HIV infection rests on a positive HIV test. However, a positive HIV antibody test is not a reliable indicator of HIV infection in early childhood (up to 18 months of age). During the pregnancy of a mother with HIV infection, the mother's 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, HIV antibody testing cannot therefore distinguish uninfected from infected children. In uninfected children, these maternal antibodies usually become undetectable by 9 months of age. Occasionally maternal antibodies remain detectable until 18 months. Most infected children make their own antibodies, so the HIV antibody test will still be positive after 18 months. PRACTICAL POINT In children under 18 months, the diagnosis of HIV infection rests on clinical features in the baby and a positive HIV test in the mother. 11 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. See Chapter 10 for the issues for discussion with adults with suspected HIV. Pre-test counselling It is important to counsel the mother and obtain her consent 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. 108
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Consider the bad news for the mother when she hears that her child may have HIV infection: · her child may have an incurable and fatal disease; · she herself may have HIV; · her husband may have HIV; · 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. The main disadvantage is the fear that her husband may beat her or leave her if she tells him that she is HIV-positive. PRACTICAL POINT The mother may like to bring her husband for joint pre-test counselling. It is usually easier for a woman to tell her husband she may be HIVpositive than to tell him afterwards that she is HIV-positive. Post-test counselling Consider a mother whose child has TB and suspected or known HIV infection. See Chapter 10 for the issues for discussion relevant to anyone who tests HIV-positive. There are other issues specific to a mother who tests HIV-positive. These include the poor outlook for the child and the risk for future babies of HIV infection. About one third of children born to HIVpositive women are also HIV-infected. When counselling women who are breast-feeding or who have delivered recently it is important to discuss breast-feeding. There may be a small risk of HIV transmission by breast-feeding. However, in many low-income countries, breast-feeding is still a safer alternative to bottle-feeding. For example, consider a child whose mother is HIV-positive and who lives in an environment where there is no clean water. The child is probably at higher risk of dying from diarrhoea if bottle-fed than from AIDS if breast-fed. 109
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SUGGESTIONS FOR FURTHER READING Chintu C, Bhat G, Luo C, et al. Seroprevalence of human immunodeficiency virus type 1 in Zambian children with tuberculosis. Pedr Infect Dis J 1993; 12: 499-504. Sassan-Morokro M, De Cock KM, Ackah A, et al. Tuberculosis and HIV infection in children in Abidjan, Cote d'Ivoire. Trans Royal Soc Tr Med and Hygiene 1994; 88: 178-181. WHO AIDS Series 8. Guidelines for counselling about HIV infection and disease. Geneva, 1990. WHO Global Programme on AIDS. Counselling for HIV/AIDS: a key to caring. Geneva 1995. 110
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CHAPTER 12 MANAGEMENT OF OTHER HIV-RELATED DISEASES IN TB/HIV PATIENTS 12 1 INTRODUCTION TB/HIV patients may have other HIV-related diseases. This chapter is a brief guide to their management at district hospital level. Therapies in "bold" are available in most district hospitals. See the WHO guidelines "Clinical management of HIV infection" and "Management of sexually transmitted diseases" for a more complete account. (Note that references to trimethoprim-sulfamethoxazole (TMP-SMX) are to the standard strength tablet, which contains 80mg of trimethoprim and 400mg of sulfamethoxazole). 12 2 SEXUALLY TRANSMITTED DISEASES A person who has un-safe sex is at risk of several sexually transmitted diseases (STDs). So a patient with one STD is at increased risk of having another STD. HIV is usually sexually transmitted. STDs other than HIV are common in TB/HIV patients. This chapter gives a brief account of the drug treatment of STDs. When you treat a patient with STD, also remember patient education, counselling, condom provision and partner management. 12 2 1 Syndromic management Accurate STD diagnosis is often not feasible. WHO has developed a "syndromic management". This is based on the recognition of consistent groups of symptoms and signs (syndromes). The treatment recommended for each syndrome cures the majority of infections responsible for causing each syndrome. The table shows the recommended plans of treatment for the common STD-associated syndromes where laboratory investigations are not available. 111
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MEN
WOMEN
SYNDROME urethral discharge cervicitis vaginitis vaginal discharge genital ulcers inguinal bubo - with ulcers - without ulcers
PLAN OF TREATMENT treat for gonorrhoea and chlamydia treat for uncomplicated gonorrhoea and chlamydia treat for candidiasis and Trichomonas vaginalis/ bacterial vaginosis treat for cervicitis and vaginitis treat for syphilis and chancroid treat for syphilis and chancroid treat for lymphogranuloma venereum
MEN AND WOMEN
12 2 2 Treatment regimens for common STDs
The table shows treatment regimens for the common STDs. Do not use ciprofloxacin or tetracyclines in pregnancy or in childhood.
STD gonorrhoea (uncomplicated) chlamydia primary syphilis (chancre)
TREATMENT REGIMEN ciprofloxacin 500mg orally as a single dose OR ceftriaxone 250mg by i.m. injection as a single dose OR cefixime 400mg orally as a single dose OR spectinomycin 2g by i.m. injection as a single dose OR trimethoprim (80mg)/sulfamethoxazole (400mg) (TMP-SMX) 10 tablets orally as a single dose OR gentamicin 240mg by i.m. injection as a single dose doxycycline 100mg orally 2x daily for 7 days OR tetracycline 500mg orally 4x daily for 7 days OR erythromycin 500mg orally 4x daily for 7 days benzathine penicillin G 2.4 million IU, by i.m. injection at a single session (often split into 2 doses at separate sites) OR procaine penicillin G 1.2 million IU daily by i.m. injection for 10 consecutive days OR (if allergic to penicillin) tetracycline 500mg orally 4x daily for 15 days OR doxycycline 100mg orally 2x daily for 15 days OR erythromycin 500mg 4x daily for 15 days
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chancroid
erythromycin 500mg orally 3x daily for 7 days OR ciprofloxacin 500mg orally as a single dose OR ceftriaxone 250mg by i.m. injection as a single dose OR spectinomycin 2g by i.m. injection as a single dose OR TMP-SMX 2 tablets orally 2x daily for 7 days
lymphogranuloma doxycycline 100mg orally 2x daily for 14 days OR
venereum
tetracycline 500mg orally 4x daily for 14 days OR
erythromycin 500mg orally daily for 14 days OR
sulfadiazine 1g orally 4x daily for 14 days
candidiasis
nystatin 100,000IU intravaginally once daily for 14 days OR miconazole or clotrimazole 200mg intravaginally once daily for 3 days OR clotrimazole 500mg intravaginally as a single dose
Trichomonas vaginalis
metronidazole 2g orally as a single dose OR metronidazole 400-500mg orally 2x daily for 7 days
bacterial vaginosis metronidazole 2g orally as a single dose OR metronidazole 400-500mg orally 2x daily for 7 days
12 3 SKIN AND MOUTH PROBLEMS
The diagnosis of these HIV-related skin and mouth problems usually rests on characteristic clinical features. The tables show diagnoses and treatments.
DIAGNOSIS SKIN PROBLEMS · VIRUS INFECTIONS Herpes simplex (oral and genital)
TREATMENT Local lesion care. Acyclovir 200 mg five times daily until healed.
Varicella zoster
Local lesion care. Acyclovir 800 mg oral 5x/day for at least 7 days.
Anal/genital warts Topical 20% podophyllin 1-2 times per week until (human papilloma virus) cleared. Trichloracetic acid. Cryotherapy.
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Molluscum contagiosum Leave the lesions alone OR Prick each lesion with a needle or sharpened orange stick and touch with phenol.
· FUNGAL INFECTIONS
Tinea (pedis/corporis/cruris)
Whitfield's ointment or Castellani's paint Topical antifungals. 1% Clotrimazole. 2% Miconazole. In resistant cases use griseofulvin 500 mg 2x daily.
Candidiasis
Local application of 1% aqueous gentian violet or nystatin ointment 2 x daily until lesions are cleared. Topical antifungals.
Cutaneous cryptococcosis/ Systemic antifungal therapy. histoplasmosis
· BACTERIAL INFECTIONS
Papular folliculitis (pruritic papular dermatosis)
Calamine lotion. Antihistamines. Topical antifungals combined with 1% hydrocortisone. Strong topical corticosteroids.
Impetigo, furunculosis
Penicillin V 500 mg orally OR Flucloxacillin or erythromycin 500 mg orally 4 x daily for 1 - 2 weeks
Pyomyositis
Surgical drainage plus antibiotics (as for impetigo)
· OTHER
Seborrhoeic dermatitis Antifungal shampoos OR topical antifungals with steroids OR topical 1% hydrocortisone. Strong topical corticosteroids.
Psoriasis
Conventional antipsoriasis treatment, eg coal tar in salicylate ointment 2 x daily.
Scabies
Topical benzyl benzoate 25%
Kaposi's Sarcoma
Local lesion care. Radiotherapy, chemotherapy.
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· MOUTH PROBLEMS Oral candidiasis Hairy leukoplakia Angular cheilitis Gingivitis / dental abscesses Aphthous ulcers
Topical antifungals such as amphotericin lozenges, nystatin pastilles/pessaries: nystatin drops 100,000 units 3 x daily OR nystatin pessaries one every 4 hours OR nystatin tabs 500,000 units 4 x daily. In resistant cases oral ketoconazole 200 mg 2 x daily. In all cases treat for 7 - 14 days. Recurrence is common unless without prophylaxis. No treatment. Topical antifungals eg 1% clotrimazole. Oral metronidazole 400 mg 3 x daily and/or penicillin V 500 mg 4 x daily for 7 days. Mouth rinses with steroid and tetracycline. Topical corticosteroids. Oral prednisolone. Oral acyclovir. (Oral thalidomide in refractory cases excluding women).
12 4 GASTROINTESTINAL PROBLEMS
12 4 1 Dysphagia There are various HIV-related causes of oesophageal inflammation. They present in a similar way with pain on swallowing. Oesophageal candidiasis is the commonest HIV-related cause of dysphagia. The diagnosis of the other causes needs endoscopy, biopsy and a good laboratory. Where there are no facilities for investigation of a known HIV-positive patient with dysphagia, treat empirically with an oral anti-fungal agent. Where available, barium swallow shows characteristic appearances of fine mucosal ulceration. Upper gastrointestinal endoscopy shows white plaques and biopsy allows confirmation.
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The table shows the treatment of the causes of dysphagia.
CAUSE OF DYSPHAGIA Candida oesophagitis Herpes simplex Cytomegalovirus Ulcers of unknown cause
TREATMENT Nystatin 500,000 units 4 x daily. Nystatin pessaries 100,000 units every 4 hours. Ketoconazole 200 mg twice daily OR fluconazole 100 mg od. (All medications taken for 1- 14 days). Prophylaxis with nystatin pastilles OR fluconazole 100 mg daily for life Acyclovir 800 mg orally five times daily for 7-10 days. Treatment usually not available and too expensive (intravenous gancyclovir). Prednisolone 40 mg daily for 2 weeks, then slowly taper to zero.
12 4 2 Diarrhoea
Introduction Chronic diarrhoea is very common, affecting up to 60% of HIV-positive individuals at some time in their illness. Common accompanying features include the following: nausea, vomiting, abdominal cramps, flatulence, weight loss and dehydration.
Rehydration Always assess the state of hydration of any patient with diarrhoea. Most patients with mild to moderate dehydration will receive oral rehydration solution. A few patients, with severe dehydration, need intravenous fluids.
Investigation Where facilities are available, send multiple stool samples for microscopy and culture. With appropriate stains it is possible on microscopy to diagnose the following pathogens: Cryptosporidium, Isospora belli, Microsporidia. Stool culture can enable the diagnosis of Salmonella, Shigella, Clostridium difficile.
Treatment In most cases, the cause is not known. So treatment in these cases is empirical. Some cases (probably due to Isospora belli) respond to
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treatment with trimethoprim-sulfamethoxazole (TMP-SMX). Other cases (probably due to Microsporidia) respond to treatment with metronidazole. Sometimes you do find a specific cause of diarrhoea. The table shows specific causes with the appropriate treatment.
DIAGNOSIS
TREATMENT
BACTERIAL INFECTIONS
Salmonella . . . . . . . . . TMP-SMX 2 tablets 2x daily for 7 days OR chloramphenicol 500 mg 4x daily for 7 days.
Shigella . . . . . . . . . . . TMP-SMX 2 tablets 2x daily for 7 days OR nalidixic acid 1g 4x daily for 5 days
Clostridium difficile. . . . metronidazole 400 mg 3x daily for 7 days.
PROTOZOAL INFECTIONS
Cryptosporidium . . . . . symptomatic treatment only
Isospora belli. . . . . . . . TMP-SMX 2 tablets 2x daily for 7 days
microsporidia . . . . . . . metronidazole 400 mg 3x daily for 7 days
Persistent diarrhoea Give symptomatic treatment if diarrhoea persists, the cause is not known, and there is no response to TMP-SMX then metronidazole. Anti-diarrhoeal agents for symptomatic treatment include codeine and loperamide.
12 5 RESPIRATORY PROBLEMS
Some TB/HIV patients fail to improve, or even deteriorate, during anti-TB treatment. They continue to have, or develop new, respiratory problems, e.g. cough, breathlessness, chest pain. First check that the patient has really been taking the anti-TB drugs. Then consider the following possibilities:
ORIGINAL DIAGNOSIS
POSSIBILITIES
sputum smear-negative PTB . . incorrect diagnosis e.g. other pathogens, heart failure, chronic obstructive airways disease
sputum smear-positive PTB . . patient not adherent to anti-TB treatment; drug-resistant TB; super-imposed infection with other pathogens.
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The flow chart shows the management approach in HIV-positive PTB patients who fail to respond or deteriorate while on anti-TB treatment.
The table below shows the main bacterial pathogens responsible for superimposed pneumonia in smear-positive PTB patients and the treatment.
PATHOGEN
TREATMENT
Streptococcus pneumoniae . . . penicillin or TMP-SMX Haemophilus influenzae . . . . . amoxycillin or TMP-SMX Staphylococcus aureus . . . . . . flucloxacillin or chloramphenicol Gram-negative bacilli. . . . . . . chloramphenicol (and gentamicin if necessary)
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12 6 NEUROLOGICAL PROBLEMS A wide variety of neurological problems may occur in TB/HIV patients. The common presentations are the following: · acute confusion · chronic behaviour change · persistent headache · difficulty in walking · poor vision · burning sensation in the feet Neurological problems by reputation are difficult to diagnose. In fact, they are no more difficult to diagnose than other problems, provided that you take time and care. You have to take time and care to obtain a detailed history and perform a proper neurological examination. It is usually necessary to obtain some, if not all, of the history from the patient's relatives or friends. Some simple district-level laboratory tests on blood and cerebrospinal fluid (CSF) are often helpful. 12 6 1 Acute confusion The differential diagnosis when a TB/HIV patient becomes acutely confused includes the following: a) acute super-imposed infection, e.g. septicaemia, meningitis, malaria; b) hypoxaemia, e.g. pneumothorax, pneumonia, heart failure, anaemia; c) metabolic disturbance, e.g. secondary to diarrhoea, hypo-adrenalism; d) adverse drug reaction, e.g. acute confusion may be the first sign of drug-induced acute fulminant liver failure (a useful test, if available, is the prothrombin time). Always check a blood film for malaria. Do a lumbar puncture if the patient has meningism and it is safe to do a lumbar puncture. Other investigations depend on the laboratory facilities available and clinical clues to the diagnosis. 12 6 2 Chronic behaviour change Chronic behaviour change, i.e. over a period of months, is usually due to AIDS dementia or progressive multi-focal leucoencephalopathy. These are untreatable. Since the diagnoses are clinical, you must rule out other treatable possibilities. Send blood for syphilis serology. If lumbar puncture is safe, send CSF to the laboratory to exclude chronic meningitis (e.g. cryptococcal, TB). 119
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12 6 3 Persistent headache The flow chart below shows the management approach to the TB/HIV patient with headache. The following features may accompany headache: reduced level of consciousness, confusion, convulsions. 120
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It is possible, but rare, for TB meningitis to develop after a TB patient has already started anti-TB treatment. For example, a cerebral tuberculoma could rupture into the subarachnoid space releasing TB bacilli not yet killed by anti-TB drugs. A commonly recommended treatment regimen for TB meningitis is as follows: 2 SHRZ, 7 HR. It is unlikely, but possible, that a patient already on TB treatment could develop acute bacterial meningitis. The diagnosis rests on CSF examination. Cryptococcal meningitis The outcome is fatal without treatment and often very poor with treatment. In many countries the drugs for treating cryptococcal meningitis are prohibitively expensive in most cases. The treatment for most patients is therefore symptomatic with analgesia and sedation. For those patients who can afford specific anti-fungal drug treatment, they should receive fluconazole 400 mg daily initially for 10 weeks. An alternative is intravenous amphotericin B (0.5 mg/kg/day) for 6 weeks. Life-long maintenance treatment with fluconazole 200 mg daily is then necessary to prevent relapse.
12 6 4 Difficulty in walking
Spinal TB may cause difficulty in walking. So first make sure (by clinical examination and spine X-ray) that the patient does not also have spinal TB. The cause of difficulty walking in a TB/HIV patient may be HIV-related (spinal cord myelopathy and occasionally peripheral neuropathy) or unrelated to HIV. A patient with difficulty walking and HIV myelopathy usually has a spastic paraparesis. It is only possible to make this diagnosis by excluding the causes of spinal cord disease unrelated to HIV. The table below shows these main causes of spinal cord disease unrelated to HIV, and the diagnostic tests. In HIV-related peripheral neuropathy, sensory disturbance tends to predominate over motor weakness.
CAUSE OF SPINAL CORD DISEASE
DIAGNOSTIC TESTS
cervical spondylosis . . . . . . . . . . cervical spine X-ray, myelography prolapsed intervertebral disc . . . . myelography epidural abscess . . . . . . . . . . . . myelography treatable tumours . . . . . . . . . . . . myelography (neurofibroma, meningioma)
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neurosyphilis . . . . . . . . . . . . . . . syphilis serology, CSF findings
subacute combined . . . . . . . . . . anaemia with raised MCV, low serum vitamin
degeneration of the cord
B12 level
schistosomiasis . . . . . . . . . . . . . identification of eggs in stool, urine,
or rectal snips
myelography
Spinal cord schistosomiasis is difficult to diagnose, but schistosomiasis is easy to treat. Consider a patient with a spinal cord problem who lives in an area endemic for schistosomiasis. Give empirical treatment with a stat dose of praziquantel (40 mg/kg) while pursuing further management.
12 6 5 Poor vision
PRACTICAL POINT If a patient receiving ethambutol develops difficulty seeing clearly, or has problems perceiving colours, stop ethambutol.
Cytomegalovirus retinitis can cause poor vision. The incidence is unknown in AIDS patients in Asia. The diagnosis rests on the characteristic appearance on fundoscopy of a necrotising retinitis with perivascular haemorrhages and exudates. The treatment with ganciclovir or foscarnet is prohibitively expensive in many countries. 12 6 6 Burning sensation in the feet HIV may cause a peripheral neuropathy, often worse when a TB patient starts isoniazid. The features which may accompany the painful burning sensation in the feet include distal weakness and atrophy with absent ankle jerks. Prevention If resources allow, all TB patients should receive pyridoxine 10 mg daily as prophylaxis against isoniazid neuropathy. Otherwise reserve pyridoxine prophylaxis for HIV-positive TB patients, TB patients who drink alcohol, and TB patients with diabetes.
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Treatment Treat patients with established isoniazid neuropathy with pyridoxine 100 mg daily. Amitryptiline (25-75 mg at night), phenytoin (100-300 mg at night), or carbamazepine (100-200 mg 2 x daily) may relieve symptoms in HIV neuropathy. 12 7 FEVER
12 7 1 Approach to management
Fever usually settles within 2-3 weeks of starting anti-TB treatment. Further fever may signal a drug reaction or a disseminated infection. The table below shows the approach to management of further or persistent fever.
FEATURES ACCOMPANYING FEVER LIKELY CAUSE
ACTION
rash . . . . . . . . . . . . . . . . drug reaction. . . . . . . Stop anti-TB drugs
weight loss . . . . . . . . . . . disseminated infection . Examine patient.
progressive anaemia
or pancytopenia
Investigations:
· blood film for malaria
· blood cultures
· consider lumbar puncture
Start antibiotics for
suspected septicaemia
12 7 2 Disseminated infection
Disseminated infection carries a high mortality. The table below shows the wide variety of pathogens which can cause disseminated infection in TB/HIV patients.
PATHOGENS CAUSING DISSEMINATED INFECTION IN TB/HIV PATIENTS
BACTERIA
MYCOBACTERIA
Salmonella typhimurium M. avium Streptococcus pneumoniae complex (MAC) Pseudomonas aeruginosa Staphylococcus aureus Other Gram-negative bacteria
VIRUSES
OTHERS
Cytomegalo Leishmania
- virus
Cryptococcus
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Bacterial septicaemia S.typhimurium and Pneumococcus are common causes of septicaemia in HIV-positive patients. Many strains of S. typhimurium are resistant to several antibiotics. If you suspect septicaemia, treat the patient with chloramphenicol or ampicillin and gentamicin. Disseminated M.avium complex (MAC) This occurs less frequently in AIDS patients in high TB prevalence countries than elsewhere. Diagnostic facilities and treatment are generally not available in district hospitals and many central hospitals. 12 8 OTHER HIV-RELATED PROBLEMS WHICH MAY OCCUR IN TB/HIV PATIENTS Tumours . . . . . KAPOSI'S SARCOMA (KS) KS can affect many parts of the body, but usually the skin and mouth, and sometimes the lung and pleura, gastrointestinal tract, and pericardium. The clinical appearance is usually distinctive. There is often oedema with KS on the face and legs. Diagnostic confusion can arise with keloids, leprosy, sarcoidosis, and melanoma. In case of doubt, a biopsy is diagnostic. Histology shows typical proliferation of spindle cells and small blood vessels. Consider a TB/HIV patient with KS. Development of a pleural effusion or progressive lung infiltrations during anti-TB treatment is probably due to KS. Many countries have limited resources for treating KS. Treatment is often unsatisfactory. Non-steroidal anti-inflammatory drugs (NSAIDs) may help relieve pain. Cytotoxic chemotherapy and radiotherapy may be available in some central hospitals. . . . . . . . . . . . . LYMPHOMA AIDS patients are at increased risk of developing atypical, aggressive lymphomas. Prognosis is poor even with cytotoxic chemotherapy. Anaemia Anaemia in TB/HIV patients may be due to any of the following: TB, HIV-induced marrow suppression, concurrent infections, drug side-effects. Treatment is supportive: iron and folic acid; blood transfusion if essential. 124
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Thrombocytopenia The main causes are HIV-induced autoimmune thrombocytopenia and drug side-effects. High-dose steroids may help if there is bleeding and the platelet count is low (less than 20 x 109 / l). Renal disease HIV-related nephropathy causes nephrotic syndrome and progressive renal damage. There is no specific treatment. Treat urinary tract infections in the usual way. Congestive cardiomyopathy Consider HIV-related congestive cardiomyopathy in the differential diagnosis of heart failure. Treat heart failure in the usual way. Arthropathy Pyrazinamide often causes joint pains but rarely arthritis. HIV-related arthropathy usually affects small joints. NSAIDs may help relieve pain. Hypoadrenalism Cytomegalovirus can cause necrotising adrenalitis. This is difficult to distinguish from TB of the adrenal glands or pseudoadrenal crisis (rifampicin). Treatment is with steroid supplements. SUGGESTIONS FOR FURTHER READING WHO Global Programme on AIDS. Guidelines for the clinical management of HIV infection in adults. Geneva, 1991. WHO Global Programme on AIDS. Guidelines for the clinical management of HIV infection in children. Geneva, 1993. WHO Global Programme on AIDS. AIDS in Africa: a manual for physicians. Geneva, 1992. WHO Global Programme on AIDS. AIDS home care handbook. Geneva, 1993. WHO Global Programme on AIDS. Management of sexually transmitted diseases. Geneva, 1994. Maher D, Mwandumba H. Cryptococcal meningitis in Lilongwe and Blantyre, Malawi. J Infect 1994, 24: 82-83 125
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CHAPTER 13 COORDINATED CARE IN DIFFERENT SETTINGS 13 1 INTRODUCTION TB/HIV patients may receive care in different settings. These settings include the patient's home, local health centre, district hospital, and tertiary referral hospital. Coordination of care in different settings promotes continuity of care for the patient. In the case of TB/HIV patients, sometimes these patients know that they are HIV-positive and later on develop TB. More often, they only find out that they are HIV-positive after developing TB. In either case, the TB control programme needs to collaborate closely with other services providing support and care for HIV-positive individuals. The clinician who treats the TB/HIV patient is in a key position to refer the patient to appropriate services. 13 2 BENEFITS OF SUPPORT FROM LOCAL HIV/AIDS CARE SERVICES The HIV/AIDS care services available vary from place to place. They include HIV/AIDS community support groups and HIV/AIDS home care schemes. The TB/HIV patient may gain the following benefits from the support of local HIV/AIDS services: a) emotional support; b) early identification of any new infections; c) symptomatic treatment in end-stage disease; d) support for his family. 13 3 INTEGRATED SYSTEM OF HIV/AIDS AND TB CARE An integrated system of HIV/AIDS and TB care uses available health systems to provide continuity of care for TB/HIV patients. The chart below shows an integrated system of HIV/AIDS and TB care. 127
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care setting
District Hospital Ј Health Centres Ј Home
care providers District Hospital staff
Health Centre staff
community-based supervisors and trained family care providers
·Diagnosis,
·Follow-up treatment ·DOT supervision
registration
of TB
and treatment of TB
·Diagnosis and treat-
types of ment of HIV-related
care
illness ·Nursing care
provided ·Counselling
·Coordination of
supervisory network
·Social support or
referral to social
services
·Follow-up treatment of HIV-related illness ·Supervision of home-based care ·Health education ·Liaison with NGOs ·Appropriate referral
·Nutrition ·Personal hygiene ·Compliance with treatment of HIVrelated illness ·Care of wounds ·Handling of linen ·Liaison with NGOs
13 3 1 Referral to local HIV/AIDS care services One of the important features of a successful NTP is integration of TB control activities with the general health services (see Chapter 7). This means that at the district and primary health care levels, the general health service staff manage TB patients according to NTP guidelines, supported by NTP staff. General health service and NTP staff need to know what local HIV/AIDS services are available for HIV-positive patients. Providers of local HIV/AIDS services include Ministry of Health, non-governmental organisations (NGOs) and community organisations. Often it is possible to refer patients directly to HIV/AIDS services.
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REFERRAL SYSTEM FOR PATIENTS WITH HIV/AIDS
PERSONNEL
INSTITUTION
ACTIVITITY
All Medical
Identifying patients with All health institutions suspected AIDS. Refer to the nearest hospital.
Physician
Investigate the patient
in order to refute or support
Non-referral institution
provisional diagnosis. Refer to the referral hospital
if suspected diagnosis could
not be ruled out.
Physician responsible for AIDS case Management (PRAM)
Referral hospital
Investigate the patient and diagnose HIV-related disease. Refer confirmed cases to the original hospital. Report confirmed cases to the State AIDS Programme Officer.
PRAM
Referral hospital with advanced diagnostic facilities
Investigate and diagnose HIV related disease. Refer confirmed cases to the State AIDS Programme Officer.
13 3 2 HIV counselling and voluntary testing centres In some towns and cities there are now HIV counselling and voluntary testing centres. Some of the people attending these centres may have TB. A study in Kampala, Uganda showed that 6% of people attending the HIV counselling and voluntary testing centre had undiagnosed TB. NTP collaboration with these centres is important. Staff in the centres should ask clients about chronic cough and refer TB suspects to the NTP for sputum microscopy.
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13 3 3 Care in the community General health services staff can refer patients directly to HIV/AIDS care services. Community care means providing the patient with access to care as close to home as possible. Some HIV/AIDS care services provide home care for AIDS patients. The home care provider may be a health care worker or community volunteer. See the WHO "AIDS Home Care Handbook" for more information. Home care alone is not enough for a TB/HIV patient on a home care scheme. The TB patient needs to continue to receive his anti-TB treatment, under direct observation by a trained and supervised home care provider. The HIV/AIDS home care scheme and the NTP can collaborate to train and supervise the HIV/AIDS home care provider to provide directly observed therapy. Also, the HIV/AIDS home care provider can recognise problems with anti-TB treatment and refer as necessary to the NTP. 13 3 4 Care at Primary Health Care Level A good NTP is integrated with general health services (see Chapter 7). So primary health care staff are in a good position to identify and treat common HIV-related problems in patients during or after anti-TB treatment. Good communication between general health service staff and HIV/AIDS care workers is important for continuity of care of TB/HIV patients. 13 3 5 Private sector Many patients choose to pay for medical services provided by a range of practitioners. Private medical practitioners Ideally there should be close collaboration between private practitioners and the NTP. This results in improved management of TB patients according to NTP guidelines. However, a private practitioner serves the community and guarantees his TB patients good care by following NTP guidelines. A private practitioner can register the patient with the NTP and share continued management. Private practitioners do not have to give up their TB patients entirely to the NTP if they do not want to. Some TB/HIV patients prefer to go to a private practitioner for perceived reasons of confidentiality. In a country where the NTP is very good, many patients will prefer the NTP to a private practitioner. 130
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13 3 6 Care at District Level Primary health care staff can manage many HIV-related problems in the health centres and dispensaries. Sometimes TB/HIV patients develop problems requiring investigations and treatment unavailable at primary health care level. Then they need referral to the District Hospital, either to the out-patient department or for admission. After appropriate district hospital management, often the district level staff can refer the patient back to the primary health care or community level. Good channels of communication promote continuity of care. 13 3 7 Tertiary referral care District level staff sometimes deal with difficult problems of diagnosis or treatment. The patient may benefit from transfer to a tertiary referral hospital. It is usually wise to obtain advice on the telephone before transferring the patient. This is to ensure that the specialist agrees that the patient is likely to benefit from the referral. SUGGESTIONS FOR FURTHER READING WHO Global Programme on AIDS. AIDS Home Care Handbook. Geneva 1993. WHO Global Programme on AIDS. Provision of HIV/AIDS care in resource-constrained settings. Report of a meeting. Geneva 1994. National AIDS Control Organization, Ministry of Health & Family Welfare, Government of India. National AIDS Control Programme, India: Country Scenario Update. September 1994. 131
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CHAPTER 14 PREVENTION OF TB 14 1 INTRODUCTION From the public health point of view, the best way to prevent TB is to provide effective treatment to the infectious TB cases. This interrupts the chain of transmission. Good treatment programmes are the best prevention programmes. HIV-infected individuals are particularly susceptible to infection with M. tuberculosis and the development of TB. What are the ways of protecting people from exposure to TB in health care settings? What is the role of BCG? What is the role of preventive treatment? Can we do anything about those HIV-infected individuals who are already infected with M. tuberculosis and have a high risk of developing active TB? This chapter addresses these questions. 14 2 PROTECTION AGAINST EXPOSURE TO TB Patients and staff in health units face daily exposure to TB. The risk of exposure is greatest in adult medical wards and TB wards where there are many PTB cases. Often the wards are crowded and badly ventilated. We do not yet know the size of this risk. Prompt diagnosis and treatment of patients with sputum smear-positive PTB helps to reduce exposure to TB. Out-patient diagnosis and treatment of PTB patients avoids hospital admission. This is an advantage in decreasing exposure to TB in hospital wards. In some NTPs there is a move away from an in-patient intensive phase towards out-patient management. Known HIV-positive health workers should not work with PTB patients. They should therefore not work in TB wards or adult medical wards. 14 2 1 Environmental control Good ventilation helps reduce TB transmission indoors. Sunlight is a source of ultraviolet light which can kill TB bacilli. So ideally, wards should have large windows. 133
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PRACTICAL POINT In wards, out-patient clinics, sputum collection rooms, and microbiology laboratories, keep the doors closed and the windows open. 14 2 2 Face-masks A face-mask decreases the risk that the person wearing the mask can infect other people. So a TB suspect or a TB patient, if possible, should wear a mask if moving from one part of a hospital to another. Often a health worker wears a mask for protection against TB, e.g. when working on the TB ward. In fact, a mask is generally not very good at protecting the person wearing the mask from inhaling other people's infectious droplets. The exception is when the health worker is supervising a cough-inducing procedure, e.g.bronchoscopy, or sputum induction using nebulised hypertonic saline. 14 2 3 Patient education Health workers should teach TB suspects and TB patients simple measures how to decrease the risk of transmitting TB. These include covering the mouth with the hand when coughing, and using sputum pots with lids. When examining TB patients or suspects, ask them to turn their head to one side. This is to avoid the patient coughing directly at the health worker. 14 2 4 PTB suspects In the majority of cases, PTB suspects attend as out-patients for the diagnosis of TB. In some cases it is necessary to admit PTB suspects to hospital. If possible admit them to a separate ward from other patients. There are often no facilities to separate PTB suspects from other patients. At least try to keep PTB suspects in a part of the ward away from other patients. 14 2 5 Patients with sputum smear-positive PTB In many NTPs, sputum smear-positive PTB patients spend at least part, and often all, of the intensive phase of anti-TB treatment in hospital. Isolation of 134
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these patients in TB wards helps reduce the risk of TB exposure to other patients. Do not admit a patient to the TB ward until you have made the diagnosis of TB. In particular, a TB suspect with HIV infection and high susceptibility to TB should avoid exposure to TB. A TB suspect may not turn out to have TB. 14 3 THE ROLE OF BCG IN PREVENTING TB 14 3 1 General BCG (Bacille Calmette-Guerin) is a live attenuated vaccine derived originally from M. bovis. The route of injection is intra-dermal. The usual dose is 0.05 ml in neonates and infants under the age of 3 months, and 0.1 ml in older children. In high TB prevalence countries, WHO recommends a policy of routine BCG immunisation for all neonates shortly after birth. The benefit of BCG is in protecting young children against disseminated and severe TB, e.g. TB meningitis and miliary TB. BCG has little or no effect in reducing the number of adult cases of PTB. 14 3 2 BCG protection against TB in HIV-infected children It is not known if HIV infection reduces the protection of BCG against TB in children. There is some evidence that conversion to a positive tuberculin test after BCG is less frequent in HIV-infected children. The significance of this finding for protection against TB is not clear. 14 3 3 BCG safety in HIV-infected children There have been a few case reports of local complications and disseminated BCG infection after BCG immunisation of HIV-infected children. However, prospective studies comparing BCG immunisation in HIV-infected and uninfected infants showed no difference in risk of complications. So, in the vast majority of cases, BCG immunisation is safe. 14 3 4 WHO recommended policy on BCG and HIV WHO recommended policy depends on the TB prevalence in a country, as shown below. In a high TB prevalence country, the possible benefits of BCG immunisation outweigh the possible disadvantages. 135
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COUNTRY TB PREVALENCE WHO RECOMMENDED POLICY high . . . . . . . . . . . . . . BCG for all children (according to standard programme) except children with symptoms of HIV disease/AIDS low . . . . . . . . . . . . . . . Do not give BCG immunisation to HIV-infected children 14 4 THE ROLE OF THE EXPANDED PROGRAMME ON IMMUNISATION (EPI) BCG is not the only immunisation in the EPI which may help to protect a child against TB. Measles and whooping cough lower a child's resistance to TB. So whenever you treat a child for TB, check the child's immunisation record. If a child has not received scheduled immunisations, encourage the mother to bring him/her for immunisations, once symptoms of TB have resolved. WHO has collaborated with UNICEF in establishing guidelines for immunisation. The recommendation for individuals with known or suspected asymptomatic HIV infection is that they should receive all EPI vaccines, according to national schedules. 14 5 PREVENTIVE TREATMENT The aim of preventive treatment is to prevent progression of M.tuberculosis infection to disease. A 6 month course of preventive treatment with daily isoniazid (5 mg/kg) is effective. However, preventive treatment for all individuals infected with M. tuberculosis is not a recommended TB control strategy. It is not feasible to try to identify all individuals infected with M. tuberculosis. TB disease develops in only 10% of all individuals infected with M. tuberculosis. So it is not cost-effective to identify and treat all infected individuals in order to prevent disease in 10%. However, it is possible to identify certain groups at high risk of progressing from M. tuberculosis infection to TB disease. It may be costeffective to target preventive treatment at these high-risk groups. 14 5 1 Target groups for preventive treatment Young children are at special risk, especially if they are HIV-infected. HIV infection, in children and in adults, is a potent cause of progression of M. tuberculosis infection to TB disease (see Chapter 9). Infants of mothers with PTB A breast-feeding infant has a high risk of infection from a mother with PTB, 136
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and a high risk of developing TB. The infant should receive 6 months' isoniazid treatment, followed by BCG immunisation. An alternative policy is to give 3 months' isoniazid, then perform a tuberculin skin test. If the skin test is negative, stop the isoniazid and give BCG. If the skin test is positive, continue another 3 months' isoniazid, then stop isoniazid and give BCG.
Children under 5 years of age It is important to screen child house-hold contacts of adults with sputum smear-positive PTB (see Chapter 3). Screening identifies those children under 5 years of age without symptoms. Give these children 6 months' isoniazid preventive treatment. Children under 5 years of age with symptoms need investigation for TB. If investigations show TB, the child receives anti-TB treatment. If investigations do not show TB, the child should receive isoniazid preventive treatment.
HIV-infected individuals Controlled clinical studies have shown that isoniazid preventive treatment reduces the risk of TB disease in HIV-positive individuals also infected with M. tuberculosis. The evidence of M. tuberculosis infection is a positive tuberculin skin test. In HIV-positive individuals, the extra benefit of a reduced risk of TB may also be a reduced rate of progression of HIV infection.
14 5 2 Role of isoniazid preventive treatment in HIV-positive individuals
The theoretical benefits of isoniazid preventive treatment are attractive. The table shows the potential disadvantages and necessary precautions.
POTENTIAL DISADVANTAGE risk of drug toxicity (especially liver damage)
NECESSARY PRECAUTION do not give to people with chronic disease or who drink alcohol regularly
emergence of drug-resistance (if the in all cases exclude TB disease by patient has undetected TB disease chest X-ray, and not just M. tuberculosis infection) in cases with cough by sputum microscopy
diversion of resources from NTP activities
funding must be from sources other than NTP (e.g. AIDS control programme, voluntary sector)
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There are limitations in the feasibility of isoniazid preventive treatment on a wide scale in developing countries like India. a) Voluntary HIV testing is not widely available, so the number of suitable known HIV-positive persons is a small proportion of all HIV-positive persons. b) Resources are often inadequate to ensure satisfactory exclusion of TB disease, treatment compliance and patient monitoring for drug toxicity. c) When HIV-positive persons develop TB, we do not how many are due to reactivation of old infection and how many to new infection. Isoniazid preventive treatment will protect against new infection only during the 6 months of treatment. So the effectiveness of a course of isoniazid preventive treatment will be limited if TB is often due to new infections. d) Many HIV-positive persons infected with M. tuberculosis have a negative tuberculin skin test. So screening for M. tuberculosis by tuberculin skin testing will not identify all persons infected with M.tuberculosis. e) HIV-positive persons who feel well may be reluctant to accept TB screening and consideration of isoniazid preventive treatment. Isoniazid preventive treatment programmes need evaluation. We need to know their cost, sustainability, potential impact, and effect on drug resistance. WHO does not at present recommend widespread isoniazid preventive treatment for HIV-positive persons in high TB prevalence countries. Isoniazid preventive treatment may have a role in selected groups (e.g. workers in a factory, health workers, soldiers) and in selected individuals. SUGGESTIONS FOR FURTHER READING WHO. Expanded Programme on Immunisation. Childhood tuberculosis and BCG vaccination. BCG - gateway to EPI. Geneva: WHO, 1989. WHO. Global Programme for Vaccines and Immunisation. Immunisation Policy. Geneva, 1995. WHO/IUATLD. Tuberculosis preventive therapy in HIV-infected individuals. A joint statement of the WHO Tuberculosis Programme and the Global Programme on AIDS, and the International Union Against Tuberculosis and Lung Disease (IUATLD). Weekly Epidemiological Record 1993; 68: 361-364. O'Brien RJ, Perriens JH. Preventive therapy for tuberculosis in HIV infection: the promise and the reality. AIDS 1995; 9: 665-673. 138
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INDEX Abscess lung . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30, 32 tuberculous lymphadenopathy . . . . . . . . . . . . . . . . . . . . . . 33 Acid-fast bacilli . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19, 27 Adrenal gland tuberculosis . . . . . . . . . . . . . . . . . . . . . . . . . 22, 43, 56 AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83, 86 WHO clinical case definition . . . . . . . . . . . . . . . . . . . . . . 87 Anal/genital warts. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 Anaemia. . . . . . . . . . . . . . . . . . . . . . . . . . . . 70, 101, 122, 123, 124 Angular cheilitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 Anti-TB drugs (see also essential TB drugs). . . . . . . . . . . . . . . . . . 57, 58 modes of action. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 Aphthous ulcers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 Ascites, tuberculous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 Aspergilloma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 Bacterial pneumonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30, 32, 97 Bacterial vaginosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 BCG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 HIV infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 infants of mothers with TB . . . . . . . . . . . . . . . . . . . . . . . . 136 WHO policy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 Biopsy diagnostic approach to extrapulmonary TB . . . . . . . . . . . . . 33 lymph node. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33, 34 peritoneal TB. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 pleural . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 Blood spread of tubercle bacilli . . . . . . . . . . . . . . . . . . . . . . . . . 20, 46 Bone TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22, 43 Breathlessness . . . . . . . . . . . . . . . . . . . . . . . . . 26, 30, 31, 36, 37, 95 Bronchial carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30, 32 Bronchiectasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30, 31 Candidiasis. . . . . . . . . . . . . . . . . . . . . . . . . . 87, 107, 113, 114, 115 Capreomycin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 Caseation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 Case definitions of tuberculosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 Case-finding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25, 78 Cavitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22, 31, 32, 93, 95 139
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Cerebrospinal fluid . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41, 119, 120 Cervicitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 Chancroid. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112, 113 Chest pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26, 36, 37, 95 Chest X-ray . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21, 30, 93 Children approach to diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 BCG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 clinical recognition of HIV infection . . . . . . . . . . . . . . . . . 107 contacts of infectious adults. . . . . . . . . . . . . . . . . . . . . . . . 50 counselling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 differential diagnosis of pulmonary TB . . . . . . . . . . . . . . . . 97 Expanded Programme on Immunisation . . . . . . . . . . . . . . 136 HIV-related TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97 HIV testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 impact of HIV infection on TB diagnosis . . . . . . . . . . . . . . . 97 preventive treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 score system for TB diagnosis . . . . . . . . . . . . . . . . . . . 47, 48 side effects of anti-TB drugs . . . . . . . . . . . . . . . . . . . . . . . . 70 "treatment trial" . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 tuberculin testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 Chlamydia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 Chronic behaviour change . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 Chronic obstructive airways disease. . . . . . . . . . . . . . . . . . . . . 30, 117 Clostridium difficile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 Code for TB treatment regimens . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 Cohort analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 Congestive cardiac failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30, 38 Conjunctivitis, phlyctenular . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Connective tissue disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 Continuation phase of treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 Cough . . . . . . . . . . . . . . . . . . . . . . . . . 19, 25, 37, 46, 87, 107, 117 Cryptococcal meningitis . . . . . . . . . . . . . . . . . . . . . . 42, 86, 120, 121 Cryptosporidium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116, 117 Culture, sputum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 Cure, definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 Cycloserine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 Cytomegalovirus . . . . . . . . . . . . . . . . . . . . . . . . . . 97, 116, 122, 125 Dactylitis, tuberculous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Default, definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 140
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Desensitisation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 Diarrhoea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44, 86, 87, 107, 116 Difficulty walking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 Disseminated infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 Dysphagia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115, 116 Directly Observed Therapy (DOT) . . . . . . . . . . . . . 59, 60, 61, 80, 130 District level care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131 Dormant TB bacilli . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21, 58 Drug resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60, 62, 63, 77 Drug side effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69, 71 Education of patients to prevent TB transmission. . . . . . . . . . . . . . . . 134 Environmental control measures to prevent TB transmission . . . . 133, 134 Erythema nodosum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Essential anti-TB drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 Ethambutol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58, 70, 71, 72, 122 Ethionamide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 Extrapulmonary TB. . . . . . . . . . . . . . . . . . . . . . . . . 22, 32, 55, 56, 91 Failure of treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61, 66 Face-masks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134 Fever . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26, 48, 87, 99, 105, 123 Fluorochrome stain. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27, 28 Flow charts identification and management of child contacts . . . . . . . . . 51 investigation of lymphadenopathy . . . . . . . . . . . . . . . . . . . 34 management of HIV-positive TB patients who fail to respond or deteriorate while on anti-TB treatment. . . . . . . . . . . . . . . . 118 management approach for persistent headache . . . . . . . . 120 Gastric suction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 Gastrointestinal tuberculosis . . . . . . . . . . . . . . . . . . . . . 22, 43, 44, 48 Genital tract TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22, 43 Genital ulcers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101, 112 Gibbus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 Gingivitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 Gonorrhoea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 Hairy leukoplakia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 Haemophilus influenzae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118 Haemoptysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26, 30, 31, 95 Hepatic TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 Hepatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70, 71, 74, 84, 99 Herpes simplex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87, 107, 113 141
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Herpes zoster . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87, 101, 113 HIV background information . . . . . . . . . . . . . . . . . . . . . . . . . . 83 epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 HIV-related TB, basic facts. . . . . . . . . . . . . . . . . . . . . . . . . 91 immunopathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 natural history . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 prevention of transmission in health units . . . . . . . . . . . . . . 84 Hypoadrenalism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43, 64, 125 Hypersensitivity reactions . . . . . . . . . . . . . . . . . . . . . . . . . . 21, 64, 74 Immunisation (see also BCG and Expanded Programme on Immunisation) . 135 Impetigo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114 Inguinal bubo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 Initial phase of treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59, 60 Integrated HIV/AIDS and TB care . . . . . . . . . . . . . . . . . . . . . 127, 128 Isoniazid. . . . . . . . . . . . . . . . . . . . 51, 58, 70, 71, 73, 122, 136, 137 Isospora belli. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116, 117 Kanamycin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 Kaposi's sarcoma . . . . . . . . . . . . . . . . . . . . 33, 37, 86, 87, 114, 124 Laryngeal swabs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 Lymph nodes approach to investigation of lymphadenopathy . . . . . . . . . . 34 biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33, 34 features of lymph nodes which indicate further investigation . 96 histological appearance . . . . . . . . . . . . . . . . . . . . . . . . . . 96 persistent generalised lymphadenopathy . . . . . . . . . . . 86, 96 tuberculous lymphadenopathy . . . . . . . . . . . . . 22, 33, 48, 97 Lymphogranuloma venereum . . . . . . . . . . . . . . . . . . . . . . . . . 112, 113 Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31, 33, 42, 97, 124 Malnutrition, children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46, 97 Meningitis, cryptococcal . . . . . . . . . . . . . . . . . . . 42, 86, 88, 119, 120 Meningitis,tuberculous . . . . . . . . . . . . . . . . . 41, 42, 61, 97, 119, 121 differential diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 subacute/chronic meningitis . . . . . . . . . . . . . . . . . . . . . . 120 Microsporidia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116, 117 Miliary TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34, 61 Molluscum contagiosum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114 Multi-drug resistant TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 Mycobacterium africanum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 Mycobacterium avium complex . . . . . . . . . . . . . . . . . . . . . . . 123, 124 142
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Mycobacterium bovis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 Mycobacterium tuberculosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 National Tuberculosis Programme . . . . . . . . . . . . . 77, 78, 79, 80, 130 Neurosyphilis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119, 120 Nocardia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95, 118 Occupational lung disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 Papular folliculitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114 Pathogenesis of TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Pericarditis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21, 22, 56, 64, 65 Pericardial effusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 Pleural effusion, tuberculous . . . . . . . . . . . . 22, 32, 36, 55, 56, 65, 95 Pneumocystis carinii pneumonia . . . . . . . . . . . . . . . . . . . . . 94, 95, 97 Pneumothorax . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31, 37 Post-primary TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21, 22, 46 Prednisolone (see also steroid treatment) . . . . . . . . 64, 65, 72, 115, 116 Pregnancy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63, 108, 112 Prevention of tuberculosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 BCG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 environmental control measures . . . . . . . . . . . . . . . . . . . . 133 Primary complex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20, 21 Private medical practitioners . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130 Pulmonary TB . . . . . . . . . . . . . . . . . . . 19, 20, 22, 33, 46, 61, 65, 92 adults chest X-rays in diagnosis . . . . . . . . . . . . . . . . . . . . . 30 clinical features . . . . . . . . . . . . . . . . . . . . . . . . 25, 26 diagnostic approach. . . . . . . . . . . . . . . . . . . . . . . . 25 diagnostic sputum smear microscopy . . . . . . . . . . . . 26 differential diagnosis. . . . . . . . . . . . . . . . . . . . . 29, 30 differential diagnosis of chest X-ray findings. . . . . . . . 31 distinguishing other HIV-related pulmonary diseases . 94, 95 patterns of disease . . . . . . . . . . . . . . . . . . . . . . . . . 31 children differential diagnosis in HIV-infected children . . . . . . . 97 Psoriasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114 Pyogenic brain abscess . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 Pyomyositis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114 Pyrazinamide . . . . . . . . . . . . . . . . . . . 58, 59, 62, 64, 70, 71, 73, 74 Pyridoxine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69, 71, 122, 123 Rehydration. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116 Relapse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55, 56, 59, 61, 99 143
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Renal disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64, 125 Renal and urinary tract TB. . . . . . . . . . . . . . . . . . . . . . . . . . 22, 43, 64 Retreatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60, 61 Rifampicin. . . . . . . . . . . . 58, 59, 62, 63, 64, 70, 71, 73, 98, 99, 125 Road to health card . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 Sarcoidosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32, 124 Scabies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72, 114 Second-line drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 Sexually transmitted diseases. . . . . . . . . . . . . . . . . . . . . . . . . . 83, 111 Salmonella . . . . . . . . . . . . . . . . . . . . . . . . . 101, 116, 117, 123, 124 Schistosomiasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 Shigella . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116, 117 Short-course chemotherapy . . . . . . . . . . . . . . . . . . . 57, 61, 74, 78, 79 Skin TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 Source of TB infection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19, 47, 78 Spastic paraparesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 Spinal block, in tuberculous meningitis . . . . . . . . . . . . . . . . . . . . . . . 64 Spinal cord disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121, 122 Spinal TB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22, 43, 44, 121 Sputum smear microscopy. . . . . . . . . . . . . . . . . . . . . . . . . . 26, 27, 78 children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 Staphylococcus aureus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118, 123 Steroid treatment, adjuvant . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64, 65 Streptococcus pneumoniae . . . . . . . . . . . . . . . . . . . . . . . 94, 118, 123 Streptomycin . . . . . . . . . . . . . . . . . 58, 59, 62, 63, 64, 70, 71, 73, 75 Syphilis primary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 meningitis . . . . . . . . . . . . . . . . . . . . . . . . 42, 119, 120, 122 Target groups for preventive treatment . . . . . . . . . . . . . . . . . . . . . . 136 Targets for TB control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77, 78 Thiacetazone. . . . . . . . . . . . . . . . . . . 58, 62, 63, 70, 71, 72, 98, 104 Thrombocytopenia . . . . . . . . . . . . . . . . . . . . . . . . . . 70, 99, 101, 125 Tinea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114 Toxoplasmosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 Transfer out, definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 Treatment of TB (see also anti-TB drugs) . . . . . . . . . . . . . . . 57, 78, 127 default, definition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 failure, definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 modes of action of anti-TB drugs . . . . . . . . . . . . . . . . . 58, 59 monitoring of patients during treatment. . . . . . . . . . . . . 65, 66 144
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National Tuberculosis Programmes. . . . . . . . . . 77, 78, 79, 80 recommended treatment regimens . . . . . . . . . . . . . . . . . . . 61 recording treatment outcome . . . . . . . . . . . . . . . . . . . . . . . 66 recurrence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92, 98, 99 response to treatment . . . . . . . . . . . . . . . . . . . . . . . . . 98, 99 special situations . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63, 64 standardised treatment categories . . . . . . . . . . . . . . . . . . . 56 steroid treatment . . . . . . . . . . . . . . . . . . . . . . . . . 64, 65, 72 treatment categories of TB. . . . . . . . . . . . . . . . . . . . . . . . . 56 treatment regimens of anti-TB drugs . . . . . . . . . . . . . . . . . . 61 Trichomonas vaginalis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112, 113 Tubercle bacilli . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19, 20, 26, 45 Tuberculin skin test . . . . . . . . 20, 25, 45, 47, 48, 49, 50, 51, 137, 138 Tuberculosis (see also individual headings) . . . . . . . . . . . . . . . . . . . . 19 basic facts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 diagnosis in adults . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 diagnosis in children . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 HIV-related, basic facts . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 pathogenesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20, 46 prevention in HIV-infected individuals . . . . . . . . . . . . 133, 137 TB suspect. . . . . . . . . . . . . . . . . . . . . . 25, 26, 78, 129, 134 treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . 57, 61 78, 127 Urethral discharge . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 Vaginal discharge . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 Vaginitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 Voluntary HIV testing centres . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129 Walking difficulty. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 Weight loss . . . . . . . . . . . . . . . . . . 25, 47, 48, 86, 87, 107, 116, 123 Ziehl-Neelsen stain. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 145
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The tuberculosis epidemic is growing larger and more dangerous each year. The World Health Organization's Global Tuberculosis Programme (GTB) monitors and surveys this epidemic. More importantly, GTB helps countries to control the epidemic by working with them to develop and implement the technical inputs, training, and research necessary to establish effective tuberculosis control programmes. If you would like further information about the tuberculosis epidemic or the WHO Global Tuberculosis Programme, please call 41 22 791 2853, send an e-mail to [email protected], or write to: Documentalist, Global Tuberculosis Programme, World Health Organization, 20 Avenue Appia, CH-1211 Geneva 27, Switzerland.

A Harries, D Maher, M Uplekar

File: a-clinical-manual-for-south-east-asia.pdf
Title: front cover (Convertito)-2
Author: A Harries, D Maher, M Uplekar
Author: G3
Published: Fri May 3 10:32:00 2002
Pages: 147
File size: 0.91 Mb


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