Essentials ofpostgraduatebooks.jaypeeapps.com/pdf/Pediatrics/...Essentials of TUBERCULOSIS IN...

Essentials ofTUBERCULOSIS IN CHILDREN

4th Edition

Vimlesh Seth MD FAMS FCAI FISCDSenior Consultant

Formerly, Senior Professor and HeadDepartment of Pediatrics and

Chief Division of Tuberculosis, PulmonologyRheumatology and Intensive Care Unit

All India Institute of Medical Sciences (AIIMS)New Delhi, India

SK Kabra MD DNBProfessor and Incharge

Division of Tuberculosis and PulmonologyAll India Institute of Medical Sciences (AIIMS)

New Delhi, India

Foreword

Peter R Donald

JAYPEE BROTHERS MEDICAL PUBLISHERS (P) LTDNew Delhi • St Louis • Panama City • London

®Ja

ypee

Brot

hers

Published byJaypee Brothers Medical Publishers (P) Ltd

Corporate Office4838/24, Ansari Road, Daryaganj, New Delhi 110 002, IndiaPhone: +91-11-43574357, Fax: +91-11-43574314

Offices in India• Ahmedabad, e-mail: [email protected]• Bengaluru, e-mail: [email protected]• Chennai, e-mail: [email protected]• Delhi, e-mail: [email protected]• Hyderabad, e-mail: [email protected]• Kochi, e-mail: [email protected]• Kolkata, e-mail: [email protected]• Lucknow, e-mail: [email protected]• Mumbai, e-mail: [email protected]• Nagpur, e-mail: [email protected]

Overseas Offices• North America Office, USA, Ph: 001-636-6279734

e-mail: [email protected], [email protected]• Central America Office, Panama City, Panama, Ph: 001-507-317-0160

e-mail: [email protected], Website: www.jphmedical.com• Europe Office, UK, Ph: +44 (0) 2031708910

e-mail: [email protected]

Essentials of Tuberculosis in Children

© 2011, Jaypee Brothers Medical Publishers

All rights reserved. No part of this publication should be reproduced, stored in a retrieval system, or transmitted in any form or byany means: electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the editors andthe publisher.

This book has been published in good faith that the material provided by contributors is original. Every effort is made to ensureaccuracy of material, but the publisher, printer and editors will not be held responsible for any inadvertent error(s). In case of anydispute, all legal matters are to be settled under Delhi jurisdiction only.

First Edition : 1997Second Edition : 2001Third Edition : 2006Fourth Edition : 2011

ISBN 978-93-5025-252-9

Typeset at JPBMP typesetting unitPrinted at

Jayp

ee B

rothe

rs

Dedicated to

My husbandProfessor SD Seth

for his constant encouragementand moral support

My grandchildren Ushmita and Udbhavfor helping me proactively

to become computer friendlyfor easing my editorial

work for the book

Jayp

ee B

rothe

rs

Contributors

AK Gupta MD

Professor and HeadDepartment of RadiodiagnosisAll India Institute of MedicalSciencesNew Delhi, IndiaE-mail: [email protected]

Alexey Kruk MD

Department of Public HealthOxford UniversityUnited KingdomE-mail: [email protected]

A Maheshwari MD

Assistant ProfessorDepartment of PediatricsKalawati Saran Children HospitalLady Hardinge Medical CollegeNew Delhi, IndiaE-mail: [email protected]

Alka Beotra PhD

Scientific DirectorNational DOPE Testing LaboratoryJN Stadium, Lodi RoadNew Delhi, IndiaE-mail: [email protected]

Anju Seth MD

ProfessorDivision of EndocrinologyDepartment of PediatricsKalawati Saran Children HospitalLady Hardinge Medical CollegeNew Delhi, IndiaE-mail: [email protected]

Arvind Bagga MD FIAP FAMS

ProfessorDepartment of PediatricsAll India Institute of MedicalSciencesNew Delhi, IndiaE-mail: [email protected]

Ashok Rattan MD

Chief ExecutiveFortis Clinical Research LtdAdvisor, Religare SRL, FortisEscorts, Delhi and NCRE-mail:[email protected],[email protected]

Ashu Seith Bhalla MD

Associate ProfessorDepartment of RadiodiagnosisAll India Institute of MedicalSciencesNew Delhi, IndiaE-mail: [email protected]

Atin Kumar MD

Assistant ProfessorRadiodiagnosisJPNA Trauma CentreAll India Institute of MedicalSciencesNew Delhi, IndiaE-mail: [email protected]

Bansidhar Tarai MD

Lab ManagerMicrobiology, Immunology andMolecular BiologyQuest Diagnostics India PrivateLimitedGurgaonHaryana, IndiaE-mail: [email protected]

Ben J Marais MRCP FCP M (Med)

ProfessorDepartment of Pediatrics and ChildHealthFaculty of Health Sciences,Tygerberg HospitalHealth Sciences, StellenboschUniversityPO Box No. 190637505 Tygerberg, South AfricaE-mail: [email protected]

BN Upendra MSAssistant ProfessorDepartment of OrthopedicsAll India Institute of MedicalSciences, New Delhi, India

BR Thapa MDProfessor and ChiefDivision of PediatricGastroenterology Hepatology andNutritionPostgraduate Institute of MedicalEducation and Research (PGIMER)Chandigarh, IndiaE-mail: [email protected]

Daphne LingDepartment of Epidemiologyand BiostatisticsMC Gill University , Quebec, Canada

Donald A Enarson MD, FRCP (Edin)

International Union AgainstTuberculosis and Lung Disease68 boulvard Saint-MichelParis 75006 FranceE-mail: [email protected] Chair in ClinicalPharmacologyIndian Council of Medical Researchand Professor and HeadDepartment of PharmacologyAll India Institute of Medical SciencesNew Delhi, IndiaE-mail: [email protected]@gmail.com

H Simon Schaaf MBChB (Stell) MMedPed (Stell) DCM (Stell) MD Ped (Stell)Professor of PediatricsDesmond Tutu TB CentreDepartment of Pediatrics and ChildHealth, and Tygerberg Children’sHospital, Faculty of Health SciencesStellenbosch UniversityPO Box 19063, 7505 TygerbergSouth AfricaE-mail [email protected]

Jayp

ee B

rothe

rs

Essentials of Tuberculosis in Childrenviii

Harleen MS Grewal MD PhD DTMH

Professor and Senior ConsultantThe Grade Institute Section forMicrobiology and ImmunologyUniversity of Bergen, NorwayE-mail: [email protected]

Heidi Syre PhD

Scientist, The Grade Institute Sectionfor Microbiology and ImmunologyUniversity of Bergen, NorwayE-mail: [email protected]

J Cunningham MD FRCP

Medical Officer, WHO/CDS/TDR/PRDUnicef/UNDP/World Bank/WHOSpecial Program for Research inTropical Diseases, 20 Appia AveGeneva-27, SwitzerlandE-mail: [email protected]

JB Sharma MD DNB FRCOG

Associate ProfessorDepartment of Obstetrics andGynecologyAll India Institute of Medical SciencesNew Delhi, IndiaE-mail: [email protected]

JL Stanford MD

Head, Division of BacteriologySchool of PathologyUniversity College andMiddlesex School of Medicine63-67, Riding House StreetLondon WIP 7PP, UK

K Gopinath PhD

ScientistDivision of Clinical MicrobiologyDepartment of Laboratory MedicineAll India Institute of Medical SciencesNew Delhi, IndiaE-mail: [email protected]

Kusum Verma MD

Senior PathologistSir Ganga Ram Hospital, New DelhiFormerly Dean, Professor and HeadDepartment of PathologyAll India Institute of Medical SciencesNew Delhi, IndiaE-mail: [email protected]

LS Chauhan MD

Senior Dy Director-General (TB)Central TB DivisionDirectorate General of HealthServices and Family WelfareGovernment of IndiaNirman Bhawan, New Delhi, IndiaE-mail: [email protected]

Madhukar Pai MD PhD

Assistant Professor and CIHR NewInvestigatorDepartment of Epidemiology andBiostatisticsMcGill University 1020 Pine AveWestMontreal, QC H3A IA2, CanadaE-mail: [email protected].

Madhulika Kabra MD

Additional ProfessorDepartment of PediatricsAll India Institute of MedicalSciencesNew Delhi, IndiaE-mail:[email protected]

Manju Ghosh PhD

Research ScientistDivision of GeneticsDepartment of PediatricsAll India Institute of MedicalSciencesNew Delhi, IndiaE-mail:[email protected]

Md Khurshid Alam HyderMedical Officer (TB)Tuberculosis ControlWorld Health OrganizationRegional Office for South-East AsiaWorld Health HouseIndraprastha EstateMahatma Gandhi MargNew Delhi, IndiaE-mail: [email protected]

Nani Nair MD

Regional Adviser TBWorld Health OrganizationRegional Office for South-East AsiaNew Delhi-110002, IndiaE-mail: [email protected]

Neena Khanna MDProfessorDepartment of Dermatology andVenereologyAll India Institute of Medical SciencesNew Delhi, IndiaE-mail: [email protected]

Nimrat BawaDiplomat of American Boards(Pathology)Director Technical AffairsAuroprobe LaboratoriesC-229, Defence ColonyNew Delhi, IndiaE-mail: [email protected],[email protected]

Nulda Beyers MBChB(Stell) FCP(SA)

PhD(Stell) MSc(Med)(UCT)

Professor TB/Community ProjectInternational Union AgainstTuberculosis and Lung Disease68 boulevard Saint-MichelParis, FranceE-mail: [email protected]

OP Semwal MBBS DCH

Former, Research AssociateDepartment of PediatricsAll India Institute of Medical SciencesNew Delhi, IndiaNow: Senior Consultant PediatricsE-mail: [email protected]

Pawan Rawal MD DM

Senior Research AssociateDivision of PediatricGastroenterology Hepatology andNutritionPostgraduate Institute of MedicalEducation and Research (PGIMER)Chandigarh, IndiaE-mail: [email protected]

PK Dave MS

Senior ConsultantDepartment of Orthopedics andDirectorRockland Hospital, New DelhiFormer Director and Professor ofOrthopedicsAll India Institute of Medical SciencesAnsari Nagar, New Delhi, IndiaE-mail: [email protected]

Jayp

ee B

rothe

rs

Contents ix

PM Udani (Late) MD DCH

Professor EmeritusDepartment of PediatricsInstitute of Child Health, JJ Groupof HospitalsMumbai, Maharashtra, India

PP Kotwal MS

Professor and HeadDepartment of OrthopedicsAll India Institute of Medical SciencesNew Delhi, IndiaE-mail: [email protected]

PR Donald MBChB (Stell) DCH (Glasg)

DTM&H (Lond) FCP(SA) FRCP (Edin) MD

(Stell)

Emeritus Professor of PediatricsDesmond Tutu TB CentreDepartment of Pediatrics and ChildHealthand Tygerberg Children’s HospitalFaculty of Health SciencesStellenbosch UniversityPO Box 190637505 Tygerberg, South AfricaE-mail: [email protected]

Prashant Mathur DCH DNB PhD

Scientist ‘D’Division of NoncommunicableDiseasesIndian Council of Medical ResearchNew Delhi, IndiaE-mail: [email protected],[email protected]

Rachna Seth DCH DNB

Assistant ProfessorDepartment of PediatricsAll India Institute of Medical SciencesNew Delhi, IndiaE-mail:[email protected]

Rajni SharmaAssistant ProfessorDivision of EndocrinologyDepartment of PediatricsKalawti Saran Children HospitalLady Hardinge Medical CollegeNew Delhi, IndiaE-mail: [email protected]

Rakesh Lodha MD

Assistant ProfessorDepartment of PediatricsAll India Institute of MedicalSciencesNew Delhi, IndiaE-mail: [email protected]

Ravi Angara MD

Senior ResidentDivision of PediatricGastroenterology Hepatology andNutritionPostgraduate Institute of MedicalEducation and ResearchChandigarh, IndiaE-mail: [email protected]

Robert P Gie MD

Desmond Tutu TB Center andDepartment ofPediatric and Child HealthFaculty of Health SciencesStellenbosh UniversitySouth AfricaE-mail: [email protected]

Rohit Sarin DTCD MD

HeadDepartment of TB Control andTrainingLala Ram Sarup Institute ofTuberculosis and Related DiseasesSri Aurobindo MargNew Delhi, IndiaE-mail: [email protected]

Roli Mathur PhD

Scientist ‘C’Division of Basic Medical SciencesIndian Council of Medical ResearchNew Delhi, IndiaE-mail: [email protected],[email protected]

Ruchi Sood PhD

Research Scientist-InfectiousDiseasesNew Drug Discovery ResearchRanbaxy Research LaboratoriesPlot No. 20, Sector 18Udyog Vihar, Industrial AreaGurgaon, Haryana, IndiaE-mail: [email protected]

S Rasool MBBS

Research OfficerRegional ResearchInstitute of Unani MedicineJamia NagarNew Delhi, India

Sandeep R Mathur MD

Assistant ProfessorDepartment of PathologyAll India Institute of Medical SciencesNew Delhi, IndiaE-mail:[email protected]

Sangeeta Sharma MD

Specialist and HeadDepartment of PediatricsLRS Institute of TB and RespiratoryDiseasesNew Delhi, India

Sarman Singh MD

ProfessorClinical Microbiology DivisionDepartment of Laboratory MedicineAll India Institute of MedicalSciencesNew Delhi, IndiaE-mail- [email protected]

S Aneja MD

Director ProfessorDepartment of PediatricsKalawati Saran Children HospitalLady Hardinge Medical CollegeNew Delhi, IndiaE-mail: [email protected]

SD Seth MD

Advisor Clinical Trials Registry –IndiaNational Institute of Medical StatisticsIndian Council of Medical ResearchNew Delhi, India

Seemab Gulati MD

Associate ProfessorDepartment of PediatricsAll India Institute of Medical SciencesNew Delhi, IndiaEmail: [email protected]

Contributors

Jayp

ee B

rothe

rs

Essentials of Tuberculosis in Childrenx

S Mukhopadhyaya MD

Senior RadiologistFormerly Professor and HeadDepartment of RadiodiagnosisAll India Institute of Medical SciencesNew Delhi, IndiaE-mail:[email protected]

SK Kabra MD DNB

ProfessorDepartment of PediatricsAll India Institute of Medical SciencesNew Delhi, IndiaE-mail: [email protected]

Suneeta Mittal MD FRCOG

Professor and HeadDepartment of Obstetrics andGynecologyAll India Institute of Medical SciencesNew Delhi, IndiaE-mail: [email protected]

S KumarHead of LaboratoriesAuroprobe LaboratoriesE-mail: [email protected]

S Kuhn MD

Consultant in PediatricsInfectious diseases atAlberta Children’s Hospital1820 Richmond Road SWCalgargy, Alberta, CanadaE-mail:[email protected]

Tahmeed Ahmed MBBS PhD

Senior Scientist and HeadNutrition ProgrammDhaka, BangladeshE-mail: [email protected]

V Kalra MD

Senior ConsultantPediatric Neurology

IP Apollo HospitalSarita Vihar, New DelhiEmail: [email protected]

Vimlesh Seth MD

Senior Consultant in PediatricsFormerly Senior Professor andHeadDepartment of PediatricsAll India Institute of MedicalSciencesNew Delhi, IndiaE-mail: [email protected],[email protected]

YK Amdekar MD

Senior Consultant Pediatrics151, Tushar, 14th RoadChembur, Mumbai, Maharashtra,IndiaE-mail: [email protected]

Jayp

ee B

rothe

rs

The epidemic proportions of tuberculosis in many countries was identified as a global emergency in 1993. Despite aconsiderable increase in international efforts aimed at tuberculosis control and investment in tuberculosis research,the perverse influence of HIV-infection combined with the effects of poverty and economic recession have combinedto ensure that the failure to control tuberculosis remains a cause for concern for National Tuberculosis ControlManagers in many countries. The magnitude of the problem is daunting and has been exacerbated by the appearanceof an increasing proportion of MDR-TB and the threat of XDR TB; under the lengthening shadow of HIV, the dreamof controlling, not to speak of eradicating TB has moved far into the future. Against this background, childhoodtuberculosis may appear to be a minor problem, but the percentage of tuberculosis occurring in children is estimatedto vary between 15% in low income countries to below five percent in United States and European countries, whilein high density peri-urban slums, the proportion may rise to much more than 20% in some cases. Even in developedcountries, MDR and XDR tuberculosis are an ever-present threat due to the increasing mobility of people acrossinternational boundaries.

The problem of the diagnosis of tuberculosis in children remains a significant obstacle and is worsened insevere forms of extrapulmonary diseases such as osteoarticular disease and meningeal tuberculosis. The lack ofstandard case definitions and low priority accorded to childhood tuberculosis in the public health agendas of manycountries are persistent problems. Nonetheless, it is pleasing that the problems of childhood tuberculosis have recentlyreceived increasing attention from the various agencies including the World Health Organization (WHO).

The belief that tuberculosis in children is not a significant cause of transmission of infection is also not true ifviewed from a long-term perspective; a significant proportion of children in the younger and vulnerable age groupwho are infected by an adult source case will very often not receive preventive therapy and will later developinfectious adult-type tuberculosis, especially during adolescence and this is particularly likely to happen incommunities with a high incidence of HIV-infection. Globally, it is estimated that 1.5 million new cases and 130,000deaths due to tuberculosis per year occur in young children. Of the total deaths due to tuberculosis, 95% occur indeveloping countries. It has been rightly emphasized that tuberculosis control programs should recognize tuberculosisas a disease of the family and community rather than only the individual and that tuberculosis infection and diseasein children of all ages should be managed simultaneously with the evaluation and management of other familymembers and members of the extended family and household and not in isolation.

It is thus pleasing that children are now specially included in the Revised National Tuberculosis ControlProgramme (RNTCP) and that antituberculosis agents will become available on a weight-for-age basis. Suboptimaldosing still remains possible and the lack of child-friendly preparations makes the accurate treatment of under-five-year-old children difficult and it is this group that is subject to more serious forms of disseminated disease. Withinfinancial constraints, active contact tracing of under-five-year-old children is now recommended and will be facilitatedby a family or household-orientated approach.

In addition to these welcome innovations, the early diagnosis and management by directly observed short-course treatment (DOTS) of all sputum microscopy smear-positive patients, whether children, adolescents or adults,remains an important cornerstone of any tuberculosis control program as does the administration of BCG to infants.Although BCG vaccination has a limited effect and prevents mainly disseminated forms of tuberculosis, efforts todevelop a new improved vaccine are gathering momentum.

One of the characteristics of tuberculosis in children, in contrast to adults, is the wide spectrum of manifestationsand there is a great need to create a greater understanding of this spectrum to fully appreciate the specific problems ofchildhood tuberculosis. This book should thus be welcomed by the childhood tuberculosis community throughout theworld. In this book, Vimlesh Seth, herself a well-known international figure in this field, has brought together63 eminent scientists and clinicians who have contributed 44 outstanding chapters that address most of the manifestationsof childhood tuberculosis. Dr Seth has made a considerable contribution to the better management of childhoodtuberculosis; included in her many activities are participation in two consensus reports (1997 and 2004) and a third thatappears in this book that summarizes the deliberations of pediatricians, program managers and laboratory workersrelating to childhood tuberculosis.

Foreword

Jayp

ee B

rothe

rs

Essentials of Tuberculosis in Childrenxii

In addition, attention is drawn to the neglected areas of tuberculosis in girls at adolescence and in children withcancer and two chapters discuss pitfalls in diagnosis and management of childhood tuberculosis, and lacunae andexperience of managing children under the National Program (DOTS). The place of contact surveillance has beenhighlighted and forms of extrapulmonary tuberculosis, such as neurotuberculosis, have been illustrated with a largenumber of clinical pictures from children of various ages in the different stages of disease. The chapter on imagingis exhaustive and based on data of pediatric TB clinic over five decades at All India Institute of Medical Sciences(AIIMS), New Delhi, India.

The book is a valuable resource not only for the pediatric fraternity but also for all practitioners who treat children;and it should find a place not only in libraries of medical colleges but also in Pediatric and Community MedicineDepartments. It is very reader-friendly and organized for easy consultation by both undergraduates and postgraduateswho need to know more about childhood tuberculosis. Appropriately in an age when the epidemic of HIV continuesto spread, there is a chapter on the organization of a pediatric and HIV clinic in the pediatric department of medicalcollege and how this can contribute to the collection of information about tuberculosis and HIV for the National DataBase about disease in children and so influence the design of future policies for diagnosis and management. Frequentlyasked questions relating to childhood tuberculosis and BCG are addressed and this is of great practical value. Dr Sethis to be congratulated on the successful compilation of a formidable compendium of information about childhoodtuberculosis which will be of value, throughout the world wherever tuberculosis is a significant problem.

Peter R DonaldMBChB (Stell) DCH (Glasg) DTM&H (Lond) FCP(SA) FRCP (Edin) MD (Stell)

Emeritus Professor of PediatricsDesmond Tutu TB Centre

Department of Paediatrics and Child Healthand Tygerberg Children’s Hospital

Faculty of Health SciencesStellenbosch UniversityTygerberg, South Africa

Jayp

ee B

rothe

rs

Tuberculosis (TB) continues to be the world’s most important infectious cause of morbidity and mortality amongadults. Nearly nine million people develop tuberculous disease each year and 1.7 million die every year (WHO,2007). Detection rates are low and morbidity and mortality is high in children also. Over the last five years, theincidence and prevalence of TB in children has not decreased. The reason is that on the preventive front, the samestrategies: (i) diagnosis and treating sputum smear-positive cases in adults and (ii) mass BCG vaccination of newbornsand infants are being practised. These have not proved effective to a significant extent because of the concurrentaddition of HIV/AIDS infection, MDR-TB and even XDR-TB. The latter two conditions need aggressive treatment inchildren along with their source cases, which are usually adults in the family.

On the diagnostic front, with the significant advances at molecular level, there has not emerged a single test fordiagnosis, that too are not cost-effective requiring huge finances and high level of technical expertise. At best, theyare categorized only supportive tests.

In the contact survey, addition of IGRAs, with the basis of release of interferon – γ after incubation of wholeblood or separated T-cells with CFT 10 peptides and ESAT-609 antigen of tubercle bacilli has been well researched.The two tests are quantiFERON-γ. TB and T-SPOT.TB; ELISPOT. These again cannot be used as the tests for diagnosisas they emphasize that they are only comparable to the existing tuberculin test, the advantages over tuberculin testare: (i) require only one visit of the patient, (ii) previous BCG vaccination does not interfere and, (iii) presence ofnontuberculous mycobacteria in the environment does not vitiate the results. However, their main advantage istheir use in contact tracing for which they have been extensively used.

In the basic format of the book there are seven sections. In each section a number of new chapters have beenadded, contributed by specialists in their respective field. In total there are 44 chapters with 63 contributors fromIndia and abroad. In the 1st three sections namely history, epidemiology and microbiology and immunopathogenesis,the chapters have been updated including the latest details at the molecular level in all aspects. In the clinical spectrum,for TB and HIV coinfection there are two chapters with one giving detailed dosage schedule of antiretroviral drugs.

The other significant additions are tuberculosis at adolescence, particularly in female children in whom it canbe a prelude to the development of sterelity later in life. Chapters on cutaneous and endocrine manifestations are theother additions. The chapter on TB in children with cancer has highlighted the point why TB is not a scurge in thesechildren. However, one should be in the lookout for this, particularly when the presentation of complications incancer are unusual and do not improve with conventional antibiotics used for the commonly occurring superaddedinfections. In the management section, the chapters on antituberculosis drugs have been completely revised andupdated to facilitate the readers to understand various regimens used in the clinical spectrum of TB in childrenspecially HIV/TB coinfection and MDR-TB. Pharmacokinetics of all antituberculosis drugs have been updated fromliterature review along with the experience at Pediatric department of All India Institute of Medical Sciences (AIIMS)with 1st-line agents. Chapter on lacunae and experience of DOTS in the management of children has been included.The Indian Academy of Pediatrics (IAP) in the third Consensus Statement has highlighted some reservations aboutmanagement of HIV and TB coinfection and MDR-TB by general pediatricians. They have emphasized that thesetwo aspects need management by experts in the field. Advances up to 2010 have been included making all thechapters well referenced with the latest literature.

The book will be useful to both undergraduates and postgraduates. Departments of Community Medicine ofMedical colleges and Tuberculosis Hospital will also benefit from the efforts of the authors. It will be a useful referencebook for Program Managers of the Tuberculosis Division of Ministry of Health and Family Welfare, Government ofIndia; Departments of Health Research and Indian Council of Medical Research, Biotechnology of the Governmentof India. Chapters on research priorities and ethics involved in clinical trial will facilitate pediatricians to write highquality scientific projects on TB in children to have research grant from funding agencies. Details of how to getNational Data Base of TB and its coinfection with HIV/AIDS are necessary. This will help in making changes inpolicies in their management from time to time. Further, it will help to make some facilities exclusively for childrensuch as medicine boxes in the four to five weight categories as per age. A chapter exclusively for how to organize aTB/HIV clinic for pediatrics has been elucidated with detailed case record forms and instruction for the juniordoctors attending the clinic to achieve goal in this direction. In toto, this book will serve as a very useful treatiseregarding all aspects of TB in children.

Vimlesh SethSK Kabra

Preface to the Fourth Edition

Jayp

ee B

rothe

rs

Preface to the First Edition

The prevalence of active tuberculosis in India is 15 to 25 per 1,000 population, of which 25 percent are infectious.About 3.4 million children in the country have tuberculosis of which 94 million are at risk of infection. Nearly 40percent of the children by the age of 6 years and 80 percent by the age of 16 years develop tubercular infection. Theannual rate of infection is 3 percent.

There is resurgence of tuberculosis both in the developed and developing countries due to the increasingoccurrence of HIV/AIDs, even children being not spared. With the availability of effective chemotherapeutic agents,a large number of children with pulmonary primary complex are overtreated and badly planned regimens are givento children with tuberculous meningitis, as there are no specific guidelines for the management of tuberculosis in itsvaried clinical spectrum. Ultimate control of tuberculosis rests on the development of shorter courses of chemotherapy,and availability of vastly improved diagnostic methods.

Trinity of functions of the faculty of All India Institute of Medical Sciences is patient care, teaching and research.For all this, there is always a need to have literature on the latest developments about epidemiology, diagnosis(newer investigations) and treatment of any disease. Tuberculosis is one of the world’s most neglected health crises.

In this treatise, attempt has been made to address the problem of tuberculosis stating from epidemiology invarious settings (hospital and community), review of recent diagnostic methods, particularly the role of nonculturetechniques in the diagnosis of paucibacillary tuberculosis of children. Based on my work in the immunology inchildren having tuberculosis, a clinico-immunoradiological profile has been defined. Work on the pharmacokineticsconducted in my laboratory has helped me to design antituberculosis drug regimens for varied clinical spectrum onsound scientific basis. The chapters on BCG vaccination and tuberculin test have exhaustively reviewed. There is achapter on practical problems in the form of questions and their answers. There is a whole lot of data on Indianchildren practically about all aspects of tuberculosis in this book.

The book is intended to be used by general practitioners treating children, pediatricians in practice, faculty ofpediatrics and community medicine of medical colleges, postgraduate students and the policy makers of theGovernment of India for its National Tuberculosis Control Program. Specific guidelines on diagnosis and managementof the children of an infectious adult can be formulated which should be incorporated in the National TuberculosisControl Program of Government of India and other developing countries.

My most sincere and grateful thanks are due to all the contributors from India and abroad for having presentedthe various topics in a comprehensive and authoritative manner. My special thanks are due to Dr OP Semwal for hispainstaking effort and assistance in giving finishing touch to the book.

Able secretarial assistance of Miss Rita Sharma, Mrs Kanta Chawla and Mr Ashok Kumar is gratefullyacknowledged.

Thanks are also due to Shri JP Vij, Chairman and Managing Director of M/s Jaypee Brothers Medical PublishersPvt. Ltd., for the publication of this book. I gratefully acknowledge the sincere efforts of Mr Ghuman, ProductionManager, for ensuring a very high quality of the book and bringing it out in such a short-time.

Vimlesh SethJayp

ee B

rothe

rs

I owe my gratitude to all the contributors for their painstakingly written chapters in an excellent, simple and lucidstyle, very well referenced and updated with thorough illustrations.

We acknowledge the efforts of Shri Jitendar P Vij, Chairman and Managing Director of M/s Jaypee BrothersMedical Publishers (P) Ltd, for publishing the book. We also acknowledge the meticulous work and sincere effortsof Mr Tarun Duneja (Director–Publishing) and Mrs Samina Khan, for ensuring quality of this edition. We are thankfulto Mr Bir Singh for his untiring secretarial assistance. He worked even on weekends to meet the deadline.

Acknowledgments

Jayp

ee B

rothe

rs

About the Review of the PreviousEdition of the Book

The appearance of the book and contents are really outstanding.

Peter R DonaldEmeritus Professor of Pediatrics

Faculty of Health SciencesStellenbosch University

7505 Tygerberg, South AfricaE-mail: [email protected]

No Western books on pediatrics have provided a comprehensive update on the subject of childhood tuberculosis,especially in the context of the developing world.

Professor Vimlesh Seth herself has written most of the early chapters on epidemiology, diagnosis,immunopathogenesis, and the immunology of BCG vaccination and the tuberculin test. These chapters are readable,comprehensive, and well referenced. There have been many recent advances in mycobacterial immunology and it isto Professor Seth's credit that she has managed to be so concise. This is an excellent book.

Anthony CostelloSenior Lecturer

Archives of Disease of Children 1991; 66: 1006

Jayp

ee B

rothe

rs

Contents

Section 1: Introduction

1. History of Tuberculosis ............................................................................................................... 3Vimlesh Seth, SK Kabra• History of Tuberculosis ......................................................................................................................................... 3• History of Tuberculosis Control in India ............................................................................................................ 4• Sanatoria in India ....................................................................................................................................................5• Tuberculosis Association of India ........................................................................................................................ 5• Tuberculosis Control Program in Independent India ....................................................................................... 5• History and Development of International Cooperation in the Conquest of Tuberculosis ........................ 6

Section 2: Epidemiology

2. Global Epidemiology of Pediatric Tuberculosis .................................................................. 11Md Khurshid Alam Hyder, Nani Nair, Tahmeed Ahmed• Presentation of Pediatric TB ................................................................................................................................ 11• TB in the World .....................................................................................................................................................13• Effect of Migration ................................................................................................................................................16

3. Interaction of Epidemiological Factors................................................................................... 19Donald A Enarson, Nulda Beyers• Determinants of Tuberculosis in Children ........................................................................................................ 21• Evaluation of Interventions with Reference to Children ................................................................................ 21• Eradication of Tuberculosis .................................................................................................................................22

4. Epidemiology: Special Reference to Children ...................................................................... 26Vimlesh Seth, SK Kabra• Pyramid of Childhood Tuberculosis .................................................................................................................. 26• Disease Burden in Children ................................................................................................................................ 28• Determinants of Infection and Disease ..............................................................................................................30• Drug-resistant Tuberculosis ................................................................................................................................ 32• Trends in Tubercular Disease .............................................................................................................................33• HIV and Tuberculosis .......................................................................................................................................... 34• Molecular Epidemiology ..................................................................................................................................... 34• Actions Being Taken in India .............................................................................................................................. 36

Jayp

ee B

rothe

rs

Essentials of Tuberculosis in Childrenxviii

Section 3: Microbiology and Immunopathogenesis

5. Mycobacterium Tuberculosis ................................................................................................... 41Sarman Singh, K Gopinath, Ruchi Sood, Ashok Rattan• Taxonomy ..............................................................................................................................................................41• Description of the Genus ..................................................................................................................................... 42

6. Nontuberculous Mycobacteria ................................................................................................. 57Sarman Singh, K Gopinath, Ashok Rattan• Taxonomy ..............................................................................................................................................................57• Classification of NTM on the Basis of Pigment Production ........................................................................... 57

7. Immunology of Tuberculosis: Basic Aspects and Relevance forImmunodiagnostic Tests ........................................................................................................... 66Heidi Syre, Harleen MS Grewal• The Immune System.............................................................................................................................................66

8. Clinicoimmunological Profile .................................................................................................. 90Vimlesh Seth• Immune Reconstitution Disease Associated with Mycobacterial Infections ...............................................96

Section 4: Clinical Spectrum

9. Pulmonary Tuberculosis ......................................................................................................... 101Vimlesh Seth, SK Kabra• Transmission .......................................................................................................................................................101• Pathophysiology ................................................................................................................................................. 101• Risk of Infection to Disease in Infants and Young Children ........................................................................102• Natural History of Tubercular Infections........................................................................................................102• Principles of Disease .......................................................................................................................................... 102• Clinical Features ................................................................................................................................................. 107• Clinical Features/Scoring Systems .................................................................................................................. 108• Methods to Diagnose Latent Tuberculosis Infection ..................................................................................... 115• Diagnostic Algorithm for Pulmonary Tuberculosis ......................................................................................115

10. Tuberculous Lymphadenitis .................................................................................................. 122Ben J Marais, PR Donald• Epidemiology ...................................................................................................................................................... 122• Pathogenesis ........................................................................................................................................................123• Clinical Findings and Diagnosis .......................................................................................................................123• Treatment ............................................................................................................................................................. 126

11. Abdominal Tuberculosis......................................................................................................... 128BR Thapa, Pawan Rawal, Ravi Angara• Causative Organisms .........................................................................................................................................128• Ulcerative Type ...................................................................................................................................................130• Stricturous/Hypertrophic type ........................................................................................................................130

Jayp

ee B

rothe

rs

Contents xix

• Presentation According to Site of Involvement .............................................................................................131• Techniques for Definitive Diagnosis ................................................................................................................132• Abdominal Ultrasound ......................................................................................................................................137• CT Abdomen .......................................................................................................................................................139• Newer Modalities ...............................................................................................................................................142• Differentiating ATB from Inflammatory Bowel Disease (IBD) .................................................................... 143

12. Neurotuberculosis ................................................................................................................... 150

12.1. Pathology and Pathogenesis .................................................................................................. 150PM Udani

• Magnitude, Changing Clinical Patterns and Syndromes Specially in BCG-vaccinated Children .........150• Abdominal Tuberculosis ...................................................................................................................................150• Pathological Aspects .......................................................................................................................................... 151• Specific Conditions .............................................................................................................................................154• Pathological Basis of Various Syndromes ...................................................................................................... 156

12.2. Clinical Manifestations, Diagnosis and Management ..................................................... 161Satinder Aneja, A Maheshwari, Vimlesh Seth

• Special Scenarios ................................................................................................................................................. 174• Tuberculoma of Brain .........................................................................................................................................175• Spinal Tuberculosis in Children .......................................................................................................................177

12.3. Case Studies ............................................................................................................................... 180PM Udani, S Gulati, Rachna Seth, V Kalra, Vimlesh Seth• Profile of TBM in Children Modified by BCG—Dr PM Udani’s Experience .............................................180• Profile of TBM: AIIMS Experience ...................................................................................................................185

13. Osteoarticular Tuberculosis ................................................................................................... 200PP Kotwal, PK Dave, BN Upendra• Joint Involvement ...............................................................................................................................................200• Tuberculosis of the Hip Joint ............................................................................................................................204• Tuberculosis of the Knee Joint ..........................................................................................................................206• Tuberculosis of the Ankle and Elbow ..............................................................................................................207• Tuberculosis of the Short Long Bones ............................................................................................................. 207• Tuberculosis of the Spine (Pott’s Spine) ..........................................................................................................207

14. Genitourinary Tuberculosis ................................................................................................... 214Arvind Bagga• Clinical Presentation .......................................................................................................................................... 214• Diagnosis ..............................................................................................................................................................215• Therapy ................................................................................................................................................................215

15. Tuberculosis and the HIV Infection ..................................................................................... 218

15.1. TB in HIV Infected Children.................................................................................................. 218BJ Marais, PR Donald• Epidemiology ...................................................................................................................................................... 218• Tuberculosis and the HIV Infection .................................................................................................................218• Diagnosis ..............................................................................................................................................................219• Treatment ............................................................................................................................................................. 219

Jayp

ee B

rothe

rs

Essentials of Tuberculosis in Childrenxx

15.2. Tuberculosis and HIV Infection ............................................................................................ 222Vimlesh Seth, Rakesh Lodha• Epidemiology of HIV-tuberculosis .................................................................................................................. 222• Prevalence of Tuberculosis in HIV-infected Children ..................................................................................223• Pathogenesis ........................................................................................................................................................224• Differential Diagnosis ........................................................................................................................................227• Treatment of TB ..................................................................................................................................................230• Treatment of Children........................................................................................................................................231• Prognosis ..............................................................................................................................................................234

16. Tuberculosis and Childhood Malignancy ........................................................................... 241Rachna Seth• Immunology of Tubercular Infection ..............................................................................................................241• Clinical Features ................................................................................................................................................. 243• Risk Factors ..........................................................................................................................................................243• Diagnosis..............................................................................................................................................................243• Pulmonary Tuberculosis and Bone Marrow Transplant (BMT) Recipients ...............................................244• Short-course Chemotherapy and Reactivation of TB ....................................................................................245• Clinical Characteristics and Treatment Responses of Tuberculosis in

Patients with Malignancy Receiving Anticancer Therapy ...........................................................................245

17. Unusual Manifestations of Tuberculosis............................................................................. 248Vimlesh Seth• Tuberculosis of Eye and Conjunctiva ..............................................................................................................248• Hematological Complications ..........................................................................................................................249• Esophageal Tuberculosis ...................................................................................................................................250• Tuberculous Otitis Media and Mastoiditis .....................................................................................................250• Isolated Hepatic Inferior Vena Cava Thrombosis in a Case of Tuberculosis ............................................251• Cement kidney: Renal Tuberculosis ................................................................................................................251• Primary Tuberculosis Clinically Presenting as Gingival Enlargement: A Case Report ...........................251• Simultaneous Tuberculous Meningoencephalitis in Two Siblings ............................................................. 251• Childhood Tuberculosis Diagnosed and Managed as Asthma: A Case Report ........................................252• Tuberculosis of the Breast in an Adolescent Girl ...........................................................................................252• Esophageal Stent Improves Ventilation in a Child with a Bronchoesophageal

Fistula Caused by Mycobacterium tuberculosis ................................................................................................. 252• Pituitary Stalk Tuberculosis .............................................................................................................................. 252• Multifocal Skeletal Tuberculosis ......................................................................................................................252• BCG Related Complications .............................................................................................................................. 253

18. Cutaneous Tuberculosis .......................................................................................................... 255Neena Khanna, Seemab Rasool• Epidemiology ...................................................................................................................................................... 255• Etiology ................................................................................................................................................................255• Pathogenesis ........................................................................................................................................................255• Classification .......................................................................................................................................................255• Clinical Features ................................................................................................................................................. 255• Unusual Patterns of Tuberculosis ....................................................................................................................259• Diagnosis of Cutaneous Tuberculosis ............................................................................................................. 259• Treatment of Cutaneous Tuberculosis ............................................................................................................. 260

Jayp

ee B

rothe

rs

Contents xxi

19. Adolescent Tuberculosis: Prelude to Future Infertility .................................................... 263Suneeta Mittal, JB Sharma, Sangeeta Sharma• Treatment ............................................................................................................................................................. 269

20. Endocrine Manifestations of Tuberculosis ......................................................................... 273Anju Seth, Rajni Sharma• Endocrine Effects of Tuberculosis Due to Chronic Systemic Disease .........................................................273• CNS Tuberculosis ...............................................................................................................................................273• Adrenal Tuberculosis .........................................................................................................................................274• Thyroid Tuberculosis .........................................................................................................................................275• Pancreatic Tuberculosis ..................................................................................................................................... 275• Genital Tuberculosis ...........................................................................................................................................275

21. Congenital Tuberculosis ......................................................................................................... 277Vimlesh Seth• Pathophysiology ................................................................................................................................................. 277• Clinical Features ................................................................................................................................................. 278• Diagnostic Criteria for Congenital Tuberculosis ...........................................................................................279• Investigations ...................................................................................................................................................... 280• Treatment ............................................................................................................................................................. 281

Section 5: Diagnosis

22. Pitfalls in Diagnosis and Treatment of Childhood Tuberculosis ................................... 287YK Ambdekar, Vimlesh Seth• Pitfalls in History Analysis ...............................................................................................................................287

23. Tuberculin Test ......................................................................................................................... 296Vimlesh Seth, Rakesh Lodha• History .................................................................................................................................................................. 297• Tuberculins ..........................................................................................................................................................297• Composition ........................................................................................................................................................ 297• Immune Basis of Tuberculin Reactivity ..........................................................................................................298• Tuberculosis and Immune System ...................................................................................................................299• Administration of Tuberculin Test ...................................................................................................................300• Infection with Nontuberculous Mycobacteria ................................................................................................301• BCG Vaccination ................................................................................................................................................. 301• Variables Affecting Interpretation ...................................................................................................................302

24. Newer Tuberculins: Profile in Developing Countries ...................................................... 310JL Stanford• The Reagents .......................................................................................................................................................310• Skin Test and the Assessment of Vaccine Efficacy ........................................................................................314• Development of New Vaccines ........................................................................................................................315• New Tuberculins and Diagnosis of Mycobacterial Disease ......................................................................... 315• Studies of Close Contacts of Patients with Disease .......................................................................................316• Detection of Risk Factor ..................................................................................................................................... 317• Prevaccination Skin Tests ..................................................................................................................................318

Jayp

ee B

rothe

rs

Essentials of Tuberculosis in Childrenxxii

25. Laboratory Diagnosis of Mycobacterial (Tuberculosis) Infection in Children ............ 322

25.1. Conventional Methods ............................................................................................................ 322Bansidhar Tarai, Nimrat Bawa, Sarman Singh, Ashok Rattan• The Diagnostic Challenges ................................................................................................................................322• Tuberculin Skin Test (Mantoux Test) ...............................................................................................................323• Radiology-based Approaches ...........................................................................................................................324• Fine Needle Aspiration Cytology (FNAC) .....................................................................................................324• Conventional Lab Diagnosis .............................................................................................................................324• Immune-based Diagnosis ..................................................................................................................................329• Novel Culture Systems and Detection Methods ............................................................................................331• Diagnosis of TB in HIV Infected Children ...................................................................................................... 331

25.2. Molecular Diagnostic Methods.............................................................................................. 332S Kumar, Bansidhar Tarai, Nimrat Bawa, Sarman Singh, Ashok Rattan• Commercially Available Assays.......................................................................................................................334• Identification of Mycobacterial Species from Culture by Molecular Methods.......................................... 336• Molecular Methods for Detecting Drug Resistance in Mycobacterial Strains ...........................................337

26. Imaging of Tuberculosis in Children ................................................................................... 344Ashu Seith Bhalla, A Kumar, AK Gupta, S Mukhopadhyaya• Pulmonary Tuberculosis ....................................................................................................................................344• Imaging Modalities ............................................................................................................................................344• Imaging Findings ................................................................................................................................................345• Prediction of Activity of Tuberculous Lesion ................................................................................................. 353• Follow-up ............................................................................................................................................................. 353• Intracranial Tuberculosis ...................................................................................................................................354• Urinary Tract Tuberculosis ...............................................................................................................................358• Abdominal Tuberculosis ...................................................................................................................................361• Osteoarticular Tuberculosis .............................................................................................................................. 362

27. Pathologic Spectrum ................................................................................................................ 368Sandeep R Mathur, Kusum Verma• Pathologic Spectrum of Tuberculosis in Children .........................................................................................368• Spectrum of Morphologic Changes .................................................................................................................373

28. New Approaches to TB Diagnosis in Children .................................................................. 380Ben J Marais, Daphne Ling, Madhukar Pai• Screening Child Contacts for Active Disease ................................................................................................. 380• Approaches to Confirm Active Disease ..........................................................................................................382

Section 6: Management

29. Principles of Therapy............................................................................................................... 395Vimlesh Seth, SK Kabra• Microbiological Principles .................................................................................................................................395

Jayp

ee B

rothe

rs

Contents xxiii

30. Antituberculosis Drugs: First-line Agents ........................................................................... 403Vimlesh Seth, SD Seth, OP Semwal• Classification of Drugs .......................................................................................................................................404• Acute Toxicity of Isoniazid ...............................................................................................................................409• Rifampicin (Rifampin) .......................................................................................................................................410• Streptomycin .......................................................................................................................................................412• Pyrazinamide ...................................................................................................................................................... 414• Ethambutol ..........................................................................................................................................................415

31. Antituberculosis Drugs: Second-line and Newer Agents ................................................ 427Vimlesh Seth, SD Seth, OP Semwal• Second-line Agents .............................................................................................................................................427• Fluoroquinolones ................................................................................................................................................430• Newer Rifamycin Derivatives ..........................................................................................................................434• Beta-Lactams with Beta-Lactamase Inhibitors ...............................................................................................436• Tuberactinomycin ...............................................................................................................................................436• Macrolides ...........................................................................................................................................................436• Phenazines ...........................................................................................................................................................437• Cycloserine ..........................................................................................................................................................438• Aminoglycosides ................................................................................................................................................439• Capreomycin .......................................................................................................................................................439• Miscellaneous Agents ........................................................................................................................................440• Phenothiazines ....................................................................................................................................................441• Nitroimidazopyrans ...........................................................................................................................................441• Oxazolidinones ...................................................................................................................................................442• The New Investigational Drugs .......................................................................................................................442

32. Antituberculosis Drugs: Pharmacokinetics ......................................................................... 449Vimlesh Seth, Alka Beotra, SD Seth, OP Semwal• General Aspects ..................................................................................................................................................449• Factors Responsible for Altered Drug Response in Children ......................................................................452• Various Factors which Change Pharmacokinetics ........................................................................................453• Pharmacokinetics of Antitubercular Drugs in Relation to Various Factors ...............................................458• Isoniazid ...............................................................................................................................................................461• Rifampicin ............................................................................................................................................................463• Pyrazinamide ...................................................................................................................................................... 464

33. Pharmacogenetics of Tuberculosis ........................................................................................ 471Manju Ghosh, Madhulika Kabra• What is Pharmacogenetics? ...............................................................................................................................471

34. Management of Tuberculosis ................................................................................................. 476Vimlesh Seth, SK Kabra• Commonly Used Drugs ..................................................................................................................................... 476• Drug Regimens ...................................................................................................................................................476• Categories and Drugs Regimen under DOTS ................................................................................................478• Corticosteroids in Tuberculosis ........................................................................................................................478• Monitoring of Treatment ...................................................................................................................................479• Monitoring for Side Effects ...............................................................................................................................480

Jayp

ee B

rothe

rs

Essentials of Tuberculosis in Childrenxxiv

35. Consensus Statement on Childhood Tuberculosis— 2010 IAPWorking Group on Tuberculosis........................................................................................... 484YK Ambdekar• Objectives ............................................................................................................................................................. 485• Recommendations ..............................................................................................................................................485• Current Trends in Chemotherapy of TB under Revised National TB ........................................................490• Management of a Neonate Born to a Mother with Tuberculosis ................................................................493• Gaps in Knowledge ............................................................................................................................................493

36. Drug-resistant Tuberculosis in Children ............................................................................. 49736.1. Drug-resistant Tuberculosis ................................................................................................... 497

HS Schaaf, PR Donald• The Development of Drug-resistance and Discovery of Basic Principles of

Drug-resistant Tuberculosis .............................................................................................................................. 497• Drug-resistant Tuberculosis in Children .........................................................................................................497

36.2. Multidrug-resistant Tuberculosis ......................................................................................... 504Vimlesh Seth, Rakesh Lodha• Epidemiology ...................................................................................................................................................... 506• Management of Patients who have Drug-resistant Disease ......................................................................... 511

37. Organization of Pediatric Tuberculosis and HIV Clinic .................................................. 522Vimlesh Seth• Starting Tuberculosis Clinic for Children .......................................................................................................523• Instructions for Resident Doctor ......................................................................................................................524• Flow of Patients in TB Clinic .............................................................................................................................525• New Cases ...........................................................................................................................................................525• Check List for the Senior Resident Doctor on Follow-up Visit ....................................................................526• Annexure I ...........................................................................................................................................................529• Annexure II ..........................................................................................................................................................537• Annexure III• Annexure IV ........................................................................................................................................................541• Annexure V..........................................................................................................................................................546

Section 7: Prevention and Control of Tuberculosis

38. Bacillus Calmette-Guerin (BCG) ........................................................................................... 555

38.1. Bacillus Calmette-Guerin (BCG) Vaccination .................................................................... 555Vimlesh Seth, SK Kabra• Need for BCG Vaccination ................................................................................................................................555• Bacillus Calmette-Guerin (BCG) .......................................................................................................................555

38.2. BCG Vaccination—Frequently Asked Questions .............................................................. 574Vimlesh Seth• Annexure• Instruction Sheet for BCG Immunization Section .......................................................................................... 574

Jayp

ee B

rothe

rs

Contents xxv

39. Latent Tuberculosis ................................................................................................................. 589

39.1. Latent Tuberculosis in Children and Adolescents............................................................. 589Vimlesh Seth, J Cunningham, SM Kuhn• Latent Tuberculosis ............................................................................................................................................ 589• Approach to Latent Tuberculosis Infection ....................................................................................................595• Treatment of Latent Tuberculosis Infection ....................................................................................................597

39.2. Symptoms-based Screening of Child Tuberculosis Contacts—Improved Feasibility in Resource Limited Settings .......................................................... 602Alexey Kruk, Robert P Gie, H Simon Schaaf, Ben J Marais

40. Tuberculosis Control Program in Children—Lacunae and Experiences ....................... 612Rohit Sarin, Sangeeta Sharma• Issues and Lacunae .............................................................................................................................................612

41. Prospective of Prevention, Diagnosis and Management ofTuberculosis in the National Program ................................................................................. 616LS Chauhan• Burden of Disease ...............................................................................................................................................616

42. Frequently Asked Questions about Tuberculosis.............................................................. 634Vimlesh Seth, SK Kabra• The Broad Status of Tuberculosis at Present in the World ...........................................................................634• Practical Point ...................................................................................................................................................... 639• Treatment of TB Patients ...................................................................................................................................646

43. Ethical Issues and Concerns about Tuberculosis Research in Children ....................... 652Roli Mathur, Prashant Mathur, Vimlesh Seth• Ethics, Human Health and Research ...............................................................................................................652• Tuberculosis Diagnosis, Treatment, Control, Prevention, Eradication and Ethics ...................................657

44. Tuberculosis in Children: Research Priorities .................................................................... 661Vimlesh Seth• Research in Pediatric Practice ...........................................................................................................................661• Tuberculosis in Children: Research Priorities ................................................................................................661• Epidemiology ...................................................................................................................................................... 662• Diagnosis ..............................................................................................................................................................662• Treatment ............................................................................................................................................................. 663• Contact-Screening and Management ...............................................................................................................663

Index ............................................................................................................................................ 665Ja

ypee

Brot

hers

Plate 2

Figs 5.4A to C: Middelbrook 7H9 broth containing OADC (Oleic Acid, Dextrose, Catalase) with antibiotic mixture (PANTA– Polymyxin, Amphotericin, Nalidixic Acid, Trimethoprim and Azlocillin) to prevent other contaminants is being used inautomated culture system with higher sensitivity. The growth rate of M. tuberculosis is faster (12-17 days) than the solid(22-30 days), egg based L-J (27-45 days) culture methods. (A) BACTEC MGIT-960 (Mycobacterial growth IndicatorTube, Becton Dickinson, USA) growth detection based on fluorescence (B) MB-BacT-240 (Biomeurieux, France) growthdetection based on colorimetry (C) laboratory mass multiplication of M. tuberculosis in Middlebrook7H9 broth

A B C

Figs 5.3A and B: A. Mycobacterium smegmatis cultured in Middlebrook7H10 agar and incubated at 37°C for 5 days,B. Mycobacterial colony and phenotypic appearance on Lowenstein-Jensen (L-J) Medium incubated at 30-37°C in thepresence or absence of light

Jayp

ee B

rothe

rs

Plate 7

Fig. 27.3: Confluent granulomas in histologic sections showinglarge areas of necrosis

Fig. 27.1: A typical epithelioid cell granuloma seen in histologicsection comprising of epithelioid cells, lymphocytes,

Langhans giant cell and necrosis

Fig. 27.2: Epithelioid cells with elongated slipper shaped,vesicular nuclei seen in a FNAC smear

Fig. 27.4: FNAC smear depicting classical picture of epithelioid cellgranuloma with necrosis (group I)

Fig. 27.5A: Smear showing epithelioid cell granulomas only(group II) as seen on Papanicolaou stain

Fig. 27.5B: Epithelioid cell granulomas as seen inMay-Grunwald Giemsa stained preparation

Jayp

ee B

rothe

rs

The disease tuberculosis is old and existed even in theearly ages. Descriptions of this disease can be found in theRig Veda, Atharva Veda (3500-1800 BC) and also in CharakSamhita (1000-600 BC).

The incidence of tuberculosis had a dramatic fall inthe Western world. However, it still continues to be aproblem in the developing countries. According to aWHO report it is still one of the chief causes of death andcrippling in many countries of the world.1 The diseasestill remains a serious health problem and is increasing.It is estimated that 1 to 6% of children with primaryinfection may develop bone and joint tuberculosis in 1 to3 years if left untreated.2,3 For purposes of descriptionosteoarticular tuberculosis can be discussed underfollowing heads:• Tuberculosis of joints• Bone tuberculosis• Spinal tuberculosis

Infection of a joint or bone with Mycobacteriumtuberculosis is almost always secondary to a primary focus,in the lymphatic glands or lungs or mesentery, from whereit disseminates by hematogenous route. Malnutrition,debilitating disease, poor sanitation, lack of sunshine andfresh air increase the incidence of the disease. Patientswith immunodeficiency disease or HIV infection are moreprone to develop tuberculosis.

Tuberculous lesions can involve any bone or joint inthe body. The lesion in the joint can be:i. Extra-articularii. Intraarticular

It can originate in the bone (osseous lesion) or in thesynovium (synovial disease).

Osteoarticular tuberculosis can involve any bone orjoint in the body, but vertebral involvement is the mostcommon and is nearly equal to tuberculosis of all otherregions put together.4-9

There may be a history of trauma, under the effect ofwhich a small hematoma may form resulting in vascularstasis in that area. The hematoma may become a nidus forthe tubercle bacilli to settle down and form a tuberculousfollicle with caseation, epitheloid cells, giant cells andfibrosis at the periphery. The original follicles enlarge andmay coalesce to form a tubercle, which may become visibleto the naked eye.

The lesion in the bone is essentially a lytic lesion whichis evident radiologically, unlike in pyogenic infectionwhich is characterized by intense sclerotic activity. As thetuberculous lesions heal, sclerosis takes place. At certainsites like the short long bones and in hand and feet or theclavicle, there is intense sclerotic activity by layer ofsubperiosteal bone and is characteristic of a tuberculouslesion. The tuberculous pus formed in the medullary canalmay travel distally or laterally thus, lifting the periosteum,may form an abscess and even burst giving rise to atuberculous sinus. Multifocal tuberculosis is occasionallyseen in children involving multiple bones/joints.

The response to a tuberculous lesion is often exudativeand may form a cold abscess, which is nothing but acollection of necrotic material, caseous tissue and theexudative reaction. These cold abscesses then track throughthe fascial planes or the neurovascular bundles and presentat a distant site. Since this abscess is away from the area ofinflammatory activity, it has no signs of inflammation inthe skin overlying the abscess. These abscesses are, therefore,termed as “cold” abscesses. A superficial abscess may burstand result into a sinus or an ulcer.

Granulation tissue is almost always present in thetuberculous lesion. Ischemic necrosis of bone due toendarteritis and thromboembolic phenomenon in boneleads to formation of sequestra, which in osseoustuberculosis hap-pens to be small. Isolated large sequestraein osteoarticular tuberculosis are rare.

JOINT INVOLVEMENT

The tuberculosis of the joints is relatively less common. Itmainly involves big joints (Tubercular arthritis). Thecommon differential diagnosis includes pauciarticularjuvenile chronic arthritis and septic arthritis. Theinvolvement of joint may be osseous or synovial but if nottreated, one would infect the other. Tuberculous synovitisleads to effusion in the joint and synovial membranebecomes edematous. At this stage the joint would lookswollen and movements may be present or limited due tomuscle spasm. The radiological picture may show anincreased joint space.

The cartilage is resistant to tuberculous infectionbecause it contains a plasmin inhibitor and the bacilli donot possess the plasminogen activator unlike the pyogenic

Osteoarticular Tuberculosis

PP Kotwal, PK Dave, BN Upendra

13

Jayp

ee B

rothe

rs

Chapter 13 Osteoarticular Tuberculosis 201

bacteria. The articular cartilage is thus not attacked byplasmin and remains intact.10 Later on the granulationtissue may extend from the periphery on to the articularcartilage or in the subchondral region in the form of apannus thus eroding it. Once the articular cartilage iseroded there is tremendous muscle spasm and allmovements are restricted. Because of the destruction of thearticular cartilage the joint space on X-ray looksdiminished.

When the lesion is osseous, it involves the subchondralbone which also leads to erosion of the cartilage. The lesionmay start from the epiphysis in children or may bemetaphyseal in origin. When the disease begins to heal,fibrosis occurs across the joint leading to a fibrousankylosis. At this stage the movements of the joint arerestricted and may be painful. There is considerable musclespasm which may produce a deformity at the joint.Prolonged muscle spasm may lead to subluxation ordislocation of the joint causing further deformity andshortening. If sinus has formed, secondary infection maybe superimposed on the tuberculous infection. Fibrousankylosis may be converted into bony ankylosis either dueto complete healing or new bone formation due tosuperadded pyogenic infection. There are no movementsin the joint after bony ankylosis and it is also painless.Radiologically, in bony ankylosis the trabeculae are seento be crossing the joint line.

Clinical Features

Osteoarticular tuberculosis mostly occurs duringchildhood, however, it is seen at any age and in allsocioeconomic groups. It is characteristically insidiousin onset, and starts as monoarticular or monoosseousinvolvement. The child complains of pain in the joint,aggravated by movement, and often wakes up at nightbecause muscle spasm gets reduced and causes pain. Itis classically called “night cries”. Low-grade fever, lossof weight and appetite are some of the symptoms ofgeneralized toxemia usually seen. Joint movements arepainful and elicit muscle spasm on attempted movement.In later stages when the cartilage gets eroded, allmovements get restricted. Muscle atrophy around the jointis a predominant feature and occurs early. Sometimes anabscess forms which bursts to form a sinus. It may getsecondarily infected and may alter the radiologicalpicture. It has been seen that material scrapped from thelining or the abscess is more likely to be positive for gram-negative bacilli than from the center of the lesion.

Investigations

Blood

A low hemoglobin, relative lymphocytosis and raisederythrocyte sedimentation rate (ESR) are often found in

the active stage of the disease. The ESR is often used as aguide in monitoring the progress of the disease duringtreatment, however, it is not a reliable parameter.

Mantoux Test

A positive Mantoux test is seen in patients infected withM. tuberculosis which may be an active or a dormantlesion. In children under two years of age, a positivetuberculin reaction indicates an active tuberculous lesion.A nega-tive test may be seen in severe or disseminateddisease or in an immunocompromised patient.

Synovial Fluid

Examination of the synovial fluid may occasionally helpin diagnosis in the early cases of tuberculosis. It may showleukocytosis (with predominently polymorphs), decreasedglucose content and raised protein content.

Serology

ELISA (Enzyme-linked Immunoabsorbent Assay) testwas described by Engvall and Perlmann11 for antibodyto mycobacterial antigen-6, in the serological diagnosisof osteoarticular tuberculosis. Although they reported asensitivity of 94% in the diagnosis of tuberculosis, it isnot considered a very reliable test in clinical practice asthe%age of false-negative and false-positive are veryhigh.

Radiology

It can be diagnostic in view of the typical radio-logicalappearance of the tuberculous lesions. In early stage ofthe joint disease, capsular markings may becomeprominent. The earliest sign is widespread osteoporosisaround a joint. Lytic lesion and periosteal reaction areseen, although latter is much more prominent in pyogenicinfection.

In case of joints, small bone erosions occur near thecapsular reflection. Joint space decreases due to cartilageerosion and lytic lesions are seen in the epiphyseal area.The radiological signs of a healing lesion are absence ofrarefaction and bony ankylosis.

Smear and Culture

Tuberculous pus, joint aspirate, granulation tissue,sputum, etc. may be examined by smear and culture fortubercle bacilli. These can be processed by varioustechniques (described elsewhere).

The culture and sensitivity tests for variousantituberculosis drugs also helpful in giving appropriatechemotherapy in resistant cases or cases of multidrugresistant tuberculosis; which are seen quite frequently intoday’s clinical practice.

Jayp

ee B

rothe

rs

Section 4 Clinical Spectrum202

Isotope Scintigraphy

Most cases of osteoarticular disease can be diagnosed byclinicoradiographic correlation. However, there would stillremain a number of cases where diagnosis may becomedifficult and doubtful. In such situations, radionuclidescanning using technetium-99 m can be useful particularlyin differentiating soft tissue infection from osteomyelitis.Three phase bone scan and SPECT (single photoneemission tomography) are also useful in the follow-up forevaluating the response to treatment.

Ultrasonography

Ultrasonography can demonstrate soft tissue abscesses. Itcan also be used to judge the effect of treatment on the sizeof these abscesses at periodic intervals.

CT Scan

CT scan is helpful in detecting small lytic/destroyed areasin the bone. The destruction of bone due to the diseaseprocess and also the soft tissue swellings or abscesses canbe seen on CT scan better and much earlier. It also helps inevaluating difficult areas in spine such as cervico-dorsaljunctions, which cannot be seen properly on plain X-rays.

MRI Scan

MRI scan is a far better diagnostic tool, than CT scan orplain X-rays. It can demonstrate not only the bony lesions(destruction) but also the soft tissue abscess, changes inthe spinal cord, etc. It can also pick up changes in thebones much earlier than the plain X-rays.

Fine Needle Aspiration Cytology (FNAC)

Occasionally, even the most modern methods of imagingmay not help the clinician to reach a final diagnosis, andtherefore, FNAC or biopsy may be undertaken to obtaintissue diagnosis. FNAC is now available for the cytologicaldiagnosis of vertebral tuberculosis. Mondal et al12

recommend that fine needle aspiration biopsy is a safeand a quick diagnostic procedure with high accuracy inthe hands of trained cytopathologists. He recommendsthat it should be practised in all diagnostic centers of ourcountry, even for suspected vertebral tuberculosis.Confirmation by FNAC has also been recommended byArora and Seth.13

Biopsy

Biopsy may have to be done in cases where there is doubtabout the diagnosis, particularly in the early stages of thedisease. Biopsy from the bone or synovium can provide anearly diagnosis for timely starting the treatment andpreventing damage to the joint. Biopsy from a cystic lesion

in bone or from synovium is more likely to be positive.14,15

Biopsy can be done as an open biopsy or a needle biopsy(CT guided).

Investigations should also be done to find out theprimary focus of the disease. An X-ray of the chest shouldalways be done. Some other investi-gations may include:sputum smear examination and culture, routine urineexamination for isolation of tubercle bacilli and anintravenous pyelogram for ruling out pulmonary andgenitourinary lesions, respectively.

Management

The patient’s response to treatment is variable as anywhereelse in the body and is dependent upon the host resistance,severity of infection, and the stage of the disease when thediagnosis is first made and treatment started. Eradicationof the disease and preservation of function are importantboth in osseous and joint diseases. In case of joints, jointmobility and stability are also the early goals to be achieved.It is possible only if treatment is started early, i.e. when thedisease is limited only to synovium. In case the articularcartilage is eroded the joint becomes unsalva-geable interms of function, mobility and stability. In such a situationthe aim of treatment is to achieve a sound bony ankylosiswhich is painless and gives stability, although the patientwill not have movements at that joint.

General Measures

Good nutrition consisting of a high calorie and proteindiet is essential to build up the resistance. General restand local rest to the specific bone and joint are essentialparts of the treatment. Local rest can be provided by meansof splints or plaster casts. However, in cases where thearticular surface is not involved a judicious blend of restand mobilization exercises have to be resorted forrestoration of function.

Hospitalization may be required for cases withcomplications and also for cases having deformities. Thedeformities may need treatment by traction.

Chemotherapy

In bone and joint tuberculosis it is customary to give atleast four antituberculous drugs to start with. Seth et al16

have recommended the use of 4 to 5 drugs in the intensivephase. (described elsewhere). Combined drug therapy alsoprevents the emergence of drug resistant strains.

There is enough evidence that 85% of osteo-articularlesions would respond to anituber-culous drugs17,18

particularly if the therapy is started early in the vascularstage of the disease.

It was earlier thought that the antituber-culosis drugsdo not penetrate into the diseased area in effectiveconcentrations since the lesion was considered ‘avascular’.

Jayp

ee B

rothe

rs


However, various studies have shown that theantituberculosis drugs do reach the lesion in effectiveconcen-trations.19-23 Further, in case of persistentlydraining sinuses which are secondarily infected, suitablebroad spectrum antibiotics have to be given. About 15% ofpatients do not respond to chemotherapy alone if the lesioncontains much caseation and sequestra. In such situationsexcision of the diseased focus not only removes the diseasedtoxic material but also increases vascularity and allowsthe anti-tuberculosis drugs to reach the site of the lesion.

A standard drug regimen is given which includesrifampicin, pyrazinamide, ethambutol, isoniazid, andin some cases even streptomycin. The latter is usefulbecause it kills the rapidly multiplying extracellulartubercle bacilli in the lungs for the initial two months.19

After two months if the lesion shows signs of healingclinically and radiologically, pyrazinamide is stoppedand isoniazid, rifampicin and etham-butol arecontinued for one year. Since the recom-mendation ofthe use of four to five drugs in the intensive phase, short-course chemotherapy can be used as in neuro-tuberculosis for a total period of 6 to 9 or at best 12months if there is no surgical debridement. This hasbeen emphasized by Hazara, and Laha24A very recently.It has been shown in the review of literature by themjustifying the use of short-course chemotherapy for 6 to9 months. If there is suspicion of multidrug resistanttuberculosis, the duration has to be prolonged may beup to 18 months. So is the case where there is associationbetween HIV and tuberculosis. (described elsewhere)In some cases therapy may be required for longer periodfor complete healing of the lesion. In case the infection issuspected to be with multidrug resistant organisms, otherdrugs such as ethionamide, ofloxacin, capreomycin,kanamy-cin, etc. may have to be given (describedelsewhere).

Surgical Treatment

Surgical treatment is an adjunct to the anti-tuberculosisdrug therapy. It cannot be a substitute for the prolongedcourse of the drug therapy. Surgical treatment has becomesafe with the advent of powerful antituberculosis drugsand one is no longer scared of a flare up of the lesion.However, a trial of conservative treatment must be givenbefore surgical treatment is undertaken. The indicationsfor surgery are specific and are as follows:• Doubtful diagnosis requiring excision of the focus or

curettage of the lesion.• An abscess or a lesion increasing in spite of adequate

chemotherapy.• Synovitis not involving the articular carti-lage;

synovectomy should be done to prevent the latter fromgetting eroded.

• Curettage of a lesion in proximity of the articularcartilage to prevent the latter from getting involved.

• Spinal tuberculosis with paraplegia:– If paraplegia has occurred during chemotherapy,– If paraplegia is worsening in spite of ade-quate

chemotherapy,– Radiological increase in the size of the abscess, and– If the paraplegia is of sudden onset.

The surgical procedures generally performed in childrenare:

• Drainage of an abscess• Excision of a focus• Curettage of the lesion• Synovectomy• Costotransversectomy• Anterolateral decompression

The general principle of surgery in tuber-culosisdemands that the abscess should be completely evacuated.In case of an osseous lesion, all sequestra, granulationtissue and caseous material should be removed till newbleeding bone is encountered, so that the drugs may reachthe site of lesion better. The cavities so produced should bepacked with autogenous bone grafts. Avoid dead spacesto prevent hematoma formation and close the woundprimarily with or without suction.

Tuberculosis can involve any bone or joint of the bodybut in children it has a special predilec-tion for the hipand knee joints commonly, ankle and elbow joints arerarely involved. Tuberculosis of spine with or withoutparaplegia is extremely common. Long bones are rarelyinvolved but the short long bone involvement is somewhatcommon. Diagnostic algorithm for osteoarticulartuberculosis is given in Figure 13.1.

Fig. 13.1: Diagnostic algorithm for osteoarticular tuberculosis

Jayp

ee B

rothe

rs


TUBERCULOSIS OF THE HIP JOINT

Tuberculosis of the hip is not uncommon and is seenafter 3 to 4 years of age. The natural history of tuberculosisof the hip joint depends upon the site of the lesion, itsduration and the treatment given. The lesion is seen inthe superior part of the head of femur or contiguous areain the acetabulum, the neck of femur, Babcock’s triangleor the greater trochanter24 (Fig. 13.2A). Tuberculosis ofthe greater trochanter may involve the bursa overlying itand is known as trochanteric bursitis.

Clinical Profile

The earliest complaint is pain in the hip joint often referredto the knee. The child walks with a painful antalgic gaitand suffers from night cries, i.e. pain due to eroded jointsurfaces rubbing against each other resulting from reliefof muscle spasm during sleep.

There may be constitutional symptoms like low gradefever, particularly in the evening, loss of appetite,irritability, etc. On examination, in the initial stages of thedisease, there will be only tenderness over the hipanteriorly (at the base of the femoral triangle) or over thetrochanter. In association, there will also be spasm in thelower abdominal muscles and in the adductor muscles ofthe hip. In an untreated case the disease follows throughthe following stages:

Stage I

This is the stage of tuberculous synovitis. In this stage,effusion in the hip joint causes a deformity of flexion,

abduction and external rotation. Movements are painfuland limited in the terminal degrees. Radiographs mayshow only soft tissue swelling—the capsular markingsappear distended due to effusion. There may or may notbe rarefaction of the bones of the hip joint (Fig. 13.2B).

Stage II

With the progression of the disease, there occursdestruction/damage to the articular cartilage. At the hipjoint, flexion, adduction and internal rotation deformitydevelops due to muscle spasm and capsular thickening.There is appreciable muscle wasting and mild shorteningof the limb. All movements are limited. X-ray shows areasof destruction, diminution of joint space and markedosteoporosis (Fig. 13.2B).

Stage III

Destruction of the femoral head and acetabulum, and trueshortening are also added to the deformity as in stage II(Fig. 13.2B). Movements are grossly restricted. X-ray showsmarked erosion of the articular cartilage and areas ofdestruction in the head and neck of femur and acetabulum.

As the destruction of the acetabulum or the head offemur increases further, it is likely to find a wanderingacetabulum or a frank dislocation of the hip. In some casesthe floor of the acetabulum is considerably weakened soas to cause protrusio acetabuli.

It is rare to see patients during the synovitis stage. Mostoften they present when the tuberculous disease hasalready established. There is flexion, adduction andinternal rotation deformity of the hip with shortening. Notuncommonly one comes across an unusual deformity, i.e.flexion, adduction and external rotation of the hip even inarthritis stage. This is usually seen in patients treated bytraction, or spica or in the unlikely event of destruction ofthe iliofemoral ligament.

Figure 13.3 shows the AP radiograph of the tuberculosiship showing destruction of the head and acetabulum andirregular joint space reduction on the right side.

Fig. 13.2A: Common sites of tuberculous involvementaround the hip joint

Fig. 13.2B: Stages of the tubercular arthritis of the hip

Jayp

ee B

rothe

rs


Although this is the usual clinicoradiological picture,one is often confronted with no cor-relation between theclinical signs and the X-ray picture.21 Shanmugasundaram,25

therefore, evolved a clinicoradiological classification withdistinct radiological pattern which not only helps informulating an appropriate treatment plan but also inpredicting the end result.

Can we predict the final outcome of the disease in children at itsinitial presentation?Tuberculosis of the hip in children often ended in fibrousankylosis before the introduction of chemotherapy. Withthe induction of chemo-therapy, more favorable resultswere seen with good range of motion and without pain oncompletion of chemotherapy. However, the outcomes werequite often poor even with effective chemotherapy.Shanmugasundaram25 (1985) showed that the radiologicalappearance of the hip at presentation accurately predictsthe final outcome.

Shanmugasundaram reported 7 types of radiologicalfeatures at initial presentation:1. Normal type,2. Traveling acetabulum type ,3. Dislocating type,4. Perthes type,5. Protrusioacetabuli type6. Atrophic type, and7. Mortar and pestle type.

He demonstrated that hips of ‘normal’ type, Perthestype and dislocating type with a normal joint space afterreduction will have a good result. A narrow joint spaceafter reduction (< 3 mm) predicted a poor result. Hips ofatrophic, traveling-acetabulum. Protrusioacetabuli andmortar and pestle types have a poor result. In a ‘normal’hip, the disease is mainly localised to the synovium.

Fig. 13.3: AP radiography of the tuberculosis of right hip showingdestruction of the head and acetabulum and irregular joint spacereduction with abduction deformity

Pannus does not proliferate over the area of joint cartilage.Protective immunity is related to granuloma formationand is seen in the ‘normal’, synovial type of tuberculouship disease. In the atrophic, traveling-acetabulum,protrusioacetabuli and mortar-and-pestle types ofdisease, irreversible damage has occurred beforepresentation. It seems possible that tissue-destroyinghypersensitivity, causing subchondral erosion, may beresponsible for the atrophic hip , traveling-acetabulum,protrusio-acetabuli, and mortar and pestle types. In the‘normal’ type of disease chemotherapy almost invariablygives a good or excellent result. Also Shanmug-asundaram25 reported that the mean duration ofsymptoms in ‘normal’, Perthes, dislocating and atrophictypes varied from 4 to 7 months, and for the travelingacetabulum, protrusio acetabuli and mortar and pestletypes, for 10 to 14 months.

The functional outcome of tuberculosis in other jointsalso usually follows the amount of joint space preservationon presentation. The lesser the joint space the worse is theprognosis and vice versa.

Management

Antituberculosis Drugs

A three or four drug regime is started initially and thenmaintained on two drugs for a total period of about 12 to18 months. People now recommend therapy in themaintenance stage for 9 to 12 months only.

Immobilization

The joint is immobilized temporarily for a period of 2 to 4weeks for relief of pain and to overcome muscle spasmor deformity. This may be done by traction or plaster cast/slab.

Aim of Treatment

The primary aim of treatment is to provide painlessfunctional range of movement without deformity.However, this may not be possible in all cases. Sinceosseous lesions are more common than the synovial ones,many cases may present with destruction or damage tothe articular cartilage. Therefore, based on the clinical andradiological profile of a case, one must decide whether theoutcome of the treatment should be a mobile joint or afixed joint.

Mobile Joint

One can achieve a mobile joint when (i) the disease isentirely synovial and the articular cartilage is not involved,and (ii) the subchondral bone may be involved in anosseous lesion but the articular surfaces are intact.

Jayp

ee B

rothe

rs


Fixed Joint

A fixed or an ankylosed joint is usually the out-come whenthe articular cartilage is destroyed due to the diseaseprocess. Any attempted movements in such a case can bepainful and at times impossible.

Treatment Directed to Achieve a Mobile Joint

In the early stage of the disease where there is an osseouslesion without involving the articular cartilage, bilateralskin traction is given to prevent spasm and deformity alongwith anti-tuberculosis drugs. Intermittent gentle exercisesare recommended in individual cases. After 12 to 16 weeksthe traction is discontinued and non-weight bearing crutchwalking is instituted, which is followed by the weight-bearing one once the disease is under effective control.Careful monitoring of these patients is absolutely necessaryotherwise these patients may develop unwanteddeformities.

In acute tuberculous arthritis arthrotomy of the joint isurgently required to relieve tension and to preserve thearticular cartilage. Postoperatively, the patient has to bekept on traction; the subsequent management is identical.The concept of early surgery aiming at mobility andstability has been proposed by Vora.26 The aim, accordingto him, was to carry out excisional surgery withoutdislocating the hip. This included partial synovectomy ofthe hip, curettage of cavities in the head and neck of femurand acetabulum. He claimed full movement in 60% of casesand painless functional range of movement in 33% ofcases.

Lesions in the roof of the acetabulum without involvingthe hip joint require curettage of the lesion from outsidewithout entering the joint.

Treatment Directed to Achieve a Fixed Joint

The aim here is to achieve fusion (ankylosis) of the affectedjoint in a functionally optimum position.

If the patient already has involvement of the articularcartilage and the movements are res-tricted, the joint as afunctional entity is finished. In such a situation a hip spicashould be applied in the functional position so as to get asound ankylosis.

Arthrodesis (fusion) of the affected joint may beachieved by surgical intervention. The affec-ted joint isexcised and raw surfaces of the bones of the joint, thuscreated, are opposed to each other and are compressed byan internal or external fixation.

In case the head and neck are completely destroyed,curettage, after dislocating the hip joint, is resorted to andthe hip is immobilized in a functional position.

Treatment of Late Sequelae

Once the disease is healed, the deformity per-sists. Acorrective osteotomy results in appre-ciable improvement

in the gait. Arthrodesis (intra-articular) of hip is not onlydifficult to achieve in children but is quite unacceptable inIndia because of the social customs and sitting habits.Extra-articular arthrodesis was done in thepreantituberculosis drug era so as not to attack the diseasedirectly for fear of disse-minating it, but it is not practisednow.

TUBERCULOSIS OF THE KNEE JOINT

Tuberculosis of the knee joint is predominantly a synoviallesion and becomes osseous only at a later stage. In thebeginning the child complains of pain and limping; thereis minimal synovial effusion with thickening. There isconsiderable wasting of the thigh muscles. Spasm ofmuscles may result in flexion deformity. Later on whenthe articular cartilage is involved, the joint gets destroyedand the knee joint may get deformed due to spasm of thehamstring muscles. This deformity is known as tripledeformity and consists of flexion at the knee joint, posteriorsubluxation of the tibia and external rotation of the leg.The movements at this stage get comp-letely restricted.X-ray appearance in the early stage may only show a softtissue shadow. Subse-q-uently involvement of the articularcartilage is shown by diminution of joint space, irregularityof the cartilage and areas of destruction in the epiphysis(Fig. 13.4).

As time passes, if the destruction increases, furtherevidence of deformity may be seen and the joint mayundergo fibrous or bony ankylosis.

Treatment

Aim of Treatment

The aim of treatment is to achieve a fully func-tionalpainless joint. The outcome of treatment will depend uponthe extent of damage to the joint. Whether to achieve amobile joint or a fixed joint can again be decided on thesame principles as discussed in the treatment of

Fig. 13.4: AP radiograph of tuberculosis of right knee joint in anadolescent showing, irregular diminution of joint space and irregulardestruction of epiphysis.

Jayp

ee B

rothe

rs


tuberculosis of the hip joint. The patient is started onantituber-culosis drugs and in the early stage of synovialdisease the patient should be treated on skin traction so asto keep the joint surfaces apart. This helps in preventingdeformities. After 3 to 4 weeks when the disease getscontrolled, nonweight-bearing exercises can be started andmaintained so that the chances of giving a good functionalrecovery increase. In synovial disease if it is hypertrophiedand the response to antituberculosis drugs is poor,synovectomy should be done.

In case the articular cartilage is involved the patientshould be treated by plaster cast immo-bilization andantituberculosis drugs. In case there is a lytic area in theepiphysis, curettage of the lesion should be carried out soas to prevent the disease from destroying the articularcartilage. If the joint gets destroyed there is no chance ofachieving a satisfactory functional recovery and therefore,the joint needs arthro-desis. Charnley’s compressionarthrodesis is performed using Charnley’s compressionclamps. Charnley27 believed that after a sound arthrodesisin children the epiphyseal cartilage continues to grow andthe growth is not hampered, but there is a possibility ofhampering growth due to the compression effect.

These days, arthrodesis can also be perfor-med byusing Ilizarov apparatus. It perhaps gives more stabilityand allows early ambulation—full-weight-bearing withcrutches.

TUBERCULOSIS OF THE ANKLE AND ELBOW

The lesion may be osseous or synovial in the ankle andelbow. The clinical picture is the same as elsewhere, givingrise to pain, swelling around the joint due to synovialthickening and effusion, and limitation of movements oncethe articular cartilage is involved (Fig. 13.5).

When the lesion is near the joint, early curettage willprevent it from getting involved. In the elbow joint once

the lesion is healed and growth is complete, arthroplastycan be perfor-med. In the ankle joint, if the movements arelost, ankle arthrodesis can be performed after the growthperiod is complete.

TUBERCULOSIS OF THE SHORT LONG BONES

Tuberculosis commonly involves the metatarsals andphalanges (Fig. 13.6).

The lesion starts in the diaphysis as opposed to themetaphysis in the long bones. This is because of the bloodsupply of the short long bones—the nutrient artery whichenters the bone in the middle of its shaft. Within a shortperiod the finger becomes fusiform and enlarged and painful.The skin becomes smooth and shiny and an abscess mayform. As the bone gets involved, new subperiosteal bone islaid down giving rise to a typical enlargement of the shaft(Figs 13.7A and B). The condition is also known as ‘spinaventosa’. The prognosis in this condition is good. The lesionsheal completely with antituberculosis drugs alone. If thediagnosis is in doubt or if there is a discharging sinus,involvement of all the flatbones including ribs, mandible,pelvic bones, patella and skull bones with tuberculosis havebeen reported.28-31 The lesion should be curetted out.

TUBERCULOSIS OF THE SPINE (POTT’S SPINE)

Spine is the most common bone involved in tuberculosis27

and accounts for nearly 50% of all cases of osteoarticulartuberculosis. Like all other skeletal tuberculosis, spinaltuberculosis is secondary to a primary focus elsewhere inthe body. Spread is hematogenous either through thearteries or through the Batson’s plexus of veins (Fig. 13.8).

Proximity of the cisterna chyli may cause lymphaticspread of the infection from foci in the mesenteric lymphnodes. According to a recent estimate more than twomillion patients all over the world have active spinaltuberculosis and the incidence is increasing.

Fig. 13.5: AP and lateral radiographs of tuberculosis of the ankle jointshowing epiphyseal and metaphyseal destruction of tibia and softtissue swelling around the ankle

Fig. 13.6: Tuberculous dactylitis involving second metatarsal head

Jayp

ee B

rothe

rs


Tuberculosis of the spine commonly affects thethoracolumbar spine, however, it is also seen in the otherregions of the spine. The thoracolumbar spine iscommonly affected because of the excessive stresses andstrains it is subjected to, due to excessive mobility in thisregion.

The disease is more severe in children less than 10years of age. The average vertebral involvement andvertebral destruction is more in children leading to moresevere deformity and disability.32-35 Atypical spinaltuberculosis mani-festing as an involvement of singlevertebral extradural extraosseous involvementpresenting as abscess, and isolated infections of theneural arch and spinal tuberculosis in newborn havebeen reported.30,31

The tuberculous infection in the vertebra starts at anyof the following sites:

Central

In this variety the central part of the body of the vertebraundergoes destruction and eventually may collapse underthe body weight resulting into a wedge shaped vertebra.

Metaphyseal

This is the most common type in which the disease startsunder the end plate of the vertebra (close to theintervertebral disc) either at its superior or inferior end.The adjacent parts of two vertebrae are generally affectedbecause the intercostal artery supplies the two adjacentvertebrae. The vertebral end plates are destroyed and thenutrition of the intervertebral disc suffers which getsreduced in size. The radiographic finding of destructionof a vertebra along with diminution of the intervertebraldisc space is considered to be pathognomonic of a tuber-culous lesion of the spine.

Anterior

This is a rare type where the disease starts in the vertebraunder the anterior longitudinal ligament.

A lesion under the posterior longitudinal ligament isextremely rare and is also termed as “spinal tumorsyndrome”.

Appendiceal

Vertebral appendages such as lamina, spinous process,etc. are rarely involved in children.

Figs 13.7A and B: ‘Spina ventosa’ of 4th metacarpals: note the destruction, thickening and soft tissue swellingwith discharging wound over dorsum of 4th metacarpals (For color version see Plate 5)

Fig. 13.8: Blood supply of vertebrae

Jayp

ee B

rothe

rs


Clinical Picture

A few patients may present with constitutional symptomssuch as fever, cough, loss of appetite and weight, butgenerally pain is the predomi-nant symptom.

The child generally complains of pain in back, more atnight time. The pain is localized over the affected area ofthe spine. Occasionally, the patient may feel referred pain(called as girdle pains) along the intercostal nerves, intuberculosis of the dorsal spine. Tenderness at the localsite and spasm of the paraspinal muscles are also evident.Any part of the spine can be affected but it most commonlyinvolves the lower dorsal and dorsolumbar regions.36,37

Cold Abscess

Tuberculous infection causes destruction, casea-tion andnecrosis of the vertebra. Pus forms and may come out ofthe vertebra and present as an abscess. The abscess mayremain close to the vertebra and present, on theradiography, as prevertebral or paravertebral abscess; ormay present clinically as a cold abscess.

Cold abscesses in tuberculosis spread along the fascialplanes or along the neurovascular bundles. In the cervicalspine it collects behind the prevertebral fascia and manypresent as a retropharyngeal abscess. It may also spreadto posterior or anterior triangle in the neck. It can alsotrack in the mediastinum. In the thoracic region, it maypresent as a paravertebral abscess or may track along theintercostal vessels on the chest wall. In the lumbar spine ittracks in the psoas sheath and may present as a psoasabscess or may present in the lumbar triangle at the back.The abscess may also present on the medial side of theupper thigh and may simulate as femoral hernia. Lesionsfrom the lumbosacral junction may present as a pelvicabscess and through the greater sciatic notch may find aplace in the gluteal region.

Paralysis

Compression of the spinal cord can result into paralysis,the extent of which depends upon the level and area of thecord involved. The para-lysis may be incomplete orcomplete with bladder and bowel involvement.

When the infection is in the cervical region, quadriplegiamay develop; the upper limbs are involved before the lowerlimbs.

Deformity

The disease causes collapse of the vertebra and a slightkyphosis may develop. As the disease progresses more,vertebrae collapse and a more severe kyphosis results(Fig. 13.9) which causes development of secondary lordoticcurves below and above the kyphotic curve. The collapseof vertebrae in children is more marked because a large

amount of cartilage is present. Influence of growth duringchildhood is a significant factor in the causation ofdeformity. When the metaphyseal region is destroyed theposterior elements continue to grow; this differentialgrowth increases the deformity even though the diseasemay become quiescent. The deformity itself may give riseto two dreaded complications, i.e. paraplegia andcardiopulmonary complications, although it must bementioned here that deformity is not a common cause ofparaplegia.

Since tuberculosis is more common in the dorsal ordorsolumbar spine, paraplegia is more common. In fact,paraplegia is quite often the presenting feature intuberculosis of the spine. Its incidence varies from 16 to35%.38-40 Paraplegia in tuberculosis has crippling compli-cations. Earlier, the paraplegia was differentiated into – (i)paraplegia of early onset, and (ii) paraplegia of late onset;but it is pragmatic to differentiate it between—paraplegiawith or without active disease. Paraplegia associated withactive disease may be early or late.

The causes of paralysis in tuberculosis of the spineare:• Pressure on the cord due to abscess, granula-tion tissue

or edema.• Mechanical pressure on the cord by sequestra, pus,

and granulation tissue.• Angular deformity of the spine with sub-luxation.• Thrombosis of the anterior spinal artery.• Tuberculoma or diffuse extradural granu-loma of the

cord.It must be appreciated that in a given patient, there

may be more than one cause for paraplegia.

Fig. 13.9: Kyphosis due to collapse of vertebrae

Jayp

ee B

rothe

rs


Unsteady gait (due to spasticity) is the earliest symptomand clonus is the most prominent early sign of paraplegia(Pott’s paraplegia).

Paralysis may increase with varying rapidity throughthe following stages—girdle pain, muscle weakness,spasticity, incoordination, paraplegia in extension, andthe pressure increases to paraplegia in flexion. Bowel andbladder control are lost and in the most severe form theparalysis becomes flaccid. Sensory involvement isuncommon and occurs usually late.

Investigations

Investigations are the same as for any other type oftuberculosis.

Radiology

Plain X-ray

The anteroposterior and lateral views is often sufficientfor the diagnosis. The lateral view is particularly importantas it gives more information than the anterior posterior(AP) veiw. The earliest features on lateral view arediminution of the intervertebral disc space (Fig. 13.10A).Later on one may also see destruction and collapse of thevertebra. Anteroposterior view may show destruction ofthe pedicle and a paravertebral shadow, cast by an abscessin that area (Fig. 13.10B). Even with resolution of the acuteinfectious process the kyphosis may continue and causecompression of the cord and late neurological sequelae.

Generally, speaking the following radio-graphicchanges are seen:• Diminution of the intervertebral disc space.• Lytic lesion in the vertebra leading to collapse.• Generalized osteoporosis of spine.• Presence of a paravertebral abscess which may be

fusiform or more globular in nature.• In early stages there is a central vertebral lesion without

diminution of the intervertebral disc space.Subsequently the disc also gets involved.

• In a large number of cases skip lesions at different levelsare also encountered.

• Bone scintigraphy with technetium-99 m will often showa “hot spot”.

• Magnetic resonance imaging (MRI) provides an earlydiagnosis since it can pick up changes like destructionof the vertebra and soft tissue abscesses much beforethey become evident on plain X-rays. Therefore, MRI isvery useful in doubtful cases (Fig. 13.10C). CommonMRI findings in tubercular spondylitis arehypointensity of the involved tissue on T1 weightedimages, hyperintensity on T2 weighted images (Fig.13.10C) destruction of 2 or more adjacent vertebral bodieswith involvement of the intervening disc and epidural andparaspinal extension and or abscess.Children have a higher deformity at presentation, a

greater tendency for collapse during the active phase ofthe disease, and continued and variable progression evenafter the disease is cured, due to variable destruction of thevertebral growth plates. Tuli et al42 observed that children

Figs 13.10A to C: Tuberculosis of the spine. A. Lateral view; B. AP view showingdestruction of D4-5 vertebrae; C. MRI Showing destruction and prevertebral andepidural abscess (T2weighted)

Jayp

ee B

rothe

rs


< 10 years of age with more than 3 adjacent vertebralinvolvement had a higher spinal deformity on follow-up.In children, the changes during the period of growth aremore important than changes during the active period ofthe disease which usually determines the progress ofdeformity. Children prone for such late progressivecollapse can be identified during the early stages by thepresence of spine at risk radiologic signs. Four radiologicsigns have been described by Rajasekaran43 to indicatethe presence of spinal instability in active stage (Fig. 13.11).a. Facet joint separation (Subluxation),b. Posterior body retropulsion,c. Lateral translation andd. Tilt or toppling.

Each of these sign is given a score of one with amaximum score of four. A spinal instability score of morethan two is associated with a significantly higher chancesof progression of kyphotic deformity.

These signs are useful clinically because they occurearly in the course of the disease and preventive surgeryfor progressive collapse can be advocated. Late progressionand surgical correction of an established deformity isassociated with a high rate of morbidity and can be avoided.Presence of these “Spine at Risk” signs should alert thepediatrician/family physician to refer the patient to aspecialist dealing with spinal deformities for early surgicalintervention to avoid late onset paraplegia withprogression of kyphosis.

Myelography

Although myelography has largely been replaced nowby other imaging modalities, but in some unusual casesof Pott’s paraplegia where the neurological picture doesnot correspond to the osseous lesion, or when multipleskip lesions are present, myelography may be useful indetermining the level of obstruction (Fig. 13.10.C).

Needle Biopsy

A needle biopsy of the vertebra done by using an imageintensifier or CT guided, may be necessary in an unusualsituation to clinch the diagnosis.

Treatment

Chemotherapy

These children need the same general treatment, i.e. goodnutrition, rest and antituberculosis drugs. Drug therapyused to be given for a total period of 18 months. Minimalduration of therapy should be six months. In a systematicreview41 of chemotherapeutic treatment for spinal TB, itwas concluded that six months of therapy is probablysufficient for the majority of cases. Both six and nine monthstreatment regimens give acceptable rate of recovery.

The United States Centers for Disease Controlrecommend that for infants and children with miliary TBor bone and joint TB, treatment should last at least

Fig.13.11: Spine at risk radiologic signs

Jayp

ee B

rothe

rs


12 months. Treatment would probably be needed to beprolonged in immuno-compromised subject such as HIVor malignancies. In children the response of conservativemanagement is generally good. The spine of thesechildren has to be protected from collapsing, which canbe achieved by providing a plaster jacket for about threemonths. A plaster jacket in the initial stages of treatmentcan restrict the degree of kyphotic deformity of the spine.The progress of the disease can be monitored by clinicaland radiological methods. Even in case of Pott’sparaplegia the response to treatment is good. Mostauthors believe that the results of conservative treatmentin children are satis-factory.44 However, in some casesthe abscess or the paraplegia may increase despiteadequate conservative treatment and may require surgicalintervention.

Indications for Surgery (Middle path regimen)42

i. Neurological deficit not improving with adequate trialof chemotherapy (3 to 4 wks)

ii. Neurological deficit developing during antitubercularchemotherapy

iii. Neurological deficit worsening during antitubercularchemotherapy

iv. Recurrence of neurological complicationv. Difficulty in deglutition/respiration with cervical

abscessvi. Advanced acute neurological deficit with flaccid/

flexor spasms and bladder involvement.In case of paraplegia associated with a ‘tense bird

nest’ type of paravertebral abscess, costotrans-versectomy may suffice. If on removing the rib andtransversed process, pus is not encountered one mayproceed to do an anterolateral decompression. In caseof a healed vertebral body lesion (Fig. 13.9) resulting inan increasing defor-mity due to differential growth,posterior spinal fusion must be done as a preventivemeasure.

HIGHLIGHTS

• Tuberculosis of the bones and joints is still commonin children in India.

• It has been discussed under the following three hands:– Bone tuberculosis– Tuberculosis of the joints– Spinal tuberculosis.

• Joint involvement is relatively less common. Mostlybig joints such as hip and knee are involved.

• Spinal tuberculosis is most common.• Newer modalities in radiology, MRI are available for

diagnosis in difficult cases and those whose response

to conservative therapy is not satisfactory.• Mainstay of management is:

– Short-course chemotherapeutic regimens lastingfor 6-9-12 months depending upon the responseof the patients along with general measures of restand good nutrition.

– Indications of surgical intervention have beenclearly defined depending upon the site ofinvolvement.

REFERENCES

1. Duthie RB, Bentley G. Skeletal tuberculosis. In: Mercer’s(Ed). Orthopedic Surgery, 9th edn. London: Arnoldpublications 1996;596.

2. Starke JR, Smith MHD. Tuberculosis. In: Feigin RD, CherryTD (Eds): Textbook of Pediatric Infectious Diseases, 4thedn. London: WB Saunders company 1998;1196-1239.

3. Luckheie M. Tuberculosis of cervical spine. South Afr MedJ 1996;86:553-6.

4. Wilkinson MC. Observations on the pathogenesis andtreatment of skeletal tuberculosis. Ann R Coll SurgeryEngl 1949;4:168-71.

5. Girdlestone GR, Somerville EW. Tuberculosis of boneand joint. 2nd edn. London: Oxford University Press; 1952.

6. Mukhopadhyaya B. The role of excisional surgery in thetreatment of bone and joint tuberculosis. Ann R Coll SurgEngl 1956;18:288-313.

7. Grewal KS, Singh M. Tuberculosis of spine. Indian J Surg1956;18:394-405.

8. Mukhopadhyaya B, Mishra NK. Tuberculosis of theSpine. Ind J Surg 1957;19:59-81.

9. Tuli SM, Srivastava TP, Verma BP, et al. Tuberculosis of Spine.Acta Orthop Scand 1967;38:445 58.

10. Lack CH. Chondrolysis in arthritis. J Bone Joint Surg1959;41-B:384.

11. Engvall E, Perlmann P. Enzyme-linked Immuno-absorbent Assay (ELISA) Test. Immunochemistry1971;8:871.

12. Mondal A, Mitra S, Mitra D, et al. Role of fine needleaspiration biopsy in cytological diagnosis of vertebraltuberculosis. Indian J Tuberc 1996; 43:15-8.

13. Arora S, Seth S. Isolated tubercular tenosynovitis inchildren. J Pediatr Orthopedics 1994;14:752-4.

14. Versefeld GA, Solomon A. A diagnostic approach totuberculosis of bones and joints. J Bone Joint Surg 1982;64-B:446.

15. Jacobs JC, Lis C, Ruzal-Sharpino C, et al. Tuberculousarthritis in children, diagnosis by needle biopsy of thesynovium. Clin Pediatr 1994; 33:344-8.

16. Seth Vimlesh. Management of tuberculosis. In: SethVimlesh and Kabra SK (Ed): Essentials of Tuberculosis inChildren. 1st edn. New Delhi: Jaypee Brothers MedicalPublishers Pvt. Ltd. 2006; 530-8.

17. Medical Research Council Working Party on Tuberculosisof Spine. A controlled trial of ambulant outpatient

Jayp

ee B

rothe

rs


treatment and inpatient rest in bed in the managementof tuberculosis of spine in young Korean patients onstandard chemotherapy. J Bone Joint Surg 1973;55-B:678.

18. Medical Research Council Working Party on Tuberculosisof Spine. A five year assessment of controlled trials ofinpatient and outpatient treatment with plaster of Parisjackets for tuberculosis of spine in children on standardchemotherapy. J Bone Joint Surg 1976;58-B: 399.

19. Fellander M, Hirtonn T, Wallmark G. Studies on theconcentration of streptomycin in the treatment of boneand joint tuberculosis. Acta Tuber Scand 1952;27:176-89.

20. Barclay WR, Elbert RH, Le Roy. Distribution and excretionof radioactive isoniazid in tuberculous patients. J Am MedAssoc 1953;151:1384-8.

21. Haungren A. Studies on the distribution and fate of C 14and T-labelled p-aminosalicylic acid (PAS) in the body.Acta Radiol (Suppl)1959;175.

22. Friedmman B, Kapur VN. Newer knowledge ofchemotherapy in the treatment of tuberuclosis of bonesand joints. Clin Orthop 1977;97:5-15.

23. Tuli SM, Brighton CT, Morton HE, et al. Experi-mentalinduction of localized skeletal tuberculous lesions andaccessibility of such lessions to antituberculous drugs. JBone Joint Surg 1974; 56-B:551-9.

24. Somerville EW, Wilkinson MC. In: Girdlestone (Ed). Tuber-culosis of bone and joints. London. Oxford UniversityPress 1965;43.

24a. Hazara A, Laha Baisakhi. Chemotherapy of osteoarticulartuberculosis. Indian J Pharmacol 2005;37:5-12.

25. Shanmugasundaram TK. Current concepts in bone andjoint tuberculosis. Chennai, Documentation Center,International Bone and Joint Club, 1985.

26. Vora PH. Role of early surgery in the management oftuberculosis of the hip: In: Shanmugasundaram TK (Ed).Current concepts in bone and joint tuberculosis. Chennai:Documentation Centre, International Bone and Joint Club,1985.

27. Charnley J. Compression arthodesis. London: E and S.Livingstone Ltd. 1953.

28. Change JH, Kim SK, Lee WY. Diagnostic issues intuberculosis of ribs with a review of 12 surgically provencases. Respirology 1999;4:244-53.

29. Unuwar E, Oghuz F, Sadikooglu B, et al. Calvarialtuberculosis. J Pediatr Child Health 1999;35:221-2.

30. Erasmus JH, Thompson JO, Vanerwesthinzen AJ.Tuberculous osteomyelitis of mandible report of a case. JOral Maxiflofac Surg 1998;56:1355-8.

31. Dillon MS, Rao SS, Sandhu MS, et al. Tuberculosis ofpatella. Skeletal Radiology 1998; 27: 40-2.

32. Rajasekaran S, Shanmugasundaram TK, Prabhakar R, etal. Tuberculous lesion of the lumbosacral region. A 15years follow-up of patients treated by ambulatorychemotherapy. Spine 1998;23:1163-7.

33. Tuli SM. Severe kyphotic deformity in tuberculosis of thespine. Int Orthop 1995;19:327-31.

34. Beekarun DD, Govender S, Rasool MN. Atypical spinaltuberculosis in children. J Pediatr Orthop 1995;15:148-51.

35. Gupta DK, Gopal, Sharma SP, et al. Neonatal tuberculosisof the spine. Trop Doctor 1998;28: 119.

36. Paus B. Treatment for tuberculosis of spine. Acta OrthopScand (suppl): 1964;72.

37. Hodgson AR, Yau ACMC. Anterior surgical approachesto the spinal column. In: Apley AG (Ed). RecentAdvances in Orthopaedics. London: J and A. Churchill,1969; 289-323.

38. Hodgson AR, Stock FE. Anterior spinal fusion fortuberculosis of spine. J Bone Joint Surg 1960;42-A:295.

39. Martin NS. Tuberculosis of the spine. J Bone Joint Surg1970;52-B:613.

40. Tuli SM. Results of treatment of spinal tuberculosis bymiddle path regime. J Bone Joint Surg 1975; 57-B:13.

41. Van Loenhout-Rooyackers JH, Verbeek AL, et al.Chemotherapeutic treatment for spinal tuber-culosis. IntJ Tuberc Lung Dis 2002;6:259-65.

42. Tuli, S.: Tuberculosis of the Skeletal System, New Delhi,Jaypee Brothers Medical Publishers Pvt Ltd 1997;241.

43. Rajasekaran S. The problem of deformity in spinaltuberculosis. Clinical Orthopaedics and Related Research2002; 398: 85-92.

44. Moon MS, Kim I, Woo YK, et al. Conservative treatmentof tuberculosis of the thoracic and lumbar spine in adultsand children. Int Orthopaedics 1987;11:314-22.

Jayp

ee B

rothe

rs

Essentials ofpostgraduatebooks.jaypeeapps.com/pdf/Pediatrics/...Essentials of TUBERCULOSIS IN...

Documents

Transcript of Essentials ofpostgraduatebooks.jaypeeapps.com/pdf/Pediatrics/...Essentials of TUBERCULOSIS IN...