API Textbook of Medicine 2 Volumes

API
Textbook of Medicine
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Editor-in-Chief
Yash Pal Munjal
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Volume 1
10EDITION
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The Association of Physicians of India
NOTICE
The editors have checked the information provided in the book and to the best of their knowledge, it is as per the standards
accepted at the time of publication. However, in view of the continuous changes in medical knowledge and the possibility of
human error, there could be variance. In view of the possibility of human error by the authors, editors, or publishers of the work
herein, or changes in medical knowledge, neither the authors, editors, publisher, nor any other party who has been involved in the
preparation of this work, warrants that the information contained herein is in every respect accurate or complete, and they are not
responsible for any errors or omissions or for the result obtained from the use of such information. Hence readers are requested
to confirm information, particularly laboratory values and drug dosages from the product information sheet included in the package
of each drug they plan to administer and from other sources as well, particularly in connection with new or infrequently used
drugs. The editor takes no responsibility for the views expressed or the material submitted by the various contributors to this API
Textbook of Medicine, Tenth Edition.
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© All rights reserved. This book is protected by copyright. No part of it and CD-ROM may be reproduced in any manner or by any
means, without written permission from the Editor-in-Chief. For all permissions apply to Dr Yash Pal Munjal, Editor-in-Chief, RT202,
Royalton Towers, Princeton Estate, DLF Phase 5, Gurgaon, Haryana - 122002.
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First Edition: 1969
Tenth Edition: 2015
ISBN 978-93-5152-415-1
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Published by:
Dr Yash Pal Munjal for and on behalf of
The Association of Physicians of India
Turf Estate # 6 & 7, Off Dr. E. Moses Road, Opp. Shakti Mills Compound, Near Mahalaxmi Station (West),
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API Textbook of Medicine
Tenth Edition
EDITOR-IN-CHIEF
Yash Pal Munjal
MD FICP MAMS FIAMS FACP FIACMS FRCP (Edin)
Medical Director and Hon Senior Consultant, Diabetes and Life Style Disease Centre
Banarsidas Chandiwala Institute of Medical Sciences, Kalkaji, New Delhi
Past President of Association of Physicians of India
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Past Dean of Indian College of Physicians
Hon Professor of Indian College of Family Physician, New Delhi, India
EXECUTIVE EDITOR
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Surendra K Sharma
MD PhD
Professor and Head
Department of Medicine, All India Institute of Medical Sciences, New Delhi, India
AK Agarwal
MD FICP FRCP (Edin) MAMS FACP FIACM FIAMS FIMSA
Professor and Head, Department of General Medicine
School of Medical Sciences and Research, Sharda University
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EDITORS
RK Singal
MD FRCP FICP FACP
Senior Consultant and Head
Department of Medicine
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Greater Noida, Uttar Pradesh Dr BL Kapur Memorial Hospital
Ex-Dean, Professor and Head, Department of Medicine, PGIMER New Delhi, India
Dr Ram Manohar Lohia Hospital, New Delhi, India
Shyam Sundar
Pritam Gupta MD FRCP FAMS FNA FSc FNASc
MD (Medicine) Professor of Medicine
Senior Consultant and Head, Department of Medicine Institute of Medical Sciences
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Sunder Lal Jain Hospital, New Delhi, India Banaras Hindu University, Varanasi
Uttar Pradesh, India
Sandhya A Kamath
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MD FICP Subhash Varma

Ex-Dean and Professor, Department of Medicine MD FICP
Lokmanya Tilak Municipal Medical College and Municipal Professor and Head
General Hospital, Mumbai, Maharashtra, India Department of Internal Medicine
PGIMER, Chandigarh, India
Milind Y Nadkar
MD FICP
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Professor of Medicine, Chief of Rheumatology and

Emergency Medicine, Seth GS Medical College and KEM Hospital
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Mumbai, Maharashtra, India
ASSOCIATE EDITORS
Ghan Shyam Pangtey Anupam Prakash
MD MD (Gen Medicine) FICP MNAMS PDCC (Hospital Management)
Associate Professor, Department of Medicine PDCDM (Dialysis Medicine)
Lady Hardinge Medical College and Associated Hospitals Professor, Department of Medicine, Lady Hardinge Medical
New Delhi, India College and Associated Hospitals, New Delhi, India
EMERITUS EDITOR
Siddharth N Shah
MD FICP FACP (Hon) FRCP (Edin)
Post-graduate Teacher in Diabetes, University of Mumbai
Consulting Physician and Diabetologist
SL Raheja Hospital and All India Institute of Diabetes
Saifee Hospital, Bhatia Hospital, Sir Hurkisondas Nurrotumdas Hospital
Visiting Consultant, Central Railway and Western Railway Hospitals, Mumbai, Maharashtra, India
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Editors-In-Chief
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Late Dr RJ Vakil Late Dr KK Datey Late Dr Shantilal J Shah
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1st and 2nd Edition 3rd Edition 4th Edition
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Dr GS Sainani Dr Siddharth N Shah

5th and 6th Edition 7th and 8th Edition
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Dr Yash Pal Munjal

9th and 10th Edition
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PREFACE
It is 45 years since the first edition of API Textbook of Medicine was published keeping the Indian milieu in focus. Enthused by the
acceptance and success of the book nine more editions were published over the years. With the dawn of the year 2015, I have
the pleasure and privilege to present to you the 10th edition of API Textbook of Medicine.
In the last two to three decades, Medicine has witnessed a torrential growth in the understanding of disease and its management.
The disease profile has also substantially changed along with the demography of various disorders. In the earlier edition of the
book, diseases such as smallpox, poliomyelitis and guinea worm infestation were quite common and were discussed in detail.
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These diseases have been eradicated or their significance greatly reduced due to immunisation, use of appropriate drugs and
better hygienic facilities. Therefore, their presentation in the book has been reduced while newer infections such as hepatitis B,
HIV, swine flu and avian flu have been discussed in greater detail as the new infective disorders. Along with these, various non-
communicable diseases have increased in an unprecedented epidemic like manner. Therefore, this edition of the book has been
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designed and covers the recent trends in diagnosis and management of these disorders.
The book is completely revised, updated and better illustrated. There are over 3000 pages with 1622 figures and 1460 tables.
These large numbers of tables and figures have been used so that the information is easily understood and reading is facilitated.
In this endeavour, many new additions have been done as compared to the previous edition. The book consists of 29 parts and
each part discusses a group of disorders. In addition, 28 new chapters have also been added.
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1. An entirely new part Future of Medicine, has been added. This part of the book deals with the anticipated progress in
medicine which will be put to clinical use in the coming one to two decades or the advances that are being used in their
early stages in clinical practice.
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2. A new chapter on Disease Profile and Epidemiology of Communicable and Non-communicable Diseases in India has been
added so that the reader has an ample understanding of the diseases commonly prevalent in this part of the world.
3. During the 9th edition, a new part had been added Clinical Approach to Key Manifestations. This has been further expanded
and six new chapters have been added out of which one deals with the selection of the imaging modality which will be
best suited to a clinical condition.
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4. Part 4 of the book on Clinical Pharmacology has been re-oriented and new authors have contributed chapters. One of the
chapters deals with National Formulatory of India in the National Health System.
5. The Part 7 on Critical Care Medicine has been thoroughly revised and to put adequate emphasis on cardiac resuscitation,
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a separate chapter has been devoted to Advanced Cardiac Life Support System.
6. The parts of the book dealing with various life-style disorders such as diabetes mellitus and cardiovascular diseases have
been re-oriented for better understanding of the newer guidelines which have emerged.
7. A chapter on life-style measures, diabetes in the elderly and prevention of cardiovascular diseases have been added and
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discussed.
8. In the part dealing with gastrointestinal disorders, Pancreatitis has been divided into two parts—a chapter on Acute
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Pancreatitis and the other on Chronic Pancreatitis have been added, while Neoplasms of the Pancreas finds a separate chapter.
9. Similarly, Tumours of the Liver has been discussed as a separate chapter.
10. Chronic pulmonary disorders and sleep-related pulmonary disorders are increasing in prevalence and to address these
issues the chapters have been thoroughly re-written and a chapter on Pulmonary Rehabilitation has been added in this
part of the book.
11. Similarly, the management of stroke has been significantly modified and the chapters on Ischaemic or Haemorrhagic Stroke
have been thoroughly revised and re-written.
12. A chapter on Oral Health and its relationship to systemic diseases has been presented separately.
13. For the first time, Futuristic Medicine and the problems of Space Travel have been delineated and highlighted.
The presentation of all disorders in a concise manner has been possible with the support, joint and collaborative effort and
useful editorial guidance from all the members of my editorial team for which I am grateful to them.
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A CD-ROM is presented along with the book. It has some of the chapters presented in the e-format of the book along with multiple
choice questions (MCQs) with their answers and a few powerpoint presentations of some of the important issues in medicine.
The various pictorial atlases along with their explanations are added. This is a useful new addition to the 10th edition of the
API Textbook of Medicine.
Professor Surendra K Sharma has provided very useful guidance and has played a significant role in planning the book despite his
busy schedule. Dr AK Agarwal and Dr RK Singal have been closely associated and have provided useful inputs and suggestions
in preparation of the book for which I am grateful to them. Two of my Associate Editors, Dr Anupam Prakash and Dr Ghan Shyam
Pangtey have stood by me and have helped me in completing this project from the beginning to the end and have provided the
support at all times during the preparation of the book. I wish to thank Dr Milind Y Nadkar and Dr Sandhya A Kamath for their
useful inputs. Dr Shyam Sundar, Dr Subhash Varma and Dr Pritam Gupta were forthcoming in their help and suggestions for which
I owe my thanks to them. I wish to thank Dr Siddharth N Shah for his continuous and enthusiastic support, and I am obliged to
him for all his help. The editors of various parts were generous with their time and suggestions, and edited the chapters allotted
to them diligently and painstakingly.
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I am grateful to the excellent group of authors who have participated in the 10th edition of the API Textbook of Medicine for their
extraordinary and timely contribution. The quick turnaround for the new edition of a textbook of this size is a tribute to the hard
work and dedication of our authors.
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I wish to thank my family for their support and many sacrifices they made to make this volume possible. They were my
moral support and mental strength during the trials and tribulations while compiling the book. I especially thank my wife
Dr Rama Munjal, my daughter Ms Jaya Munjal and my son Dr Akshay Munjal for their help. On the completion of this onerous
task, I am humbled and express my sincere thanks to President and Dr A Muruganathan, Dr Shashank R Joshi, and the Members
of the Governing Body of Association of Physicians of India (API).
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I along with my editorial team who were assigned the task of compiling the 10th edition are excited about the content, which
has been presented and the quality material which it is going to offer to our readers. The journey though difficult has taught us
many new things, and I hope that it will be useful for the readers. If the book proves useful, our efforts will be rewarded.
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Dr Yash Pal Munjal
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Editor-in-Chief
10th Edition
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Let a man learn thoroughly whatever he may learn, and let his conduct be worthy of his learning.
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– Thirukkural
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ACKNOWLEDGEMENTS
I am happy to present to you the 10th edition of the API Textbook of Medicine in the year 2015. This is a momentous occasion, as
it coincides with the platinum jubilee year of the foundation of the Association. This has been possible due to the collaborative,
co-operative and untiring efforts of the editorial team and many others. Thanksgiving is always a pleasure and on the occasion of
the successful completion of this gigantic task, I have the privilege to thank the members of my team who made this task possible.
The help rendered by Dr Aditya Prakash Misra, Dr Anurag Saxena, Dr Vibhu Mendiratta and others is duly acknowledged. The task
of proofreading and organising the manuscript was painstakingly carried out by Mr Rakesh K Gupta and Ms Seema Soni, and their
respective teams. The efforts of Mr Rakesh K Gupta and his keen eye for checking manuscripts in-minute detail stand out. For
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this, his services need special mention. Ms Seema Soni was able to put the language correctly and in right perspective. Chief of
Text-O-Graphics, Mr Atin Chatterjee, and his team were instrumental in the initial typesetting of the book.
We express our appreciation and gratitude to Shri Jitendar P Vij (Group Chairman) and Mr Ankit Vij (Group President) of
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M/s Jaypee Brothers Medical Publishers (P) Ltd, New Delhi, India, which is one of the largest Medical Publishers in the world, for
their assistance and help.
Mr Tarun Duneja (Director-Publishing) has been instrumental in getting the final shape of the book. The other members of his
team worked diligently and tirelessly for the final production of the book. They were receptive and bore the brunt of this task
willingly. They co-ordinated with the office of the editorial board as a team and carried out the instructions meticulously. They
deserve our appreciations and thanks.
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I would like to express my sincere thanks to my Secretary, Ms Pushap Lata, for having taken up the additional responsibility with
due diligence and carried out all the hard work willingly and with a smile on her face at all times. Ms Beatrice Mendes assisted
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in all sections of the preparation of the book in the initial phases for which I thank her. Ms Archana Makhija, who joined at a
later stage, but integrated the previous work and carried it forward with enthusiasm and vigour. She co-ordinated the work very
effectively and efficiently both in compiling as well as proofreading till the final stages of the book.
I wish to express my sincere thanks to Shri Autar Krishna (Chairman) and Shri Bhuwan Mohan (Secretary), Shri Banarsidas
Chandiwala Sewa Smarak Trust Society for providing the office space and allowing the use of infrastructure during the entire
course of the publication of this assignment. Not only they provided the infrastructural support, but they also encouraged me
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in my task as the Editor-in-Chief of the book.

The help of the editors of the parts for editing diligently and providing editorial inputs, which were very useful and timely is
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highly appreciated. I would like to extend our thanks on behalf of the editorial board and the authors who have been provided
useful assistance by their colleagues in preparation of their respective manuscripts.
Our grateful thank to our advisors, Dr A Muruganathan, Dr BB Thakur, Dr Ashok Seth, Dr Man Mohan Mehndiratta, Dr Kamlesh Tewary,
Dr Manjari Tripathi, Dr Ravi Kasliwal, Dr Praveen Gulati, Dr Harsh Mahajan, Dr Vikash Bajaj and Dr NK Soni.
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The other distinguished teachers, who provided useful guidance in the formulation of the book, are duly acknowledged.
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Dr Yash Pal Munjal

and the Editorial Board
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Part/Chapter Authors Assisted By
PART 1: INTRODUCTION
2 Disease Profile and Epidemiology of Communicable Jugal Kishore Tanu Anand
and Non-communicable Diseases in India
PART 2: CLINICAL APPROACH TO KEY MANIFESTATIONS
13 Syncope Pushpa Yadav Diki Palmu Theengh
15 Appropriate Ordering of Radiological Investigations Chandan J Das Ananya Panda
16 A Clinical Approach to Patients with Ascites Richa Dewan Abhilekh Srivastava
18 Approach to a Patient with Dyspnoea Praloy Chakraborty Mayuresh Chaudhari
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PART 3: DIAGNOSTIC IMAGING
1 Conventional Radiology Ashu Seith Bhalla Ankur Gadodia
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PART 4: CLINICAL PHARMACOLOGY
6 Role of National Formulary of India in National Health Jai Prakash Pooja Gupta and
Care System GN Singh
PART 6: MEDICAL GENETICS
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PART 7: CRITICAL CARE MEDICINE
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Pharmacogenomics and Personalised Medicine C Adithan S Sureshkumar
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1 Basic Considerations in Critical Care RK Mani R Aggarwal
9 Non-invasive Positive Pressure Ventilation Dhruva Chaudhry Atulya Atreja
PART 9: DIABETES MELLITUS
2 Pathogenesis of Type 1 Diabetes Mellitus Carani B Sanjeevi Chengiun Sun
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PART 11: DERMATOLOGY

11 Sexually Transmitted Infections Yogesh S Marfatia Ankit H Bharti and
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Mahima Talwar
13 Leprosy Hemanta Kumar Kar Amrita Chauhan
PART 12: CARDIOLOGY
10 Treatment of Heart Failure Veronica Franco Ragavendra Baliga
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13 Valvular Heart Disease (ll) VK Bahl Ishwar Chandra Malav

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17 Acute Coronary Syndrome—NSTEMI Ambuj Roy Shrenik Doshi

26 Disorders of the Myocardium KK Talwar Pawan Poddar
PART 14: HEPATOLOGY
9 Extrahepatic Portal Venous Obstruction Yogesh K Chawla Vijay Bodh
PART 15: HAEMATOLOGY
16 Bleeding Disorders Kanjaksha Ghosh Kinjalka Ghosh
17 Platelet Disorders Prantar Chakrabarti Dibyendu De
18 Idiopathic Thrombocytopenic Purpura Cecil Ross Sanjukta Rao
PARTS 16: HIV AND AIDS
6 Non-opportunistic Infections Anil Kumar Tripathi Shailendra P Verma
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Part/Chapter Authors Assisted By
PART 17: INFECTIOUS DISEASES

11 Pneumococcal Infections DP Bhadoria Raghav Bansal
13 Gonococcal Infections Chander Grover Amit Dhawan
17 Diseases Caused by Gram-negative Enteric Bacilli Richa Dewan Vivek Kumar
27 Other Spirochaetal Infections: Lyme Disease and Kamlesh Tewary Amit Kumar Das
Rat Bite Fever
PART 18: DISORDERS OF METABOLISM
3 Lipids and Lipoprotein Metabolism Soneil Guptha Ravinder Singh Sambi
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6 Porphyrias Dhanpat Kumar Kochar Abhishek Kochar
9 Inherited Disorders of Membrane Transport SK Singh Rahul Singh
PART 19: NEPHROLOGY
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10 Polycystic Kidney Disease and Inherited Tubular Disorders PP Varma A Jairam
PART 20: NEUROLOGY
1 Neurological Disorders: Basic Consideration MV Padma Srivastava Tanu Talwar
and Clinical Approach
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15
Haemorrhagic Cerebrovascular Diseases
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Fungal and Parasitic Diseases of the Nervous System
MV Padma Srivastava
Ashok Panagariya
Tanu Talwar
Bhawna Sharma
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22 Demyelinating Diseases of Nervous System Man Mohan Mehndiratta Natasha Singh Gulati
PART 21: ONCOLOGY
5 Principles of Radiotherapy GK Rath AK Gandhi
11 Gynaecological Malignancies PP Bapsy Vaishnavi S
PART 22: PSYCHIATRIC MEDICINE
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2 Organic Mental Disorders SK Khandelwal Priyanka Yadav

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3 Substance Use Disorders Debasish Basu Siddharth Sarkar

5 Mood Disorders Yatan Pal Singh Balhara Siddharth Sarkar
8 Emergency Psychiatry Dipesh Bhagabati Sachin Aurora
PART 23: PULMONARY MEDICINE
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5 Bronchial Asthma Virendra Singh Nishtha Singh

6 Chronic Obstructive Pulmonary Disease Surendra K Sharma Sajal Ajmani
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PART 24: RHEUMATOLOGY

5 Gout and Other Crystal Arthritides URK Rao C Shiva Shankar
14 Mixed Connective Tissue Disease and Overlap Syndromes G Narsimulu Avinash Kusuma
PART 26: POISONING AND TOXICOLOGY
1 Poisoning: Basic Considerations and Epidemiology Narinder Pal Singh Anish Kumar
7 Drug Overdose Narinder Pal Singh Anish Kumar
9 Scorpion Sting HS Bawaskar PH Bawaskar
PART 28: MISCELLANEOUS
4 Polypharmacy in Elderly Jyotirmoy Pal Tony Ete
10 Adult Immunisation AK Agarwal RK Singal
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EDITORS OF THE PARTS
VOLUME 1
No. Part’s Name Editor
1. Introduction Yash Pal Munjal
2. Clinical Approach to Key Manifestations AK Agarwal

3. Diagnostic Imaging Raju Sharma
4. Clinical Pharmacology SK Gupta
5. Immunology Sita Naik
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6. Medical Genetics Late Shyam Swarup Agarwal
7. Critical Care Medicine Surendra K Sharma
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8. Bone Disorders SNA Rizvi
9. Diabetes Mellitus Anil Bhansali
10. Endocrinology Nikhil Tandon
11.
12.
Dermatology
Cardiology
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Gurpreet Singh Wander
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13. Gastroenterology Rakesh Tandon
14. Hepatology Rajesh Upadhyay
15. Haematology Rajat Kumar
16. HIV and AIDS Alaka Deshpande and BB Rewari
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VOLUME 2
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17. Infectious Diseases Shyam Sundar

18. Disorders of Metabolism BK Sahay
19. Nephrology Vinay Sakhuja
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20. Neurology MV Padma Srivastava

21. Oncology Lalit Kumar
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22. Psychiatric Medicine Rakesh Lal

23. Pulmonary Medicine Surendra K Sharma
24. Rheumatology Rohini Handa
25. Nutrition SV Madhu
26. Poisoning and Toxicology Narinder Pal Singh
27. Environmental Medicine Randeep Guleria
28. Miscellaneous RK Singal
x 29. Future of Medicine Shashank R Joshi
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CONTRIBUTORS
OC Abraham MD MPH Vikas Agarwal MD DM (Clinical Immunology) DN Amarapurkar MD (Med) DM DNB

Department of Medicine Unit 1 and Additional Professor Gastroenterologist and Hepatologist
Infectious Diseases, Christian Medical College Department of Clinical Immunology Bombay Hospital and Medical
Vellore, Tamil Nadu, India Sanjay Gandhi Post-graduate Institute of Research Centre, Jagjivanram Hospital
Medical Sciences Mumbai, Maharashtra, India
Philip Abraham MD DNB FCPS FICP
Lucknow, Uttar Pradesh, India
Consultant Gastroenterologist YK Amdekar MD DCH
PD Hinduja Hospital, Mahim Amita Aggarwal MD DM Medical Director
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Mumbai, Maharashtra, India Professor Bai Jerbai Wadia Hospital for Children, Mumbai
Department of Clinical Immunology Consultant Paediatrician
SK Acharya DM Sanjay Gandhi Post-graduate Institute of Jaslok Hospital and Research Centre
Professor and Head Medical Sciences Mumbai, Maharashtra, India
Department of Gastroenterology Lucknow, Uttar Pradesh, India
All India Institute of Medical Sciences AC Ammini
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MD DM (Endo)
New Delhi, India Praveen Aggarwal MD DNB FICP Professor and Head
Professor and Head, Department of Department of Endocrinology
Prabha Adhikari MD Emergency Medicine All India Institute of Medical Sciences
Professor and Head, Department of Medicine All India Institute of Medical Sciences New Delhi, India
Kasturba Medical College New Delhi, India
Mangaluru, Karnataka, India AC Anand MD (Medicine) DM (Gastroenterology)
Ramesh Aggarwal MD (Medicine)
C Adithan MD PhD DNB (Clin Pharmacol) FAMS
Senior Professor and Head
Department of Clinical Pharmacology
Jawaharlal Institute of Post-graduate Medical
Education and Research
Assistant Professor
Department of Medicine
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Lady Hardinge Medical College and Dr Ram
Manohar Lohia Hospital, New Delhi, India
FICP FACP FACG FAMS
Senior Consultant, Hepatology and
Gastroenterology
Indraprastha Apollo Hospital, New Delhi
Professor and Head of Department
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Puducherry, India Aparna Agrawal MD (Medicine) (Gastroenterology and Hepatobiliary Unit)
Director Professor, Department of Medicine Army Hospital Research and Referral
P Advaitham MD DM Lady Hardinge Medical College and New Delhi, India
Professor, Department of Medical Associated Hospitals, New Delhi, India
Gastroenterology Inder S Anand MD FRCP D Phil (Oxon.)
Sri Ramachandra Medical College Gautam Ahluwalia MD (Medicine) Professor of Medicine, University of
Sri Ramachandra University Professor Minnesota Medical School
Chennai, Tamil Nadu, India Department of Medicine Director, Heart Failure Program
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Dayanand Medical College and Hospital VA Medical Center, Minneapolis MN, USA
SH Advani MD DNB FICP PhD FNAMS Ludhiana, Punjab, India
Director, Medical Oncology Dharamvir Singh Arya MD
Jamal Ahmad MD DM (Endo) FCCP(USA) Professor, Department of Pharmacology
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Jaslok Hospital and Research Centre

Mumbai, Maharashtra, India PhD FRCP (UK) All India Institute of Medical Sciences
Professor of Endocrinology and Director New Delhi, India
AK Agarwal MD FICP FRCP (Edin) MAMS FACP Rajiv Gandhi Centre for Diabetes and
FIACM FIAMS FIMSA Endocrinology, Faculty of Medicine Naved Aslam DM (Cardiology)
Professor and Head Aligarh Muslim University Professor, Department of Cardiology
Department of General Medicine Aligarh, Uttar Pradesh, India Dayanand Medical College and Hospital
Unit Hero DMC Heart Institute
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School of Medical Sciences and Research

Sharda University, Greater Noida Mansoor Ahmed DM (Cardiology) Ludhiana, Punjab, India
Ex-Dean, Professor and Head Medical Officer, Department of Cardiology
Sawai Man Singh Medical College and K Govind Babu MD DM (Oncology)
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Department of Medicine, Post-graduate Associate Professor, Department of Medical

Institute of Medical Education and Research Associated Hospitals, Jaipur, Rajasthan, India
Oncology, Kidwai Memorial Institute of
Dr Ram Manohar Lohia Hospital Vineet Ahuja MD DM MNAMS Oncology, Bengaluru, Karnataka, India
New Delhi, India Professor, Department of Gastroenterology
All India Institute of Medical Sciences Ajay Bahl MD DNB
MB Agarwal MD MNAMS Associate Professor, Department of Cardiology
New Delhi, India
Haematologist and Haemato-oncologist Post-graduate Institute of Medical Education
Bombay Hospital, Lilavati Hospital and Parag Aland DNB (Nuclear Med) DRM and Research, Chandigarh, India
Breach Candy Hospital Junior Consultant
Head, Department of Haematology Department of Nuclear Medicine VK Bahl MD DM
Bombay Hospital Jaslok Hospital and Research Centre Professor and Head, Department of Cardiology
Mumbai, Maharashtra, India Mumbai, Maharashtra, India All India Institute of Medical Sciences
New Delhi, India
Late Shyam Swarup Agarwal MD FRCP FAMS Alan F Almeida MD (Internal Medicine)
FNA FNASc MNAMS (Nephrology) FISN BK Bajaj MD (Medicine) DM (Neurology)
Senior Medical Consultant and Honorary Consultant Nephrologist and Transplant Professor, Department of Neurology
Director (Academic and Research) Physician, Post-Doctoral Fellow of the Post-graduate Institute of Medical Education
Vivekanand Polyclinic and Institute of Medical University of Missouri, Columbia (USA) and Research, Dr Ram Manohar Lohia Hospital
Sciences, Lucknow, Uttar Pradesh, India Fellow, Indian Society of Nephrology New Delhi, India
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V Balaji MD FRCP (UK) Sandeep B Bavdekar MD (Paed) DCH Professor and Head
Director and Senior Consultant Professor and Head, Department of Paediatrics Department of Neurology, Bombay Hospital
Dr V Seshiah Diabetes Research Institute and Topiwala National Medical College and Institute of Medical Sciences, Mumbai
Dr Balaji Diabetes Care Centre BYL Nair Charitable Hospital Head, Department of Neuroepidemiology
Chennai, Tamil Nadu, India Mumbai, Maharashtra, India Medical Research Centre, Bombay Hospital
V Balakrishnan MD DM Usha K Baveja MD
Professor, Department of Gastroenterology Head, Division of Microbiology, Medanta—The Atul Bhasin MD DNB (Internal Medicine) MNAMS
Amrita Institute of Medical Sciences and Medicity, Gurgaon, Haryana, India Senior Consultant, Department of Internal
Research Centre, Kochi, Kerala, India Medicine, Dr BL Kapur Memorial Hospital

HS Bawaskar MD
New Delhi, India
Yatan Pal Singh Balhara MD DNB (Psychiatry) Bawaskar Hospital and Research Centre
MNAMS Raigad, Maharashtra, India Deepak Kumar Bhasin MD DM FAMS FASGE
Assistant Professor, Department of Psychiatry AGAF
Digambar Behera MD DNB
Professor and Head
National Drug Dependence Treatment Centre
Senior Professor, Department of Pulmonary Department of Gastroenterology
All India Institute of Medical Sciences
Medicine, Post-graduate Institute of Medical Post-graduate Institute of Medical Education
New Delhi, India
Education and Research, Chandigarh, India
rs
and Research, Chandigarh, India
Pradeep Bambery MD FRCP (Glas) FRACP
DP Bhadoria MD (Medicine) DM (Pulmonary/
Associate Professor of Medicine Eesh Bhatia MD (Internal Medicine)
Critical Care Medicine)
The University of Queensland DNB (Endocrinology)
Professor, Department of Medicine Professor and Head
Rural Medical School (Bundaberg Campus) Maulana Azad Medical College, Lok Nayak
Department of Endocrinology
he
Director of Medicine Bundaberg Hospital (Irwin) and GB Pant Hospitals, New Delhi, India
Queensland, Australia Sanjay Gandhi Post-graduate
Dipesh Bhagabati MD Institute of Medical Sciences
Debabrata Bandyopadhyay MD
Professor, Department of Psychiatry Lucknow, Uttar Pradesh, India
Professor and Head, Department of Gauhati Medical College and Hospital
Dermatology, Venereology and Leprosy Jagriti Bhatia MD
Guwahati, Assam, India
RG Kar Medical College Additional Professor, Department of
ot
Kolkata, West Bengal, India Ashit M Bhagwati MD (Med) FICA FICP ADHA Pharmacology, All India Institute of Medical
(Hosp Adm) Sciences, New Delhi, India
Amal Kumar Banerjee MD DM FACC FACP FICP Honorary Physician, Bhatia Hospital,
Senior Consultant and Interventional Shobna Bhatia MD (Med) DNB (Gastroenterology)
Wockhardt Hospital, Smt Motiben Dalvi
Cardiologist, Howrah, West Bengal, India Professor and Head
Hospital, Mumbai, Maharashtra, India
Department of Gastroenterology
Br
Samar Banerjee MD Ashu Seith Bhalla MD MAMS FICR Seth GS Medical College and KEM Hospital
Professor, Department of Medicine Professor Mumbai, Maharashtra, India
Vivekananda Institute of Medical Sciences Department of Radiodiagnosis
Kolkata, West Bengal, India Vijayalakshmi Bhatia MD (Paediatrics)
Professor
Atma Ram Bansal MD DM (Neurology) New Delhi, India
Department of Endocrinology, Sanjay Gandhi
Associate Consultant Air Vice Marshal Rajvir Bhalwar MD MPhil Post-graduate Institute of Medical Sciences
Institute of Neurosciences, Medanta—The Lucknow, Uttar Pradesh, India
e
PhD FAMS
Medicity, Gurgaon, Haryana, India Commandant and Principal Command
Neerja Bhatla MD
Beena Bansal MD DM Hospital and PG College of Medical Education
Professor, Department of Obstetrics and
Air Force, Agram Bengaluru, Karnataka, India
pe
Consultant, Division of Endocrinology Gynaecology, All India Institute of Medical

and Diabetes, Medanta—The Medicity Anil Bhansali DM (Endocrinology) Sciences, New Delhi, India
Gurgaon, Haryana, India Professor and Head, Department of
Mohit Bhatt MD DM
NO Bansal MD (Medicine) DM (Cardiology)
Endocrinology, Post-graduate Institute of
Consultant and Head, Department of
Medical Education and Research
DNB (Cardiology) Neurology, Kokilaben Dhirubhai Ambani
Secretary General Chandigarh, India
Hospital and Medical Research Institute
y
Indian College of Interventional Cardiology Somnath Bhar MRCPI MRCPS (Glas) Mumbai, Maharashtra, India
Mumbai, Maharashtra, India Consultant Physician, GD Hospital and
M Bhattacharjee
Diabetes Institute, Kolkata, West Bengal, India
Ja
Reema Bansal MS (Ophthalmology) Consultant Neurophysician and Director of

Assistant Professor, Advanced Eye Centre SKD Bhardwaj Research, Lilavati Hospital and LKMM Trust
Post-graduate Institute of Medical Education Senior Consultant Cardiologist Research Centre, Mumbai, Maharashtra, India
and Research, Chandigarh, India Muzaffarnagar, Uttar Pradesh, India
Prasanta Kumar Bhattacharya MD (Medicine)
PP Bapsy MD DM Swati Bhardwaj PhD PhD (Cardiology)
Senior Consultant, Medical Oncology Nutritionist and Senior Research Officer Professor and Head, Department of General
Apollo Hospitals, Bengaluru, Karnataka, India Diabetes Foundation (India) and N-DOC Medicine, North Eastern Indira Gandhi
Centre for Nutrition and Metabolic Research Regional Institute of Health and Medical
Jahangeer Basha MD DM
(C-NET), New Delhi, India Sciences, Shillong, Meghalaya, India
Scientific Pool Officer
Department of Gastroenterology Pallavi Bhargava MD Sujit K Bhattacharya MD FNA FNASc FAMS
Post-graduate Institute of Medical Education Consultant in Infectious Diseases and Travel Medical Officer, World Health Organization
and Research, Chandigarh, India Medicine, Allegiance Health South East Asia Regional Office
Jackson, Michigan, USA New Delhi, India
Debasish Basu MD DNB
Professor, Drug De-addiction and Treatment Nadir E Bharucha MD (Bom) FAMS (India) Jina Bhattacharyya DM
Centre, Department of Psychiatry FRCP (Lond) FRCP (Neurology) Professor, Department of Clinical
xii Post-graduate Institute of Medical Education Diplomate, American Board of Neurology and Haematology, Gauhati Medical College
and Research, Chandigarh, India Psychiatry (N) and Hospital, Guwahati, Assam, India
API _ Prelims _ Vol-1 for (TRADE).indd xii 29-01-2015 14:22:07

Prabhash Chandra Bhattacharyya MD Mammen Chandy MD FRACP FRCPA FRCP Gourdas Choudhuri MD DM FICP FAMS FACG FRCPI
Ex-Professor and Head, Department of Director, Tata Medical Centre Director and Head, Department of
Medicine, Gauhati Medical College, Senior Kolkata, West Bengal, India Gastroenterology and Hepatobiliary Sciences
Consultant, Department of Medicine Fortis Memorial Research Institute
Down Town Hospital, Guwahati, Assam, India Mitali Chatterjee MD PhD
Gurgaon, Haryana, India
Professor, Department of Pharmacology
Sanjeev Bhoi Institute of Post-graduate Medical Education Anumita R Chowdhury
Additional Professor of Medicine and Research, Kolkata, West Bengal, India Executive Director (Research and Advocacy)
Department of Emergency Medicine Centre for Science and Environment
Contributors
JPN Apex Trauma Centre, All India Institute of Sarit Chatterjee MD DNB New Delhi, India
Medical Sciences, New Delhi, India Consultant Physician, Assistant Professor
Department of Medicine, Post-graduate MK Daga MD FCCP FICP MNAMS
Aspi R Billimoria MD Institute of Medical Education and Research Director Professor, Department of Medicine,
Ex-Head and Dr Ram Manohar Lohia Hospital Maulana Azad Medical College
Department of Cardiology, St George’s New Delhi, India New Delhi, India
Hospital and Grant Medical College, Mumbai
Cardiologist, Conwest Jain Clinic Group of Anil Chaturvedi MD Surendra Daga MD
Chief Consultant, Life-style Disease and Senior Consultant Cardiologist and Physician
rs
Hospitals, Mumbai, Maharashtra, India
Preventive Health, Apollo Health and Life-style Kolkata, West Bengal, India
Anita M Borges MD FRCPath Ltd, The Apollo Clinic, New Delhi, India
Consultant Histopathologist, Asian Institute of
Ashwin Dalal MD (Paediatrics) DM
Lt General Ved Chaturvedi MD DM (Medical Genetics)
Oncology, SL Raheja Hospital, Mumbai
Chief Consultant Rheumatologist Head, Diagnostics Division, Centre for DNA
he
Director, Centres of Excellence, Histopathology
Armed Forces Medical Services Fingerprinting and Diagnostics, Nampally
SRL Diagnostics, Mumbai, Maharashtra, India
Research and Referral Hospital Hyderabad, Telangana, India
Khadijah Breathett MD New Delhi, India PM Dalal MD FAMS
The Ohio State University, Wexner Medical
Dhruva Chaudhry MD (Med) DNB (Med) Consultant Neurophysician and Director of
Center, Department of Internal Medicine
DM (PCCM) FICP FICCM Research, Lilavati Hospital and LKMM Trust
Division of Cardiology, Columbus, Ohio, USA
Senior Professor and Head/Dean Faculty of Research Centre, Mumbai, Maharashtra, India
Nishigandha Burute MD
Fellow, Department of Medical Imaging
St. Michael’s Hospital, University of Toronto
Toronto, ON, Canada
Critical Care Medicine
ot
Medical Super-speciality Pulmonary and
Pt BDS University of Health Sciences

Rohtak, Haryana, India
Debashish Danda MD (General Medicine)
DM (Clinical Immunology) FRCP
Professor and Head, Clinical Immunology and
Rheumatology, Christian Medical College and
Br
Ashok Chacko MD DM FRCP FAMS Kusumita Chaudhuri MD Hospital, Vellore, Tamil Nadu, India
Director and Head, Institute of Ex-Microbiologist, Department of Ashok Kumar Das MD FAMS FICP PhD FRCP
Gastroenterology and Liver Diseases, Madras Microbiology, Moolchand Hospital Professor, Department of Medicine
Medical Mission, Chennai, Tamil Nadu, India New Delhi, India Pondicherry Institute of Medical Sciences
Rakesh K Chadda MD FAMS FRCPsych Col Anuj Chawla MD (Physiology) Puducherry, India
Professor, Department of Psychiatry, All India DNB (Physiology) MNAMS FCGP Chandan J Das MD DNB MNAMS
Institute of Medical Sciences, New Delhi, India Professor and Head, Department of
e
Assistant Professor, Department of Radiology

Prantar Chakrabarti MD (Med) DNB (Med) Physiology, Armed Forces Medical College All India Institute of Medical Sciences
DM (Clinical Haematology) Pune, Maharashtra, India New Delhi, India
Professor, Department of Haematology
pe
Rajesh Chawla MD EDIC FICCM FCCM Madhumita P Das MD

Institute of Haematology and Transfusion Senior Consultant Respiratory, Critical Care Professor, Department of Medicine
Medicine, Medical College and Sleep Medicine Gauhati Medical College
Kolkata, West Bengal, India Indraprastha Apollo Hospital, New Delhi, India Guwahati, Assam, India
Partha Pratim Chakraborty MD Yogesh K Chawla MD Shyamal Kumar Das DM
Assistant Professor, Department of Medicine Director, Post-graduate Institute of Medical Professor and Head, Department of Neurology
y
Midnapore Medical College and Hospital Education and Research, Chandigarh, India Bangur Institute of Neurosciences
Paschim Medinipur, West Bengal, India
Mala Chhabra MD (Microbiology)
Kolkata, West Bengal, India
Praloy Chakraborty MD (Medicine)
Ja
Joint Director, National Centre for Disease Siddharth Kumar Das MD (Medicine)
DM (Cardiology) Control, New Delhi, India Professor and Head, Department of
Associate Professor, Department of Cardiology
Rheumatology, King George’s Medical
Vardhman Mahavir Medical College and Shibba Takkar Chhabra MD DM (Cardiology)
University, Lucknow, Uttar Pradesh, India
Safdarjung Hospital, New Delhi, India Assistant Professor
Dayanand Medical College and Hospital Biswa B Dash MD DNB MICOG
Hemraj B Chandalia MD FACP Unit Hero DMC Heart Institute Department of Obstetrics and Gynaecology
Director, Endocrinology, Diabetes and Ludhiana, Punjab, India All India Institute of Medical Sciences
Metabolism Jaslok Hospital and Research
New Delhi, India
Centre, Dr Chandalia’s Diabetes Endocrine SK Chhabra MD FCCP
Nutrition Management and Research Centre Consultant, Pulmonary and Critical Surabhi Dayal MD (Skin and VD)
Mumbai, Maharashtra, India Care Medicine, Head, Department of Professor, Department of Dermatology
Cardiorespiratory Physiology Venereology and Leprology
P Sarat Chandra MCh
Vallabhbhai Patel Chest Institute Pt BDS Post-graduate Institute of Medical
Professor, Department of Neurosurgery New Delhi, India Sciences, Rohtak, Haryana, India
New Delhi, India Dharma R Choudhary DM Koushik Sinha Deb MD (Psychiatry)
Fellow UCLA, Faculty 1000 ILAE Director, Bone Marrow Transplant Assistant Professor, Department of Psychiatry
Visiting Professor, INI, Hannover BLK Super-speciality Hospital All India Institute of Medical Sciences xiii
Lower Saxony, Germany New Delhi, India Jodhpur, Rajasthan, India
API _ Prelims _ Vol-1 for (TRADE).indd xiii 29-01-2015 14:22:08

Deepshikha MD (Medicine) Pankaj Dhawan MD DNB DM (Gastro) Rene P Eapen MD
Assistant Professor Chief Interventional Gastroenterologist Assistant Professor, Department of Medicine
Department of Medicine Digestive Diseases and Endoscopic Lady Hardinge Medical College and Smt
Baba Raghav Das Medical College Centre, Motiben Dalvi Hospital; Consultant Sucheta Kriplani Hospital, New Delhi, India
and Hospital Interventional Gastroenterologist, Jaslok
Bhatia and Breach Candy Hospitals Faraz Ahmed Farooqui MD
Gorakhpur, Uttar Pradesh, India
Mumbai, Maharashtra, India Department of Medicine, All India Institute of
Sripurna Deepti MD (Medicine) Medical Sciences, New Delhi, India
Meenakshi Institute of Medical Sciences Radha K Dhiman MD DM FAMS FACG
Veronica Franco
MD
Kanchipuram, Tamil Nadu, India Professor, Department of Hepatology
The Ohio State University Wexner Medical
Post-graduate Institute of Medical Education
Avinash Deo MD Center, Department of Internal Medicine
Consultant, Medical Oncologist and Division of Cardiology, Columbus, Ohio, USA
Haematologist Sahajal Dhooria MD DM
Assistant Professor
MJ Gandhi MD FAMS FICC FICP FICE
Holy Family, Guru Nanak and Dhanwantari
Cardiologist, Professor Emeritus
Hospital, Mumbai, Maharashtra, India Department of Pulmonary Medicine
Nanawati Hospital Heart Institute
rs
Anita Desai and Research, Chandigarh, India
Department of Neurovirology VP Gangadharan MD
National Institute of Mental Health and Sunil Dogra MD DNB FRCP (London)
Department of Medical Oncology
Neurosciences Associate Professor
Lakeshore Hospital and Research Centre
Bengaluru, Karnataka, India Department of Dermatology, Venereology and
Kochin, Kerala, India
Leprology, Post-graduate Institute of Medical
he
Mukesh Desai MD DNB Education and Research, Chandigarh, India Dwijendra Nath Gangopadhyay MD
Professor, Department of Paediatric (Dermatology)
Haematology Oncology Tuphan Kanti Dolai MD DNB
Professor and Head, Department of
Honorary Haematologist Oncologist and DM (Clinical Haematology)
Dermatology, Burdwan Medical College
Immunologist, Chief, Division of Immunology Assistant Professor
Burdwan, West Bengal, India
Department of Paediatric Haematology Department of Haematology, NRS Medical
ot
Oncology College, Kolkatta, West Bengal, India Sandipan Ganguly PhD
BJ Wadia Hospital for Children, Mumbai Assistant Director (Scientist D)
Parul Dubey MD DM (Neurology)
Consultant Haematologist National Institute of Cholera and Enteric Diseases
Consultant, Department of Neurology
Nanavati Hospital, Sir HN Hospital and Saifee New Delhi, India
Goa Medical College and Hospital
Hospital, Mumbai, Maharashtra, India Tiswadi, Goa, India
Br
Ajay Garg MD
Neelu Desai MD Consultant, Department of Neuroradiology
Ajay Duseja MD DM MNAMS FACG
Paediatrician, PD Hinduja National Hospital All India Institute of Medical Sciences
Department of Hepatology
and Medical Research Centre New Delhi, India
Mumbai, Maharashtra, India and Research, Chandigarh, India Pramod Kumar Garg MD DM
Niyati Desai Sub-Dean (Research)
Roman Dutta MS
Microbiologist Professor of Gastroenterology
Consultant Thoracic Surgeon
e
Department of Microbiology All India Institute of Medical Sciences

Pushpanjali Crosslay Hospital
PD Hinduja National Hospital and Medical New Delhi, India
Ghaziabad, Uttar Pradesh, India
Research Centre, Mumbai, Maharashtra, India Ravindra Kumar Garg MD DM
pe
Sangit Dutta DM
Shrinivas B Desai MD Professor and Head
Professor, Department of Medicine
Head, Department of Imaging and Department of Neurology
Gauhati Medical College and Hospital
Interventional Radiology, Jaslok Hospital and King George’s Medical University
Guwahati, Assam, India
Research Centre, Mumbai, Maharashtra, India Lucknow, Uttar Pradesh, India
Tarun Kumar Dutta MD
Vinay H Deshmane MS DNB FRCS (Glas) Taru Garg MD (Dermatology and Venereology)
Professor, Department of Medicine
Professor, Department of Dermatology
y
MD (London) FICS Head, Division of Clinical Haematology

Consultant, Department of Surgical Oncology Lady Hardinge Medical College and
Jawaharlal Institute of Post-graduate Medical
and Breast Diseases, PD Hinduja Hospital Associated Hospitals, New Delhi, India
Education and Research, Puducherry, India
Ja
Breach Candy Hospital, Asian Institute of AR Gayathri MD FCCP

Oncology, Mumbai, Maharashtra, India Usha Dutta MD DM MSc (HRM)
Respiratory Medicine Specialist
Additional Professor, Department of
Alaka Deshpande MD MAMS FIMSA FICP
Apollo Hospitals, Chennai, Tamil Nadu, India
Gastroenterology, Post-graduate Institute of
Professor of Medicine and Chief HIV Unit Medical Education and Research Muhammad Abid Geelani MCh (CTVS)
Grant Medical College and Sir JJ Group of Chandigarh, India Professor
Government Hospitals Department of Cardio-thoracic Vascular
Mumbai, Maharashtra, India Shridhar Dwivedi MD PhD (Cardiology)
Surgery, GB Pant Hospital and Maulana
FRCP (London)
Azad Medical College, New Delhi, India
Richa Dewan Dean/Principal, Professor of Medicine/
Director Professor and Head, Department of Preventive Cardiology, Hamdard Institute of R Gerzer
Medicine, Maulana Azad Medical College Medical Sciences and Research, Associated Institute of Aerospace Medicine
New Delhi, India Hakeem Abdul Hameed Centenary Hospital German Aerospace Center DLR
Jamia Hamdard (Hamdard University) Linder Hoehe, Cologne, Germany
Sandipan Dhar MD (Dermatology)
New Delhi, India
DNB (Dermatology) Alakendu Ghosh MD DNB
Professor and Head CE Eapen MD DM Professor, Department of Medicine
Department of Paediatric Dermatology Professor and Head, Department of Clinical Head, Department of Rheumatology
xiv Institute of Child Health Gastroenterology and Hepatology, Christian Institute of Post-graduate Medical Education
Kolkata, West Bengal, India Medical College, Vellore, Tamil Nadu, India and Research, Kolkata, West Bengal, India
API _ Prelims _ Vol-1 for (TRADE).indd xiv 29-01-2015 14:22:08

Kanjaksha Ghosh MD (Med) DNB (Haem) FRC Randeep Guleria MD DM (Pulmonary and Sudeep Gupta MD DM
Path (Lond) FACP (USA) MRCP (Ire) MRCP (UK) FNASc Critical Care) Professor
FICP FRCP (Glas) Professor and Head, Department of Pulmonary Department of Medical Oncology
Director (NIIT) Medicine, All India Institute of Medical Convener, Gynaecology Oncology Working
Honorary Professor (KEMH) Sciences, New Delhi, India Group, Tata Memorial Centre/Hospital
Department of Haematology, KEM Hospital Mumbai, Maharashtra, India
Mumbai, Maharashtra, India Amod Gupta MS
Head Vaibhav Gupta MD
Manab Kumar Ghosh DCH (Cal) DTM & H (Cal) Department of Ophthalmology Consultant
Contributors
MD (Tropical Medicine) (Cal) Post-graduate Institute of Medical Education Department of Gastroenterology
Assistant Professor and Research, Chandigarh, India Rockland Hospital, New Delhi, India
Calcutta School of Tropical Medicine
Ankur Gupta DM (Nephrology) YK Gupta MD
Consultant In-charge, Nephrology Services Professor and Head, Department of
Uday Chand Ghoshal MD DNB DM FACG RFF Max Super-speciality Hospital, Shalimar Bagh Pharmacology, All India Institute of Medical
Professor New Delhi, India Sciences, New Delhi, India
Department of Gastroenterology
Anu Gupta DM (Neurology) Soneil Guptha MD FACC FESC FCCP FICA Dip
rs
Sanjay Gandhi Post-graduate Institute of
Department of Neurology Pharm Med
Medical Sciences
Post-graduate Institute of Medical Education Honorary Director
Lucknow, Uttar Pradesh, India
and Research, Chandigrah, India Jaipur Heart Watch Foundation
Ashish Goel Jaipur, Rajasthan, India
Deepak Kumar Gupta MD (Med)
he
Associate Professor, Department of
DNB (Gastroenterology) Anil Gurtoo MD
Hepatology, Christian Medical College
Assistant Professor Director Professor, Department of Medicine
Vellore, Tamil Nadu, India
Department of Gastroenterology Lady Hardinge Medical College and
Hemant Gopal MD Seth GS Medical College and KEM Hospital Associated Hospitals, New Delhi, India
Associate Professor, Department of Medicine Mumbai, Maharashtra, India
Ashutosh Halder MD DNB DM MRCOG-I
Adesh Institute of Medical Sciences and
Neha Gupta DNB FNB ID Professor, Department of Reproductive
Research, Adesh University
Bhatinda, Punjab, India
Sankar Prasad Gorthi
Senior Advisor
MD DNB
Department of Medicine and Neurology

Nitin Gupta MD DM
ot
Associate Consultant, Department of General
Medicine and Infectious Diseases, PD Hinduja
Hospital, Mumbai, Maharashtra, India
Biology, All India Institute of Medical Sciences
New Delhi, India
Rohini Handa
FRCP (Glasgow)
MD DNB FAMS FICP FACR
Br
Consultant Senior Consultant Rheumatologist, Apollo
Army Hospital Research and Referral
Department of Gastroenterology Indraprastha Hospital, New Delhi, India
New Delhi, India
Rajiv Gandhi Cancer Institute
New Delhi, India Sanjeev Handa MD MNAMS FAAD FRCP (Edin)
Ravinder Goswami MD DM FNASc FASC
Professor and Head
Piyush Gupta MD MAMS FIAP Department of Dermatology, Venereology and
Endocrinology and Metabolism
Professor, Department of Paediatrics Leprology, Post-graduate Institute of Medical
University College of Medical Sciences Education and Research, Chandigarh, India
e
New Delhi, India

New Delhi, India
CV Harinarayan MD (Int Med) DM (Endocrinology)
Abhishek Goyal DM (Cardiology)
Praveen Gupta MD DM FAMS FRCP (Glas) FRCP(Edin)
Assistant Professor, Department of Cardiology
Director and Head Director, Institute of Endocrinology
pe
Dayanand Medical College and Hospital

Department of Neurology Diabetes and Osteoporosis, Sakra World
Unit Hero DMC Heart Institute
Fortis Memorial Research Institute Hospitals, Deverabeesanahalli, Varathur Hobili
Ludhiana, Punjab, India
Gurgaon, Haryana, India Marathahalli, Bengaluru, Karnataka, India
RK Goyal MD
Pritam Gupta MD (Medicine) NK Hase MD DNB
Ex-Senior Professor and Head, Department of
Senior Consultant and Head, Department of Professor and Head
Medicine, Jawaharlal Nehru Medical College
y
Medicine, Sunder Lal Jain Hospital Department of Nephrology

Ajmer, Rajasthan, India
New Delhi, India Seth GS Medical College and KEM Hospital
Chander Grover MD DNB MNAMS Mumbai, Maharashtra, India
Rajeev Gupta MD PhD
Ja
Assistant Professor
Consultant, Department of Medicine D Himanshu MD
Department of Dermatology, Venereology
Fortis Escorts Hospital, Jaipur, Rajasthan, India Unit In-charge, Department of Medicine
and Leprology, University College of
Chhatrapati Sahu Ji Maharaj Medical
Medical Sciences and Guru Tegh Bahadur Rakesh K Gupta MD
University, Lucknow, Uttar Pradesh, India
Hospital University of Delhi Director and Head, Department of Radiology
New Delhi, India Fortis Memorial Research Institute AK Hooda MD DM
Gurgaon, Haryana, India Senior Advisor (Medicine and Nephrology)
Subhasish Kamal Guha DTM & H MD
Command Hospital (Eastern Command)
Associate Professor SK Gupta PhD DSc (Hon) FIACS FIPS FISER FRAMS
Department of Tropical Medicine Professor Emeritus, Delhi institute of
Calcutta School of Tropical Medicine Pharmaceutical Sciences and Research G Immanuel MD PhD MAMS
Kolkata, West Bengal, India Ex-Professor and Head, Department of Director, Centre for AIDS and Antiviral
Pharmacology, All India Institute of Medical Research, Tuticorin, Tamil Nadu, India
PD Gulati MD FAMS FAIID FICAI FIMSA
Sciences, New Delhi, India
Senior Honorary Consultant Arun C Inamadar MD FRCP (Edinburgh)
Tirath Ram Shah Hospital, New Delhi Subash Gupta MS FRCS (Ed) FRCS (Glas) Professor and Head
Ex-Head, Division of Nephrology Senior Consultant, ANG Centre for Liver and Department of Dermatology
Maulana Azad Medical College and Associated Biliary Sciences, Indraprastha Apollo Hospital Sri BM Patil Medical College, BLDE University
Hospitals, New Delhi, India New Delhi, India Bijapur, Karnataka, India xv
API _ Prelims _ Vol-1 for (TRADE).indd xv 29-01-2015 14:22:08

Vara Prasad IR MD Pranaw Kumar Jha MD DNB J Kalita DM
Assistant Professor Associate Consultant, Department of Professor, Department of Neurology, Sanjay
Department of Rheumatology Nephrology and Transplant Medicine Gandhi Post-graduate Institute of Medical
Nizam’s Institute of Medical Sciences Medanta—The Medicity Sciences, Lucknow, Uttar Pradesh, India
Hyderabad, Telangana, India Gurgaon, Haryana, India
OP Kalra MD DM FAMS FACP FICP FISN FIACM
Manish W Itolikar MD DNB Farah Jijina MD Commonwealth Fellow in Nephrology
Assistant Professor Consultant (Leicester General Hospital, UK)
Seth GS Medical College and KEM Hospital Haematologist/Haemato-oncologist Professor of Medicine
Mumbai, Maharashtra, India PD Hinduja Hospital (Mahim) and Hinduja Head, Division of Nephrology
Healthcare, Mumbai, Maharashtra, India Principal, University College of Medical
SA Jabeen Sciences, Guru Tegh Bahadur Hospital
Associate Professor, Department of Neurology Surinder K Jindal MD (Medicine) FAMS FCCP
New Delhi, India
Nizam’s Institute of Medical Sciences FNCCP
Hyderabad, Telangana, India Professor and Head, Department of Pulmonary Sandhya A Kamath MD FICP
Medicine, Post-graduate Institute of Medical Ex-Dean and Professor
Priya Jagia MD DNB (Radiology)
Education and Research, Chandigarh, India Department of Medicine
rs
Lokmanya Tilak Municipal Medical College
Cardiovascular and Interventional Radiology George T John MD DM FRCP FRACP
and Municipal General Hospital
Cardiothoracic Sciences Centre Senior Consultant, Department of Renal
All India Institute of Medical Sciences Medicine, Royal Brisbane and Women’s
New Delhi, India Hospital, Herston Qld, Australia Devasenathipathy Kandasamy MD DNB
he
FRCR
DG Jain MD FRCP (Edin) FRCP (Glas) FICP Jyotsna M Joshi MD
Assistant Professor
Honory Affiliate Professor Professor and Head, Department of Pulmonary
Department of Medicine, Manipal University Medicine, BYL Nair Hospital
Mumbai, Maharashtra, India New Delhi, India
Karnataka Trustee, Tirath Ram Shah Hospital
New Delhi, India Hemanta Kumar Kar
Prashant P Joshi MD (Medicine)
Professor and Head, Department of Medicine Medical Superintendent
Krishan K Jain MD
ot
Indira Gandhi Government Medical College Dr Ram Manohar Lohia Hospital and Post-
Consultant, Department of Radiology and
Nagpur, Maharashtra, India graduate Institute of Medical Education and
Imaging, Fortis Memorial Research Institute
Research, New Delhi, India
Shashank R Joshi MD DM FICP FACP (USA)
FACE (USA) FRCP (Glsg and Edin)
Madhuchanda Kar MD (Medicine)
Narender Pal Jain MD FICP
Br
PhD (Cancer Research)
Associate Professor, Department of Medicine (Padma Shri Awardee 2014)
Endocrinologist Visiting Medical Oncologist, Peerless Hospital
Dayanand Medical College and Hospital
Joshi Clinic, Lilavati and Bhatia Hospital Kolkata, West Bengal, India
Ludhiana, Punjab, India
Past President, API Premashis Kar MD DM (Gastroenterology)
Piyush Jain MD (Medicine) Emeritus Editor, JAPI FRCP FACG FAMS
Assistant Professor President, Indian Academy of Diabetes Professor of Medicine and Gastroenterologist
Department of Medicine, Post-graduate Past President, RSSDI (Research Society for the Department of Medicine, Maulana Azad
Institute of Medical Education and Research Study of Diabetes in India 2011)
e
Medical College, New Delhi, India

and Dr Ram Manohar Lohia Hospital Past President, AIAARO (All India Association
New Delhi, India of Advancement for Research in Obesity) N Karthik
Chapter Chair India AACE Department of Neurology, National Institute
pe
Sachin K Jain
of Mental Health and Neurosciences
Director and Professor, Department of Shilpa S Joshi Bengaluru, Karnataka, India
Medicine, Lady Hardinge Medical College Director, Mumbai Diet and Health Centre
New Delhi, India Mumbai, Maharashtra, India Sellam Karunanithi MD
Consultant, Malabar Institute of Medical
Sanjay Jain MD DM VR Joshi MD Sciences, Calicut, Kerala, India
Professor, Department of Internal Medicine Director Research, Consultant Physician and
y
Post-graduate Institute of Medical Education Rheumatologist, PD Hinduja National Hospital Upendra Kaul MD DM FCSI FACC FSCAI FAMS
and Research, Chandigarh, India and Medical Research Centre (Awarded Padma Shri and Dr BC Roy Award
Mumbai, Maharashtra, India Executive Director and Dean
Manisha Jana MD DNB FRCR
Ja
Cardiology Fortis Escorts Heart Institute and

Department of Radiodiagnosis Madhulika Kabra MD Fortis Vasant Kunj, New Delhi, India
All India Institute of Medical Sciences Additional Professor, Genetics Unit
New Delhi, India Department of Paediatrics, All India Institute Gurleen Kaur
of Medical Sciences, New Delhi, India Research Associate, Pushpanjali Crosslay
Bhavin Jankharia MD
Hospital, Ghaziabad, Uttar Pradesh, India
Radiologist, Jankharia Imaging Tamilarasu Kadhiravan MD
Mumbai, Maharashtra, India Associate Professor, Department of Medicine Rohini Kelkar MD DPB
Jawaharlal Institute of Post-graduate Medical Professor and Head, Department of
MS Jawahar MD MSc DLSHTM
Education and Research, Puducherry, India Microbiology, Tata Memorial Centre
Former Deputy Director (Senior Grade) and
Scientist ‘F’, Department of Clinical Research PN Kakar MD FICA
National Institute for Research in Tuberculosis Director Medical Affairs, Anaesthesia and SICU SV Khadilkar MD
Indian Council of Medical Research Panacea New Rise Hospital Professor, Department of Neurology
Chennai, Tamil Nadu, India Gurgaon, Haryana, India Bombay Hospital and Medical Research
Centre, Mumbai, Maharashtra, India
RV Jayakumar MD DM MNAMS FRCP V Kalaiselvan M Pharm PhD
Professor, Department of Endocrinology Principal Scientific Officer Deepak Khandelwal MD DM
Amrita Institute of Medical Sciences Indian Pharmacopoeia Commission Consultant Endocrinologist, Maharaja Agrasen
xvi Kochi, Kerala, India Ghaziabad, Uttar Pradesh, India Hospital, New Delhi, India
API _ Prelims _ Vol-1 for (TRADE).indd xvi 29-01-2015 14:22:08

SK Khandelwal MD MNAMS MRCPsych (Hon) Bindu Kulshreshtha MD DM S Lahiri
Professor and Head, Department of Psychiatry Associate Professor, Endocrinology Consultant Cardiology
All India Institute of Medical Sciences Post-graduate Institute of Medical Education Delhi Heart and Lung Institute, New Delhi, India
New Delhi, India and Research and Dr Ram Manohar Lohia
Hospital, New Delhi, India Moti Lal MD (Medicine)
Sudeep Khanna MD DM Associate Professor, Department of Medicine
Senior Gastroenterologist Ajay Kumar MD DM MAMS FRCP (Glasgow) Lady Hardinge Medical College and
Pushpawati Singhania Research Institute for Senior Consultant, Gastroenterology and Associated Hospitals, New Delhi, India
Liver, Renal and Digestive Diseases Hepatology, Indraprastha Apollo Hospital
Contributors
New Delhi, India New Delhi, India Rakesh Lal
Professor
Vijay Kher MD DM FAMS FRCPE Arvind Kumar MD National Drug Dependence Treatment Centre
Chairman, Division of Nephrology and Department of Medicine, Maulana Azad All India Institute of Medical Sciences
Transplant Medicine, Medanta Kidney and Medical College and Associated Hospitals New Delhi, India
Urology Institute, Medanta—The Medicity New Delhi, India
Gurgaon, Haryana, India Amit Langote MD DNB (Nephrology)
Jaya Kumar MD Nephrologist, The Ottawa Hospital
Shilpa Khullar MD (Physiology) MHA Associate Consultant, Department of Ottawa, Ontario, Canada
rs
Assistant Professor, ESIC Dental College Respiratory Medicine, Max Hospital, Saket
Rohini, New Delhi, India New Delhi, India RD Lele MRCP (Edin) FRCP
Director of Nuclear Medicine and PET/CT
Donald Kikta Jr MD Lalit Kumar MD DM FAMS FASc Jaslok Hospital and Research Centre and
Cardiovascular Medicine, University Hospitals Professor and Head Lilawati Hospital and Research Centre
he
Case Medical Center, Cleveland, Ohio, USA Department of Medical Oncology Mumbai, Maharashtra, India
Ashok L Kirpalani MD (Medicine) Dr Bhim Rao Ambedkar Institute of Rotary
Cancer Hospital, All India Institute of Medical Vikram R Lele MD (Med) DNB (Nuclear Med) DRM
MNAMS (Nephrology) Director, Department of Nuclear Medicine
Professor and Head, Department of Sciences, New Delhi, India
Jaslok Hospital and Research Centre
Nephrology, Bombay Hospital Institute of Neeraj Kumar Mumbai, Maharashtra, India
Medical Sciences, Mumbai, Maharashtra, India Department of Transplant Immunology and
Suman Kirti MD FRCP (London) FRCP (Edin) FICP
Senior Consultant Medicine
Holy Family Hospital, New Delhi, India
Jugal Kishore
R Krishna Kumar
Professor and Head
ot
Immunogenetics, All India Institute of Medical
MD DM FAHA
Yash Y Lokhandwala
Arrhythmia Associates
DM (Cardiology)
Mumbai Quintiles Cardiac Safety Services

Br
MD PGDCHFWM PGDEE Netravathi M
MSc (SD MH) FIAPSM FIPHA FAMS Department of Paediatric Cardiology
Amrita Institute of Medical Sciences and Assistant Professor, Department of Neurology
Director Professor, Department of Community National Institute of Mental Health and
Medicine, Maulana Azad Medical College Research Centre, Kochi, Kerala, India
Neurosciences, Bengaluru, Karnataka, India
New Delhi, India Raj Kumar MD
Professor and Head, Department of Kaushal Madan
Girisha KM MD (Paediatrics) DM (Medical Genetics) Senior Consultant, Hepatologist and
Professor and Head, Department of Medical Respiratory Allergy and Applied Immunology
National Centre of Respiratory Allergy, Asthma Gastroenterologist, Medanta Institute
e
Genetics, Kasturba Medical College of Digestive and Hepatobiliary Sciences

Manipal, Karnataka, India and Immunology, Vallabhbhai Patel Chest
Institute, University of Delhi, New Delhi, India Medanta—The Medicity
Dhanpat Kumar Kochar MD DN (Vienna) Gurgaon, Haryana, India
pe
Visiting Professor, Medical Research Rajat Kumar MD (Med) DNB (Med) FICP FRCP (Edin)
FRCP (London) FRCPC
SV Madhu MD DM (Endocrinology)
Rajasthan University of Health Sciences, Jaipur Professor and Head
Ex-Professor and Head, Cerebral Malaria Professor, Department of Medical Oncology
and Haematology, Cancer Care Manitoba Division of Endocrinology and Metabolism
Research Centre, Sarder Patel Medical College Department of Medicine, University College
Bikaner, Rajasthan, India Professor, University of Manitoba, Canada
of Medical Sciences and Guru Tegh Bahadur
Rakesh Kochhar MD DM Rakesh Kumar DNB PhD Hospital, New Delhi, India
y
Professor, Department of Gastroenterology Professor and Head, Diagnostic Nuclear

Medicine Division, Department of Nuclear Rahul Mahajan MD
Medicine, All India Institute of Medical Department of Dermatology
Venereology and Leprology, Post-graduate
Ja

Abraham Koshy MD DM Institute of Medical Education and Research
Director, Division of Hepatology Soumitra Kumar Chandigarh, India
Lakeshore Hospital and Research Centre Ltd Professor, Division of Cardiology, Department
of Medicine, Vivekananda Institute of Medical Sandeep Mahajan MD DM
Maradu, Kochi, Kerala, India
Sciences, Kolkata, West Bengal, India Professor
Prakash Kothari MD PhD Department of Nephrology, All India Institute
Professor and Head, Department of Sexual Uma Kumar MD of Medical Sciences, New Delhi, India
Medicine, Seth GS Medical College and Professor, Department of Medicine
Head, Clinical Immunology and Rheumatology M Mahapatra MD
KEM Hospital, Mumbai, Maharashtra, India
All India Institute of Medical Sciences Associate Professor, Department of
Shyam S Kothari MD DM
New Delhi, India Haematology, All India Institute of Medical
Professor, Department of Cardiology Sciences, New Delhi, India
All India Institute of Medical Sciences Vinod Kumar MD
New Delhi, India Emeritus Professor, Department of Medicine PK Maheshwari MD DM (Neurology)
St Stephen’s Hospital, New Delhi, India Professor and Head
JS Kulkarni MD (Medicine) Department of Neurology, Post-graduate
Associate Professor, Department of Medicine Debal Laha MD DM Department of Medicine
Maharashtra Institute of Medical Education Neurologist, Lakhotia Medical Centre Sarojini Naidu Medical College xvii
and Research, Pune, Maharashtra, India Howrah, West Bengal, India and Hospital, Agra, Uttar Pradesh, India
API _ Prelims _ Vol-1 for (TRADE).indd xvii 29-01-2015 14:22:08

Sunita Maheshwari ABP ABPC (USA) Aijaz H Mansoor DM (Cardiology) Prachi Mehndiratta MD
Senior Paediatric Cardiologist Medical Officer, SMS Medical College Vascular Neurology Fellow, University of
Telerad RxDx, Bengaluru, Karnataka, India Jaipur, Rajasthan, India Virginia, Charlottesville, VA, USA
M Maiya FRCP (Lond) FRCP (Edin) FRCP (Glasg) BG Mantur Narinder K Mehra
FICP (Ind) Professor and Head, Department of Professor and Head, Department of Transplant
Ex-Professor of Medicine Microbiology, Belgaum Institute of Medical Immunology and Immunogenetics, All India
Karnataka Medical Service Sciences, Belgaum, Karnataka, India Institute of Medical Sciences, New Delhi, India
Consulting Physician, Maiya Multispeciality
Yogesh S Marfatia Vibhu Mendiratta
MD (Dermatology and VD)

Hospital, Bengaluru, Karnataka, India
Head and Professor, Department of Skin and Professor, Department of Dermatology
Govind K Makharia MD DM DNB Venereal Diseases, SSG Hospital and Medical Venereology and Leprology, Lady Hardinge
Professor, Department of Gastroenterology College, Vadodara, Gujarat, India Medical College, New Delhi, India
and Human Nutrition, All India Institute of
Medical Sciences, New Delhi, India
Shubha Laxmi Margekar MD Vandana Midha MD
Assistant Professor, Department of Medicine Professor, Department of Medicine
M Malathi MD Lady Hardinge Medical College and Dayanand Medical College and Hospital
Assistant Professor, Dermatology and STD Associated Hospitals, New Delhi, India Ludhiana, Punjab, India
rs
Department, Jawaharlal Institute of Post-
Neelam Marwaha MD FAMS Aditya Prakash Misra MD
graduate Medical Education and Research
Professor and Head Head, Department of Medicine, Fortis Jessa
Puducherry, India
Department of Transfusion Medicine Ram Hospital, Karol Bagh, New Delhi, India
AN Malaviya MD FRCP (Lond) ACR ‘Master’ FACP Post-graduate Institute of Medical Education
he
FICP FAMS FNASc and Research, Chandigarh, India Anoop Misra MD
Consultant Rheumatologist, ‘A and R Clinic’ Fortis-C-DOC Centre of Excellence
Shariq Rashid Masoodi MD (Medicine) for Diabetes, Metabolic Diseases and
Visiting Senior Consultant Rheumatologist DM (Endocrinology)
Indian Spinal Injuries Centre Super-speciality Endocrinology, Centre of Internal Medicine
Additional Professor and Head of Unit (CIM), Fortis Hospital, Vasant Kunj
Hospital, New Delhi, India Department of Endocrinology, Sher-i-Kashmir New Delhi, India
Hemant Malhotra MD FRCP (London) Institute of Medical Sciences
ot
MNAMS FICP Srinagar, Jammu and Kashmir, India Ramnath Misra MD FRCP
Senior Professor of Medicine and Head Dean, Professor and Head, Clinical
Dilip Mathai MD PhD FRCP (Lond) FICP Immunology, Sanjay Gandhi Post-graduate
Division of Medical Oncology Dean, Apollo Institute of Medical Sciences and
Sawai Man Singh Medical College Hospital Institute of Medical Sciences
Research, Apollo Health City Campus Lucknow, Uttar Pradesh, India
Jaipur, Rajasthan, India
Br
Hyderabad, Telangana, India
Pankaj Malhotra MD FICP UK Misra DM FAMS
Vikram Mathews MD DM
Professor and Head, Department of Neurology
Additional Professor Professor of Clinical Haematology
Department of Internal Medicine Dean, Sanjay Gandhi Post-graduate Institute
Department of Haematology
Post-graduate Institute of Medical Education of Medical Sciences
Christian Medical College and Hospital
and Research, Chandigarh, India Lucknow, Uttar Pradesh, India
Prabhat Singh Malik Ambrish Mithal MD DM
Arvind Mathur MD
e
Assistant Professor, Medical Oncology Chairman, Division of Endocrinology and

Director and Managing Trustee
Dr Bhim Rao Ambedkar Institute of Rotary Diabetes, Medanta—The Medicity
Asian Centre for Medical Education, Research
Cancer Hospital, All India Institute of Medical Gurgaon, Haryana, India
and Innovation
pe
Sciences, New Delhi, India Ex-Principal and Controller, Professor of Amit Mittal MD DM
Sourabh Malviya MD Medicine, Dr Sampurnanand Medical College Assistant Professor
Consultant Rheumatologist, Medanta—The Jodhpur, Rajasthan, India Department of Cardiology
Medicity, Indore, Madhya Pradesh, India Ashwin Mathur MD (Medicine)
GB Pant Hospital and Maulana Azad Medical
Associate Professor, Department of Medicine College, New Delhi, India
RK Mani MD MRCP (UK) FCCP FICCM CEO
Sawai Man Singh Medical College Hospital Asit Mittal MD (Dermatology, Venereology, Leprosy)
y
(Medical Services)
Chairman, Critical Care, Pulmonology and Jaipur, Rajasthan, India Professor
Sleep Medicine, Nayati Group of Hospitals, DLF Rajani Mathur BPharm MSc (Drug Assay) PhD Department of Dermatology
Corporate Park, Gurgaon, Haryana, India RNT Medical College and Hospital
Ja
Assistant Professor
Delhi Institute of Pharmaceutical Sciences and Udaipur, Rajasthan, India
UV Mani PhD FICN
Formerly, Head and Director Research, New Delhi, India BR Mittal MD DRM DNB FICNM FAMS
WHO Collaborating Centre, Department of PS Mathuranath DNB DM (Neurology) Clinical Professor and Head
Foods and Nutrition, MS University of Baroda Additional Professor, Department of Departments of Nuclear Medicine and PET
Vadodara, Gujarat, India Neurology, Sree Chitra Tirunal Institute Post-graduate Institute of Medical Education
for Medical Sciences and Technology and Research, Chandigarh, India
CN Manjunath MD DM
Thiruvananthapuram, Kerala, India
Professor and Head Veena Mittal MD
Department of Cardiology AK Meena MD DM Additional Director (Microbiology) and Head
Director, Sri Jayadeva Institute of Professor, Department of Neurology Zoonosis Division, National Centre for Disease
Cardiovascular Sciences and Research Nizam’s Institute of Medical Sciences Control, New Delhi, India
Bengaluru, Karnataka, India Hyderabad, Telangana, India
Manish Modi MD (Med) DM (Neuro)
Sachin Manocha MD (Pharmacology) Man Mohan Mehndiratta MD DM (Neurology) Assistant Professor
Assistant Professor, Department of FAMS FRCP Department of Neurology
Pharmacology, Vardhman Mahavir Medical Director, Professor and Head, Department of Post-graduate Institute of Medical Education
College and Safdarjung Hospital Neurology, Janakpuri Super-speciality Hospital and Research
xviii New Delhi, India Janakpuri, New Delhi, India Chandigarh, India
API _ Prelims _ Vol-1 for (TRADE).indd xviii 29-01-2015 14:22:08

Alladi Mohan MD (Medicine) FAMS FRCP (Edin) Milind Y Nadkar MD FICP Jyotirmoy Pal MD
FCCP (USA) FICP Professor of Medicine and Chief of Associate Professor, General Medicine
Professor and Head, Department of Medicine Rheumatology, Seth GS Medical College and Institute of Post-graduate Medical Education
Chief, Division of Pulmonary and Critical Care KEM Hospital, Mumbai, Maharashtra, India and Research and Seth Sukhlal Karnani
Medicine, Sri Venkateswara Institute of Medical Memorial Hospital
Sciences, Tirupati, Andhra Pradesh, India D Nagaraja DM (Neuro) DPM (Psych) MAMS
Faculty In-Charge, Geriatric Clinic
Professor
Bishav Mohan Department of Neurology
Professor, Department of Cardiology Ex-Director and Vice Chancellor Pramod Kumar Pal MD
Contributors
Dayanand Medical College and Hospital National Institute of Mental Health and Professor, Department of Neurology
Unit Hero DMC Heart Institute Neurosciences, Bengaluru, Karnataka, India National Institute of Mental Health and
Ludhiana, Punjab, India Neurosciences, Bengaluru, Karnataka, India
Dukhabandhu Naik MD DM (Endocrinology)
E Mohandas MD (Psych) Assistant Professor Aparna Palit MD
Head and Chief Consultant, Department of Christian Medical College Professor, Department of Dermatology
Psychiatry, Sun Hospital and Research Centre Vellore, Tamil Nadu, India Sri BM Patil Medical College
Thrissur, Kerala, India BLDE University, Bijapur, Karnataka, India
Sita Naik MD
rs
KM Mohandas MD DNB Ex-Professor and Head, Department of Ashok Panagariya MD DM (Neurology) FRCP (UK)
Senior Consultant, Department of Digestive Immunology, Sanjay Gandhi Post-graduate Member (State Planning Board), Health,
Diseases, Tata Medical Centre Institute of Medical Sciences Medical Education, Research and Allied Areas
Kolkata, West Bengal, India Lucknow, Uttar Pradesh, India Professor Emeritus (Neurology)
he
Sawai Man Singh Medical College, Jaipur
Prasanta Raghab Mohapatra MD MAMS FICP Maj Gen Velu Nair AVSM VSM
Honorary Neurologist, Armed Forces of India
Professor and Head, Department of Pulmonary Senior Consultant in Clinical Haematology and
Medicine, Certified Medical Oncologist Bone Marrow Transplant
All India Institute of Medical Sciences Dean and Dy- Commandant, Armed Forces Anjana Pandey MD (Gen Medicine)
Bhubaneswar, Odisha, India Medical College, Pune, Maharashtra, Inidia Assistant Professor, Post-graduate Department
of Medicine, Sarojini Naidu Medical College
V Pratap Mouli MD DM Ranjith Nair MD DM
Consultant Gastroenterology, Anjani SS
Hospital (VGS Hospitals)
Guntur, Andhra Pradesh, India
Sukumar Mukherjee MD FRCP FRCPE FICP FSMF
Praveen Namboodiri
Consultant
ot
Army Hospital (Research and Referral)
Delhi Cantt, New Delhi, India
MD DM (Nephrology)
and Hospital, Agra, Uttar Pradesh, India
Ramesh Balwant Pandit MD
Honorary Physician and Cardiologist, MGM
Hospital and Fortis Hiranandani Hospital
Vashi, Navi Mumbai, Maharashtra, India
Br
FICN FISE FIMSA FIAMS Department of Nephrology
Ex-Professor and Head of Medicine Sankar’s Institute of Medical Sciences Sanjay Pandit MD (Medicine)
Medical College, Kolkata Kollam, Kerala, India Assistant Professor, Department of Medicine
Consultant Physician Maulana Azad Medical College and Associated
R Narasimhan MD FRCP (UK) FCCP (USA)
Calcutta Medical Research Institute Hospitals, New Delhi, India
Pulmonologist, Apollo Hospitals
GD Hospital and Diabetes Institute
Chennai, Tamil Nadu, India Ghan Shyam Pangtey MD
Kothari Medical Centre
Associate Professor, Department of Medicine
e
G Narsimulu MD FICP FIACM

Lady Hardinge Medical College and Associated
Senior Consultant Rheumatologist
Rita Mulherkar PhD FNASc Hospitals, New Delhi, India
Yashoda Hospital
Professor
Ex-Professor and Head Department of Gopi Krishna Panicker
pe
MD
Advanced Centre for Treatment, Research and
Rheumatology, Nizam’s Institute of Medical Quintiles Cardiac Safety Services
Education in Cancer, Tata Memorial Centre
Sciences, Hyderabad, Telangana, India Mumbai, Maharashtra, India
Kharghar, Navi Mumbai, Maharashtra, India
AS Narula MD DM FACP Manotosh Panja MD DM FICP FACC
Akshay Munjal MDS
Additional Director General Ex-Professor and Director (Cardiology)
Reader in Periodontics, SGT Dental College
Armed Forces Medical Services Head of the Department, Institute of Post-
Professor, Department of Medicine graduate Medical Education and Research
y
Yash Pal Munjal MD FICP MAMS FIAMS FACP Army College of Medical Sciences Director, Interventional Cardiology, Belle Vue
FIACMS FRCP (Edin) New Delhi, India Clinic Kolkata, West Bengal, India
Ja
Medical Director and Hon Senior Consultant

Prashant Nasa MD FNB (Critical Care) Neeraj Parakh MD DM
Diabetes and Life Style Disease Centre
Specialist, Critical Care Medicine Assistant Professor, Department of Cardiology
Banarsidas Chandiwala Institute of Medical
NMC Speciality Hospital Dubai, UAE All India Institute of Medical Sciences
Sciences, Kalkaji, New Delhi
New Delhi, India
Past President of Association of Physicians of Aruna Nigam MS (Obs & Gynae)
India, Past Dean of Indian College of Physicians, Associate Professor Rajiv Parakh MS (Surgery) FRCS
Hon Professor of Indian College of Family Department of Obstetrics and Gynaecology Division of Peripheral Vascular and
Physician, New Delhi, India Hamdard Institute of Medical Sciences and Endovascular Sciences, Medanta—The
Research, Jamia Hamdard University Medicity, Gurgaon, Haryana, India
BS Rama Murthy MD DMRD DNB
New Delhi, India
Consultant Radiologist Satish Kumar Parashar MD FACC FCSI
Srinivasa Ultrasound Scanning Centre Swapan Kumar Niyogi Senior Consultant Cardiologist and Director
Bengaluru, Karnataka, India Deputy Director Non-invasive Cardiac Laboratory
National Institute of Cholera and Enteric Diseases Metro Hospitals and Heart Institute
A Muruganathan MD FRCP (Glasg) FRCP (London)
Kolkata, West Bengal, India New Delhi, India
FACP (USA) FPCP (Philippines) FICP
Adjunct Professor, The Tamilnadu Dr MGR Nagaraja Rao Padaki MD DM Vibhor Pardasani DM (Neurology)
Medical University, Vice President, Indian Red Chief of Hepatology Consultant Neurologist and Epileptologist
Cross Society, Tamil Nadu State Branch Asian Institute of Gastroenterology Bombay Hospital Institute of Medical Sciences xix
Chairman, AG Hospital, Tirupur, Tamil Nadu, India Hyderabad, Telangana, India Mumbai, Maharashtra, India
API _ Prelims _ Vol-1 for (TRADE).indd xix 29-01-2015 14:22:08

Falguni S Parikh MD DNB MNAMS FICP Shruti Prem MD DM Prema Ramachandran MD MNAMS
Consultant Internal Medicine, Kokilaben Consultant Haematology, Department of Director, Nutrition Foundation of India
Dhirubhai Ambani, Hospital, Mumbai Medical Oncology, Regional Cancer Centre New Delhi, India
Ex-Associate Professor, TN Medical Thiruvananthapuram, Kerala, India
College and BYL Nair Charitable Raja Ramachandran MD DM (Nephrology)
Hospital, Mumbai, Maharashtra, India Susanne A Pulimood MD Assistant Professor, Department of
Department of Dermatology, Venereology and Nephrology, Post-graduate Institute of
PM Parikh MD DNB FICP PhD ECMO CPI MB Leprosy, Christian Medical College Medical Education and Research
Department of Medical Oncology and Vellore, Tamil Nadu, India Chandigarh, India
Haematology, BSES Hospital

Mumbai, Maharashtra, India Pankaj Puri MD (Medicine) DM (Gastroenterology) Shaji V Ramachandran MSc PhD
Professor and Head, Department of Professor, Department of Haematology
Kirti C Patel MD (Mumbai) FRCP (UK) Gastroenterology and Hepatobiliary Unit Christian Medical College and Hospital
Honorary Physician Army Hospital Research and Referral Vellore, Tamil Nadu, India
Bharatiya Arogya Nidhi Hospital, and BSES New Delhi, India
Hospital, Mumbai, Maharashtra, India BS Ramakrishna MD DM PhD FAMS FNA
Ratna Dua Puri MD DM Senior Consultant, Gastroenterology
Lekha Adik Pathak DM (Cardiology) MD (Med) SRM Institutes for Medical Sciences
rs
Professor, Sir Ganga Ram Institute of Post-
FRCS FCCP (USA) FICP FICC FICE FACP (USA) graduate Medical Education and Research Chennai, Tamil Nadu, India
Executive President, Indian College of Senior Consultant, Centre of Medical Genetics V Ramasubramanian MD FRCP (Glas)
Interventional Cardiology Sir Ganga Ram Hospital, New Delhi, India DTM & H (Lon)
D Raghunadharao MD DM Senior Consultant, Department of Infectious
he
Binoy J Paul MD PhD DNB Professor, Department of Medical Oncology Diseases, HIV and Tropical Medicine, Apollo
Professor of Medicine and Chief of Nizam’s Institute of Medical Sciences Hospitals, Chennai, Tamil Nadu, India
Rheumatology, Kunhitharuvai Memorial Hyderabad, Telangana, India V Ramesh MD
Charitable Trust Medical College
M Raghunath MSc PhD Professor and Head, Department of
Kozhikode, Kerala, India
Scientist F, National Institute of Nutrition Dermatology and Apex Regional STD Centre
Apoorva Pauranik MD DM Hyderabad, Telangana, India Vardhman Mahavir Medical College and
ot
Professor, Department of Neurology Safdarjung Hospital, New Delhi, India
Mahatma Gandhi Memorial Medical College Abhay Narain Rai MD FRCP FICP
Ex-Professor and Head Surinder S Rana MD (Internal Medicine)
and Maharaja Yeshwantrao Hospital DM (Gastroenterology) MAMS FASGE
Indore, Madhya Pradesh, India Department of Medicine
Assistant Professor
Principal, Anugrah Narayan Magadh Medical
Br
K Pavithran MD DM Department of Gastroenterology
College, Gaya, Bihar, India
Professor, Department of Medical Oncology Post-graduate Institute of Medical Education
Amrita Institute of Medical Sciences and Madhukar Rai MD and Research, Chandigarh, India
Research Centre, Cochin, Kerala, India Professor, Department of Medicine
Bharath Rangarajan MD DM ECMO
Institute of Medical Sciences, Banaras Hindu
Shubha R Phadke MD (Paediatrics) Medical Oncologist, Department of Medical
University, Varanasi, Uttar Pradesh, India
DM (Medical genetics) Oncology, Kiran Mazumdar Shaw Cancer
Professor, Department of Medical Genetics Nishant Raizada MD Centre, Bengaluru, Karnataka, India
e
Sanjay Gandhi Post-graduate Institute of Department of Endocrinology and

M Hanumantha Rao
Medical Sciences Metabolism, All India Institute of Medical Senior Professor and Head, Department of
Lucknow, Uttar Pradesh, India Sciences, New Delhi, India Anaesthesiology and Critical Care and Pain
pe
S Prabhakar MD DM FAMS FIAN Senthil Rajappa MD DNB DM Medicine, Sri Venkateswara Institute of
Professor and Head Senior Consultant, Medical Oncology Medical Sciences, Tirupati, Andhra Pradesh, India
Department of Neurology Basavatarakam Indo-American Cancer Murlidhar S Rao MD FACP FCCP FICP FICC FCSI
Post-graduate Institute of Medical Education Hospital and Research Institute Former President, API, RSSDI and HIS
and Research, Chandigarh, India Hyderabad, Telangana, India Ex-Professor and Head of Medical College
Gulbarga, Karnataka, India
y
MP Ram Prabhu MD Gopalakrishna Rajesh MD DNB (Gastro)

Department of Medical Oncology Associate Professor, Department of TS Sathyanarayana Rao MD
Dr Bhim Rao Ambedkar Institute, Rotary Gastroenterology, Amrita Institute of Medical Professor and Head, Department of
Ja
Cancer Hospital, All India Institute of Medical Sciences, Kochi, Kerala, India Psychiatry, Jagadguru Sri Shivarathreeswara
Sciences, New Delhi, India Medical College Hospital, Jagadguru Sri
Rajesh Rajput MD DM (Endocrinology)
Anupam Prakash MD (Gen Medicine) FICP FIACM FIMSA Shivarathreeswara University
FICP MNAMS PDCC (Hospital Management) Senior Professor and Head Mysuru, Karnataka, India
PDCDM (Dialysis Medicine) Department of Endocrinology URK Rao MD (Medicine)
Professor, Department of Medicine Post-graduate Institute of Medical Sciences Rheumatologist, Sri Deepti Rheumatology
Lady Hardinge Medical College and Rohtak, Haryana, India Centre, Hyderabad, Telangana, India
Associated Hospitals, New Delhi, India
Sree B Raju MD DM (AIIMS) DNB FISN FICP FIACM GK Rath MD
Jai Prakash M Pharm PhD Additional Professor and Head Professor, Department of Radiotherapy
Principal Scientific Officer Department of Nephrology Chief, Dr Bhim Rao Ambedkar Institute of
Indian Pharmacopoeia Commission Nizam’s Institute of Medical Sciences Rotary Cancer Hospital, All India Institute of
Ghaziabad, Uttar Pradesh, India Hyderabad, Telangana, India Medical Sciences, New Delhi, India
Prabhu Prakash A Ramachandran MD DSc V Ravi MD FAMS FASc
Associate Professor Chairman, Dr A Ramachandran’s Diabetes Professor and Head, Department of
Department of Microbiology Hospitals, and President Neurovirology, National Institute of Mental
xx Dr Sampurnanand Medical College India Diabetes Research Foundation Health and Neurosciences
Jodhpur, Rajasthan, India Chennai, Tamil Nadu, India Bengaluru, Karnataka, India
API _ Prelims _ Vol-1 for (TRADE).indd xx 29-01-2015 14:22:08

K Ravishankar MD Banshi Saboo MD FICP FICN Vivek Anand Saraswat MD DM
Consultant In-charge, The Headache and MNAMS (Diabetology) FACE Professor
Migraine Clinic, Jaslok Hospital and Research Consultant Diabetologist, DIACARE Department of Gastroenterology
Centre, Lilavati Hospital and Research Centre Ahmedabad, Gujarat, India Sanjay Gandhi Post-graduate Institute of
Mumbai, Maharashtra, India Medical Sciences, Lucknow, Uttar Pradesh, India
S Sacchidanand MD (Dermatology) DVD DHA
D Raja Reddy FRCS (Edin) FRACS Dermatologist/Cosmetologist Kavitha Saravu MD DNB (Med)
Senior Consultant, Neurosurgeon Sujala Poly Clinic and Lab Additional Professor, Department of Medicine
Apollo Hospitals, Hyderabad Bengaluru, Karnataka, India Kasturba Medical College, Manipal University
Contributors
Emeritus Professor Neurosurgery Manipal, Karnataka, India
Nizam’s Institute of Medical Sciences Bibhuti Saha DTM&H (Cal)
Hyderabad, Telangana, India MD (Tropical Medicine) (Cal) Rajiv Sarin
Professor and Head In-Charge, Cancer Genetics Unit
YC Janardhan Reddy DPM MD Department of Tropical Medicine Director, ACTREC Tata Memorial Centre
Professor Calcutta School of Tropical Medicine Kharghar, Navi Mumbai, Maharashtra, India
Department of Psychiatry Obsessive- Kolkata, West Bengal, India
Compulsive Disorder (OCD) Clinic AS Savitha MD (Dermatology) DVD DHA
BK Sahay Dermatologist/Cosmetologist
rs
National Institute of Mental Health and MD
Neurosciences, Bengaluru, Karnataka, India Consultant Physician and Diabetologist Sujala Poly Clinic and Lab
Hyderabad, Telangana, India Bengaluru, Karnataka, India
BB Rewari MD
Associate Professor, Dr Ram Manohar Lohia Manisha Sahay MD DNB MAMS Anurag Saxena MD (Medicine)
Hospital and Post-graduate Institute of Professor and Head Senior Consultant, Physician, Primus Super-
he
Medical Education and Research Department of Neurology Osmania General speciality Hospital, New Delhi, India
New Delhi, India Hospital and Medical College
P Saxena MD EDIC (Europe) FCCP
Hyderabad, Telangana, India
SNA Rizvi MD FICP FAIID FIMSA FIAMS FISM
Head and Senior Consultant
Senior Honorary Consultant Rakesh K Sahay MD DNB DM (Endo) FICP FACE (Pulmonology, Critical Care and Sleep
Sanjeevan Medical Research Centre, Delhi Professor Medicine)
Department of Endocrinology Saket City Hospital, New Delhi, India
Ex-Director Professor and Head of Medicine
Maulana Azad Medical College and Associated
Hospitals, New Delhi, India
Yasir S Rizvi MD DM
Assistant Professor, Department of
Tapan Kumar Saikia ot
Osmania Medical College and Osmania
General Hospital, Hyderabad, Telangana, India
MD
Head of Medical Oncology and Director of
Pikee Saxena MD FICOG PGCC (Hospital
Management) PGDCR (Clinical Research)
Professor
Department of Obstetrics and Gynaecology
Br
Nephrology, Vardhman Mahavir Medical Research, Prince Aly Khan Hospital, Mazagaon Lady Hardinge Medical College and Smt
College and Safdarjung Hospital Mumbai, Maharashtra, India Sucheta Kriplani Hospital
New Delhi, India New Delhi, India
GS Sainani MD FRCP (Lond) Hon FRACP PhD DSc
Camilla Rodrigues MD FICP (Ind) Renu Saxena MD
Consultant Microbiologist, PD Hinduja Director, General Medicine Department Professor and Head
National Hospital and Medical Research Jaslok Hospital and Research Centre Department of Haematology
Centre, Mumbai, Maharashtra, India Emeritus Professor of Medicine All India Institute of Medical Sciences
e
Grant Medical College and JJ Hospital New Delhi, India

Cecil Ross MD (General Medicine) Mumbai, Maharashtra, India
Professor and Head, Division of Haematology MS Seshadri MD PhD FRCP (Edin)
Consultant Physician and Endocrinologist
pe
St John’s Medical College Rajesh Sainani MD DNB

Bengaluru, Karnataka, India Consultant Gastroenterologist, Jaslok Hospital Honorary Medical Director, Thirumalai Mission
Bhatia Hospital, Raheja Fortis Hospital and Hospital
Ambuj Roy MD DM Jagjeevan Ram Railway Hospital Ex-Professor and Head
Additional Professor Mumbai, Maharashtra, India Department of Endocrinology
Department of Cardiology Diabetes and Metabolism
All India Institute of Medical Sciences R Sajithkumar MD PhD Christian Medical College and Hospital
y
New Delhi, India Chief, Infectious Diseases Vellore, Tamil Nadu, India
Government Medical College Hospital
Mrinal Kanti Roy MD DM FICP Kottayam, Kerala, India V Seshiah MD FRCP DSc (Hony)
Ja
Professor, Department of Medicine Chairman

Calcutta National Medical College Vinay Sakhuja MD DM Dr V Seshiah Diabetes Research Institute and
Kolkata, West Bengal, India Director Dr Balaji Diabetes Care Centre
Nephrology and Transplant Medicine Chennai, Tamil Nadu, India
Rakesh Roy MD (Pharmacology) Max Super-speciality Hospital
In-Charge of Palliative Care Mohali, Punjab, India KK Sethi MD DM FACC FHRS FCSI
Saroj Gupta Cancer Centre and Research Director of Cardiology, Delhi Heart and Lung
Institute, Kolkata, West Bengal, India AM Samuel MD (Paed) DCH FAMS Institute, New Delhi, India
Ex-Director, Bio-Medical Group, Bhabha
Priscilla Rupali MD DTM & H
Atomic Research Centre Ashok Shah MD
Professor, Department of Medicine, Christian Mumbai, Maharashtra, India Professor, Department of Respiratory Medicine
Medical College, Vellore, Tamil Nadu, India Fellow, National Academy of Medical Sciences
Jaspal S Sandhu MS DSM (India), Immediate Past President
M Sabir MD
Professor and Dean, Faculty of Sports The Indian College of Allergy, Asthma and
Professor and Head Medicine and Physiotherapy, Guru Nanak Dev Applied Immunology
Department of Medicine University, Amritsar, Punjab, India
Maharaja Agrasen Medical College, Agroha Bela Shah MD (Dermatology)
Ex-Professor and Head, Respiratory Division Carani B Sanjeevi MD MSc PhD Professor and Head, Department of
Department of Medicine, Sarder Patel Medical Professor, Department of Medicine Dermatology, BJ Medical College and Civil
xxi
College, Bikaner, Rajasthan, India Karolinska Institute, Stockholm, Sweden Hospital, Ahmedabad, Gujarat, India
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Hardik Shah MD (Med) DNB (Nephro) Health and Neurosciences RK Singal MD FRCP FICP FACP
Honorary Assistant Professor Bengaluru, Karnataka, India Chairman, Department of Medicine
Department of Nephrology, Bombay Hospital Dr BL Kapur Memorial Hospital
Institute of Medical Sciences
MP Sharma MD DM FAMS FACG
New Delhi, India
Head, Department of Gastroenterology
and Member Advisory Board AK Singh MS MCh (Neurosurgery)
Nalini S Shah DM Rockland Hospital, New Delhi, India Executive Director
Professor and Head, Department of Department of Neurosciences
Endocrinology, Seth GS Medical College and Praveen Kumar Sharma MD DM
Fortis Hospital Noida and Vasant Kunj
Department of Neurology
KEM Hospital, Mumbai, Maharashtra, India New Delhi, India

King George’s Medical University
Pankaj Manubhai Shah MD Lucknow, Uttar Pradesh, India Daljit Singh
Vice President, Gujarat Cancer Society Professor, Department of Neurosurgery
Special Advisor to Chairman, GCRI Raj Kumar Sharma FISN FASN FAMS
Maulana Azad Medical College and GB Pant
Professor Emeritus, Medical Oncology Trustee- Professor and Head, Department of
Hospital, New Delhi, India
Sadvichar Parivar, Ahmedabad, Gujarat, India Nephrology, Sanjay Gandhi Post-graduate
Institute of Medical Sciences Narinder Pal Singh MD MBA FRCP (Edin) FAMS
Siddharth N Shah MD FICP FACP (Hon) Lucknow, Uttar Pradesh, India FISN FICP
rs
FRCP (Edin) Chairman, Medicine and Allied Specialities
Post-graduate Teacher in Diabetes, University Raju Sharma MD MNAMS
Senior Consultant in Nephrology and
of Mumbai Professor, All India Institute of Medical
Medicine, Pushpanjali Crosslay Hospital,
Consulting Physician and Diabetologist Sciences, New Delhi, India
Ghaziabad, Uttar Pradesh, India
SL Raheja Hospital and All India Institute of
he
Sangeeta Sharma MD (Pharmacology) MBA Navneet Singh MD DM
Diabetes, Saifee Hospital, Bhatia Hospital (Health Care Administration)
Sir Hurkisondas Nurrotumdas Hospital Assistant Professor
Visiting Consultant, Central Railway and Department of Pulmonary Medicine
Neuropsychopharmacology
Western Railway Hospitals Post-graduate Institute of Medical Education
Institute of Human Behaviour and Allied
Mumbai, Maharashtra, India and Research, Chandigarh, India
Sandeep Singh MD DM
ot
Viral N Shah Sanjiv Sharma MD (Radiology)
Professor and Head Additional Professor, Department of
Professor and Head, Department of Cardiac Cardiology, All India Institute of Medical
Department of Endocrinology Radiology, All India Institute of Medical
Post-graduate Institute of Medical Education Sciences, New Delhi, India
and Research, Chandigarh, India SK Singh MD DM (Endocrinology)
Br
Shefali Khanna Sharma MD MAMS
Shalimar DM Assistant Professor, Department of Internal
Assistant Professor Endocrinology and Metabolism, Institute of
Medicine, Unit of Rheumatology, Post- Medical Sciences, Banaras Hindu University
Department of Gastroenterology graduate Institute of Medical Education and
All India Institute of Medical Sciences Varanasi, Uttar Pradesh, India
Research, Chandigarh, India
New Delhi, India Sumit Singh MD DM (Neurology)
Surendra K Sharma MD PhD Head, Department of Neuromuscular
PS Shankar MD FRCP (Lond) FAMS DSc (hcGul) DSc
Professor and Head, Department of Medicine
(hcNTR) DSc (hcRGUHS) Disorders, Institute of Neurosciences
e
All India Institute of Medical Sciences Medanta—The Medicity

Emeritus Professor New Delhi, India
Department of Medicine Gurgaon, Haryana, India
Rajiv Gandhi University of Health Sciences Shweta Shenoy PhD Surjit Singh
pe
MD DCH (Lon) FRCP (Lon) FRCPCH

Gulbarga, Karnataka, India Associate Professor, Faculty of Sports Medicine (Lon) FAMS
and Physiotherapy, Guru Nanak Dev University Professor, Department of Paediatrics and
SK Shankar MD FAMS FNASc FICP
Amritsar, Punjab, India
Emeritus Professor, Department of In-Charge, Paediatric Allergy Immunology Unit
Neuropathology and Principal A Shobhana MD Advanced Paediatrics Centre, Post-graduate
Co-ordinator, Human Brain Tissue Repository Consultant, Critical Care and Stroke Institute of Medical Education and Research
(Human Brain Bank), Neurobiology Research Institute of Neurosciences, Kolkata Chandigarh, India
y
Centre, National Institute of Mental Health and Secretary, Stroke Foundation of Bengal Virendra Singh
Neurosciences, Bengaluru, Karnataka, India West Bengal, India Professor of Medicine
Ja
G Shanmugasundar MD DM Garima Shukla Head, Division of Allergy and Pulmonary

Endocrinologist, KM Speciality Hospital Associate Professor, Department of Neurology Medicine
Chennai, Tamil Nadu, India Neurosciences Centre, All India Institute of Sawai Man Singh Medical College
Aman Sharma MD MAMS FRCP (London) Medical Sciences, New Delhi, India
Assistant Professor, Rheumatology and HIV Sattik Siddhanta MD
Vivek Pal Singh MD
Wing, Department of Internal Medicine Associate Consultant, Department of Medicine
Assistant Professor
Post-graduate Institute of Medical Education Dr BL Kapur Memorial Hospital
General Medicine
and Research, Chandigarh, India New Delhi, India
Institute of Post-graduate Medical Education
Atul Sharma MD DM and Research and Seth Sukhlal Karnani Yudh Dev Singh MD (Medicine) FIACM DIT
Additional Professor Memorial Hospital Professor, Department of Internal Medicine
Department of Medical Oncology, Dr Bhim Faculty Member, Geriatric Clinic Smt Kashibai Navale Medical College and
Rao Ambedkar Institute of Rotary Cancer Kolkata, West Bengal, India General Hospital, Pune, Maharashtra, India
Hospital, All India Institute of Medical Sciences
Mohammad Asim Siddiqui MD (Gen Med) BS Singhal MD FRCP (London and Edinburgh)
New Delhi, India
MRCP (UK) FAMS
Manoj K Sharma PhD Senior Consultant, Apollo Centre for Obesity Director of Neurology, Bombay Hospital
xxii Associate Professor, Department of Clinical Diabetes and Endocrinology, Indraprastha Institute of Medical Sciences
Psychology, National Institute of Mental Apollo Hospital, New Delhi, India Mumbai, Maharashtra, India
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Rajiv Singla MD DNB MNAMS DKS Subrahmanyam MD Nikhil Tandon MD PhD (Cantab)
Department of Medicine, Maulana Azad Professor, Department of Medicine Professor and Head, Department of
Medical College, New Delhi, India Jawaharlal Institute of Post-graduate Medical Endocrinology and Metabolism
Education and Research, Puducherry, India All India Institute of Medical Sciences
Sumeet Singla MD DNB MNAMS MIRA
New Delhi, India
Assistant Professor, Department of Medicine AP Sugunan
Maulana Azad Medical College and Associated Scientist ‘E’, Regional Medical Research Centre PN Tandon MD FRCS DSc (hc) FAMS FNASc FASC
Lok Nayak Hospital, New Delhi, India Port Blair, Andaman and Nicobar Islands, India FTWAS
Emeritus Professor, Department of
Sanjeev Sinha
Contributors
MD S Sukumaran MD (Med) MSc (International Health Neurosurgery, All India Institute of Medical
Additional Professor Management)
Department of Medicine Assistant Professor, KJ Somaiya Medical
All India Institute of Medical Sciences College and Hospital Rakesh Tandon MD PhD FRCP (Edin) FAMS FICP
New Delhi, India Mumbai, Maharashtra, India FAGA
Head, Department of Gastroenterology
Sanjib Sinha MD DM TK Suma MD DNB Medical Director and Head, Pushpawati
Additional Professor, Department of Professor, Department of Medicine Singhania Research Institute for Liver
Neurology, National Institute of Mental Medical Superintendent, Government
rs
Renal and Digestive Diseases
Health and Neurosciences Tirumala Devaswom Medical College New Delhi, India
Bengaluru, Karnataka, India Kerala, India
Kamlesh Tewary MD FICP FIAMS
Pradyot Sinhamahapatra Vivek Suman MD Professor and Head
Associate Professor (Rheumatology) Assistant Professor Department of Medicine
he
Department of Medicine, North Bengal Department of Medicine Sri Krishna Medical College
Medical College, Darjeeling, West Bengal, India Lady Hardinge Medical College and Muzaffarpur, Bihar, India
C Snehalatha MSc DSc
Associated Hospitals, New Delhi, India
Ashish K Thakur MD DM FRCP FESC FICP FRSM
Director Jamshed D Sunavala MD FCCP (USA) FICP FISE Consultant Cardiologist and Honorary Senior
Research, India Diabetes Research Foundation Director, Department of Critical Care Medicine Lecturer, The Mid Yorkshire NHS Trust and
Egmore, Chennai, Tamil Nadu, India Jaslok Hospital and Research Centre
Rumneek Sodhi
Division of Peripheral Vascular and
Endovascular Sciences
Medanta—The Medicity
A Shyam Sundar
ot
MD DNB
Assistant Professor, Department of Psychiatry
National Institute of Mental Health and
University of Leeds Medical School, UK
BB Thakur MD FICP FIAMS FIACM FISPD
Consultant Physician and Cardio-diabetologist
Muzaffarpur, Bihar, India
Br
Gurgaon, Haryana, India Neurosciences, Bengaluru, Karnataka, India Smita Thakur MRCGP (UK)
General Practitioner, United Kingdom
Rajeev Soman MD Shyam Sundar MD FRCP FAMS FNA FSc FNASc
Consultant Physician, PD Hinduja Hospital Professor of Medicine DM Thappa MD DHA FAMS FIMSA
Mumbai, Maharashtra, India Institute of Medical Sciences Professor, Dermatology and STD Department
Banaras Hindu University, Varanasi Jawaharlal Institute of Post-graduate Medical
Ajit Sood MD (Medicine) DM (Gastro) Education and Research, Puducherry, India
Professor and Head Uttar Pradesh, India
e
Department of Gastroenterology Vikas Suri MD

R Thara MD
Dayanand Medical College and Hospital Assistant Professor, Department of Internal Director, Schizophrenia Research Foundation
Ludhiana, Punjab, India Medicine, Post-graduate Institute of Medical (SCARF), Chennai, Tamil Nadu, India
pe
Rita Sood MD MMEd Education and Research, Chandigarh, India Nihal Thomas MD MNAMS DNB (Endo) FRACP
Professor, Department of Medicine Rupjyoti Talukdar MD
(Endo) FRCP (Edin) FRCP (Glas)
All India Institute of Medical Sciences Professor and Head, Department of
Clinical Pancreatologist and
New Delhi, India Endocrinology, Christian Medical College
Gastroenterologist, Asian Institute of
D Sreeramulu PhD Gastroenterology, Clinician Scientist
Endocrinology and Metabolism Division (Wellcome-DBT Fellow), Asian Healthcare Sanjeev V Thomas MD DM FANA
y
National Institute of Nutrition Foundation, Hyderabad, Telangana, India Professor, Department of Neurology
Hyderabad, Telangana, India Sree Chitra Tirunal Institute for Medical
KK Talwar MD DM (Cardiology)
Sciences and Technology
Ja
GR Sridhar MD DM FRCP (Glasgow) FAMS Chairman, Department of Cardiology Max Thiruvananthapuram, Kerala, India
Director, Endocrine and Diabetes Centre Healthcare Institute Ltd, New Delhi
Vishakhapatnam Ex-Chairman, Board of Governors Medical Anil Kumar Tripathi
Editor in Chief, International Journal of Council of India, New Delhi, India Vice Chairman and Head
Diabetes in Developing Countries Department of Clinical Haematology and
AB Taly MD DM Oncology Chhatrapati Sahu Ji Maharaj
Shiva Prakash Srinivasan MD ABPN Professor Medical University
Consultant Psychiatrist Department of Neurology, National Institute Lucknow, Uttar Pradesh, India
Schizophrenia Research Foundation (SCARF) of Mental Health and Neurosciences
Chennai, Tamil Nadu, India Bengaluru, Karnataka, India CD Tripathi MD (Pharmacology)
Director, Professor and Head
MV Padma Srivastava MD DM FAMS Shruti M Tandan MD FNB (Critical Care) Department of Pharmacology
Professor, Department of Neurology Senior Intensivist, Department of Critical Care Vice Principal, Vardhaman Mahavir Medical
All India Institute of Medical Sciences Medicine, Jaslok Hospital College and Safdarjung Hospital
New Delhi, India Mumbai, Maharashtra, India New Delhi, India
Sushma Srivastava PhD PDCR Abhinav Tandon MD Pankaj Tyagi MD DM (Gastroenterology)
Research Scientist, Delhi Institute of Lecturer, Department of Psychiatry Consultant Gastroenterologist, Department
Pharmaceutical Sciences and Research Maharani Laxmi Bai Medical College of Gastroenterology, Sir Ganga Ram Hospital xxiii
New Delhi, India Jhansi, Uttar Pradesh, India New Delhi, India
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Sanjay Tyagi MD DM FACC FCSI FAPI FAMS B Vengamma DM (Neuro) Jyotsna VP DM (Endocrinology)
Director, GB Pant Institute of Post-graduate Director, Professor and Head Associate Professor
Medical Education and Research Department of Neurology Department of Endocrinology and
Director, Professor and Head, Department of Sri Venkateswara Institute of Medical Sciences Metabolism
Cardiology, Maulana Azad Medical College Tirupati, Andhra Pradesh, India All India Institute of Medical Sciences
New Delhi, India New Delhi, India
Sundaram Venkatraman MD DM (Neurology)
Seema Tyagi FICA FICP FIAN Jyoti Wadhwa
Professor, Department of Haematology Consultant Physician and Neurologist Associate Professor, Department of Medicine
All India Institute of Medical Sciences Mata Chanan Devi Hospital, New Delhi, India Jawaharlal Institute of Post-graduate
New Delhi, India Medical Education and Research
SK Verma MD FICP FIACM Puducherry, India
Vrajesh Udani MD Professor, Department of Medicine, HIHT
Consultant, Child Neurology and Epilepsy University and In-Charge, Medical Oncology RS Wadia MD FIAN FICP
PD Hinduja National Hospital and Division, Cancer Research Institute Director Professor, Department of Neurology
Medical Research Centre Dehradun, Uttarakhand, India Ruby Hall Clinic Pune, Maharashtra, India
UL Wagholikar
rs
JC Vij MD DM (Gastroenterology)
Rajesh Upadhyay MD MRCP (UK) FRCP Head and Director Consultant Histopathologist
(Glasgow) FICP Centre for Digestive and Liver Diseases Pune, Maharashtra, India
Senior Consultant and Head BLK Super-speciality Hospital
Department of Gastroenterology and Anupam Wakhlu MD DM
Max Super-speciality Hospital Associate Professor, Department of
Hepatology, Max Super-speciality Hospital
he
Saket, New Delhi, India Rheumatology, King George’s Medical
Shalimar Bagh, New Delhi, India
VK Vijayan MD PhD DSc FAMS University, Lucknow, Uttar Pradesh, India
Muktha V MD (General Medicine)
Advisor to Director General, Indian Council of
Assistant Professor Gurpreet Singh Wander MD (Medicine)
Medical Research, Bhopal Memorial Hospital DM (Cardiology)
Department of Medicine, Jawaharlal Institute
and Research Centre, National Institute for Professor and Head
of Post-graduate Medical Education and
Research in Environmental Health, Bhopal Department of Cardiology
Research, Puducherry, India
ot
Ex-Director Vallabhbhai Patel Chest Institute Dayanand Medical College and Hospital
Rajmohan V MD University of Delhi, New Delhi, India Unit Hero DMC Heart Institute
Associate Professor Ludhiana, Punjab, India
Department of Psychiatry Shanthi Vijayaragavan MD DM
Muslim Educational Society Medical College Professor and Head Naveet Wig MD
Br
Kerala, India Department of Medical Gastroenterology Professor
Sri Ramachandra Medical College Department of Medicine, All India Institute of
Sameer Vankar Sri Ramachandra University Medical Sciences, New Delhi, India
Department of Emergency Medicine Chennai, Tamil Nadu, India
JPN Apex Trauma Centre, All India Institute of Pushpa Yadav MD
Medical Sciences, New Delhi, India Auro Viswabandya MD DM Senior Consultant, Internal Medicine
Professor Max Hospital, Pitampura, New Delhi, India
PP Varma SM VSM MD DNB (Med) DM MNAMS Fellowship in Malignant Haematology and
e
(Nephro) FACP FICP FISN Stem Cell Transplantation ME Yeolekar MD MNAMS (Med) FICP
Dy Chief Integrated Defence Staff (Medical) (Toronto, Canada) Professor
President Elect, Indian Society of Nephrology Department of Clinical Haematology, Christian Department of Internal Medicine
Secretary, Indian Society of Nephrology KJ Somaiya Medical College and Hospital
pe
Medical College Vellore, Tamil Nadu, India

(North Zone), New Delhi, India Mumbai, Maharashtra, India
Vijay Viswanathan MD PhD FRCP (London) FICP
Subhash Varma MD FICP Head and Chief Diabetologist Sanjay Zachariah MD (Medicine)
Professor and Head, Department of Internal MV Hospital for Diabetes Assistant Professor
Medicine, Post-graduate Institute of Medical Chennai, Tamil Nadu, India Department of Medicine
Education and Research, Chandigarh, India Sree Uthradom Thirunal Academy of
R Kasi Visweswaran MD DM (Nephrology) Medical Sciences
y
Varsha MSc PhD RD CNIS FRCP (Edin) Thiruvananthapuram, Kerala, India

Consultant, Clinical Nutritionist Professor, Department of Nephrology
Certified Nutrition Injury Specialist Pushpagiri Institute of Medical Sciences Abdul Hamid Zargar DM
Ja
Founder Chair, Indian Institute of Nutritional Kerala, India Member, Medical Council of India
Sciences Ex-Professor and Head
Executive Director, Parvatiben Trikamji Bhatt Amit Vora MD DM DNB Department of Endocrinology, Sher-i-Kashmir
Gujarati Sahayakari Hospital Glenmark Cardiac Centre Institute of Medical Sciences
Chennai, Tamil Nadu, India Mumbai, Maharashtra, India Srinagar, Jammu and Kashmir, India
xxiv
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CONTENTS
Volume 1
Part 1 Introduction
1. The Practice of Medicine 2
rs
Yash Pal Munjal
2. Disease Profile and Epidemiology of Communicable and Non-communicable Diseases in India 11
Jugal Kishore
he
Part 2 Clinical Approach to Key Manifestations
1. Pain: Mechanism and Management 22
PN Kakar
2.
3.
Headache
K Ravishankar
Chest Pain
Sanjay Tyagi and Amit Mittal ot 24
34
Br
4. Acute Abdomen: Non-surgical Causes 40
Sumeet Singla and AK Agarwal
5. Cough 47
Suman Kirti
6. Haemoptysis 52
Randeep Guleria and Jaya Kumar
7. Jaundice 56
e
Aparna Agrawal
8. Clinical Approach to Upper Gastrointestinal Bleeding 62
pe
JC Vij
9. Approach to Patient with Lower Gastrointestinal Bleeding 65
Surinder S Rana
10. Fever of Unknown Origin 69
Priscilla Rupali
11. Generalised Lymphadenopathy 76
y
SK Verma
12. Dizziness and Vertigo 79
Ja
M Maiya
13. Syncope 83
Pushpa Yadav
14. Coma 87
B Vengamma
15. Appropriate Ordering of Radiological Investigations 94
Chandan J Das
16. A Clinical Approach to Patients with Ascites 107
Richa Dewan
17. Anasarca: A Clinical Approach 111
Yash Pal Munjal
18. Approach to a Patient with Dyspnoea 115
Praloy Chakraborty
19. Clinical Approach to Exanthematous Fever 120
Bibhuti Saha and Manab Kumar Ghosh
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Part 3 Diagnostic Imaging
1. Conventional Radiology 126
Ashu Seith Bhalla and Manisha Jana
2. Ultrasound in Medicine 141
BS Rama Murthy
3. Computed Tomography 147
Bhavin Jankharia and Nishigandha Burute

4. Magnetic Resonance Imaging 156
Raju Sharma and Devasenathipathy Kandasamy
5. Nuclear Imaging 173
BR Mittal
6. Positron Emission Computed Tomography and Positron Emission Magnetic Resonance Imaging 186
rs
Rakesh Kumar and Sellam Karunanithi
Part 4 Clinical Pharmacology
he
1. Drug Discovery and Clinical Evaluation of New Drugs 196
SK Gupta and Sushma Srivastava
2. Introduction to Pharmacology 204
CD Tripathi and Sachin Manocha
ot
3. Rational Use of Medicines 210
Sangeeta Sharma
4. Pharmacokinetic and Pharmacodynamic Basis of Pharmacotherapy 213
Rajani Mathur
Br
5. Pharmacovigilance: Safety Monitoring of Medicines 221
V Kalaiselvan
6. Role of National Formulary of India in National Health Care System 227
Jai Prakash and YK Gupta
e
Part 5 Immunology
pe
1. An Overview of the Immune System 232

Sita Naik
2. General Concepts of Immuno-inflammatory Disorders 242
Ramnath Misra
3. Immunology of Infectious Diseases 246
Sita Naik
y
4. Approach to a Patient with Suspected Primary Immunodeficiency Disorder 249

Surjit Singh
Ja
5. Laboratory Investigations in Immune-mediated Diseases 256

Amita Aggarwal
6. Pharmacological Manipulation of the Immune System 261
Mitali Chatterjee and Alakendu Ghosh
7. Immunology of Organ and Haematopoietic Stem Cell Transplantation 270
Narinder K Mehra and Neeraj Kumar
Part 6 Medical Genetics

1. Introduction to Medical Genetics 278
Late Shyam Swarup Agarwal
2. Mendel and Beyond 282
Ratna Dua Puri
xxvi 3. Clinical, Conventional and Molecular Cytogenetics 290
Ashutosh Halder
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4. Genetic Tests 301
Ashwin Dalal
5. Inborn Errors of Metabolism 306
Madhulika Kabra
6. Molecular Genetics, Human Genome Project and Genomic Medicine 316
Girisha KM
7. Gene Therapy 322
Contents
Rita Mulherkar
8. Genetic Counselling and Prenatal Diagnosis 325
Shubha R Phadke
9. Pharmacogenomics and Personalised Medicine 332
C Adithan
10. Cancer Genetics 335
Rajiv Sarin
rs
Part 7 Critical Care Medicine
he
1. Basic Considerations in Critical Care 342
RK Mani and P Saxena
2. Monitoring of Critically Ill Patients 346
M Hanumantha Rao
3. Fluid and Electrolyte Balance in Health and Disease 352
4.
Sanjay Jain
Acid-Base Disorders
Alladi Mohan and Surendra K Sharma ot 360
Br
5. Enteral and Parenteral Nutrition in Critically Ill Patients 368
Shilpa S Joshi
6. Acute Respiratory Failure 374
Ashit M Bhagwati
7. Sepsis and Acute Respiratory Distress Syndrome 381
Alladi Mohan and Surendra K Sharma
8. Mechanical Ventilation 388
e
Tamilarasu Kadhiravan
9. Non-invasive Positive Pressure Ventilation 395
pe
Dhruva Chaudhry and Rajesh Chawla

10. Hypotension and Shock 404
Piyush Jain and Rene P Eapen
11. Advanced Cardiac Life Support 407
Sanjeev Bhoi and Sameer Vankar
y
12. Brain Death and Support of Brain Dead Organ Donor 417
Rajesh Chawla and Prashant Nasa
Ja
Part 8 Bone Disorders

1. Bone and Mineral Metabolism in Health and Disease 424
Deepak Khandelwal and Ravinder Goswami
2. Investigation and Diagnosis of Bone Disorders 430
Sukumar Mukherjee and Somnath Bhar
3. Rickets and Osteomalacia 437
Bindu Kulshreshtha and Sachin K Jain
4. Osteoporosis 442
SNA Rizvi
5. Developmental Disorders of Bone 448
Rakesh K Sahay
6. Miscellaneous Bone Disorders 451 xxvii
CV Harinarayan
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Part 9 Diabetes Mellitus
1. Epidemiology and Basic Considerations of Diabetes 457
A Ramachandran and C Snehalatha
2. Pathogenesis of Type 1 Diabetes Mellitus 461
Carani B Sanjeevi and Vijay Viswanathan
3. Pathogenesis of Type 2 Diabetes Mellitus 465

Hemraj B Chandalia
4. Clinical Features and Diagnosis of Diabetes Mellitus 470
Anupam Prakash
5. Life-style Modification in the Management of Diabetes 477
Banshi Saboo
6. Oral Antidiabetic Drugs 480
rs
Anil Bhansali and Viral N Shah
7. Insulins 486
Yash Pal Munjal
8. Newer Modalities of Treatment in Type 2 Diabetes Mellitus 492
he
Anil Bhansali and G Shanmugasundar
9. In-Hospital Management of Diabetes Mellitus 497
Dukhabandhu Naik and Nihal Thomas
10. Hypoglycaemia 502
Siddharth N Shah
ot
11. Diabetic Ketoacidosis, Hyperosmolar Hyperglycaemic State and Lactic Acidosis 508
Rajesh Rajput
12. Infections in Diabetes Mellitus 514
Samar Banerjee
Br
13. Macrovascular Complications of Diabetes 519
Murlidhar S Rao
14. Microvascular Diseases: Pathogenesis of Chronic Complications 524
Suman Kirti
15. Diabetes and Kidney Disease 528
Raj Kumar Sharma
e
16. Diabetic Retinopathy 534

Amod Gupta and Reema Bansal
17. Diabetic Neuropathy 539
pe
Manish Modi and Anu Gupta

18. Sexual Dysfunction in Diabetes 542
Shashank R Joshi
19. Management of Diabetic Foot 545
Rumneek Sodhi and Rajiv Parakh
y
20. Diabetes and Pregnancy 550

V Seshiah and V Balaji
21. Diabetes in the Elderly 554
Ja
Jamal Ahmad and Mohammad Asim Siddiqui

22. Prevention of Diabetes Mellitus 557
Yash Pal Munjal
Part 10 Endocrinology
1. Basic Considerations of Endocrinology 566
Ashok Kumar Das
2. Endocrine Disorders: A Clinical Approach 571
MS Seshadri
3. Disorders of Hypothalamus and Pineal Gland 576
Abdul Hamid Zargar and Shariq Rashid Masoodi
xxviii 4. Disorders of Anterior Pituitary 580
RV Jayakumar
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5. Disorders of Posterior Pituitary 589
GR Sridhar
6. Disorders of Thyroid Glands 592
Nikhil Tandon and Nishant Raizada
7. Disorders of Parathyroid Glands 606
Ambrish Mithal and Beena Bansal
8. Disorders of Adrenal Glands 610
Contents
Eesh Bhatia and Vijayalakshmi Bhatia
9. Disorders of Puberty 621
AC Ammini and Jyotsna VP
10. Disorders of Growth and Development 626
Nalini S Shah
11. Disorders of Gonads 634
Shashank R Joshi
rs
12. Endocrine Disorders of Female Gonads 645
Pikee Saxena and Aruna Nigam
he
Part 11 Dermatology
1. Introduction and Principles of Diagnosis in Dermatology 656
Vibhu Mendiratta
2.
3.
Infections and Infestations
Surabhi Dayal
Allergic and Inflammatory Disorders
Sanjeev Handa
ot 665
674
Br
4. Psoriasis and Papulosquamous Disorders 678
Bela Shah
5. Acne and Acneiform Eruptions 685
V Ramesh
6. Bullous Diseases 691
Vibhu Mendiratta
e
7. Pigmentary Disorders 695

Sandipan Dhar
8. Cutaneous Responses to Environmental Factors 702
pe
DM Thappa and M Malathi

9. Skin Manifestations of Systemic Diseases 708
Sunil Dogra and Rahul Mahajan
10. Pre-malignant Conditions and Malignant Tumours of the Skin 720
Arun C Inamadar and Aparna Palit
y
11. Sexually Transmitted Infections 724

Yogesh S Marfatia
12. Hair and Nail Disorders 733
Ja
S Sacchidanand and AS Savitha

13. Leprosy 741
Hemanta Kumar Kar
14. Dermatology Therapy 747
Asit Mittal
Part 12 Cardiology
1. Basic Considerations in Cardiology 757
Upendra Kaul and Aijaz H Mansoor
2. Cardiovascular Diseases: A Clinical Approach 763
GS Sainani
3. Electrocardiology 774 xxix
MJ Gandhi
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4. Exercise Testing 785
Yash Pal Munjal
5. Echocardiography 794
Satish Kumar Parashar
6. Cardiac Imaging 809
Priya Jagia and Sanjiv Sharma
7. Nuclear Cardiology 821
Vikram R Lele and Parag Aland

8. Cardiac Catheterisation and Angiocardiography 827
Lekha Adik Pathak and NO Bansal
9. Heart Failure 834
Donald Kikta and Veronica Franco
10. Treatment of Heart Failure 838
rs
Veronica Franco and Khadijah Breathett
11. Acute Rheumatic Fever 845
R Krishna Kumar
12. Valvular Heart Disease (I) 854
he
CN Manjunath
13. Valvular Heart Disease (II) 862
VK Bahl and Neeraj Parakh
14. Infective Endocarditis 873
Shyam S Kothari
ot
15. Atherosclerosis 884
KK Sethi and S Lahiri
16. Ischaemic Heart Disease 890
Inder S Anand and Shibba Takkar Chhabra
Br
17. Acute Coronary Syndrome—NSTEMI 898
Ambuj Roy
18. Acute Myocardial Infarction—STEMI 904
Naved Aslam and Abhishek Goyal
19. Hypertension and Its Management 916
Sandhya A Kamath
e
20. Resistant Hypertension 930

BB Thakur and Smita Thakur
21. Bradyarrhythmias 935
pe
Yash Y Lokhandwala and Gopi Krishna Panicker

22. Tachyarrhythmias 943
Amit Vora
23. Sudden Cardiac Arrest 950
Ashish K Thakur
y
24. Congenital Heart Disease 959

Sunita Maheshwari
25. Heart in Systemic Diseases 968
Ja
Aspi R Billimoria
26. Disorders of the Myocardium 973
KK Talwar and Ajay Bahl
27. Diseases of the Pericardium 985
Sanjay Tyagi and Amit Mittal
28. Surgical Management of Heart Disease 996
Muhammad Abid Geelani
29. Diseases of the Aorta 1005
Manotosh Panja and Soumitra Kumar
30. Vascular Disorders of the Extremities 1015
Gurpreet Singh Wander and Bishav Mohan
31. Pregnancy and Heart Disease 1023
Amal Kumar Banerjee
xxx 32. Prevention of Cardiovascular Diseases 1029
SKD Bhardwaj
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Part 13 Gastroenterology
1. Basic Considerations in Gastroenterology 1034
Vineet Ahuja and V Pratap Mouli
2. Clinical Approach to a Patient with Gastrointestinal Disease 1038
AC Anand and Pankaj Puri
Contents
3. Investigations: Gastrointestinal Disorders 1042
Ashok Chacko
4. Diagnostic and Therapeutic Utility of Endoscopy 1045
Gourdas Choudhuri
5. Oesophageal Disorders 1051
Shobna Bhatia and Deepak Kumar Gupta
6. Diseases of the Stomach and Duodenum 1061
rs
Pankaj Dhawan and Rajesh Sainani
7. Gastrointestinal Bleeding 1069
Rakesh Kochhar and Jahangeer Basha
8. Acute Pancreatitis 1079
he
Pramod Kumar Garg
9. Chronic Pancreatitis 1092
V Balakrishnan and Gopalakrishna Rajesh
10. Neoplasms of the Pancreas 1098
V Balakrishnan and Gopalakrishna Rajesh
11.
12.
Philip Abraham
ot
Functional Gastrointestinal Disorders
Constipation: Diagnosis and Management

Uday Chand Ghoshal
1103
1108
Br
13. Diarrhoea and Malabsorption 1112
BS Ramakrishna
14. Abdominal Tuberculosis 1120
Govind K Makharia
15. Inflammatory Bowel Disease 1128
Ajit Sood and Vandana Midha
e
16. Ischaemic Bowel Disorders 1134

Deepak Kumar Bhasin
17. Gastrointestinal Symptoms in Extra-abdominal and Systemic Diseases 1137
pe
Sudeep Khanna and Rakesh Tandon
Part 14 Hepatology
y
1. Basic Considerations of Hepatobiliary Disorders 1144

Vivek Anand Saraswat
Ja
2. Hepatobiliary Disorders: Clinical Approach and Investigations 1148

Nagaraja Rao Padaki
3. Hepatobiliary Disorders: Imaging 1158
Shrinivas B Desai
4. Acute Viral Hepatitis 1167
DN Amarapurkar
5. Chronic Viral Hepatitis 1174
Radha K Dhiman
6. Chronic Non-viral Hepatitis 1181
CE Eapen
7. Alcoholic Liver Disease 1184
Rajesh Upadhyay and Nitin Gupta
8. Cirrhosis of the Liver 1190
Philip Abraham
9. Extrahepatic Portal Venous Obstruction 1196 xxxi
Yogesh K Chawla
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10. Non-alcoholic Fatty Liver Disease 1199
Ajay Duseja
11. Acute Liver Failure 1204
SK Acharya and Shalimar
12. Inherited Metabolic Disorders of the Liver 1210
P Advaitham and Shanthi Vijayaragavan
13. Parasitic Diseases of the Liver 1216
MP Sharma and Vaibhav Gupta

14. Toxic and Drug-induced Liver Injury 1220
Abraham Koshy
15. Liver Transplantation 1222
Subash Gupta and Ajay Kumar
16. Pregnancy and Liver Diseases 1225
rs
Ashish Goel
17. Liver in Systemic Diseases 1230
Premashis Kar and Rajiv Singla
18. Tumours of the Liver 1234
he
Kaushal Madan and Pankaj Tyagi
19. Diseases of the Gall Bladder and Biliary Tract 1238
Usha Dutta and Rakesh Tandon
Part 15 Haematology
1. Haematopoiesis
ot
Shaji V Ramachandran and Vikram Mathews
1245
Br
2. Anaemia: A Clinical Approach 1253
Renu Saxena and M Mahapatra
3. Splenomegaly: A Clinical Approach 1258
Pankaj Malhotra
4. Iron Deficiency Anaemia 1262
Subhash Varma
e
5. Megaloblastic Anaemia 1268

Tarun Kumar Dutta
6. Hereditary Haemolytic Anaemia 1274
pe
MB Agarwal
7. Acquired Haemolytic Anaemia 1285
Farah Jijina
8. Aplastic Anaemia 1291
Dharma R Choudhary and Tuphan Kanti Dolai
y
9. Acute Leukaemia 1297

SH Advani
Ja
10. Chronic Myeloid Leukaemia and Other Myeloproliferative Neoplasms 1306

Tapan Kumar Saikia
11. Myelodysplastic Syndromes 1310
Rajat Kumar and Seema Tyagi
12. Chronic Lymphocytic Leukaemia 1316
M Mahapatra and Renu Saxena
13. Hodgkin’s Lymphoma 1321
Bharath Rangarajan and PM Parikh
14. Non-Hodgkin’s Lymphoma 1327
Auro Viswabandya
15. Plasma Cell Dyscrasias 1331
Pankaj Manubhai Shah
16. Bleeding Disorders 1337
Kanjaksha Ghosh
xxxii 17. Platelet Disorders 1341
Prantar Chakrabarti
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18. Idiopathic Thrombocytopenic Purpura 1346
Cecil Ross
19. Disorders of Coagulation 1351
Jina Bhattacharyya and Sangit Dutta
20. Hypercoagulable Disorders 1355
Mammen Chandy
21. Transfusion Medicine 1360
Contents
Neelam Marwaha
22. Haematopoietic Stem Cell Transplantation 1365
Velu Nair
Part 16 HIV and AIDS
rs
1. Epidemiology of Human Immunodeficiency Virus Infection 1374
OC Abraham and Susanne A Pulimood
2. HIV Virology and Immunology Including Diagnosis 1376
he
V Ravi and Anita Desai
3. Pathophysiology and Clinical Features 1380
UL Wagholikar and Alaka Deshpande
4. Antiretroviral Therapy 1386
BB Rewari
5. Drug Resistance 1390
6.
7.
Alaka Deshpande
Non-opportunistic Infections
Anil Kumar Tripathi and D Himanshu
Opportunistic Infections
ot 1394
1398
Br
Jyoti Wadhwa
8. Non-pharmacologic Interventions and Prevention 1403
R Sajithkumar
Volume 2
e
Part 17 Infectious Diseases

pe
A. General Considerations
1. Basic Considerations of Infections 1411
Subhasish Kamal Guha
y
2. Laboratory Diagnosis of Infections 1414

Camilla Rodrigues and Niyati Desai
Ja
3. Syndromic Approach to Infectious Diseases 1422

Rajeev Soman and Neha Gupta
4. Antimicrobial Therapy 1429
Jagriti Bhatia and Dharamvir Singh Arya
5. Infection in the Immunocompromised Host 1437
Ghan Shyam Pangtey and Anupam Prakash
6. Hospital-acquired Infections/Nosocomial Infections 1440
A Shobhana
7. Prevention of Healthcare Associated Infections 1446
BB Rewari and Usha K Baveja
8. Hospital Infection Control 1452
Rohini Kelkar
B. Bacterial Infections
9. Staphylococcal Infections 1455 xxxiii
Rita Sood
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10. Streptococcal Infections 1460
Abhay Narain Rai
11. Pneumococcal Infections 1463
DP Bhadoria and Sanjay Pandit
12. Meningococcal Infections 1467
RK Singal and Vivek Pal Singh
13. Gonococcal Infections 1472
Chander Grover
14. Typhoid Fever (Enteric Fever) 1476
Swapan Kumar Niyogi
15. Bacillary Dysentery 1480
Pankaj Tyagi
16. Cholera 1483
Sujit K Bhattacharya and Sandipan Ganguly
rs
17. Diseases Caused by Gram-negative Enteric Bacilli 1486
Richa Dewan
18. Haemophilus Influenzae Infections 1491
he
M Sabir and Mansoor Ahmed
19. Legionnaires’ Disease 1495
PS Shankar
20. Plague and Other Yersinia Infections 1498
Veena Mittal
21. Clostridial Infections 1502
22.
23.
MK Daga and Arvind Kumar
Diphtheria
Sandeep B Bavdekar
Pertussis: Whooping Cough ot 1508
1511
Br
YK Amdekar
C. Miscellaneous Bacterial Infections

24. Syphilis 1514
Debabrata Bandyopadhyay
25. Non-syphilitic Treponematoses 1519
e
Taru Garg
26. Leptospirosis 1522
pe
AP Sugunan
27. Other Spirochaetal Infections: Lyme Disease and Rat Bite Fever 1526
Kamlesh Tewary
28. Anaerobic Infections 1529
R Sajithkumar
29. Atypical Mycobacterial Infection 1531
y
Surendra Daga
30. Brucellosis 1534
Ja
BG Mantur
31. Donovanosis 1537
Dwijendra Nath Gangopadhyay
32. Actinomycosis and Nocardiosis 1539
A Muruganathan
33. Bartonella Infections 1542
Pallavi Bhargava
34. Melioidosis 1544
Kavitha Saravu
D. Rickettsial, Chlamydial and Mycoplasma Infections

35. Rickettsial Infections 1547
Mala Chhabra and Veena Mittal
36. Chlamydial Infections 1553
xxxiv TK Suma
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37. Mycoplasma Infections 1556
Dilip Mathai
E. Viral Infections
38. Basic Considerations of Viral Diseases 1558
Usha K Baveja
39. Herpes Simplex Virus Infections 1565
Contents
Aditya Prakash Misra
40. Human Papillomavirus and Parvovirus Infections 1569
Neerja Bhatla and Biswa B Dash
41. Swine Flu/Avian Flu 1575
Arvind Mathur and Prabhu Prakash
42. Dengue 1580
ME Yeolekar and S Sukumaran
rs
43. Ebola and Marburg Infections 1584
Partha Pratim Chakraborty
44. Japanese Encephalitis 1586
Deepshikha
he
45. Rabies 1590
Tarun Kumar Dutta
46. Viral Gastroenteritis 1595
Prabhash Chandra Bhattacharyya and Rupjyoti Talukdar
47. Mumps 1597
48.
49.
Falguni S Parikh
Measles (Rubeola)
RK Goyal
Smallpox
ot 1599
1602
Br
Ramesh Balwant Pandit
50. Lymphocytic Choriomeningitis 1604
Praveen Gupta
51. Prion Disease 1607
PK Maheshwari and Anjana Pandey
52. Human Babesiosis 1609
e
Yash Pal Munjal and Kusumita Chaudhuri
F. Protozoal Diseases
pe
53. Malaria 1611

AK Agarwal and Sarit Chatterjee
54. Amoebiasis and Giardiasis 1620
MP Sharma and Vaibhav Gupta
55. Leishmaniasis 1624
y
Shyam Sundar
56. Toxoplasmosis 1629
Ja
Madhukar Rai
57. Trypanosomiasis 1632
Prashant P Joshi
58. Cryptosporidiosis, Trichomoniasis, Balantidiasis and Isosporiasis 1636
Atul Bhasin
G. Helminthic Diseases
59. Ankylostomiasis, Ascariasis and Other Nematodal Infections 1639
Narender Pal Jain
60. Tapeworm and Hydatid Diseases 1650
Anurag Saxena
61. Filariasis and Other Related Infestations 1658
Sanjay Zachariah
62. Schistosomiasis/Bilharziasis 1664
Kirti C Patel xxxv
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H. Fungal Infections
63. Systemic Fungal Infections 1667
Shruti Prem and Rajat Kumar
64. Pneumocystis Jirovecii Pneumonia 1678
V Ramasubramanian
Part 18 Disorders of Metabolism

1. Basic Considerations of Metabolism 1682
BK Sahay
2. Inborn Errors of Carbohydrate Metabolism 1684
Siddharth N Shah
rs
3. Lipids and Lipoprotein Metabolism 1687
Soneil Guptha
4. Disorders of Purine and Pyrimidine Metabolism 1698
RV Jayakumar
he
5. Iron Metabolism and Iron Overload Syndrome 1700
Mukesh Desai
6. Porphyrias 1711
Dhanpat Kumar Kochar
7. Wilson’s Disease 1716
ot
Sanjib Sinha and AB Taly
8. Lysosomal Storage Disorders 1722
Prasanta Kumar Bhattacharya
9. Inherited Disorders of Membrane Transport 1726
Br
SK Singh
10. Amyloidosis 1730
Manisha Sahay
11. Disorders of Adipose Tissue and Obesity 1735
Shashank R Joshi
12. The Metabolic Syndrome 1740
e
Anoop Misra and Swati Bhardwaj

pe
Part 19 Nephrology
1. Structure and Function of the Kidney 1744
Sandeep Mahajan and Yasir S Rizvi
2. Kidney Disease: A Clinical Approach 1750
y
Vijay Kher and Pranaw Kumar Jha

3. Acute Kidney Injury 1757
Ja
Alan F Almeida and Amit Langote

4. Chronic Kidney Disease 1762
Ashok L Kirpalani and Hardik Shah
5. Primary Glomerular Diseases 1772
Vinay Sakhuja and Raja Ramachandran
6. Secondary Glomerular Diseases 1783
OP Kalra and Sandeep Mahajan
7. Urinary Tract Infections 1791
R Kasi Visweswaran and Praveen Namboodiri
8. Nephrolithiasis and Urinary Tract Obstruction 1797
PD Gulati
9. Vascular Injury to Kidney 1802
AK Hooda and AS Narula
10. Polycystic Kidney Disease and Inherited Tubular Disorders 1807
xxxvi PP Varma and Ranjith Nair
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11. Dialysis and Other Extracorporeal Therapies 1814
NK Hase
12. Renal Transplantation 1827
George T John
13. Tubulointerstitial Diseases of the Kidney 1833
Sree B Raju
14. Drug Nephrotoxicity and Renal Dosage Adjustment 1839
Contents
Ankur Gupta and Pritam Gupta
Part 20 Neurology
1. Neurological Disorders: Basic Consideration and Clinical Approach 1847
rs
MV Padma Srivastava and RS Wadia
2. Clinical Neurophysiology 1859
J Kalita and UK Misra
3. Neuroimaging 1867
he
Rakesh K Gupta and Krishan K Jain
4. Epilepsy 1874
Sanjeev V Thomas
5. Disorders of Speech 1890
Apoorva Pauranik
6.
7.
Disorders of Cranial Nerves
ot
Sankar Prasad Gorthi and Sundaram Venkatraman
Ischaemic Cerebrovascular Diseases
PM Dalal and M Bhattacharjee
1900
1912
Br
8. Haemorrhagic Cerebrovascular Diseases 1926
MV Padma Srivastava and Ajay Garg
9. Cerebrovenous Thrombotic Disorders 1933
D Nagaraja and N Karthik
10. Bacterial Meningitis and Brain Abscess 1937
Ravindra Kumar Garg and Praveen Kumar Sharma
e
11. Neurotuberculosis 1944

Shyamal Kumar Das and Debal Laha
pe
12. Neurosyphilis 1954

S Prabhakar and Manish Modi
13. Viral Infections of Central Nervous System 1958
Nadir E Bharucha
14. Slow Virus Infections and Prion Diseases 1966
SK Shankar
y
15. Fungal and Parasitic Diseases of the Nervous System 1971

Ashok Panagariya and Parul Dubey
Ja
16. Raised Intracranial Pressure and Hydrocephalus 1977

Daljit Singh
17. Dementia 1981
PS Mathuranath
18. Extrapyramidal Disorders 1987
BS Singhal
19. Cerebellar Disorders 1993
Netravathi M and Pramod Kumar Pal
20. Hyperkinetic Movement Disorders 2013
Mohit Bhatt
21. Amyotrophic Lateral Sclerosis and Other Motor Neuron Diseases 2018
BK Bajaj
22. Demyelinating Diseases of Nervous System 2026
Man Mohan Mehndiratta and Prachi Mehndiratta xxxvii
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23. Nutritional and Toxic Disorders of the Nervous System 2034
UK Misra
24. Metabolic Disorders of Nervous System 2041
Vrajesh Udani and Neelu Desai
25. Intracranial Space-occupying Lesions 2055
P Sarat Chandra and PN Tandon
26. Head Injury 2065
AK Singh
27. Peripheral Neuropathy 2073
AK Meena and SA Jabeen
28. Disorders of Autonomic Nervous System 2086
Garima Shukla
29. Myasthenia Gravis 2090
rs
Sumit Singh and Atma Ram Bansal
30. Diseases of Muscles 2094
SV Khadilkar
31. Non-compressive Myelopathies 2107
he
Mrinal Kanti Roy
32. Compressive Myelopathies 2113
Vibhor Pardasani
Part 21 Oncology
1. Developments in Oncology
ot
Lalit Kumar and Prabhat Singh Malik
2120
Br
2. Principles of Cancer Biology and Pathology 2125
Anita M Borges
3. Cancer Screening and Prevention 2131
Atul Sharma and MP Ram Prabhu
4. Principles of Drug Treatment of Cancer 2134
Lalit Kumar and Prabhat Singh Malik
e
5. Principles of Radiotherapy 2143

GK Rath
6. Head and Neck Cancers 2147
pe
VP Gangadharan
7. Breast Cancer 2150
Vinay H Deshmane
8. Tumours of the Gastrointestinal Tract (Stomach and Oesophagus) 2157
KM Mohandas
y
9. Colorectal Cancer 2164

K Govind Babu
10. Genitourinary Cancers 2167
Ja
Sudeep Gupta
11. Gynaecological Malignancies 2173
PP Bapsy
12. Bone and Soft Tissue Sarcoma 2180
Avinash Deo
13. Cancer of Unknown Primary Site 2184
Hemant Malhotra and Ashwin Mathur
14. Paraneoplastic Syndromes 2191
Senthil Rajappa and D Raghunadharao
15. Cancers in the Predisposed Host 2197
K Pavithran
16. Oncological Emergencies 2202
Avinash Deo
xxxviii 17. Supportive Care in Cancer 2206
Madhuchanda Kar and Rakesh Roy
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Part 22 Psychiatric Medicine
1. Introduction and Basic Considerations in Psychiatry 2212
Yatan Pal Singh Balhara and Koushik Sinha Deb
2. Organic Mental Disorders 2222
SK Khandelwal
Contents
3. Substance Use Disorders 2229
Debasish Basu
4. Psychosis and Schizophrenia 2236
R Thara and Shiva Prakash Srinivasan
5. Mood Disorders 2241
Yatan Pal Singh Balhara
6. Anxiety Disorders 2247
rs
A Shyam Sundar and YC Janardhan Reddy
7. Somatoform Disorders 2254
Rakesh K Chadda
8. Emergency Psychiatry 2260
he
Dipesh Bhagabati
9. Sexual Disorders 2266
TS Sathyanarayana Rao and Abhinav Tandon
10. Biological and Somatic Treatment of Psychiatric Disorders 2276
E Mohandas and Rajmohan V
11. Psychotherapies in Mental Health
Manoj K Sharma
ot 2284
Br
Part 23 Pulmonary Medicine
1. Respiratory System: Basic Anatomy and Physiology 2290
SK Chhabra
2. Pulmonary Disorders: A Clinical Approach 2300
Jyotsna M Joshi
e
3. Diagnostic Procedures in Pulmonary Disorders 2306

Gautam Ahluwalia and Surendra K Sharma
4. Upper Respiratory Tract Infections 2313
pe
DG Jain
5. Bronchial Asthma 2317
Virendra Singh
6. Chronic Obstructive Pulmonary Disease 2328
Surendra K Sharma
y
7. Pneumonia 2339
Digambar Behera
Ja
8. Suppurative Pleuro-pulmonary Diseases 2352

Sahajal Dhooria and Navneet Singh
9. Pulmonary Tuberculosis 2363
MS Jawahar
10. Fungal Infections of the Lungs 2371
Ashok Shah
11. Diffuse Interstitial Lung Diseases 2378
Surinder K Jindal
12. Eosinophilic Lung Diseases and Tropical Pulmonary Eosinophilia 2388
VK Vijayan
13. Sarcoidosis 2395
VK Vijayan
14. Sleep-related Breathing Disorders 2403
R Narasimhan and AR Gayathri
15. Deep Venous Thrombosis and Pulmonary Embolism 2408 xxxix
Jamshed D Sunavala and Shruti M Tandan
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16. Diseases of Pleura, Mediastinum, Diaphragm and Chest Wall 2417
Alladi Mohan
17. Benign and Malignant Tracheobronchial Tumours 2428
Lalit Kumar and MP Ram Prabhu
18. Atelectasis and Pulmonary Fibrosis 2438
Prasanta Raghab Mohapatra
19. Cor Pulmonale 2447
Sandeep Singh
20. Pulmonary Rehabilitation 2454
Sanjeev Sinha and Faraz Ahmed Farooqui
Part 24 Rheumatology
rs
1. Basic Considerations of Rheumatology 2458
Rohini Handa
2. Soft Tissue Rheumatism and Regional Rheumatic Pain Syndromes 2463
he
Ved Chaturvedi
3. Low Back Pain 2469
Ghan Shyam Pangtey and Hemant Gopal
4. Osteoarthritis 2478
Siddharth Kumar Das
5. Gout and Other Crystal Arthritides 2483
6.
7.
URK Rao and Sripurna Deepti
Rheumatoid Arthritis
AN Malaviya
Spondarthritides ot 2492
2513
Br
Milind Y Nadkar and Manish W Itolikar
8. Sjögren’s Syndrome 2522
Uma Kumar
9. Systemic Lupus Erythematosus 2525
VR Joshi
10. Antiphospholipid Syndrome 2534
e
Vikas Agarwal and Anupam Wakhlu

11. Inflammatory Muscle Diseases 2539
pe
Alakendu Ghosh and Pradyot Sinhamahapatra

12. Systemic Sclerosis 2545
Shefali Khanna Sharma
13. The Vasculitides 2549
Pradeep Bambery
14. Mixed Connective Tissue Disease and Overlap Syndromes 2560
y
G Narsimulu
15. Rheumatic Manifestations of Systemic Diseases 2564
Ja
Debashish Danda
16. Miscellaneous Rheumatic Disorders 2568
Binoy J Paul
17. Emergencies in Rheumatology 2574
Madhumita P Das
18. Tropical Rheumatic Diseases 2579
Aman Sharma
Part 25 Nutrition
1. Nutrition: Basic Considerations 2584
SV Madhu
2. Assessment of Nutritional Status 2589
xl Prema Ramachandran
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3. Protein Energy Malnutrition 2593
Piyush Gupta
4. Water-soluble Vitamins 2598
Milind Y Nadkar
5. Fat-soluble Vitamins 2603
Ghan Shyam Pangtey and Moti Lal
6. Minerals, Trace Elements and Antioxidants 2608
Contents
M Raghunath and D Sreeramulu
7. Food Allergy and Food Intolerance 2615
UV Mani
8. Eating Disorders 2618
Anupam Prakash
9. Enteral and Parenteral Nutrition Support 2621
Varsha
rs
Part 26 Poisoning and Toxicology
he
1. Poisoning: Basic Considerations and Epidemiology 2628
Narinder Pal Singh and Gurleen Kaur
2. Aluminium Phosphide Poisoning 2632
Surjit Singh
3. Organophosphorous Poisoning 2634
4.
5.
Surjit Singh
Corrosive Poisoning
Rakesh Kochhar
Alcohol Poisoning
ot 2637
2640
Br
Pritam Gupta and Ankur Gupta
6. Plant Poisoning 2644
DKS Subrahmanyam and Muktha V
7. Drug Overdose 2649
Narinder Pal Singh
8. Snake Bite Poisoning 2656
e
HS Bawaskar
9. Scorpion Sting 2662
pe
HS Bawaskar
10. Fluorosis 2670
D Raja Reddy
11. Lathyrism 2677
UK Misra and J Kalita
12. Epidemic Dropsy 2679
y
Vivek Suman and Shubha Laxmi Margekar

13. Heavy Metal Poisoning 2681
Ja
Praveen Aggarwal
14. Miscellaneous Poisonings 2693
Subhash Varma and Vikas Suri
Part 27 Environmental Medicine

1. Basic Considerations of Environmental and Occupational Diseases 2704
Randeep Guleria
2. Climate Change: Health and Disease 2707
Anil Gurtoo
3. Air Pollution and Public Health 2713
Anumita R Chowdhury
4. Air-borne Pollutants and Smoke-related Hazards 2719
Rajeev Gupta xli
API _ Prelims _ Vol-1 for (TRADE).indd xli 29-01-2015 14:22:10

5. Drowning, Near Drowning and Submersion Injury 2725
Yudh Dev Singh
6. Electric Shock and Lightning Injury 2728
Naveet Wig and Sourabh Malviya
7. Effects of Extremes of Temperature 2731
Rajvir Bhalwar
8. High Altitude Medicine 2738
Anuj Chawla
9. Aerospace Medicine 2746
JS Kulkarni
10. Radiation Hazards 2752
AM Samuel
11. Environmental Disasters 2757
G Immanuel
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Part 28 Miscellaneous
he
1. Oral Health and Systemic Diseases 2762
Akshay Munjal and Shilpa Khullar
2. Geriatric Medicine: An Overview 2766
Vinod Kumar
3. Frailty Syndrome 2771
ME Yeolekar and S Sukumaran
4.
5.
Polypharmacy in Elderly
ot
Jyotirmoy Pal and Sattik Siddhanta
Sexual Medicine
Prakash Kothari
2774
2778
Br
6. Sports Medicine 2783
Jaspal S Sandhu and Shweta Shenoy
7. Life-style Modifications to Prevent and Control Diseases 2787
Shridhar Dwivedi and Ramesh Aggarwal
8. Diet in Medical Diseases 2790
Siddharth N Shah
e
9. Tobacco Smoking-related Diseases and Tobacco Cessation 2800

Raj Kumar
10. Adult Immunisation 2805
pe
AK Agarwal and Sumeet Singla

11. Travel Medicine 2818
Yash Pal Munjal and Aditya Prakash Misra
12. Perioperative Management 2825
Prabha Adhikari
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13. Law and Medicine 2829

A Muruganathan and Yash Pal Munjal
Ja
14. Care of Terminally Ill 2834

Anil Chaturvedi
Part 29 Future of Medicine

1. Futuristic Medicine 2840
Yash Pal Munjal and Anupam Prakash
2. Regenerative Medicine 2846
Velu Nair
3. Introduction to Space Medicine 2854
R Gerzer
4. Nanotechnology and Nanomedicine 2861
RD Lele
5. Robotic Surgery 2868
xlii
Roman Dutta
Index I–1
API _ Prelims _ Vol-1 for (TRADE).indd xlii 29-01-2015 14:22:10

Part 16
HIV and AIDS
Editors of the Part: Alaka Deshpande and BB Rewari
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1. Epidemiology of Human Immunodeficiency Virus Infection 1374
he
2. HIV Virology and Immunology Including Diagnosis 1376
3. Pathophysiology and Clinical Features 1380
4. Antiretroviral Therapy 1386

5.
BB Rewari
Drug Resistance
Alaka Deshpande ot 1390
Br
6. Non-opportunistic Infections 1394
7. Opportunistic Infections 1398
Jyoti Wadhwa
8. Non-pharmacologic Interventions and Prevention 1403
R Sajithkumar
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1
Epidemiology of Human Immunodeficiency
PART 16
Virus Infection
HIV and AIDS
INTRODUCTION and 25 million people have died of HIV-related causes,

since the time the first case was reported from USA in
The acquired immunodeficiency syndrome (AIDS) was 1981. The regions most affected by the HIV epidemic
first recognised in the United States in 1981 among men are the regions of sub-Saharan Africa and Asia. India
who were sexually involved with men (MSM). Human accounts for roughly 50% of Asia’s HIV prevalence. In
rs
immunodeficiency virus (HIV), the agent that caused the last decade, there has been a significant decline in
AIDS was discovered in 1983 by Luc Montagnier, the number of new HIV infections and AIDS-related
Francoise Barre-Sinoussi (Pasteur Institute, Paris, deaths. due to success of prevention and treatment
France) and Robert Gallo (National Institutes of programmes.
he
Health, Bethesda, Maryland, USA). Drs. Montagnier
The United Nation’s global summary of the AIDS
and Barre-Sinoussi were awarded the 2008 Nobel Prize
epidemic as per their Programme on HIV/AIDS
in Medicine for this discovery.
(UNAIDS) is given in Table 2.
Molecular studies have revealed the possibility that
HIV originated from the cross-species transmission
to man of the simian immunodeficiency virus (SIV),
which naturally infects non-human primates in Africa
and has very close genetic similarity to HIV. The HIV
viruses are broadly classified into HIV-1 and HIV-2 and
ot Table 2: Global Summary of the AIDS Epidemic, 2012
Number of people
living with HIV in
2012
Total
Adults
Women
35.3 million (32.2–38.8 million)
Br
Children <15 3.3 million (3.0–3.7 million)
are further subdivided into groups and subtypes or years
clades (Table 1). People newly Total 2.3 million (1.9–2.7 million)
infected with HIV Adults 2.0 million (1.7–2.4 million)
Table 1: Classification of HIV in 2012 Children <15 260,000 (230,000–320,000)
Type Group Subtype Distribution years
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(clades) AIDS-related Total 1.6 million (1.4–1.9 million)

HIV-1 M (major) A1, A2, A3, A4, Global deaths Adults 1.4 million (1.2–1.7 million)
B, C, D, F1, F2, Subtype C most prevalent in 2012 Children <15 210,000 (190,000–250,000)
pe
G, H, J, and K in India years

O (outlier) Limited to equatorial Source: UNAIDS.
west Africa
N (non-major and Limited to equatorial
non-outlier) west Africa BURDEN OF HIV EPIDEMIC IN INDIA
y
HIV-2 Limited to west Africa

In India, the first cases of HIV infection were
The major routes for HIV transmission are: documented in 1986 among female sex workers (FSW)
Ja
in Chennai, Tamil Nadu. Subsequently, there have been

1. Unprotected sexual intercourse with a partner reports on cases of HIV infection from every state. The
already infected with HIV. HIV epidemic in India has followed the ‘type 4 pattern’,
2. Exposure to blood and blood products infected with where the new infections are found to have occurred
HIV (e.g., blood transfusion, sharing of infected first among the most susceptible populations, such as
needles, needle-stick injuries, etc.) FSWs and injecting drug users (IDU]), then spreading
3. Peri-partum (vertical) transmission from an HIV-
to ‘bridge’ populations, i.e., clients of sex workers and
infected mother to her child.
sexual partners of drug users, and ultimately entering
the general population.
GLOBAL AIDS SCENARIO
According to the National AIDS Control Organization
Human immunodeficiency virus infection has evolved to (NACO), in India there are nearly 2.09 million
become one of the greatest pandemic in human history. HIV infected people. Among these, 39% are women
1374 Nearly 60 million people are suspected to be infected and 7% children less than 15 years. Young adults
(15 years to 49 years) account for 86% of the burden The pre-dominant mode of transmission of the disease
of HIV infection. The overall HIV prevalence among in the country is heterosexual exposure, while it is
CHAPTER 1
adults is 0.27%. Over the past decade, HIV epidemic injecting drug use in the north-eastern states.
has shown a decline at the national level. National
adult HIV prevalence, or the number of adults living NATIONAL RESPONSE TO THE HIV EPIDEMIC
with HIV as a proportion of the total population, has
The first phase of the National AIDS Control
declined by over 0.10% points from 2000 to reach an
Programme (NACP) was launched in 1992 and the
Epidemiology of Human Immunodeficiency Virus Infection

estimated 0.31% in 2009.
third phase (NACP-III) in 2007. The overall goal of
India’s HIV epidemic is concentrated among vulnerable NACP-III is to stop and turn round the HIV epidemic
groups at high risk for HIV infection, the prevalence in India over the next 5 years. Since more than 99%
being significantly higher among various high-risk of the country’s population is free from HIV infection,
groups (IDUs, MSMs, FSWs and sexually transmitted NACP-III’s highest priority is on the efforts to prevent
disease clinic attendees) than among antenatal clinic
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further occurrence of the disease. Further, it seeks to
attendees. integrate prevention with care, support and treatment.
The HIV epidemic in India is also heterogeneous in In the third phase, populations with the highest risk
geographic distribution and the statewise distribution of exposure to HIV (FSWs, MSMs and IDUs) will be
he
is available on www.racoonline.org. The four ‘high given the priority in the prevention and comprehensive
prevalence states’ (HIV prevalence higher than management. All infected persons will have access to
1% among antenatal women)—Andhra Pradesh, treatment. NACP-IV (2012–2017) aims accelerate the
Karnataka, Maharashtra and Tamil Nadu—account process of epidemic reversal and further strengthen the
for 53% of the total HIV infected population in the epidemic response.
country. Nagaland and Manipur are also considered
as high prevalence states. But, at the district level, 87
districts have HIV prevalence more than 1% among
ANC clinic attendees, and 47 have more than 5% among
ot
SUGGESTED READING
1. Joint United Nations Programme on HIV/AIDS (UNAIDS)
Br
report on the global AIDS epidemic 2013. Available at http://
FSWs. Several of these districts are in moderate and www.unaids.org/en/media/unaids/contentassets/documents/
low prevalence states like Bihar, Chattisgarh, West epidemiology/2013/gr2013/UNAIDS_Global_Report_2013_
Bengal, Gujarat, etc. en.pdf. Accessed on 3rd December, 2013.
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1375
2
HIV Virology and Immunology
PART 16
Including Diagnosis
HIV and AIDS
INTRODUCTION that infect sooty mangabey monkeys (SIVsm). Human

immunodeficiency virus HIV-2 has also been reported
More than three decades have elapsed since the from countries other than western Africa specially
discovery of human immunodeficiency virus (HIV)— India and has been subclassified into clades A to H.
the causative agent of acquired immune deficiency
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syndrome (AIDS). Almost 75 million people have been HIV STRUCTURE
infected with the HIV and about 36 million people
have died since the beginning of the epidemic. Across As depicted in Figure 1, HIV is an enveloped
the globe, 35.3 million (32.2 million to 38.8 million) positive stranded ribonucleic acid (RNA) virus that
he
people were living with HIV at the end of 2012. While measures 120 nm in diameter and consists of a lipid
HIV-1 is responsible for majority of the infections, bilayer with uniformly arranged 72 spikes or knobs of
HIV-2 remains a significant minority of HIV infections glycoprotein—gp120 and gp41 (HIV-1) or gp 36 (HIV-2).
in some countries including India. The virion gp120 located on the virus surface contains
the binding site for cellular receptor(s). The two plus
CLASSIFICATION OF HIV
Human immunodeficiency viruses belong to the family
Retroviridae and subfamily Lentivirinae. Table 1 ot stranded RNA molecules are embedded in a protein
capsid (p24) together with certain viral enzymes (viral
RNA-dependent DNA polymerase [pol], also called the
reverse transcriptase or RT (p66, p51) and nucleocapsid
Br
shows the subgroups. Two types of human viruses are proteins (p9, p7)). The capsid (p24) is surrounded by
recognised in this subfamily HIV-1 and HIV-2. Both types a matrix layer (p17) that in turn is enclosed in lipid
of virus differ in geographical distribution, biological bilayer, called the envelope.
and molecular characteristics as well as the extent of
transmissibility. There are three groups of HIV-1, they Genome Organisation
are, HIV-1 major group (HIV-1 M), HIV-1 new (HIV-1 N)
The genome of HIV-1 measures about 9.8 kb while that
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and outlier (HIV-1 O) group. Human immunodeficiency

of HIV-2 measure 10.3 kb (Figure 2). Long terminal
virus-1 M can be further categorised into subtypes or
repeats (LTRs) of nucleotides flank the structural and
clades designated A to K; these subtypes have envelope
pe
gene sequences that vary by 20% to 50% or more

between subtypes. The subtypes vary in geographical
distribution, biological characteristics and major modes
of transmission. Human immunodeficiency virus-1
subtypes O and N are more distantly related genetically
y
to all other HIV-1 subtypes but less so compared to

HIV-2. Studies of HIV-2 genomes have shown that
Ja
there exists a remarkably close relationship between

HIV-2 and simian immunodeficiency virus (SIV) strains
Table 1: Sub-groups of HIV
Sub-groups
M major A K
clades
HIV-1 N new
Figure 1: A cartoon depicting the structure of human immuno-
HIV O outlier deficiency virus
(This image is a work of the National Institutes of Health, part of the
HIV-2 A H
United States Department of Health and Human Services. As a work of
1376 clades
the US federal government, the image is in the public domain)
CHAPTER 2
HIV Virology and Immunology Including Diagnosis
Figure 2: The genome of HIV and the genes encoded in a single positive-stranded RNA. Note that both HIV-1 and HIV-2 have similar genetic
organisations except the accessory gene vpu is unique for HIV-1 and is replaced by vpx in HIV-2
rs
(This figure is generated by Department of Neurovirology, NIMHANS, is not copyrighted and is in public domain. Hence, no permission is required to
use this figure)
regulatory genes. Both HIV-1 and HIV-2 have similar making use of CD4 and CCR5 (receptor for RANTES).
he
genetic organisations encoded in a single positive- After attachment to CD4, gp120 is displaced leading
stranded RNA. The accessory gene, viral protein to uncovering of domains on the envelope gp41 needed
unique (vpu), is unique for HIV-1 and is replaced by for virus cell fusion. Glycoprotein 41 is involved in
viral protein x (vpx) in HIV-2. The primary transcript infectivity as well as syncytium formation.
of HIV is a full length viral mRNA, which is translated
into the gag and pol proteins. The gag gene codes for the
proteins p24, p17, p9 and p7. The pol gene codes for RT,
the protease (PR) and the integrase (IN) proteins. The otShortly after the viral capsid enters the cell, the
enzyme RT releases the single-stranded RNA genome
from the attached viral proteins and copies it into a
complementary deoxyribonucleic acid (cDNA). The
Br
envelope gene codes for the gp120 and gp41 proteins
cDNA and its complement form a double-stranded viral
which are made from a precursor gp160. One of the
DNA that is then transported into the cell nucleus
regulatory proteins is tat, a trans activating protein,
where it is integrated into the host cell’s genome by the
which along with certain cellular proteins, interacts
enzyme IN (Figure 3). The integrated DNA provirus
with an RNA loop structure formed in the 3’ portion
is transcribed into mRNA, which is then spliced into
of the viral LTR and up-regulates HIV replication.
e
smaller pieces during viral replication. These small

The other viral regulatory proteins include, regulation
of viral protein expression (rev), which is needed for pieces are sent out from the nucleus into the cytoplasm
the synthesis of viral proteins, negative factor (nef), where translation into the proteins takes place. The
pe
whose actual function remains unclear is believed to final step of the viral cycle, the assembly of new HIV-1
down regulate viral expression the accessory HIV virion, starts at the plasma membrane of the host cell
viral gene products and vif, vpr, vpu or vpx appear to where the various structural components assemble to
influence events such as assembly and budding, as well produce a mature HIV virion. This cleavage step can be
as infectivity involved in the production of infectious inhibited by protease inhibitors. The mature virus has,
y
viruses. thereafter, the ability to infect another cell.

Ja
REPLICATION OF HIV IMMUNOLOGY OF HIV INFECTION

Human immunodeficiency virus enters the body when The principal impact of HIV infection on the immune
an individual comes in contact with infected blood, system is destruction of the CD4 T lymphocytes.
semen and/or vaginal secretions. The principal target During primary infection, HIV and HIV infected cells
site for HIV attachment is the CD4 receptor; however reach the lymph nodes and other lymphoid tissues. The
specific chemokine receptors appear to serve as virus rapidly disseminates during this early phase of
important secondary cellular receptors for HIV. Human HIV infection. As a result, there is a significant fall
immunodeficiency virus-1 strains have been divided in CD4 cells and viral levels may be as high as 106 to
into T-tropic (preferring to replicate in T lymphocytes) 107 viral copies/mL. The next stage is down-regulation
and M-tropic (macrophages) viruses. The chemokine of viraemia. This occurs along with a robust, intense
receptor usage differs for each of these viruses, with immune response by the host (Figure 4). Effective
T-tropic viruses making use of CD4 and CXCR4 (or cellular immune response mediated by HIV specific
fusin, the receptor for SDF-1) and M-tropic viruses cytotoxic T lymphocytes (CTL) and humoural response 1377
PART 16
HIV and AIDS
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Figure 4: Immune events in relation to natural course of HIV
he
infection
(This image is made available under the Creative Commons CC0 1.0
Universal Public Domain Dedication. The person who associated a
work with this deed has dedicated the work to the public domain by
waiving all of his or her rights to the work worldwide under copyright
law, including all related and neighbouring rights, to the extent al-
ot lowed by law. You can copy, modify, distribute and perform the work,
even for commercial purposes, all without asking permission)
Br
The advanced stage of HIV infection is distinguished by
increase in all the virological parameters (virus load,
p24 antigen, etc.) in peripheral blood and lymph nodes.
Lymphoid tissue, which is totally destroyed is replaced
by fibrous tissue. Consequently, there is profound
immune suppression and a variety of opportunistic
e
infections set in, which may prove fatal. The CD4 count
at this stage is usually <200 cells/µL and progressively
declines further.
pe
Figure 3: A schematic representation of the various steps in the LABORATORY DIAGNOSIS

replication of HIV
(Permission is granted to copy, distribute and/or modify this document
OF HIV INFECTION
under the terms of the GNU Free Documentation License, Version 1.2 or
Diagnosis of HIV infection can be achieved by the
y
any later version published by the Free Software Foundation; with no

Invariant Sections, no Front-Cover Texts, and no Back-Cover Texts) detection of: (1) antibodies in blood and body fluids;
(2) antigen in blood and body fluids; (3) viral nucleic
Ja
acid by polymerase chain reaction (PCR); and (4) virus

mediated by complement fixing and neutralising HIV isolation from blood and tissues. However, the world
specific antibodies comes into play. As a result, there over diagnosis of HIV infection is largely based on the
is a drop in viraemia and CD4 levels bounce back to detection of antibodies to HIV in the patient’s serum
values slightly lower than the normal levels. The lymph sample. According to the Department of AIDS Control
nodes and lymphoid organs are the sites for active and (DAC), Government of India Testing Guidelines, a
continuous virus replication. A gradual reduction is seen three-tiered strategy is adopted for diagnosis of human
in the number of CD4 cells with a steady increase in immunodeficiency virus infection in clinical settings.
viral load during the long asymptomatic stage. During Initially a sample is tested by an enzyme-linked
the asymptomatic stage humoural immunity is intact immunosorbent assay (ELISA) or rapid test. If it is
and specific antibodies are produced against different found reactive, it is subjected to second and third ELISA
viral proteins, but the antibodies are not protective and or rapid assay using different antigen or principle of
are unable to interfere with cell to cell transmission. testing. Only, if all the three tests are reactive, the
1378 This period on an average lasts for 8 years to 10 years. sample is considered positive for antibodies to HIV.
Samples that are negative in the first and second levels infection. However, its detection has limited
of testing are considered negative while samples that diagnostic potential because antigenaemia is
CHAPTER 2
are positive in the two tests and negative in the third restricted to two stages of HIV infection early in the
are considered equivocal and subjected to Western Blot illness during the latter half of the window period and
for confirmation. late in the illness (end stages) when immune collapse
has set in.
Detection of HIV-specific Antibodies
HIV Virology and Immunology Including Diagnosis

Immunoassays for the detection antibodies to HIV-1
Detection of Viral Nucleic Acid
were developed in a series of stages, called generations. Detection of HIV nucleic acid in plasma or serum is
The first generation assays were very sensitive but used for diagnosis of HIV infection in children aged
not specific and the technology was improved by using <18 months (early infant diagnosis-EID) and for
recombinant and synthetic peptides as antigens (second estimation of viral loads. It is not recommended by
rs
and third generation kits). More recently, fourth DAC as a routine diagnostic procedure to detect
generation immunoassays have been developed that HIV infection in other clinical situations. Human
detect both antibody and p24 antigen simultaneously. immunodeficiency virus nucleic acid is usually detected
The different HIV-1 antibody detection tests available by polymerase chain reaction (PCR). For EID, the DAC
he
currently are ELISA, rapid immunoassays such as HIV recommends the use of a HIV DNA PCR using dried
spot tests and other rapid immunochromatography- blood spot specimens.
based assays. Antibodies to HIV-2 in clinical samples
are detected by ELISA with synthetic gp36 (TM portion SUGGESTED READING
of the HIV-2 envelope) antigens.
Detection of Viral Antigen in Blood

and Body Fluids ot
1.
2.
NACO (2007). Guidelines on HIV testing http://www.nacoonline.
org/Quick_Links/Publication/Blood_Safety_Lab_Services/
Operational_Technical_guidelines_and_policies/Guidelines_for_
HIV_test/. Accessed on 15th May, 2014.
Zuckerman AJ, Banatvala JE, Griffiths PD, et al. Principles and
Br
The p24 antigen of HIV can be detected in the Practice of Clinical Virology. 6th ed. London: Wiley-Blackwell;
blood of infected individuals early during acute 2008: pp. 897-939.
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1379
3
Pathophysiology and Clinical Features
PART 16

HIV and AIDS
INTRODUCTION antibodies may cross react with host tissues to cause

autoimmune lesions in the course of HIV disease.
Human immunodeficiency virus (HIV) is a human-
specific retrovirus. Two types of viruses, namely, HIV-1
and HIV-2 are identified by their unshared antigens. The
rs
viral genes encode for various components of the virus
like viral proteins, viral enzymes and viral ribonucleic
acid (RNA). The protein and the glycoproteins are
indicated by letters ‘p’ and ‘gp’, respectively, and these
he
are allotted numbers as per molecular weight in micro-
daltons, e.g., p24, p17, gp120. Figure 1 depicts viral
genes in a typical virus.
Invasion by pathogen incites immune attack involving
both humoral (B cell) and the cell mediated immunity
(T-cell). The T lymphocytes, identified by cluster
determinants (CD) receptors, play a pivotal role
(Figure 2). ot
Br
Once gp 120 binds with CD4, there is a transformational
change in gp 41, which unfolds in a spring like manner
and anchors the virus to the CD4 cell membrane. At
this stage gp120 binds to the co-receptors like CCR5
or CXCR4. After the fusion of the viral and CD4 cell
membranes, the virus is uncoated and released inside
e
the CD4 cell and begins its life cycle (Figure 3).
Viral components are antigenic to man. Antibody
pe
responses to them differ from antigen-to-antigen,

person-to-person and time-to-time (in a person). Some
antigens resemble human components (e.g., p17 and
thymosin, gp120 and neuroleukin, etc.). Anti-HIV Figure 2: Role of CD4 in immune system
y
Ja
1380 Figure 1: Human immunodeficiency virus genes Figure 3: Beginning of life cycle of HIV
INVASION OF TARGET CELLS with greater ease and success. Later, it mutates to T
tropism and switches on to the most susceptible target.
CHAPTER 3
The ‘CD4’ molecules on cells and ‘gp120’ molecules on T tropic strains, with syncytium inducing (SI) capacity
HIV have affinity for each other (Figure 3). A chance on targets, are more devastating.
contact leads to firm bondage and lays the foundation
Other retroviruses can replicate only in cells capable
for cell invasion. T-helper lymphocytes (including
of multiplication. But HIV has the capacity, albeit
immature, mature and derived cells), monocytes,
limited, of replication, even in terminally differentiated

macrophages, dendritic cells (DCs), in epidermis
non-dividing macrophages. Viral protein R (p15) makes
(Langerhans cells), mucosal surfaces of alimentary and
this possible.
genital tracts, lymphoid depots and tissues, epithelial
cells lining mucosae of the said tracts and microglial Activation status, co-receptor profile and nature are
cells of the central nervous system (CNS) carry CD4 significant cell-related factors. In an individual, co-
molecules. HIV targets them all. receptor production (quality and quantity) is genetically
rs
controlled. Co-receptor produced in excess, may be
shed by the cell. Co-receptors floating in the micro-
FACTORS INFLUENCING REPLICATION
environment around a cell can hinder meeting of gp120
Interplay, between regulatory factors of the virus and and cell-bound co-receptor, thus protect it partially.
he
of the host cell, determines when, in which cell and how Delta-32 chromosomal mutation causes a homozygous
much the virus replicates. Virulence, mutations and defect in the gene responsible for expression of CCR5 in
tropism of HIV are significant viral factors. HIV-1 is about 1% of population in western European Caucasians
more virulent than HIV-2. Group M is most virulent. and their American descendents. M tropic HIV-1 cannot
Infections by more virulent strains are more prevalent replicate in them. In individuals with a heterozygous
and progress at a faster pace. Arguably, differences in
virulence are related to efficiency of replication. Human
immunodeficiency virus-1 (M) is the most common
isolate all over the world. Clade B is the most common
ot
defect, the virus cannot replicate rampantly; in them
the disease progresses slowly.
EFFECTS OF VIRUS ON CELLS

Br
in USA and Europe and Clade E in Thailand. Clade C
is emerging as the fastest spreading subtype in India, The effects of HIV virus on host cells can be following
Ethiopia and South Africa. Isolates from different cases (Figure 4):
of HIV infection (even when of same type, group or 1. The virus is known to kill cells by replicating,
clade), are seldom identical, on account of mutations. budding from them and harming the cell memory.
Mutations are clustered in POL, ENV and regulatory
e
2. The T4 cells may also get killed indirectly by HIV,

genes. Some mutations favour viral replication. by means of a viral protein gp120, which is present
Some act the other way. Recently some circulating
on the surface of the infected cells. The CD4
pe
recombinant forms (CRF) have also been identified.

receptor present on the healthy T4 cell has a strong
Cells have an inherent mechanism of protecting them affinity for gp120 and can bind to it and merge with
selves against any viral invasion. They produce ‘APOBEC the infected cell. The end result is called syncytium
3G’, a factor which inhibits viral replication. Its effect which cannot survive and all the healthy cells along
is counteracted by p23, encoded by the gene VIF. By with the infected cell are eliminated.
y
corollary, ‘VIF negative’ mutants will be impotent. 3. Human immunodeficiency virus can also evoke
Strains which bind only with CXCR4 are called X4 normal cellular immune defences opposing the
Ja
strains. The CXCR4 is present only on T-lymphocytes. infected cells.

Thus, X4 strain is ‘T tropic’. Strains with affinity for 4. The free protein may attach itself to the CD4
CCR5 are R5 strains. Since, CCR5 co-receptors are receptor of uninfected cells thus making it seem that
predominant on macrophages and monocytes (MM they are infected. This evokes an immune response.
series); R5 strain is ‘M tropic’. Strains with affinity for Interactions between HIV and the host cell are
both receptors are ‘dual tropic’. summarised in Table 1.
Besides MM series, CCR5 is present on DCs and
T-lymphocytes also. So, M tropic strain has a large CD4+ T Lymphocytes
extent of target cells. Normally, in the early phase of Infected cells suffer most and by various mechanisms.
infection, M tropic strains predominate in viral isolates Even non-infected cells suffer accelerated apoptotic
from patients. In the later phases, T tropic strains death (AAD), induced by excess, prolonged activation.
predominate. It is likely that M tropic virus, with many Molecular basis of AAD is not clear. Non-infected cells,
targets at the portal of entry, establishes infection carrying viral antigens on the surface, are sequestered 1381
PART 16
HIV and AIDS
rs
he
ot
Br
e
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Figure 4: Effects of HIV virus on host cells

Ja
(Adapted from Scientific American Oct 1988).
by antiviral IgM/IgG antibodies and killed by cytotoxic The CD4+ counts start dropping, when the virus kills
lymphocyte (CTL) T-cells. Cells with lesser viral loads lymphoid precursor cells and replenishment of lost
may not die; these get functionally impaired. Deficient cells becomes increasingly inadequate. Not all research
antigen-induced proliferation and cell-mediated workers accept this as a satisfactory and complete
immune (CMI) response are the major defects. explanation of drop in count.
In active phase of infection, CD4+ loss can be up to
Cells of MM Series and DCs
two million cells per day. Sometime loss of non-infected
cells can be more than that of infected cells. In the initial Viral replication in these cells is less profound but not
phases of infection, enormous loss does not reflect as less significant. Migratory monocytes transport HIV
an immediate, proportionate drop in their blood count, to many organs, including CNS. Tissue macrophages
1382 due to compensatory proliferation of precursor cells. establish viral reservoirs in gonads, kidneys, genital
Table 1: Interactions Between HIV and Host Cells Adaptive Immune Response of the Host
Peaceful co-existence of cell and virus
CHAPTER 3
In an immunologically normal adult, immune response,
When virus is non-replicating, the infected cell is unharmed as in other infections, would be expected in HIV
Latent virus retains viability, can start replicating at opportune time
infection too. Immune control of any viral replication is
Pathogenetic virus-cell relationship (Figure 4)
achieved through virus specific CD4+ T-cells, antibody
When virus replicates, host cell is always damaged
dependent cellular toxicity and by CTLs. But, in HIV
Cell may be killed by direct or indirect effects of the virus

infection CD4+ T-cells, themselves, are the viral targets.
Direct cell death of infected cells: due to enormous replication of virus:
Due to the vagaries of HIV antigens, the magnitude
By ‘fragmentation’ of cell due to excess ‘budding’
By ‘lysis’ of cell due to cytotoxic protein components of virus
and pattern of antibody response can be unreliable.
By ‘causing fusion’ of cells (only by ‘X4’ strains of HIV) Antibody levels may be high, but viral neutralisation,
(It is also called syncytium inducing (SI) effect of virus) not proportionately so. Moreover, mutant strains can
Indirect cell death of infected as well as non-infected cells: escape immune surveillance. Cytotoxic lymphougtes
rs
Due to apoptosis are the body’s major effective measure of inhibiting
Due to IgM and IgG antibodies and cytotoxic lymphocytes HIV replication. Efficiency of their action determines
When viral replication is not sufficient to kill the cell, it causes dysfunction: the future course of events. Initially, in HIV infection,
Functional damage these are variably successful but later on these fail.
he
Reduced normal function As infection continues, CTL counts fall, due to AAD.
Abnormal function On exhaustion of CD8+ cells, CTL response gets
suppressed (immunosuppression). Other reasons for
lack of effective immune control of viral replications are
mucosa, etc. In transmucosal (rectal/vaginal/oral) magnitude of HIV reservoirs in body, functional defects
infections, DCs get infected first. These carry the virus
on the surfaces of their processes, migrate and present
it to susceptible cells in the regional lymph nodes. Cell-
to-cell transfer is a more efficient mechanism of cellular
ot
in immunocompetent cells, life-style (intravenous drug
abuse) of patient and his genetic make-up.
Balance of forces ‘producing and killing HIV’ sets a level
of viral load in body. Higher the ‘set point’, worse is the
Br
infection than random contact between the free virus prognosis. When CTL response declines, the ‘set point’
and receptors on cell. gets raised. Disease progresses faster. Antiretrovirus
When CD4+ counts drop, MM series and DCs act as therapy, aiming at lowering the load, has to be life-long.
virus supplying factories. These infected cells show
significant functional defects. Their microbicidal PROGRESS AND CLINICAL STAGES
e
activity is reduced, response to chemotactic agents is

OF DISEASE
decreased and capacity to present antigens to T-cells is
poor. Secretion of useful IL-1 is reduced. These produce The CD4 count in peripheral blood is used as an
pe
harmful IL-6. indicator of immune function. It is, however, not a

perfect guide. Two percent of the total pool of CD4 cells
B-cells is in blood; rest is in tissues. Even a bit of change in the
These are not infected, but are functionally affected distribution can bring about a vast change in the count.
In some studies, CD4 percentage was a more reliable
y
by viral replication in other cells. The IL-6 and

gp41 molecules instigate proliferation of B-cells and indicator than CD4 count. As of today, absolute CD4
synthesis of abnormal immunoglobulins in excess count is used and has served as a useful practical guide.
Ja
quantity (hypergammaglobulinaemia). The abnormal The CD4 cells are gradually destroyed. As the
immunoglobulins form immune-complexes with other immunodeficiency advances, the patient becomes
microbial antigens. Circulating immune-complexes can vulnerable to various minor and major opportunistic
initiate type III allergic lesions. infections (OIs) (Table 2).
CD8+ Lymphocytes Pathogenesis of CNS Lesions

These also are ‘indirectly’ damaged. In the initial phases When HIV cannot cross the blood-brain barrier (BBB),
of infection, these produce CTLs, which minimise infected monocytes carry HIV across the BBB. A pre-
viral replication by killing infected CD4 lymphocytes existing inflammatory focus in brain attracts HIV
and also by producing cytokines, which inhibit viral infected macrophages and facilitates CNS infection. The
replication. As infection prolongs, the number of CTLs M tropic strain is the main invader. CNS macrophages
tends to fall, due to AAD. In terminal phases, CD8+ and microglial cells pick-up HIV and suffer. Virus and
cells get exhausted. antibodies are present in cerebrospinal fluid (CSF). 1383
Table 2: AIDS Defining Lesions in HIV Infection
Type of lesion Disease Distribution/Disease
PART 16
Protozoal and helminthic infections Cryptosporidiosis/Isosporiasis Enteritis

Toxoplasmosis Pneumonia/CNS
Fungal infections Candidiasis Oesophageal/tracheal/pulmonary
Pneumocystis jirovecii pneumonia Pneumonia
HIV and AIDS
Cryptococcosis CNS
Coccidioidomycosis Disseminated
Histoplasmosis Disseminated
Bacterial infections Disseminated/extrapulmonary
Mycobacterium tuberculosis Pulmonary/extrapulmonary
Nocardiosis Pulmonary/meningeal/disseminated
rs
Salmonellosis Pneumonia/CNS/disseminated
Atypical mycobacteriosis
Viral infections Cytomegalovirus Pulmonary/intestinal/retinal/CNS
he
Herpes simplex disease Localised/disseminated
Varicella-zoster disease Localised/disseminated
JC polyomavirus disease Progressive multi-focal leukoencephalopathy
Tumours Kaposi’s sarcoma Anywhere
B-cell non-Hodgkin’s lymphoma Anywhere
ot
Primary lymphoma of brain
Invasive cancer of cervix
Brain
Uterus
Br
Clinical manifestations depend on the severity of WHAT WE DO NOT KNOW
immune depletion (Figure 5).
T-lymphocytes are very versatile. Their homeostatic
1. Acute HIV infection: It is characterised by high control, in health/disease, is very efficient. Despite
viraemia leading to host immune response, i.e. enormous daily turnover, their number and proportion
seroconversion. This seroconversion syndrome of subsets in blood/tissues are constant. In other
e
presents with flu like syndrome or acute infectious infections there are outbursts of increase in number,
mononucleosis like features. Fever, myalgia, but homeostatic control brings the counts back to
lymphadenopathy may be seen. Usually, it goes normal, once the antigen is cleared from the body.
pe
unnoticed unless patient gives history of risk Their progressive depletion is the unique theme in
behaviour. Aseptic meningitis may also be seen. HIV infection. Mechanisms of loss of lymphocytes in
2. Seroconversion syndrome: It is followed by an HIV disease are well understood. What is not equally
extended period of clinical latency when CD4 is well understood (and accepted) is the reason why the
y
more than 500. In this stage, there is polyclonal destroyed cells are not replenished at the same rate,
stimulation of IgGs, hence a variety of autoimmune despite the remarkable capacity of CD4+ cells to self-
phenomenon like ITP, Guillain-Barre syndrome, replicate. Mechanism of progressive T-cell depletion is
Ja
polymyositis, etc. can be seen. under shroud.

3. Intermediate immune depletion: The CD4 350–500 Further, in HIV infection, depletion of the CD4 pool
During this stage, many skin manifestations and coincides with the activation of all the cellular elements
minor opportunistic infections (OIs) can develop. In of the immune system. In other infections, activation of
India, re-activation of TB is commonly seen. immunocytes leads to heightening of their performance,
4. Advanced immune depletion CD4<200: With which is favourable to the host. Paradoxically, in
advanced immunodeficiency AIDS defining OIs HIV infection, activation leads to reduced function
like neurotoxoplasmosis, fungal meningitis, of CD4+, CD8+, CTL and natural killer cells, AAD of
cryptosporidial diarrhoea, disseminated tuberculosis, even non-infected immunocompetent cells and elevated
cytomegalovirus retinitis, etc. can manifest. production of pro-inflammatory cytokines. Weak
With antiretroviral treatment, the incidence of the OIs CTL response allows ongoing viral replication, which
has markedly decreased. However, with prolongation of escalates the level of activation of immunocompetent
1384 survival of many HIV-related malignancies are rising. cells. It is conceptually acceptable that the level
CHAPTER 3
rs
he
ot
Br
e
y pe
Figure 5: Detailed correlation between the immune depletion, pathological changes and the clinical manifestations
Ja
of immune activation (if it could be measured in and there is no immune activation. SIV infected SMM
numerical figures) would be a more precise estimate of do not get immunodepleted. Obviously, up its sleeve,
the advancement of the disease than the CD4 count. We HIV has secrets, we do not know yet.
do not know the cause and mechanism of HIV-induced
widespread, progressive immune activation. SUGGESTED READINGS
‘Sooty mangabeys’ monkeys (SMM) are natural hosts to 1. Lane HC. Pathogenesis of HIV infection: total CD4+ T-cell pool,
rimian immunodeficiency virus (SIV). The magnitude immune activation and inflammation. Top HIV Med. 2010;18:2-6.
and mechanisms of death of SMM CD4+ cells by SIV 2. Mosier DE. How HIV changes its tropism: evolution and
are identical to those of human CD4+ cells by HIV. adaptation. Curr Opin HIV AIDS 2009;4:125-36.
However, in infected SMM, CD4+ counts remain normal 3. Robertson M. What we still do not know about AIDS? J Biol; 2009;8:1.
1385
4
Antiretroviral Therapy
PART 16
BB Rewari
HIV and AIDS
INTRODUCTION has to sequence the drug therapy in view of easy and

repeated viral mutability. Therefore, long-term toxicity,
The advent of antiretroviral drugs in the early drug-to-drug interaction and drug resistance, besides
1990s began a revolution in the management of monitoring facilities such as CD4 counts, viral load
human immunodeficiency virus (HIV) infection. The estimation and drug resistance assay are important
combination of at least three antiretroviral drugs
rs
considerations for HIV management.
from different groups is the current standard of care,
commonly referred to as highly active antiretroviral PRINCIPLES OF ANTIRETROVIRAL
therapy (HAART) or simply as combination THERAPY
he
antiretroviral therapy (cART) or antiretroviral therapy
(ART). There is enough epidemiological and clinical A continuous high level of replication of HIV takes place
evidence that effective combinations of antiretroviral in the body right from the early stages of infection.
drugs inhibit the replication of HIV and reduce At least one billion viral particles are produced and
viraemia to undetectable levels. Treatment slows down destroyed each day. The antiretroviral drugs act on
various stages of replication of HIV in the body and
ot
the disease progression, improves the quality of life
and increases the longevity, though it cannot eradicate
the virus with currently available antiretroviral (ARV).
Successes achieved by antiretroviral therapy (ART)
interrupt the process of viral replication. Theoretically,
these drugs can act at the following steps in viral
replication. Most commonly used drugs target the virus
mainly by inhibiting the enzymes reverse transcriptase
Br
have now transformed the common perception about
(RT) inhibitors and protease inhibitors (PIs). The
HIV infection from being a ‘virtual death sentence’
Figures 1A and B depict the various enzymes involved
to a ‘chronic manageable illness’. A recent study HIV
in viral replication and the points where ARVs target
Prevention Trials Network (HPTN) 052 has shown 96%
the virus. The Table 1 lists the classes of various ARV
reduction in chances of transmission of HIV among HIV
drugs.
serodiscordant couples by early initiation of ART. This
e
has led to development of a new concept of ‘Treatment

as Prevention’.
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GOALS OF ANTIRETROVIRAL THERAPY

The currently available ARV drugs cannot eradicate the
HIV infection from human body. This is so because a
pool of latently infected CD4 cells is established during
y
the earliest stages of acute HIV infection and persists

with a long half-life, even with prolonged suppression
Ja
of plasma viraemia to <50 copies/mL. The primary

goals of ART are maximal and durable reduction in
plasma viral levels and restoration of immunological
functions. The reduction in viral load also leads to
reduced transmissibility.
Antiretroviral drugs can also be used to reduce the risk Figure 1A: Therapy targets
of vertical transmission from infected pregnant women Based on the scientific evidence, therapy guidelines
to her new born child. The ARVs can be used after have been developed by various international agencies
exposure to HIV too, as in cases of accidental needle such as World Health Organization (WHO), Department
stick injury and in cases of sexual assault and rape. It of Health and Human Services (DHHS), British HIV
is called post-exposure prophylaxis (PEP). Association (BHIVA), International AIDS Society
Nineteen of the 26 ARV agents approved by United (IAS), National AIDS Control Organisation (NACO),
1386 States Food And Drug Administration are available etc. They define the optimum time, parameters and
in India. Considering the lifelong management, one drugs to initiate and sequence treatment. Since, the
conditions such as hepatitis B virus (HBV), hepatitis
C virus (HCV) need to be evaluated for proper selection
CHAPTER 4
of ARVs considering the efficacy and drug interactions.
The guidelines on when to start ART are depicted in
Tables 2 and 3.
As regards what ART regimen to start in a treatment
naïve patient, the principle is to start a combination of
at least three agents from different classes of ARV drugs
as this gives maximal achievable suppression of HIV
replication over a prolonged period of time and reduces
the chances of emergence of drug resistant strains.
The current national guidelines on various ART
rs
Figure 1B: Antiretroviral drugs regimens are depicted in Table 4.
drug therapy is lifelong the selection of patients for However, the WHO 2013 ARTguidelines, recommend
therapy is based on clinical, immunological and viral use of fixed dose combination (FDC) of tenofovir
he
parameters. Patients’ preparedness for such a prolonged (TDF) with emtricitabine (FTC) or lamivudine [3TC])
therapy and monitoring ensures their adherence. in a single pill as initial regimen for all patients
Opportunistic infections (OIs), if any, should be treated unless there are specific indications for other drugs
first. Patients should undergo therapy counselling. or contraindication to this regimen. The alternative
Along with detailed clinical evaluation, co-morbid regimen includes combination of zidovudine (AZT)
Table 1: Classes of ARV Drugs

Nucleoside reverse transcriptase inhibitors
(NRTIs)
Non-nucleoside reverse
ot
transcriptase inhibitors
(NNRTIs)
Protease inhibitors (PIs) Integrase inhibitors
Br
Zidovudine (AZT) Nevirapine (NVP) Atazanavir (ATV) Raltegravir (RAL)
Lamivudine (3TC) Efavirenz (EFV) Ritonavir (RTV) Dolutegravir (DTG)
Abacavir (ABC) Etravirine (ETR) Lopinavir (LPV) Fusion inhibitor (FI)
Didanosine (ddI) Saquinavir (SQV)
Emtricitabine (FTC) Darunavir (DRV) Enfuviritide (ENF)
CCR 5 co-receptor
e
Stavudine (d4T) Indinavir (IDV)

Zalcitabine (ddC) Nelfinavir (NFV) antagonists
Nucleotide reverse transcriptase inhibitors Amprenavir (APV)

pe
(NtRTI) Fosamprenavir (FPV) Maraviroc (MVC)

Tenofovir (TDF) Tipranavir (TPV)
Table 2: Indications to Start Antiretroviral Therapy (WHO 2013 ART Guidelines)

Clinical stage CD4 count value
y
Stage I or II ART if CD4 <500 mm3

Stage III and IV ART regardless of CD4
Ja
These guidelines also recommend initiating ART for all patients with HIV TB co-infection, HIV-infected pregnant women and sero-discordant couples
regardless of CD count
(Guidelines by National AIDS Control Organisation still recommend the cut-off at CD<350.
Table 3: Treatment in Specific Situations

HIV and tuberculosis (start efavirenz-based regimen)
Pulmonary and extrapulmonary TB and HIV: Start ART for all patients irrespective of CD4 count (start TB treatment first and start ART as soon as
possible after 2 weeks of ATT but definitely within 8 weeks)
HIV and pregnancy (Efavirenz not to be prescribed in first trimester)
WHO stages I and II: start ART at CD4 <350 cells/mm3
WHO stages III and IV: start ART irrespective of CD4 count
All pregnant positive women should be initiated on ART from 14 weeks onwards for prevention of HIV transmission to their infant. Those not eli-
gible for ART for their own health may stop ART 1 week after the breastfeeding period is over. 1387
with lamivudine, with nevirapine (NVP) or efavirenz Regular CD4 count every 6 months is minimum
(EFV) or combination of tenofovir and lamivudine with requirement for monitoring of immunological response.
PART 16
nevirapine. The 2013 WHO guidelines recommend viral load

monitoring for all patients on ART at least once in a year.
MONITORING OF THERAPY
ANTIRETROVIRAL DRUG TOXICITY
Frequent and regular follow-up especially during the
HIV and AIDS
initial months of the treatment is very important in Antiretroviral drugs have a broad range of toxicities,
order to ensure timely diagnosis and management of ranging from low-grade intolerance which may be self-
adverse events, to work with the patient on adherence limiting to life-threatening side effects and are depicted
issues and to diagnose any clinical manifestations like in Table 5. Differentiating between complications
OIs and immune reconstitution inflammatory syndrome of HIV disease and ART toxicity is very important.
(IRIS). Generally, morbidity and mortality on ART Conside rations should also include intercurrent
rs
occur in the first 3 months to 6 months of initiation of illness (e.g., hepatitis A, malaria, etc.) or reactions to
therapy. Clinical assessment and adherence monitoring medications other than ARVs, e.g., isoniazid-induced
should be done initially at 2 weeks and then regularly hepatitis or rash induced by co-trimoxazole. However,
on a monthly basis. Once the patient is stable on ART, most of the toxicity/effects can be adequately co-
he
a quarterly review is recommended. managed with good clinical monitoring at all levels
Table 4: Initial Regimen for ART (NACO ART Guidelines 2012) (likely to be revised soon)
Regimen ARV drug combinations Indications
Regimen I
Regimen I(a)
Zidovudine + Lamivudine
+ Nevirapine
Tenofovir + Lamivudine +
Nevirapine ot
First-line regimen for patients with Hb ≥9 g/dL and not on concomitant ATT
First-line regimen for patients with Hb <9 g/dL and not on concomitant ATT
Br
Regimen II Zidovudine + Lamivudine + First-line regimen for patients with Hb ≥9 g/dL and on concomitant ATT
Efavirenz
Regimen II(a) Tenofovir + Lamivudine + First-line regimen for patients with Hb <9 g/dL and on concomitant ATT
Efavirenz First-line regimen for all patients with hepatitis B and/or hepatitis C co-infection
First-line regimen for pregnant women, with no exposure to sd-NVP in the past
Regimen III Zidovudine + Lamivudine Regimen for patients on AZT containing first line regimen, who develop toxicity to both NVP and EFV
e
+ Atazanavir/Ritonavir Also second-line regimen for those who are on TDF containing first line regimen if Hb ≥9 g/dL
Regimen III(a) Zidovudine + Lamivudine For patients of regimen III who develop severe atazanavir toxicity
+ Lopinavir/Ritonavir First-line regimen for patients with HIV-2 infection with Hb ≥9 g/dL
pe
Regimen IV Tenofovir + Lamivudine + Second-line regimen for those who are on AZT/d4T containing regimen in the first line
Atazanavir/Ritonavir Also for patients on TDF containing first-line regimen who develop toxicity to both NVP and EFV
Regimen IV(a) Tenofovir + Lamivudine + For patients on regimen IV who develop severe atazanavir toxicity
Lopinavir/Ritonavir First-line regimen for patient with HIV/2 infection with Hb <9 g/dL
First-line regimen for all women exposed to sd-NVP in the past
y
Regimen V Stavudine + Lamivudine + Second-line for those who are on TDF containing regimen in the first-line if Hb <9 g/dL
Atazanavir/Ritonavir
Ja
Regimen V(a) Stavudine + Lamivudine + For patients on regimen V who develop severe atazanavir toxicity
Lopinavir/Ritonavir
Table 5: Toxicity of Commonly Used Antiretroviral Drugs

Occurrence Zidovudine Stavudine Nevirapine Efavirenz Protease inhibitors
Short-term Nausea, vomiting, diarrhoea Nausea, vomiting Hypersensitivity Rash, hepatotoxicity, Abdominal pain, abnormal stools
rash, drowsiness, dizziness, or bowel movements, diarrhoea,
hepatotoxicity confusion, vivid dreams nausea
Medium-term Bone marrow suppression, Lactic acidosis, Dyslipidaemia Weakness/tiredness,
anaemia, hyperpigmentation, peripheral neuritis, headache, hyperglycaemia,
lactic acidosis pancreatitis hypertriglyceridaemia,
hyperuricaemia
Long-term Lipodystrophy Lipodystrophy, Lipodystrophy
1388 dyslipidaemia
of the healthcare system. As a general principle, mild in presence of rifampicin, but remain at therapeutic
toxicity does not require discontinuation of ART or levels. It is recommended to use the standard dose of
CHAPTER 4
substitution. Symptomatic treatment may be given. EFV (usually 600 mg/day) in patients receiving EFV
Moderate or severe toxicities may require substitution and rifampicin or use rifabutin if patient is on LPV/r
with a drug of the same ARV class but with a different based ART. Details on initiation guidelines have
toxicity profile. Severe life-threatening toxicity requires already been discussed.
discontinuation of all ARV drugs until the patient is
stabilised and the toxicity is resolved. Human Immunodeficiency Virus and
Hepatitis B, Hepatitis C Co-infection
Treatment Failure: When to Change and Liver-related morbidity and mortality is very common
What to Change in patients on ART. The common cause for liver related
deaths is co-infection with hepatitis viruses. All HIV-
The adherence to ART is one of the most crucial deter-
infected patients should be screened for HBsAg, anti-
rs
minants of success of ART on long-term basis. The
HBcAb (if possible), HCV-RNA and HCV genotype
adherence of 95% or more is crucial for patients to achieve
at the baseline. It should be ensured that additional
desirable suppression of viral replication. However,
baseline investigations like liver function tests (LFTs),
even with good adherence levels, resistance occurs to
he
prothrombin time (PT), serum proteins, HBeAg and
ARV drugs over a period of time due to viral mutation
HBV-DNA are also done.
and this requires change of ARV drugs. The virological
failure appears first followed by immunological failure 1. Human Immunodeficiency Virus + Hepatitis B
which finally leads to clinical failure. It is desirable to virus:
switch the entire regimen from first- to second-line as (a) If treatment is not indicated for either infection,
soon as virological failure is detected.
Table 6 depicts the criteria for suspecting and
confirming treatment failure. ot monitor the patient.
(b) If treatment is indicated for HIV, then initiate
with TDF+3TC/FTC-based regimen along with
EFV.
Br
Table 6: Defining Antiretroviral Failure (c) If treatment is indicated only for HBV, pegylated
Clinical failure New or recurrent WHO Stage-IV condition, after interferon is recommended.
at least 6 months of ART 2. Hepatitis C virus treatment: Hepatitis C virus
Immunological Fall of CD4 count to pre-therapy baseline (or infection increases the risk of developing hepatic-
failure below); or
toxicity with ART. With regards to treatment, chronic
50% fall from the on-treatment peak value (if
e
known); or HCV should be treated first if the patient does not

Persistent CD4 levels below 100 cells/mm3 qualify for anti-HIV treatment. Patients who qualify
for anti-HIV treatment should be first initiated on
pe
Virological failure Plasma viral load >1,000 copies/mL

ART and when the CD4 rises to more than 350 cells/
The second-line regimen for patients failing on first-line mm3, anti-HCV treatment may be considered. The
ART is AZT + 3TC + ATV/r (atazanavir/ritonavir) for treatment of choice for HCV is pegylated interferon
those on TDF in first line regimen and TDF+3TC+ATV/r and ribavirin. If the patient is also on anti-HCV
for those on AZT or d4T-(stavudine) based regimen in treatment, care should be taken not to administer
y
first-line. a regimen that has AZT or Didanosine (ddI) as they

are contraindicated with ribavirin.
Human Immunodeficiency Virus/Tuberculosis
Ja
Co-infection SUGGESTED READING

Initiation of treatment for active tuberculosis (TB) 1. Guidelines for Management of HIV-infected Adults and
should always be on priority followed by initiation of Adolescents Including Post-exposure Prophylaxis, NACO.
ARV therapy as per the guidelines and should be started Ministry of Health and Family Welfare, May, 2007 (updated
2012). Available at http://naco.gov.in/NACO/Quick_Links/
as soon as the patient is stabilised on antituberculosis Publication/Treatment_Care__Support/.
treatment (ATT). In HIV-infected patients with TB 2. Panel on Antiretroviral Guidelines for Adults and Adolescents.
who are not currently on ART and who are provided Guidelines for the use of antiretroviral agents in HIV-1-infected
rifampicin-based anti-TB treatment, initiate ART adults and adolescents. Department of Health and Human
directly with EFV. No lead in dose is required for Services, USA. 27th January, 2012. Available at http://www.
aidsinfo.nih.gov/guidelines. Accessed on 10th July, 2013.
EFV. Nevirapine or PIs should not be administered
3. WHO consolidated Guidelines on Antiretroviral Therapy for
along with rifampicin because of the enzyme-inducing HIV Infection: Recommendations for a public health approach.
effect of rifampicin which renders NVP levels sub- July, 2013. Available at http://www.who.int/hiv/pub/guidelines/ 1389
therapeutical. Efavirenz blood levels are also decreased arv2013/download/en/.
5
Drug Resistance
PART 16
Alaka Deshpande
HIV and AIDS
INTRODUCTION presence of serial dilutions of inhibitor drugs. The

concentrations which are required to inhibit virus
Self-survival and replication for propagation are the two replication by 50%, i.e., Ic 50 or 90%, i.e., Ic 90, are the
main goals of every living organism. To achieve them, most commonly used methods. The process is expensive,
all organisms follow Darwinian model of continuous cumbersome and time consuming.
rs
selection of the ‘fittest’. Under adverse circumstances,
including drug pressures which pose a threat to their MECHANISMS OF DRUG RESISTANCE
survival, the microbes mutate and select those mutants
which can survive in the presence of drugs. Two distinct mechanisms are involved in HIV resistance
he
to nucleoside reverse transcriptase inhibitors (NRTI)
Human immunodeficiency virus (HIV) drug resistance
drugs:
can be broadly defined as any change that improves
viral replication and survival in the presence of the Impairment of the Incorporation of the
inhibitors. It can appropriately be termed as ‘altered Analogue into DNA
drug susceptibility’. It is an altered phenotype resulting
from a change in viral genotype.
Human immunodeficiency virus lacks the proofreading
ot
mechanism; therefore while replicating, the reverse tran-
Figure 1 show the development of resistance by the
incorporation of a nucleoside analogue into drug-
sensitive viruses resulting in the termination of the
viral DNA chain. Mutations in drug-resistant viruses
Br
scription of viral RNA into DNA is error prone introduc- prevent the incorporation of the nucleoside analogue
ing on an average one mutation for each transcription. into the growing viral DNA chain.
Primary/Major Resistance Mutations

These are directly responsible for conferring drug
resistance. They inhibit the drug action. In case of the
e
protease inhibitors (PIs), the terms are interchanged.

pe
Secondary/Minor Mutations
These mutations include:
1. Compensatory mutations, which aid in restoring
the rate of viral replication despite the presence of
resistant mutations.
y
2. Mutations that contribute to resistance in the

presence of primary mutations.
Ja
DETECTION OF RESISTANCE
Genotypic Assay
Figure 1: Resistance by interference with the incorporation of
The various genes such as RT gene, and Prot gene nucleoside analogue
are sequenced. The observed mutations are compared
with algorithms of large data base of Stanford, Agence Pyrophosphorolysis
Nationale de Recherches sur le SIDA (ANRS) and It is removal of the analogue from the prematurely
International AIDS Society (IAS). terminated DNA chain. Figure 2 shows the mechanism
of adenosine triphosphate (ATP)-mediated excision of
Phenotypic Assay the nucleoside analogue.
Phenotypic resistance of HIV is an in vitro test. Human Adenosine triphosphate in drug-sensitive viruses does
1390 immunodeficiency virus-1 isolates are cultured in the not have access to a reverse transcriptase that has
CHAPTER 5
Drug Resistance
rs
he
ot
Figure 3: Mechanism of resistance to action of non-nucleoside
reverse transcriptase inhibitors (NNRTIs)
Br
Figure 2: Resistance by ATP-mediated excision of the nucleoside
analogue the polymerisation of DNA by reverse transcriptase. In
drug-resistant viruses, mutations prevent the binding
formed a complex with a nucleoside analogue. Mutations of NNRTIs, allowing DNA polymerisation to proceed
that cause resistance to nucleoside analogues, referred normally.
e
to as thymidine analogue mutations (TAMs), allow

ATP to bind reverse transcriptase near the 3’ end Protease Inhibitors (PIs)
of viral DNA terminated by the incorporation of a The three-dimensional structure of wild type HIV-1 is
pe
nucleoside analogue. Adenosine triphosphatase then shown in Figures 4A and B. The PIs bind to certain
excises the analogue from viral DNA, allowing reverse sites and block the protease activity.
transcription to proceed normally.
Fusion Inhibitors
Thymidine Analogue Mutations
y
The fusion inhibitors destabilise the process of binding

Mutations at positions 41, 67, 70, 210, 215 and 219 to hydrophobic region HR1, thus blocking the infectivity
are referred to as TAMs because they are most often of HIV-1. Viral resistance to fusion inhibitors results
Ja
selected by zidovudine (ZDV) and stavudine (Stav) from mutations located in a stretch of ten amino acids
containing regimens. These mutations occur gradually in HR1.
and their order of emergence can vary. Thymidine
analogue mutations promote ATP or pyrophosphate Convention for Describing Drug-Resistant
mediated removal of nucleoside analogue from 3’ end of Mutation
terminated DNA strand.
Based on the amino acid sequences of RT and Protease,
NON-NUCLEOSIDE REVERSE a standard numbering system has been developed in
TRANSCRIPTASE INHIBITORS reference to wild type virus (mainly subtype B). For
example, a change in genotype from ATG to GTG
Figure 3 shows non-nucleoside reverse transcriptase at codon 184 would be reported as a change from
inhibitors (NNRTIs) have a strong affinity for a pocket methionine to valine at residue 184 or as M184V. The
next to the active site of reverse transcriptase. In drug- resistant mutations to different drugs are listed in
sensitive viruses, NNRTIs bind this pocket and block Tables 1 and 2. 1391
PART 16
HIV and AIDS
rs
A B
Figure 4A and B: Mechanism of action of protease inhibitors and resistance
he
Table 1: Resistant Mutants to Various Drugs The various factors which are responsible for drug-
ARV NsRTI/NtRTI ARV NNRTI
resistant mutations are:
AZT 41L, 67N, 70R, 210W, NFV 100I, 103N, 106A/M, 108I, 1. Gastrointestinal intolerance
215Y/F, 219Q/E NVP 181C/I, 188C/L/H, 190A
2. Episodic compliance failure
3. Poor adherence
d4T
3TC
41L, 67N, 70R, 210W,
215Y/F, 219Q/E
65R, 184V/I
EFV 100I, 103N, 106M, 108I,
181I/C, 188L, 190S/A,
225H
ot 4.
5.
6.
Drug toxicity
High pill burden
Drug interactions
Br
7. Irrational combinations
FTC 65R, 184V/I 8. Inadequate duration of therapy
ddI 65R, 74V 9. Infection with resistant strain.
ABC 65R, 74V, 115F, 184V
TDF 65R, 70E Clinical Implications
ARV = Antiretroviral; NsRTIs = Nucleoside analogue reverse transcriptase The HIV replication rates are very high. About 20 billion
e
inhibitors; NtRTI = Nucleotide analogue reverse transcriptase inhibitors; copies are produced per day. In absence of proof reading
NNRTI = Non-nucleoside reverse transcriptase inhibitors; AZT =
mechanism, replicated viruses show changes in the
Azidothymidine; d4T = 2′,3′-didehydro-2′,3′-dideoxythymidine; 3TC =
pe
2′,3′-dideoxy-3′-thiacytidine; ABC = Abacavir; FTC = Emtricitabine; genomic sequences. Under the drug pressure there is
ddl = Didanosine; TDF = Tenofovir disoproxil fumarate; NFV = Nelfinavir; a continuous selection of the ‘fittest’ virus for survival.
NVP = Nevirapine; EFV = Efavirenz. The HIV mutates and develops drug resistance.
Table 2: Resistant Mutants to Protease Inhibitors and Fusion Inhibitors

y
Drug Major mutation Minor mutation

Protease inhibitors
Ja
IDV and IDV/r 46I/L, 82A/F/T, 84V 101/F/I/R/V, 20M/R, 24I, 32I, 36I, 54V, 71V/T, 73S/A, 76V, 77I, 90M
NFV 30N, 90M 10F/I, 36I, 46I/L, 71V/T, 77I, 82A/F/T/S, 84V, 88D/S
SQV and SQV/r 48V, 90M 10I/R/V, 24I, 54L/V, 62V, 71V/T, 73S, 77I, 82A/F/T/S, 84V
FPV and FPV/r 50V, 84V 10F/I/R/V, 32I, 46I/L, 47V, 54L/V/M, 73S, 76V, 82A/F/T/S, 90M
LPV/r 32I, 47V/A, 84A/F/T/S 10F/I/R/V, 20M/R/V, 24I, 33F, 46I/L, 50V, 53L, 54V/L/A/M/T/S, 63P, 71V/T, 73S, 76V, 84V, 90M
TPV/r 33F, 82L/T, 84V 10V, 13V, 20M/R/V, 35G, 36I, 43T, 46L, 47V, 54A/M/V, 58E, 69K, 74P, 83D
DRV/r 50V, 54M/L, 76V, 84V 11I, 32I, 33F, 47V, 50V, 54L/M, 74P, 76V, 84V, 89V
ATV and ATV/r 50L, 84V, 88S 10I/F/V/C, 16E, 20R/M/I/T/V, 24I, 32I, 33I/F/V, 36I/L/V, 46I/L, 48V, 53L/Y, 54L/V/M/ T/A, 60E, 62V,
64I/M/V, 71V/I/T/L, 73C/S/T/A, 82A/T/F/I, 85V, 90M, 93L/M
Fusion inhibitors: gp41 mutations
ENF 36D/S, 37V, 38A/M/E, 39R, 40H, 42T, 43D
1392 Source: www.iasusa.org/http://hivdb.stanford.edu.
With efficacious antiretroviral (ARV) therapy, the wild
type or drug sensitive virus is destroyed. As a result,
CHAPTER 5
the viral load in the blood is suppressed to undetectable
levels. Suppression to <400 copies/mL is considered as
successful therapy. To achieve the same, the therapeutic
concentration of the drug has to be maintained in the
blood. However, with the factors mentioned above,
Drug Resistance
the serum concentration fluctuates and may reach
suboptimal levels (Figure 5) at which resistant virus
flourishes.
Figure 6: Treatment failure and drug resistance: virologic,

immunologic and clinical definitions
rs
If therapy is not changed, the number of mutations
increase, TAMs accumulate and may cause cross-
resistance with reduced susceptibility to other drugs.
he
Undetected virological failure is followed by
immunological failure which later on leads to clinical
failure (Figure 6).
In resource-limited countries, the public health
ot
approach may not monitor the viral load as it is
expensive. Immunological and clinical failure criteria
has shown poor performance in identifying HIV drug
resistance in a timely manner.
Br
The strategy using public health approach potentially
allows for long periods of unrecognisable viral failures
during which drug resistant virus can be transmitted.
The transmitted drug resistance (TDR) is rising. In
certain groups it is reported to be 18% in young people.
e
Figure 5 : Drug levels and growth of resistant virus As the number of new infections with resistant virus
(TDR) will increase, it will be a grave challenge to AIDS
pe
Emergence of drug resistance can be delayed by control programme.

maintaining the therapeutic concentration in the blood Therefore, it is now being advocated to initiate the ART
which can be achieved by: early so that suppression of viral load will decrease
1. Rational combination of ARVs the transmissibility. The present policy envisages
2. Adherence to therapy ‘treatment as prevention’. Therapeutic adherence plays
y
3. Regular monitoring of viral load. a crucial role.

The viral load is expected to be suppressed at 6 months
Ja
after initiation of antiretroviral treatment (ART). SUGGESTED READING

Thereafter it may be checked every 6 months. As long 1. Cortex KJ, Maldarelli F. Clinical management of HIV drug
as the viral load remains suppressed, the same ARVs resistance. Viruses 2011;3:347-78.
are continued. Whenever the viral load increases to a 2. Hamkar R, Mohraz M, Lorestani S, et al. Assessing subtype
and drug-resistance-associated mutations among antiretroviral-
level of 1,000 copies/mL it indicates virological failure
treated HIV-infected patients. AIDS 2010;24:S85-91.
probably due to emergence of drug resistance. At this
3. Imaz A, Falcó V, Ribera E. Antiretroviral salvage therapy for
stage, genotypic assays help in detecting the resistance multiclass drug-resistant HIV-1-infected patients: from clinical
patterns and guide the selection of second-line drugs. trials to daily clinical practice. AIDS Rev 2011;13:180-93.
1393
6
PART 16

HIV and AIDS
The advanced stage of human immunodeficiency seen which include meningitis, encephalitis, myelopathy,
virus (HIV) has been defined primarily on the basis Guillain-Barré syndrome (GBS) or peripheral neuropathy.
of opportunistic infections (OIs). Therefore, OIs have
been the main focus in the treatment of acquired Table 1: Clinical Manifestations of Acute HIV Syndrome
immunodeficiency syndrome (AIDS). With the Symptoms Incidence (%)
rs
availability of highly active antiretroviral therapy Fever 96
(HAART), more and more patients have been able Lymphadenopathy 74
to maintain sustained higher T-helper cell (or CD4)
Pharyngitis 70
counts, and thus, prone to lesser number of OI episodes.
he
Rash 70
However, this brought to the limelight many non-OI
problems which increase the morbidity in people living Myalgias or arthralgias 54
with HIV (PLHIV). Few of these conditions are well- Diarrhoea 32
recognised entities due to the virus per se but others Headache 32
are due to the side effects of HAART. Nausea/Vomiting 27
ACUTE HIV SYNDROME

This syndrome presents after 3 weeks to 6 weeks of ot Hepatosplenomegaly
Weight loss
Thrush
14
13
12
Br
Neurological manifestations 12
primary infection and corresponds to seroconversion
phase of HIV infection. It is seen in 50% to 90% of The other systemic manifestations are discussed in the
infected persons and is clinically difficult to differentiate following paragraphs:
from other acute viral infections. The syndrome is
self-remitting with resolution occurring over a period Cardiovascular Manifestations
of 2 weeks to 4 weeks due to the formation of HIV
e
antibodies. Clinically, at this point one needs to have Prevalence of cardiac involvement in HIV disease
a high degree of suspicion to reach a diagnosis as the varies from 5% to 50% but symptomatic involvement
occurs in 5% to 7% only. The cardiac involvement may
pe
patients are seronegative during this phase (window

period). Since the acute syndrome falls in the window be due to HIV per se or due to drug toxicities and OIs.
period the diagnosis can be arrived at by enzyme- Human immunodeficiency virus has been isolated from
linked immunosorbent assay (ELISA) based tests, myocardial cells and is known to cause myocarditis.
namely HIV p24 and HIV ribonucleic acid (RNA) levels Diagnosis can be supported by chest radiograph,
electrocardiograph, echocardiography and elevated
y
can be useful. If the enzyme-linked immunosorbent

assay (ELISA)-based test is used then it should be serum N-terminal-pro-brain naturetric peptide (NT-
pro-BNP). Generally, these patients have low CD4+
Ja
repeated after 3 months and 6 months of clinical

presentation. No definitive recommendations about counts mostly >200/cumm. Human immunodeficiency
the use of antiretroviral therapy (ART) are available. virus cardiomyopathy has poor prognosis.
However, treatment in acute viraemia is recommended Other findings on echocardiography include diastolic
to avoid dissemination to other organs. Symptoms dysfunction, pericardial effusion, right ventricular
and their incidence in acute HIV syndrome are given hypertrophy, pulmonary arterial hypertension and
in Table 1. non-bacterial thrombotic endocarditis.
Flu-like symptoms are the most common presenting
features in these patients. The other commonly seen
Gastrointestinal Manifestations
clinical features include rash and lymphadenopathy. Non-OI manifestations of gastrointestinal (GI) tract
Maculopapular rashes are the most common presenting may range from simple aphthous ulcers to AIDS
feature and are mainly painless, non-pruritic and enteropathy. Aetiologically, these can be due to the virus
erythematous found on the trunk, face and occasionally or HAART. Aphthous ulcers are generally found in the
1394 on extremities. Neurological manifestations are also posterior oropharynx and oesophagus. The ulcers may
produce dysphagia and severe odynophagia. Several macrophages and glial cells in central nervous system.
studies have demonstrated HIV-infected inflammatory Release of various cytokines/neurotoxins, such as
CHAPTER 6
cells in the base of these lesions suggesting aetiological interleukin (IL)-1β, tumour necrosis factor-a, IL-6 and
role. Endoscopically, the lesions resemble the tumour growth factor (TGF)-β may be responsible for
cytomegalovirus (CMV) infections and may be one or involvement of neuronal cells.
multiple with normal intervening areas. Short-term Human immunodeficiency encephalopathy is a slowly
steroids and thalidomide are effective but relapse rates progressive subcortical dementia. Typical complaints are
are high. forgetfulness, poor concentration, slowing of reasoning,
Acquired immunodeficiency syndrome enteropathy lack of energy drive, mild depression and emotional
is due to direct intestinal involvement of the virus blunting. Patients look apathetic and slow, and become
leading to villous blunting, low mitotic figures and socially withdrawn. Sexual dysfunction is common.
decreased villous-crypt ratio. Patients usually present Signs of HIV encephalopathy include impaired gait,
with chronic diarrhoea and weight loss. Stool studies, slowing of rapidly alternating movements, tremor, brisk
rs
sigmoidoscopy and/or upper GI endoscopy should be deep tendon reflexes, positive Babinski sign, slowed gaze
done to rule out other aetiologies. Treatment includes saccades, sphincter impairment including incontinence
dietary fibre supplementation, antimotility agents, and frontal release signs. Neuropsychological findings,
he
octreotide and oral rehydration solution. such as slowing of psychomotor speed, impaired short-
term memory and mental flexibility, problem with
Hepatobiliary Manifestations recalling events in correct order, disorientation to time,
Liver involvement in HIV infections is most commonly place and person and finally mutism can occur.
due to co-infection with hepatitis B and hepatitis C and Magnetic resonance imaging (MRI) is a preferred
drug reactions to HAART.
In India, hepatitis B co-infection is present in 2% to 9%
cases and hepatitis C in 2% to 3% cases. Intravenous ot
imaging modality. It reveals patchy or diffuse, hyperin-
tense and relatively symmetrical lesions of white matter
suggestive of leukoencephalopathy. Cerebrospinal fluid
(CSF) examination should be done to exclude alternative
Br
drug users may have hepatitis C virus co-infection in
up to 50% to 90%. diagnosis. A systematic mental status examination is
an important part of the examination. Quantitative
Drugs like nevirapine, protease inhibitors (atazanavir)
neuropsychological tests can be done to see progressive
can cause severe acute hepatitis or hepatic failure and
decline in neurological functions. Metabolic disorders,
their use should be properly monitored. Lactic acidosis
depression and anxiety should be ruled out.
syndrome occurs due to impaired mitochondrial DNA
e
synthesis by nucleoside reverse transcriptase inhibitors Antiretroviral therapy should be optimised. Highly
(NRTIs) such as zidovudine (AZT), didanosine (ddI) and central nervous system penetrant drugs should best be
used from the list of lamivudine, zidovudine, nevirapine
pe
stavudine. It has high mortality and the only curative

treatment is liver transplantation. and indinavir. Outlook for prolonged independent life is
guarded.
Acquired immunodeficiency syndrome cholangiopathy
is a syndrome resembling sclerosing cholangitis with HIV Myelopathy
papillary stenosis. Diagnosis is made by endoscopic Myelopathy is present in 20% patients with AIDS.
y
retrograde cholangiopancreatography (ERCP) and Vacuolar myelopathy is pathologically similar to

papillotomy can relieve the obstruction. subacute combined degeneration of cord. The histological
Ja
hallmarks are vacuoles and lipid laden macrophages

Neurological Manifestations most prominent in cervical and thoracic spinal cord. It is
Neurological diseases due to direct HIV infection occur characterised by insidious onset of leg weakness and gait
throughout the course of infection and may be due to abnormalities. Vague leg discomfort and paraesthesiae
basic pathology like inflammation, demyelination or are main sensory symptoms. Bladder and bowel
degeneration. dysfunction is also common. Posterior columns of cord
can also be separately involved producing pure sensory
AIDS-Dementia Complex (HIV Encephalopathy)
myelopathy and pure sensory ataxia. Magnetic resonance
It is an AIDS defining illness and usually occurs at CD4+ imaging of spinal cord is usually normal. Treatment of
counts >200/cumm. If untreated, 15% to 20% of HIV myelopathy with ART is not much rewarding.
patients will develop this entity. The AIDS-dementia
complex (ADC) or HIV encephalopathy (HIVE) is Peripheral Neuropathy
the term used to describe the advanced neurological It can present like acute inflammatory demyelinating
involvement. Human immunodeficiency virus infects polyneuropathy resembling Guillain-Barré syndrome. 1395
Chronic inflammatory demyelinating polyneuropathy or minimal increase in blood pressure. End-stage renal
(CIDP) with relapsing and remitting course has also disease commonly occurs in 6 months to 12 months.
PART 16
been documented. Distal sensory neuropathy is most Kidney biopsy is diagnostic. Histology is similar to
common type of neuropathy which can be due to HIV that of idiopathic focal segmental glomerulosclerosis
itself or nucleoside analogue drugs. Mononeuritis (80%) and mesangial proliferation in 10% to 15%
multiplex can also be present. Pregabalin, cases. The HIV-AN also exhibits sclerosis of the whole
carbamazepine, gabapentin, tricyclic antidepressants glomerular tuft which is distinctly known as collapsing
HIV and AIDS
and analgesics can provide symptomatic improvement. glomerulopathy. Majority of patients have CD4+ T-cell
counts <200/cumm. Angiotensin converting enzyme
Haematological Manifestations (ACE) inhibitors and prednisolone with tapering doses
Anaemia is the most common haematological finding. have been effective in preventing the progress of the
Normocyctic normochronic anaemia is found in HIV- disease. Immunoglobulin A (IgA) nephropathy can also
associated bone marrow suppression. Reticulocyte count occur in HIV patients.
rs
is inappropriately low. Drugs like zidovudine are the Acute tubular necrosis can result from nephrotoxic
other main culprit. It can block erythroid maturation drugs, hypovolaemia, shock and sepsis. Drugs like
earlier than other components of bone marrow. Mean pentamidine, amphotericin, adefovir, tenofovir,
he
corpuscular volume of RBCs is increased. Human non-steroidal anti-inflammatory drugs (NSAIDs)
immunodeficiency virus-induced anaemia may respond and radiocontrast agents can cause acute tubular
well to ART therapy. Erythropoietin is also effective necrosis. Patient should be closely monitored and dose
if its levels are less than that expected for severity of adjustments or stoppage of drug should be considered
anaemia. Zidovudine should be replaced. once renal dysfunction develops.
Neutropenia is mostly mild but sometimes it can be
or therapy-induced. Presence of neutropenia generally

indicates advanced disease. The G-CSF or GM-CSF
ot
severe. The cause of neutropaenia can be a direct effect
Rheumatological Manifestations
Rheumatological manifestations include Reiter’s
syndrome, non-specific reactive arthritis, psoriatic
Br
can be of use in increasing counts of neutrophils arthritis and septic arthritis. Myopathy, vasculitis
regardless of the cause. Myelosuppressive drugs should and diffuse infiltrative lymphocytosis syndrome
be removed. can also occur. But most commonly seen are the
Thrombocytopenia can be due to decreased platelet simple arthralgias which are intermittent, mild and
survival probably by immunological mechanism polyarticular, mainly seen in the later stages of the
e
and decreased platelet production due to infection disease. Myopathy occurs in 1% to 2% of all HIV
of megakaryocytes with HIV. Treatment should be patients and can appear at any stage of the disease.
initiated in patients having platelet count <20,000/ Myopathy can be drug-induced, inflammatory or non-
pe
cumm. Intravenous immunoglobulin (IVIG) and anti- inflammatory. Drug notorious for causing myopathy
Rh(D) are equally effective but sustained responses is zidovudine, probably due to mitochondrial
are few. Prednisolone 0.5 mg/kg to 1.0 mg/kg is used toxicity. Inflammatory myopathy indistinguishable
cautiously. Splenectomy may be needed in relapsed/ from idiopathic polymyositis can also be seen.
refractory cases. Zidovudine should be replaced first before starting
y
immunosuppressive drugs.
Persistent generalised lymphadenopathy is an early
clinical presentation of body response to HIV infection. Vasculitis should be considered in the setting of
Ja
The condition is defined as lymph node enlargement unexplained multi-system disease, unexplained myo
of two or more extrainguinal sites of size >1 cm for pathy or arthritis, unexplained organ ischaemia and in
at least more than 3 months without obvious cause. the presence of mononeuritis multiplex.
Histologically follicular hyperplasia of lymph nodes is Diffuse infiltrative lymphocytosis syndrome is
present. presumably of autoimmune origin. Dryness of mouth,
eyes and massive enlargement of parotids are common.
Renal Manifestations Histopathological study of salivary gland shows
Human immunodeficiency virus-associated nephro- infiltrating lymphocytes which are CD8+ cells.
pathy (HIV-AN) is a true direct complication of HIV
Endocrine and Metabolic Disorders
infection occurring in 2% to 10% of HIV infected
individuals. Clinical presentations of HIV-AN consist Hyperglycaemia can occur due to various drugs used
of heavy proteinuria (90% have nephritic range), rapid in the treatment of HIV disease. Protease inhibitors,
1396 deterioration of renal function, normal size of kidneys, no pentamidine and didanosine are main culprits.
Hypercholesterolaemia is usually seen with protease diarrhoea or fatigue lasting more than 30 days in the
inhibitors and efavirenz. In the HAART era, high absence of a defined cause other than HIV infection.
CHAPTER 6
density lipoprotein (HDL) cholesterol levels are Dietary assessment and weight monitoring should
reduced, total and low density lipoprotein (LDL) be done. Key to prevention and management of HIV
cholesterol levels are increased with concomitant wasting is aggressive management of infection.
severe hypertriglyceridaemia. Hydroxy-methyl-glutaryl
CoA reductase (or 3-hydroxy-3-methyl-glutaryl- Pulmonary Manifestations
CoA reductase or HMGCR) inhibitors (statins) with diet
Most of the pulmonary manifestations are due to OIs and
modification and exercises should be used to treat these
should be ruled out before attributing it to HIV disease.
conditions. Lipohypertrophy and lipoatrophy can occur
Lymphocytic interstitial pneumonitis (LIP), non-specific
with protease inhibitors and stavudine on long-term
interstitial pneumonitis (NIP) and increased incidence
use. Mitochondrial toxicity is the probable mechanism.
of pulmonary arterial hypertension (PAH) are seen as
Hypogonadism is common in HIV patients. Patients
rs
the non-OI manifestations of HIV disease. Lymphocytic
present with decreased libido, impotence, gynaecomastia interstitial pneumonitis is common in children and
or amenorrhoea. Production of gonadotrophin-releasing around 1% of adults with untreated HIV infection. It
hormone (GnRH) is decreased or its release is abnormal. is generally self-limiting and no specific treatment is
he
Diagnosis is made by low or normal levels of follicle- required. In severe cases, glucocorticoids are given in
stimulating hormone (FSH) and luteinising hormone short course. Non-specific interstitial pneumonia is
(LH) in response to GnRH. Magnetic resonance seen in half of all patients untreated with ART. This is
imaging of brain should be done to see pituitary gland. also self-limiting and requires no therapy. Pulmonary
Management includes hormone replacement therapy. arterial hypertension is seen in 0.5% of HIV infection.
Hypothyroidism, hyperthyroidism and adrenal
dysfunction are rare. Less than 5% of patients with
AIDS have adrenal insufficiency.
HIV-associated Wasting
ot
There is no clear benefit of ART in PAH with a median
survival of 2 years.
SUGGESTED READING
Br
1. American Academy of HIV medicine. Fundamental of Global
It is an AIDS defining illness. Centers for Disease HIV Medicine; 1st ed. IHL Press; 2009; info@ihlpress.com; www.
Control and Prevention (CDC) definition of HIV- ihlpress.com.
associated wasting is a weight loss of >10% associated 2. Raphael D, Masur H, Saag HS, et al. AIDS Therapy; 3rd ed.
with intermittent or constant fever and chronic Philadelphia: Churchill Livingstone/Elsevier; 2008.
e
y pe
Ja
1397
7
PART 16
Jyoti Wadhwa
HIV and AIDS
INTRODUCTION name Pneumocystis carinii now refers only to the

Pneumocystis that infects rats and P. jirovecii refers to
Opportunistic infections (OIs) are so called as they the distinct species that infects humans.
manifest in a host with impaired immunity in
In a study conducted by Udwadia, et al from Mumbai,
advanced stages of human immunodeficiency virus
PCP was the second commonest pulmonary disease in
rs
(HIV) infection. They cause substantial morbidity
HIV patients after tuberculosis accounting for 13% of
and mortality in HIV patients throughout the world.
all the HIV positive admissions.
Even though highly active antiretroviral therapy
(HAART) has reduced the incidence of OIs seen today, About 90% of PCP cases occur in patients with CD4
he
these infections continue to manifest in patients with counts less than 200 cells/µL. Other predisposing factors
advanced stages of HIV infection or in patients with include oral candidiasis, previous episodes of PCP,
reduced compliance or drug resistance. recurrent bacterial pneumonia and high HIV RNA levels.
It is not only the HIV virus which creates a favourable Clinical Features
atmosphere for these infections; these pathogens also
alter the natural history of HIV virus and aid in viral
replication.
The more severe and life-threatening complications of ot Clinical features include usually a subacute indolent
course with presentation after several weeks of
symptoms which usually consist of progressive
exertional dyspnoea (95%), non-productive cough
Br
HIV infection occur in patients with CD4+ T cell counts
(95%), fever (80%), weight loss and chest discomfort.
<200 cells/µL. A diagnosis of acquired immunodeficiency
Rarely haemoptysis may be present.
syndrome (AIDS) is made in a patient with HIV
infection and a CD4 + T-cell count <200 cells /µL or the Pulmonary examination may be normal or may reveal
one who develops one of the HIV-associated diseases fine crepitations with rhonchi. Arterial blood gas (ABG)
considered to be indicative of a severe defect in cell- analysis may reveal severe hypoxaemia with Type 1
e
mediated immunity. Table 1 is showing conditions respiratory failure which carries a poorer prognosis.
listed in AIDS surveillance case definition.
Diagnosis
pe
Table 1: Conditions Listed in AIDS Surveillance Case Definition Diagnosis may be based upon the classical clinical
features apart from the chest X-ray which shows
Candidiasis of bronchi, trachea, lungs or oesophagus
Pneumocystis jirovecii pneumonia
perihilar infiltrates extending up to lung bases. Less
Extrapulmonary cryptococcosis commonly patchy asymmetric infiltrates may be
present with pneumatocoeles. Pleural effusion is
y
Cryptosporidiosis
Cytomegalovirus (other than liver, spleen or nodes) very rare and its presence should raise the doubt of
an alternative diagnosis. High resolution computed
Ja
Herpes simplex: chronic ulcer(s) (>1 month’s duration); or bronchitis,

pneumonia, or oesophagitis tomography (HRCT) may show patchy ground glass
Mycobacterium tuberculosis attenuation. Definitive diagnosis is based upon
Mycobacterium avium complex the histological confirmation of cysts in sputum
Burkitt’s lymphoma examination or bronchoalveolar lavage (BAL). Cysts
Kaposi’s sarcoma usually stain with toluidine blue, Gonori methenamine
Invasive cervical cancer silver stain and periodic-acid Schiff (PAS) stain or
Toxoplasmosis of the brain direct immunofluorescent stain. The cysts resemble
Recurrent Salmonella septicaemia crushed ping-pong balls and are present in aggregates
of 2 to 8 in contrast to Histoplasma or Cryptococcus
PNEUMOCYSTIS PNEUMONIA which typically do not form aggregates of spores or
cells. Gallium scans may be used when chest X-ray is
Pneumocystis pneumonia (PCP) is caused by a normal, especially in early stages of the disease which
fungus Pneumocystis jirovecii which also shares some shows an increased diffuse symmetrical pulmonary
1398
of its biological features with protozoa. The older uptake. Its sensitivity is as high as 100%, but specificity
may be as low as 20%. Nevertheless, it may be used as Clinical Features
an adjunctive test when chest X-ray is normal in initial
CHAPTER 7
Symptoms of tuberculosis include fever, productive
stages and sputum fails to reveal the organism.
cough, shortness of breath, anorexia and weight loss.
Treatment In patients with advanced HIV disease, lower lobe,
middle lobe and miliary infiltrates (Figure 1) are more
Trimethoprim-sulphamethoxazole (TMP-SMX) is common than cavitation. Severe immunodeficiency
the recommended treatment and prophylactic agent.
(CD4 counts <200 cells/µL) favours extrapulmonary
Trimethoprim 15 mg/kg/day to 20 mg/kg/day and SMX tuberculosis development (lymph nodes, meningitis,
75 mg/kg/day to 100 mg/kg/day, given per orally in three gastrointestinal [GI] involvement, etc.) with poor
divided doses should be given for 21 days. Patients with formation of granulomas.
moderate to severe disease defined by PaO2<70 mmHg or
alveolar arterial O2 gradient ≥35 mmHg should receive Diagnosis
rs
adjunctive steroids. Prednisolone is given as 40 mg bid for
Diagnosis is based on the history, chest radiographs
5 days, then 40 mg/day for 5 days and 20 mg/day for next
and acid-fast bacteria (AFB) staining and tissue
11 days.
histology of the involved site (lymph node). Nucleic acid
amplification tests yield rapid diagnosis of tuberculosis
he
MYCOBACTERIUM TUBERCULOSIS and more sensitive than AFB smear producing positive
India is the highest TB-burden country globally results for 50% to 80% of smear negative culture
(29.9 million patients), accounting for one-fifth of the positive specimens.
global incidence and two-third of the cases in south-east
Treatment
Asia. Each year, 1.9 million new cases of TB occur in the
country, of which about 0.8 million are infectious new
smear positive pulmonary TB cases. The 2007 survey
on tuberculosis demonstrated that the prevalence of otTreatment of suspected TB in HIV-infected individuals
is the same as for those who are HIV uninfected and
should include an initial intensive phase of four-drug
Br
HIV among TB patients varied between 1% and 13.8% combination of isoniazid, rifampin, pyrazinamide
among the 15 surveyed districts. and ethambutol followed by maintenance phase with
Tuberculosis can occur at any CD4 T lymphocyte two drugs (INH + Rif) for 4 months. The success of
(CD4 cell) count, although the risk increases with treatment is greatly enhanced when given as directly
progressive immunodeficiency. The estimated annual observed treatment, short-course (DOTS) though
risk of active TB among HIV-infected patients with several studies have shown increased risk of treatment
e
latent tuberculosis infection (LTBI) is 3 to 12 times failure or acquired resistance to rifamycin class when
higher than for the general population. Furthermore, given treatment is given less than daily therapy.
pe
development of TB increases viral load and the risk Adjunctive corticosteroid therapy increases survival
of HIV disease progression and death in TB-HIV for patients with HIV-related TB involving the central
co-infected patients. nervous system (CNS) and pericardium.
y
Ja
Figure 1: Chest radiograph and HRCT of chest in a HIV positive patient with miliary tuberculosis 1399
Antiretroviral therapy (ART) is recommended in all cases of cryptococcal meningitis are diagnosed
HIV-infected persons with TB. worldwide every year and the disease accounts for
PART 16
For ART-naive patients, ART should be started within more than 600,000 deaths. Most cases are observed
2 weeks when the CD4 count is <50 cells/µL and by in patients who have CD4 T lymphocyte (CD4) cell
8 weeks to 12 weeks for all others. counts <100 cells/µL.
The preferred treatment regimen for HIV-related Clinical Features

HIV and AIDS
TB disease is rifampin-based TB therapy with an

antiretroviral (ARV) regimen of efavirenz plus two It usually presents with insidious onset fever, headache
nucleoside (tide) analogues. For patients who are and malaise. Personality changes, insomnia, memory
absolutely unable to take efavirenz due to intolerance loss may be seen. Neck stiffness, photophobia and focal
or early pregnancy, nevirapine-based ART can be used, deficits are less commonly observed.
but the lead-in dose of nevirapine should be omitted for Any organ may be involved. Lung involvement may be
rs
patients who are established on rifampin for at least in the form of lobar consolidation or nodular infiltrates.
2 weeks and plasma HIV RNA levels should be monitored Skin involvement in the form of raised umbilicated
closely. If the patient is unable to tolerate any of the non- papulonodular lesions (cryptococcomas) mimicking
nucleoside reverse transcriptase inhibitor (NNRTIs) or molluscum contagiosum may be seen. Chest X-ray
he
HIV strains with resistance to both NNRTIs, ritonavir may show reticulonodular infiltrates, cavities and
boosted protease inhibitor (PI) needs to be given lymphadenopathy. Diagnosis is made by demonstration
with rifabutin based antitubercular therapy. All PIs of Cryptococcus in cerebrospinal fluid (CSF) after
markedly increase serum concentration of rifabutin, staining with India-ink preparation or CSF culture
hence a lower dose of 150 mg/day of rifabutin is and by CSF cryptococcal antigen detection by latex
recommended with PI-based ART. Close monitoring
of the patient, taking this regime is important as the
serum levels of rifabutin will be inadequate if the
patient stops taking PI during the course.
ot agglutination.
Treatment
Br
Treatment consists of intravenous amphotericin B
Sputum cultures should covert to negative by four
(0.7 mg/kg) daily or liposomal amphotericin (4 mg/kg
months of treatment, failure of this to happen should
to 6 mg/kg) daily, with flucytosine 25 mg/kg qid for at
prompt a physician to evaluate for treatment failure
least 2 weeks or until the CSF culture turns negative.
and possible drug resistance.
This is followed by fluconazole 400 mg/d PO for 8 weeks
Infection with atypical mycobacteria is also seen with and then fluconazole 200 mg/day until the CD4+ T-cell
e
increasing frequency in patients with HIV infection count has increased to >200 cells/µL for 6 months in
specially with CD4 <50 cells/µL. The most common response to ART.
atypical mycobacterial infection is with M. avium or
pe
M. intracellulare species—the Mycobacterium avium TOXOPLASMOSIS

complex (MAC). Atypical mycobacteria are ubiquitous
in the environment, including both soil and water. There Toxoplasmosis is caused by protozoan Toxoplasma
is little evidence for person-to-person transmission of gondii. Toxoplasmosis is a late complication of HIV
MAC infection. Prior infection with Mycobacterium infection and occurs at a CD4 count <200 cells/µL.
y
tuberculosis confers some immunity and decreases Cerebral toxoplasmosis usually represents reactivation
the risk of MAC infection. Clinical features are same of latent tissue cysts. Primary infection occurs by
Ja
as that of mycobacterial tuberculosis with chest X-ray consumption of undercooked meat containing tissue
abnormalities in only 25% of the cases. Chest X-ray shows cysts or handling cat faeces containing oocysts.
predominantly lower lobe involvement and miliary
mottling. Hilar and/or mediastinal lymphadenopathy Clinical Features
may also occur. Diagnosis is usually by demonstration Most common clinical features of toxoplasmosis
of MAC in sputum, blood or marrow. Treatment consists are headache, focal seizures, focal deficits, altered
of clarithromycin, rifabutin and ethambutol. Therapy sensorium and fever.
can be discontinued with CD4 counts improving to >100
cells/µL for 3 months to 6 months. Diagnosis
CRYPTOCOCCOSIS Diagnosis is usually made by demonstration of anti-
toxoplasma immunoglobulin (Ig) G antibody. Cerebral
Most of the HIV associated cryptococcal infections are imaging typically shows contrast enhancing lesions
1400 caused by Cryptococcus neoformans. Nearly 1 million in grey matter and basal ganglia with perilesional
oedema. If feasible, CSF polymerase chain reaction Hence indication to treat a patient for hepatitis B in a
(PCR) for Toxoplasma gondii may be performed. It has HIV hepatitis B co-infected individual is an indication
CHAPTER 7
a sensitivity of 50% and specificity of 96% to 100%. for ART initiation irrespective of the CD4 count.
Though considered as gold standard for diagnosis
of toxoplasmosis, stereotactic brain biopsy is rarely HEPATITIS C
performed and may be considered as an option in
Hepatitis C virus (HCV) is a linear single-stranded
patients deteriorating with empirical treatment for
RNA positive sense virus; the estimated worldwide
toxoplasmosis.
prevalence of HCV infection is 2% to 3%. Seven distinct
Treatment HCV genotypes have been described though worldwide
genotype 1 is the most common. Since HCV does not
Treatment consists of sulphadiazine and pyrimethamine replicate via DNA intermediate, it does not integrate
with leukovorin as needed for a minimum of 4 weeks to into the host genome. Most cases of hepatitis C are
rs
6 weeks. Alternative therapeutic regimens include TMP acquired through percutaneous exposure while sexual
+ SMX (5 mg/kg/day to 25 mg/kg/day), clindamycin contact is relatively inefficient mode of transmission.
with pyrimethamine; atovaquone plus pyrimethamine; Hepatitis C virus RNA represents the gold standard
and azithromycin plus pyrimethamine plus rifabutin. test for HCV diagnosis especially in HIV patients as
he
anti-HCV antibody may be false low or absent in HIV/
Hepatitis B HCV co-infected patients.
Human immunodeficiency virus infection is associated
with approximately a three-fold increase in the devel-
Treatment
opment of persistent hepatitis B surface antigenaemia. After acute HCV infection, the likelihood of developing
Clinical Features
With acute infection, patient may be asymptomatic ot
chronic hepatitis is 85% to 90% and is even more
progressive and severe in HIV co-infected patients;
hence all HIV/HCV co-infected patients should be
considered for treatment for HCV in contrast to HCV
Br
or may present with jaundice, fever, right upper
quadrant pain, nausea and vomiting. Patients with mono-infected patients.
chronic infection may be asymptomatic or may develop Hepatitis C virus genotype should be determined prior
jaundice, ascites, coagulopathy or encephalopathy. to treatment initiation as it is an important determinant
Rarely, they may present with glomerulonephritis with of response to interferon treatment for hepatitis C
nephrotic syndrome, arthritis and cutaneous vasculitis (genotype 2>3>1 and 4). Before initiating HCV therapy,
e
(palpable purpura). a patient’s HIV disease should be clinically stable with

or without ART. Human immunodeficiency virus/HCV
Treatment co-infected patients with CD4 counts <350 cells/µL who
pe
are receiving ART, should receive at least 6 months of

Treatment is indicated for patients with chronic
ART before starting HCV treatment; HCV treatment
hepatitis B with persistence of HBsAg for more than six
is not routinely recommended in patients with CD4
months and presence of IgG anti-HBc antibody. Anti-
counts <200 cells/µL.
HBV therapy is indicated for chronic hepatitis B with
y
elevated alanine transaminase (ALT) levels (>2 times The combination of peginterferon-alfa (PegIFN) plus
normal) and elevated HBV DNA >2,000 international ribavirin is the recommended treatment for HIV/
HCV-co-infected patients (48 weeks for genotype 1 and
Ja
units/mL or clinically manifesting as cirrhosis or

significant fibrosis on histopathology. 24 weeks for genotype 2 and 3). Two ongoing phase
2 clinical trials of boceprevir or telaprevir plus PegIFN/
For HIV/HBV co-infected individuals, ART must include ribavirin for the treatment of HCV genotype 1 infection
two drugs active against HBV, preferably tenofovir in HIV/HCV co-infected patients also demonstrate
and emtricitabine, regardless of the level of HBV greater efficacy than PegIFN/ribavirin alone.
DNA. This reduces the likelihood of development of
immune reconstitution inflammatory syndrome (IRIS)
CYTOMEGALOVIRUS
against hepatitis B. Tenofovir is active against wild
type and lamivudine resistant strains of hepatitis B. Usually manifests as cytomegalovirus (CMV) retinitis
In case of renal dysfunction, entecavir can replace and is a late complication of HIV infection. It usually
tenofovir. Since these drugs are active against HIV manifests at a CD4 count of less than 100 cells/µL. It
also, they should not be used alone for the treatment of usually presents as progressive painless loss of vision
hepatitis B in a HIV-hepatitis B co-infected individual. though patient may complain of floaters or blurring
1401
Table 2: CDC Guidelines for Opportunistic Infection Prophylaxis
Opportunistic infection Indication Treatment (I line) Alternative treatment
PART 16
Pneumocystis pneumonia CD4 <200/µL TMP-SMX DS 1 tab OD Dapsone 100 mg OD

(PCP) Oropharyngeal candidiasis
Prior episode of PCP
May stop prophylaxis when CD4 >200/µL
for ≥3 months
HIV and AIDS
Toxoplasma gondii encephalitis Toxoplasma IgG +ve with CD4 <100/µL TMP-SMX DS 1 tab OD Dapsone 100 mg daily + (pyremethamine
May stop prophylaxis when CD4 >200/µL 50 mg + leukovorin 25 mg) PO weekly
for ≥ 3 months
Mycobacterium avium complex CD4 <50/µL Azithromycin 1,200 mg Rifabutin 300 mg/day PO
(MAC) Prior documented disseminated disease PO weekly
May stop prophylaxis when CD4 >100/µL
rs
for ≥3 months
Cryptococcus neoformans Prior documented disease Fluconazole 200 mg/ Itraconazole 200 mg/day PO
May stop prophylaxis when CD4 >200/µL day PO
for ≥6 months with no evidence of active
he
disease
Syphilis For individuals exposed to a sex partner Benzathine penicillin G Doxycycline 100 mg PO BID for 14 days
with a diagnosis of primary, secondary, 2.4 million units IM for Or
or early latent syphilis within the past 90 1 dose Ceftriaxone 1 g IM or IV daily for 8–10 days
days
of vision. Diagnosis is made on fundus examination

showing perivascular haemorrhage and exudates. ot
Br
Treatment
Therapy for CMV retinitis consists of oral valganciclovir,
IV ganciclovir, or IV foscarnet with cidofovir as an
alternative. Combination therapy with ganciclovir and
foscarnet has been shown to be slightly more effective
e
than either ganciclovir or foscarnet alone in the patient

with relapsed CMV retinitis. A three-week induction
pe
course is followed by maintenance therapy with oral

valganciclovir.
CANDIDIASIS Figure 2: Oral candidiasis in buccal mucosa of an HIV positive patient

Oral candidiasis usually occurs at a CD4 count
y
<300 cells/µL. Patients may be asymptomatic or may

complain of burning sensation with odynophagia. SUGGESTED READING
Ja
Diagnosis is clinical with visualisation of white cheesy 1. Pradeep Seth. The situation of HIV/M tuberculosis co-infection in
exudates on hard or soft palate, buccal mucosa or on India. The Open Infectious Diseases Journal 2011;5: 51-9.
the tongue surface (Figure 2). The exudates can be 2. Su YS, Lu JJ, Perng CL, Chang FY. Pneumocystis jirovecii
scraped off and directly examined under microscope pneumonia in patients with and without human immunodeficiency
virus infection. J Microbiol Immunol Infect 2008;41:478-82.
with potassium hydroxide (KOH) stain. Treatment
3. The HIV-TB Co-infection. National AIDS Control Organisation
consists of oral fluconazole 100 mg/day to 200 mg/day for and Central TB Division. Ministry of Health and Family Welfare,
7 days which should be extended to 14 days to 21 days Government of India, 2008 (available at http://www.nacoonline.
for oesophageal candidiasis (Table 2). org).
1402
8
Non-pharmacologic Interventions and Prevention
CHAPTER 8
R Sajithkumar

INTRODUCTION ABC OF HIV PREVENTION
Human immunodeficiency virus (HIV) is one with a long A—Abstinence, B—Being faithful with an uninfected
incubation period and florid disease takes a long time partner and C—Condom use, proper and consistent,
before manifesting clinically. This, therefore, provides has been the cornerstone of prevention of sexual
a unique window period to the healthcare providers transmission of HIV. Such a strategy has been found to
rs
and the infected persons to prevent its progression be useful and successful but the first practice is hard to
and, in case of disease, to reduce its morbidity. This follow and, in the second, the HIV status of the partner
chapter deals with interventions in asymptomatic and has to be known, which at times is difficult. But effective
he
symptomatic persons living with HIV/AIDS (PLWHAs) use of condom is possible and quite useful even when
during any stage of HIV disease. Counselling is a the HIV serostatus is not known. This again helps in
useful tool right from the stage when the tests are the prevention of many other infections as well.
being planned to crisis situations. Nutritional support
is another well-recognised intervention. Periodic INTERVENTIONS FOR SPECIAL GROUPS
screening and monitoring will assist in early detection
and treatment of infections and malignancies. There are
effective preventive vaccines for many infections which
can be used in PLWHAs. Human immunodeficiency ot
Interventions in this category can be divided into two
main groups: (1) those practising high-risk sexual
behaviour, and (2) those indulging in IV drug use.
Br
virus vaccine development is advancing. Many vaccines
are being studied for their potential therapeutic efficacy Reducing Sexual Transmission
(delaying progress) even when primary prevention is The high-risk sexual behaviour includes: (1) male
not possible. Many alternative therapies (like yoga) homosexuality with multiple partners; (2) multi-
have been occasionally reported as useful. partner sex; and (3) sex with casual (non-regular)
The interventions in HIV disease can be grossly sex partners. All forms of paid sex can be considered
e
classified as follows: dangerous. In heterosexual practice (sex between

1. Interventions for general public opposite sexes), the risk is graded differently as
pe
2. Interventions for vulnerable groups unprotected anal intercourse, unprotected vaginal

3. General interventions amongst PLWHAs intercourse, unprotected oral sex and as protected sex
4. Specific interventions at certain stages. using condoms. The strategies aim at shifting a person
from practices of higher risk to safer practices. Condom
INTERVENTIONS FOR GENERAL PUBLIC promotion plays a major role in all these modalities.
y
These include information, education and communi- Syndromic Approach to Sexually Transmitted
Ja
cation (IEC) strategies, e.g., general education, sex Infections (STIs)

education, health awareness programmes, etc. They
Management is dealt with in Chapter 11 of Part 11.
aim at generating knowledge which leads to healthy
attitudes, improved behaviour translating to better
Reducing Transmission by IV Drug Use
practices. The behaviour change must be regularly
reinforced with repeated attempts. Health issues and Intravenous drug users have been recognised as a
safe sex education at various levels have been found to vulnerable group from the early days of the epidemic.
be useful in prevention and care. The IEC also generates Sharing syringes used for IV injection particularly was
healthy attitudes in infected persons, special categories, an efficient mode of transmission in many populations.
i.e., intravenous drug users (IVDUs), men having sex Recreational drug use is illegal in many countries and
with men (MSM) and commercial sex-workers (CSWs). unacceptable in many cultures. Even non-injectable
Across cultures, this is the most commonly tried drug use makes people vulnerable by modifying their
intervention and adjudged the most acceptable. These level of judgement and taking away inhibitions leading
will also ensure protection from many other recognised to unsafe sex behaviours. Intravenous drug users 1403
or unrecognised infections as well. have been targeted in many activities across the globe.
Supply reduction, demand reduction and harm Reducing Transmission in Healthcare Settings
reduction are three major strategies in this group.
It is dealt with in Chapter 9 of Part 17.
PART 16
Supply reduction aims to prevent illegal trafficking,

confiscation and destruction of drug supplies and
Targeted Intervention Approach of NACO
supply lines. Demand reduction is practised in many
(India)
educational institutions. Proper IEC programmes on
the risks of drug use are acceptable to all societies and National AIDS Control Organisation (NACO),
HIV and AIDS
all ages. Rehabilitation and detoxification clinics modify Ministry of Health and Family Welfare, Government
use pattern by scientific methods like counselling, of India has adopted targeted intervention as a regular
methadone or buprenorphine substitution, etc. These strategy. It envisages comprehensive and integrated
will gradually reduce dependency and promote approach to marginalised and vulnerable populations
adherence to counselling and healthy lifestyles. Walk- like CSWs, MSMs, IVDUs, migrant labourers, street
in centres with facilities for sterilisation or sterile children, prisoners, etc. There are hundreds of projects
rs
injections are beneficial. Needle exchange programmes run by non-governmental organisations (NGOs) and
which aim at providing clean needles have the objective other agencies across the country. They perform
of reducing the sharing of needles and syringes need assessment, counselling, education, peer group
he
and preventing transmission of many infections. activities, behaviour change communication monitoring
Community-based rehabilitation packages including and care and support activities. They are run with
promotion of safer sex practices are needed for IVDUs. financial assistance and scrutinised by the state AIDS
There is evidence from multicentric studies that these control societies.
significantly reduce HIV transmission.
Reducing Transmission among MSM

Men having sex with men (male homosexuals) have ot Voluntary Counselling and Testing (VCT)
One major activity aimed at making the above facilities
available to the public at low cost includes voluntary
Br
been recognised as vulnerable from the early days of counselling and confidential testing centres (VCTs) in
the epidemic. Many of them have problems like having all states. The services of male and female counsellors
sex with many partners (regular and non-regular) at for pre-/post-test counselling and laboratory technician
any point in time, having STIs, propensity for anal for serological testing are available. These centres have
intercourse, habituation to injecting/other drug use become integrated counselling and testing centres
and having sex with female partners. Polydrug use, (ICTCs). These will act as the portal of entry for people
e
partner violence, depression and other psychosocial with high-risk behaviour to enter the care set-up
issues are also important. Specialised sex education voluntarily and confidentially. They will start the pre-
pe
packages, condom promotion, integrated STI care, ART care for PLWHAs in designated ART centres too.
context-specific counselling, etc. are strategies found
successful for them. GENERAL INTERVENTIONS AMONGST
HIV-INFECTED PERSONS
Reducing Transmission by Blood and
Life-style Changes
y
Blood Products
All health establishments handle emergencies where Avoidance of high-risk behaviour and change to safer
Ja
blood is required. Proper screening, donor selection, sex and safer injection practices are the most important
storage and delivery are vital. Quality of screening is issues for PLWHAs at all stages. The usage of condoms
ensured. Licensing of blood banks and avoidance of and sterile needles must be insisted. Avoidance of both
all unauthorised blood collections are needed across needle-sharing and dangerous sex practices (multi-
the globe. Recruitment of voluntary low risk donors is partner sex, unprotected sex) do help. Even among
encouraged and all professional donors excluded. The well-educated people, there is a wrong belief that if both
risk of transmission through a sero-negative blood partners are infected, there is no need for protected
during window period remains as a rare but important sex. Protected sex at any stage will help in preventing
possibility. Curtailing the unnecessary and casual use first or subsequent infection with various subtypes of
of blood and blood products should be discouraged. HIV and more importantly other sexually transmitted
Use of better methods like antigen tests, PCR can pathogens. It is well known that any infection (including
reduce the window period risk. Supply of non-human common infections and self-limited infections) like
blood components, component transfusion, autologous herpes or candida can activate immunologic cells and
1404 transfusion, etc., are important strategies. increase the viral load. Therefore, PLWHA must clearly
avoid contact with other infectious disease patients, and infection control practices in children. All vaccines
pets and other animals, untreated animal products, etc. must be given to the newborn as in any other child.
CHAPTER 8
Use of habit forming drugs like alcohol, psychedelic
drugs, etc., can lead to chronic systemic ailments, EMERGING AVENUES IN PREVENTIVE
hampering the health status. The person should be INTERVENTION
cautious when working or travelling to high-risk
Human Immunodeficiency Virus Vaccines
environments including endemic areas. They should

take only boiled water and well-washed vegetables to Even though a vaccine is the most sought after
avoid gastrointestinal infections. preventive intervention in any disease, HIV vaccine
development must overcome many obstacles like
Regular exercise must be promoted. All life-style risk
variations in antigen configurations, rapidity of new
factors like smoking, sedentary life-style, high intake of
mutant evolution, sanctuaries of virus persistence in
fatty foods, etc. should be curtailed. Interventions like
the body and the difficulty in immunologically active
rs
counselling, yoga, etc. can create a good mental make-
cells being part of the disease process. However under
up for the affected individuals.
The International AIDS Vaccine Initiative (IAVI),
Nutrition plays a major role. Improvement in nutritional many countries (including India) are enthusiastic about
he
status of all family members of PLWHA gets reflected vaccines. Many candidate materials have been tried
in the survival. High-calorie, high-protein diet rich in as prophylactic and therapeutic vaccines. The DNA
micronutrients must be encouraged. Early screening for vaccines (either alone or with adjuvants), live vector
diabetes, metabolic syndrome and other such ailments based vaccines, subunit vaccines, peptide vaccines,
are to be done systematically. virus like particle (VLP) vaccines, fusion competent
Specific Interventions at Certain Stages

Crisis situations can occur any time in human life.
Issues related to marriage, contraception, conception,
ot
vaccines, tat toxoid vaccines, inactivated vaccines are
all being tried. Many of them act through cytotoxic
T-cell (CTL) production or by inducing neutralising
antibodies. There are many ethical and psychological
Br
childbirth, breastfeeding, death, etc. might make the issues involved in any vaccine trial and, hence, an easy
services of a well trained counsellor absolutely essential. solution is not likely to evolve soon. A prophylactic
Many vaccinations covered under adult immunisations vaccine is not going to prevent HIV infections in
are to be administered in the early years. This will everybody and the importance of all other preventive
include vaccination against hepatitis B, Haemophilus strategies should not be underestimated. According
influenzae type b and pneumococcal vaccines. to a model developed by IAVI, a 30% effective vaccine
e
given to 20% of the risk population could reduce

PREVENTION OF MOTHER-TO-CHILD new infections by just 17%. There have been several
pe
TRANSMISSION advanced-phased HIV vaccine trials to date that have

been conducted in developed and developing countries.
Human immunodeficiency virus affects women of the Phase 3 trials involve thousands of high-risk volunteers
childbearing age and, hence, pregnancies associated to test the effectiveness of an HIV vaccine on HIV
with HIV infection are bound to happen. Proper sero-incidence. Phase 2B trials involve a smaller
y
contraceptive counselling in PLWHAs can prevent a number of volunteers and can determine a preliminary
large number of avoidable pregnancies and thus help assessment of efficacy. They can guide future vaccine
efforts, but are not enough for licensing or release of
Ja
reduce the number of infected children being born.

In many instances antenatal screening is the first a vaccine. Currently, there is no licensed preventive
time a woman is found to be infected. Apart from the (in HIV-negative participants) or therapeutic (in HIV-
psychological support needed for the expectant mother, positive participants) HIV vaccine. Despite the recent
proper use of antiretrovirals (ARVs) can ensure a encouraging progress from the Thai RV144 trial, we
significant reduction in vertical transmission. The use remain a long way from an affordable, effective vaccine
of ARV drugs before labour, reduction in the time spent against HIV.
in labour (may be by elective caesarean section), and
avoidance of breastfeeding have all been shown to be Microbicides
effective. Exclusive formula or breastfeeding is superior Microbicides are chemicals that work in the vagina by
to mixed feeding. Routine screening of antenatal women different mechanisms. They are materials that can be
(with informed consent and counselling) has become used by a woman without depending on the partner to
the standard practice. Infected persons are given full protect her. Some of them are foaming agents, acidifying
care and further counselling regarding childrearing gels, entry inhibitors or vaginal defence enhancers. 1405
The initial euphoria associated with the introduction of infections in communities where at least 10% males are
vaginal microbicides has given way to a more realistic circumcised every year. The reduction in male infection
PART 16
approach that looks at the side effects and actual rate will lead in future to a similar fall in female
statistically proven effectiveness. Many agents are infection rate as well. However, male circumcision is to
being discarded and newer ones are being studied. A be considered along with proper and consistent condom
detailed evaluation of microbicides is not within the use as the most important intervention.
purview of this book.
HIV and AIDS
SUGGESTED READING
Male Circumcision
1. Cade WT, Reeds DN, Mondy KE, et al. Yoga lifestyle intervention
Many reports have highlighted the decreased risk of reduces blood pressure in HIV-infected adults with cardiovascular
HIV transmission if the male partner is circumcised. disease risk factors. HIV Med 2010;11:379-88.
The inner part of the foreskin has a higher number 2. Derman EW, Whitesman S, Dreyer M, et al. Healthy lifestyle
interventions in general practice: HIV/AIDS. SA Fam Pract
of Langerhans’ cells with receptors for HIV. The skin
rs
2010;52:11-6.
over the penis is different in circumcised man which
3. Kathleen V Fitch, Ellen J Anderson, Jane L Hubbard, et al. Effects
reduces trauma during penetrative sex. Many models of a lifestyle modification program in HIV-infected patients with
have shown a possible reduction of 10% to 20% new the metabolic syndrome. AIDS 2006;20:1843-50.
he
ot
Br
e
y pe
Ja
1406

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PART 17: INFECTIOUS DISEASES

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PART 24: RHEUMATOLOGY

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