5 курс / Пульмонология и фтизиатрия / Clinical_Tuberculosis_Friedman_Lloyd_N_,_Dedicoat

gaps in my education. My school advised that I shouldn’t bother taking my GCSEs and instead focus on getting better.

However, at the start of this horrible journey of ill health, one day in the Easter holidays aged 10, when I was recovering from my burst appendix, my parents had taken me for a day out in Oxford. After stumbling across a sign outside Balliol College inviting the public to look around, I made up my mind that I was going to Oxford University. In the years which followed, my academics got me through. When everything else was so beyond my control, studying became my unwavering focus. I taught myself from the hospital and home and while, over time, other aspects of my life became more limited, studying was the one thing I could do “from the sofa.” Oxford University constantly remained the goal. You can, therefore, imagine the frustration and upset when doctors would suggest I was a “lazy teenager,” who needed to “get off the sofa” and “do some exercise,” and that I must stop labelling myself as “ill.” This couldn’t have been further from the truth. All I wanted was to be “normal.”

Lorraine

Over the years, a distinct pattern emerged; exertion equalled pneumonia. Now by this, I do not mean going to the gym or going on a run, but rather walking to the shop at the end of the road, climbing a flight of stairs or, in later years, having a shower. This was a pattern which emerged again and again. Kate was getting worse; how could I help her if I was too ill myself? By this stage I had given up my career, hardly went out and the saving grace turned out to be living in a bungalow. While I was far from well, losing weight every year (at my worst a BMI of 16), having a persistent dry cough throughout the day and night, having recurrent chest infections and depleted energy levels, I found that by moving as little as possible, I could prevent myself from becoming seriously ill. I resigned myself to this but Kate was a teenager and was desperately trying to live a “normal” life, which meant she became seriously ill more frequently. The crazy thing was we knew the recipe; we could force ourselves to move in the moment but we knew the end result would be the same—more weight loss, sweats, shivers, exhaustion, days of lying down, eventually sickness and a dry cough, and ultimately, more antibiotics or IVS.

Initially, the reason each of Kate’s admissions proved so scary and each appointment proved so frustrating was that we were constantly battling to be believed. I was very much labelled the “overprotective mother” and fought for years to be listened to. The more we told doctors about this overwhelming weakness, the fact that we couldn’t stand up for long periods and spent most of our lives lying down, the more we were labelled. In between these infections, Kate was always smiling, always positive, was achieving brilliant grades on her exams and most significantly, never showed the usual signs, leading to the consensus that she “couldn’t be that ill.” The only time anyone really saw how bad things could get was in A&E and even then it was a fight, a fight to convince the doctors to give her the IVs. She would be drenched in sweat and uncontrollably shaking but her temperature never reached higher than 36.8. The only person who really understood was our GP. He had been Kate’s GP since birth and had seen this entire journey unravel. He became adept at spotting the signs and realized that for Kate, 36.8 was a

very high temperature. He would make phone call after phone call trying to warn and convince A&E and hospital departments to listen to us. He’d seen what happened if they waited too long; it seemed from nowhere Kate’s body realized it was ill and started showing every sign—violent tremors, pain, cough, sickness, diarrhea, sweats, and shivers but still no temperature.

By now all different parts of Kate’s body were being affected:

Gastroenterology

●●Bloating

●●No appetite

●●Laxatives

●●Pain

●●Vomiting

Respiratory

●●Recurrent infections

●●Persistent cough

●●Pain in right lung

●●Sinusitis

Dermatology

●●Skin infections

●●Crumbling nails

Rheumatology

●●Erythromelalgia

Endocrinology

●●FSH/LH levels

●●Period lasting for months

●●Then periods stopped for years

Blood Pressure

●●Postural orthostatic tachycardia syndrome (POTS)

●●Severely low blood pressure

Sleep

●●Heart palpitations

●●Night sweats

●●Awake all night

The list was endless and each department was treating the symptoms but not the cause.

The diagnosis ranged from polycystic ovaries, to hypermobility, to blood cancer, a sodium channelopathy, IBS, cystic fibrosis; the list goes on but we knew none of these fit the whole picture. Occasionally, I’d bring myself in, trying to illustrate that we shared many of the same symptoms, hoping it might help them with their investigations. The doctors treated me as the overbearing mother: “This appointment is for Kate, Mrs. Tuohy.”

Kate

By this stage I hardly went to school, but somehow I managed to achieve my grades and was offered a place to study English Literature and Language at Jesus College, Oxford University.

The next problem: how was I going to obtain a degree at the top university in the world when my life was becoming increasingly restricted to lying on the sofa? Well, I was given a ground floor room (stairs meant pneumonia), the dining hall was just a few steps away, and a member of staff delivered my books to my door. However, as I said previously, my worst fear was being labelled and I so desperately wanted to take part in all that Oxford had to offer. It was a constant toss-up—Is this night out worth being ill for? Is this party worth ending up in the hospital for?

Prophylactic antibiotics were now a way of life but even these weren’t preventing the recurrent infections. It was in my second year of uni that things hit rock bottom. I was admitted to the hospital with yet another bout of pneumonia and given 2 weeks of IV meropenem. The problem was, the antibiotics weren’t as effective as they once were and this infection returned within a few days. This meant a further week of IVs and 6 weeks (out of an 8-week term) off uni. I’d surpassed the 6-week residency rule at Oxford University and was told I needed to take a year off to focus on getting better. I knew I wasn’t getting better, only worse; what difference would a year make? My GP had referred me to the Mayo Clinic and it was around this time that I was supposed to be going. This was our final resort but I was turned down, deemed too ill to travel. The doctors in the UK told me every test had been done. They had stopped looking for the cause; it was now a case of palliative care. Whatever it was, was going to kill me.

Lorraine

It was our bodies, not our minds which were affected. I spent years researching on the Internet. I knew this was a physical illness which in some way responded to antibiotics, in particular clarithromycin. By now we had worked out the pattern: exertion led to pneumonia which would only be dampened down by oral clarithromycin or IVS.

It was in Kate’s second year of university, after weeks of meropenem, that I insisted the doctors did more tests. After Kate was discharged from this particular admission, the consultant called me at home. She had requested a QuantiFERON Gold blood test and she was calling to say it had come back positive. This was the first test in 12 years which had given a positive result. The more I read, the more I realized we had every symptom of TB.

Sadly, the next part of our journey was far from straightforward. In between this phone call and Kate’s subsequent appointment, I made it my mission to learn everything I could about TB. At the appointment, the consultant began drawing up the prescription for 3 months of latent TB drugs. To me, this made no sense. Kate had every symptom of active TB—night sweats, weight loss, no appetite, recurrent pneumonias, extreme weakness, all exacerbated by even the mildest exertion. I’d even read that the terminal ileum was often affected. By this stage, we had reflected on the unpasteurized milk we had drunk in 1997 and the picture was coming together. It was in this appointment that I questioned whether QuantiFERON Gold tested for bovine TB. When the consultant said it did not test for that strain, I knew I couldn’t let Kate take the latent drugs. I was certain I had read online that it did.

That evening I emailed the scientists in America who produced the test. By the next morning my email had been forwarded to

Professor Peter Davies in Liverpool. I received a response saying QuantiFERON did test positive for bovine TB and under no circumstance must my daughter take those latent drugs.

Kate

Professor Davies was one of the first doctors, other than our GP, who seemed to listen. He took on board every symptom and the entire history.

During one of my previous laparoscopies, the surgeon had taken images which we were meant to give to the Mayo Clinic. He had noticed some strange white spots on my intestine. Professor Davies noticed them immediately and felt they could well be tubercles. While he was prepared to treat me for active TB, he knew I would need to be carefully monitored and that really, I needed to be under the care of my local hospital.

The hospital who had carried out the initial QuantiFERON test still wanted to treat me for latent TB. Professor Davies then referred me to another hospital who said I was “British, white, middle class,” and it did not make sense that I had TB at all and discharged me.

In the end, under the care of my local GP (the only doctor willing to work with Professor Davies), I started a course of 9 months of isoniazid, rifampicin, and pyrazinamide. Unfortunately, within two weeks, three hard lumps appeared on my neck and my body went into anaphylactic shock. After being rushed to A&E in an ambulance, it was concluded that I could never take those drugs again. This was one of our lowest points. What we never expected was that, once I’d recovered from the shock, in 12 years I had never appeared healthier; my symptoms depleted, my energy levels improved, and most significantly, I didn’t develop a chest infection for 5 months, which was unheard of. Something in the treatment had worked.

Professor Davies observed this and eventually decided on a combination of moxifloxacin and ethambutol for 18 months.

This treatment transformed my life.

Lorraine

The treatment had worked for Kate and although I never had a positive test, I was prescribed the same combination of drugs.

I’d coughed every day and night for 18 years but within a few weeks of the treatment commencing, my cough had completely disappeared. I started to put on weight and I was more active than I could ever remember.

Summary

In total we went to 15 hospitals and were seen by over 30 consultants.

We describe this illness as a “cruel” one, for our journey was not just a case of being ill, the way the TB manifested itself meant it was a battle; a battle to be listened to, a battle to be believed and eventually a battle to be treated.

The picture is now very different, we have our lives back. I (Kate) obtained my Oxford degree (albeit in 4, rather than 3 years) and have set up my own business. I (Lorraine) have returned to

work and have an active social life. We eat, we exercise and, most importantly, we no longer spend our lives on the sofa.

Kate and Lorraine Tuhoy, 2018

Afterword

Though I have never quite encountered this combination of history, symptoms, and signs, after over a year of consultations with Kate, I came to the conclusion that she was suffering from some form of occult or cryptic disseminated bovine tuberculosis. I decided to treat her empirically for this disease. First-line treatment proved almost fatal to Kate because of an anaphylactic reaction. Rethinking the drug regimen, I treated her as though she had a resistant form

of TB, giving moxifloxacin and ethambutol for 18 months. This seemed to provide cure.

When then consulted by Lorraine, who I had seen on every visit with Kate and who had very similar symptoms dating from the same event, empirical treatment again seemed appropriate. Lorraine refused the shorter first-choice regimen on the grounds that Kate had such a bad reaction so again we chose moxifloxacin and ethambutol for 18 months. Again cure seemed to be achieved.

Even in developed countries with all laboratory tests available, almost 50% of patients with non-respiratory tuberculosis are treated empirically. Here, in all probability, are two more such cases.

Peter D. O. Davies

If you were to ask anyone outside the small circle of enthusiasts in the fight against communicable diseases to place the following burdens of death by the disease they relate to, I am sure the answers you would receive would be mostly incorrect: 1.8 million,

1.4million and 0.5 million: HIV/AIDS, TB, malaria.

When individuals are asked, no one scores more than 1/3 of

answers correctly. The perception is that HIV and malaria are the big killers while TB comes a distant third. In fact, the correct disease mortalities are 1.8 million for TB, 1.4 million for HIV, 400,000 of whom also die from TB, and under 500,000 for malaria.

An article in The Economist published in October 2017 devoted four pages to the diseases of poverty and how they are being defeated. The majority concerned AIDS and malaria, and a bit about the rarer tropical diseases, but not a mention of TB.

When the millennium goals to defeat HIV, TB, and malaria were set up almost 20 years ago, HIV was perceived as the biggest threat. Perhaps rightly, from that time, malaria has received twice as much money as TB, and HIV twice as much as malaria, leaving TB with 1/7 of the total. It is perhaps no surprise that after so much money and publicity over HIV and malaria, the battle against these killers is doing well while the battle against TB is hardly succeeding at all.

As a consequence, TB has been left behind in terms of resources to combat the disease. It is not surprising therefore that deaths from this communicable disease now nearly exceed those from HIV/AIDS and malaria combined.

The publication of the sixth edition of Clinical Tuberculosis therefore is timely. The intent is to supply those joining us in the war with the essential knowledge, both academic and practical, to help conquer this disease. The book is aimed at all those working in tuberculosis, whether in public health, clinical, or laboratorybased work. As more resources become available, even in the poorest settings, it is hoped the book will be of practical value in the first and third worlds.

Diligent readers of prefaces might wonder why I (PD) am continuing to edit a textbook on tuberculosis. Reading the preface of the fifth edition it seemed as though I was retiring from the fray. I wrote in 2014 “Should there be a call for subsequent editions…I can pass the baton on to [a younger generation] knowing that it is in safe hands.” As so often happens I am here again out of simple serendipity. At every American Thoracic Society meeting I attend I find myself in close company with Lloyd Friedman. Our common interest in tuberculosis would always throw us together. Lloyd had edited two editions of his textbook, which was similar to my own: a single-volume synopsis of practical and theoretical aspects of the disease. By a series of sales of titles between publishers, my title had come to rest on the desk of Taylor & Francis Group, who had been the publishers of Lloyd’s book.

It therefore made sense to me that when Lloyd suggested that we combine a joint editorship for a third and sixth joint edition, respectively, that we join forces to do so. Because I have now retired from the National Health Service and no longer manage patients directly I have asked Martin Dedicoat from Birmingham, UK to join the team and he has graciously agreed.

By mutual agreement we have used the opportunity of a joint venture between the USA and the UK to seek authorship for most chapters from both sides of the pond. We can then combine the science and experience of much wider sources than if we were to “go it alone.” As rates of tuberculosis have declined in both the USA and UK over the past decade, expertise in tuberculosis is more and more associated with joint work in developing countries, particularly on the continent of Africa and countries of South and Southeast Asia. Most of our authors therefore have extensive experience from these areas. As one of the editors-in- chief of the International Journal of Tuberculosis and Lung Disease

I see many papers submitted from developing countries with joint authorship from the USA and/or a Western European country.

I am most grateful to my two co-editors for their hard work and dedication in drawing this edition together. The task of transAtlantic co-ordination has often not been easy. I am also very grateful to all the authors who have put in so much time and hard work to what I believe is a world-class and groundbreaking textbook on tuberculosis. Having authored many chapters in my 40 years of tuberculosis work, I know how back-breaking the task can be, but also how enjoyable it can be as the current scientific knowledge and experience on an aspect of tuberculosis is brought together into a readable synopsis.

My thanks go especially to two patients, Kate and Lorraine Tuohy, who have recorded their experience as tuberculosis sufferers in the Foreword. Not since the second edition have we had a patient contribution to the book and it is high time we did. Their experience of being misdiagnosed and fobbed off by a host of medical professionals with a supposed expertise in tuberculosis is salutary. All workers in the field would do well to read their stories.

The outline and contents of the sixth edition follow the patterns of previous editions with sections on background, diagnosis, drugs, clinical aspects, prevention and control, HIV, and drug resistance. In addition, we have included a section on transmission. The chapter on BCG (Bacille Calmette–Guérin) also references diseases caused by BCG, particularly in the treatment of bladder cancer. We have continued with a chapter on TB in animals as it remains a topic of considerable interest, especially in the UK.

We no longer have a chapter on the so-called non-tuberculous mycobacteria as this has become such a large topic that a separate book on the subject is proceeding through a long gestation process.

Lastly, we are gratified that the TB community is focusing on preventing latent tuberculosis from developing into active disease. As many as 80% of new cases each year are derived from the infected pool. Short-course treatment of latent tuberculosis infection (LTBI) has been a welcome addition, and a new vaccine in trial phase that prevents the development of active tuberculosis in individuals with latent tuberculosis is a promising addition to

the armamentarium. A good vaccine will obviate the issues with treatment compliance and the worry about drug-resistant infection. We are looking forward to further development in this area.

Lloyd Friedman, Martin Dedicoat and Peter Davies

New Haven, CT, Birmingham, UK, and Liverpool, UK January 2020

Lloyd N. Friedman, MD is a clinical professor of Pulmonary, Critical Care and Sleep Medicine at the Yale School of Medicine, New Haven, CT. He is director of Inpatient Quality and Safety for the Department of Internal Medicine.

Dr. Friedman graduated in 1975 from Columbia University, New York with a BA in biochemistry and obtained his MD in 1979 from Yale University. He completed an internship in Internal Medicine at Beth Israel Medical Center in 1980, and residency training at Oregon Health Sciences University in 1983. He completed his fellowship training in Pulmonary and Critical Care Medicine at Yale School of Medicine in 1988.

Dr. Friedman began his work with tuberculosis in 1984 when he evaluated welfare applicants who used drugs or alcohol in New York City at the beginning of the AIDS crisis. He has had numerous grants, scientific publications, chapters, and speaking engagements, and has participated in the development of regional and national guidelines. He has published two editions of his book, Tuberculosis: Current Concepts and Treatment. He is a recipient of the David Russell Lyman Award for Meritorious Achievement in Tuberculosis.

Dr. Friedman is a member of the American Thoracic Society, a member of the Society of Critical Care Medicine, a fellow of the American College of Chest Physicians, and a member of the International Union Against Tuberculosis and Lung Disease. He is Chairman of the Connecticut Tuberculosis Elimination Advisory Committee.

Martin Dedicoat, PhD, FRCP, BSc, DTM&H is a consultant physician in infectious diseases at the University Hospitals Birmingham.

Dr. Dedicoat qualified in medicine from University College London in 1992. He trained in internal medicine, infectious diseases, and tropical medicine in Birmingham and South Africa.

He is currently clinical lead for tuberculosis for Birmingham and Solihull, UK. His main research interests center around tuberculosis transmission in urban settings.

Dr. Dedicoat is a member of the British Thoracic Society drugresistant tuberculosis management group advising on management of complex tuberculosis patients across the UK. He also sits on the National Tuberculosis board for England.

Peter D. O. Davies graduated in 1966 from Marlborough College, Wiltshire, UK and obtained his BM, BCh, and MA from University College, Oxford, UK in 1971 and St. Thomas’s Hospital in London in 1973. He gained a DM from Oxford in 1984. He was a consultant general and respiratory physician at Aintree University Hospital from 1988 to 2011 and at Liverpool Heart and Chest Hospital from 1988 to 2015.

Dr. Davies has published over 100 peer-reviewed papers and has given over 600 invited lectures. He is or has been a member of the British Medical Association, the British Thoracic Society, the European Respiratory Society, the Royal College of Physicians of London (Fellow), the Royal Society of Medicine, the American Thoracic Society, the North Western Society of Respiratory Physicians where he served as president in 2007, the International Union Against Tuberculosis and Lung Disease where he was chair of the Tuberculosis Section, president of the European Section, and editor in chief of the International Journal of Tuberculosis and Lung Disease, and a member of NICE where he was chair of the Tuberculosis Section. He co-founded the UK-based TB charity in 1998.

Dr. Davies is an expert in tuberculosis, edited the inaugural edition of the textbook Clinical Tuberculosis in 1994, and has continued as editor for the subsequent five editions.

Contributors

Laura F. Anderson

Global Tuberculosis Programme

World Health Organization

Geneva, Switzerland

Mercedes C. Becerra

Harvard Medical School and

Brigham and Women’s Hospital and

Partners In Health Boston, Massachusetts

and

Advance Access & Delivery

Durham, North Carolina

Graham Bothamley

Homerton University Hospital

NHS Foundation Trust

London, United Kingdom

Jane E. Buikstra

School of Human Evolution and Social Change

Arizona State University

Tempe, Arizona

Lindsay H. Cameron

Baylor College of Medicine

Texas Children’s Hospital

Houston, Texas

Ted Cohen

Epidemiology of Microbial Diseases

Yale School of Public Health

New Haven, Connecticut

Anne McB. Curtis

Department of Radiology and Biomedical Imaging

Yale School of Medicine

New Haven, Connecticut

Charles L. Daley

Department of Medicine

National Jewish Health

Denver, Colorado

and

Department of Medicine

University of Colorado Aurora, Colorado

Gerry Davies

Institutes of Infection and Global Health & Translational

Medicine

University of Liverpool

Liverpool, United Kingdom

J. Lucian Davis

Epidemiology of Microbial Diseases Yale School of Public Health

and

Section of Pulmonary, Critical Care, and Sleep Medicine

Department of Internal Medicine Yale School of Medicine

New Haven, Connecticut

Martin Dedicoat

University Hospitals Birmingham

Birmingham, United Kingdom

and

University of Warwick

Coventry, United Kingdom

Charles S. Dela Cruz

Section of Pulmonary, Critical Care, and Sleep

Medicine

Department of Internal Medicine

Yale School of Medicine

New Haven, Connecticut

Keertan Dheda

Centre for Lung Infection and Immunity Division of Pulmonology

Department of Medicine and

UCT Lung Institute & South African MRC/UCT Centre for the Study of Antimicrobial Resistance University of Cape Town

Cape Town, South Africa

and

Faculty of Infectious and Tropical Diseases Department of Immunology and Infection London School of Hygiene and Tropical Medicine London, United Kingdom

Anzaan Dippenaar

Centre of Excellence for Biomedical Tuberculosis Research Division of Molecular Biology and Human Genetics Stellenbosch University

Tygerberg, South Africa

Lucica Ditiu

Stop TB Partnership

Geneva, Switzerland

Christopher Dye

Department of Zoology

University of Oxford

Oxford, United Kingdom

Jerrold J. Ellner

Division of Infectious Disease

Department of Internal Medicine

Rutgers New Jersey Medical School

Newark, New Jersey

Aliasgar Esmail

Centre for Lung Infection and Immunity Division of Pulmonology

Department of Medicine and

UCT Lung Institute & South African MRC/UCT Centre for the Study of Antimicrobial Resistance University of Cape Town

Cape Town, South Africa

Paul E. Farmer

Harvard Medical School and

Brigham and Women’s Hospital and

Partners In Health Boston, Massachusetts

Clementine Fraser

Respiratory Infections Section

Imperial College London and Imperial College Healthcare

NHS Trust

London, United Kingdom

Gerald Friedland

Epidemiology and Public Health

Yale School of Public Health

Section of Infectious Diseases

Department of Internal Medicine

Yale School of Medicine

New Haven, Connecticut

Lloyd N. Friedman

Section of Pulmonary, Critical Care, and Sleep Medicine

Department of Internal Medicine

Yale School of Medicine

New Haven, Connecticut

Jennifer Furin

T.H. Chan School of Public Health

Harvard Medical School

Boston, Massachusetts

William R. Jacobs, Jr.

Department of Microbiology and Immunology and

Department of Molecular Genetics Albert Einstein College of Medicine Bronx, New York

Salmaan Keshavjee

Harvard Medical School and

Brigham and Women’s Hospital and

Partners In Health Boston, Massachusetts

and

Advance Access & Delivery

Durham, North Carolina

Aamir J. Khan

Interactive Research and Development

Singapore

Ajit Lalvani

Respiratory Infections Section Imperial College London

and

Imperial College Healthcare NHS Trust London, United Kingdom

Christoph Lange

Clinical Infectious Diseases Research Center and

German Center for Infection Research (DZIF) Clinical Tuberculosis Unit

Borstel, Germany

and

International Health/Infectious Diseases

University of Lübeck

Lübeck, Germany

and

Department of Medicine

Karolinska Institute

Stockholm, Sweden

Charisse Mandimika

Section of Infectious Diseases

Department of Internal Medicine

Yale University School of Medicine

New Haven, Connecticut

Helen McShane

The Jenner Institute and

Nuffield Department of Medicine University of Oxford

Oxford, United Kingdom

James Millard

Institute of Infection and Global Health

University of Liverpool

Liverpool, United Kingdom

and

Africa Health Research Institute

Durban, KwaZulu-Natal, South Africa

Edward A. Nardell

Harvard Medical School

Boston, Massachusetts

Tom Nicholson

Advance Access & Delivery

Durham, North Carolina

Camus Nimmo

Division of Infection and Immunity

University College London

London, United Kingdom

and

Africa Health Research Institute

Durban, KwaZulu-Natal, South Africa

Manish Pareek

Department of Infection, Immunity and Inflammation

University of Leicester

Leicester, United Kingdom

Charles Peloquin

Department of Pharmacotherapy and Translational Research

College of Pharmacy

University of Florida

Gainesville, Florida

Alexander S. Pym

Africa Health Research Institute

Durban, KwaZulu-Natal South Africa

Divya B. Reddy

Division of Pulmonary Medicine

Department of Medicine

Albert Einstein Medical College/Montefiore Medical

Center

Bronx, New York

Charlotte A. Roberts

Department of Archaeology

Durham University

Durham, United Kingdom

Barbara Seaworth

University of Texas Health Science Center

Tyler, Texas

Benjamin J. Silk

Division of Tuberculosis Elimination

U.S. Centers for Disease Control and Prevention Atlanta, Georgia

Lynn E. Sosa

Connecticut Department of Public Health

Hartford, Connecticut

Jeffrey R. Starke

Baylor College of Medicine

Texas Children’s Hospital

Houston, Texas

Richard S. Steyn

University Hospitals Birmingham Foundation Trust

Birmingham Heartlands Hospital

Bordesley Green East

Birmingham, United Kingdom

Sarah Talarico

Division of Tuberculosis Elimination

U.S. Centers for Disease Control and Prevention Atlanta, Georgia

Rachel Tanner

The Jenner Institute

Nuffield Department of Medicine

University of Oxford

Oxford, United Kingdom

Grant Theron

DST/NRF Centre of Excellence for Biomedical Tuberculosis Research

SA MRC Centre for Tuberculosis Research

Division of Molecular Biology and Human Genetics Faculty of Medicine and Health Sciences Stellenbosch University

Tygerberg, South Africa

Robin Warren

South African Medical Research Council Centre for Tuberculosis Research

Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research

Division of Molecular Biology and Human Genetics Stellenbosch University

Tygerberg, South Africa

Catherine Wilson

Wellcome Trust Clinical PhD Fellow

Faculty of Health Sciences

University of Liverpool

Liverpool, United Kingdom