escmid postgraduate education course...2 escmid postgraduate education course tuberculosis and...

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ESCMID Postgraduate Education Course

Tuberculosis and Mycobacterial Infections: An Educational Update

Singapore 26 – 28 September 2019

TABLE OF CONTENTS

COURSE INFORMATION ................................................................................................................. 1

FACULTY ........................................................................................................................................... 3

FLOOR PLAN ................................................................................................................................... 14

PROGRAMME .................................................................................................................................. 15

LECTURE ABSTRACTS.................................................................................................................. 18

SESSION 1: THE EPIDEMIOLOGY OF TB ............................................................................... 18

SESSION 2: PATHOLOGY OF TUBERCULOSIS ..................................................................... 20

SESSION 3: DIAGNOSING TUBERCULOSIS ........................................................................... 21

SESSION 4: TREATING TB AND DELIVERING CARE ......................................................... 23

SESSION 5: UPDATE ON THE CUTTING EDGE OF TB SCIENCE ....................................... 25

SESSION 6: COMPLEX PATIENTS: CASE-BASED DISCUSSIONS ...................................... 26

SESSION 8: NON-TUBERCULOUS MYCOBACTERIA........................................................... 27

POSTER ABSTRACTS ..................................................................................................................... 28

ACKNOWLEDGEMENTS............................................................................................................... 37

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COURSE INFORMATION

COURSE DIRECTORS

• Jon S Friedland, London, United Kingdom

• Delia Goletti, Rome, Italy

• David Lye, Singapore

• Catherine Ong, Singapore

• Paul Tambyah, Singapore

COURSE VENUE

National University of Singapore

Yong Loo Lin School of Medicine

Clinical Research Centre Auditorium

MD11, 10 Medical Drive

Singapore 117597

WIFI AND LOGIN DETAILS

WIFI SSID: NUS-GUEST WIFI

WIFI PIN: UORS4V

PROGRAMME BOOKLET

There are 2 versions of programme booklet. A hardcopy programme booklet, distributed upon

registration, will contain only faculty listing and the programme. The E-copy of the programme

booklet will contain Faculty Biographies, Lecture Abstracts and Poster Abstracts. This

can be downloaded from the official website at https://escmid-sids.wizlink.com.sg.

CME ACCREDITATION

This course has been granted 11 European CME credits (ECMEC®s) by the European

Accreditation Council for Continuing Medical Education (EACCME®) and 8 CME credit points by

the Singapore Medical Council.

CERTIFICATE OF ATTENDANCE

The Certificate of Attendance will be issued on Saturday, 28th September 2019. Kindly collect at

the registration counter when you sign your attendance for the day.

For participants who signed up for single day programme, kindly collect your certificate of

attendance at the end of the day, at the registration counter.

POSTER PRESENTATION

Each presenter will be allocated a poster board (one side only) with an area of 1m x 2m. Each poster

board will be marked with a poster panel number. Poster should be set up on Thursday, 26

September 2019 between 1230 – 1300 hours and removed on Saturday, 28th September 2019 after

1030 hours. Poster judging will be on Friday, 27th September 2019, from 1130 – 1230 hours and

prizes will be awarded on Saturday, 28th September 2019.

https://escmid-sids.wizlink.com.sg/

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FACULTY GROUP PHOTOGRAPH

All faculty kindly assemble on stage on Friday, 27th September at 10.00am, just before the morning

tea break.

FACULTY DINNER (by invitation)

Faculty members who require transport to the Dinner Venue, please inform the Course Secretariat

and assemble at the Foyer on Friday, 27th September by 1800 hours.

PERSONAL DATA

Participants should be aware that the organisers through others on behalf of organisers and third

parties, may be taking photographs and videos during the Postgraduate Course. Organisers may use

such photos in marketing materials, publications or media including social media, and we may

identify participants by name.

LOST AND FOUND

For lost and found items, please approach the Registration Counter.

LIABILITY

The Organisers are not liable for any personal accidents, illnesses, loss or damage to private

properties of delegates during the Course. Delegates are advised to make their own arrangements

with respect to personal insurance.

DISCLAIMER

Whilst every attempt will be made to ensure that all aspects of the Course will take place as

scheduled, the Organising Committee reserves the right to make appropriate changes should the

need arises with or without prior notice.

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FACULTY

Assoc. Prof. Sylvie ALONSO

Associate Professor

Department of Microbiology and Immunology


Singapore

Associate Professor Alonso obtained her PhD degree in Microbiology and Molecular Biology from

the University Claude Bernard Lyon I (France) in 1998. She subsequently moved to Pasteur

Institute of Lille (France) for a 4-year post-doctoral training where she developed bacterial vaccine

delivery systems. Associate Profesor Alonso then spent 2 years at Cornell University (NY, USA) as

a Research Fellow where she worked on Tuberculosis. In 2004, she was awarded the Lee Kuan

Yew post-doctoral fellowship and joined the Department of Microbiology at NUS. She was

recruited as an Assistant Professor in 2007 and promoted to Associate Professor with tenure in 2013.

Assoc. Prof. Sophia ARCHULETA Head & Senior Consultant, Division of Infectious Diseases

University Medicine Cluster

National University Hospital

Director, National HIV Programme

National Centre for Infectious Diseases

Singapore

Associate Professor Sophia Archuleta is Head of the Division of Infectious Diseases at the National

University Hospital, and Director of the National HIV Programme, National Centre for Infectious

Diseases, Singapore. She is also a clinician educator and serves on the faculty of the National

University Health System Infectious Diseases Senior Residency Programme. Her clinical expertise,

and primary interest, is in the care of people living with HIV and its associated conditions.

Associate Professor Archuleta received her Bachelor of Science from Yale University in 1994 and

her M.D. from Albert Einstein College of Medicine in 1998. She completed her internal medicine

and infectious disease training at Mount Sinai Medical Center in New York and is board certified in

internal medicine and infectious diseases. In 2003, she joined the faculty of the Division of

International Medicine and Infectious Diseases at Weill Medical College of Cornell University

where she focused on HIV medicine and postgraduate education. A/Prof Archuleta joined the

Division of Infectious Diseases of the National University Hospital in Singapore in 2008 where she

established and led the HIV Programme until 2017. She was appointed Director of the National

HIV Programme, National Centre for Infectious Diseases in 2018. She is an Associate Professor of

Medicine at the Yong Loo Lin School of Medicine of the National University of Singapore, and

serves in various educational leadership roles and national committees on graduate medical

education. She is active in teaching learners across health professions and the entire medical

education continuum.

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Prof. Emmanuelle CAMBAU

Professor in Bacteriology-Virology-Hygiène

Medical School, University Paris Diderot

Head, Bacteriology laboratory

Lariboisiere Hospital, Hopitaux Universitaires Saint Louis-Lariboisière

Assistance Publique-Hôpitaux de Paris

Paris, France

Professor Cambau is a Professor in Bacteriology-Virology-Hygiène with the Medical School -

University Paris Diderot. She is also the Head of the Bacteriology Laboratory at Lariboisiere

Hospital, Hopitaux Universitaires Saint Louis-Lariboisière, Assistance Publique-Hôpitaux de Paris,

since 2010 and is a Member of the research team IAME UMR 1137 in Inserm-University Paris

Diderot

Professor Cambau obtained her Master’s Degree in Pharmacology from the University Paris 7 in

1989 and continued to pursue her Medical Doctor (M.D.) degree in Medical Biology from

University Paris 7 in 1991. In 1995, she received her Ph.D. degree in Microbiology and in 2001 her

Research Director Degree, both from the University Paris 5.

Professor Cambau has been the Associate Director of the French National Reference Center for

Mycobacteria since 2006. She is also a Member of the European network of national reference

laboratories for tuberculosis (ERLnet-TB) granted by the ECDC since 2010. She has been

appointed an Expert by the European Medical Agency, since 2011, and WHO network for

surveillance of resistance in leprosy, since 2008. She is also member of the WHO Technical

advisory group for Global Leprosy Program and has been a Member of the Executive Committee of

the European society for clinical microbiology and infectious diseases (ESCMID) since May 2018.

Professor Cambau was the Chair of the ESCMID Study group on mycobacterial infections

(ESGMYC) from 2011 to 2016 and Chair of the EUCAST subcommittee for antimycobacterial

susceptibility testing since 2016. She has published more than 230 papers, 170 communications

and 130 invitations for conferences.

Assoc. Prof. Cynthia CHEE

Director, Singapore TB Elimination Programme

National Centre for Infectious Disease

Director, Tuberculosis Control Unit

Tan Tock Seng Hospital

Singapore

Associate Professor Cynthia Chee is the Director of the Singapore TB Elimination Programme,

National Centre for Infectious Disease, and Director of the TB Control Unit, Tan Tock Seng

Hospital, Singapore. She obtained her medical degree from the National University of Singapore.

She underwent post graduate training in internal medicine, followed by advanced specialty training

in adult respiratory medicine. She has been working in TB control in Singapore since 1996 and was

involved in the implementation of the initiatives of the Singapore TB Elimination Programme since

its launch in 1997. Her research interests and publications pertain to the clinical and public health

aspects of TB.

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Assoc. Prof. Alex COOK Associate Professor

Biostatistics and Modelling Domain

Vice Dean (Research) & Domain Leader (Biostatistics & Modelling)

Saw Swee Hock School of Public Health


Associate Professor

Department of Statistics and Applied Probability


Associate Professor

Program in Health Services and Systems Research

Duke-NUS Graduate Medical School Singapore

Singapore

Associate Professor Alex Cook is an Associate Professor in the Saw Swee Hock School of Public

Health (SSHSPH) at the National University of Singapore (NUS), where he is also the Vice Dean of

Research and the Domain Leader of the Biostatistics and Modelling Domain. He also holds joint

appointments at the Duke-NUS Medical School Singapore, at the Department of Statistics and

Applied Probability, NUS. He works on infectious disease modelling and statistics, including

dengue, influenza and other respiratory pathogens, and on population modelling to assess the effect

of evolving demographics on non-communicable diseases such as diabetes.

Prof. Jon S FRIEDLAND Deputy Principal (Research & Enterprise)

St George’s, University of London

London, UK

Professor Jon Friedland is Deputy Principal (Research & Enterprise) at St George’s, University of

London having been Hammersmith Campus Director and Head of Infectious Diseases and

Immunity at Imperial College London. He is an honorary consultant in Infectious Diseases at St

George’s Hospital University NHS Trust.

His major research interests are in development of host mediated therapies targeting innate immune

responses in tuberculosis and in migrant health. He has published over 230 peer reviewed papers,

invited editorials and reviews, and edited 3 books.

Jon Friedland was awarded the Royal College of Physicians Weber-Parkes Prize Medal for research

in tuberculosis in 2005 and was elected Fellow of the UK Academy of Medical Sciences in 2008.

He was elected President of the British Infection Society (2007-09). He was elected Fellow of the

Royal College of Physicians of Ireland in 2010. In 2017, he was awarded an inaugural Fellowship

of the European Society of Clinical Microbiology and Infectious Diseases. He is currently a

Commissioner on the UK Commission for Human Medicines and Chair of the MHRA Expert

Advisory Group on Infection. He has previously served on the Joint Committee on Vaccination and

Immunisation and The Chief Medical Officers National Expert Panel on New and Emerging

Infections as well as on many grants committees including for the Medical Research Council (UK)

and The Wellcome Trust.

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Prof. Delia GOLETTI Infectious Diseases Specialist

Head, Translational Research Unit

Department of Epidemiology and Preclinical Research

National Institute for Infectious Diseases

Rome, Italy

Professor Delia Goletti is an Infectious Diseases Specialist, responsible of the Translational

Research Unit at the National Institute for Infectious Diseases in Rome, Italy. She has clinical

duties in the Lung Infectious Diseases outpatient clinic twice a week. Her research focus is on

tuberculosis immune pathogenesis, tuberculosis immunodiagnostic tests, biomarkers, autophagy,

impact of helminth infection on HIV and tuberculosis disease, impact of immune-suppressive

therapy on infectious diseases. She also works on the immune-pathogenesis of echinococcosis.

Professor Goletti is the chair of the ESCMYC group (working on Mycobacteria) at ESCMID and

she has ongoing collaborations worldwide (India, Africa, Europe, United States) on the translational

aspects of immune assays for tuberculosis. She collaborates with the World Health Organization

(WHO) and European Respiratory Society (ERS) on tuberculosis elimination and advocacy, with

the New Diagnostics Working Group Task Force on tests for progression of latent infection to

active disease supported by WHO and FIND

She is currently the academic editor of several journals including Journal of Infection, BMC

Infectious Diseases, PLoS ONE. She is also the co-chair of the group working on conventional T

cells within the “Collaboration for TB Vaccine Discovery” (CTVD) supported by the Bill and

Melissa Gates Foundation. She is present in the list of the top Italian scientists from 2014. She

publishes many papers with H index: Scopus 49; Web of Science: 47; Google Scholar 56.

Assoc. Prof. Li Yang HSU Head, Infectious Diseases Programme

Associate Professor


Yong Loo Lin School of Medicine


Head and Senior Consultant

Department of Infectious Diseases, Tan Tock Seng Hospital

Deputy Clinical Director, Communicable Diseases Centre

Ministry of Health, Singapore

Associate Professor Li Yang Hsu is an infectious diseases physician who has spent the past decade

researching and treating patients with antibiotic-resistant bacterial and invasive fungal infections.

He is currently Clinical Director of the National Centre for Infectious Diseases and Programme

Leader of the Infectious Diseases Programme at the Saw Swee Hock School of Public Health. He

was formerly the Director of the Singapore Infectious Diseases Initiative, which was established to

spur collaborative biomedical and clinical research in infectious diseases.

Associate Professor Hsu has served in several Ministry of Health committees, in particular co-

chairing the RIE2020 infectious diseases workgroup, promoting the causes of antimicrobial

stewardship, better control of antimicrobial resistance (leading to the launch of Singapore’s

National Strategic Action Plan on Antimicrobial Resistance in November 2017), as well as

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tuberculosis. He continues to work with MOH on the part-time professional scheme. He has also

served as a technical advisor on surveillance of antimicrobial resistance to the western pacific

regional office of the World Health Organization.

Associate Professor Hsu was the founding director of the Centre for Infectious Disease & Research

(CIDER) at the Saw Swee Hock School of Public Health in 2012, and has briefly worked in the

private sector as an infectious disease physician, providing specialist services between 2014 and

2016.

Dr. Tauhidul ISLAM Coordinator, End TB and Leprosy Unit

Division of Programmes for Disease Control

Western Pacific Regional Office

World Health Organization

Manila, Philippines

Dr Tauhid Islam is leading End TB and Leprosy Unit of the Division of Disease Control in the

Western Pacific Regional Office of WHO. He is responsible for coordinating technical support,

monitoring the Regional TB situation and promoting innovative interventions through translation of

new policies into practice and through addressing system challenges. Dr Islam has over 15 years of

experience in TB control with experience at global, regional and national level. He has worked

closely with numerous stakeholders including Member States, civil society, as well as national and

international partners. He contributed to the development of WHO guidelines and policies on TB

and MDR-TB.

Prof. Yee-Sin LEO Director, Institute of Infectious Disease and Epidemiology

Clinical Director, Communicable Disease Centre

Senior Consultant

Tan Tock Seng Hospital

Singapore

Professor Yee-Sin Leo, an adult Infectious Disease specialist, is the Executive Director of the

National Centre of Infectious Diseases. She is known for leading her team battling through multiple

outbreaks in Singapore in recent decades. Her encounters include the Nipah outbreak in 1999,

SARS in 2003, pandemic influenza in 2009 and multiple surges of vector-borne diseases including

the recent zika outbreak in Singapore.

Her work won her many awards including the most prestigious Public Service Star in recognition of

her contributions during the SARS outbreak. Other awards include the Excellence Star Award in

2005, the Red Ribbon Award in 2014 and the National Healthcare Group (NHG) Distinguished

Senior Clinician Award in 2016.

Professor Leo is extremely active in academic advancement. Her key research interests are

emerging infectious diseases, dengue, and HIV. Her recent focus on point-of-care testing (POCT)

attests to her work in improving patient care and outbreak control. To date Professor Leo has

published more than 200 scientific papers and is highly sought after as an advisor and conference

speaker.

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Asst. Prof. Catherine ONG Principal Investigator

Department of Medicine, Yong Loo Lin School of Medicine

Institute for Health Innovation & Technology


Consultant, Division of Infectious Diseases

University Medicine Cluster, National University Hospital

Singapore

Assistant Professor Catherine Ong is Principal Investigator in the Department of Medicine (Yong

Loo Lin School of Medicine) and Institute for Health Innovation & Technology (iHealthtech) at the

National University of Singapore, Honorary Secretary of the Chapter of Infectious Disease

Physicians (Academy of Medicine, Singapore), Council Member of the College of Clinician-

Scientists and Vice-President of Society of Infectious Disease (Singapore). Her clinical interests are

in TB in immunocompromised hosts including people living with HIV and in the transplant setting.

Assistant Professor Ong joined the Division of Infectious Diseases at National University Hospital

in 2007 where she developed a passion for TB. She was awarded the competitive 2008 NRF-MOH

Healthcare Research Scholarship funded by the Singapore National Medical Research Council

(NMRC) and pursued full-time research on TB host immunopathology with Professor Jon Friedland

at Imperial College London which led to the conferment of her PhD in 2013. During her UK

research, she was awarded a Presidential Award prize at the American Society for Leukocyte

Biology, the Keystone Symposia Global Health Travel Award by Bill and Melinda Gates

Foundation and the International Investigator Award by the Infectious Diseases Society of America.

On return, she was awarded the Exxon-Mobil NUS Research Fellowship in 2014, the NUHS

Clinician-Scientist Programme 2014-15, the NMRC Transition Award in 2015, the NMRC

Clinician Scientist Award in 2018 and the Institut Merieux- Society of Infectious Disease

(Singapore) Young Investigator Award 2018. Her research interests are in TB host-pathogen

interactions, biomarker discovery and host-directed therapies.

Asst. Prof. Rick ONG

Assistant Professor



Singapore

Assistant Professor Rick Ong is a bioinformatician who combines computer science, statistics,

population genetics and genomics to develop and apply novel algorithms and software in the

research and analysis for molecular epidemiology, pathogenesis, tracking and control of outbreaks

in infectious diseases, including monitoring of antimicrobial resistance for public health

surveillance. He is currently an Assistant Professor with the Saw Swee Hock School of Public

Health at the National University of Singapore. He has a BEng (Computer Engineering), MSc

(Computer Science) and PhD from National University of Singapore and a Msc (Bioinformatics)

from Nanyang Technological University.

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Prof. Nick PATON Professor of Infectious Diseases


Senior Consultant, Division of Infectious Diseases

University Medicine Cluster


Singapore

Prof Nicholas Paton trained in Medicine and Infectious Diseases in Cambridge, Sydney and London,

and in Epidemiology at the London School of Hygiene and Tropical Medicine. From 1997 to 2005,

he worked at Tan Tock Seng Hospital Singapore, serving terms as Head of Department of

Infectious Diseases and as Hospital Research Director. He then returned to the UK, to work in the

MRC Clinical Trials Unit (MRC CTU) leading large scale HIV treatment trials, such as PIVOT and

EARNEST (for which he is the Chief Investigator). He also worked with international research

networks such as INSIGHT and NEAT. In 2011, he accepted the Professor of Medicine position, in

the Department of Medicine at the National University of Singapore (NUS). At NUS, he is working

on a programme of international TB research, focused on developing novel endpoints for TB trials

and on clinical trials evaluating new TB drug combinations.

Assoc. Prof. Kevin PETHE Associate Professor of Infectious Disease

Principal Investigator

Microbiology and Systems Biology Laboratory

Lee Kong Chian School of Medicine

Nanyang Technological University

Singapore

Before joining the Nanyang Technological University, Associate Professor Kevin Pethe gained

expertise in Research & Development in the private sector as research investigator and project

manager at the Novartis Institute for Tropical Disease (Singapore) from 2004 to 2011. He then took

a position of principal investigator at Institut Pasteur Korea to pursue his interest on host-pathogen

interactions and chemical biology applied to tuberculosis and multidrug resistant bacteria. He

became head of the departments of disease biology & chemical genomics in 2013, and nominated

acting CEO of Institut Pasteur Korea the same year.

Kevin is interested in the pathogenesis of Mycobacterium tuberculosis, microbial bioenergetics, and

on strategies to discover novel antibacterial agents. Notably, he led interdisciplinary teams that

developed clinical-stage drug candidates for tuberculosis and related mycobacteria.

Kevin Pethe is teaching microbiology, antibiotic drug development, infectious diseases and

pharmacokinetics to undergraduate and graduate students in the Lee Kong Chian School of

Medicine, the College of Science, and the College of Engineering of the Nanyang Technological

University.

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Dr Zubaidah SAID Public health physician and Deputy Director

Communicable Diseases Division

Ministry of Health, Singapore

Zubaidah Said is a public health physician and Deputy Director at the Communicable Diseases

Division in the Ministry of Health, Singapore. Her areas of interest are in epidemiology, public

health policy and health economics.

Dr. Chew Swee SEOW

Senior Consultant Dermatologist

National Skin Centre

Singapore

Dr Seow Chew Swee is a Senior Consultant Dermatologist responsible for the treatment and

teaching of skin diseases in the Department.He is especially passionate about treatment common

skin conditions like eczema, acne, psoriasis, infections of the skin and pigment problems

and diseases of the hair and nail. His research interest centers on infection of the skin, including

Leprosy, and diseases peculiar to Asian population.

Dr Seow Chew Swee graduated from the University Malaya in Malaysia and subsequently obtained

the Master’s Degree in Medicine in Singapore. He proceeded with the training in Dermatology and

Medical Mycology at Institute of Dermatology, University of London in the United Kingdom. He is

Fellow of Asian Academy of Dermatology and Venereology (FAADV).

Adj Asst. Prof. Amit SINGHAL Adjunct Assistant Professor



Principal Investigator

Singapore Immunology Network

Agency for Science, Technology and Research

Singapore

Adjunct Assistant Professor Amit Singhal began his career in the field of infectious disease

immunology as a PhD fellow at All India institute of Medical Sciences, India. After doing

postdoctoral stints at Institute Pasteur and Novartis Institute for Tropical Disease he started his

group in SIgN in 2014. He is applying various basic and advanced approaches (at both population

and single cell level), to understand the mechanisms utilized by bacteria for evading host’s

immuno-metabolic circuits. The information gained from these experiments is being currently

exploited for designing clinically relevant biomarkers and host-directed therapeutic interventions.

He is also an Adjunct Assistant Professor (Honorary) at the Lee Kong Chian School of Medicine,

Nanyang Technological University, Singapore

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Dr. Li Hwei SNG Senior Consultant

Head, Central Tuberculosis Laboratory

Singapore General Hospital

Co-director

The Infectious Diseases Research Institute (IDRI)

Singapore

Dr Sng Li-Hwei is a pathologist specializing in medical microbiology, a Senior Consultant and the

Head of the Central Tuberculosis Laboratory (CTBL), Singapore General Hospital (SGH) since

2003. She graduated from the National University of Singapore, received microbiology training at

the SGH, Department of Pathology and the Cleveland Clinic Foundation, USA; and

Mycobacteriology specialist training at the Centers of Disease Control and Prevention, Atlanta,

USA.

She is actively involved in various workgroups for mycobacterial diagnosis and control. Her

interests involve novel diagnostic methods and the integration of advanced technology and testing

platforms in clinical diagnostic laboratories, antimicrobial resistance and epidemiological studies,

especially mycobacteria. The CTBL serves as the national reference laboratory for tuberculosis and

has collaboration with local and international scientists and researchers in developing TB

diagnostics, fingerprinting assays, and studies involving whole genome sequencing and

evolutionary biology.

Prof. Paul TAMBYAH Professor

Department of Medicine, Yong Loo Lin School of Medicine

National University Singapore

Senior Consultant

Division of Infectious Diseases, University Medicine Cluster


Singapore

Paul Ananth Tambyah is currently Professor of Medicine at NUS and senior consultant Infectious

Diseases Physician at the National University Hospital and also head of the Infectious Diseases

Research Coordinating Office at the National Center for Infectious Diseases. He is also President of

the Asia Pacific Society of Clinical Microbiology and Infection. His research interests are in device

associated infection and emerging infectious diseases

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Prof. Guy THWAITES Director

Oxford University Clinical Research Unit

Wellcome Trust Major Overseas Programme

Vietnam

Professor of Infectious Diseases

University of Oxford

Honorary Consultant in Infectious Diseases and Clinical Microbiology

Guy’s and St. Thomas’ NHS Foundation trust

UK

Professor Thwaites qualified from Cambridge University and the United Medical and Dental

schools of Guy’s and St Thomas’ and trained in Infectious Diseases and Microbiology in Brighton,

the Oxford University Clinical Research Unit (OUCRU) in Vietnam, Imperial College London, and

the Hospital for Tropical Diseases in London. His research interests focus on the management of

severe bacterial infections, especially those involving the central nervous system. He has held

Wellcome Trust Training (2001-2004) and Intermediate (2006-2011) Fellowships, and was recently

awarded a Wellcome Trust Investigator Award (2016-2023) to further his research on tuberculosis

in Vietnam.

In 2013 he was appointed Director of the Oxford University Clinical Research Unit and Wellcome

Trust Major Overseas Programme in Viet Nam. He is responsible for the scientific strategy and day-

to-day management of the entire programme, which includes research units in Viet Nam, Nepal and

Indonesia.

Professor Thwaites has published more than 160 articles in international journals and has an H

index of 39 (Scopus)

Prof. Reinout van CREVEL Professor in Global Health and Infectious Diseases

Radboud University Medical Center

Nijmegen, The Netherlands

Professor Reinout van Crevel studied medicine in Amsterdam and now works as an internist-

infectious diseases specialist in Nijmegen, the Netherlands. His clinical work covers the full specter

of infectious diseases, including severe or treatment-refractory cases of tuberculosis and infections

caused by non-tuberculous mycobacteria. His research mainly focusses on TB, integrating patient

studies and laboratory sciences, and focussing on TB meningitis, TB and diabetes and M.

tuberculosis infection. He has a collaborated for 20 years with researchers in Indonesia, where he

has lived for 3 years, and currently has a part-time position at the Oxford Clinical Research Unit in

Jakarta.

13



Assoc. Prof. Tsin Wen YEOAssociate Professor of Infectious Disease

Principal Investigator, Malaria, Tuberculosis and Global Health Laboratory



Singapore

Associate Professor Yeo is an Associate Professor at the Lee Kong Chian School of Medicine,

Nanyang Technological University. Associate Professor Yeo graduated from the National

University of Singapore, and went on to complete an internal medicine residency at the University

of Hawaii as well as an infectious disease fellowship at the University of Utah. He did his PhD at

the Menzies School of Health Research and University of Queensland on the treatment and

pathogenesis of severe malaria based in Indonesia Papua. Upon completion of his PhD, he worked

as a research fellow at the Menzies School of Health Research and as an infectious physician at

Royal Darwin Hospital in Australia. In 2016, he was awarded the Clinician-Scientist Award (CSA)

in the Investigator (INV) category from Singapore’s National Medical Research Council (NMRC).

Associate Professor Yeo’s research group at NTU’s Lee Kong Chian School of Medicine focuses

on clinical and epidemiological studies of malaria including the three species most prevalent in

South East Asia, namely Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi

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FLOOR PLAN

Poster Area

Auditorium

Exh

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OFFICES

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Lobby

Registration

CAFE

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PROGRAMME

Day 1: Thursday, 26th Sept 2019

Session 1: The Epidemiology of TB

Chair: Prof Jon FRIEDLAND

1300 – 1320 Registration

1320 – 1330 Opening Remarks

1330 – 1400 Epidemiology of TB in Singapore and TB

Control Efforts

Dr Zubaidah SAID (SG)

Communicable Disease Division,

Ministry of Health

1400 – 1430 The Global and Regional Experiences and the

End of TB Strategy

Dr Tauhidul ISLAM (PH)

World Health Organisation

1430 – 1500 TB and Migration Assoc Prof Alex COOK (SG)

Saw Swee Hock School of Public

Health, NUS

1500 – 1530 TB Biomarkers Prof Delia GOLETTI (IT)

ESGMYC Chair

1530 – 1600 Refreshment Break

Session 2: Pathology of Tuberculosis

Chair: Asst Prof Catherine Ong

1600 – 1640 Host Immune Defence in Tuberculosis, A

Clinical Perspective

Prof Reinout van CREVEL (NL)

Radboud University

1640 – 1720 Physiology and Pathology of TB Prof Jon FRIEDLAND (UK)

St George’s, University of London

1720 Question-Answer Session, Light Refreshments and Networking

End of Day 1

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Day 2: Friday 27th Sept 2019

Session 3: Diagnosing Tuberculosis

Chair: Assoc Prof Sophia ARCHULETA

0900 – 0930 Understanding the Use of Interferon Assays Prof Delia GOLETTI (IT)

ESGMYC Chair

0930 – 1000 The Role of the Microbiology Laboratory Prof Emmanuelle CAMBAU (FR)

ESCMID Council and Past

ESGMYC Chair

1000 – 1030 Refreshment break and Faculty Photo Taking

Session 4: Treating TB and Delivering Care (Part 1)

Chair: Assoc Prof Tsin Wen YEO

1030 – 1100 Whole Genome Sequencing in TB Assoc Prof Li Yang HSU (SG)

Asst Prof Rick ONG (SG)

Saw Swee Hock School of Public Health, NUS

1100 – 1130 Public Health and Social Aspects of TB

Management

Assoc Prof Alex COOK (SG)

Saw Swee Hock School of Public

Health, NUS

1130 – 1230 Lunch Break, Poster Judging

Session 4: Treating TB and Delivering Care (Part 2)

Chair: Prof Emmanuelle CAMBAU

1230 – 1300 Managing Drug-Resistant TB Assoc Prof Cynthia CHEE (SG)

TB Control Unit

1300 – 1330 Extra-Pulmonary TB Assoc Prof Tsin Wen YEO(SG)

Lee Kong Chian School of

Medicine, NTU

1330 – 1400 CNS-TB Prof Guy THWAITES (VN)

Oxford Clinical Research Unit

Session 5: Update on the Cutting Edge of TB Science

Chair: Assoc Prof Sylvie ALONSO

1400 – 1420 Clinical Trials in TB Prof Nick PATON (SG)

Yong Loo Lin School of

Medicine, NUS

1420 – 1440 Host-Directed Therapy in TB Adj Asst Prof Amit SINGHAL

(SG)

Singapore Immunology Network,

A*Star

1440 – 1500 New Kids on the Block Assoc Prof Kevin PETHE (SG)

Lee Kong Chian School of

Medicine, NTU


17



Day 2: Friday 27th Sept 2019 (Cont’d)

Session 6: Complex Patients: Case-Based Discussions

Chair: Prof Delia GOLETTI

1530 – 1600 TB and HIV Prof Yee Sin LEO (SG)

National Center for Infectious

Diseases

1600 – 1630 TB and DM Prof Reinout van CREVEL (NL)

Radboud University

1630 – 1700 Managing TB in the Immunocompromised Asst Prof Catherine ONG (SG)

Yong Loo Lin School of

Medicine, NUS

1700 – 1730 Challenging TB Cases in Asia Prof Guy THWAITES (VN)

Oxford Clinical Research Unit

1900 – 2100 Faculty Dinner (by invitation)

End of Day 2

Day 3: Saturday 28th Sept 2019

Session 7: Debate

Chair: Asst Prof Catherine ONG

0900 – 1000 Topic: – The focus in TB must be on research in diagnostics and treatment, not

social aspects of the disease

Proposed by: Prof Paul TAMBYAH (SG)

Opposed by: Prof Jon FRIEDLAND (UK)


Session 8: Non-Tuberculous Mycobacteria

Chair: Prof Paul TAMBYAH

1030– 1100 Microbiological Diagnosis Prof Emmanuelle CAMBAU (FR)

ESCMID Council and Past

ESGMYG Chair

1100 – 1130 An update on the diagnosis and management of

non-tuberculous mycobacterial infections –

Perspectives from the Singapore Laboratory

Dr Li-Hwei SNG (SG)

Central TB Laboratory

1130 – 1200 Leprosy Dr Chew Swee SEOW (SG)

National Skin Centre

1200 – 1300 Closing Remarks, Poster Prize Presentation, Lunch and Future Planning

End of Course

18



LECTURE ABSTRACTS

SESSION1: THE EPIDEMIOLOGY OF TB

Epidemiology of TB in Singapore and TB Control Efforts

Dr Zubaidah SAID

TB in Singapore was prevalent in Singapore until 1970s, when it started to decline due to improved

hygiene and sanitation, and medical treatment. In 1997, the Singapore TB Elimination Program

(STEP), was set up to further reduce the TB incidence in Singapore. STEP runs the national

Directly Observed Treatment (DOT) program, and coordinates the treatment, investigation, and

contact tracing around active TB cases. This has led to a further reduction in TB incidence rates in

Singapore.

Singapore adopts a multipronged approach to reduce TB incidence rates. To further strengthen TB

control efforts, novel approaches are being explored, and this presentation will detail some of these

approaches.

The Global and Regional Experiences and the End of TB Strategy

Dr Tauhidul ISLAM

Worldwide, TB is one of the top ten causes of death and the leading cause from a single infectious

agent. In 2017, TB caused an estimated 1.6 million deaths, around 10 million people developed TB

disease which includes 1.0 million children. Drug-resistant TB continues to be a public health crisis.

More than half a million people developed TB that was resistant to rifampicin (RR-TB), the most

effective first-line drug. Burden of TB disease is still high, affecting all countries, all ages, men,

women and children. In the Western Pacific region, an estimated 1.8 million people developed TB

and also had estimated 114,231 incident multi-drug resistant (MDR) TB cases in 2017. There is

progress, but it is slow - not fast enough to reach End TB targets or make major headway in closing

persistent gaps. This Region is in the crossroad of old and new challenges. Old challenges include

missing TB cases, huge pool of latent TB infection, slow uptake of innovations and catastrophic

cost incurred by TB affected person and families. New Region specific emerging challenges include

rapid economic growth, urbanization and ageing of the population. Rapid economic growth quickly

changes the funding landscape and health financing modalities, flourishes private sectors. Rapid

urbanization makes interventions complex. TB in elderly requires more comprehensive package of

patient centred care including co-morbidity management. Policy - practise pathway remains a major

challenge – it takes a huge ‘time’ toll, sometime ‘pilot’ becomes the enemy of ‘scale-up’. In the

Western Pacific, WHO will address these issues in partnership with Member States by

operationalizing the strategic shifts by focusing on innovation, back casting, systems approach,

building solutions from the ground up, championing health, beyond the health sector, driving and

measuring country impact and strategic communications as a means to deliver on new ways of

working. The declaration of the first-ever United Nations High Level Meeting on TB created a

major momentum to reach all people by closing the gaps on TB diagnosis, treatment and prevention

and commit to decisive and accountable leadership.

19



TB and Migration

Assoc Prof Alex COOK

TB Biomarkers

Prof Delia GOLETTI

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is still an important global health

problem with 10 million cases worldwide estimated in 2017 by the World Health Organization

(WHO) and 1.7 million deaths. This number of deaths is unacceptably high because with prompt

diagnosis and appropriate treatment, almost all TB patients can be cured. Almost one-fourth of the

world’s population is latently infected with Mtb with a risk of progression to active disease of about

3-15% during their lifetimes. Being latent TB infection (LTBI) an important reservoir for TB

disease progression, an effectively elimination of TB epidemic is feasible only diagnosing and

treating LTBI.

Accurate and fast TB diagnosis can be difficult, due to several limitations in the currently available

diagnostic tests. In the case of pulmonary TB, sputum-based tests require a Mtb-positive sputum

even though many active TB patients, including HIV-coinfected individuals, diabetes patients and

children, often do not present with Mtb-positive sputum and thus cannot provide microbiologically

positive specimens. Moreover, in extra-pulmonary disease, sputum-based diagnostics are

inapplicable, and diagnosis relies on samples often collected by invasive procedures. For all of these

reasons, a sensitive and specific diagnostic tests for TB to rapidly identify—or rule out—the

presence of active disease is needed. The World Health Organization recently defined high-priority

target product profiles for TB diagnostics. These include a rapid non-sputum-based test for

detecting TB with the purpose of starting specific TB therapy on the same day. These tests need to

perform in endemic settings with limited laboratory facilities, at low cost, using easily accessible

non-sputum-based samples such as (finger prick) blood, urine or breath. Therefore, there is an

urgent need to search for biomarkers (BM) that could be used in such tests. Disease-related TB-BM

could find application in improved and fast clinical decision making, for example in developing

improved tests that more accurately and differentially diagnose TB disease. New promising

experimental tests will be discussed.

20



SESSION 2: PATHOLOGY OF TUBERCULOSIS

Host Immune Defence in Tuberculosis, A Clinical Perspective

Prof Reinout van CREVEL

Host immunity is critical for protection against Mycobacterium tuberculosis, and decreased host

immunity may lead to disseminated or severe manifestations of tuberculosis as well as infections

with non-tuberculous mycobacteria. The host inflammatory response may also lead to unwanted

tissue pathology, and thereby worsen patients’ clinical outcome. This discussion will discuss

clinical cases to provide practical guidance for diagnosis and management of host immune defects

and immunopathology associated with TB.

Physiology and Pathology of TB

Prof Jon FRIEDLAND

Tuberculosis still kills more people than any other single infection and the rise of drug resistance

necessitates a search for new approaches to treatment potentially harnessing the human immune

response to fight disease. Patients with tuberculosis (TB) are often characterized by having

extensive pathology most typically pulmonary cavitation. However, patients have also frequently

lost weight, have a fever and on blood gas analyses, are likely to be both hypoxic and acidotic

reflecting severe accompanying physiological changes. Tissue destruction in Tb is not primarily a

result of pathogen activity but due to the innate inflammatory immune response and in particular,

the destructive effect of enzymes, particularly the matrix metalloproteinase (MMPs) which are

unique in being able to destroy the triple helix of collagen.

In the talk, I shall review some recent work on the regulation of MMPs and the impact on tissue

damage in tuberculosis. I shall consider aspects of the influence of metabolic change, hypoxia and

acidosis on the regulation of MMPs and the inflammatory response in tuberculosis. I shall first

address the question of whether TB lesions are even hypoxic since current dogma is that the disease

location in the upper lowers of the lung reflects a predilection of the organism for an aerobic

environment. There are almost no data on the impact of acidosis on macrophage function even in

the absence of tuberculosis and so I shall examine both the impact of acidosis on macrophage

function before considering what happens in tuberculosis in the presence of acidosis. There will be

emphasis in the talk on what actually happens in the TB patient since understanding

pathophysiological change is key in considering the development of host directed therapies.

21



SESSION 3: DIAGNOSING TUBERCULOSIS

Understanding the Use of Interferon Assays

Prof Delia GOLETTI

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is still an important global health

problem with 10 million cases worldwide estimated in 2017 by the World Health Organization

(WHO). Almost one-fourth of the world’s population is latently infected with Mtb with a risk of

progression to active disease of about 3-15% during their lifetimes. Being latent TB infection (LTBI)

an important reservoir for TB disease progression, an effectively elimination of TB epidemic is

feasible only diagnosing and treating LTBI.

Currently, there are no gold standard tests for LTBI diagnosis. Tuberculin skin test (TST) and T-cell

interferon-γ release assays (IGRAs) are the routine tools used. TST is based on an immune reaction

to the intradermal injection of purified protein derivate of tuberculin, a mixture of antigens that,

however, is shared by Mtb and bacille Calmette–Guérin (BCG), as well as other mycobacteria,

affecting the test specificity.

To overcome this limitation, two IGRAs, Quantiferon®-TB Gold Plus (QFT) and T-Spot®.TB

(TSPOT), were developed. IGRAs measure the IFN-γ production to Mtb specific peptides (ESAT-6,

CFP-10) located in the region of difference (RD) 1 of Mtb and this leads to a higher specificity for

LTBI detection compared to TST. However, since both TST and IGRAs imply an immune reaction,

these tests have a suboptimal diagnostic accuracy in immunocompromised patients as well as in

children who have an immature immune system. Finally, TST and IGRAs do not differentiate

between active TB and LTBI, between active TB and cured TB, between recent and remote

infections. New promising experimental tests that may overcome these limitations are available and

will be discussed.

The Role of the Microbiology Laboratory

Prof Emmanuelle CAMBAU

Tuberculosis is due to the multiplication of bacteria speciated as Mycobacterium tuberculosis

complex, grouping different variants and lineages. The disease is mainly respiratory TB, which

accounts for 75% of cases and is highly contagious. Extra-respiratory TB may involve any organ

and lymphatic nodes since it resulted from the dissemination of the bacilli. The challenge of clinical

microbiology laboratories is first to make the diagnosis as early as possible to implement measures

to prevent air-borne transmission, and second to detect the multidrug resistant TB cases since these

patients will not be cured following the standard HRZE treatment. The detection of acid-fast bacilli

(AFB) on sputum smears using Ziehl-Neelsen staining under light microscopy remains a quick and

reliable test for the diagnosis of pulmonary TB and the cheapest. Staining with auramine with

reading using LED microscopy improves the detection and the easiness. About half of the

pulmonary TB cases are smear-positive, depending on the area. Cultures are difficult since they

require a decontamination step, which in theory is supposed to kill bacteria others than

mycobacteria while leaving alive the mycobacteria. Practically this is not that obvious and needs an

equilibrium between the two actions of kill and preserve, and needs good indicators. If culture in

liquid medium gives a positive signal earlier than solid medium, both are necessary to increase the

sensitivity of the culture, i.e. the positive diagnosis of smear-negative TB cases. Smear-positive

cases can be rapidly confirmed as TB cases by performing nucleic acid amplification tests (NAAT)

directly on specimen. NAAT can be also useful to diagnose a smear-negative TB case although it is

less sensitive than culture, and cost-effectiveness should be evaluated with regards to the area where

22



it is applied. It is now recommended for any person with high suspicion of TB. Susceptibility

testing is much more difficult for MTb than for other bacteria and requires laboratories with

expertise, safety rooms BSL3 and specific equipment. Different methods and many techniques are

available although they need to be validated with regards to the reference. EUCAST worked on a

reference protocol to be tested for new antituberculous drugs in order to homogenize the results

over the world. TB is developing in persons who have been infected in the previous years and these

persons may show interferon gamma response (IGRA) when their lymphocytes are stimulated with

specific antigens. All these diagnostic tools help in the management and prevention of TB

transmission, including whole genome sequencing for comparing isolates.

23



SESSION 4: TREATING TB AND DELIVERING CARE

Whole Genome Sequencing in TB

Assoc Prof Li Yang HSU & Asst Prof Rick ONG

The recent advancements in molecular sequencing technologies and bioinformatics have enabled

the high-throughput and cost-effective examination of the entire genetic composition of infectious

pathogenic microorganisms. By tracking the genomic variations in bacteria over their evolution

across time and space; correlating with phenotypes such as antimicrobial resistance will allow

greater resolution than current methods in investigation of disease outbreaks to determine their

spread and transmission. In this lecture, I will introduce the basic techniques and concepts to

sequencing technologies and bioinformatics approaches underlying the inference of antimicrobial

resistance for clinical treatment and disease transmission between individuals for public health

surveillance from Mycobacterium tuberculosis genomic data.

Public Health and Social Aspects of TB Management

Assoc Prof Alex COOK

Managing Drug-Resistant TB

Assoc Prof Cynthia CHEE

Multidrug resistant (MDR) and rifampicin resistant (RR) TB are difficult to treat and pose a

challenge to TB control efforts worldwide. Global programmatic treatment outcomes for MDR-TB

have been poor at around 50% with high defaulter rates due to second-line drug toxicity and

prolonged treatment duration.

The 2019 World Health Organization (WHO) MDR / RR TB treatment guidelines significantly

departs from previous editions in that the second-line drugs are re-grouped, and the injectable

agents (kanamycin and capreomycin) are no longer recommended. These guidelines strongly

recommend a later generation fluoroquinolone (levofloxacin or moxifloxacin), bedaquiline and

linezolid (Group A medications) to be included, with the addition of clofazimine and/or cycloserine

or terizidone (Group B medications) to form a regimen comprising at least 4 effective drugs in the

first 6 months, followed by at least 3 effective drugs for a total duration of 18-20 months. Group C

medications comprise all other medications which can be used, ranked by the relative balance of

benefit to harm, when a regimen cannot be composed with Group A and B agents. TB laboratories

will have to build capacity to provide appropriate drug susceptibility testing in response to these

latest guidelines.

For eligible patients, WHO recommends the standardized shorter (“Bangladesh”) MDR-TB

regimen of 9-11 months comprising 7 drugs in the intensive phase of 4-6 months followed by 5

months of 4 drugs in the continuation phase. This regimen was shown in a large-scale randomized

controlled study to be non-inferior to the 18-24 month WHO-recommended (2011) MDR-TB

regimen with treatment completion rates of 79.8% vs 78.8% for the long and shorter regimens

respectively.

Although WHO recommends patients with RR but isoniazid-susceptible TB be treated with MDR-

TB regimens, the evidence base for this is lacking. For rifampicin mono-resistant cases, North

American guidelines have recommended 9 -18 month regimens comprising isoniazid, ethambutol,

24



pyrazinamide with a fluoroquinolone, which may be augmented by an injectable agent in the initial

months of therapy for those with extensive disease.

Psychosocial and financial support to foster patient adherence, and active TB drug safety

monitoring and management (aDSM) are essential to achieve the best possible treatment outcome

for MDR-TB patients.

Extra-Pulmonary TB

Assoc Prof Tsin Wen YEO

CNS-TB

Prof Guy THWAITES

25



SESSION 5: UPDATE ON THE CUTTING EDGE OF TB SCIENCE

Clinical Trials in TB

Prof Nick PATON

Host-Directed Therapy in TB

Adj Asst Prof Amit SINGHAL

An effective host immune response is important to control Mycobacterium tuberculosis (Mtb) insult,

and to contain its latent persistence. A new paradigm in TB treatment, host-direct therapy (HDT),

uses adjunctive drugs to harness intrinsic antimicrobial and immunoregulatory mechanisms for better

treatment outcomes. Using chemical genetics approach we have demonstrated that activating AMP-

activated protein kinase (AMPK) and Sirtuin 1 (SIRT1), regulators of whole-body energy

metabolism, by FDA approved drugs / supplements could control inflammation and Mtb infection.

This indicates a deep engagement of Mtb pathogenicity with host’s immuno-metabolic machinery.

We hypothesize that the functional connections between immunity and pathways controlling

metabolic signaling could be harnessed to advance the host-directed therapy (HDT) pipeline,

leading to the development of clinically relevant anti-tuberculosis arsenal. We are currently

utilizing gain- and loss- of function strategies to further understand the molecular and cellular

mechanisms of AMPK and SIRT1 activators. The data related to this effort will be presented and

discussed.

New Kids on the Block

Assoc Prof Kevin PETHE

The rapid emergence and spread of multi-drug resistant Mycobacterium tuberculosis and other

pathogenic bacteria is a serious concern worldwide that advocates for the development of new

classes of antibacterials with a novel mode of action. Current antibiotics derive mainly from natural

sources and inhibit a narrow spectrum of cellular processes such as DNA replication, protein

synthesis and cell wall biosynthesis. With the spread of drug resistance, there is a renewed interest

in the investigation of alternate essential cellular processes, including central metabolic and

bioenergetics pathways, as a drug target space for the next generation of antibiotics. Oxidative

phosphorylation as recently emerged as a relevant target space for the development of new drug for

tuberculosis. In this context, I will discuss the relevance of targeting the terminal respiratory

oxidases for the development of a rational drug combination for tuberculosis and other

mycobacterial diseases.

26



SESSION 6: COMPLEX PATIENTS: CASE-BASED DISCUSSIONS

Tuberculosis and HIV

Prof Yee Sin LEO

Tuberculosis and Diabetes Mellitus

Prof Reinout van CREVEL

People with diabetes mellitus (DM) are an estimated 3.7 times more likely to develop TB than those

without DM, and this risk is higher with poorly controlled DM. It is estimated that DM now

accounts for >10% of TB globally, and this will increase significantly in the coming decades due to

the dramatic rise in type 2 DM in TB endemic settings.

This presentation will discuss clinical management of combined TB and DM which can be

challenging in terms of achieving good disease outcomes and avoiding toxicity, drug-interactions

etc. Diabetes management during anti-TB treatment should consist of glycaemic control and

measures to reduce the risk of cardiovascular disease. Tuberculosis treatment should be monitored

more closely, as DM is associated with an increased risk of drug-resistance, lower exposure of TB

drugs, treatment failure and recurrent TB.

Managing TB in the Immunocompromised

Asst Prof Catherine ONG

TB in immunocompromised hosts presents its own set of challenges. Rates of active TB

reactivation are higher, extra-pulmonary dissemination are more common, and treatment

complications including drug interactions are often encountered. In this talk, I shall discuss latent

TB screening and TB diagnosis in this special group of patients, illustrating with case examples,

and elaborating on treatment pitfalls to avoid.

Challenging TB Cases in Asia

Prof Guy THWAITES

27



SESSION 8: NON-TUBERCULOUS MYCOBACTERIA

Microbiological Diagnosis of Infections Due to Nontuberculous Mycobacteria

(NTM)

Prof Emmanuelle CAMBAU

Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies many of which can

produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites.

NTM are present in the environment and are usually nonpathogenic. Some of them are

opportunistic respiratory pathogens, causing infections that mimic tuberculosis. Some others cause

opportunistic infections observed in immunocompromised patients or as healthcare-associated

infections.NTM infections are not usually transmissible between humans and epidemic cases, but

may be linked to the same contamination event from a common reservoir. They are rare, even

though their numbers increased during the last 20 years. For respiratory cases, the diagnosis is

often fortuitous, while looking for signs of tuberculosis. Although the clinical and bacteriological

diagnoses show now a consensus, the treatment is still at the clinical research stage. Therapeutic

management is difficult also partly due to the small number of effective antibiotics, and partly

because the long-term treatment produces side effects. Mycobacterium avium complex,

Mycobacterium kansasii, Mycobacterium chelonae and Mycobacterium abscessus are the most

frequent NTM observed as opportunistic pathogens causing lung and extrarespiratory infections,

beside M. ulcerans and M. marinum that are pathogens causing specific skin and soft tissue

infections. Disseminated infections occur only in severe immunosuppressed conditions such as

AIDS or long-term corticosteroids. The diagnosis is based on repeated isolations of the same

mycobacterium associated with clinical and radiological signs, and the absence of tuberculosis or

other pathogens. Precise species identification can be obtained by molecular biology and mass

spectrometry and often requires a laboratory with NTM expertise. Therapeutic antibiotic regimens

differ with regard to the NTM species involved. Prevention of iatrogenic infections relies on using

sterile water in all injections, healthcare and cosmetic occupations. Future perspectives are to set

effective antibiotic regimens tested in randomized therapeutic trials.

An Update on the Diagnosis and Management of Non-tuberculous

Mycobacterial Infections – Perspectives from the Singapore Laboratory

Dr Li-Hwei SNG

Leprosy

Dr Chew Swee SEOW

28



POSTER ABSTRACTS

Clinical Profile and Outcomes of Patients with Tuberculous Arthritis Admitted

in a Tertiary Hospital in the Philippines

Poblete J1, Salamat MS2, Manapat-Reyes H3

1Department of Medicine, Philippine General Hospital 2Section of Infectious Diseases, Department of Medicine, Philippine General Hospital 3Section of Rheumatology, Department of Medicine, Philippine General Hospital

Objective: This study aims to describe the clinical profile and outcomes of patients with

tuberculous (TB) arthritis admitted in a public tertiary hospital in the Philippines.

Methodology: Clinical, laboratory, radiologic, histopathologic characteristics, and outcomes of

patients with TB arthritis admitted in the Philippine General Hospital from 2006 to 2015 were

obtained retrospectively.

Results: Among 39 patients with TB arthritis, majority were male and mean age was 50 years.

Pulmonary/disseminated TB, hypertension, diabetes, chronic kidney disease, and other

rheumatologic diseases were reported co-morbidities. A history of TB, intake of

immunosuppressive therapy, and trauma to affected joint were present in some patients. Majority

presented with chronic monoarthritis of the knees and hips with a mean diagnosis time of 18.7

months. Septic arthritis was the most frequent initial diagnosis upon consult. Anemia and elevated

Inflammatory markers (ESR and CRP) were observed in the majority. Radiographically, joint space

narrowing was common. All biopsy results showed chronic granulomatous inflammation with

caseation necrosis. All had no growth on routine bacterial culture except for one patient with

concurrent septic arthritis. All patients received standard HRZE treatment upon diagnosis. The most

common surgical interventions were debridement and arthrotomy.

Conclusion: There should be a high index of suspicion for TB arthritis in any patient from an

endemic country presenting with chronic monoarthritis in weight-bearing joints. Negative bacterial

cultures, anemia, elevated inflammatory biomarkers, and joint space narrowing on radiologic

studies could also provide potential clues in accurate diagnosis. Prompt initiation of treatment is

necessary in order to prevent significant joint destruction and disability.

29



Comparative Genomic Analysis of Mycobacterium Tuberculosis from Pulmonary

and Central Nervous System Infections to Determine Factors of Neurotropism

Saw SH1,2, Yap SF1 and Ngeow YF1

1Department of Pre-Clinical Sciences, Faculty of Medicine and Health Sciences, Universiti Tunku

Abdul Rahman, Malaysia 2Department of Biomedical Science, Faculty of Science, Universiti Tunku Abdul Rahman, Malaysia

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB) and the major

mycobacterial species associated with central nervous system (CNS) infection. Tuberculous

meningitis (TBM) is a global challenge due to difficulties with diagnosis, treatment and high

mortality rate. It is not clear what factors promote CNS invasion and pathology in TB, but it has

been reported that Mtb isolates from meningitis patients show specific genetic traits not found in

respiratory isolates. Thus, in this study, genomic features of Mtb isolates from CSF and respiratory

specimens were compared to identify factors that could contribute to neurotropism in the

pathogenesis of CNS TB. First, suppression subtractive hybridisation (SSH) combined with T/A

cloning technology was utilized to build a subtracted cDNA library of genes showing DNA

sequence differences between two strains of Mtb from the CSF of Malaysian patients with

meningitis and two strains from sputum samples. Subsequently, the whole genome sequences

(WGS) of eight CSF strains from Malaysian patients presenting with TB meningitis (TBM) were

analysed against the WGS of 30 to 85 respiratory strains, including the reference strain H37Rv,

downloaded from public databases. All WGS were examined for gene rearrangements, indels,

inversions, micro-variants, as well as structural and globularity changes in proteins. In addition,

they were searched for homologs of genes previously reported to be associated with meningitis in

Mtb and three other neuropathogens, Neisseria meningitidis, Streptococcus pneumoniae and

Escherichia coli K1.

With SSH, 7 subtracted DNA fragments of various sizes were generated. With the use of BLASTN

and BLASTX, these subtracted sequences were shown to be similar to those found in Mtb strain

isolated from the brain of an Indian patient. They encode mycobacterial PE/PPE proteins which

play an important role in the evasion of host immune responses, and other conserved hypothetical

proteins with unknown function. Genome-wide comparisons revealed rearrangements

(translocations, inversions, insertions and deletions) and non-synonymous single nucleotide

polymorphisms (ns SNPs) in the CSF-derived strains that were not observed in the respiratory Mtb

genomes used for comparison. These rearranged segments were rich in genes for PE/PPE,

transcriptional and membrane proteins. Similarly, most of the ns SNPs common in CSF strains were

found in genes encoding PE/PPE proteins. Protein globularity differences were observed among

mycobacteria from both CSF and respiratory sources and in proteins previously reported to be

associated with TBM. Transcription factors and other transcription regulators featured prominently

in these proteins. Homologs of TBM-associated genes were found in the WGS of Mtb, M. bovis, M.

leprae, M. lepromatosis and two environmental non-tuberculous mycobacteria. However,

only two of these homologs were identified in all eight CSF-derived Mtb genomes. Three homologs

of 141 genes reported to be associated with S. pneumoniae meningitis and two of 164 virulence

genes reported in N. meningitidis were also found in the CSF-derived Mtb genomes. The detection

of common meningitis-associated genes in mycobacterial and non-mycobacterial neuropathogens

raises speculations on the existence of a pan-bacterial mechanism of CNS infection. However, all

the genes shared by CSF Mtb strains and other neuropathogenic bacterial spp. were also found to be

common in the comparison respiratory Mtb genomes examined. Hence, although some genetic traits

were found in CSF-derived but not sputum-derived Mtb examined in this study, there are

indications that neurotropic traits may not be specifically or universally found in Mtb causing CNS

disease. Overall, the findings from this study suggest that CNS infection in TB is more likely to be

directed by the expression of multiple virulence factors selected by the interaction between

pathogen and host immune responses, than the presence of specific genetic traits.

30



Prevalence of Multidrug Resistant Tuberculosis and its Detection by Using

Xpert MTB/Rif Assay

Ahmad HF, Mustakim S, Gan B

Microbiology Unit, Pathology Department, Hospital Tengku Ampuan Rahimah Klang

Respiratory Unit, Department of Medicine, Hospital Tengku Ampuan Rahimah Klang

Background. Tuberculosis has still remained a major public health threat and with the emergence

of multidrug-resistant tuberculosis (MDRTB), worsened and complicates the issues. It is estimated

that in 2017, incidence rate of MDRTB in Malaysia is 1.5 per 100 000 populations with 3.1%

occurring in previously treated TB cases. The aim of our study is to know the prevalence of

MDRTB in our hospital by using Xpert MTB/Rif Assay.

Methods. A prospective study was done at Hospital Tengku Ampuan Rahimah Klang from May

2017 till May 2019. 103 smear-positive sputum samples were collected and analyzed by using

Xpert MTB/Rif Assay.

Results. Among 103 patients, 58 (56.3%) were newly diagnosed TB patients while 45 (43.7%)

were among previously treated TB patients. The median age was 39.5, ranges from 18 to 83 years

old. Males were more likely to be infected with MDRTB (62.5%) and non-MDRTB (71.6%) when

compared with females. Among all TB cases, 82.5 % were Malaysians (46.6% Malays) and only

17.5% were non-Malaysians. We detect 8 (7.8%) cases of MDRTB, in which all of them were

occurring in previously treated TB patients (p=0.008). 6 cases (75%) were treated for pulmonary

TB while the other 2 were extrapulmonary TB. 66.7 % (4 out of 6) of previously treated pulmonary

TB patients defaulted their treatment, hence pose a risk of developing MDRTB.

Conclusions. Our result demonstrated that the prevalence of MDR TB in our hospital is 7.8% with

75% occurring in previously treated pulmonary TB patients. Therefore, ensuring the adherence and

compliance to TB treatment as well as tightening follow-up strategies are crucial for better TB

control.

31



Abdominal Cocoon Syndrome from Nontuberculous Mycobacterial Infection

Masquerading as Tuberculosis in an Incidentally-diagnosed Multiple Myeloma

Patient

Cruz MG1, Tuazon CA1, Olivar CM2, Buensalido JA1, Odoño E2, Lucero JA1, Dela Torre MK1

1Department of Medicine, Philippine General Hospital, Philippines 2Department of Laboratories, Philippine General Hospital, Philippines

Background/Aim:

Abdominal cocoon syndrome, or sclerosing encapsulating peritonitis, is a rare condition of

peritoneal fibrosis that can manifest as gut obstruction due to extrinsic bowel compression. It has

been reported in various conditions such as sarcoidosis, peritoneal dialysis, and tuberculosis.

Methods:

This paper reports the first case of abdominal cocoon syndrome caused by a rapidly-growing

nontuberculous mycobacterium, Mycobacterium fortuitum, in a 50-year old male from a high

tuberculosis burden country, the Philippines.

Results:

The patient presented at the emergency room with symptoms of gut obstruction. CT scan revealed

air-fluid level and massive fluid collection in the abdomen, suggestive of intraabdominal abscess

formation. Pigtail catheter insertion was done for diagnostic and therapeutic drainage. Culture and

sensitivity studies showed polymicrobial infection: Mycobacterium, Candida, Klebsiella, and

Citrobacter freundii – a gas-producing bacterium which may have caused the pneumoperitoneum at

the onset. Culture-guided antibiotic therapy was started. Further investigations regarding his

susceptibility to overwhelming infections led to the diagnosis of multiple myeloma. Unfortunately,

the patient succumbed to septic shock from hospital-acquired pneumonia and bacteremia. Autopsy

findings later revealed the presence of a thick fibrinous sac encasing the entire intraabdominal

viscera, suggestive of abdominal cocoon syndrome.

Conclusion:

Definitive diagnosis of abdominal cocoon syndrome is confirmed via laparotomy. Immediate

surgical intervention is warranted to provide adequate source control, and to relieve the obstruction.

The team, however, opted for conservative treatment since the patient was a poor surgical

candidate. Early diagnosis and aggressive management of infection could have been life-saving for

this case.

32



Disseminated Mycobacterium Abscessus Infection and Multiple Myeloma in a

Patient from a Country with High Tuberculosis Burden

Villanueva CAG1, Bartolo S2, Vallente JR3, Roxas EA2

1Department of Medicine, Philippine General Hospital, University of the Philippines Manila,

Philippines 2Division of Infectious Diseases, Department of Medicine, Philippine General Hospital,

University of the Philippines Manila, Philippines 3Division of Hematology, Department of Medicine, Philippine General Hospital,

University of the Philippines Manila, Philippines

Background/Aim: There is sparse data on nontuberculous mycobacteria (NTM) infections in the

Philippines. Disseminated infection with Mycobacterium abscessus complex, which are rapidly

growing mycobacteria, is uncommon.

Methods: We discuss the clinical presentation and course of the first reported case of M. abscessus

pulmonary disease and bone marrow involvement of NTM in an HIV-negative patient from the

Philippines.

Results: A 55-year-old Filipino man presented with chronic hip pain, anemia, hypercalcemia and

acute kidney injury. He previously received an incomplete course of treatment for pulmonary

tuberculosis. A plaque with scaling on the neck was biopsied and revealed granulomatous

dermatitis. Sputum smear showed acid-fast bacilli but was negative for tuberculosis on polymerase

chain reaction. Tracheal aspirate specimens grew NTM and species identification led to M.

abscessus. Bone marrow aspirate was also positive for NTM. Osteolytic lesions on the femur were

supported by bone marrow findings suggestive of multiple myeloma. Outpatient antimycobacterial

treatment with clarithromycin, cotrimoxazole and ciprofloxacin was given based on susceptibility

testing. The patient initially received melphalan and prednisone for multiple myeloma. As of

writing, the patient was on the ninth month of treatment and was recently hospitalized due to

symptomatic anemia. Repeat sputum smears were negative for acid-fast bacilli.

Conclusion: Even in areas of high tuberculosis burden, clinicians should consider NTM in the

differential diagnoses of patients with chronic respiratory symptoms and cutaneous infections

especially in the setting of immunocompromising conditions like hematologic malignancies.

33



The Cascade of Care of Rifampicin-Resistant Tuberculosis: Experience from a

Tertiary Hospital in Bandung, Indonesia

Larasmanah ASN1, Lestari BW1,2,3, Santoso P4, Soeroto AY4, van Crevel R3,5, Hill PC6

1Infectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran, Bandung,

Indonesia 2Department of Public Health, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia3Department of Internal Medicine, Radboud Institute for Health Sciences, Radboud University

Medical Center, Nijmegen, The Netherlands 4Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran/Dr. Hasan

Sadikin General Hospital, Bandung, Indonesia 5Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of

Oxford, Oxford, United Kingdom 6Center for International Health, University of Otago, Dunedin, New Zealand

Background:

The emergence of rifampicin-resistant TB (RR-TB) is threat for TB control program in Indonesia.

The TB cascade of care is useful to identify where patients are lost or have sub-optimal

management from initial screening to the end of treatment. We aimed to describe the cascade of

care for newly diagnosed RR-TB, including characterising a ‘secondary cascade’ in those without

phenotypic drug-susceptibility testing (DST) results at the time of treatment initiation.

Methods:

We analysed a cohort of RR-TB patients registered in Hasan Sadikin Hospital over period of 2015-

2016. We identified the following cascade steps for newly diagnosed RR-TB patients: 1) the

number of presumptive RR-TB; 2) RR-TB confirmed by GenXpert; 3) RR-TB with initial

assessment; 4) RR-TB starting second-line treatment; and 5) successfully treated RR-TB. We

compiled a secondary cascade after step 2, for patients starting treatment without available DST

result.

Results

Of 3415 patients registered as presumptive RR-TB , 3215 (94%) were tested by GenXpert, of whom

376 (11.7%) were diagnosed as RR-TB. 333/376 (89%) were newly diagnosed while 43 had

received RR-TB treatment previously. 283/333 (85%) initiated treatment, 143/333 (43%) were

confirmed as MDR-TB through DST, 190 had no DST result available. The treatment success rate

was 89/140 (64%; 27% of all newly diagnosed) for those with baseline phenotypic DST results who

commenced treatment, compared to 76/143 (53%) in those without DST confirmation (p value =

0.05).

Conclusion

Only 27% of RR-TB patients successfully progressed through a full ‘primary’ cascade of care.

Baseline phenotypic DST is important for the best treatment outcome.

34



Matrix Metalloproteinase (MMP) Inhibitor Doxycycline Suppresses Systemic

and Respiratory MMPs in Patients with Pulmonary TB

Miow QH1, Wang Y1, Teo F2, Wang DA2, Loh HR1, Hong JM1, Tan TZ3, Ding Y4, Gan SH5, She

HW5, Paton NI1, Singhal A6, Tambyah PA1,2, Chee C5, Wang YT5, Elkington PT7, Friedland JS8,

Ong CWM1,2,5

1Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore,

Singapore 2Division of Infectious Diseases, National University Health System, Singapore 3Cancer Science Institute of Singapore, National University of Singapore, Singapore 4Clinical Services, National Centre for Infectious Diseases, Singapore 5Tuberculosis Control Unit, Tan Tock Seng Hospital, Singapore 6Singapore Immunology Network, A*Star, Singapore 7Medicine, University of Southampton, United Kingdom 8Institute of Infection and Immunity, St George’s, University of London, United Kingdom

Background/Aim: Tuberculosis (TB) causes tissue destruction where the activity of matrix

metalloproteinases (MMPs) are unopposed to tissue inhibitors (TIMPs). We hypothesize that

doxycycline, a licensed MMP inhibitor, decreases matrix degradation in TB patients.

Methods: 30 HIV-negative pulmonary TB patients were randomized to 14 days of doxycycline or

placebo in addition to standard anti-TB treatment. Subjects were followed-up at days 14, 28 and 56.

Clinical data, sputum and blood were collected. Primary endpoint was change in N-terminal pro-

peptide of Type III collagen (PIIINP) from day 0 to day 14. Secondary endpoints were change of

sputum M. tuberculosis (Mtb) colony forming units (cfu), chest radiograph (CXR), MMPs, TIMPs,

as well as Type I collagen and elastin degradation activities. PIIINP, MMPs and degradation

activities were assessed by ELISA, luminex array and quantitative fluorometry, respectively.

Results: Median age of TB patients was 47.5 years old and 20% were women. 66% of TB patients

had grade 1 and 2 adverse events which were mainly nausea and vomiting. None experienced

serious adverse events. Plasma PIIINP increased at day 14 with doxycycline (p < 0.05). Sputum

MMP-1, -8, -9, -12 and -13 decreased with doxycycline at day 14, with concomitant decrease in

sputum Type I collagen and elastin degradation activities (all p < 0.05). Plasma MMP-1 and -8

were also decreased with doxycycline (all p < 0.05). CXR, pulmonary cavities and sputum Mtb cfu

were unchanged between groups.

Conclusion: 2 weeks of adjunctive doxycycline is safe with standard anti-TB treatment and

resulted in sputum and systemic MMPs suppression in TB patients.

35



Low Uptake of Window Prophylaxis in High Risk Children After Exposure to

Pulmonary Tuberculosis from a Healthcare Worker

Sinnathamby A1, Ang SBN1, Bagdasarian N2,3,4, Chan HC3, Chan SM1,3

1Department of Paediatrics, Khoo Teck Puat National University Children’s Medical Institute,

National University Hospital, Singapore 2National University Hospital, Department of Medicine, Division of Infectious Diseases, Singapore 3Yong Loo Lin School of Medicine, National University of Singapore, Singapore 4Department of Infection Prevention, National University Hospital, Singapore

Background: A nurse caring for paediatric inpatients was diagnosed with smear positive

pulmonary TB after 5 months of cough. 173 children (<2 years old, immunocompromised or >40

hours of contact) were contact traced.

Methods: Children received clinical review, chest X-ray, and a tuberculin skin test (TST) (<5 years

old) and/or an interferon gamma release assay (Quantiferon TB-Gold) (>5 years old). Infants <6

months old and children screened <2 months from time of exposure were recommended isoniazid

window prophylaxis (WP) until a repeat TST at 6 months old or 8-10 weeks later respectively.

Empiric treatment of 9 months isoniazid for latent tuberculosis infection (LTBI) was considered for

immunocompromised patients on an individual basis. Patient information leaflets and counselling

were provided.

Results: 126 immunocompetent and 36 immunocompromised children were screened. 2 were

uncontactable, 7 refused screening. 2 immunocompromised children were excluded. 8

immunocompetent children were diagnosed with LTBI (initial TST positive n=7, TST conversion

n=1); 7 (88%) accepted LTBI treatment. 15 (47%) of 32 immunocompetent children accepted the

recommended WP; 1 was non-compliant after 1 month.

6 (86%) of 7 immunocompromised children accepted recommended empiric LTBI treatment due to

severe immunosuppression (n=5) or initial indeterminate Quantiferon TB-Gold result (n=2). 5 (33%)

of 15 immunocompromised children accepted the recommended WP; 1 developed rash and

discontinued isoniazid after 2 weeks.

Conclusion: There was low uptake of isoniazid WP in high risk children exposed to pulmonary TB.

Perception of exposure risk and reluctance to take medication with potential adverse effects should

be explored further.

36



MMP-2 and -9 are Increased in Paediatric Tuberculous Meningitis (TBM)

Patients and a Murine Central Nervous System Tuberculosis (CNS-TB) Model

Poh XY1, Hong JM1, Miow QH1, Yeo TW2, Ong CWM1

1Department of Medicine, National University of Singapore, Singapore 2Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore

Background/Aim: CNS-TB patients develop extensive brain inflammation and tissue destruction,

characterised by a matrix-degrading phenotype. 45% patients also develop strokes. However, the

mechanisms underlying inflammation, tissue destruction and strokes remain undefined.

Methods: The cerebrospinal fluid (CSF) of 62 paediatric patients with tuberculous (TBM),

bacterial (BM), viral (VM) and non-infectious meningitis were analysed for matrix

metalloproteinases (MMPs) by luminex array and neutrophil extracellular traps (NETs) by

quantitative fluorometry. To develop a murine CNS-TB model, mouse strains Nos2-/- and

C3HeB/FeJ, Mycobacterium tuberculosis (M.tb) strains H37Rv and CDC1551 and routes of

infection by intra-cerebroventricular (ICV) and intravenous (IV) were evaluated. Murine expression

levels of MMPs, tissue-specific inhibitors of metalloproteinases (TIMPs), adhesion molecules,

cytokines and chemokines in the brain were analysed by luminex array.

Results: CSF EMMPRIN, MMP-2 and -9 concentrations were significantly increased in TBM

patients compared to BM patients. CSF extracellular DNA concentration was increased in TBM

patients compared to non-infectious and VM patients, showing a significant negative correlation

with clinical neurological scores. Nos2-/- mice developed myoclonic jerks, seizures and limb

weakness from 3 weeks post-infection while C3HeB/FeJ remained normal. Murine brain MMP-2

and -9 concentrations in infected Nos2-/- mice were increased relative to saline controls. Nos2-/-

mice infected with CDC1551 strain via the ICV route had a significantly higher mortality (100%

mortality by 42 days post-infection) compared to the IV route (0% mortality).

Conclusion: The increase in MMP-2 and -9 concentrations is found both in humans and in our

murine model, and may drive CNS-TB immunopathology.

37



ACKNOWLEDGEMENTS

The Organising Committee would like to thank the following for their kind and

generous contributions for the course:

SUPPORTING ORGANISATIONS

SPONSORS

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