Tuberculosis and Mycobacterial Infections: An Educational Update - ESCMID Postgraduate Education Course - ESCMID Postgraduate ...
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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
ESCMID Postgraduate Education Course 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. Tuberculosis and Mycobacterial Infections: An Educational Update 1
ESCMID Postgraduate Education Course 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. Tuberculosis and Mycobacterial Infections: An Educational Update 2
ESCMID Postgraduate Education Course
FACULTY
Assoc. Prof. Sylvie ALONSO
Associate Professor
Department of Microbiology and Immunology
National University of Singapore
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.
Tuberculosis and Mycobacterial Infections: An Educational Update 3
ESCMID Postgraduate Education Course
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
ProfessorCambau 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.
Tuberculosis and Mycobacterial Infections: An Educational Update 4
ESCMID Postgraduate Education Course
Assoc. Prof. Alex COOK
Associate Professor
Biostatistics and Modelling Domain
Vice Dean (Research) & Domain Leader (Biostatistics & Modelling)
Saw Swee Hock School of Public Health
National University of Singapore
Associate Professor
Department of Statistics and Applied Probability
National University of Singapore
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.
Tuberculosis and Mycobacterial Infections: An Educational Update 5
ESCMID Postgraduate Education Course
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
Saw Swee Hock School of Public Health
Yong Loo Lin School of Medicine
National University of Singapore
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
Tuberculosis and Mycobacterial Infections: An Educational Update 6ESCMID Postgraduate Education Course
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.
Tuberculosis and Mycobacterial Infections: An Educational Update 7ESCMID Postgraduate Education Course
Asst. Prof. Catherine ONG
Principal Investigator
Department of Medicine, Yong Loo Lin School of Medicine
Institute for Health Innovation & Technology
National University of Singapore
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
Saw Swee Hock School of Public Health
National University of Singapore
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.
Tuberculosis and Mycobacterial Infections: An Educational Update 8ESCMID Postgraduate Education Course
Prof. Nick PATON
Professor of Infectious Diseases
National University of Singapore
Senior Consultant, Division of Infectious Diseases
University Medicine Cluster
National University Hospital
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.
Tuberculosis and Mycobacterial Infections: An Educational Update 9ESCMID Postgraduate Education Course
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
Lee Kong Chian School of Medicine
Nanyang Technological University
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
Tuberculosis and Mycobacterial Infections: An Educational Update 10ESCMID Postgraduate Education Course
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
National University Hospital
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
Tuberculosis and Mycobacterial Infections: An Educational Update 11ESCMID Postgraduate Education Course
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.
Tuberculosis and Mycobacterial Infections: An Educational Update 12ESCMID Postgraduate Education Course
Assoc. Prof. Tsin Wen YEO
Associate Professor of Infectious Disease
Principal Investigator, Malaria, Tuberculosis and Global Health Laboratory
Lee Kong Chian School of Medicine
Nanyang Technological University
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
Tuberculosis and Mycobacterial Infections: An Educational Update 13OFFICES
FLOOR PLAN
Meeting Room Meeting
Lifts
Medical Student Symposium Room
Stairway
Lounge Room
Meeting Room
Riser
Store
Meeting
Room
CAFE Mechanical Room Lifts
Entrance
Tuberculosis and Mycobacterial Infections: An Educational Update
Store Lobby
Exhibitors
Registration
Auditorium
Poster Area
14
ESCMID Postgraduate Education CourseESCMID Postgraduate Education Course
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 Dr Zubaidah SAID (SG)
Control Efforts Communicable Disease Division,
Ministry of Health
1400 – 1430 The Global and Regional Experiences and the Dr Tauhidul ISLAM (PH)
End of TB Strategy 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 Prof Reinout van CREVEL (NL)
Clinical Perspective 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
Tuberculosis and Mycobacterial Infections: An Educational Update 15ESCMID Postgraduate Education Course
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 Assoc Prof Alex COOK (SG)
Management 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
1500 – 1530 Refreshment Break
Tuberculosis and Mycobacterial Infections: An Educational Update 16ESCMID Postgraduate Education Course
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)
1000 – 1030 Refreshment Break
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 Dr Li-Hwei SNG (SG)
non-tuberculous mycobacterial infections – Central TB Laboratory
Perspectives from the Singapore 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
Tuberculosis and Mycobacterial Infections: An Educational Update 17ESCMID Postgraduate Education Course 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. Tuberculosis and Mycobacterial Infections: An Educational Update 18
ESCMID Postgraduate Education Course 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. Tuberculosis and Mycobacterial Infections: An Educational Update 19
ESCMID Postgraduate Education Course 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. Tuberculosis and Mycobacterial Infections: An Educational Update 20
ESCMID Postgraduate Education Course 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 Tuberculosis and Mycobacterial Infections: An Educational Update 21
ESCMID Postgraduate Education Course 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. Tuberculosis and Mycobacterial Infections: An Educational Update 22
ESCMID Postgraduate Education Course 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, Tuberculosis and Mycobacterial Infections: An Educational Update 23
ESCMID Postgraduate Education Course 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 Tuberculosis and Mycobacterial Infections: An Educational Update 24
ESCMID Postgraduate Education Course 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. Tuberculosis and Mycobacterial Infections: An Educational Update 25
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