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Welcome to Week 1

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Welcome to Week 1. Now that we have introduced the course and you have had a chance to
introduce yourselves, let’s begin learning about antimicrobial resistance, its importance in the
global health agenda and the role of diagnostics in the response to AMR.

We encourage you to share your reflections and experiences with your fellow learners
throughout the course of this first week. We will be joining your discussions throughout the steps
in the Comments area.

The activities are available to view now, but if you decide to view them early you may want to
return to the comments and discussions while the week is live to see the perspectives of other
learners and to offer your own.

At the end of each week, we collate the key thoughts, themes, and any questions from your
conversations in a summary document added to the Downloads section at the bottom of this
page.

Let us get started.

© London School of Hygiene and Tropical Medicine 2019

Welcome to the course


55 comments

Welcome to our course, The Role of Diagnostics in the Response to Antimicrobial Resistance
(AMR). Your Lead Educators are Professor Rosanna Peeling, Director of the International
Diagnostics Centre at the London School of Hygiene & Tropical Medicine, Dr. Noah Fongwen,
clinical research fellow at the London School of Hygiene & Tropical Medicine, and Dr. Robert
Luo, clinician consultant at the International Diagnostics Centre at the London School of
Hygiene & Tropical Medicine. Let’s begin!

This six week course is brought to you by the International Diagnostics Centre at the London
School of Hygiene & Tropical Medicine. The course aims to create awareness of the role of
diagnostics in the response to AMR.

Who is this course for?

This course is intended for health professionals, students and anyone interested in the use of
diagnostics in the prevention and control of antimicrobial resistance.
How is the course structured?

Over the next six weeks we will review the role of diagnostics in the AMR response.

Week 1: Introduction - We will cover the global crisis of AMR and the consequence of inaction

Week 2: Common clinical syndromes - We will show how diagnostics can help reduce
inappropriate use of antibiotics in common clinical syndromes.

Week 3: Healthcare associated infections - We will show you how diagnostics can be used to
detect and track outbreaks of resistant pathogens associated with health care settings.

Week 4: Enteric infections and One Health - We will show the interplay between food borne
or enteric infections and the One Health approach.

Week 5: Mycobacterium tuberculosis and Neisseria gonorrhoeae - We will discuss in detail


two pathogens of public health importance, Mycobacterium tuberculosis and Neisseria
gonorrhoeae, that will rapidly become untreatable if we do not test, treat and track their
resistance trends to optimise control measures.

Week 6: The way forward - We will discuss the way forward as there is something you can do
wherever you are. The future is in our hands!

© London School of Hygiene and Tropical Medicine 2019

Learning with us
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If this is your first course, please review ‘Using FutureLearn’ for an introduction to learning with
FutureLearn.

We’re delighted that you’ve joined the course and wish you a warm welcome to the London
School of Hygiene and Tropical Medicine. The school is renowned for its research, postgraduate
studies and continuing education in public and global health. In addition to our course
participants, we have more than 4,000 students and 1,300 staff working in over 100 countries —
all with a collective purpose to improve health worldwide.

How will we learn?

Throughout our six weeks together we will use articles, mini-lectures, and interviews with
experts in the field to highlight some of the key issues and thinking around the role of
diagnostics in the response to antimicrobial resistance. We will also build on our learning using a
number of case studies, educational videos and animations. We encourage you to assess your
learning through quizzes and share your experiences and views through discussion with fellow
learners and the course team. Some steps include reference lists and supplementary reading that
you may find useful for further study.

There is no single way to approach the course that guarantees success. The way you learn
depends on many factors and will not necessarily be the same as everyone else. However, in
order to maintain enthusiasm and gain confidence about your studies, why not take a more active
role within the course? You could:

 Take notes on course steps. Which aspects of the material are most interesting to you and why?
Is there anything you have struggled to understand? Why might that be?
 Analyse connections between the current step and previous ones to help build a clearer picture
of a topic
 Ask yourself questions about what you’re learning and how it relates to your own experiences
 Discuss your learning with others and consider how you can apply new knowledge, either in
your personal life or a professional situation
 Explain what you have learned to others if they are struggling.

In summary, one great way to figure out how to learn is to think about how you can use your
learning in your personal and professional life to combat the global AMR crisis.

What will you achieve?

By the end of this course, learners should:

 Have a greater awareness of AMR and how it is caused

 Be able to list infections and/or conditions for which AMR is posing the greatest public
health threat, such as respiratory tract infections, urinary tract infections, healthcare
associated infections, sepsis, gonorrhoea, and tuberculosis

 Have a greater awareness of the role of diagnostics in reducing the misuse of antibiotics
for above conditions, in surveillance and in assessing the effectiveness of antibiotic
stewardship strategies

Translations

Please note that there are PDF transcripts available in additional languages at the bottom of each
Step, to support your learning. However, the course and the course discussion will be in English.

Join the discussion

Almost every step has space for conversation and debate: the Comments area. While Discussion
steps feature more focused conversational tasks, anyone can talk about material within each
step’s Comments area. We will regularly prompt you to share your thoughts and ideas with
questions or suggestions at the end of a step. You can contribute to these conversations as and
when you are able to. Please note that you should not share your own personal contact
information, and please remember relevant professional standards of conduct, such as not
revealing information that may identify one of your patients or students. You might like to read
six tips and tools for social learning on FutureLearn to help you get the most out the platform’s
social features.

Re-using course materials

If you’re an educator or work in an aligned field, we encourage you to download, adapt, and re-
use the content from this course for teaching and learning purposes. Materials will be made
available on the School’s Open Study platform.

© London School of Hygiene and Tropical Medicine 2019

Introduce yourself
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Can you tell us one or two key reasons why you have decided to join us? Do you work in health
or research? Do you have a personal reason for wanting to learn more about antimicrobial
resistance and diagnostics?

The School is based in London, but both our teaching and research are internationally-focused
and our students come from all over the world. Our FutureLearners do too! Why not add your
location to the interactive map? To add a marker:

• Click the link here to open the map (you may want to open it in a new tab or new window, by
right clicking on the link).

• Ignore the Demo/Upgrade window that pops up, simply close it.

• Using the search field in the top left of the screen, type your location (please keep this in a
rough approximation area, e.g. city.)

• When prompted, click on Add Marker. A little blue marker becomes visible.

• Select the Edit/Measure tool (arrow icon on the top toolbar) and click on the blue marker. A
pencil icon will show up on the left hand side of the marker.

• Click on this pencil icon and enter your first name under the Title field (please do not
provide other personal information e.g. full name, exact location or profile photo).

• Click Save

• Click on the Menu tab in the top menu and select Save Map. When prompted, enter the
password LSHTM and click Save Map. This will ensure your marker is allocated to the map.
• When prompted, select Continue Working and close the Save map window.

• You can navigate the map by clicking and dragging with your mouse. Use your mouse wheel
to zoom in and out, or the + and - buttons on the top right hand side.

By following the above link you will be taken to a third party website, the use of which has been
arranged by and is the responsibility of London School of Hygiene and Tropical Medicine. On
this website you will be asked to submit some information about yourself. Please make sure you
are familiar with the terms and conditions and privacy policy of the third party website before
submitting your information. London School of Hygiene and Tropical Medicine will only use
your personal information for the purpose stated above and in accordance with the terms of the
third party website. Whether you follow the above link and submit your personal information or
not, your course progress will in no way be affected. Nor will your course marks or FutureLearn
profile. For the purposes of any personal information submitted via the third party website
London School of Hygiene and Tropical Medicine will be the data controller, not FutureLearn.

In addition to the map, you might also like to refer to the Welcome discussion that took place
before the start of the course. Can you see anyone who is from or working in a similar location to
you? Try to reply to at least one comment that interests you, for example when your background
or reason for joining the course is similar to that of another learner.

Discussion tips

If you have already begun to contribute, other learners may have replied to you. You can view
these replies quickly using the ‘Replies’ tab at the top of every page. You can ‘like’ comments if
you agree with what’s been said or if you have found something particularly interesting. You can
also filter the comments by ‘Most liked’, and ‘Follow’ those individuals who are of particular
interest to you. You can follow members of the course team to track their contributions to
discussions by accessing their highlighted profiles below.

Meet the course team

Educators: Rosanna Peeling, Noah Fongwen, Robert Luo

LSHTM academic team: Robert Luo, Helen Kelly, Bernard Nsah, Philomena Raftery,
Priayanka Shrestha, Debi Boeras

BD expert team: Renuka Gadde, Courtney Maus, Nuphar Rozen-Adler, Traci Prouser

LSHTM MOOC team: Josie Gallo, Dominic Forrest

Contributors from London School of Hygiene and Tropical Medicine:


Manuel Dewez
David Mabey
David Moore
Peter Piot
Richard Stabler
Joe Tucker
Shunmay Yeung

Contributors from other organisations:

Adele Benzaken, Ministry of Health, Brazil


Daniel Berman, Longitude Prize, Nesta, UK
Catharina Boehme, Foundation for Innovative New Diagnostics (FIND), Switzerland
Hong Chen, Hong Kong Hospital Authority, Hong Kong
Xiang-Sheng Chen, National Center for STDs, China
Sally Davies, Chief Medical Officer, England
Claudia Denkinger, Foundation for Innovative New Diagnostics (FIND), Switzerland
Jeremy Farrar, Wellcome Trust, UK
Chris Gilpin, World Health Organization, Geneva, Switzerland
Robert Hall, National Institutes of Health, USA
John Nkengasong, Africa Centres for Disease Control and Prevention (Africa CDC), Ethiopia
Madhu Pai, McGill University, Canada
V. Ramasubramanian, Chair of the Antimicrobial Stewardship Program Initiative, Indian
Council of Medical Research (ICMR), India
Vanessa Tran, Canadian Association for Clinical Microbiology and Infectious Diseases
(CACMID), Canada
Dominic Tsang, Hong Kong Hospital Authority, Hong Kong
Kamini Walia, Indian Council of Medical Research (ICMR), India
Andrew Whitelaw, University of Cape Town, South Africa
Teodora Wi, World Health Organization, Geneva, Switzerland
Andrew Wong, Hong Kong Hospital Authority, Hong Kong

MOOC advisory group:

Najiba Abdulrazzaq, National AMR Committee, United Arab Emirates


Regina Berba, Ministry of Health, Philippines
Cecilia Ferreyra, Foundation for Innovative New Diagnostics (FIND), Switzerland
Henry Kajumbula, Makerere University, Uganda
Philip Onyebujoh, Africa Centres for Disease Control and Prevention, Ethiopia
Francis Moussy, World Health Organization (WHO)
Alwarith Nasser, Ministry of Health, Oman
Pham Hong Nhung, Hanoi Medical University/Bach Mai Hospital, Vietnam
Pascale Ondoa, African Society of Laboratory Medicine
Harry Parathon, University of Airlangga/ Dr. Soetomo Hospital, Chair, Antimicrobial Resistance
Control Committee, Ministry of Health, Indonesia
Samuel Ponce de Leon Rosales, National Autonomous University of Mexico, Mexico
V. Ramasubramanian, Chair of the Antimicrobial Stewardship Program Initiative, Indian
Council of Medical Research (ICMR), India
Vanessa Tran, Canadian Association for Clinical Microbiology and Infectious Diseases
(CACMID), Canada
Kamini Walia, India Council of Medical Research (ICMR), India
Xuan-Ding Wang, ZheJiang University College of Medicine, China
Andrew Whitelaw, University of Cape Town, South Africa
Tri Hesty Widyastoeti, Ministry of Health, Indonesia

© London School of Hygiene and Tropical Medicine 2019

Microbes, colonization and infection


17 comments

To understand antimicrobial resistance, we must first introduce the concept of microbes (or
microorganisms) and the relationship between microbes and humans. In particular, we have a lot
of bacteria in or on our bodies that are not harmful and do not require treatment. We call this
colonization.

However, when bacteria gain access to sterile sites in our bodies such as the blood stream and
bones, then we become infected and our bodies can be harmed by these infections. In this case,
we need treatment with antibiotics to kill the bacteria.

© London School of Hygiene and Tropical Medicine 2019

Diagnostics to detect infection


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In this step Dr. Robert Luo defines what are diagnostics and describe different diagnostic
methods that can be used to detect infection and enable the infection to be treated. We also
define performance characteristics for diagnostics in terms of sensitivity, specificity and positive
and negative predictive values.

© London School of Hygiene and Tropical Medicine 2019

Antimicrobial vs Antibiotic Resistance and


mechanism of resistance
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Among priorities for AMR, antibiotic resistance poses the most serious problem in global public
health. This MOOC will focus on bacterial infections for which antibiotic resistance has become
a threat to public health. We start with defining what are antibiotics, show their mode of action
and mechanisms by which bacteria develop antibiotic resistance.

It is important to note that antibiotics are not effective against viruses as viruses do not have the
same structure or mechanism of replication as bacteria

Please watch this cartoon which provides a good re-cap of what you have learnt so far in Step 1.5
to 1.7 on infection, colonization and AMR

How do we detect resistance?


6 comments

Now that you understand what is AMR and how resistance emerges, we will next examine how
we can detect resistance. There are two ways to detect resistance:

1. Identification and isolation of the pathogen


2. There are two ways to detect resistance:

i) we can culture the bacteria in the presence of antibiotics and see which antibiotic inhibit their
growth – This is called antimicrobial susceptibility testing (AST);

ii) we can use molecular methods to determine if the bacteria carry any resistance genes in its
genome. This is called antimicrobial resistance testing (ART).

Each method has its advantages and disadvantages.

© London School of Hygiene and Tropical Medicine 2019

What is the global AMR crisis and what can


be done about it?
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Now that you understand what AMR is, we present a video interview with Professor Dame Sally
Davies, Chief Medical Officer for England and Co-Convener of the UN Interagency Coordinator
Group (IACG) on AMR in which she explains the current global burden of AMR and according
to the 2016 O’Neill Report, if we do not take action now, by 2050, the number of deaths from
AMR will exceed 10 million and push another 28.3 million people into poverty. She also
addresses the complexity of balancing excessive use of antibiotics in some societies with lack of
access to antibiotics in other settings.

Also in the video, Dr. Jeremy Farrar, Director of the Wellcome Trust which provides
funding for many AMR initiatives, warns of the AMR crisis, how it threatens not only our
ability to treat infectious diseases but all of the practice of modern medicine. He speaks
about the importance of using diagnostics to tell clinicians what the infection is and what
antibiotics to use. He stressed the importance of driving the adoption of existing diagnostics
and investing in the development of more effective diagnostics and drugs to combat AMR.

UN Global Action Plan for AMR

Now that you understand the urgency of combating AMR, let us examine five priority actions
recommended by the World Health Organization (WHO) and endorsed by the FAO and other
UN agencies. Diagnostics underpin all five priority actions.

In 2015, Member States of the World Health Organization (WHO), Food and Agriculture
Organization (FAO) and World Organisation for Animal Health (OIE) endorsed a Global Action
Plan on AMR, which includes five strategic objectives that, taken together, offer a framework for
national action.

At the 2016 UN General Assembly High-Level Meeting on Antimicrobial Resistance, countries


reaffirmed their commitment to develop national action plans to combat drug resistance, and
pledged to:

 To improve awareness and understanding of antimicrobial resistance


 To strengthen knowledge through surveillance and research
 To reduce the incidence of infection
 To optimize the use of antimicrobial agents
 Develop the economic case for sustainable investment that takes account of the needs of
all countries, and increase investment in new medicines, diagnostic tools, vaccines and
other interventions.

Source: https://www.who.int/antimicrobial-resistance/global-action-plan/en/

Diagnostics are critical for all five pillars of the WHO AMR Strategy.

Surveillance of antimicrobial resistance (AMR) tracks changes in microbial populations, permits


the early detection of resistant strains of public health importance, and supports the prompt
notification and investigation of outbreaks.

Diagnostics can be used:

 To guide patient management and reduce inappropriate use of antimicrobials


 To screen for antimicrobial resistance to enable infection prevention and control (IPC) in
health care settings
 To conduct AMR surveillance and assess the impact of interventions such as IPC

In the next three steps, we will examine the role that diagnostics can play in the AMR response.

© London School of Hygiene and Tropical Medicine 2019

Diagnostics in the AMR response: patient


management
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In this video Dr Ramasubramanian, Chair, Antimicrobial Stewardship Program Initiative, Indian


Council of Medical Research, warns us of the inappropriate use and overuse of antibiotics and
the need for diagnostics.

In the next step, we will show you the challenges clinicians face in the management of infectious
diseases and the decisions they have to make on whether to prescribe antibiotics or not. We will
use fever, one of the most common reasons why people seek care, as an example.

© London School of Hygiene and Tropical Medicine 2019

Role of diagnostics in the AMR response -


Fever as an example
3 comments

We start with how diagnostics can be used to reduce the overuse of antibiotics in the
management of common clinical syndromes. Fever is one of the most frequent reasons why
people seek medical care.

Prof. David Mabey explains what is the syndromic approach to patient management and its
relevance to AMR. This will be followed by interviews with Drs. Manuel Dewez and Shunmay
Yeung who will speak about the management of fever in children and how with proper
diagnostics, we can improve clinical care for the patients and reduce the risk of AMR.

David Mabey is a Professor of Communicable Diseases at the London School of Hygiene &
Tropical Medicine (LSHTM). He worked with Rosanna Peeling to establish the International
Diagnostics Centre at the School in 2012. He is currently the Principal Investigator on the Febrile
Illness Evaluation in a Broad Range of Endemicities (FIEBRE) study at LSHTM.
Manuel Dewez is a paediatrician from Bolivia and Belgium and worked with Médecins Sans
Frontières (MSF) before joining LSHTM. Manuel works with Shunmay Yeung in an EU funded
research consortium, PERFORM (www.perform2020.eu). The aim of PERFORM is to develop
new diagnostic tests to improve the management of children with fever.

Shunmay Yeung is a paediatrician specialising in infectious disease and global health with a
background in health economics and operational research. She is the Principal Investigator for
the PERFORM study and the lead paediatrician for the FIEBRE consortium.

© London School of Hygiene and Tropical Medicine 2019

Role of diagnostics in the AMR response -


Fever as an example
3 comments

We start with how diagnostics can be used to reduce the overuse of antibiotics in the
management of common clinical syndromes. Fever is one of the most frequent reasons why
people seek medical care.

Prof. David Mabey explains what is the syndromic approach to patient management and its
relevance to AMR. This will be followed by interviews with Drs. Manuel Dewez and Shunmay
Yeung who will speak about the management of fever in children and how with proper
diagnostics, we can improve clinical care for the patients and reduce the risk of AMR.

David Mabey is a Professor of Communicable Diseases at the London School of Hygiene &
Tropical Medicine (LSHTM). He worked with Rosanna Peeling to establish the International
Diagnostics Centre at the School in 2012. He is currently the Principal Investigator on the Febrile
Illness Evaluation in a Broad Range of Endemicities (FIEBRE) study at LSHTM.

Manuel Dewez is a paediatrician from Bolivia and Belgium and worked with Médecins Sans
Frontières (MSF) before joining LSHTM. Manuel works with Shunmay Yeung in an EU funded
research consortium, PERFORM (www.perform2020.eu). The aim of PERFORM is to develop
new diagnostic tests to improve the management of children with fever.

Shunmay Yeung is a paediatrician specialising in infectious disease and global health with a
background in health economics and operational research. She is the Principal Investigator for
the PERFORM study and the lead paediatrician for the FIEBRE consortium.

© London School of Hygiene and Tropical Medicine 2019


Role of diagnostics in the AMR response -
Screening
6 comments

Diagnostics play a very important role in identifying asymptomatic individuals who are carriers
of resistant bacteria in health care settings. Screening for resistant bacteria enables infection
prevention and control (IPC) measures to be carried out, which is critical in preventing the
spread of resistance within health care settings.

Professor Andrew Whitelaw of Stellenbosch University speaks on the use of diagnostics to


screen patients in health care facilities for resistant infections so that they can be isolated and
precautions taken to prevent transmission in health care settings.

© London School of Hygiene and Tropical Medicine 2019

Role of diagnostics in the AMR response -


Surveillance
1 comment

Dr. Kamini Walia, Senior Scientist and Program Officer, Antimicrobial Resistance Initiative at
the Indian Council of Medical Research (ICMR) speaks about the role of diagnostics in AMR
surveillance, especially in low and middle income countries (LMICs) from which data on
antimicrobial resistance to guide treatment and monitor trends are sparse. Each of these uses of
diagnostics will be discussed in more detail in the coming weeks.

© London School of Hygiene and Tropical Medicine 2019


Question 1
All microbes found in or on the body cause infections and should be treated with antimicrobials.
True
False
Correct
Only <1% of microbes causes disease. People can be colonized with bacteria without causing
any symptoms or disease. These do not need to be treated with antibiotics

Question 2
Antibiotics are natural or synthetic compounds that inhibit the growth of or kill bacteria.
Resistance to antibiotics can emerge from:
Mutations in the antibiotic that prevent it from getting into human cells
Mutations in the human body that prevents the antibiotic from working properly
Mutations in bacterial cell wall that prevent the antibiotic from binding or going into the cell
Mutations in the antibiotic that prevent it from binding to the bacteria
Correct

Question 3
Diagnostic tests can be used in the response to AMR to:
Identify the organism causing infection and/or disease to help pick the right bug-drug combination
Screen for resistance to enable effective infection control measures to prevent the spread of
resistance
Provide information for the surveillance of AMR
All of the above
Correct

Question 4
Febrile illness (‘fever’) is one of the major reasons healthcare workers prescribe antibiotics.
Which of the following contributes to the excessive prescription of antibiotics for febrile illness
(‘fever’)?
Symptoms are not specific
Some of the diagnostic tests are very slow (have a long turn around time)
There are many causes of fever and it would be very costly to test for all of them
Some of the diagnostic tests (e.g. blood cultures) are not readily available
All of the above
Correct
Question 5
Which of the following is not a type of diagnostic test used in the detection of microbial
pathogens?
Culture
Blood pressure monitoring
Molecular assays
Antigen detection assays
Correct

Question 6
The sensitivity of a diagnostic test is the percentage of true negatives and the specificity is the
percentage of true positives.
True
False
Correct
Sensitivity is the percentage of truly infected people who test positive and specificity is the
percentage of truly uninfected people who test negative.

Question 7
Which of the following is not a target of antibiotics?
Bacterial cell wall
Bacterial proteins involved in DNA synthesis
Bacterial protein synthesis
Human protein synthesis
Correct

Question 8
Diagnostic tests can help guide the treatment of infection by:
Identifying what microbe is causing the infection
Testing what antimicrobials the microbe is susceptible to
Determining whether the microbe has any antimicrobial resistance genes
All of the above
Correct
Question 9
Antimicrobial resistance is only a problem in lower and middle income countries.
True
False
Correct
AMR is a global problem and everyone has a role in preventing the rise and spread of AMR

Question 10
Which of the following contributes to the rise and spread of antimicrobial resistance?
Misuse of antibiotics
Overuse of antibiotics
Lack of awareness
Lack of effective diagnostic tools and surveillance systems
All of the above
Correct

Summary of Week 1
18 comments

In this section, Professor Peeling summarises Week 1, where she highlights the key takeaway
points that we have covered. Additionally, she introduces the topics for Week 2 and encourages
you to continue discussions about Week 1.

We hope you have enjoyed the first week and we look forward to starting Week 2 with you.

© London School of Hygiene and Tropical Medicine 2019

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