Leicester Medical School

MBChB Phase 1: Infection Unit Workbook (Student Version)

Undergraduate Course Workbook 2022
For use in Semester 2 of MBChB and BSc Clinical Sciences

This workbook has been designed for use on an iPad, although as a PDF it can be viewed and printed as normal from any computer.
You can use any PDF reader app on the iPad to view the workbook: and some apps will also let you add notes and your own bookmarks,
and complete the workbook entries by writing or typing in the gaps.
To increase text size, or study illustrations in more detail, use the usual ‘pinch’ gestures to zoom in or out on the page.
This workbook and its contents are for use in teaching at Leicester Medical School (University of Leicester) and are not to be shared
outside of the University except with prior agreement.
PLEASE NOTE TIMINGS & ONLINE/F2F OPTIONS ARE CORRECT AT THE TIME OF PUBLISHING BUT MAY BE SUJECT TO CHANGE
 Leicester Medical School

Important Information for 2021/2022

Please be aware that this year there is a mix of F2F and online teaching in order to deliver the full content of this module. Please be assured that you will still be
taught the same content as in previous years.

a) The pre-recorded lecture times are included in the timetable in order for you to use those times to access them through blackboard – this is merely a suggestion
to help you. These are not live and are freely accessible for the duration of your course. MOST LECTURES WILL BE LIVE AND WILL BE SHOWN AS SIMULCASTS –
PLEASE CHECK BLACKBOARD FOR UPDATES. PLEASE NOTE THE MANDATORY LECTURES.

b) Be aware that there is preparatory work for each session (see workbook session for details) usally consisting of revision of the previous week’s lectures, YouTube
videos or websites to look up. Do also prepare for your lectures by looking through the slides ahead of these live events.

c) The group work sessions will be F2F as last semester EXCEPT FOR THE WEEK COMMENCING 21 FEBRUARY WHEN BOTH THE Q&A SESSION AND GROUP WORK
WILL BE ONLINE – please see your individualised timetables for times and information.

d) There will be one short Introduction to the Module Q&A Session on the first day – this will be part of the mandatory Introduction to the Unit lecture and is the
time to ask any questions about the unit – how it works, staffing, F2F etc.

e) There will be a further three live Q&A sessions as indicated in your timetable. These will be online but will be live and will be a time for the lecturers on the
module to answer pre-submitted questions in front of everyone – there will be a bacteriology, virology and immunology session on different days.

f) Please refer to blackboard infection site regularly as this will be used to give you the must up to date information – this is available under the Welcome to the
Unit banner and will be signed and dated by myself.

g) Please refer to the Notes and Self Study at the end of each sesssion for any further work associated with the group work that should help guide your own study
and revision.

Important Notice: When attending face-to-face teaching on campus and elsewhere, it is important that you follow existing COVID-19
regulations and advice especially wearing face masks at all times while in the medical school and wider university. Please also promptly
follow instructions from all members of staff when given, in order to protect yourselves, our staff and the wider community.

Return to Unit Overview

p1
 Leicester Medical School

Infection Unit Overview

Session Themes Times & Information relating to Sessions

Session 1: Wed 12 Jan 10:00 – 10:50 11:00-11:50 12:30-13:30 Notes & Self-study
2022 SIMULCAST SIMULCAST F2F LIVE
An introduction to infection and Lecture 1 Lecture/Q&A Lecture 2 Small Group Work 1 Notes:
microbes What is an Infection Welcome to Introduction What is an Infection? agar plates
Dr Jenkins Infection to Microbes Hot topics in infection bacterial cell wall
(This needs to be Dr Mitcheson Dr Jenkins Gram stain
viewed before group
work 1)

Session 2: Wed 19 Jan 09:00 – 10:30 11:00-11:50 12:00-12:50 Notes & Self-study
F2F LIVE SIMULCAST SIMULCAST
2022
Group work - Skin flora & Small Group Work 2 Lecture 3 Lecture 4 Notes:
infections linked to microbiota Follow-up on gram stain An Infection Model Innate Immunity Cellulitis
Lectures – Infection Model & Skin flora and microbiota Dr Jenkins Dr Amrani Candida
Innate Immunity Case studies Full Blood Count
Make Infection Model Charts

Session 3: Wed 26 Jan 09:00 – 10:30 11:00-11:50 12:00-12:50 Notes & Self-study
F2F LIVE SIMULCAST SIMULCAST
2022
Group work - applying the Small Group Work 3 Lecture 5 Lecture 6 Notes:
infection model & innate Case studies Acute Sepsis in the Adaptive Immunity Pneumonia
immunity Innate immune response – CRP, Emergency Department Part 1 Adenovirus
Neutrophils Dr Lim Dr Amrani Do some reading about
Lectures - Sepsis & Adaptive Streptococcus Pneumoniae
Immunity (Part 1)

Return to Unit Overview

p2
 Leicester Medical School

Session 4: Wed 02 Feb 09:00 – 10:30 11:00-11:50 12:00-12:50 Notes & Self-study
F2F LIVE SIMULCAST SIMULCAST
2022
Group work – sepsis Small Group Work 4 Lecture 7 Lecture 8 Notes:
Sepsis & Assessment of Infection Blood Borne Viruses Antibiotics and meningitis
Lectures - HIV/Antibiotics Case studies HIV Resistance sepsis
Dr Sahota Dr Lim Additional notes:
sepsis screening
NEWS

Session 5: Wed 09 Feb 09:00 – 10:30 11:00-11:50 12:00-12:50 Notes & Self-study
F2F LIVE F2F Live/Simulcast F2F Live/Simulcast
2022
Group work - HIV/AIDS case Small Group Work 5 Lecture 9 Lecture 10 Notes:
studies HIV/AIDS Case studies; Blood Borne Viruses Antimicrobial HIV
Lectures - Blood Borne including some ethical aspects Hepatitis Stewardship Needle Stick Injury
Dr Sahota Dr Jenkins
Viruses (hepatitis) &
Antimicrobial Stewardship

Session 6: Wed 16 Feb 09:00 – 10:30 11:00-11:50 12:00-12:50 Notes & Self-study
F2F LIVE F2F Live/Simulcast F2F Live/Simulcast
2022
Group work - Principles of Small Group Work 6 Lecture 11 Lecture 12 Notes:
diagnosis and management Case studies to demonstrate Infections at a Adaptive Immunity biofilms
Lectures - Infections at a the use of UHL Antimicrobial Surface Part 2 Staph epidermidis
Website/Rx Guidelines app Dr Jenkins Dr Amrani endocarditis
surface & Adaptive Immunity
Make notes on the three case
(Part 2)
studies with special reference
to the antimicrobials.

Return to Unit Overview

p3
 Leicester Medical School

Session 7: Wed 23 Feb 09:00 – 10:30 11:00-11:50 12:00-12:30 12.:30 – 13:20 Notes & Self-study
Online LIVE Online Online LIVE Online
2022
Group work – immunity & Small Group Work 7 Lecture 13 Q&A Session Lecture 14 Notes:
infections at a surface case Questions on Hospital Acquired Bacteriology Infection Clostridioides
studies Immunity Infections Dr Mitcheson Prevention difficile
Case studies linked to Dr Jenkins Dr Jenkins Dr Jenkins MRSA
infections at a surface (This needs to be Dr Lim (This needs to be norovirus
Lectures - hospital acquired viewed before group viewed before
infections & Infection work 8) group work 8)
prevention

Session 8: Wed 02 Mar 09:00 – 10:30 11:00-11:50 12:00 – 12:30 12:30-13:20 Notes & Self-study
F2F LIVE Online Online LIVE Online
2022
Group work - hospital Small Group Work 8 Lecture 15 Q&A Session Lecture 16 Make your own summary
acquired infection case Case studies linked to Travel-related Virology COVID-19 notes/infection model for
studies hospital acquired Infections Dr Mitcheson Dr Mitcheson each infection in the case
infections Dr Sahota Dr Sahota Dr Toh studies.
(This needs to be (This needs to
Lectures - travel-related viewed before group be viewed
infections & COVID-19 work 9) before group
work 9)

Session 9: Wed 09 Mar 09:00 – 10:30 11:00-11:50 12:00-12:50 Notes & Self-study
F2F LIVE F2F Live/Simulcast Online (Required)
2022
Group work - travel-related Small Group Work 9 Lecture 17 Mini- Lecture Complete notes on Malaria
infections case studies Travel related Infections Immunocompromised Vaccinations
Returning from Sierra Leone Host Dr Amrani Additional notes & questions:
Returning from Malawi Dr Amrani (This needs to be viewed Legionnaires’ Disease
Lectures – vaccinations & the before group work 10)
Returning from Saudi Arabia
immunocompromised host

Return to Unit Overview

p4
 Leicester Medical School

Session 10: Wed 16 Mar 09:00 – 10:30 11:00-11:50 12:00 – 12:30 12:30 – 13:20 Notes & Self-study
F2F LIVE Online Online LIVE Online
2022
Group work - The Small Group Work 10 Lecture 18 Q&A Session Lecture 19 Notes:
immunocompromised host Case studies related to E. coli Immunology Influenza Herpes Zoster
case studies an immunocompromised Dr Jenkins Dr Mitcheson Dr Mitcheson Staphylococcus aureus
individual (This needs to be Dr Amrani (This needs to Immunocompromised host
viewed before be viewed Febrile neutropenia
Lectures - E. Coli & Influenza group work 11) before group
Influenza on varicella zoster
work 11)

Session 11: Wed 30 Mar 09:00 - 09:50 10:00-11:40 12:00-12:50 Notes & Self-study
F2F Live/Simulcast F2F LIVE F2F Live Mandatory
2022
Group work – pharyngitis & Small Group Work 11 Lecture Study notes on Streptococci
Lecture 20 Complete study notes on EBV
viral case studies Various case studies Unit Summary &
Streptococcus
Review
Dr Jenkins
Dr Mitcheson
Lectures – Streptococcus & (This needs to be viewed before group
unit summary/review work 11)

Appendix 1 Themes, Infections & Microbes

Appendix 2 Antimicrobials

Appendix 3 Host Immune Response In Relation To

Infection

Return to Unit Overview

p5
 Leicester Medical School

Introduction to the Infection Unit It will only be at the end of the Unit that you will be able to appreciate the
microbiology and immunology that was covered.

Aim Indeed, it is likely that in the early sessions you will be acutely aware of the gaps in
your knowledge. This is deliberate. The challenge for you, the learner, is to
The term “Infection” covers a large topic that is of central importance to the practice understand this balance and to begin a process of seeking out information. The more
of medicine in all specialties. It crosses many boundaries, both in terms of you are willing to do this the greater will be the control you have over your own
understanding the relevant basic science and in the clinical application of this learning and the more likely it will be that the information will be something that you
knowledge. It is not possible to cover all of this material in a single unit; and there is are able to retain and take with you into the clinical years.
no intention of doing so.
The Infection Unit is not complex. Any individual part is relatively straightforward.
As a consequence of the above paragraph the aim of this unit is to provide a structure However:
for a student to consider a patient who presents with a possible infection. Material
There are lots (and lots) of microbes. Some have long names.
will be presented in a clinical context and will seek to identify patterns of disease and
presentation. We have chosen a limited number of clinical problems and for each of There are many antimicrobial agents (also with potentially long names)
these identified selected micro-organisms. Each is chosen to highlight principles of
There are many infections; and not always a direct relationship between
microbial physiology with links to a common ‘infection model’.
one infection and one microbe.
The ‘infection model’ will be used in different contexts so that your knowledge of
Many patients have to be treated without knowing exactly which microbe
how to apply this model will grow as the semester progresses.
is causing the problem
Understanding the patient-pathogen interaction is an important first step in the The design for each session: – each week there will be two lectures (or several small
infection model. This will also allow for a progressive accumulation of knowledge of
lecture chunks) and group work. Each session will also include self-study and notes
how the body responds to infection and the role of the immune system.
to help. Some weeks these notes will be written for you – other weeks you will need
Learning During the Infection Unit to make your own additional notes. The Intended Learning Outcomes (ILOs) will be
in the workbook at the beginning of the session – these will apply to the whole
‘Infection’ is potentially complex, with a risk that the amount of information hinders
session including the lectures as some lecturers may not include these in the
an understanding of some simple core principles.
lecture. Use these to help you prepare and to study the topics. There will be
We will start the Unit by outlining a clinical approach to a patient who may have an
signposts to other units indicated by .
infection. We will provide you with an ‘infection model’ to contextualize an infection
The causative agents you need to know may sometimes be highlighted - you should
in an individual which you will need to build for yourselves. As the weeks proceed
we will add to this model and cover relevant microbiology and immunology. BUT on gather these names into your own document for revision and add in pictures of your
every occasion this will be done within the context of the infection model. own. There is an additional THEMES, INFECTIONS AND MICROBES document in the
appendix – feel free to alter this document and add any additional information that

Return to Unit Overview

p6
 Leicester Medical School

might help. Please be aware that although it may seem that you might never Useful icons:
remember the names of bugs, YOU WILL and you will get to know how to treat these
in patients. Be patient, constantly revisit, revise and learn from the lectures, group
Where you see this icon, it links to helpful web-based resources or
work questions and self-study materials. Use the techniques of the Learning
textbooks to help you read more around the subject to help you answer
Scientists - try spaced revision and retrieval practice that you have learnt from your
the question.
induction week – “Getting the most from lectures and self-directed study”

The most common question we receive as unit leads is – “Do I need to know this?”
The purpose of this icon is to link content or questions to other
or “What do I need to know?” We would advise you to use the intended learning Link to… lectures in the infection unit (blue colour) or even to other units
outcomes as your guide to revising this module.
in the curriculum in either year 1 or 2 (orange colour). This is
designed to help you integrate material as you go through this
Good luck and enjoy the Unit!
unit, making references to themes or content you have either
already covered, or will cover in more depth during other units this semester or even
next year.
Using this Workbook

This picture will indicate the name of a microbe that you should make an
Each week you will find:
infection model for and commit to your memory. On occasion there may be
A timetable for the session a link to more information.

Specific learning outcomes for that session

Preparatory work: this may include questions or links to useful chapters in NOTE: Please be aware that the lecture summaries included in the workbook are
NOT INTENDED to replace your own notes or are in any way indicative of all the
relevant text books for you to read beforehand
important details you need to know. They are intended as a brief overview to
Group work questions supplement your own learning.
Lecture summaries
How to maximise your experience of the infection unit:
Self-study/notes

Return to Unit Overview

p7
 Leicester Medical School

You were introduced to some techniques to help with effective study and learning
during your time at med school. In particular Getting the Most from Studying 2. Group work
Medicine in Phase 1 Drs Lisa Quinn & Dr Hannah Bonfield - available on blackboard. Start by trying to recall key information from the lecture/s. We will put some
tasks in the workbook to encourage this approach. Go through the questions
Or if link is not working this is available in and tasks. Work out what you know before looking up answers. Look up the
Getting the Most from Studying in Phase 1 recommended pages in the textbooks - most of the links will be provided.
under under Key Resources in the Induction Look at the additional recommended resources.
Section of Semester 1. NOTE: The Infection group work will contain new microbes and infections
not covered in the lectures. The group work tasks are absolutely essential
to your learning and the exams.
You will be required to look up information and make notes for yourself. We
will be including clinical cases to provide a different angle to learning
infection. Work with your group to help each other understand the material.

3. Study Notes – some will be provided in the workbook but others you will
need to create yourself. To do this follow this guide:
Have available: Lecture and lecture notes, group work notes, notes provided
in the workbook, text book pages, intended learning outcomes for the
session.
Make a condensed version. Do this in your own words and style. This is likely
to be a mix of phrases, short paragraphs, tables, charts and diagrams.
Aim for 2 to 3 pages per session. You may need 4 pages depending on
1. Prepare for the session/lecture diagrams and layout. This should take about one and a half hours.
You MUST do the recommended preparatory work. It is intended to be
interesting and set the scene. Do look at your lecture slides BEFORE the When coming back to revising a particular session, avoid listening to the
lecture session and try to work out what it is all about. This will help during whole Panopto lecture to make notes – do this as a RECALL exercise. Only
the lecture as you will be able to listen out specifically for the points/slides go to Panopto if there is an explanation linked to one or two slides that you
you did not understand and you may even have a question about it at the want to hear again. There is no value in making a transcription of everything
end of the lecture to submit as a question for the live Q&A sessions or post that was said in the lecture. We will help with this process by indicating the
on the discussion board or direct to the person giving the lecture.

Return to Unit Overview

p8
 Leicester Medical School

main areas on which you need to make study notes. The learning outcomes Remember that in its most simplistic form, infection is about deciding what is the
will also guide you. likely explanation of cause when a patient presents with a fever – is it a virus,
bacteria, parasite, fungus or other? You do not need to know every single causative
4. Notes & Self-study agent rather a few selected ones which we will attempt to highlight through the
Ensure you do the self-study and read through the notes at the end of each course. BUT a patient could present with anything so consider knowing more than
session – there may be specific questions/tasks you will need to do before those we draw your attention to.
the next session and they may not be obvious at first glance. Please be aware
that these tasks are intended to help you in self-directing your study.
Assessments and Assessment Methods
5. Do the Infection Quiz for that session.
The quiz will be on Exam soft / Examplify. Upload your completed quiz. If Formative:
you upload the quiz you will then have a permanent record of the questions. There will be a number of mini-assessments in the form of the infection weekly
You can also keep track of how you are progressing. It is designed to be part quizzes throughout the Unit using Examsoft. This will enable you to monitor your
of your learning at the time the session runs. progress.
6. Infection Model Charts
Make an infection model diagram for each microbe/infection you come
Summative:
This unit will be examined in all summative assessments in Phase 1 including the IUA
across including viruses, bacteria, fungi and parasites – these need not be
and IUPA and the topic of infection will be included in assessments in the clinical
detailed initially – you add to them each time you revisit the topics. The
years in both the written papers and the OSCE examinations.
infection model builds the story of an infection and sets everything in context
making it much easier to retain the knowledge and help your deeper learning
and understanding of the unit.

Return to Unit Overview

p9
 Leicester Medical School

Reading (click on textbook for direct link) Other textbooks that can be used include:
The recommended textbook is: - Infectious Disease; Pathogenesis, Prevention and Case Studies – N. Shetty,
J.W. Tang, J. Andrews. Wiley-Blackwell. A combined clinical and
Lippincott’s Illustrated Reviews: Microbiology. (Fourth Edition 2020), Cynthia Nau microbiological approach to infections
Cornelissen author. Bruce D. Fisher M.D. author. c2020 - Medical microbiology and infection at a glance – Stephen Gillespie and
Kathleen Bamford (for a quick overview of the subject)
- The viral storm – Nathan Wolfe (for entertainment as well as education)
This is an excellent textbook and will be of value throughout your - Principles and practice of infectious diseases – Gerald Mandell, John
course. Each chapter is relatively short with a clear layout and useful Bennett, Raphael Dolin (just to glance at to get an idea of the range of
pictures and diagrams. We especially like the first five chapters, which infectious diseases and the approach to understanding and managing them)
covers all you need to know about microbial physiology and the
The recommended Immunology text is:
principles of diagnosis of an infection. There are sections at the back
Immunology for Medical Students by M. Helbert
of the book (chapters 32 – 34) that cover a systems-based approach to infection: e.g.
Urinary Tract Infection, etc. These are useful for overviews and summaries of
diseases and clinically important microorganisms – definitely worth a look alongside This e-book has to be navigated as a single book and so is less helpful
some additional case studies if you want more practice of questions. There are (from that perspective) than the Lippincott series.
separate chapters for individual microorganisms and you can look at these
selectively. You can access the electronic version directly.
Online Resources: While there are plenty of online sites my favourite two are the 1)
Microbiology Society.org which has plenty of links to all things microbiological - in
Another digital book is Schaechter's Mechanisms of Microbial Disease
particular this link gets you to information about microbes but feel free to explore
This book takes a slightly different approach to looking at infection the site. There are lots of great pictures and information on the site.
and includes some interesting chapters on zoonoses (relevant
particularly to the COVID pandemic) and prion disease. My
suggestion would be to use this to supplement the knowledge in
Microbiology (above) and for additional information. There are also
some useful immunity chapters.

Return to Unit Overview

p10
 Leicester Medical School

Another great site where you can find lots of information for immunology stuff is Staff
the British Society for Immunology – if you scroll down to “For students” there is a Dr Debbie Mitcheson, Infection Unit Lead/Lead Teaching Fellow
section entitled BiteSized Immunology which is useful for the basics.
Dr David Jenkins, Consultant Medical Microbiologist
Dr Yassine Amrani (Phase 1 Lead for Immunology)
Dr Amandip Sahota, Consultant in Infectious Disease
Dr Benedict Rogers, SpR Infectious Diseases & Medical Microbiology
Dr Felicia Lim, Consultant Medical Microbiologist
Dr Tieng Toh, Clinical Teaching Fellow Lead for Infection
Dr Kim Hayer, CQMU Infection Lead
Dr Melissa Haines,
Further sites/articles which may be useful will be added to the sessions
on the blackboard site. Please do keep an eye on the site regularly. Tutors & CTFs:
Additional resources may also be referred to in the relevant sessions Dr David Jenkins
in this workbook. Dr Felicia Lim
Dr Yassine Amrani
Dr Benedict Rogers
Dr Maciej Krawczyk
Dr Kim Hayer
Dr Melissa Haines
Dr Sameer Mahmood
Dr Julia Roope
Dr Lucy Bleazard
Dr Neil Thakrar
Dr Miles Whitfleld
Dr Sara Assadi
Dr Esther Netto
Dr Alice Delmonte

Student Representative:
Muhammad Taimoor

Return to Unit Overview

p11
 Leicester Medical School

Learning Outcomes
Session 1: Introduction to Microbes & Infection
Understand and describe the principles of “an infection” and how an
12 January 2022 individual develops an infection
Preparatory Work View lecture 1 Describe how micro-organisms cause disease and some disease
(08:30 – 09:30) Lecture 1 What is an Infection? determinants

(This needs to be viewed Describe how to identify that a patient has an infection, including history,
before group work 1) examination and investigations

10:00 – 10:50 Lecture/Q&A Session Welcome to the Infection Describe the ‘microbial world’, the key features of bacteria, viruses and
Unit fungi and broadly how they are classified.
LIVE F2F Mandatory
Describe the structure of bacteria and the difference between gram-
11:00 – 11:50 Lecture 2 Introduction to microbes positive and gram-negative bacteria.
LIVE F2F Mandatory Describe the principles of the Gram stain and consequently the staining
12:30 – 13:30 Small Group Work 1 Introduction to Infection characteristics of a gram-positive and gram-negative bacteria.
(LIVE F2F)
NOTES and Self-study Agar plates Session 1: Preparatory Work
Bacterial cell structure and 1) Preparation for group work: Read through the slides for the first lecture
The Gram stain What is an infection? and watch it online – the group work will draw on both
the ideas in this lecture and any prior knowledge you might have.

This first week of the Infection Unit serves to do the following: 2) View, recall and review: View the lecture on the What is an Infection?
Introduce the organisation of the Unit (Lecture 1) Recall and review the information from the lectures before you
start the group work. You could do this on your own before the session or
Introduce the learning principles required to work effectively with your group at the beginning of the session or a combination of both.
Introduce the concept of a “patient with an infection”
3) Preparation for lecture Introduction to Microbes: Read through the lecture
Revise the key features of microorganisms
slides/summary and add any additional notes before and after you view the
lecture.

Return to Unit Overview

p12
 Leicester Medical School

Lecture 1 Summary: What is an Infection? (iii) super antigens - microbial proteins that bind both class II MHC
Learning Outcomes: molecules and T-cell receptors (causing activation of the T cell)
(iv) enzymes – destroy tissue into which bacteria is trying to invade
Understand and describe the principles of “an infection” and how an
individual develops an infection b) endotoxins - cell wall components in particular lipopolysaccharide-protein
complexes – all of which cause host cell damage either directly or as a result of the
Describe how micro-organisms cause disease and some disease
immune response to the virulence factor which causes the damage e.g. cytokine
determinants
storms/SEPSIS.
Describe how to identify that a patient has an infection , including history,
examination and investigations
This lecture looks at what an infection is and the routes via which people get There are several factors which determine if a pathogen causes a disease in any one
infections – these can be via air, water, food, surfaces, animals, physical contact. In individual as follows: a) The pathogen’s virulence factors, b) inoculum size or c)
some cases there may even be a vector involved e.g. the mosquito carrying the antimicrobial resistance while the site of infection in the patient
Plasmodium falciparum parasite which causes malaria. The method and the presence/absence of co-morbidities all determine the
of transmission depends on the microorganism. There may be extent and seriousness of an infection. How do we know if a patient has an infection?
horizontal transmission (transmission by direct contact between infected and We base that on the symptoms, the history which involves asking the patient specific
susceptible individuals or between disease vectors and susceptible individuals) or questions, examination of the patient and both specific investigations ((i)
vertical transmission (generational transmission of viruses from parents to their bacteriology (specimens, M,C & S, antigen or nucleic acid
offspring), e.g., HIV-1 can be acquired in utero (via breaks in the detection), (ii) virology (antigen, antibody or viral nucleic acid
placental barrier or transcytosis of cell-associated virus), during detection) ) and supportive investigations (FBC, CRP, liver & kidney function tests,
delivery (intrapartum), or via breastfeeding. imaging (X-ray, ultrasound, MRI) & histopathology). All those involved in health care
The microorganism moves into the host and causes symptoms following a series of must be aware of the possibility of infections in patients whether it is the primary
steps – exposure, adherence, invasion, multiplication, dissemination. There are cause of their symptoms or as a consequence of another condition.
various methods (or virulence factors) it can employ, which depend on the individual A further note on toxins:
microbe, to cause the disease symptoms and these include the following –
Exotoxins are usually heat labile proteins secreted by certain species of bacteria
a) Exotoxins (i) cytolytic - membrane damaging (usually gram positive) which diffuse into the surrounding medium. They are usually
(ii) AB toxins - two part toxins where B binds to the cell and delivers highly toxic and highly antigenic – they are often enzymes and usually have specific
A to the cytosol which is often an enzyme that interferes with cell function receptors to which they can bind. Example – toxins produced by Staphylococcus
aureus.

Return to Unit Overview

p13
 Leicester Medical School

Note: Toxin production for individual organisms is covered under the Small Group Work 1: An Introduction to Infection
chapter dedicated to the particular organism in the book. Also, you
may be able to understand & apply the above characteristics of endo-/exo-toxins to 1.1 How do we know that a patient has an infection?
the properties of enzymes learnt in MCBG.
Endotoxins are heat stable lipopolysaccharide-protein complexes which form
structural components of cell wall of Gram Negative Bacteria and liberated only on
cell lysis or death of bacteria. They are usually only mildly toxic and antigenic and do
not bind to specific receptors. Example – toxins produced by Escherichia coli.
Note: LPS consists of polysaccharide, composed of repeating sugar
subunits (O antigen), which protrude from the exterior cell surface,
a core polysaccharide, and a lipid component called lipid A that is responsible for the
toxicity of this molecule. You may be able to link this to the structure of
polysaccharide in ICPP.

Click on the textbook to go straight to Chapter 3. Here, you will

learn more and expand on what we have covered in lecture 1
and use it to help you answer some of the self-study questions.

Within your group, identify 3 common types of infection. You could include an
infection you have experienced. What has the group experienced?
For each infection identify the following:

What symptoms were present (or would you expect)?

What EXPOSURE was related to the infection? i.e. “where have you been,
what have you been doing, who were you with and were you in contact with
any animals?”

Return to Unit Overview

p14
 Leicester Medical School

1.2 Can you name an infection you might get from the following?
a. Infection 1
a. Mammal
Symptoms

Exposure

b. Insect
b. Infection 2
Symptoms

Exposure c. Surface

c. Infection 3
Symptoms
d. Water borne
Exposure

e. Air borne

Return to Unit Overview

p15
 Leicester Medical School

1.3 What specific investigations could you order for a patient who presents with a 1.5 AGAR PLATES
fever, tiredness and swollen glands? What supportive investigations would you
During the COVID-19 pandemic we were being asked to wash our hands regularly
order?
in order to avoid spreading the virus but what constitutes good hand hygiene? Why
is it important even without a pandemic? What is on your hands?
INSTRUCTIONS FOR FINGER DABS USING AGAR PLATES EXPERIMENT (see Notes)
Using two agar plates an individual student/patient first presses their fingers and
thumb onto plate A and then repeats with plate B after washing their hands
thoroughly for 20 seconds with soap and water OR hand gel.

PLATE A: DO FINGER DABs WITHOUT WASHING OR CLEANING FINGERS:

The finger dabs:
1.4 If a patient presents with the following, what tests might you order? Find out With the finger dabs it is better to take ‘fingerprints’ from all five fingers, first 4 held
what you can about these tests and make some notes. like so:

a. COVID

b. Bacterial diarrhoea These fit nicely on the plate, increase the number of colonies, give a better visual
result and are a better before and after comparison.
It’s easy to practice/demonstrate on the lid of the plate if you are not sure what to
do or how hard to press.

c. Malaria
PLATE B: DO FINGER DABs WITH WASHING (SOAP & WATER) OR CLEANING
(HAND GEL) FINGERS:
Either WASH hands with soap and water OR CLEAN hands with alcoholic hand gel.
Repeat the finger dabs on second plate as above.

Return to Unit Overview

p16
 Leicester Medical School

Use a marker pen to label the bottom of the plates. The plates will then be c. How many different types of colony might you expect before? How many
incubated overnight upside down at 37oC. The plates are then examined for after?
bacterial growth.

a. Do you expect any bacteria to grow from the ‘finger dabs’ on the agar in the
‘before’ plate (Plate A)? What about the ‘after’ plate (Plate B)? Explain your
reasoning.

d. Do you think hand washing is effective? And if so, how effective would you
expect it to be?

Look at the results below – this is before and after using hand gel:

b. If bacteria grow, do you have any idea of how many bacteria you might
expect?

Before After

Return to Unit Overview

p17
 Leicester Medical School

1.6 HOT TOPICS IN INFECTION – if you do not get to this in group work do
e. Do you think alcohol gel is effective? And if so, how effective? complete as self-study – it is purely to make you aware that different and new
infections are continually arising.

f. Do you think soap and hand gel work in different ways?

g. Does soap kill bacteria?

h. Does alcoholic hand gel kill bacteria?

a. Have you heard of any new pathogens in the news? List any below.
NOTE:
i. Why do you need to use hand-gel in the hospital? The following web sites are a useful starting point for looking up information on
new pathogens
The Centre for Disease Control https://www.cdc.gov/
The World Health Organisation http://www.who.int/en/
https://www.who.int/csr/don/en/
Both of these organisations deal with a wide range of health issues on an
j. What does each ‘colony’ on the agar plate represent? international and global scale. They help to track and monitor new or emerging
infections.

Return to Unit Overview

p18
 Leicester Medical School

As an example of how the global community deals with a ‘new’ infection look up c. Have you previously heard of antibiotic resistance? If so, write down 4 or 5
the following: points that you recall. Aim to identify the clinical relevance of this
information.
Zika virus – this caused some concern when is emerged just prior to the Rio
Olympics in 2015. Lecture 2 Summary: An Introduction to Microbes
Learning Outcomes:

Describe the ‘microbial world’, the key features of bacteria, viruses and
fungi and broadly how they are classified.
b. Has anyone in your group travelled to a part of the world where Zika virus is
transmitted? Describe the structure of bacteria and the difference between gram-
positive and gram-negative bacteria.
Describe the principles of the Gram stain and consequently the staining
EBOLA virus – a major problem a few years ago; but largely controlled at present. characteristics of a gram-positive and gram-negative bacteria.
Microorganisms can be broadly categorised into bacteria, viruses, parasites and
fungi. There are various ways of distinguishing between them. Their relative size is
important to know – broadly speaking viruses are the smallest with parasites the
biggest. They are classified in different ways – bacteria are usually classified
Coronavirus - ongoing pandemic which is now endemic worldwide. according to whether they are gram negative or positive and whether they are cocci
or bacilli and also whether they are aerobes (require O2) or anaerobes (do not require
O2) whereas viruses are most often classified according to the type of genetic
material in their genome – DNA or RNA or whether they are have an envelope or not.
Parasites encompass the protozoa (e.g. Plasmodium falciparum (malaria) – which are
Nipah Virus – sporadic outbreaks in Asia subject of a 2019 film.
single celled - and helminths (roundworms (e.g. Enterobius vermicularis), tapeworms
(e.g. Taenia saginata) and flukes (e.g. Schistosoma mansoni) – which are
multicellular. Fungi are classified similarly – single celled (e.g. Candida albicans
(yeast)) and multicellular e.g. aspergillus species.
Look at the first three pages of Lippincott’s Chapter 1 “Introduction to Microbiology”.
It will take five minutes to read. Try to pick out information to answer the following
questions:

Return to Unit Overview

p19
 Leicester Medical School

Which microbes are prokaryotic? NOTES: AGAR plates

What shapes are bacteria?
Does a virus have a cell wall?
Agar plates are commonly used for the culture of bacteria. In the laboratory bacteria
How does a virus compare to a bacteria in size?
are also cultured using a liquid medium but agar plates are easier to handle.
Where do viruses multiply?

This will be covered in the lecture and you should read these three pages with the Agar is a polysaccharide derived from seaweeds. Agar has remarkable physical
lecture slides as part of your self-study. properties: it melts when heated to around 85oC, and yet when cooled it does not
solidify to gel until 34-42oC. Agar is also clearer than gelatine and it resists digestion
by bacterial enzymes. The use of agar allows the creation of a medium that can be
Note: there is more detail on prokaryotes and eukaryotes plus gram staining in the
inoculated at 40oC in its cooled molten state and yet incubated at 60oC without
notes at the end of this session.
melting.

Click to go straight to Chapter 1. Agar plates commonly contain additional ingredients to facilitate bacterial growth,
including proteins and sodium chloride. The standard Agar plate is red due to the
addition of blood. Find out what blood is used for these agar plates.

It is therefore an ‘enriched’ medium as the plate with the protein and blood provides
nutrients for a number of common bacteria.

However, some bacteria are inhibited by the presence of the blood.

Some bacteria, including Haemophilus influenza will only grow if the blood cells have
been lysed, releasing intracellular nutrients. The lysed blood is a darker brown colour
and is called ‘chocolate agar’.

Return to Unit Overview

p20
 Leicester Medical School

NOTES: Bacterial structure and the Gram stain

You have had an introduction to microbes in the lectures this week. The notes
below will help enhance your understanding of this topic. We will return to the
details of the lecture in future weeks so that you can refer to the lecture as you
make notes of specific infections and microbes. The lecture does set out the
principles of how to think about microbes and how they are classified
The notes below relate to bacteria, as it is critical that you understand these
principles as soon as possible. You can reinforce the information as we go through
the Unit.
The names of the layers surrounding bacteria are potentially confusing.

The following notes are taken directly from Lippincott’s Illustrated Reviews Chapter i) The Cell Envelope is all the material external to and enclosing the
4 and 5. cytoplasm. It consists of several chemically and functionally distinct
1. The basic and cell wall structure of bacteria layers, the most prominent of which are the cytoplasmic membrane and
2. The Gram stain and the difference between gram-positive and gram-
the cell wall. The cell envelope also includes the capsule, if present.
negative bacteria

ii) The Cell Membrane or Cytoplasmic membrane (just called plasma

1. Bacterial Structure: Read the Overview and The Cell Envelope sections
membrane in the diagram above)
The cell membrane is composed of phospholipid. The membrane
acts as a permeability barrier. Note: Remind yourself of the
structure of phospholipid membranes.

iii) The Cell Wall:

The cellular world is divided into two major groups, based on whether or not the cells
have a nucleus (that is, an internal membrane-enclosed region that contains the
ALL bacteria have a cell wall. The common feature of the cell wall is a Peptidoglycan
genetic material). Cells that have a well-defined nucleus are called
layer. The peptidoglycan layer determines the shape of the cell. It is composed of a
eukaryotic, whereas cells that lack a nucleus are called prokaryotic.
cross-linked polymeric mesh. The molecular structure of this layer
All bacteria are prokaryotes.
helps render the bacterial wall resistant to host peptidases such as

Return to Unit Overview

p21
 Leicester Medical School

those in the intestine. This helps the bacteria survive in a hostile environment. It is have a spleen then they are at an increased risk of infections from these bacteria.
the target for several antibiotics. Such patients will commonly need to be immunised against these bacteria (to be
covered again later in the Unit) and/or receive prophylactic antibiotics.
iv) The Capsule
2. Differences between Gram-positive and Gram-negative Bacteria
Many bacteria secrete a sticky, viscous material that forms an extracellular coating (see notes below on the Gram stain):
around the cell. The material is usually a polysaccharide. This is the CAPSULE. It is
not present in all bacteria. It can be found in both some gram-positive bacteria and Gram-positive: Gram-positive bacteria have thick, multi-layered, peptidoglycan cell
some gram-negative bacteria. walls that are exterior to the cytoplasmic membrane

The capsule allows cells to adhere to surfaces, protect bacteria from antibodies and Gram-negative: Gram-negative bacteria have a more complex cell wall structure
phagocytosis, and act as diffusion barriers against some antibiotics, thus contributing composed of two membranes (an outer membrane and an inner, that is, cytoplasmic,
to the organisms’ pathogenicity. Capsules can also protect bacteria against membrane). The two membranes are separated by the periplasmic space, which
desiccation, or drying, which facilitates transmission. contains the peptidoglycan layer. In contrast to gram-positive cells, the
peptidoglycan layer of gram-negative cells is thin, and the cells are consequently
Later in the Unit you will learn of some specific bacteria that have capsules and the more susceptible to physical damage. The outer membrane is distinguished by the
clinical relevance of the capsule. To complete the topic at this stage the important presence of embedded lipopolysaccharide (LPS) The polysaccharide portion of LPS
bacteria containing a capsule include: (O-polysaccharide) is antigenic and can, therefore, be used to identify different
strains and species. The lipid portion (called lipid A) is embedded in the membrane
and is toxic to humans. Because lipid A is an integral part of the membrane, it is
Streptococcus pneumoniae (pneumococcus) called an endotoxin, as opposed to exotoxins, which are secreted substances
Neisseria meningitidis (meningococcus)
TASK: make yourself a simplified diagram showing the difference between a gram-
Group B streptococcus (GBS) positive bacteria and a gram-negative bacteria

Haemophilus influenzae type b (Hib) We will return to this concept repeatedly (e.g. Session 3 on ‘sepsis’)

The spleen is especially important in recognising these

particular bacteria and dealing with them. If a patient does not

Return to Unit Overview

p22
 Leicester Medical School

THE GRAM STAIN REMEMBER

Gram positive bacteria retain the crystal violet dye = BLUE / PURPLE
An important principle you must understand is the use of a GRAM stain. It is critical
to the classification of bacteria. We will refer to it repeatedly. You will be asked to Gram negative bacteria: a counterstain (commonly safranin or fuchsine) added
identify bacteria on the basis of the Gram stain in exams. after the crystal violet gives all Gram-negative bacteria a red or pink coloring. =
PINK

Click to go to chapter 4. Read under the subsection: Direct Gram POSITIVE Gram NEGATIVE
Visualization of the Organism.

Cocci

• What is a Gram stain?

Bacilli
• How is it performed? Write down the main principles. We will not ask you
to perform a gram stain or to list every step. However the more you
understand the easier it will be to make the link between the classification
and some of the clinical features.
You can use the above table (or something like it) and add the names of all the
bacteria you have read about or heard about to date. You can continue to add
• What component of the bacteria is the stain linked to? additional names throughout the unit. It is a very visual picture of the organisms’
classification and you will begin to know the names!

Return to Unit Overview

p23
 Leicester Medical School

Session 2: The Microbiome & Innate Immunity Describe how microbes, normally present as commensals (part of the
19 January 2022 microbiome) can cause disease / infections in certain situations and give
Preparatory Work Review lectures 1 & 2 examples.
View HMP videos/articles
9.00-10.30 Small Group Work 2 Skin flora and microbiota With regard to the innate host response you should:
(LIVE F2F) Case studies Describe the different innate barriers to infection, including physical,
physiological, chemical and biological.
11:00 – 11:50 Lecture 3 An Infection Model
Describe how these different barriers work together to maximise the
(Live F2F Simulcast Session)
response against microbes
12:00 – 12:50 Lecture 4 Innate Immunity
Recognize the different interventions that affect integrity of the innate
(Live F2F Simulcast Session) barriers
NOTES Cellulitis Understand the risk of infection associated with these interventions
Candida
Describe the second line of defence, including the role of phagocytes and
Full Blood Count
chemicals (complement and cytokines)
Self-Study Complete Group Work Describe how pathogens are recognised by cells of the innate immune
Questions system
Infection Model Charts Name and describe important opsonins
Describe how a clinical evaluation of the innate immune response helps to
identify the presence of infection, and in particular that of acute
Learning Outcomes
inflammation and acute infection. As examples describe the role and
Understand and describe a model of infection evaluation of neutrophils and C-reactive protein
With reference to the classification of microbes you should start to
accumulate names and key characteristics of some common microbes. This
is an on-going objective for all of the remaining weeks.
To understand how to apply the model of infection to a specific illness
Describe the human microbiome
Identify microbes commonly found on the skin and other body sites

Return to Unit Overview

p24
 Leicester Medical School

Session 2: Preparatory Work

1) Preparation for group work: Read the background information on the Click to go to Chapter 2. The suggested sub sections to read
human microbiome and watch the suggested videos as detailed below. are: The Human Microbiome, Beneficial Functions of
Normal Flora, Harmful Effects of Normal Flora
2) View, recall and review: View the lectures on the Introduction to Microbes
(Lecture 2). Recall and review the information from the lecture before you
start the group work. You could do this on your own before the session or
with your group at the beginning of the session or a combination of both. We will return to a number of these principles during the Unit.

3) Preparation for lectures: Read through the lecture slides/summaries for Read this article “FAQ: Human Microbiome”. It can be downloaded from
today’s lectures An Infection Model (lecture 3) and Innate Immunity
http://www.asmscience.org/content/report/faq/faq.3
(lecture 4) and add any additional notes before and after you view the
This is a more extensive written version of the animation.
lecture.

1) Learn about the HUMAN MICROBIOME using the links below. If you prefer listening to a talk then the following video covers similar material to
the article and will take about the same time as reading the article. Both are
interesting.

Look at this short animation. Although only an animation, it sets the scene
nicely. http://www.ted.com/talks/rob_knight_how_our_microbes_make_us_who_we_a
re

https://www.youtube.com/watch?v=5DTrENdWvvM

Return to Unit Overview

p25
 Leicester Medical School

Small Group Work 2: Learning about the Microbiome

2.1 Skin Microbiome

a. Read the paragraph in Lippincott on the flora of the skin chapter 2.

Scroll down to Distribution of Normal Flora in the Body and look under skin.

b. The diagram from Lippincott is opposite. Note the names of bacteria

found on the skin. Have you previously heard of these bacteria?

Note: “Skin popping” is the injection of illicit drugs such as opiates, cocaine,
barbiturates into the dermis or subcutaneous tissue.

Return to Unit Overview

p26
 Leicester Medical School

c. Gram stain: If you were to perform a gram stain of one of the colonies on 2.2 CLINICAL CASE STUDY – CELLULITIS – an example of an infection caused
the finger dab Agar plate from last week, what colour would the Gram by bacteria that are part of the normal skin microbiome.
stain be?

d. What does the gram stain tell you about the cell wall structure of these
bacteria?

a. Describe what you see

b. What might the patient complain of?

Return to Unit Overview

p27
 Leicester Medical School

f. The patient is otherwise generally well. How would you manage the
c. What history would you seek? patient?

You order a full blood count. After 2 days the test results are available.
These are as follows (normal values are in brackets):
(The main point of this question is not to ask the right questions but to have some
appreciation of what to ask and to rule out other diagnosis)
Clinical details: Rash on leg. ? Infection
d. What else would you look for on examination? WCC: 11.5 x109/l (4-11 x109/l)
Neutrophils: 7.0 x109/l (2.0-7.0 x109/l)
Hb: 135g/l (130-165g/l)
MCV: 92fl (80-100fl)
MCH: 29pg (27-32pg)
Platelet count: 204 x109/l (150-400 x109/l)

e. What investigations would you consider? Blood culture: No growth after 48 hours

Clinical
g. What details: Rash
is your on leg? Infection
interpretation of the results?
WCC: 11.5 x109/l (4-11 x109/l)
Neutrophils: 7.0 x109/l (2.0-7.0 x109/l)
Hb: 135g/l (130-165g/l)
MCV: 92fl (80-100fl)
MCH: 29pg (27-32pg)
Platelet count: 204 x109/l (150-400 x109/l)
Return to Unit Overview
Blood culture: No growth after 48 hours
p28
 Leicester Medical School

2.3 CLINICAL CASE STUDIES - CANDIDA – an example of a fungal microbe

h. How does this affect the diagnosis you have made? that is part of the microbiome and can cause infections

Case 1
A patient who is HIV positive presents to the clinic with a painful mouth and difficulty
swallowing. (We will cover HIV in detail later in the course)

i. How does it change your management?

a. Describe what you see?

j. Based on your knowledge of the skin microbiome, what microbes are

likely to cause this infection?
b. What is the diagnosis?

c. Why does he have difficulty swallowing?

Return to Unit Overview

p29
 Leicester Medical School

Case 2 2.4 MICROBIOTA AT OTHER SITES

A young women presents to her GP with a white vaginal discharge, vulvar redness
and itching. The finger dab looked at microbes on your skin. The two pages in Lippincott’s
Ten days ago she was treated with a course of amoxicillin for a respiratory tract already referred to contain essential knowledge. Chapter 2: Normal Flora
infection.

A sample of the discharge is sent for microscopy and culture.

a. Describe the picture below? You need to know about this organism.
Complete the following table (complete in your own time if you run out of time
during group work):

Microbe* Microbial Normal How this microbe can

classification: distribution cause infection.
Virus, Bacteria
(Gram +/-),
fungus, parasite
Streptococcus
mutans

b. What is the common vaginal commensal organism that is reduced following

Streptococcus
a course of a broad-spectrum antibiotic? pneumonia

You will revisit these microorganisms in the year 2 reproduction

unit.

Return to Unit Overview

p30
 Leicester Medical School

Escherichia Lecture 3 Summary: An Infection Model

coli
Learning Outcomes:

Understand and describe a model of infection

With reference to the classification of microbes you should start to
accumulate names and key characteristics of some common microbes.
This is an on-going objective for all of the remaining weeks.
To understand how to apply the model of infection to a specific illness
Candida Describe the human microbiome
albicans Identify microbes commonly found on the skin and other body sites
Describe how microbes, normally present as commensals (part of the
microbiome) can cause disease / infections in certain situations and give
examples.

This model provides a tool (or “scaffold”) to enable you think about all aspects of an
infection – the pathogen that causes it, the symptoms that a patient may present
with, the way in which the patient may have acquired the infection (contact,
droplets, blood etc.), why/how the pathogen causes the symptoms i.e. the process
of infection, the management of the patient (how you diagnose and treat) and the
likely prognosis/outcome for the patient. Therefore for any patient you are
examining – think:

1) Patient – age, gender, social status, health status, time of year, home, recent
travel

2) Pathogen – virus, bacteria, fungus, parasite

3) Mechanism of infection - contiguous (direct) spread, inoculation,

haematogenous, ingestion, inhalation, vector, vertical transmission

Return to Unit Overview

p31
 Leicester Medical School

4) Process of the infection – attachment, interaction with host defences, host Lecture 4 Summary: Innate Immunity
damage
Learning Outcomes:
5) Management of the patient – history, examination, investigations,
Describe the different innate barriers to infection, including physical,
treatment (specific and supportive)
physiological, chemical and biological.
6) Patient outcomes – cure, disability, chronic infection or death. Describe how these different barriers work together to maximise the
response against microbes
Recognize the different interventions that affect integrity of the innate
barriers
Understand the risk of infection associated with these interventions
Describe the second line of defence, including the role of phagocytes and
chemicals (complement and cytokines)
Describe how pathogens are recognised by cells of the innate immune
system
Name and describe important opsonins
Describe how a clinical evaluation of the innate immune response helps
to identify the presence of infection, and in particular that of acute
inflammation and acute infection. As examples describe the role and
It is important to remember that a patient in the hospital setting may have had an evaluation of neutrophils and C-reactive protein.
operation e.g. hip replacement and may acquire an infection in the
process therefore infection prevention is extremely important. Innate immunity is one part of the immune response – it is a fast, non-specific
immediate response to any foreign pathogen that breaks the lines of defence.
There are several barriers to entry for any foreign object – these first lines of
defence include:
1) Physical barriers – skin, mucous membranes and bronchial cilia
2) Physiological barriers – diarrhoea, vomiting, coughing and sneezing
3) Chemical barriers – low pH and antimicrobial molecules such as IgA, lysozyme,
mucus, β-defensins and gastric acid

Return to Unit Overview

p32
 Leicester Medical School

4) Biological barriers – normal flora in strategic locations which provide us with complement proteins (C3b, C4b), antibodies (IgG, IgM), and acute phase proteins
several benefits including synthesise of some vitamins (e.g. K, B12) and immune (C-reactive protein (CRP), mannose-binding lectin (MBL)).
maturation. Once the phagocyte has recognised and bound to the microbe via the PAMP to
Infections can arise when a) normal flora is displaced from its usual location to PRR interactions and the opsonin to opsonin receptor interactions, it can now
another environment which may be sterile, b) the host becomes destroy the microbe by a process of engulfment and digestion of the microbe. It
immunocompromised and the normal flora can start to overgrow and become destroys the microbe either by a) oxygen dependent pathway – free oxygen
pathogenic and c) when normal flora is depleted due to antibiotic treatment. radicals or b) oxygen independent pathways – enzymatic digestion.
Now the body needs to respond with its second line of defence which causes The complement system pathway compromises 20 serum proteins of which the
inflammation and include: most important ones for your study are as follows:
1) Phagocytes – macrophages, monocytes, neutrophils 1) C3a/C5a – which are responsible for recruitment of phagocytes
2) Other key cells of the innate immune system - basophils (mast cells), 2) C3b/C4b – opsonisation of pathogens
eosinophils, natural killer cells and dendritic cells 3) C5 – C9 – killing of pathogens
3) Chemicals – complement system and cytokines Complement system proteins circulate in the blood as inactive precursors which
Phagocytes must first recognise a microbe as foreign – there are several are activated in a cascade fashion culminating in phagocyte activation and
molecules on the microbe surface which identify it as alien – these are called microbe digestion. There are two distinct pathways which are activated by
PAMPs – pathogen associated molecular patterns - and include carbohydrates, different molecules a) alternative pathway – initiated by cell surface components
lipids, proteins and nucleic acids, e.g. peptidoglycan (a component of bacterial such as endotoxins in E.Coli or b) MBL – initiated when MBL binds to mannose
cell walls), lipopolysaccharide (a lipid/carbohydrate moiety found in bacterial cell sugar components of proteins on microbes. Remember that although the
membranes), ß-glucan (found in fungal cell walls) or dsRNA (some viruses). For pathways of activation of complement are different they have the same
recognition to occur there must also be something on the surface of the outcome.
phagocyte for the PAMP to interact with and essentially say “hey there I am Cytokines also play a role in innate immunity and many are derived from
foreign and I am sending you this message by binding my receptor to your macrophages (IL-1/IL-6 and TNFα). They have a role to play in inflammation and
surface”. These molecules or receptors are called PRRs – pathogen recognition so called cytokine storms occur when the immune system essentially overreacts
receptors – they are proteins that span the phagocyte membrane and they and triggers a cascade of events which may culminate in death – e.g. in COVID-
essentially bind, for example, lipopolysaccharide (via TLR4) or peptidoglycan (via 19 and Spanish flu pandemics.
TLR2).
Opsonisation of microbes enhances the interaction between the phagocyte and
the microbe. Opsonins are proteins that bind to and coat the surface of the
microbe. These are produced by various components of the immune system –

Return to Unit Overview

p33
 Leicester Medical School

Cytokine Release
© Scientificanimations.com

At all stages of the innate immune response these are various mediators released
which cause certain outcomes such as vasodilation and are as follows:
• Vasodilatation – Histamine, Serotonin, Prostaglandins, Nitric Oxide
• Increased vascular permeability – Histamine, Bradykinins, Leukotrienes, C3a &
C5a
• Chemotaxis – C5a, LTB4, TNF-a, IL-1, Bacterial Peptides
• Fever – Prostaglandins, IL-1, TNF-a, IL-6
• Pain – Bradykinin, Substance P, Prostaglandins
Additional note on CRP (C-Reactive Protein) – this is an acute phase protein that is
produced in the liver with several roles:

Activates complement
Recognises self and foreign molecules based on pattern recognition
Binds to Fc receptors (on cell surface which bind Fc region of antibodies
bound to antigen) leading to generation of pro-inflammatory cytokines
Acts as an opsonin for pathogens OR binds to micro-organisms to make
them more susceptible to phagocytosis

Return to Unit Overview

p34
 Leicester Medical School

NOTES: CELLULITIS NOTES: CANDIDA

Cellulitis: is severe inflammation of dermal and subcutaneous layers of the skin.

Candidiasis is caused by the yeast Candida albicans and other Candida species,
The features of cellulitis are those of acute inflammation, which you will also cover which are normal body flora found in the skin, mouth, vagina, and intestines.
in Pathological Processes (session 2). Although considered a yeast, C. albicans is dimorphic and can form a true mycelium.

While the patient in the case previously had a negative result when a blood culture Infections occur when competing bacterial flora are eliminated, for example, by
was done all you can conclude is that the organism is not found in circulating blood; antibacterial antibiotics, allowing the yeast to overgrow. Candida infections have
it could still be in the tissue. When you were asked “How does this affect the various manifestations, depending on the site and the degree of immune-
diagnosis you have made?” – you should have answered as follows: incompetence of the patient.

The patient clearly has cellulitis and there is a high probability this is due to infection. For example, oral candidiasis (thrush) presents as raised, white plaques on the oral
Because of risk of further complications it must be treated with antibiotics; even if mucosa, tongue, or gums. The plaques can become confluent and ulcerated and
tests for infection are negative. Treat the patient and not the test (in this particular spread to the throat. Most HIV-positive individuals eventually develop oral
case) candidiasis, which often spreads to the oesophagus. The latter condition is
considered an indicator of full-blown AIDS. Vaginal candidiasis presents as itching
Common pathogens that causes cellulitis include Group A streptococcus, and burning pain of the vulva and vagina, accompanied by a white discharge.
Staphylococcus aureus and Haemophilus influenza type B. You will commonly see
children, elderly patients or immunocompromised patients presenting with cellulitis. Both oral and vaginal infections are treated topically with nystatin or clotrimazole.

Other important types to know:

o Anaerobic form of cellulitis can cause skin necrosis and foul-smelling

wound.
o Necrotizing fasciitis is a life threatening infection of the skin,
subcutaneous tissue, muscle layers or fascia. It presents as intense
pain, rapid spread of cellulitis and systemic symptoms of sepsis or
septic shock.

We will cover the recommended antibiotic in a later session.

Return to Unit Overview

p35
 Leicester Medical School

NOTES: The “Full Blood Count” (FBC) TEST NAME INCREASED/DECREASED

WBC White Blood May be increased with infections, inflammation,
Cell cancer, leukaemia; decreased with some
The ‘Full Blood Count’ [FBC] medications, some autoimmune conditions, some
Note: You have covered some of the key aspects of the viral or severe infections, bone marrow failure,
components of the blood in Metabolism, Endocrinology and enlarged spleen, liver disease, alcohol excess and
Haematology (MEH). Some of the cells of the blood have already congenital marrow aplasia (marrow doesn't
been mentioned in Body Logistics. develop normally).
% Neutrophil Neutrophil This is a dynamic population that varies somewhat
In clinical practice the Full Blood Count is a common test used in many situations. from day to day depending on what is going on in
We will show you FBC results as this is a standard investigation for a patient who the body. Neutrophils are one of the first lines of
might have an infection. We do not expect you to know all the details at this stage, defence against bacterial infection. Neutrophils
but you should become familiar with the components that relate to infection. can be increased in some bacterial infections and
would support a diagnosis of bacterial infection
In some infections the white count and neutrophil
NOTE: In examinations, we will give you the normal values. However, you should
count can be suppressed.
become familiar with the normal ranges for the main components.
% Lymphocyte Can be increased or decreased by viral infections.
Lymphocytes Can be increased in conditions such as chronic
The FBC is used as a broad screening test to check for such disorders as anaemia, lymphocytic leukaemia
infection, and many other diseases. It includes the following: The red cell values are also reported in a FBC, but are not the focus
of this Unit - (you’ll cover this more in MEH).
White blood cell (WBC) count is a count of the actual number of white blood
cells per volume of blood. Both increases and decreases can be significant. Red blood cell (RBC) count: is a count of the actual number of red blood cells
White blood cell differential: looks at the types of white blood cells present. per volume of blood. Both increases and decreases can point to abnormal
There are five different types of white blood cells, each with its own function. conditions.
The differential classifies a person's white blood cells into each type: Haemoglobin measures the amount of oxygen-carrying protein in the blood.
neutrophils (also known as PMNs or polymorphonuclear leukocytes), Haematocrit measures the amount of space red blood cells take up in the
lymphocytes, monocytes, eosinophils, and basophils. blood. It is reported as a percentage (0 to 100) or a proportion (0 to 1).
Mean corpuscular volume (MCV) is a measurement of the average size of
The WBC and the neutrophil count will commonly be reported in your RBCs.
relation to infection. The lymphocyte count is also relevant. Try to
link these with the lecture on adaptive immunity. The platelet count is the number of platelets in a given volume of blood.

Return to Unit Overview

p36
 Leicester Medical School

Session 2 Self-study:

1. Complete all the case studies

2. Make sure you completed the table with ‘microbiota at other sites’
3. Add any new organisms to your table and begin to make infection model
charts for the organisms in this session using the slide below. This will help
you remember the details of each individual organism.

4. Add your own additional notes to the NOTES on cellulitis and candida.

Return to Unit Overview

p37
 Leicester Medical School

Describe the main features of community-acquired pneumonia

Session 3: Sepsis, Adaptive Immunity & Applying the
Infection Model 26 January 2022 Streptococcus pneumoniae
Preparatory Work Read about pneumonia Describe the main microbiological features of Streptococcus pneumoniae
View, recall & review NOTE: there will be more detailed learning outcomes for the lecture on
lectures 3 & 4 Streptococci later in the unit (see session 11).
Sepsis videos/articles
Adenovirus
9.00-10.30 Small Group Work 3 Case studies
(LIVE F2F) Aspects of the innate Describe and identify Adenovirus as a cause of upper respiratory tract
immune response infections

With regard to Sepsis

11:00 – 11:50 Lecture 5 Acute Sepsis in the
Understand the features of acute sepsis
(Live F2F Simulcast Session)
Emergency Department
Understand the mechanism by which micro-organisms trigger the
inflammatory cascade
12:00 – 12:50 Lecture 6 Adaptive Immunity – Part 1
Understand the principles of supportive and specific treatment for acute
(Live F2F Simulcast Session) sepsis
NOTES Pneumonia Describe the Sepsis Six Bundle
Adenovirus
With regard to Adaptive Immunity
Self-Study Streptococcus pneumoniae Describe features of Antigen Presenting Cells
Describe MHC molecules in relation to microbe presentation
Describe the processing and presentation of microbial antigens to T
Learning Outcomes lymphocytes
Describe T cells and their role with regard to infections
With regard to Pneumonia
Describe how antigen presenting cells activate the right adaptive immune
Describe the relevant anatomy and physiology linked to pneumonia response
Describe the role of the innate immune system and microbiota relating to
infections of the lower respiratory tract

Return to Unit Overview

p38
 Leicester Medical School

Look at the related article highlighting that Sepsis is hard to diagnose. The Sepsis
Trust (http://sepsistrust.org/) have identified important symptoms and signs to
Session 3: Preparatory Work look out for.

1) Preparation for group work: Read the background information on Pneumonia

at the end of this workbook session.

2) View, recall and review: View the lectures on the Infection Model (Lecture 3)
and Innate Immunity (Lecture 4) Recall and review the information from the
lectures before you start the group work. You could do this on your own before
the session or with your group at the beginning of the session or a combination
of both. http://www.bbc.co.uk/news/health-35409266

Write (or copy and paste) the six most common signs of Sepsis.
3) Preparation for lectures: Read through the lecture slides/summaries for today’s
lectures Acute Sepsis in the Emergency Department (lecture 5) and Adaptive
Immunity (Part 1) (lecture 6) and add any additional notes before and after you
view the lecture.

4) Preparation for Sepsis lecture (below): There has been a lot in the media over
the past few years regarding sepsis. In 2020 there were new guidelines and
definitions of ‘sepsis’.

Look at the following news page and listen to the video of the mother of William
Mead talking about her experience.

http://www.bbc.co.uk/news/health-36774751

Return to Unit Overview

p39
 Leicester Medical School

b. What clues in the history and examination suggest a potential source of his
Small Group Work 3: Infection Model Case Studies infection?

3.1 CASE STUDY – An example of the Infection Model

A 65-year-old man with known diabetes was admitted with a 3 day history of
shortness of breath and feeling generally unwell. On further questioning he
reported a cough productive of yellow sputum for the past 4-5 days. He denied any
headaches, nausea, vomiting or diarrhoea. He denied any dysuria but does not think c. As part of his initial investigations he has a Chest X-ray (shown below) – could
he has passed urine today. you describe what you see?

He has no other past medical history and his only current medication is Metformin
(an oral drug for diabetes). He is a retired plumber and lives with his wife. He is an
ex-smoker with a 20 pack-year history, and gave up 5 years ago. He drinks 20-25
units of alcohol per week.
On examination he appears flushed and looks quite unwell. His temperature is
38.1oC and his blood pressure is 135/82 with a heart rate of 108bpm. His respiratory
rate is 20/min and his O2 saturation levels are 94% on air.
He does not have a rash or any abnormal skin/nail changes. There are no palpable
lymph nodes. He does not have any neck stiffness or other features of meningitis.
His heart sounds are normal but on listening over his lungs you can hear coarse
crackles and bronchial breathing over the mid-zone of his right lung. His abdominal
examination is normal.

a. What features of his history suggest an infective cause of his presentation?

A 65 year old man with known diabetes was admitted with a 3 day history of
shortness of breath and feeling generally unwell. On further questioning he
reported a cough productive of yellow sputum for the past 4-5 days. He denied any
headaches, nausea, vomiting or diarrhoea. He denied any dysuria but does not think
he has passed urine today.
He has no other past medical history and his only current medication is Metformin
(an oral drug for diabetes). He is a retired plumber and lives with his wife. He Return
is an to Unit Overview
ex-smoker with a 20 pack-year history, and gave up 5 years ago. He drinks 20-25 p40
 Leicester Medical School

NOTE: When looking at a chest X-ray it is worth knowing that

tissues with increasing density look whiter. SO:

Air looks black

Fat (as in subcutaneous tissue) looks dark grey
Water and soft tissue looks light grey (e.g. solid organs)
Bone looks off-white

The lung tissue contains airways and lots of air and so is normally black (although
you can also see the marking of the airways). If the lung tissue and airways
becomes filled with fluid or with inflammatory cells then it becomes more solid and
will look light grey.
f. What organism do you think is causing his infection? This is an important
d. How might you confirm the infective agent? microorganism – check you have the right name.

e. What treatments should this patient be given?

g. Which features given in his history might place him at increased risk of
infections like this?

A blood culture was taken on admission. You receive a telephone call from the lab
the next day telling you that the gram stain shows gram positive cocci which are
forming chains. (See picture above right).

Return to Unit Overview

p41
 Leicester Medical School

3.2 QUESTIONS ON Innate Immunity & C-REACTIVE PROTEIN (CRP) III. What are the receptors on phagocytes that recognise the pathogen called?
This question relates to the lecture on the innate immune response. The foundation
doctor (case above) also sends a blood sample for a full blood count and a measure
of the CRP. The results are below:
IV. Which components of the pathogen are important in triggering a reaction
WCC: 20.5 x109/l (4-11 x109/l)
from the phagocyte?
Neutrophils: 17.0 x109/l (2.0-7.0 x109/l)
Hb: 135g/l (130-165g/l)
9
Platelet count: 204 x10 /l (150-400 x109/l)
C-Reactive Protein = 120 mg/L (Normal < 5) V. What are these “triggers” generically known as?

C-Reactive Protein (CRP) is measured daily on many medical and surgical wards. It is
VI. Name some of the molecules (mediators) produced by this immune cell in
therefore worth understanding the principles behind the test and exactly what CRP
response to the pathogen
is able to tell you about the host immune response.

Look at the slides from the Immune lecture.

VII. Where is CRP produced (i.e. which organ)?
There is also information in Immunology for Medical
Students Box 20.1 – you will need to scroll through to find
this box and the information on CRP is further down in the
VIII. What triggers this organ to produce CRP and other acute phase proteins?
box.

Use the questions below to help you understand more about CRP.

I. Which immune cell recognises the invading pathogen?

II. Name the different cells which are classed as phagocytes https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908901/#:~:text=The%20stim
ulation%20of%20CRP%20synthesis,modified)%20CRP%20(mCRP)

Return to Unit Overview

p42
 Leicester Medical School

IX. How quickly is CRP produced? 3.3 CASE STUDY – An example of the Infection model

The first year students moved in to the University residence last week.
Over the past week, a series of students became unwell and attended the
X. Why is CRP measurement useful in clinical practice? University Health Centre. Some students decided to ‘treat themselves’ and stay
away from the Health Centre.
The commonest set of symptoms was as follows:
- Sore throat with a blocked nose (nasal congestion)
- Fever
- Some, but not all, developed a cough.
XI. What is the function of CRP? - Two of the students developed conjunctivitis (red eye)
One student (Thomas Brown) became increasingly unwell with increased cough and
shortness of breath. The GP at the Health Centre referred him to the Accident &
Emergency Department for review.

XII. Can the CRP level help to identify the pathogen or the correct treatment?

a. What patient factors do you consider in assessing the possible infection?

XIII. The production of CRP is part of the “Acute Phase Response”. Name one
other important feature of the acute phase response (also triggered by the
substances produced by the immune cell).

b. What is the likely mechanism of infection?

Return to Unit Overview

p43
 Leicester Medical School

c. How would you make a diagnosis for one of the students presenting with the Thomas Brown:
above symptoms? What is the most likely diagnosis?
Full blood count
White Cell Count 6.5 x 109/l (4-11)
Neutrophils 3.0 x109/l (2.0-7.0)
Haemoglobin 145 g/l (130 -165)
Mean Cell volume 92 fl (80-100)
Mean Cell Haemoglobin 29 pg (27-32)
Platelet Count 310 x 109/l (140-400)
Throat swab for viral studies:
Viral PCR:
d. What treatment do you suggest? Influenza A Negative
Influenza B Negative
ParaInfluenza Negative
Sars- CoV-2 Negative

Adenovirus Positive
RSV Negative
(Note: RSV stands for Respiratory Syncytial Virus)

e. Does this confirm the microbiological diagnosis?

The GP is concerned at the number of students presenting and decides to send off
some investigations. He sends investigations for Thomas Brown.
Two days later the following results come back to the GP surgery:

Return to Unit Overview

p44
 Leicester Medical School

Lecture 5 Summary: Acute Sepsis in the Emergency Micro-organisms trigger inflammatory responses via special methods in the
following processes:
Department
Learning Outcomes: Gaining entry into the host (e.g. via respiratory, GI, urogenital, skin)
Adherence to host cells (e.g. via cell surface adhesion molecules,
Understand the features of acute sepsis fimbriae/pili)
Understand the mechanism by which micro-organisms trigger the Invasive into host cells / mucosal surfaces (e.g. via enzymes such as
inflammatory cascade collagenase and hyaluronidase)
Understand the principles of supportive and specific treatment for acute This would then result in inflammation (either pyogenic or granulomatous)!
sepsis
Clinical Features:
Describe the Sepsis Six Bundle
Features of localised infection:
What is sepsis?
rubor (redness)
Lay definition: ‘Sepsis is a life-threatening condition that arises when the body’s tumor (swelling)
response to an infection injures its own tissues and organs.’ calor (heat)
Professional definition: ‘Sepsis is characterised by a life-threatening organ dolor (pain)
dysfunction due to a dysregulated host response to infection.’ loss of function
‘Septic shock is a subset of sepsis where particularly profound circulatory, cellular Physiological Features of sepsis:
and metabolic abnormalities substantially increase mortality.
Respiratory: Raised respiratory rate (tachypnoea). Peri-capillary oedema & reduced
‘Red Flag Sepsis’ is not a formal diagnosis! It identifies septic patients that are at high pulmonary compliance (fluids leaking into interstitial tissues)
risk of deterioration/ end organ dysfunction.
Cardiac: Low blood pressure (due to vasodilation and increased capillary leakage).
Sepsis pathophysiology: This would result in tachycardia & end-organ damage (kidneys, liver, and brain)
Vasodilation Central Nervous System: As a result of reduced blood perfusion to the brain,
Capillary leakage patients can present with confusion, drowsiness, slurred speech, agitation, anxiety,
Amplification of the immune system and reduced level of consciousness.

Note: From your knowledge in Body Logistics, what is the Renal: As a result of reduced blood transfusion to the kidneys, there is reduction in
consequence of leaky capillaries? urine output.
Pyrexial (hypothalamic response to infection) BUT remember hypothermia for
elderly or even normal temperature for children/immunocompromised patients!

Return to Unit Overview

p45
 Leicester Medical School

Other systems affected: liver and gastrointestinal tract. Consider critical care if patient continues to deteriorate. Continue reviewing patients
daily & chase results +/- liaise with microbiology.
However, sepsis is very difficult to recognise by healthcare professionals!
Other non-emergency treatments:
Who is at risk?
Vaccination
Very young (< 1 year old).
Prophylaxis for close contacts
Elderly (>75 years) or very frail.
Pregnant, post-partum (within last 6 weeks). Public Health England (if this is notifiable disease.)
Patients with impaired immune system due to illness (diabetes, chronic
kidney failure, HIV etc.) or drugs (steroids, immunosuppressant etc.)

Common organisms: Lecture 6 Summary: Adaptive Immune Response – Part 1

Urinary tract: Enterobacteriaceae or enterococci Learning Outcomes:
Pneumonia: Streptococcus pneumoniae
Describe features of Antigen Presenting Cells (APCs)
Meningitis: Neisseria meningitidis or S. pneumoniae
Skin sepsis: Streptococcus pyogenes or Staphylococcus aureus Describe MHC molecules in relation to microbe presentation
Normal flora: May become invasive (e.g. dental abscess, cholecystitis, Describe the processing and presentation of microbial antigens to T
appendicitis or diverticulitis) lymphocytes
Following surgery: A wide range of organisms may be involved and can Describe T cells and their role with regard to infections
involve prosthetic devices (orthopaedic, cardiovascular, neurosurgical) Describe how antigen presenting cells activate the right adaptive immune
response
How is sepsis diagnosed? Via nursing baseline observations (NEWS)! See Notes
Respiration rate, oxygen saturation, systolic blood pressure, pulse rate, level of
consciousness or new confusion*, temperature When considering adaptive immunity, the main cells of interest are a) antigen
presenting cells (four types - dendritic cells, Langerhans cells, macrophages, B cells)
Management plan:
and b) T-cells (either naïve or effector). Naïve T-cells have not seen the antigen
SEPSIS 6 within the first hour! Each hour delay in giving antibiotics increases mortality before while effector T-cells have and respond in particular ways depending on the
by 7.6%! Therefore, do NOT delay in administering antibiotics within the hour! APC. If the APC is a macrophage – then T-cells phagocytose the pathogen. If the APC
(Remember: 3 in and 3 out!)
is a B-cell then T-cells respond by stimulating the production of antibodies – the
IN: oxygen, antibiotics, fluids (only if appropriate) humoral response.
OUT: blood cultures, lactate & Hb, urine output.

Return to Unit Overview

p46
 Leicester Medical School

APCs are in strategic locations: mucosal membranes (gut, lung), skin (i.e., Langerhans Exogenous Pathway: presentation of the microbial peptides from extracellular
cells), blood (i.e., plasmacytoid cells), lymph nodes (i.e., follicular dendritic cells), and microbes (e.g. bacteria, parasites, toxins, etc.) via MHC II complexes occurs only on
spleen. There is diversity in the type of pathogens sensed and the methods in which APCs – the APCs activate CD4+ T cells.
these APCs capture these pathogens.

APCs present pathogen antigenic peptide attached to major histocompatibility

complexes. MHC II complexes are expressed on dendritic cells, B-cells and
macrophages and they present microbial peptides from extracellular microbes while
MHC I complexes exist in all nucleated cells and present microbial peptides from
intracellular microbes. Note: APCs and non-APCs present peptides from intracellular
Refer to Dr Amrani’s lecture notes for more details of the above diagram– but this is
pathogens to CD8+ T cells.
a comparison of the a) endogenous (intracellular microbes such as viruses) and b)
Endogenous Pathway: in the endogenous pathway intracellular pathogens (e.g. exogenous (extracellular microbes such as bacteria) pathway for presenting
viruses, mycobaterium, Salmonella, Listeria and in some situations E Coli and microbial peptides via MHC I and MHC II respectively.
Staphylococcus can all replicate inside the host cell) are processed by both non APCs
and APCs and the antigens presented at the surface via MHC I molecules. But only
APCs can stimulate the immune system response via CD8+ cells.

Return to Unit Overview

p47
 Leicester Medical School

It is important to note that APCs can also process intracellular microbes (viruses) to NOTES: Pneumonia – Background Information
activate naive CD4 T cells (TH1) by expressing the viral peptides via the MHC class II
1) ANATOMY
molecules as well as presenting viral peptides via MHC class I (the latter defined as
The airways of the lung start with the trachea, dividing into bronchi and then into
cross presentation). This is an important step as it allows both APCs and virus specific smaller bronchioles. At the end of the bronchioles are the small alveolar sacs.
CD4+ helper T cells to fully activate virus specific CD8+ T cells to become CTL and kill
virally infected cells. The
mechanisms of cross
presentation (that works
also for presenting
antigen from cancer cells)
are not clear, but several
mechanisms (depending
on how the microbes is
acquired) have been
proposed (see diagram no
need to remember them).

The highly polymorphic residues in the peptide binding cleft make it a highly variable
region with the ability to bind to a diverse range of microbial peptides – this gives a
broad specificity and means that no one individual has precisely the same
susceptibility to a disease as another. MHC complexes can also be problematic and
MHC molecules are implicated in two autoimmune diseases IDDM (or type I
diabetes) and ankylosing spondylitis and are the main reason for graph/organ
rejection in transplants.

Return to Unit Overview

p48
 Leicester Medical School

Each lung is divided into LOBES. The right lung has three lobes. The left lung has There are also nonspecific cellular and humoral factors produced in the lung
two lobes. including immunoglobulin A (IgA), complement, neutrophils, and macrophages that
are able to destroy many potential respiratory pathogens by binding, engulfing, or
directly killing them. Opsonization by antibody and complement aids the phagocytic
process by neutrophils and macrophages. The recruitment of macrophages from
the reticuloendothelial system, especially the spleen, is particularly important for
destroying capsulated organisms such as S. pneumoniae and H. influenzae, and
therefore patients without a functioning spleen are particularly susceptible to these
organisms.

PNEUMONIA & ALTERED PHYSIOLOGY

Air enters into the lung and reaches the alveoli. In the alveoli OXYGEN moves from
the air into capillaries where it is bound to haemoglobin.
Pneumonia is infection of the terminal air sacs (“alveoli”) and tissue of the lung.
2) MICROBIOTA & INNATE IMMUNE RESPONSE (in the lower respiratory Since the alveoli are the main air-exchange surface for replenishing the blood
tract) oxygen levels, infection and damage to the alveoli in viral and/or bacterial
Many of the organisms that cause pneumonia are part of the normal flora of the pneumonias can be severe and life-threatening.
upper respiratory tract (i.e. mouth and throat – as we reviewed in Session 2).
However, the lower part of the respiratory tract is virtually sterile despite the large Pathogenesis of pneumococcal lobar pneumonia (and similarly for other bacterial
numbers of microorganisms present in the upper airway and in inspired air. causes)
A variety of host defence mechanisms exist to maintain this sterile environment Pneumococci, characteristically in pairs (diplococci), multiply rapidly in alveolar
and one or more of these may be overcome leading to the development of lower spaces and induce extensive oedema. They also incite an acute inflammatory
respiratory tract infection including pneumonia. response in which neutrophils and congestion are prominent. As the inflammatory
Important physical host defences include the cough reflex that guards the lower process progresses, macrophages replace the neutrophils and ingest debris. The
respiratory tract from respiratory secretions. The mucociliary escalator is another process usually resolves.
mechanism. Cilia (tiny hairs in the mucosa of the respiratory tract) bind
microorganisms that are inhaled and waft them upwards and out; this greatly FIGURE (below): Alveoli are packed with an exudate composed mainly of
reduces the number of organisms entering the lower respiratory tract. Cigarette neutrophils. Looking at this picture it is easy to understand why air and oxygen
smoking, narcotics and alcohol consumption can reduce the efficiency of this cannot get into the alveoli and across into the blood stream. It also explains why
important defence mechanism. Recent respiratory viral infections can also affect patients cough up purulent sputum (i.e. sputum with pus = dead neutrophils).
the function of the mucociliary barrier.

Return to Unit Overview

p49
 Leicester Medical School

Community-acquired pneumonia (CAP) is defined as pneumonia (infection of the

lung parenchyma seen on chest X-ray) which develops outside the hospital.
CAP is the sixth most common cause of death worldwide and the leading cause of
infectious death in the USA.
It may be a primary disease occurring in an otherwise healthy patient or it may be
secondary to a predisposing factor such as chronic lung disease, diabetes mellitus,
or malignancy. There are many organisms associated with CAP, with S. pneumoniae
being the most important in all age groups apart from the under 2 year olds.
Respiratory syncytial virus (RSV) is the most common cause in this age group. No
CLINICAL FEATURES OF PNEUMONIA causative agent is found in up to 40% of patients with CAP.
Pneumonia can present with fever, malaise, tachypnea (increased respiratory rate),
and tachycardia (increased heart-rate). In more serious cases, a patient can present Common causes of Community-Acquired Pneumonia
with shock (due to a large drop in blood pressure as the circulation fails resulting in
Streptococcus pneumoniae
multi-organ failure).
Haemophilus influenzae
Patients with acute pneumonia usually have a cough (often productive of purulent
Moraxella catarrhalis
sputum but can be nonproductive).
Staphylococcus aureus
The most important consequence of acute pneumonia is impairment of respiratory
“The atypicals”
function and the patient needs to be assessed urgently by studying their
o Legionella pneumophila
respiratory rate and the oxygen saturation of their blood.
o Mycoplasma pneumoniae
o Chlamydia pneumoniae
CLASSIFICATION OF PNEUMONIA
o Chlamydia psittaci
The broad classification of pneumonia is:
Primary viral pneumonia: Influenza, Parainfluenza, Respiratory syncytial
1. Community acquired pneumonia (CAP). This is the focus of today’s case
virus
study
2. Hospital acquired pneumonia. We will return to this in a later session on
X-ray PATTERNS
hospital acquired infections.
Three main patterns of acute pneumonia on chest X-ray are recognized; lobar,
3. Opportunistic pneumonia affects people whose immune status is defective
bronchopneumonia and interstitial.
(we will have a case of a fungal pneumonia in the session on the
immunocompromised host). Lobar pneumonia is pulmonary consolidation demarcated by border of lung
segment or lobe.
Community-Acquired Pneumonia Bronchopneumonia is seen as patchy consolidation around the larger
airways

Return to Unit Overview

p50
 Leicester Medical School

Interstitial pneumonia is demonstrated by fine areas of shadowing in the NOTES: Adenovirus

lung fields and there is usually no sputum production at presentation. It is
usually seen in mycoplasma, legionella, and viral pneumonia
ADENOVIRUS – An example of a common viral infection
Lobar consolidation – right middle lobe Look up some information on Adenovirus either in a textbook or on the internet.

Chapter 24; See section Adenoviridae.

Make some brief notes – up to 10 points.

Focus on:
Bronchopneumonia – patchy consolidation around the airways
Epidemiology
Clinical significance
Respiratory tract disease
Laboratory identification.
You do not need to know the detailed structure and replication (we will include this
for some other important viruses where understanding the structure and
replication has clinical importance – e.g. HIV/influenza)

Return to Unit Overview

p51
 Leicester Medical School

ADENOVIRUS INFECTIONS: Session 3 Self-Study:

1. Complete the two case studies.

2. Summary notes on Community acquired pneumonia are provided (above) we
will follow this up in a later session by adding in the antibiotic treatment of
pneumonia.
3. Streptococcus pneumoniae. We will have a whole lecture on Streptococcus
towards the end of the Unit. At this stage you should look up some basic
information on Streptococcus pneumoniae as it is such an important microbe
and is highly likely to come up in exams.

Return to Unit Overview

p52
 Leicester Medical School

Understand the principles of supportive and specific treatment for acute

Session 4: Sepsis & Assessment of Infection Group sepsis
Work – HIV & Antibiotics Lectures 02 February 2022
Describe the Sepsis Six Bundle
Preparatory Work Read about meningitis &
sepsis Apply the infection model and the principles of sepsis

View, recall & review MENINGITIS

lectures 5 & 6 Outline the relevant anatomy of the cerebrospinal fluid (CSF)
Watch Katie’s Story Describe the biochemical and cellular composition of CSF and diagnostic
9.00-10.30 Small Group Work 4 Case Studies comparison in meningitis

(LIVE F2F) Describe the clinical features and assessment of meningitis

11:00 – 11:50 Lecture 7 Blood-borne Viruses: HIV Neisseria meningitidis

(Live F2F Simulcast Session)

Describe microbiological features of Neisseria meningitidis

12:00 – 12:50 Lecture 8 Introduction to Antibiotics Describe clinical features of meningococcal disease
& Resistance Describe the pathophysiology of meningococcal meningitis and/or sepsis
(Live F2F Simulcast Session)
Outline the management of Neisseria meningitidis infection
Notes Notes on meningitis, sepsis,
sepsis screening & Neisseria Describe the role of vaccination for Neisseria meningitidis
meningitidis. Antimicrobials
Self-study
Complete case studies Outline a classification of antimicrobials
Learning outcomes for Sepsis, Meningitis, Neisseria meningitidis, Antimicrobials Describe the mechanism of action of the main groups of antimicrobials
SEPSIS (Reminder) Describe the principles of antimicrobial resistance and its impact on
antimicrobial prescribing.
Apply the infection model to a patient presenting with an acute infection Blood-borne Viruses
Understand the features of acute sepsis The learning outcomes related to the two lectures in this series – HIV & hepatitis
Understand the mechanism by which micro-organisms trigger the are included under session 5.
inflammatory cascade

Return to Unit Overview

p53
 Leicester Medical School

Session 4: Preparatory Work Small Group Work 4: Case studies linked to sepsis

1) View, recall and review: View the lectures on Acute Sepsis in the Emergency 4.1 CASE STUDIES - Case Study A
Department (Lecture 5) and Adaptive Immunity (Part 1) (Lecture 6) Recall and A 19-year-old first year university student, living in halls of residence, took to his bed
review the information from the lectures before you start the group work. You
early one Friday evening, complaining of a flu-like illness and headache. He told his
could do this on your own before the session or with your group at the beginning
of the session or a combination of both. friends he was feeling miserable and not able to go out for the evening. The next
morning he did not come for breakfast and his friends went to his room to check how
2) Prepare for the lecture on HIV: he was getting on. They found him drowsy and confused and clearly not well. They
were not sure what to do, but one of the students decided they should call an
Watch this video. This is Katie’s story. Katie lives in the Midlands ambulance and get him to hospital. On arrival at the Emergency Department he was
seen quickly.
An initial assessment by the nurse showed the following:

Temperature: 38.8oC
BP: 109/50 mmHg
3) Preparation for group work questions on meningitis: Read the background Pulse rate: 115/min
information on meningitis at the end of this workbook session or use this during Respiratory rate: 14/minute
group work to help you answer the questions. Oxygen saturation: 94% in room air

4) Preparation for group work questions on sepsis: Read the background The nurse agreed that he was drowsy and confused. She recorded
information on sepsis at the end of this workbook session or use this during his Glasgow Coma Scale (GCS) GCS = 12. We have not covered the
group work to help you answer the questions. Glasgow Coma Scale and you will do this in Year 2. For the present you should know
that this is an assessment of neurological status that is helpful in monitoring patients
5) Preparation for lectures: Read through the lecture slides/summaries for today’s with a range of neurological conditions who are at risk of deteriorating.
lectures Blood-borne Viruses: HIV (lecture 7) and Introduction to Antibiotics &
Resistance (lecture 8) and add any additional notes before and after you view
the lecture.

https://www.bmj.com/content/bmj/365/bmj.l1296.full.pdf

Return to Unit Overview

p54
 Leicester Medical School

a. Calculate the Early Warning Score (using NEWS Tool in Notes section)

The doctor wisely asks the nurse to start some management steps while waiting
for the investigations.
The nurse calls a Foundation Year 2 (FY2) doctor to see the patient urgently.
d. What should these include?
On examination the doctor noted:

The patient protested when his neck was moved (head tilted forward)
The patient did not like it when he used a torch to look at his eye pupils
Rash: the doctor noted a fine rash, which was non-blanching with a slightly
larger lesion on his hand. See figure.

With advice from a senior doctor the FY2 performs a lumbar puncture and sends
the CSF to the lab. The initial result from the lab is:
Specimen Appearance Cells (per Protein Glucose (mg/dL)
mm3) mg/dL
Normal CSF Clear 0–5 12–60 40–70 (should be interpreted as
lymphocytes approx. 50% of blood glucose)

Patient’s CSF Cloudy 800 polymorphs* 75 8;

( Blood glucose = 120)
b.Based on the Sepsis Screening Tool does the patient meet the criterial for
Note: *Polymorphs are granulocytes and neutrophils are the most abundant of
infection and/or sepsis and/or Red Flag sepsis?
these.
e. What is your interpretation?

c. What investigations does the doctor request?

Return to Unit Overview

p55
 Leicester Medical School

An hour later the lab reports on the gram stain of the CSF – see picture below. 4.2 CASE STUDIES - Case Study B – a contrast to Case A
A 4-year-old child was taken to the emergency department by her parents with a 1-
f. What does this show? What is the likely organism? Please ensure you have the day history of fever and irritability. The child was otherwise well, eating and
drinking and alert. There was no cough.
correct name
On examination the doctor noted the following:

Temperature: 38.5oC (Normal 36-38 oC)

Respiratory rate: 25/min (Normal 22-34)
Pulse: 90/min (Normal 80-120)
Oxygen saturation: 98% (Normal 98-100%)
Alert and fully conscious

g. What is the cause of the rash shown above in Q1? Examination of the throat and ears was normal (note: this is a common source of
infection and a fever in a child and so it is important to exclude it).
The abdomen was soft and the chest clear.
However, the doctor noted a faint blanching rash (see below).
The child was alert and fully conscious. The doctor carefully examined the
The patient was transferred to the Intensive Care Unit (ICU). Fortunately he made neurological system (which requires skill in a young child). The doctor decided that
a full recovery. During the recovery it was established that the patient had there was evidence of neck stiffness.
received the Men ACWY vaccine.
h. Why was he not protected by the vaccine?

Return to Unit Overview

p56
 Leicester Medical School

A lumbar puncture was performed. Analysis of the CSF showed the following:
Specimen Appearance Cells (per mm3) Protein Glucose (mg/dL)
mg/dL

Normal Clear 0 –5 lymphocytes 12–60 40 –70 (should be interpreted as

CSF
approx. 50% of blood glucose)

Patient’s Clear 89 mainly 60 50;

CSF
lymphocytes Blood
glucose = 120

a. Based on this information what diagnosis do you consider? c. What is your interpretation?

d. Based on the clinical findings and the CSF, what is the likely microbiological
cause?

b. Is there evidence of sepsis?

e. Will the patient likely have any any residual neurological sequelae following
the acute illness?

Return to Unit Overview

p57
 Leicester Medical School

4.3 CASE STUDIES – Case Study C Ordinarily, the peritoneal cavity is only of capillary thinness; however, it is referred
to as a potential space because excess fluid can accumulate in the peritoneal cavity
A 75-year-old man presented to his GP with a 6 week history of weight loss, resulting in the clinical condition of ascites.
anorexia* and loose stools. The GP referred the patient under the two week wait
scheme to his local hospital where a diagnosis of caecal (large bowel)
adenocarcinoma is made.
The patient is put on the waiting list to have surgery to remove his tumour but two
weeks before this he develops lower abdominal pain whilst at home with his son.
This quickly becomes severe and generalised over his whole abdomen. He also
feels hot and sweaty. His son decides to take him to the Emergency Department.
The doctor who assesses him there is worried that he has developed peritonitis.

Note: You have yet to do the Gastrointestinal Unit and so will not be
familiar with the details of the anatomy. The following is some brief
information on the peritoneum.
Note: *anorexia is used in this context to mean lack or loss of appetite for food (as a
medical condition)
The Peritoneum
http://teachmeanatomy.info/abdomen/areas/peritoneal-cavity/
The peritoneal cavity is a potential space between the parietal and visceral
peritoneum. There are normally NO bacteria in the peritoneal cavity.
It contains only a thin film of peritoneal fluid, which consists of water, electrolytes, This is different to the bowels which contain a large number of bacteria as
leukocytes and antibodies. commensals.
The fluid serves two main functions: If bacteria get into the peritoneal cavity they can cause a severe infection known as
It acts as a lubricant, enabling free movement of the abdominal viscera. peritonitis.
The antibodies fight infection.

Return to Unit Overview

p58
 Leicester Medical School

a. From the history, please identify patient factors that may increase his chance
of developing an infection?

b. The doctor goes to see the patient at 6pm. Review the observation chart (left).
NOTE: Most hospital wards now use observation charts linked to the Early
Warning Score. See EWS table in the notes section. The UHL ‘Adult Sepsis
Screening and Immediate Action Tool’ is also included. Based on the history
and the observation chart:-

Is there clinical suspicion or evidence of an infection?

Does this fulfil the criteria for Red Flag Sepsis?

Return to Unit Overview

p59
 Leicester Medical School

c. The doctor decides to request an urgent chest x-ray. CHEST X-ray for patient with abdominal sepsis
Note - the patient must be standing erect to see this abnormality.
NOTE: When looking at a Chest X-ray it is worth knowing that
tissues with increasing density look whiter. SO REMEMBER:

- air looks black

- fat (as in subcutaneous tissue) looks dark grey
- water and soft tissue looks light grey (e.g. solid organs)
- bone looks off-white

What abnormality is visible on the x-ray?

d. What, therefore, is the most likely mechanism of infection?

Return to Unit Overview

p60
 Leicester Medical School

e. What further investigations would you request to assess this patient? For each f. The doctor notices that the patient has a blood pressure of 106/50 mmHg
investigation please identify the reason you are requesting it. Relating to the following formula taken from the Cardiology Module;

Mean Arterial Pressure = Total Peripheral Resistance (TPR)

x Cardiac Output (CO)

Please explain how sepsis leads to a reduction in blood pressure?

Return to Unit Overview

p61
 Leicester Medical School

g. Considering this, please outline some basic management steps you may consider h. The next day the junior doctor receives a call from the lab. Gram negative rods
in treating this patient – consider both supportive and specific steps? (bacilli) have been identified in the blood culture specimen. (See picture) What is
the likely causative agent? Please make sure you know the correct name of this
organism

Note: As part of your self-study you should then look up some key facts about this
organism. We will cover this microbe again (Lecture 18) in more detail but it may
come up in other case studies before that lecture.

Return to Unit Overview

p62
 Leicester Medical School

Lecture 7 Summary: Blood-borne Viruses: HIV HIV acquisition by risk group (2014)
Learning Objectives
Understand the relevance of HIV in a global and UK context
Describe the principles of HIV structure, replication, testing and MSM
Heterosexual
treatment
IVDU
Apply the infection model to a patient with HIV and acquired Other
immunodeficiency syndrome (AIDS)
Describe the principles of infection transmission and prevention with
regard to HIV.
Over last decade there has been a fall in incidence of new infections but approx. 7%
Global & local relevance of HIV of HIV patients do not know they are infected.

No change in numbers over the last decade there are still many millions of people HIV structure & replication
living with HIV.TB & HIV go hand in hand globally. Substantially fewer deaths due to HIV is a single stranded RNA retrovirus whose structure is below:
HIV in the UK. Biggest burden of HIV infections in Africa. Untreated leads to AIDS and
NOTE: link the structure of the HIV virus to other viruses
unusual infections such as oral candidiasis, Kaposi’s sarcoma and Pneumocystis
and how the adaptive immune response helps to fight off
pneumonia (PCP) which is a serious infection caused by the fungus Pneumocystis
the infection.
jirovecii.
HIV/AIDS – infection model
Reactivated viruses, yeast, mould and protozoan infections are common in untreated Attachment to cells is accomplished via the gp120 portion
AIDS patients. Most people live with a chronic infection but left untreated, death is of the env (envelope) gene product on the HIV surface,
the consequence. Overall rates in the UK are approx. 1.1/1000 with 69% of cases in which preferentially binds to the CD4 molecule (a
men, 31% in women but in Leicester this rate is much higher at 3.8/1000. glycoprotein found on the surface of T cells) Thus, the
virus infects helper T cells, lymphocytes, monocytes, and
dendritic cells, which produce this glycoprotein on their
surface. The ssRNA is converted to dsDNA and incorporated into the cell’s genome.

Return to Unit Overview

p63
 Leicester Medical School

Life cycle of HIV Transmission and prevention of infection

Transmission is as follows: Contact of infected bodily fluids with mucosal tissue /
blood / broken skin – sexual contact, blood transfusion, contaminated needles,
vertical transmission to fetus during delivery. Some medical procedures carry a risk
of transmission, e.g.: - blood/blood-products, skin grafts, organ donation – now all
screened for HIV in the UK. The graph below shows the progress of the infection:

Once CD4 cell count drops below 350 cells/µl you begin to get more symptoms – a
cold you can’t shake, athlete’s foot – more frequent infections that perhaps you have
never had before. Once less than 200 cells/µl – you begin to see severe infections,
For an animation describing HIV replication AIDS defining symptoms and cancers linked with HIV/AIDS.
Acute HIV infection presents with symptoms which may not send you to your doctor
– a cough/cold. But highly infectious at this point as high viral load. But as CD4 cell
count falls you begin to see more recurrent infections and diseases associated with
severe HIV including CMV, Cryptococcal meningitis, reactivation of TB, fevers that do
not go away, wasting of the body etc.

Return to Unit Overview

p64
 Leicester Medical School

Certain factors affect HIV transmission unexplained blood abnormality, lymphoma, anal cancer, cervical intraepithelial
neoplasia (CIN), any STI/ Hep B/ Hep C.
Type of exposure
type of sexual act Every patient is treated as soon as possible with ARVs (anti-retroviral drugs)
transfusion vs needlestick vs mucous membrane regardless of CD4 (significant benefits in AIDS & non-AIDS morbidity and mortality).
Anti-retroviral drugs (ARVs) are used to treat patients in order to ensure an
Breaks in skin or mucosa undetectable HIV viral load allowing the CD4 count /immune system to recover,
other STI (Inflammation of genital tract) reduce general inflammation, and reduce risk of transmission, with the ultimate goal
sexual assault of both a good quality of life and a more normal lifespan.
Anti-retroviral drugs work by targeting the binding (CCR5 – entry inhibitor), the
Any protective measure to reduce transmission: Condom use, use of clean new enzymes responsible for incorporation of viral DNA into host DNA (Integrase
needles, treatment during pregnancy. inhibitor), for breaking down the large proteins into smaller units (protease inhibitor)
during the maturation phase of the viral life cycle and reverse transcriptase (Non-
Viral level (viral load) in blood nucleoside reverse transcriptase inhibitor (NNRTI) – non-competitive inhibitor or
Transmission unlikely if undetectable viral load Nucleoside reverse transcriptase inhibitor (NRTI) - competitive substrate inhibitor)
Three ARVs are given since there are millions of rounds of viral
replication each day. In addition the virus mutates every 2-3 rounds
Living with HIV in the UK which means that resistance to drugs develops in days. Therefore with 3 drugs there
Life expectancy and quality of life are now excellent: 90:90:90 i.e. diagnose 90% of is less chance to develop resistance. Common strategy in treating infections – e.g.
cases, treat 90% of these cases and of those expect 90% to live with HIV under two types of antimalarial to treat malaria. Patient must keep taking drugs all their
control. A HIV patient can expect to live to 78 years provided there has been early life.
detection and good CD4 counts alongside good adherence to the treatment regimen
with healthy lifestyle – likely to die of normal causes. Late detection leads to the Potential strategies to treat and reduce the prevalence of HIV
worst case prognosis (x10 greater risk of death in first year)
• Increase condom usage
HIV Tests & Treatments • ARV treatment as prevention
• Wide-spread testing/screening
There are several diagnostic tools we can use to detect HIV – a) serology – detects
• Prevention of mother-to-child transmission
both antigens (viral proteins) and antibodies to HIV in the blood, b) PCR – detects the
• Post-exposure prophylaxis (PEP)
viral nucleic acid and c) rapid testing – usually picks up the antibodies to HIV in either
• Pre-exposure prophylaxis (PrEP)
blood or saliva. Everyone should be tested especially if the rate in the community is
greater than 2 in 1000. Any patients presenting with any of the following conditions • Male circumcision
should also be tested: bacterial pneumonia/TB, meningitis/dementia, severe • Combine the above
psoriasis, recurrent/multi-dermal shingles, chronic diarrhoea/weight loss, any • ? future vaccine

Return to Unit Overview

p65
 Leicester Medical School

What is the half-life (decides dosing frequency)?

There are obviously several ethical dilemmas surrounding HIV - the psychological Does it interact with other drugs?
impact of diagnosis and dealing with the stigma associated with HIV. Of course Is there toxicity issues?
clinicians need to consider patient confidentiality versus the health of the mother, Does it require therapeutic drug monitoring?
the health of an unborn child, the health of a sexual contact (husband), the health of
General Antibiotic Characteristics:
the older child alongside the risk to patients / staff at workplace.
Therapeutic window – some medications have a narrow therapeutic window e.g.
gentamicin – therefore, we need to measure its levels to monitor activity.
What are the different ways to measure antibiotic activity?
Lecture 8 Summary: Introduction to Antibiotics &
Disc Sensitivity/Diffusion Testing – putting the organism on the agar plate and
Resistance
putting ‘paper discs’ containing antibiotics and reading the zone of clearance.
Learning Outcomes:
Minimum Inhibitory Concentration (MIC) – The first concentration of antibiotic that
Outline a classification of antimicrobials inhibits the growth of bacteria. Done via: broth microdilution OR E-test strip.
Describe the mechanism of action of the main groups of antimicrobials
Types of antibiotic resistance:
Describe the principles of antimicrobial resistance and its impact on
antimicrobial prescribing. Intrinsic: a bacterial species is naturally resistant to a certain antibiotic or family of
Describe the concept of antimicrobial stewardship antibiotics, without the need for mutation or gain of further genes. The antibiotic
Outline measures to ensure the appropriate use of antimicrobials does not target the specific characteristics of the bacteria, therefore, unable to gain
Describe the principles of antibiotic resistance. access to bacteria – this is usually a permanent ‘resistance’.
Acquired: occurs when a particular microorganism obtains the ability to resist the
Antimicrobials is a broad term that is includes anti-bacterials (aka antibiotics), anti-
activity of a particular antimicrobial agent to which it was previously susceptible.
fungal, anti-viral, anti-protozoal agents.
This change is usually permanent and via chromosomal gene mutation/horizontal
How to choose an antibiotic? gene transfer (via plasmids), there are several mechanism for resistance:
Is it active against target organism? Think about what characteristics of the Enzymatic modification or destruction of antibiotics
bacteria that is being targeted by the antibiotics. Enzymatic alteration of antibiotic targets or mutations of bacterial target
Does it reach the site of infection? Think about HOW the drug is sites
administered (i.e. is it available in the right formulation (IV vs oral)?). Also, Overexpression of efflux pumps (multi drug resistance)
think about what mechanisms are in place for access to infection site? (i.e.
blood-brain barrier)

Return to Unit Overview

p66
 Leicester Medical School

Adapted: if there are a sub-therapeutic levels of antibiotics, this only causes a mild Metronidazole - SHOULD NOT TAKE THIS WITH ALCOHOL!
stress response to the bacteria – hence it will respond by becoming resistant to the
Facts of different antibiotics:
antibiotic
Examples of beta-lactam antibiotics: penicillin, carbapenem, cephalosporin
Anti-fungals:
One of the major side-effects of cephalosporin is clostridiodes difficile
Azoles (inhibit cell membrane synthesis): infection
Fluconazole treats candida (yeast infection) Carbapenem is usually considered as reserve antibiotic for Gram-negative
Itra-/Vori-/Posa-conazole treats hospital-acquired fungal infections such as infections & generally safe in penicillin allergy.
aspergillus (mould infection). Vancomycin is not easily absorbed – therefore, a perfect treatment for
C.difficile infection (taken via oral route). Also, this is the reason why we
Polyenes (inhibit cell membrane function) don’t prescribe IV vancomycin for severe C-difficile infection. It also has a
Nystatin treats candida narrow therapeutic window.
Amphotericin (IV) treats SYSTEMIC fungal infections (due to aspergillus). SE: Tetracyclines (e.g. doxycycline) should NOT be given to children <12 years,
nephrotoxic. pregnant and breastfeeding women (causes staining of developing teeth).
Side effects of fluoroquinolones are tendinitis and rupture, aortic
Anti-virals: dissection, central nervous system effects & C.difficile infection.
Aciclovir: Side effects of co-trimoxazole (trimethoprim/sulphamethoxazole): aplastic
anaemia, Stevens Johnson syndrome.
Treatment for Herpes Zoster (shingles, chicken pox) / Herpes Simplex
(genital herpes, viral encephalitis)
Prevents viral replication – given at early stages of infection.

Oseltamivir (Tamiflu)
Treatment for Influenza A & B.
Prevents viral replication by inhibiting viral neuraminidase – therefore,
reducing spread of virus.

Metronidazole (anti-bacterial and anti-protozoal)

1. Amoebae (dysentery & systemic)
2. Giardia (diarrhoea)
3. Trichomonas (vaginitis)

Return to Unit Overview

p67
 Leicester Medical School

Antibiotics that prevent protein synthesis – 2 methods:

1. Acting on 30S ribosome subunit
Tetracycline
Aminoglycoside
2. Acting on 50S ribosome subunit
Macrolide
Linezolid

Nitrofurantoin
Mixed between preventing protein synthesis and DNA/RNA synthesis.

Return to Unit Overview

p68
 Leicester Medical School

NOTES: Meningitis – Background Information 2. INTERPRETING THE CSF TO MAKE A DIAGNOSIS

Appearance White cell Usual cell Protein Glucose

Meningitis is the name for inflammation of the meningeal lining of the brain and
count type g/litre mmol/litre
spine. The preciseanatomical details are beyond the scope of
(cells/µl)
this unit but will be covered in more detail in your second year.
NORMAL Clear <5 - <0.4 2.6 – 4.6 (≈
2/3rds
However you do need to understand plasma is filtered from the blood by the
serum
epithelial cells to produce cerebro-spinal fluid (CSF). In this way, the exact chemical
concen-
composition of the fluid can be controlled. Cerebrospinal fluid (CSF) is a clear,
tration)
plasma-like fluid. It contains glucose (about 2/3rds that of the blood) and some
Bacterial Often Increased Neutrophils increased Low
protein. There are few or no cells (and any there are - are likely to be lymphocytes).
cloudy (normally
We can use samples of CSF to make a diagnosis of meningitis and interpret the likely
>100
causative pathogen – bacterial, viral or fungal. How these samples are obtained will
Tuberculous Clear / Increased Lymphocytes- Significant low
be covered in Phase 2. meningitis cloudy 5-500 see note increase
below
1. CAUSES OF MENINGITIS Lymphocytes
Viral Clear Increased 5- Moderate Normal or
This table has some of the commonest causes of meningitis in adults worldwide.
1000 increase slightly
There are differences seen depending on age and geography. Neonates have a
decreased
different list of microbes. Clear/cloudy Lymphocytes
Fungal Increased 5- Increased low
500

BACTERIA VIRUSES FUNGI

**You must know the pattern for bacterial and viral infections for the Phase 1
Neisseria meningitidis Enteroviruses: Cryptococcus
exams. It is logical if you think it through.
Streptococcus pneumoniae Echoviruses neoformans (occurs
Haemophilus influenzae Coxsackie viruses A and B in HIV/AIDS which
Note:- Bacterial meningitis is often characterized by increased white cells in
poliovirus we cover in a later
CSF microscopic examination with mostly neutrophils (>80%) while in viral
Herpes viruses: session)
meningitis, lymphocytes predominate (>50%) but with traces of
Herpes simplex virus 1 and 2
neutrophils. Be aware that sometimes neutrophils will be written as
polymorphs – this refers to the fact that the cells are granulocytes of which
neutrophils are the predominant cells visible.

Return to Unit Overview

p69
 Leicester Medical School

In the case of TB meningitis, the presence of lymphocytes can be explained by NOTES: SEPSIS
the fact that the immune response against mycobacterium tuberculosis (MT)
mostly involves the type IV hypersensitivity reaction that is driven primarily T
cells. Although MT is a bacterium, the host requires a T cell response to SEPSIS
effectively contain the infection as it is extremely difficult to get rid of MT
(hence the formation of granulomatous reaction in the lungs for example). Definition:
Another example of the immune response to MT, is during the tuberculin Sepsis describes a syndrome of life-threatening organ dysfunction caused by a
hypersensitivity reaction, also known as the mantoux test, where you see a dysregulated host response to infection. It is usually caused by bacterial infection.
local skin reaction due an influx of T lymphocytes as well as macrophage Septic shock occurs when severe sepsis leads to circulatory failure and metabolic
activation at the site of injection with MT antigen (tuberculin). abnormalities, defined as persisting hypotension requiring active medical treatment
and biochemical evidence of disturbed metabolism (raised lactate).
The sample of CSF is also sent for
1) Gram stain Causative agents:
2) PCR for viruses & some bacteria
3) Culture Causative agents depend on the syndrome, host and clinical context. Gram-negative
infections account for an increasingly large proportion of cases, particularly of
3. CLINICAL FEATURES OF MENINGITIS healthcare-associated infections

A patient will have: Clinical features:

General features of an infection such as fever, increased pulse rate
Symptoms and signs due to inflammation of the meninges: Common presenting syndromes include pneumonia, intra-abdominal and urinary
a) headache sepsis, and skin and soft tissue infections. You will therefore expect to see all the
b) photophobia (difficulty looking at bright lights) common features of an infection, with the addition of features of a body organ that
c) vomiting is not functioning and failing to work properly. Commonly more than one body
d) neck stiffness on flexion of the neck system is affected. This can include:
e) irritable (progressing to reduced level of consciousness) Cardiac
Other findings dependent on severity (e.g. sepsis) or complications. Respiratory
Central Nervous System
Liver
Gastro-intestinal tract

Return to Unit Overview

p70
 Leicester Medical School

Investigations: respiratory distress syndrome, and renal replacement therapy for acute kidney
Aim to confirm the presence, source and severity of infections and alternative injury. Patients who present in septic shock or who fail to respond to initial therapy
diagnoses. Where possible, it is important to obtain samples for microbiology before should be referred early to intensive care for further organ support.
administering antibiotics to maximize culture sensitivity. Except in exceptional
circumstances, at least one set of blood cultures should be obtained. The timing of Pathophysiology:
other cultures (e.g. urine, cerebrospinal fluid, and repeat blood cultures) depends on The pathophysiology of sepsis is complex. The lecture on sepsis mentioned this
the clinical presentation, illness severity and likely delay in obtaining a sample; in briefly. The lecture on the Innate Immune response covered the standard response
general, however, antibiotics should not be delayed in true sepsis. of the innate immune system in more detail.

Management: In ‘sepsis’ the normal immune response which is designed to recognise and
The key principles of management are prompt recognition, early appropriate eliminate the microbe becomes greatly exaggerated (or dysregulated) so that the
antimicrobial therapy and supportive treatment. consequence for the patient is damage inflicted by their own immune response.
That response is not only exaggerated but also perpetuates itself so that the patient’s
Elements of the initial management of sepsis are incorporated into the Sepsis Six clinical condition deteriorates and may be fatal.
bundle of care (this will be tested and we suggest you write it out). Rapid clinical The following is a brief summary of some of the key factors linked to the immune
assessment is indicated for all patients with suspected sepsis. Rapid delivery of a system that cause problems with sepsis. NOTE: the combination of factors in an
bundle of care comprising elements of the Sepsis Six has been associated with individual patient will vary depending on the microbe, genetics and local factors.
reduced mortality in sepsis.
Immune-system activation (See Dr Amrani’s Lecture from Week 2):
Treatment: The innate immune system is activated by bacterial cell wall products, such
as lipopolysaccharide (endotoxin) binding to host receptors, including Toll-
Antimicrobial therapy should be administered as rapidly as possible in sepsis, and like receptors (TLRs). These are widely found on monocytes and
within 1 hour, as early appropriate antibiotics are associated with improved survival. macrophages, and some types are found on endothelial cells. These have
The choice of initial empirical antibiotic therapy depends on the presenting clinical specificity for different bacterial, fungal, or viral products.
syndrome (including likely focus of infection, neutropenia, etc.) and should follow Activation of the innate immune system results in a complex series of cellular
local guidelines based on the most likely pathogens and susceptibility profiles. and humoral responses, each with amplification steps:
o Pro-inflammatory cytokines such as tumour necrosis factor (TNF)
Supportive treatment includes oxygen to treat hypoxia and ensure good tissue and interleukins 1 and 6 are released, which in turn activate immune
oxygenation, and intravenous fluids to optimize tissue perfusion. Vasopressors and cells.
inotropes (drugs to improve cardiac output and maintain blood pressure) may be
required in septic shock, mechanical ventilation for severe pneumonia or acute

Return to Unit Overview

p71
 Leicester Medical School

o The complement system is activated, and mediates activation of

leukocytes, attracting them to the site of infection where they can Each of the above statements has a complex pathway of molecules and receptors.
directly attack the organism. At this stage we will not cover these in detail. However, they will link with other
units you are studying.
The endothelium and coagulation system:
The vascular endothelium plays a major role in the host’s defence to an
invading organism, but also in the development of sepsis. Activated
endothelium not only allows the adhesion and migration of stimulated
immune cells, but becomes porous to large molecules such as proteins,
resulting in the tissue oedema.
Alterations in the coagulation systems include an increase in procoagulant
factors, such as plasminogen activator inhibitor type I and tissue factor, and
reduced circulating levels of natural anticoagulants. Clinically this is seen as
clotting in small vessels but often a tendency to bleeding at other sites. This
is the typical picture seen in sepsis caused by Neisseria meningitides (as in
the lecture).

Inflammation and organ dysfunction:

Through vasodilatation (causing reduced systemic vascular resistance) and
increased capillary permeability (causing extravasation of plasma), sepsis
results in relative and absolute reductions in circulating volume.
A number of factors combine to produce multiple organ dysfunctions.
Relative and absolute hypovolemia are compounded by reduced left
ventricular contractility to produce hypotension. Initially, through an
increased heart rate, cardiac output increases to compensate and maintain
perfusion pressures, but as this compensatory mechanism becomes
exhausted, hypoperfusion, and shock may result.
Impaired tissue oxygen delivery is exacerbated by pericapillary oedema.
This means that oxygen has to diffuse a greater distance to reach target cells.
There is a reduction of capillary diameter due to mural oedema and the pro-
coagulant state results in capillary microthrombus formation.

Return to Unit Overview

p72
 Leicester Medical School

Additional Information: Sepsis Screening & NEWS

Return to Unit Overview

p73
 Leicester Medical School

The NEWS is based on a simple scoring system in which a score is allocated to

physiological measurements already undertaken when patients present to, or are
being monitored in, hospital.

Six simple physiological parameters form the basis of the scoring system:
1 respiratory rate
2 oxygen saturations
3 temperature
4 systolic blood pressure
5 pulse rate
6 level of consciousness or new confusion

A score is allocated to each as they are measured, the magnitude of the score
reflecting how extreme the parameter varies from the norm. This score is then
aggregated, and uplifted for people requiring oxygen. It is important to emphasise
that these parameters are already routinely measured in hospitals and recorded on
the clinical chart.

National Early Warning Score NOTE: For level of consciousness or new confusion: The patient has new-onset
confusion, disorientation and/or agitation, where previously their mental state was
The NEWS provides the basis for a unified and systematic approach to the first normal – this may be subtle. The patient may respond to questions coherently, but
assessment of acutely ill patients and a simple track-and-trigger system for there is some confusion, disorientation and/or agitation. This would score 3 on the
monitoring clinical progress for all patients in hospitals. This is allied to NEWS system
recommendations on the urgency and competency of the clinical response, as well
as the most appropriate environment for ongoing care of the most acutely ill
patients. In so doing, the NEWS provides a template for the staff and infrastructure
requirements for modern acute clinical care.
https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news

Return to Unit Overview

p74
 Leicester Medical School

NOTES: Neisseria Meningitidis What are the main clinical features?

Neisseria meningitidis causes both meningitis and septicaemia. They can occur
together or separately.
Neisseria meningitidis
Neisseria meningitidis is a Gram negative diplococcus that may be found within
Meningitis relates to the bacteria in the cerebrospinal fluid that surrounds the brain
polymorphonuclear leukocytes (neutrophils). About 20% of the population carry this
and spine. The bacteria attach to the meningeal lining and cause intense
bacterium in the oropharynx. The organism is surrounded by a polysaccharide
inflammation. This is responsible for the symptoms of meningitis that include
capsule. There are 13 antigenic “serogroups,” depending on the antigenic differences
headache, photophobia (difficulty looking at bright lights) and vomiting.
in the polysaccharide capsule.
Septicaemia relates to the bacteria in the blood.
Refer to Lippincott’s Illustrated Reviews Microbiology Chapter 11 Neisseria. Scroll
Neisseria meningitidis in the blood triggers an intense host immune response.
down to Neisseria meningitides
Fever: The patient will have a fever.

Sepsis: The patient will have the features of ‘sepsis’ as outlined in the lecture
and sepsis notes. Typical features will include reduced level of
On the basis of the lecture and Lippincott’s make your own notes including an consciousness, tachycardia, low blood pressure, poor peripheral circulation,
infection model diagram. You should have about two pages of notes. You do not reduced urine output.
need to know the culture conditions.
Disseminated Intravascular Coagulation (DIC) – see below
NOTE: Neisseria meningitidis septicaemia is commonly referred to as meningococcal
septicaemia.
Rash - see below

Clinical features of Neisseria meningitidis infection

What is DIC? Disseminated intravascular coagulation is a syndrome of widespread
This was outlined in the lecture but is not well covered in Lippincott’s. You can look
intravascular activation of coagulation. You will be taught about coagulation
this up in a clinical textbook. To make it easier I have added some notes on the
separately in the MEH module. Coagulation is a balance of coagulation and anti-
clinical features of Neisseria meningitidis infection where there is relevant
coagulation factors. Details will not be covered here.
information that is additional to the notes on sepsis
The main mechanisms of DIC are inflammatory cytokine-initiated
Who gets Neisseria meningitidis infection?
activation of tissue factor-dependent coagulation and insufficient
Rates of meningococcal disease are highest for young children and increase again for
control of anticoagulation pathways. At a simplistic level the coagulation process
adolescents and young adults.
goes out of control. Lots of small clots form. These use up many of the

Return to Unit Overview

p75
 Leicester Medical School

anticoagulation factors. The consequence is that there is bleeding occurring at the

same time as the small clots are being formed. As an example platelets (which are Figure 1. Petechiae and tumbler test
important in forming clots) are used up in making the clots and the platelet count
becomes low. This allows for the small bleeds into the skin (petechiae). DIC is more
than the low platelet count. The consumption and dysfunction of anticoagulant
proteins and the widespread damage to blood vessels occurring at the same time
makes this potentially lethal and difficult to manage.

Are there other causes of DIC? There are many causes of DIC in addition to severe
infections. You will come across these separately e.g. trauma, some obstetric
calamities, transfusion reactions and others.
2. Ecchymoses: The petechial lesions can coalesce and form larger lesions that
appear ecchymotic. Ecchymoses (diameter >10 mm) are mainly noted in patients
Rash
with severe DIC. These lesions are secondary to subcutaneous hemorrhage. See
Do all patients have a rash? This is present in many but not all patients (30 – 75%)
figure 2.
How is the rash described? The rash can take different forms as the illness develops
Figure 2 Ecchymoses
(see 1 – 3 below)
1. Petechiae
2. Ecchymoses
3. Necrosis

1. Petechiae: Initially it is discrete lesions 1 to 2 mm in diameter, most frequently on

the trunk and lower portions of the body (see figure 1) but also on mucosal
membranes and sclera. These lesions are described as petechial. A petechial rash is
commonly associated with a low platelet count and is a tiny bleed into the skin.
Petechiae of meningococcemia are usually larger and bluer than pinpoint petechiae
caused by thrombocytopenia – reflecting the complex pathophysiology of DIC and 3. Necrosis: Necrosis is the death of tissue. In meningococcal sepsis, necrosis can
meningococcal sepsis. occur affecting digits or limbs and may require amputation. Necrosis is due to the
Tumbler test: The rash does not blanch when pressure is applied. This is the basis combination of vascular damage, lack of blood and oxygen (i.e. perfusion) to skin
of the tumbler test. This is the case for all petechial rashes. See figure 1. and the periphery, clots in small vessels and haemorrhage. See figure 3.

Return to Unit Overview

p76
 Leicester Medical School

Figure 3 Necrosis Session 4 Self-Study:

1. Complete the case studies

2. Notes on meningitis and CSF have been provided. You will be required to know
this.
3. Notes on sepsis have been provided that you should use alongside the lecture.
The case studies provide examples of how this will be tested in the exams. You
may want to make your own version.
4. Notes on Neisseria meningitidis have been provided with just a few points that
you need to look up and add to these notes. It is important you do this.
5. At this stage do not make additional notes on antimicrobials. In session 6 we
Management of Neisseria meningitidis septicaemia
will provide case studies linked to management and that is the time you need
The management was covered in the lecture and follows the principles of sepsis
to consider how best to learn about antimicrobials.
management:
Early recognition
Early administration of antibiotics. The recommendation if Neisseria
meningitidis is suspected is to give intravenous CEFTRIAXONE
Urgent investigation
Supportive care, often in an intensive care unit to manage organ
dysfunction and DIC.
Notify Public Health
Prevention

Vaccination for Neisseria meningitides

Look at the NHS site on meningitis vaccination. Make a list of the vaccines available
for Neisseria meningitides.

Return to Unit Overview

p77
 Leicester Medical School

Apply the infection model to a patient with HIV and acquired

Session 5: HIV Case Studies & Antimicrobial immunodeficiency syndrome (AIDS)
Stewardship 09 February 2021
Apply the infection model to a patient with Hepatitis B and Hepatitis C
Preparatory Work View, recall & review Describe the principles of infection transmission and prevention with
lectures 7 & 8 regard to blood borne viruses
Visit the BHIVA website &
read the testing guidelines. Antimicrobial Stewardship
9.00-10.30 Small Group Work 5 HIV/AIDS Case Studies Describe the concept of antimicrobial stewardship
(LIVE F2F) including some ethical Outline measures to ensure the appropriate use of antimicrobials
aspects

11:00 – 11:50 Lecture 9 Blood-borne Viruses: Session 5: Preparatory Work

(Live F2F Simulcast Session)
Hepatitis
1) View, recall and review: View the lectures on Blood Borne Viruses HIV (Lecture
12:30 – 13:20 Lecture 10 Antimicrobial Stewardship 7) and Antibiotics & Resistance (Lecture 8) Recall and review the information
from the lectures before you start the group work. You could do this on your
(Live F2F Simulcast Session) own before the session or with your group at the beginning of the session or a
Notes HIV combination of both.
Needle Stick Injury
2) Preparation for lectures: Read through the lecture slides/summaries for today’s
Self-Study Complete case studies lectures Blood-borne Viruses: Hepatitis (lecture 9) and Antimicrobial
Stewardship (lecture 10) and add any additional notes before and after you
view the lecture.
Learning Outcomes: 3) Preparation for group work on HIV: Look at the pages in Lippincott’s Illustrated
Reviews Microbiology – Chapter 28 on Retroviruses and AIDS
Blood borne viruses
Understand the relevance of HIV, Hepatitis B and Hepatitis C in a global and
UK context
Describe the principles of HIV structure, replication, testing and treatment

Return to Unit Overview

p78
 Leicester Medical School

It has more detail than you need; especially the RNA/DNA details but the diagrams links to the treatment and how drugs work to control HIV. The basic actions of the
are a useful summary. drugs was covered in the lecture.
On the next page is guidance for the group work. You must do the reading before
the group work session so that you are prepared to start the case studies.

You will also need to access the following information for the case studies. The British
HIV Association guidelines on testing can be viewed on this link. It is easy to read.
The Terrence Higgins Trust is also a useful source of information.

The document can be downloaded as a PDF. It is worth reading and will be useful for
the group work. In particular the sections on who should be tested, the conditions
with which patients may present which would warrant testing for HIV and barriers
to testing. We will pick up on some of these points in the group work session.

The following videos are also very useful to understand more about HIV and its
treatment. These give more information on How HIV infects human cells and
replicates.
The first is very general

The second is better and contains details on the molecules and receptors as well as
the genetics. The reason for understanding the replication process is that it directly

Return to Unit Overview

p79
 Leicester Medical School

Small Group Work 5: HIV

5.1 CASE STUDY A

A 38-year-old woman is admitted to the Acute Medical Unit having being

bought to the hospital by her partner. She has been having fever and cough for
the last 2 weeks, as well as a severe headache. There has also been 10kg of
weight loss over the last 6 months.

On examination she looks to be in pain. Her speech is confused and incoherent.

She is very thin and has white patches on her tongue. Her temperature is
38.5 C, respiratory rate is 20 breaths/minute, heart rate is 92 beats per minute,
blood pressure is 105/75mmHg, and O2 saturations are 97% on air. Her chest
sounds clear. She has mild pain on bending her neck forwards (neck stiffness)
but no neurological abnormality.
b. Which initial investigations would you request and why?

a. You are concerned that this patient may be immunocompromised. Using

information from the lecture, what else do you want to know from the history
and/or examination to help make a diagnosis?

Return to Unit Overview

p80
 Leicester Medical School

c. You would like to test the patient for HIV infection. Due to her confusion, she d. The Medical Registrar on-call organizes an investigation, which is shown in the
does not have the capacity to give informed consent (see BHIVA testing guidelines image below.
section 9). What might be the issues regarding HIV testing in this situation? Can
What kind of investigation is it, and which organ is shown?
you test without her consent? Should you ask her partner for his permission to
test? What abnormalities can you detect?
Note: Capacity & consent will be covered in further detail through CHDD & SIMS.

Return to Unit Overview

p81
 Leicester Medical School

h. Below is the patient’s chest X-ray. Can you describe the abnormality?
The following blood test result is obtained: Note: - Although you have not done the respiratory system nor Imaging, you can
still point out the main abnormal area.
HIV serology - positive

e. Which of the following two statements is true and why?

I. The presence of HIV antibody means the patient has confirmed infection with
HIV
II. The presence of HIV antibody means the patient has been exposed to HIV,
but has mounted an immune response and is clearing the infection

f. A CD4 count is requested for the patient. What is the result likely to be?

g. Which conditions could be the cause of the appearance in the investigation (Qd)?

Return to Unit Overview

p82
 Leicester Medical School

i. The patient’s sputum is sent to the laboratory and on microscopy shows acid-fast k. After treatment is started, the patient begins to improve. On further questioning,
bacilli. What special stain is used to detect these bacilli? Which infection is likely to she informs you that she has been in a relationship with her current partner for the
be present in both the images above? last 6 months. She is divorced and has a 10-year old son. She works as a theatre
nurse in the hospital she has been admitted to, and is worried about other staff
members finding out about the diagnosis. What are the wider social, public health
and infection control issues that need to be considered? Think about consent and
confidentiality.

Scroll down to ‘Direct visualisation of the organism’ and ‘B’ Acid-fast stain.

j. What steps would you take to treat this patient, in the short and long-term?
Consider the acute symptoms, the diagnosis of HIV, and the management of
additional infection(s). Also consider the potential risk of transmission to others,
and how you would protect them. Indicate principles only.

Return to Unit Overview

p83
 Leicester Medical School

b. He tells you that he had unprotected sex with someone he met on the internet
5.2 CASE STUDY B - HIV a week ago. He admits to having had unprotected sex with casual partners before,
including with a commercial sex worker. On examination, his penis is inflamed and
You are a GP and your next patient is a 28 year old man whom you have never there is a creamy discharge from the urethral meatus.
met before. You see from the notes that he has been attending the practice Which infection(s) could be causing these symptoms? What type of
regularly over the last 12 months. Initially, he was seen for a flu-like illness infection is it? How is it treated?
where he developed muscle aches, mouth ulcers and a rash, and was
Note: Sexually Transmitted Infections, other than HIV, will be covered in the
diagnosed with glandular fever. This improved with simple pain-relief.
Reproductive Unit in Year 2. However, these infections often co-exist and HIV may
only be detected when the patient attends a genitourinary medicine (GUM) or
Since then, he has been treated for a chest infection which required 2 weeks sexual health clinic.
of antibiotics; 2 episodes of shingles on his back which needed acyclovir (anti-
viral treatment); and tinea pedis (athlete’s foot) requiring anti-fungal cream.
He has now come to see you because of pain and burning on passing urine
for the last 3 days. His wife has attended with him as she is very worried about
him.

a. You are concerned that his current presentation may be a sexually transmitted
infection. You want to ask further questions including a sexual history. What would
be the best way to do this?

Return to Unit Overview

p84
 Leicester Medical School

c. A number of features in his history give you concern that he may have underlying Gastroenterology
HIV infection. What are they? Look at the following website, and document
medical problems that would be an indication for HIV testing:

Oncology

Put down at least one condition for each system. The object of this question is to
illustrate the range of conditions where HIV must be considered.
Neurology

Conditions where HIV testing should be

offered

Respiratory
Other

Dermatology

Return to Unit Overview

p85
 Leicester Medical School

d. He agrees to have a HIV blood test, and this comes back as positive. You ask If I tell my wife about the HIV, she might leave me. She looks healthy
him to come and see you again, on his own, to discuss the result. He is deeply enough so she can’t have HIV, right? As long as I use condoms she won’t
upset by the conversation, and has a number of questions for you. How would be at risk, will she?
you respond to each of his questions below?

I wish I’d never had the test! I’ve heard there’s nothing that can get rid of
it. Am I going to die?

Will you tell my wife, even if I don’t give my permission?

Where and when did I get it?

I have a 6-year old son. What is the chance of him being positive?
Is everyone going to find out about my result? Who needs to know?

Return to Unit Overview

p86
 Leicester Medical School

5.3 Table of Conditions Associated with HIV/AIDS PCP

The following table shows a list of AIDS-defining opportunistic infections. Complete
the table (next page). You may use web references, including
https://www.cdc.gov/hiv/basics/livingwithhiv/opportunisticinfections.html
Note: I suggest you put in two facts linked to presentation for each infection. The
intention is for you to appreciate the wide range of infections and presentations Cryptococcal
that occur with AIDS. If this is taking up too much time then complete this as self- disease
study.

INFECTION TYPE & NAME OF PRESENTATION (Symptoms /

ORGANISM signs / investigation findings)
(virus/bacteria/
fungus/
protozoa/helminth) CMV
Tuberculosis

Crypto-
Toxoplasmosis sporidiosis

Return to Unit Overview

p87
 Leicester Medical School

Lecture 9 Summary: Blood-borne Viruses: Hepatitis

Learning Objectives

Understand the relevance of Hepatitis B and Hepatitis C in a global and

UK context
Describe the principles of Hepatitis structure, replication, testing and
treatment An “Icteric sclera” means the white of the eye is yellow. This is usually a sign of
jaundice, which has a variety of causes.
Apply the infection model to a patient with Hepatitis B and Hepatitis C
Describe the principles of infection transmission and prevention with
regard to Hepatitis

The global and local relevance of Hepatitis B & Hepatitis C

Greater numbers living with hepatitis than HIV worldwide – go on to develop end
stage liver disease if left untreated. Far greater numbers of untested individuals since The structure and function of the liver is covered in more detail in other units – in
it is not on screening programmes where it is endemic. particular the liver will be covered in much more detail in the GI unit in year 2. The
production and excretion of bilirubin is also covered in more detail in other units.
Viral hepatitis & its detection You need to understand that if the liver is not functioning properly and is inflamed
due to the presence of hepatitis it cannot work well and as a result cannot conjugate
Hepatitis is a general name for liver inflammation. Many systemic viruses cause bilirubin for excretion and it is elevated in liver function tests (LFTs).
“collateral” liver damage e.g. EBV, CMV, VZV but hepatitis viruses specifically target
the liver and they replicate specifically in hepatocytes (hepatotropic) leading to
destruction of hepatocytes. Family of five known viruses (A-E) which vary in their
mode of transmission, incubation periods and resulting illness. Hep A most common
but there is a vaccine and little long-term consequences. Of more concern are Hep B
and Hep C – the blood borne viruses – often very mild symptoms and you do not
know you have the virus so potential for onward transmission and both could
become chronic. There is more information on structure as follows:

Return to Unit Overview

p88
 Leicester Medical School

Jaundice can be either pre-hepatic, intrahepatic or

extrahepatic depending on where the problem is.
Viral hepatitis causes intrahepatic jaundice – the
problem is within the liver itself. Taking a look at
LFTs –
If bilirubin is raised there is a problem with
either the pre-hepatic, intrahepatic or extrahepatic
processing of this product.
If ALT (Alanine transaminase) or AST
(Aspartate aminotransferase) are elevated it tells
us there is hepatocyte damage and the problem is
intrahepatic.
If ALP (Alkaline phosphatase) is elevated
there is a problem in the biliary tract – i.e.
extrahepatic.
Other liver tests check for albumin (Albumin helps maintain the oncotic
pressure of blood so that fluid does not leak into other tissues) and various
coagulation tests such as clotting factors (INR (International Normalised
Ratio) and Prothrombin time (PT)) are synthesised in liver.

Transmission and prevention of infection – Hepatitis B

Transmission is predominantly vertical (75% of cases globally) but also through

sexual contact, intravenous drug use, close household contacts (low risk) where
there is significant blood exposure and health care workers via needle stick injuries.
The main symptoms are jaundice, fatigue, abdominal pain, Note on Hepatitis B Serology – in a blood test you can detect HBsAg & HBsAb, HBeAg
anorexia/nausea/vomiting and arthralgia (joint pain). There is an incubation period & HBeAb, HBcAb (IgM followed by IgG (HBcAg is undetectable in blood)). At this stage
of six weeks to six months. Patients present with AST/ALT in the 1000s although up it is important that you know such antibodies are used to determine hepatitis B
to 50% have either no or vague symptoms. If you get an acute infection most people status but you do not need to be able to interpret/remember the different levels in
clear the infection within 6 months (80-90% of patients) and less than 1% exhibit liver HepB serology.
disease at that time. Only about 10% will go on to develop chronic infection. Tests
for Hep B include serology and HBV DNA PCR test. Chronic Hep B infection is defined as the persistence of HBsAg after 6 months. In 25%
of cases chronic infection leads to cirrhosis and about 5% will develop hepatocellular

Return to Unit Overview

p89
 Leicester Medical School

carcinoma. There is no cure as the virus integrates its genetic material into the host fluid. Continue to test and monitor for Hep B/C and HIV. Note further advice would
genome. Therefore, patients will need life-long anti-virals to suppress viral be to continue HIV PEP for 28 days (if required), to have counselling and follow-up
replication although that will not be required for everyone – some patients’ immune tests and advise to use condoms while at risk. No PEP is available for Hep C and
systems can keep the virus under control without the need for drugs – they will repeat HIV and Hep C tests at 12 weeks.
however need to be monitored (e.g. “inactive” carrier) Hep B vaccine is given to
babies at 8, 12 and 16 weeks old – consists of part of surface antigen to induce
immune response. Lecture 10 Summary: Antimicrobial Stewardship
What is it?
Transmission and prevention of infection – Hepatitis C Why is it important?

Infection is predominantly among intravenous drug users – these account for more How does it work in practice?
than 90% of those with Hep C in the UK. Sexual contacts and mother to child • What is it? Antimicrobial stewardship is defined in the lecture as: Coordinated
transmission risks are quite low. Unfortunately, there was a risk from blood interventions designed to improve and measure the appropriate use of
transfusion prior to 1991. Health care workers are also at particular risk from needle antimicrobials by promoting the selection of the optimal antimicrobial drug
stick injuries. Approximately 80% of those infected will go on to develop a chronic regimen, dose, duration of therapy, and route of administration. Antimicrobial
infection resulting in cirrhosis. Any symptoms are vague (fatigue, anorexia, nausea, stewards seek to achieve optimal clinical outcomes related to antimicrobial use,
abdominal pain (RUQ)) and about 80% have no symptoms at all. Serology – presence minimize toxicity and other adverse events, reduce the costs of health care for
of anti-hep C antibody confirms either cleared or ongoing infection. HepC virus is infections, and limit the selection for antimicrobial resistant strains.
confirmed by PCR testing. Treatment is with a directly acting antiviral drug combo
(as HIV) over 8-12 weeks and there is a greater than 90% chance of cure but very • Why is antimicrobial stewardship important? While there has always being
expensive at £10,000 - £60,000 per course. There is also the risk of re-infection as resistance to antibiotics existing in bacteria, it is important to seek an approach
there is no vaccine currently. to prescribing and the use of antibiotics which ensures their effectiveness while
attempting to minimise the emergence of resistance. There are several levels of
Post-exposure prophylaxis resistance:

a) MDR (multi-drug resistant) - Non-susceptibility to at least one

Risks of transmission via needle stick injury are as follow: HIV 1/300 (or even 0 if viral
agent in three or more antimicrobial categories
low undetectable), Hep C 1/30, Hep B 1/3 (or 0 if vaccinated). There are protocols in
place to deal with each scenario and first measures are basic first aid – bleed and b) XDR (extensively drug resistant - Non-susceptibility to at least
wash wound. Collect blood from the patient (with consent) and from med student. one agent in all but two or fewer antimicrobial categories
Inform Occupational Health and check med student’s Hep B vaccination status. Lastly
assess the risk and need for immediate HIV post-exposure prophylaxis as early c) PDR (pan-drug resistant) - Non-susceptibility to all agents in all
initiation of ARVs reduces dissemination and replication of HIV in tissue and bodily antimicrobial categories

Return to Unit Overview

p90
 Leicester Medical School

This comes with quite a significant cost burden to the health system in each
country. Various studies (laboratory, ecological & individual) have provided
evidence of the use of antibacterials causing resistance.
• How does it work in practice? It depends on a the multidisciplinary team (MDT)
working alongside the quality/safety team to ensure that various process
(antibiotic use in terms of dose, class, appropriateness, comparison to other
institutions) and outcome measures (Patient outcomes, emergence of
resistance, Clostridium difficile infection rate) are in place in conjunction with
various interventions (persuasive, restricted, structural).

Successful stewardship depends on the long term availability of confirmed and

appropriate resources, hospital leadership support and delegated authority to
challenge/change inappropriate antimicrobial therapy alongside integration into
organisational patient safety and quality of care structure and processes.

1. Does the patient need antibiotics?

Have they finished their course?
2. Can we switch this to oral from IV?
Can they swallow?
Are they clinically improving? Based on baseline observations,
investigation results and physical symptoms/signs.
3. Can we change broad-spectrum antibiotics to narrow-spectrum & targeted
antibiotics?
This will be based on culture & sensitivity results
4. Do you need special authorisation from microbiology?
For ‘restricted’ antibiotics such as meropenem and you need to
have a valid reason to prescribe this!

Return to Unit Overview

p91
 Leicester Medical School

NOTES: HIV Make a one page summary of needle stick injuries based on the six slides relating
to Case 2 of the Hepatitis lecture.
HIV is a major topic and you must have study notes on it. The lecture, small group
work and Lippincott’s contain all the information you need.
If you need to look up information on needle stick injuries the following review article
You will need to divide the notes and I suggest you do so based on the two case is excellent: Management Of Sharps Injuries In The Healthcare Setting
studies.
i) The second case study focused on acute HIV infection and you should have this as
the topic linked to the infection model.
ii) The first case study was of chronic HIV infection with AIDS.
You should have at least two pages for each of these scenarios. Both make good SAQ
questions.
You can then add in additional information on the biology and treatment. Remember
to think about and include ideas around the sociological approach to HIV as a long-
term condition.

NOTES: Needle Stick Injury

Needle stick injury (Risk of hepatitis and/or HIV)

Hepatitis is a challenging topic if you set out to learn all the information.
My advice is to take a strategic approach. You will revisit liver disease in the GI Unit
and in Phase 2.
Session 5 Self-Study:
1) Complete the case studies and the table.

A critical topic that has the potential to affect your working practice as a student on 2) Notes on HIV and needle Stick Injury have been provided. You will be
the ward and as a junior doctor is that of a needle stick injury. This also makes a required to know this especially as you might receive a needle stick injury in
good exam question. Look back at the Hepatitis Lecture Summary. the course of your career.

Return to Unit Overview

p92
 Leicester Medical School

Session 6: Principles Of Diagnosis And Management &

Use Of UHL Rx App/Guidelines 16 February 2022
Preparatory Work View, recall & review lectures
9 & 10 Learning Outcomes for Infections at a Surface
Download the RxGuidelines Describe the range, importance and origins of surface infections on both
app natural and prosthetic surfaces
9.00-10.30 Small Group Work 6 Case studies on the use of Describe the importance of the microbiota in this setting with examples for
UHL treatment guidelines mucosal surfaces
(LIVE Online OR F2F)
Describe the pathogenesis of infections at a surface.
11:00 – 11:50 Lecture 11 Infections at a Surface
Explain a ‘biofilm’ and the implications for an infection on a surface
(Live F2F Simulcast Session)
Describe the management of infected surfaces
12:00 – 12:50 Lecture 12 Adaptive Immunity (Part 2)
(Live F2F Simulcast Session)
Learning Outcomes for Adaptive Immunity
• Describe the antigen receptor present on both B cells and T cells
Notes Biofilms
Coagulase Test • Describe how antigen presenting cells select the appropriate immune
response against intracellular vs extra-cellular microbes
Endocarditis
Links to text books • Understand the mechanisms leading to B cells and T cells activation

• Describe the effector mechanisms of cell-mediated immunity and humoral

Self-study Complete the case studies immunity
and notes • Describe the structure/function of antibodies and their isotypes including
IgM, IgE, IgA and IgG.

Return to Unit Overview

p93
 Leicester Medical School

Session 6: Preparatory Work Session 6: Small Group Work

In all the case studies please use the UHL Rx Guidelines website (accessed
1) View, recall and review: View the lectures on Blood Borne Viruses: Hepatitis through blackboard) or the RxGuidelines App on your smart phone (more
(Lecture 9) and Antimicrobial Stewardship (Lecture 10) Recall and review up to date)
the information from the lectures before you start the group work. You could
do this on your own before the session or with your group at the beginning
of the session or a combination of both. 6.1 CASE STUDIES – Case Study A

2) Preparation for group work questions involving the use of the UHL In Week 1 you looked at a case of Cellulitis. The picture is below
treatment guidelines: Make sure you have accessed the UHL Antimicrobial
website through blackboard on your iPad and download the RxGuidelines
app onto your smart phone.

Anti-Microbial website link on blackboard under infection Unit

Rx Guidelines via your smart phone

3) Preparation for lectures: Read through the lecture slides/summaries for

today’s lectures Infections at a Surface (lecture 11) and Adaptive Immunity
(Part 2) (lecture 12) and add any additional notes before and after you view
the lecture.
Cellulitis is an infection of the deep dermis and subcutaneous tissue, presenting
4) Prepare for the lecture on Infections on a Surface by looking through the with expanding erythema, warmth, tenderness, and swelling
slides ahead of time. Natural and prosthetic surfaces are frequent sites of
infection. The lecture today will outline the importance of these infections.
We will also discuss the pathogenesis of infections on a surface and the In week 2 you discussed the symptoms and the initial investigations.
formation of a BIOFILM.

Return to Unit Overview

p94
 Leicester Medical School

MICROBIAL ORGANISM:
d. Outline the basic process used by the phagocytic cell to kill the organism – there
a. When you examine the patient you look for a cut or puncture mark to indicate a are 2 pathways to consider here – how do they differ?
site that the bacteria could have entered from the skin surface. What bacteria are
likely to cause Cellulitis?

e. The leg is red and swollen. This is acute inflammation. What substances has
the phagocytic cell produced to trigger the inflammation?
HOST IMMUNE RESPONSE:

b. As the bacteria enter the skin they will encounter the Innate Immune system.
Which phagocytic cell is in the tissue waiting to detect an invading organism?
Note the question is specific for the ‘tissue’ rather than the blood where a different
sub-set of phagocytic cells reside.

f. List some components of the acute inflammatory response that account for the
signs you see in the picture?

c. How does the phagocytic cell recognise the pathogen?

Return to Unit Overview

p95
 Leicester Medical School

INITIAL TREATMENT: i. Can you use Penicillin?

You can look up additional information in Lippincott’s Illustrated Review
The patient is unwell with a fever and pain related to the Cellulitis. Microbiology in relation to the two likely bacteria.
You decide to treat the patient. You will recall that treatment is always divided
into ‘Supportive’ and ‘Specific’.

g. What supportive treatment do you suggest?

h. You have yet to receive any results of the investigations you sent. However, j. What is the mechanism of action of the Penicillin group of antibiotics?
you decide to start the patient on an antibiotic. You have to choose an antibiotic
that covers the two main organisms that might cause the cellulitis. Which
antibiotic do you recommend?
• Look up the answer on the UHL Treatment guidelines.
• Look under skin-soft tissue-bone-joint.
• For the purpose of this session it does not matter if you classify this as
‘mild’ or ‘severe’

Return to Unit Overview

p96
 Leicester Medical School

IDENTIFICATION OF MICROBE: l. Which of the two likely organisms does this Gram stain suggest? Please ensure
you have the correct name of this organism
In addition to sending off a Full Blood Count, CRP and blood culture, you also take
a skin swab at the puncture site which is evident in the skin as there appears to be
some pus at the site. You ask the laboratory to do a Gram stain.
The laboratory phone back later that day to say that they have obtained the
following results on the Gram stain. VIRULENCE FACTORS:

m. Review the virulence factors for this microbe.

• Write down a cell wall virulence factor and up to three exotoxins
• What is an exotoxin?
The following should help:

Or look back to the lecture summary on An Introduction to Infection in Session 1.

k. Describe what you see on the Gram stain?

Return to Unit Overview

p97
 Leicester Medical School

6.2 CASE STUDIES – Case Study B common causes of pyuria. BUT need to do cultures to ascertain the bacterial species
properly.
You will cover Urinary Tract infections again in the Urinary Unit in
Semester 3. This case study will focus on the microbiology and the The GP also sends a sample of urine to the microbiology lab for culture.
antibacterial treatment of a standard UTI.
MECHANISM OF INFECTION:
Celia is 32 years old and presents to her GP with symptoms of dysuria and
frequency. a. Refer back to the lecture on ‘The Infection Model’. What is the likely
mechanism of infection?
Dysuria = difficulty, pain or discomfort when passing urine. Sometimes described as
burning
Frequency = A frequent urge to urinate, even though little comes out when the
patient goes to the toilet HOST IMMUNE RESPONSE:

• The GP takes a history and examines Jane’s abdomen. b. What innate barriers are present in the urinary tract?
• The GP requests a urine sample.
• The GP does a dipstick test on the urine sample that shows the following:

Nitrites positive
Leukocyte Esterase positive
TREATMENT:
Nitrites are generally found in urine due to reduction of nitrates to nitrites by some
c. The GP makes a diagnosis of a Urinary Tract Infection.
Gram-negative bacteria such as E. coli. The detection of bacteria in urine by nitrite
positive dipstick is also dependent on nitrates from the patient’s diet (vegetables)
• Look on the Rx Guidelines web site.
and sufficient bladder incubation time. Gram-positive uropathogens such as
• Write your antibiotic prescription below.
Staphylococcus saprophyticus and enterococcus do not produce nitrate reductase
and therefore when infection is due to these bacteria, the dipstick will be negative
for nitrite.
Leukocyte esterase is an enzyme released by neutrophils and macrophages. A urine
dipstick positive for this enzyme indicates pyuria (an increased number of leukocytes
/white blood cells). Urinary tract infections including cystitis and urethritis are

Return to Unit Overview

p98
 Leicester Medical School

MICROBIOLOGICAL DIAGNOSIS:
d. What is the mechanism of action of this antibiotic?
A Gram stain of urine sample is below:

e. Describe the Gram stain appearance

You can look up additional information in Lippincott’s Illustrated Reviews

Pharmacology Chapter 40. All you need is the paragraph entitled ‘Overview’
f. What is the likely organism? Ensure you have the correct name

g. Where is this organism normally found?

Each time you look up an antimicrobial, go back to the lecture slides. Pick out a
few key points for that antimicrobial. Become familiar with these common drugs.

Return to Unit Overview

p99
 Leicester Medical School

h. What other infections does this microbe cause? Use the following to help: 6.3 CASE STUDIES – Case Study C

Mary is 55 years old and presents with a two-day history of increasing cough. She
has a fever of 37.8oC and a respiratory rate of 24/minute (normal 12 to 20/minute).
She has normal oxygen saturation (i.e. does not require extra oxygen). On
examination she has the clinical features of pneumonia.

MICRO-ORGANISM
a. You consider this a case of community acquired pneumonia – as described in
week 3. What organisms might be causing her pneumonia?

Go back and review the main microbes that cause pneumonia in a community
setting.

Return to Unit Overview

p100
 Leicester Medical School

TREATMENT: MICROBIOLOGICAL DIAGNOSIS:

b. On the basis of the information you have available what treatment do you The following day the microbiology lab phones to say a gram stain of a sputum
recommend? sample show the following with equivalent colonies growing on an Agar plate.
Consider both supportive and specific treatment.
Look at the UHL Rx guidelines.
Look at the information for Community-acquired pneumonia

c. Write your prescription for an antibiotic below.

e. Describe the findings of the Gram stain

d. What group of antibiotics does this belong to?

Return to Unit Overview

p101
 Leicester Medical School

f. What is the organism? Please ensure you have the correct name of this Lecture 11 Summary: Infections at a Surface
organism Learning Outcomes:
Describe the range, importance and origins of surface infections on both
natural and prosthetic surfaces
Describe the importance of the microbiota in this setting with examples
for mucosal surfaces
Describe the pathogenesis of infections at a surface.
Explain a ‘biofilm’ and the implications for an infection on a surface
Describe the management of infected surfaces

What is a surface? This is an interface between a solid and a liquid/gas. Infections

can affect either the external natural body surface (eg skin, GI tract, urinary tract)
or an internal natural body surface (eg heart valves, prosthesis in joint spaces, bone
g. Is your antibiotic choice appropriate for this organism? metal implants).
How do people get infections?

Invasion e.g. Strep pyogenes causing pharyngitis

Migration e.g. Escherichia coli causing urinary tract infection
Innoculation e.g. Coagulase-negative Staphylococcus causing prosthetic
joint infection
Haematogenous e.g. Strep viridans causing infective endocarditis

What is the pathophysiology of infections at surfaces?

Adherence to host cells or prosthetic surface
Biofilm formation
Invasion and multiplication
Host response
Pyogenic (neutrophils ‐> pus)
Granulomatous (fibroblasts, lymphocytes, macrophages ‐> nodular
inflammatory lesions)

Return to Unit Overview

p102
 Leicester Medical School

What is a biofilm? Biofilms comprise of microbial communities that are attached to Additional Information: Useful Links to Lippincott’s
surfaces and encased in an extracellular matrix of microbial origin. Most hospital-
These links may be useful for this session:
acquired infections are due to biofilms because they can be life-threatening
colonizers of biomedical devices. Biofilms protect the bacteria by prevent bacterial
phagocytosis, antibodies and complement recognition/binding of receptors. (There a) Virulence factors in Staphylococcus aureus
are further notes on biofilms in Session 8 Notes)
How do treat these patients? Our aim is to sterilize tissue and reduce bioburden on
the tissue. We can do this via antibacterial drugs, removing prosthetic material with
surgery. The challenges are poor antibacterial penetration into biofilm, low
metabolic activity of biofilm micro‐organisms and dangers/difficulties of surgical
procedure. b) For additional information on the mechanism of action of folate antagonists,
follow the link below to Lippincott’s Illustrated Reviews Pharmacology Chapter 40.
All you need is the paragraph entitled ‘Overview’

Session 12 Summary: Adaptive Immunity Part 2

There is no summary for this lecture – please use it as an opportunity to create your
own notes. As it is a tough topic this will be immensely beneficial for your own
learning. You could use next week’s group work questions to help you do this.
c) Escherichia coli

d) Community-acquired pneumonia

Return to Unit Overview

p103
 Leicester Medical School

Biofilms in infectious diseases

Biofilms are a major cause of human infections. The majority of hospital-acquired
infections are due to biofilms because they can be life-threatening colonizers of
biomedical devices. Indeed, a large proportion of nosocomial infections (Nosocomial
= hospital acquired) are related to the colonization of pathogens on the surface of
NOTES: Biofilms implanted medical devices such as respirators, catheters (central venous, urinary),
We have covered important topics today. In order to help you will find notes on prosthetic heart valves, and orthopaedic devices. In fact, 95% of urinary tract
biofilms and on endocarditis below. Together with your notes from the small group infections are associated with a urinary catheter, 80% of pneumonias are associated
session, these will serve you well. with mechanical ventilation, and 87% of bloodstream infections are associated with
You may choose to make an even briefer summary using the infection model. intravascular devices. Staphylococci and enterococci are responsible for the
Make sure you understand the coagulase test and the diagnostic and clinical frequent cases of hospitalization-acquired infections
relevance.
These two bacterial genera are commensal inhabitants of the human Bacterial
Biofilms are microbial communities attached to surfaces and encased in an biofilm flora of the skin, upper respiratory tract, lower gastrointestinal tract, and
extracellular matrix of microbial origin. They represent the predominant form of urogenital tract. For this reason, they are amongst the most likely organisms to
microbial life. Biofilms are everywhere and can develop on virtually every natural and colonize implanted medical devices. Coagulase-negative staphylococci (CoNS);
man-made surface. Biofilms are also ubiquitous in both normal and pathogenic Staphylococcus epidermidis and Staphylococcus aureus are the predominant
human processes. Biofilm formation has been demonstrated for numerous bacterial species connected to device-associated infections.
pathogens and is clearly one of the main strategies for bacterial survival in a variety
of sites within the human body. In almost all instances, the biofilm lifestyle helps NOTE: part of the group work is to look up the classification of Staphylococci. You
bacteria survive and persist within the environment. will learn that they are divided into:
Historically, many studies have assumed that microbes lead solitary, asocial lives. On 1. those that are ‘Coagulase positive’ such as Staph aureus. We have included
the contrary, bacteria predominantly live in dense biofilm populations interacting Staph aureus in case studies (Cellulitis) and you have looked up the other
extensively with each other. Indeed, most bacteria in nature do not exist infections that can be caused by Staph aureus (i.e. it causes a range of nasty
independently but persist in co-ordinated, spatially organized, and metabolically infections).
integrated biofilm communities. Biofilms are ubiquitous and can develop on virtually 2. those that are ‘Coagulase negative’ such as Staph epidermidis. Staph
every natural and man-made surface. In natural habitats, biofilms generally provide epidermidis (and the whole group of Coagulase negative Staphylococci) are
homeostasis in the face of fluctuating and harsh environmental conditions usually commensal on the skin and cause no problems. The lesson from this

Return to Unit Overview

p104
 Leicester Medical School

week’s session is that they can cause problems when they are part of a Schematic representation of the distinct steps in microbial biofilm development. The
biofilm on a surface inside the body where they are not meant to be. different stages in biofilm formation include initial attachment to the surface,
formation of a monolayer along the surface with formation of micro-colonies, biofilm
CoNS are an important cause of infection of intravascular catheters, either by maturation with formation of a three-dimensional structure, and cell dispersion.
tracking along their external surface or by entering via the catheter hub during
manipulation by healthcare workers. S. epidermidis nosocomial infections tend to be
chronic and less acute, while S. aureus is involved in acute infections because of its Resistance of bacteria in a biofilm to antibiotics:
ability to elicit a more acute immune response from the host.
Enterococci have emerged in recent years as pathogens associated with serious One of the major problems with biofilms causing infections is that they are difficult
nosocomial infections despite their low level of virulence. They cause infection to treat and clear away.
almost exclusively in hospitalized patients who have significantly compromised Again, Dr Jenkins will cover this in his lecture. He will explain the term ‘quorum
immune defenses. Enterococci are among the most frequent cause of nosocomial sensing’.
infections, particularly in intensive care units where enterococci can be transmitted The diagram below is a useful one which summarises several of the reasons why a
from one patient to another via the hands of clinical staff. biofilm makes it difficult for antibiotics to kill the bacteria.
The consequence is that sometimes the only solution to treat the infection is to
Formation of a biofilm: Dr Jenkins will cover this in his lecture and this diagram is remove the artificial surface on which the biofilm is growing. In the case of the
simply a variation on the slides he will show. But it is clear and reasonably simple. biofilm growing on a heart valve (a natural surface) treatment may require
replacement of the valve.

Return to Unit Overview

p105
 Leicester Medical School

Schematic representation of the different mechanisms involved in the multi-drug

tolerance of biofilms. The matrix acts to restrict the penetration and diffusion of
some antimicrobials. Bacteria within the biofilm can also secrete b-lactamases into
their surrounding environment and/or increase the expression of multi-drug
resistance (MDR) efflux pumps. The activation of quorum-sensing systems along with
different concentration gradients of nutrients, oxygen, and metabolic waste
products also make important contributions to antibiotic tolerance and resistance to
the host immune system. The presence of “persisters” (dormant variants of regular
cells that form stochastically in microbial populations and are highly tolerant to
antibiotics) that are resistant to killing by all antibiotics may also be responsible for
recalcitrant biofilm infections.

NOTES: Coagulase Test

Staphylococcus aureus produces coagulase which coverts fibrinogen (soluble) into

fibrin (insoluble)

NOTES: Endocarditis

Look at ‘Identification of bacteria’. There is a useful diagram and a statement of Bicuspid Aortic Valve and Endocarditis
what the coagulase test helps to differentiate. There is more background science to this case than initially appears.

You do not need to learn all the tests used to differentiate bacteria. BUT the
The aortic valve normally has three cusps or leaflets.
COAGULASE test is commonly reported and used to describe Coagulase Negative
Bacteria and so is important to know.
Bicuspid aortic valve is the most common congenital cardiac defect. It is both
structural – with the bicuspid aortic valve, AND has a range of tissue, molecular and
genetic abnormalities.

Return to Unit Overview

p106
 Leicester Medical School

Bicuspid Aortic Valves are the result of abnormal aortic cusp formation during
valvulogenesis. Adjacent cusps fuse to form a single aberrant cusp, larger than its
counterpart yet smaller than 2 normal cusps combined.

Microorganisms that enter the blood stream from skin, mucosa or other sites of local
infection bind to the vegetation and cause local infection leading to a pro-coagulant
state. Further fibrin deposition, platelet aggregation and bacterial invasion lead to
an infection cascade causing infective endocarditis. Staphylococcus aureus possesses
Patients with a bicuspid aortic valve are at increased risk of developing endocarditis. fibronectin binding proteins and is capable of binding to intact endothelium and
This is linked to the abnormal flow of blood over the valve and the associated therefore can infect previously uninfected endocardium.
abnormal valve tissue. The patient is at greater risk of microbes in the blood sticking Bacterial micro colonies deep within the vegetation are dormant and therefore
to the valve cusp and setting up a local infection (with a biofilm). difficult to eradicate. Superficial bacterial colonies tend to embolise (i.e. to lodge in
and obstruct) distally causing septic phenomenon as well as reinfection of
vegetation. A constant infection leads to the three hallmarks of the disease:
ENDOCARDITIS 1. constitutional symptoms which are cytokine mediated
The endocardium is non sticky and normally resists bacterial seeding. Most cases of 2. local spread of infection causing destruction of myocardium
infective endocarditis relate to structural defects. 3. distal blood borne septic embolisation
Other risk factors include injectable drug use
The hallmark of endocarditis is formation of vegetation that binds to valves or mural
BIOFILM: It is now clear that the ‘vegetation’ is a biofilm with all the
endocardium. Aberrant flow predisposes to a collection of fibrin, platelets and
characteristics of a biofilm.
scant inflammatory cells.

The Figure is of Aortic Valve Vegetation

Return to Unit Overview

p107
 Leicester Medical School

Biofilm hypothesis. (1) Bacterial adherence. (2) Biofilm growth and maturation.
(3) Recalcitrant biofilm causing persistent inflammation, dispersion of biofilm
fragments causing septic embolization, and new biofilm formation.

Figure: Janeway Lesions

b) Splinter Haemorrhages: These are linear minute capillary

engorgements usually in distal third of the nail bed.

Clinical features of Endocarditis

Fever
Heart murmur
Other cardiac complications
Embolic features: These are small bits of the vegetation (or biofilm) that
become loose and travel to small capillaries where they can block the
capillary or cause local infection at that site. Examples:

a) Janeway Lesions: These are haemorrhagic nodular lesions with an

irregular border present on palms and soles. They are related to micro-
abscess formation and localised necrosis.

Return to Unit Overview

p108
 Leicester Medical School

c) Roth spots in the eye: These are described as linear haemorrhagic

spots seen in the retina of the eye

Duke Criteria for diagnosing endocarditis

Cardiologists have developed criteria to diagnose endocarditis. You do NOT

need to know these at this stage. This is for information only.

d) Oslers nodes: These are painful, erythematous nodules on pads of BUT you will note that the criteria include
fingers and toes. They may have a dual aetiology as they are related the standard features of infection such as fever,
to both: septic micro-emboli and immune complex related vasculitis cardiac features - such as a murmur
microbiological features – such as a positive blood culture
embolic features relating to the vegetation / biofilm and release of bits
of the vegetation into the blood stream (and sometimes with other
immune consequences).

References: These are for reference only to enhance your own understanding.

Return to Unit Overview

p109
 Leicester Medical School

This paper “Current Hypotheses in Cardiac Surgery: Biofilm in Infective Endocarditis”

gives more information and contains the figures used above. You will need to access
it through a university account in order to view to the full article.

This is an overview of endocarditis – this is a very informative easy to read article.

Return to Unit Overview

p110
 Leicester Medical School

Session 6 Self-Study:

1. Complete the three case studies – they are a perfect example of how you need
to bring together information using the infection model.
2. Make an infection model of each case - each should take about 30 minutes. It
will serve you well for the exams.

Note: Trying to learn all the antimicrobials in isolation is difficult (i.e. almost
impossible). You must learn about the antimicrobials in the context of an infection
and a particular microbe. This is why the infection model is useful. In the remainder
of the Unit we will have case studies and examples that identify the antibiotics you
need to know.

Return to Unit Overview

p111
 Leicester Medical School

Session 7: Hospital Acquired Infections & Infection

Prevention plus LIVE Q&A MICROBIOLOGY SESSION Learning Outcomes
23 February 2021 Apply the infection model to a patient presenting with a hospital infection.
Preparatory Work View, recall & review To further expand the description of pathogen/person/practice/place as it
lectures 11 & 12 applies to hospital acquired infections
Read David’s article Understand the range of hospital acquired infections
9:00 – 11:00 Small Group Work 7 Case studies: Infections at a Describe the principles of antibiotic resistance
(LIVE Online) Surface Describe principles relating to infection control in a hospital setting
Immunity Describe the use of Personal Protective Equipment with regard to
infections in a hospital setting
11:00 – 11:50 Lecture 13 Hospital Acquired Infections To appreciate and describe some of the global concerns relating to hospital
(pre-recorded) acquired infections and drug resistance.
(This needs to be viewed
before group work 8) To describe the characteristics of Clostridioides difficile, its pathogenesis
and management
12:00 – 12:30 LIVE Q&A Session Microbiology
To describe the characteristics of Staphylococcus aureus with regard to
ONLINE
hospital acquired infections and drug resistance
12:30 – 13:20 Lecture 14 Infection Prevention
To describe the characteristics of Norovirus and application of infection
(This needs to be viewed (pre-recorded) prevention principles
before group work 8)
Notes Clostridioides difficile
MRSA
Norovirus
Self-Study Complete the case studies.

Return to Unit Overview

p112
 Leicester Medical School

Session 7: Preparatory Work

1) Please summit any questions either via email or the discussion board for
the Microbiology Q&A session live online at midday. All questions will be https://doi.org/10.1016/j.mpmed.2017.07.005
anonymised.
6) In preparation for lectures on hospital acquired infections & infection
2) View, recall and review: View the lectures on Infections at a Surface prevention: Read the background information on MRSA as these will also
(Lecture 11) and Adaptive Immunity Part 2 (Lecture 12) Recall and review help with session 8 group work.
the information from the lectures before you start the group work. You could
do this on your own before the session or with your group at the beginning In Lippincott’s Illustrated Reviews Microbiology you need to go to Chapter 8
of the session or a combination of both. (Staphylococci) and then Staph aureus and scroll down to Section on
Treatment. There are a few brief paragraphs on the treatment of resistant
3) This week’s group work will be in two parts: Staph aureus. Read these paragraphs
a) 9:00 – 10:00 – work collaboratively with your group to answer the
immunity/infections at a surface case study questions
b) 10:00 – 11:00 – a CTF will help to answer some of your questions and
you can complete the group work questions.

The notes on biofilms, coagulase test & endocarditis at the end of the
previous group work session will be helpful in answering your questions
during the group work.
Look at the CDC website:
4) Preparation for lectures: Read through the lecture slides/summaries for
today’s lectures Hospital Acquired Infections (lecture 13) and Infection
Prevention (lecture 14) and add any additional notes before and after you
view the lecture.

5) In preparation for the lecture: Hospital acquired infections by Dr Jenkins,

please read the review article by him which will form the basis for the Look at some patient leaflets on MRSA:
lecture. “Nosocomial infections and infection control” by David R Jenkins.
Medicine Volume 45, Issue 10, October 2017, Pages 629-633.

Return to Unit Overview

p113
 Leicester Medical School

Small Group Work 7: Immunity & Infections on a Surface

Note: Additional summary Notes on MRSA are included at the end of this session
as part of the Study Notes.
7.1 Immunity Questions
Answer the following questions before the session:
Immunity is a complex topic and the following questions should help to increase
What does MRSA stand for? your understanding of the topic.

What are the sites of colonisation by Staph aureus?

a) Name the different types of antigen presenting cells:
What percentage of the population are colonised by Staph aureus?

b) Which of these APCs present the pathogen antigens to:

What percentage of the population are colonised by MRSA?
Naïve T cells –
Effector T cells –

c) The function of which molecules in the adaptive immune response could be

described as follows – “to bind peptide fragments derived from pathogens
and display them on the cell surface for recognition by the appropriate T
cells”.

d) Which MHC molecules are present on APCs?

e) Can you suggest why two non-related students in the same university year
respond in different ways to the same infection – one individual gets
extremely ill while the other just feels a little more tired than normal?

Return to Unit Overview

p114
 Leicester Medical School

f) Please fill in the blanks on the following slide for a Staphylococcus aureus g) Please fill in the blanks on the following slide for an adenovirus infection:
infection:

Return to Unit Overview

p115
 Leicester Medical School

h) Co-stimulation of T cells is an important concept – three signals are 7.2 CASE STUDIES – Case Study A
required to activate the T cell response.
A 45 year-old man goes to his GP because he has not been feeling well. He has
Signal 1 - On the APC the MHC I or II complex presents the pathogen
no energy, has noticed a reduction in his appetite and has lost 5kg in weight. He
fragment to the T cell receptor (which is a receptor molecule combined
reports that he has been suffering hot and sweaty episodes. On reflection, he
with a CD3 complex and a CD4+ or CD8+ accessory molecule) hasn’t been feeling right for five or six weeks.
Signal 2 – on the APC the B7 molecule interacts with the T cell CD28
On examination, the GP notices the patient has a heart murmur.
molecule
Signal 3 – The APC releases cytokines that act on the T cells to activate The heart murmur is loudest at the upper right sternal border at the 2nd right
particular T cells to activate the most appropriate T cell response intercostal space. The murmur is described as being a systolic murmur.

Therefore, which of the following set of proteins present on T cells needs

to be engaged in order for them to be fully activated: You are presently doing the Cardiovascular Unit. You have yet to do the clinical
A. CD28 and TCR features of heart disease and will do Cardiac Failure in Session 10. However, you
B. B7 and TCR have had an introduction to the structure of the heart and the heart valves and the
C. B7 and MHC class II (+ foreign peptide) cardiac cycle. Read through the notes on endocarditis in this session to help you with
D. CD28 and MHC class II (+ foreign peptide) the group work.

A heart murmur is the sound of blood flow turbulence in the heart. Blood flow is
normally smooth with no murmurs present. Turbulent blood flow can occur if a heart
valve is abnormal and creates turbulence as blood flows over it. Note: it is also
possible to get a murmur with a normal heart valve if the flow is increased.

a. Based on your understanding of the heart and related surface anatomy, which
valve is likely to be the cause of this murmur?

Note: Linking the site of the murmur with the anatomy is more complex than
simply knowing the anatomy. It is also dependent on the direction of flow of the
blood and whether the valve is narrow (stenotic) or does not close properly
(incompetent)

Return to Unit Overview

p116
 Leicester Medical School

The diagram below gives some information

The GP then looks in the patient’s mouth.

The GP notes the poor state of a number of his teeth and his gums.
Review the normal microbial commensals that exist in the mouth.

Mouth commensals / microbiota:

b. Note the names of the mouth commensals. Identify those we have already
mentioned thus far in the unit.

Return to Unit Overview

p117
 Leicester Medical School

f. What do you think the cardiologist’s plan of action is likely to be?

The patient has a fever of 38.5oC (Normal 36.5 – 37oC)
This information, together with the heart murmur leads the GP to
be concerned that there could be an infection involving the heart.

c. How could the state of the patient’s mouth be linked to a possible heart
infection?
The cardiologist takes some blood for testing and immediately admits the patient
to the cardiology ward for further management. By the end of the day, the
following results are available:
Hb 109 g/L (reference range 115-165g/L)
WBC 11.5 X 10^9/L (reference range 4.0-11.0 x 10^9/l)

d. Are there any questions you would like to ask the patient? Platelets 312 x 10^9/L (reference range 150-400 x 10^9/l)
CRP 65 mg/L (reference range 0-5 mg/L)
Urea 12 mmol/L (reference range 2.5-7.8mmol/L)
Creatinine 121 umol/L (reference range 60-120 umol/L)

Note: You will do the Urinary Unit in Semester 3. For the purpose of this question:
The patient admits to the GP that he has not seen a dentist for years; in fact, two Creatinine is an important indicator of renal health because it is an easily measured
months ago he tried pulling out a painful tooth himself with pliers and managed by-product of muscle metabolism that is excreted unchanged by the kidneys.
to pull out a tooth fragment. The liver produces urea as a waste product of the digestion of protein. Urea is
The GP sends the patient to a cardiac outpatient clinic that day. The cardiologist excreted via the kidney.
confirms the GPs findings. Both creatinine and urea levels in the blood are an indicator of the health of the
kidney. Levels will rise if the kidney is not functioning properly (although there are
other causes of raised urea and creatinine)
e. What do you think might be the problem?

Return to Unit Overview

p118
 Leicester Medical School

g. What abnormalities are present in these blood results? What conclusions can
you make from the results?

The next day, the patient is sent for echocardiography. A trans-thoracic echo
reports that the aortic valve is bicuspid and a mobile mass is attached to it.

h. What is the significance of the bicuspid valve?

j. What does the Gram stain show?

i. What might the mobile mass be?

k. What is the most likely explanation for the blood culture result?

Note: see notes on Biofilms and Endocarditis later in the session.

That afternoon, the microbiology registrar contacts the cardiologist to tell her that
the blood cultures she took in the emergency clinic appointment are growing
bacteria. The Gram stain is below.

Return to Unit Overview

p119
 Leicester Medical School

l. What connection can you make between the blood culture results and the
patient’s dental condition?

The patient is commenced on high dose intravenous penicillin and gentamicin on

the advice of microbiology. After one week, the patient is feeling much better.
Three weeks later the patient is taken to theatre for aortic valve replacement
surgery. The damaged value is pictured below.

m. Explain the findings highlighted by the arrows in the picture.

Return to Unit Overview

p120
 Leicester Medical School

Lecture 13 Summary: Hospital-acquired Infections Bacteria: Staph aureus including MRSA, Clostridioides difficile, Escherichia
coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Mycobacterium
Learning Outcomes:
tuberculosis
To further expand the description of pathogen/person/practice/place as Fungi: Candida albicans, Aspergillus species
it applies to hospital acquired infections. Parasites: Malaria
Understand the range of hospital acquired infections.
Pathogen Factors:
To appreciate and describe some of the global concerns relating to
hospital acquired infections and drug resistance. Virulence factors
Ecological interactions - other bacteria -antibiotics/disinfectants
Healthcare infections occurs in healthcare settings. It includes hospital-acquired
infections, community GP settings and will affect anyone (including doctors, nurses, Patient factors:
physiotherapist, OT, patients, relatives etc.). Hospital-acquired infections is defined
extremes of age
as infections acquired in hospitals 48 hours after admission.
obesity/malnourished
diabetes
cancer
immunosuppression
smoker
surgical patient
emergency admission
Interaction with other healthcare professionals

Practice factors:
General and specific activities of healthcare workers
Policies and their implementation
Organisational structure and engagement
Different pathogens: Regional and national political initiatives
Leadership at all levels from government to the ward
Viruses: blood borne viruses (hepatitis B, C, HIV), norovirus, influenza
chickenpox, COVID-19 Place factors:

Return to Unit Overview

p121
 Leicester Medical School

Healthcare environment: fixed features (number of beds in a bay), variable Lecture 14 Summary: Infection Prevention
features.
Learning Outcomes:
Different interventions to prevent hospital-acquired infections:
Describe principles relating to infection control in a hospital setting.
Patient (self-infection): Describe the use of Personal Protective Equipment regarding infections in
o General) stop smoking, good nutritional status, controlled diabetes, a hospital setting.
give antimicrobial prophylaxis, adequate skin preparation prior to
Common sources of infection:
any invasive procedures, adequate hand hygiene.
o (Specific) MRSA screening system (give mupirocin nasal ointment Environment: Legionella
and disinfectant body wash) Food/Water: E.coli, Salmonella, Listeria
Patient to patient transmission Animals: Rabies
o Physical barriers: For isolation of infected patients & protection of Person-to-person transmission: influenza, norovirus, gonorrhoea
susceptible patients Vector-to-person transmission: malaria
Healthcare workers to patient transmission:
o Healthy - Disease free, Vaccinated Endemic disease: The usual background rate (dependant on the time of year)
o Good practice - Good clinical techniques (e.g. sterile non-touch), Outbreak: Two or more cases linked in time and place
hand hygiene, PPE, Antimicrobial prescribing (being mindful that
some antibiotics use can increase risk of infections! E.g. cefuroxime Epidemic: A rate of infection greater than the usual background rate
and C.difficile infections) Pandemic: Very high rate of infection spreading across many regions, countries and
Environment to patient transmission: continents
o Built environment: Space/Layout, Toilets, Wash hand basins,
Factors affecting transmissibility
Furniture and furnishings
o Cleaning: Disinfectants, Steam cleaning, Hydrogen peroxide vapour The method of spread - ?airborne/aerosol? Droplets ?direct contact
o Medical devices: Single use equipment, Sterilisation, (shingles) ?sexual encounter (i.e. mucous membranes)
Decontamination Number of organisms required to cause disease
o Appropriate kitchen and ward food surfaces Immunity status of the host
o Good food hygiene practice
o Theatres SIR curve – epidemic curve!
o Positive/Negative pressure rooms The stochastic nature of small scale outbreaks – this can be misleading as people
o Immunosuppressed patients can infer to conclusions without considering the fact that this may normally occur
without any interventions!

Return to Unit Overview

p122
 Leicester Medical School

Smallpox is the only bacteria that we have eradicated completely.

Pathogen (+ vector) - reduction or eradication
Patient improved health- immunity (i.e. vaccination, immunoglobulin), nutrition,
and medical treatment
Practice behavioural change - protective equipment
Place - environmental engineering

Return to Unit Overview

p123
 Leicester Medical School

NOTES: Clostridioides difficile The spores can be transferred to patients via the hands of healthcare personnel;
therefore, good hand hygiene with soap and water and regular vinyl glove use is
crucial to interrupt the transmission
Clostridioides difficile [klos–TRID–e–OY-dees dif–uh–SEEL] In addition to the environment, potential reservoirs for C. difficile also include
Clostridioides difficile is a gram-positive, anaerobic, spore-forming bacillus that is asymptomatic carriers and infected patients, where spores are transmitted by the
responsible for the development of antibiotic-associated diarrhoea and colitis faecal-oral route
(bowel inflammation).
Gram stain of the blood culture Coloured electron micrograph of C.
This bacterium was formally known as Clostridium difficile. Clostridium difficile was showing Gram-positive rods with difficile forming an endospore (red)
reclassified in 2016 when it became necessary to assign C. difficile to a new genus. spores
Textbooks will continue to use the old name until new textbook versions are
published. Many online articles will do the same. Both names are likely to be used
interchangeably for a number of years.
Microbiology
C. difficile is an anaerobic bacteria. The presence of oxygen is inhibitory to its growth.
Their sensitivity to oxygen limits the conditions under which it can colonise the
human body or cause disease.
C. difficile is a minor component of the bowel microflora. Colonisation of the large
bowel is present in up to 5% of the population. The colonisation prevalence is several
times higher in hospitalised patients.

C. difficile is able to form SPORES. Infection with C. difficile mostly occurs as a result
of spore transmission.
The spores are resistant to heat, acid and antibiotics and survive for several months.
Spores are widely present in the environment. This is especially true for hospitals
(and nursing homes). Toilets, clinic furnishings, phones, and medical devices
(thermometers, stethoscopes) may all serve as reservoirs for C. difficile spores.

Return to Unit Overview

p124
 Leicester Medical School

Pathogenesis The most commonly implicated agents include the cephalosporins (especially second
and third generation), the fluoroquinolones, ampicillin/amoxicillin, and clindamycin.
Infection with C. difficile mostly occurs as a result of spore transmission. After Most antibiotics have been implicated.
reaching the intestine, bile acids play an important role in the induction of C. difficile Even brief exposure to any single antibiotic can cause C difficile colitis. A prolonged
spore germination. This results in the production of C. difficile bacterial cells in the antibiotic course or the use of 2 or more antibiotics increases the risk of disease.
intestine.
Advanced age (>60 y) and hospitalization (particularly sharing a hospital room with
The main protective barrier against C difficile infection (CDI) is the normal intestinal an infected patient, intensive care unit stays, and prolonged hospital stays) are
microflora. known risk factors for infection with C difficile.
When the balance of gut microorganisms is disrupted, C. difficile starts to dominate
and colonize the large intestine. Only a portion of colonized patients will develop Other risk factors include:
symptoms of CDI. The pathogen is not invasive, and virulence is mostly due to Severe illnesses, immune suppression, and gastric acid suppression are also well-
enzymes, such as collagenase, and toxins, which damage the epithelial cells leading established risk factors.
to fluid secretion, neutrophil adhesion, and local inflammation. In addition, in recent years, inflammatory bowel disease (IBD) has been implicated
as a strong risk factor for C difficile infection.
TOXINS: C. difficile produces two important types of toxins, A and B.
Toxin A is an enterotoxin that causes excessive fluid secretion, but also stimulates an CLINICAL FEATURES of Clostridioides difficile infection (CDI)
inflammatory response and has some effect on damaging cell structure. CDI clinical picture can vary from the asymptomatic carrier state to life-threatening
Toxin B is a cytotoxin and damages protein synthesis and the cell structure. colitis

Risk factors associated with CDI The diagnosis of C difficile colitis should be suspected in any patient with diarrhoea
Antibiotic exposure, older age and hospitalisation are key factors for CDI who has received antibiotics within the previous 3 months, has been recently
development hospitalized, and/or has an occurrence of diarrhoea within 48 hours or more after
hospitalization.
Antibiotic exposure
Asymptomatic carriage - No signs or symptoms of CDI
The primary risk factor for C difficile colitis is previous exposure to antibiotics.
Although the normal gut flora resists colonization and overgrowth with C difficile, the Mild or moderate CDI
use of antibiotics, which alter and suppress the normal flora, allows proliferation of C Diarrhoea (≥3 unformed stools in a 24 h period)
difficile and toxin production. Presence of mucus or occult blood in stool

Return to Unit Overview

p125
 Leicester Medical School

Fever fulminant cases, combined therapy with intravenous metronidazole and oral
Abdominal cramping, discomfort or pain vancomycin may be considered
In the USA Fidaxomicin is used initially instead of Metronidazole. In the UK
Severe CDI it is used in severe or complex cases with the advice of the microbiology
Leukocytosis (>15,000 white blood cells/μL) team.
Elevated serum creatinine levels
Pseudomembranous colitis Relapse
Relapse occurs in 20-27% of patients.
Severe, complicated CDI A number of options are available for the treatment of relapse infection. Local
Ileus (loss of bowel motility)
guidelines should be followed. Among various investigational therapies, faecal
Hypotension, shock or sepsis
microbiota transplantation (faecal enemas or infusion of donor faeces through a
Toxic megacolon / Abdominal perforation
nasoduodenal tube) has been reported to repopulate the colonic flora and treat
Death attributable to CDI (rare)
recurrent CDI.
DIAGNOSIS
Tests aim to identify the C. difficile bacteria and the presence of toxin. WHAT ARE THE STEPS TO PREVENT SPREAD?
Stool assays for C difficile include the following: Prevention strategies should be implemented in every suspected case, not only in
Enzyme immunoassay (EIA): for glutamate dehydrogenase produced by C. confirmed patients
difficile. C difficile is recognized as a major nosocomial pathogen, and universal precautions
Real-time polymerase chain reaction (PCR) assay for toxin gene against it should be implemented.
EIA for detecting toxins A and B
The most important preventive measure is the judicious use of antimicrobial
CDI Treatment – see UHL guidelines for latest advice. agents.
Treatment for CDI varies according to its severity. Educate the medical and nursing staff, as well as family and visitors,
Asymptomatic carriers: No treatment is necessary regarding the disease and its epidemiology, and emphasize compliance with
Mild, antibiotic-associated diarrhoea without fever, abdominal pain, or hand hygiene practices (such as washing with soap or antimicrobial soap and
leucocytosis: Cessation of antibiotic(s) may be the only treatment necessary water)
Mild to moderate diarrhoea or colitis: Metronidazole (oral or intravenous) or
vancomycin (oral) for 10 days
Severe or complicated disease: Vancomycin is considered to produce faster In a hospital setting - If a patient has had ≥3 unformed stools in 24 hours
symptom resolution and fewer treatment failures than metronidazole; in Order a C. difficile test if other aetiologies are ruled out

Return to Unit Overview

p126
 Leicester Medical School

Isolate patients with C. difficile immediately, even if you only suspect CDI
Wear disposable gloves and gowns when treating patients with C. difficile,
even during a short visit.
Perform hand hygiene after removing gloves. Alcohol does NOT kill C.
difficile spores. The use of soap and water is more effective than alcohol-
based hand rubs.
Treat according to local guidelines

If patient is positive for CDI

Continue isolation and contact precautions
Use antibiotics judiciously
Clean room surfaces thoroughly on a daily basis. Hospital transmission is
likely associated with the survival of spores on inanimate objects; therefore,
close attention to cleanliness and disinfective measures are important (e.g.,
use of contact precautions for 48 hours or longer following resolution of
diarrhoea, disposable electronic rectal thermometers, chlorine-containing
cleansers or other sporicidal agents)

INCIDENCE of C. difficile infections

The incidence of C. difficile infections increased rapidly in the 1990’s and early 2000’s.
Strict control measures were then introduced.
The incidence has decreased and has plateaued over recent years.
It remains an important problem.

Return to Unit Overview

p127
 Leicester Medical School

Clostridioides difficile – pathogenesis of C. difficile Infection (CDI)

C. difficile transmission
• Symptomatic and asymptomatic or undiagnosed patients excrete C. difficile, often for
prolonged periods
• Transmission is faecal-oral and probably occurs via the hands of health-care workers,
patients and their friends or family
• Spores can persist in the environment on surfaces, in food, soil and water for several
months

Host susceptibility to CDI

• In non-susceptible hosts, C. difficile spores can be excreted or result in asymptomatic C.
difficile colonization

• In susceptible hosts, bowel colonization resistance is diminished by reduction in the

diversity of the host microflora, usually due to antibiotics

Germination
• Spores interact with small molecular germinants, such as bile acids, triggering
germination into toxin-producing bacteria that multiply and adhere to host epithelium
• Sporulation provides vectors for onward transmission

Return to Unit Overview

p128
 Leicester Medical School

Toxin production and effects on colonic epithelium

• Non-toxigenic C. difficile strains do not produce toxin or disease, but have the
potential to be converted into toxin producers
• Toxigenic C. difficile strains produce toxin B with or without toxin A
• Toxin production causes changes to the colonic epithelium in patients with
CDI. Histological section of a colonic mucosal biopsy from a patient with
pseudomembranous colitis (left) shows areas of focal epithelial necrosis
associated with an inflammatory exudate. Endoscopic photograph (right)
shows superficial circumferential ulceration with overlying pseudomembranes
in a patient with CDI.

Symptomatic infection
• Clinical features of CDI include diarrhoea, abdominal pain and fever •
Severe infection can result in gross dilatation of the bowel and ileus,
risking bowel perforation.

Modified from Martin et al, 2016 Nature Reviews Gastroenterology & Hepatology

Return to Unit Overview

p129
 Leicester Medical School

Additional notes on treatment for C. difficile infection

Metronidazole Faecal Microbiota Transplantation

Metronidazole is the oldest antibiotic used to treat CDI.
Faecal microbiota transplantation (FMT) is a novel therapy that involves the transfer
It is a broad-spectrum antibiotic used to treat anaerobic infections. Metronidazole of stool from a healthy donor to a patient with C difficile infection (CDI) in order to
kills the vegetative forms of the Clostridioides bacteria but not the spores. Thus, it reconstitute the normal colonic microbial flora. FMT has been reported to
terminates the infection but leaves the patient susceptible to recurrences in the face repopulate the colonic flora, with efficacy rates of greater than 90% demonstrated
of persistent risk factors for CDI.
even in cases refractory to antibiotic therapy. Several studies have shown that FMT
In the USA, where CDI and recurrent CDI is a greater problem than in the UK, it is not by colonoscopy or enema is an effective approach for patients with recurrent C
recommended for treatment difficile colitis, with clinical success rates of up to 95%.
However, it should be noted that FMT carries the risk of infection transmission
Vancomycin (a Glycopeptide) (human immunodeficiency virus [HIV], hepatitis, and retrovirus). Administration of
Vancomycin has excellent activity against C difficile. This agent kills the organism by other bacterial preparations is under investigation.
inhibiting cell wall synthesis.
Oral vancomycin does not get absorbed and acts directly at the site of infection.
Vancomycin does not cross in the bowel from blood so is only effective when given
enterally. Therefore, IV vancomycin is not used here as it does not act directly on the NOTES: MRSA
site of infection.
Staphylococcus aureus and MRSA with regard to hospital acquired infections and
Fidaxomicin infection control.
Fidaxomicin is a novel macrocyclic antibiotic that inhibits bacterial nucleic acid
These notes are not a comprehensive review of Staph aureus and you should look at
synthesis. The drug is only available in an oral formulation and systemic absorption
the chapter in Lippincott’s on Staphylococcus aureus. These notes are related to
is minimal. Fidaxomicin has bactericidal activity against C. difficile, but reduced
activity against several enteric commensal bacterial species, particularly those hospital acquired infections and infection control
thought to confer colonization resistance against C. difficile
What is the source of Staphylococcus aureus infection?
Traditional CDI antibiotic therapies, including metronidazole and vancomycin, Staphylococcal bacteria are relatively common. S. aureus is both a commensal
suppress the intestinal microbiota. This persistent dysbiosis is postulated, in part, to organism and a pathogen. The anterior nares are the main ecological niche for S.
cause increased CDI recurrences. Thus, microbiota-sparing antibiotics promote C. aureus. Approximately 20% of individuals are persistently nasally colonized with S.
difficile colonization resistance and, at least in part, overcome this limitation. aureus, and 30% are intermittently colonized. However, numerous other sites may

Return to Unit Overview

p130
 Leicester Medical School

be colonized, including the axillae, groin, and gastrointestinal tract. Colonization Up to 1 in every 30 people are colonised by MRSA bacteria. Like other types of
provides a reservoir from which bacteria can be introduced when host defenses are staphylococci, it's usually harmless and not a cause for concern for most healthy
breached. Colonization clearly increases the risk for subsequent infection. Those people. However, it can cause problems if it's able to enter the body or it infects
with S. aureus infections are generally infected with their colonizing strain someone in poor health.
Colonization also allows S. aureus to be transmitted among individuals in both health MRSA infections can include syndromes of bacteraemia, pneumonia, endocarditis,
care and community settings. joint infections, and skin or soft-tissue infections.

MRSA = Meticillin-Resistant Staphylococcus aureus How MRSA is spread

Meticillin = Methicillin
MRSA bacteria are usually spread through skin-to-skin contact with someone who
What is MRSA? has an MRSA infection or has the bacteria living on their skin.
The bacteria can also spread through contact with towels, sheets, clothes, dressings
MRSA is a type of Staphylococcus aureus that is resistant to most beta-lactam or other objects that have been used by a person infected or colonised with MRSA.
antibiotics, antistaphylococcal penicillins (e.g., methicillin, oxacillin), and MRSA can survive for long periods on objects or surfaces, such as door handles, sinks,
cephalosporins. floors and cleaning equipment.
Methicillin is still used to describe resistance because of its historical role.
Treatment for MRSA
MRSA produces penicillin binding protein 2a, which confers resistance to all β lactam
antibiotics. Treatment of an in-patient with invasive MRSA:
This is a question in the small group work and you will need to look it up. Add that
MRSA was first reported in 1961, shortly after methicillin became available. information to these notes.
However, it took several decades before it became a problem. For example, in the
US and the United Kingdom the proportion of S aureus strains causing bacteraemia Infection Control for MRSA
that were methicillin resistant started to increase around 1990, and by the start of Infection control takes into account the properties of MRSA and the manner in which
the 21st century about half of the strains causing bacteraemia were resistant. That it is spread.
proportion has now dropped significantly in the UK to just a few percent. Strict infection control measures were introduced in the 1990’s and early 2000’s as
MRSA infections increased. These measures have been important in reducing the
Colonisation vs. Infection incidence of MRSA infections. However, they were introduced as a ‘bundle’ and it

Return to Unit Overview

p131
 Leicester Medical School

has proved difficult to dissect out which components are more important and Number of MRSA Blood
Financial Year
whether some should be removed. Stream Infections
2008/2009 14
The policy varies between countries and hospitals; but most include: 2009/2010 13
Active screening of high risk patients and exposed healthcare workers for 2010/2011 13
carriage 2011/2012 9
Strict implementation of transmission based precautions 2012/2013 2
Treatment of carriage using topical applications of mupirocin nasal cream (a
2013/2014 3
topical antibiotic) and washing with disinfectant agent, such as Stellisept® or
2014/2015 6
chlorhexidine.
2015/2016 1
Transmission based precautions: This includes hand washing and isolation
Hand hygiene remains the cornerstone for effective control in hospitals
How effective is hand hygiene? MRSA spreads from patient to patient via the hands
of health-care providers. Therefore, most experts agree that hand hygiene during
patient care is the most important measure to reduce the spread of MRSA in the
health-care setting. The results of a pan-European study showed that increased use
of alcohol-based hand rubs correlated with reduced MRSA rates, after adjustment
for multiple confounders. After the Clean Your Hands campaign in England and
Wales, MRSA bacteraemia rates declined from 1·88 cases per 10 000 bed-days to
0·91 cases per 10 000 bed-days. The use of barrier precautions is commonly used but
the evidence is less clear.

POLICY IN UHL:
The UHL policy can be viewed on this web-page. You do NOT need to read it all.
UHL uses a selective screening policy of high risk patients. Subsequent management
is also risk-based. However, you should note that the process of active screening and
management has had a dramatic effect on the incidence of MRSA Blood Stream
infection in UHL.

Return to Unit Overview

p132
 Leicester Medical School

NOTES: Norovirus Session 7 Self-study:

Norovirus
Complete the case studies and make any notes/infection models to help you
Lippincott’s Illustrated Reviews Microbiology only has a short paragraph on remember and retain the information you worked on during lectures and group
Norovirus. work.

Norovirus is a small, non-enveloped single stranded RNA virus that is a major cause
of acute gastroenteritis outbreaks. There is no specific treatment available so
treatment consists of supportive measures.
Transmission is mainly faecal-oral and also thought to be respiratory. Can be spread
following ingestion of contaminated food, direct person-to-person contact or
through contact with contaminated surfaces.
We used it in this case study to illustrate how to think about infection control
measures using the 4P model outlined in the lecture.

Return to Unit Overview

p133
 Leicester Medical School

Understand the importance of a travel history

Session 8: Hospital Acquired & Travel Related Infections
Form a differential diagnosis based on region of travel, incubation period
02 March 2021 and clinical presentation
Preparatory Work View, recall & review Describe common global and imported tropical infections and their
lectures 13 & 14 pathogenesis, including malaria, enteric fever, and dengue fever
MALARIA: Understand and describe the life cycle of malaria. Describe the
Find out about malaria
main symptoms and clinical features of presentation, the process of
9.00-10.30 Small Group Work 8 Hospital Acquired Infections diagnosis and principles of management.
(LIVE Online OR F2F) & Infection Prevention
Describe common travel related respiratory infections, including emerging
11:00 – 11:50 Lecture 15 Travel Related Infections infections
(This needs to be viewed Understand where and how to look up information on travel related
before group work 9) infections
With regard to COVID-19:
12:00 – 12:30 LIVE Q&A Session Virology
ONLINE Describe the structure of the coronavirus.
12:30 – 13:20 Lecture 16 COVID-19 Define the concept of an animal reservoir for coronaviruses (including bats,
snakes, pangolin, camels and other animals) & its major surface antigen -
(This needs to be viewed
spike (S) protein
before group work 9)
Explain how the virus gains entry to the human host and its subsequent
Notes & Self-Study Finish case studies
uptake and spread from person to person.
Describe the clinical symptoms and complications of this infection.
Describe how you would diagnose COVID-19 in a clinical setting
Learning Outcomes Briefly outline the management of COVID-19 including treatment options
and prevention including vaccination.
With regard to travel-related infections:
Define the concepts of mutation rate and production of variants
Apply the infection model to a patient presenting with an infection linked
to travel
Expand the description of pathogen/person/practice/place as it applies to
travel related infections

Return to Unit Overview

p134
 Leicester Medical School

Session 8: Preparatory Work

1) Please summit any questions either via email or the discussion board for
the Virology Q&A session live online at midday. All questions will be
anonymised. Below is a diagram of the Life Cycle of Plasmodium falciprium – the causative agent
of the most virulent form of malaria. The life cycle is quite complex but an overview
2) View, recall and review: View the lectures on Hospital Acquired Infections will be useful for understanding why it is difficult to treat this infection which still kills
(Lecture 13) and Infection Prevention (Lecture 14). Recall and review the
one child under 5 every 2 minutes.
information from the lectures before you start the group work. You could do
this on your own before the session or with your group at the beginning of
the session or a combination of both.

3) Preparation for group work: Read through notes on Clostridioides difficile,

MRSA and Norovirus (see session 7 notes). The case studies are related to
the lectures last week.

4) Preparation for lectures: Read through the lecture slides/summaries for

today’s lectures Travel-related Infections (lecture 15) and COVID-19 (lecture
16) and add any additional notes before and after you view the lecture.
There are other microbes which have similar patterns of replication and need two
5) Preparation for Travel-related Infections lecture (below): The lecture is on hosts – e.g. Toxoplasma gondii which causes toxoplasmosis – a relatively common
Travel-related infections. The most important of these is MALARIA. This will infection.
be included in the group work for next week and you can revisit this in
preparation for that session as well.

However, it would be good to have an understanding of Malaria before the lecture

on travel-related infections.
Below are links to two videos you should watch before the Travel-related
lecture. They are easy to watch and contain important and interesting information
on Malaria.

Return to Unit Overview

p135
 Leicester Medical School

You can then look up additional information in preparation for the group work next Fun malaria facts (only for your information):
week and to help you make study notes next week.
Europe was only declared malaria free by the WHO in 1975
Early studies on malaria were conducted on the mosquito species Anopheles
The CDC web site has a lot of information on Malaria and is worth reading. claviger which carried malaria in this country
Fevers which are suggestive of malaria are mentioned in Shakespeare
The ancient Egyptians fed their pyramid builders garlic in an attempt to help
stave off malaria
Tonic water was first introduced in 1852 as a prophylactic treatment for
malaria as Britain expanded its overseas territories – unfortunately many
people did not like the taste so they added gin thus the G&T was borne.

Lippincott’s Illustrated Reviews Microbiology only has a single page on Malaria. It is

fine for the basics of the life cycle which is under Blood and tissue protozoal
infections.

Schaechter's Mechanisms of Microbial Disease is better with more information;

although some details are beyond this session.

Return to Unit Overview

p136
 Leicester Medical School

Small Group Work 8: Hospital Acquired Infections

8.1 CASE STUDIES – Case Study A

A 78-year-old gentleman presented to Leicester ED in the early hours of

the morning with profuse diarrhoea. He is seen by a Foundation Year 2
(FY2) doctor and admitted up to the Acute Medical Unit (AMU) for review. 12.02.20 0430 Dr Smith
The FY2 who saw the patient was very busy. His brief clerking is opposite. Presenting Complaint: 2-day history of diarrhoea (6 times a day)
and associated abdominal discomfort.
No recent holidays
A 78 year old gentleman presented to Leicester ED in the early hours of Had take-away for dinner 2 days ago
the morning with profuse diarrhoea. He is seen by an SHO and admitted
up to the Acute Medical Unit (AMU) for review. The SHO who saw the Past medical History; Osteoarthritis, hypertension, gall stones
patient was very busy. His brief clerking is below. Drug History; Paracetamol, dihydrocodeine, bendroflumethiazide
No known allergies
Family History; nil
Social History; Lives with wife, retired teacher, smokes 10 cigarettes
daily

On examination
RR: 14 Heart sounds normal
Pulse 88 Chest Clear
Sats: 100% on air Abdomen: soft but generalised tenderness
BP 100/58
Temp: 38.3

Plan: IV fluids
Admit Medics
Paracetamol
?may need side room
S Smith FY2

Return to Unit Overview

p137
 Leicester Medical School

b. In addition to the information from the clerking, what other questions would
Imagine that you are one of the junior doctors working on the AMU and you are you like to ask in your history to establish the likely cause of his symptoms?
asked to go and see this patient.
a. What personal protection methods will you employ when you go to see this
patient?

On further questioning, it is apparent that the patient recently had a course of

amoxicillin for a community acquired pneumonia infection. As far as he knows, he
has not been in contact with anyone else with diarrhoea or vomiting. He and his wife
eat the same food and she has not developed any symptoms. He has not been abroad
in 8 years.

Using the clerking notes and the additional history above, please complete the ‘D&V
Patient Assessment Emergency Department & AMU’ Pathway (See pathway at end
of the case)

c. What advice is recommended for this patient?

Return to Unit Overview

p138
 Leicester Medical School

d. Having clerked this patient, what investigations would you like to request to g. Apart from amoxicillin, what other antibiotics are frequently associated with
aid your assessment of his condition? For each explain what you are looking a Clostridioides difficile infection?
for.

h. C. difficile exerts its pathological effects by producing toxins. What are these
e. Stool investigations come back positive for C. difficile. What type of bacteria toxins and how do they work?
is C. difficile? PLESAE NOTE THIS BACTERIUM IS NOW CALLED Clostridioides
difficile – make sure you know it

Using the RxGuidelines app (or RxGuidelines website) please look at the
treatment advice for Clostridioides difficile (found under abdominal infections).
i. How is the severity of the infection assessed? What different antibiotics are
advised for treatment?

f. Use of some antibiotics is linked to an increase in susceptibility to C. difficile

infections. What is the mechanism behind this?

Return to Unit Overview

p139
 Leicester Medical School

8.2 CASE STUDIES – Case Study C

In January, an 85-year-old woman presented to the LRI with a 48-hour history of

vomiting and diarrhoea. She appeared to be dehydrated and was admitted to a 6
patients bay on the ward for IV fluids.
The following day 3 patients and one member of staff seem to develop similar
symptoms and things only got worse when the day after, 9 patients appear to have
developed gastroenteritis and 5 members of staff call in sick.

a. What is the likely infectious agent at work here?

b. What is the transmission route of this pathogen?

Return to Unit Overview

p140
 Leicester Medical School

c. What precautions should have been considered to avoid this situation e. Using the 4 P’s model of infection control consider Norovirus and what
developing? measures could help prevent its spread.

d. What are the complications associated with this infection?

Return to Unit Overview

p141
 Leicester Medical School

Further information can be obtained from ‘Guidelines for the management of

norovirus outbreaks in acute and community health and social care settings’
available on the HPA website. See:
http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/Norovirus/
You should focus on the principles and see this as an example of a hospital acquired
infection.

Return to Unit Overview

p142
 Leicester Medical School

Lecture 15 Summary: Travel-related Infections “When did you return to the UK? When did the symptoms develop?” - This
is to allow us to calculate the incubation time of the infection.
Learning Outcomes:
“What are the symptoms?” - The symptoms and signs can give you an idea
Apply the infection model to a patient presenting with an infection linked of what body systems may be affects and the cause may be.
to travel “Did you do these activities....? How do you think you’ve contracted the
Expand the description of pathogen/person/practice/place as it applies to infection? Did you get any insect, tick or animal bites?” - Some activities that
travel related infections you must note include swimming, sexual activity and recreational activity.
Understand the importance of a travel history “Have you taken the appropriate vaccinations prior to the holiday/business
Form a differential diagnosis based on region of travel, incubation period trip etc?” - This is to ensure that they are covered for these infections.
and clinical presentation MALARIA – the most common travel-related infection in the UK
Describe common global and imported tropical infections and their
5 main species of Plasmodium (in the order of most common organism):
pathogenesis, including malaria, enteric fever, and dengue fever
MALARIA: Understand and describe the life cycle of malaria. Describe the falciparum
main symptoms and clinical features of presentation, the process of vivax
diagnosis and principles of management. ovale
Describe common travel related respiratory infections, including emerging malariae
infections knowlesii
Understand where and how to look up information on travel related Vector: female Anopheles mosquito.
infections
It is fairly uncommon to encounter with patients with travel-related infections. Incubation Period: Minimum 6 days. However, P. falciparum, this can be by 4 weeks
However, if this diagnosis is missed, then this can have deadly consequences on whilst for P. vivax/ovale, this can go up to 1 year!
patients and the infection can potentially spread between healthcare staff and the Symptoms and Signs: Fever, chills, headache, confusion, seizures, jaundice
public! Therefore, taking a travel history is important and your role is to be a haemoglobinuria.
detective in determining the organism and method of transmitting the infection!
Investigation:
Here are the aspects of the travel history that are important:
Blood film (thick and thin smears)
"Where have you come from?” - Depending on where patients have been, it
Blood test: FBC, U&E, LFT
is important to think of the common prevalent infections that can be found
CXR
especially in the sub-saharan Africa, South-east Asia and South American
CT-Head
countries.

Return to Unit Overview

p143
 Leicester Medical School

Management: Prevention methods: Vaccination (only 50-70% protective), good water and food
hygiene
Removal of the vector (mosquito): bed nets, sanitation facilities.
Drugs: artesunate, quinine (IV/PO), doxycycline. Don’t use chloroquine Complications include intestinal haemorrhage & perforation, seeding – 10%
(unless for P.vivax). Primaquine is given for liver-related malaria. (However, mortality (untreated). There is also possibility to be a chronic carrier in 1-5% of cases.
you don’t give this for G6PD patients – why? Relate this back to MEH
Please be aware that there are other ‘food poisoning’ salmonella that is not under
module!).
the category of enteric fever. This is usually caused by Salmonella typhimurium or
ENTERIC FEVER (TYPHOID FEVER – secondary to Salmonella typhi or salmonella enteritidis. This is usually self-limiting disease. However, it can cause
Salmonella parathyphi) bacteraemia, sepsis and deep-seated infections for immunocompromised patients.

Mechanism of infection – faecal-oral from contaminated food/water – source is NOVEL VIRUS INFECTIONS
cases or carriers
Examples include:
Virulence factors:
Infleunza pandemic cases such as in 1918-1919 ‘Spanish flu’ (H1N1), 1957
Low infectious dose ‘Asian flu’ (H2N2), 1968 ‘Hong Kong flu’ (H3N2), 2009 ‘Swine flu’ (H1N1).
Survives gastric acid Coronavirus pandemic cases such as 2003-2004 ‘SARS-CoV’, 2012-present
Fimbriae adhere to epithelium over ileal lymphoid tissue (Peyer’s patches) ‘MERS’, 2019- present ‘COVID-19’.
→ RE system / blood
In summary:
Reside within macrophages (liver/ spleen/ bone marrow)

Susceptible patients: Usually children. Travellers from Asian countries (can also be
found in African and South America).
Incubation Period: 7-14 days
Symptoms and Signs: systemic manifestation: fever, headache, abdominal
discomfort, dry cough, bradycardia.
Diagnostic investigations: blood culture
Treatment options: IV ceftriaxone, Azithromycin, Ciprofloxacin (but there is
increasing resistance to this antibiotic)

Return to Unit Overview

p144
 Leicester Medical School

Lecture 16 Summary: COVID-19

Learning Outcomes:

Describe the structure of the coronavirus.

Define the concept of an animal reservoir for coronaviruses (including
bats, snakes, pangolin, camels and other animals) & its major surface
antigen - spike (S) protein
Explain how the virus gains entry to the human host and its subsequent
uptake and spread from person to person.
Describe the clinical symptoms and complications of this infection.
Describe how you would diagnose COVID-19 in a clinical setting
Briefly outline the management of COVID-19 including treatment options
and prevention including vaccination.
Define the concepts of mutation rate and production of variants
Please be aware that the information in this summary and lecture are correct at
the time of writing – 02 February 2021.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19 is a virus

approximately 100nm in diameter. It belongs to the viruses known as coronaviridae
which are large, enveloped, pleomorphic particles with a distinctive arrangement of
spikes projecting from their surfaces (“corona”). It has a large genome of
approximately 28-32 KBs and is composed of positive single stranded RNA. This
strand is used as mRNA for replication of viral particles while the + strand RNA is
converted to –negative stranded RNA to use as the template for the new + strand
RNA that is packaged into the emerging particles. A major spike protein on the
surface is the major antigen, used to gain entry (via attachment to the Ace2
transmembrane protein) into cells and the target of vaccines. The entire replication
process is approximately 10 hours. This short replication period combined with the

Return to Unit Overview

p145
 Leicester Medical School

use of RdRp - RNA-dependent RNA polymerase (which is error prone) - means that hospitalisation and death have been estimated to be 13 x higher and 630 x higher,
the virus has a high mutation rate and numerous variants have emerged across the respectively, in the 85+ age group. The incubation period is unclear but seems to be
world. approximately seven days and people with mild or no symptoms can still infect
others. The major symptoms may include any or all of the following: fever, headache,
COVID-19 is an acute viral infection of the respiratory tract (nose, mouth, throat,
muscle/joint pain, extreme fatigue, dry cough and loss of taste/smell.
bronchial tubes and lungs). it is a highly infectious illness which spreads rapidly in
communities and even people with mild or no symptoms can infect others. It seems
COVID-19 is diagnosed by nasopharyngeal swab which detects the viral RNA using
to have originated by zoonotic transfer in Wuhan, China in December 2019 and
reverse transcription polymerase chain reaction (RT-PCR). While lateral flow
spread rapidly around the world with WHO declaring it a pandemic on 11 March
(antibody/antigen detection systems) exist there is some question as to their
2020.
reliability and sensitivity. Several new vaccines have been approved for use in the UK
Until 2002 the identified coronaviruses caused mild symptoms – accounting for 10- – they are different in their design but all aim to provoke an immune response in
30% of winter colds. But new viruses emerged in 2002, 2012 and 2019 - SARS-CoV-1, order to decrease severity of the disease particularly in vulnerable patients.
MERS & SARS-CoV-2 respectively. All appear to have arisen through zoonotic transfer
from other animals although all three are suspected to have originated in bats.
Coronaviruses are transmitted from person to person via the respiratory route
(coughing, sneezing, and inhaling) and it would seem that COVID-19 is no different
with potential transmission routes as follows:
a. small droplets (<5 µm in diameter) can evaporate into ’droplet nuclei’,
remain suspended in air for significant periods of time and could be inhaled.
b. large droplets (>5 µm in diameter) that fall rapidly to the ground and are thus
transmitted only over short distances
c. larger droplets are also known to transmit viruses, usually by settling onto
surfaces that are touched and transported by hands onto mucosal
membranes such as the eyes, nose and mouth. The characteristic diameter
of large droplets produced by sneezing is ~100 µm while the diameter of
droplet nuclei produced by coughing is on the order of ~1 µm
The symptoms range from none (asymptomatic) to very severe causing
hospitalisation and even death in some patients especially those who are
immunocompromised and/or older. The biggest risk factor is age. The risk of

Return to Unit Overview

p146
 Leicester Medical School

Session 8 Self-study:

1. Consider making your own summary notes and/or infection model on the three
case studies and infections. Each case study makes a good exam question.

2. Finish the case studies.

Return to Unit Overview

p147
 Leicester Medical School

Session 9:
8: Travel
Case Studies
Related
Linked
Infection
To Biofilms
Case Studies
March
09 March
2021
2021 Learning Outcomes – related to the immunocompromised host

Preparatory Work View, recall & review Apply the infection model to a patient who is immunocompromised
lectures 15
13 & 16
14
Describe the main reasons for a patient to be immunocompromised
Find out about malaria
Understand the links between the innate and adaptive immune system and
9.00-10.30 Small Group Work 9
8 CaseInfection
Line studies in&individuals
Staph situations and illnesses where a patient is immunocompromised
(LIVE Online
F2F) OR F2F) epidermisfrom travelling
returning
To consider primary immune deficiencies linked to patterns of infection.
abroad
Endocarditis
To further expand your knowledge of microbial pathogenesis
11:00
11:00 –– 11:50
11:50 Lecture
Lecture 17
15 Immunocompromised Host
Travel Related Infections
To consider aspergillus as a cause of fungal infection in the
(Live F2F Simulcast Session)
(This needs to be viewed immunocompromised
12:00 – 12:30 beforeLecture
Mini group work 9) Vaccinations To consider the manifestations of varicella-zoster infections in the
12:00 – 12:30 LIVE Q&A Session
(This needs to be viewed Virology immunocompetent and immunocompromised
ONLINE
before group work 10) Learning Outcomes – related to vaccinations
12:30 – 13:20 Lecture 16 COVID-19 Know the key definitions – immunisation, vaccination & vaccines
Notes (This needs to be viewed Legionnaires’ Disease
before group work 9)
Understand the concepts of active and passive immunisation
Self-Study Complete case studies
Notes Clostridioides
Malaria Notesdifficile Understand the impact of active immunisation (vaccination)

Be cognisance of routine immunisations in the UK

Learning Outcomes
With regard to travel-related infections: Appreciate the general contraindications to immunisation
Apply the infection model to a patient presenting with an infection linked
Comprehend the risks and misconceptions around vaccines

Return to Unit Overview

p148
 Leicester Medical School

Session 9: Preparatory Work Small Group Work 9: Three Case Studies A, B and C involving
Travellers Returning to the UK
1) View, recall and review: View the lectures on Travel-Related Infections
(Lecture 15) and COVID-19 (Lecture 16). Recall and review the information 9.1 CASE STUDY A – Traveller Returning from the DRC
from the lectures before you start the group work. You could do this on your
own before the session or with your group at the beginning of the session or
a combination of both. A 45-year-old businessman presented to the emergency
department with a 2 day history of fever. He had returned 2
2) Preparation for group work: In particular look at information on Malaria.
This is an important topic and you will need to make notes. While you can weeks age from a trip to visit family in the Democratic Republic of
do this after the group work case studies today, you should start the process Congo (DRC). He felt lethargic and had loose motions and a mild
if you have time. cough, but no other symptoms. He was originally from DRC but
had lived in the UK for 8 years.
3) Preparation for lectures: Read through the lecture slides/summaries for
today’s lectures The Immunocompromised Host (lecture 17) and The department is very busy and he has to be seen on a trolley in
Vaccinations (mini-lecture) and add any additional notes before and after the corridor. On examination he is alert and conversant. He has a
you view the lectures. temperature of 38.8 C with BP 135/78 and HR 96 bpm. He has
slightly dry mucous membranes. Cardio-respiratory, abdominal
4) There is no specific preparation for the lecture on the and neurological examination are normal.
Immunocompromised Host.

a. What additional questions would you like to ask in the history? (Suggestion –
think about questions related to his travel history and then questions relating to
his symptoms).
Note: refer to the slide from lecture 1 Introduction to Infection (see below) – this
may help you come up with questions.

Return to Unit Overview

p149
 Leicester Medical School

b. Where might you look for information regarding any potential ‘outbreaks’ of
infection in the area he has travelled to?

Return to Unit Overview

p150
 Leicester Medical School

c. Considering his region of travel and the potential incubation period, what are the Fungus
possible infecting organisms?
NOTE: You may refer to the lecture on Travel Infections, or this useful article from the
British Infection Association (http://www.journalofinfection.com/article/S0163-
4453(09)00154-6/pdf , Tables 2 and 3).
Protozoa

Start by working out the likely incubation period and then the part of the world the
Helminth
patient travelled to. Those two bits of information will help to narrow down the
options.

Put in up to six examples in the table below. Do not spend too long on this
question.

Type of Common/ Occasional Rare but

microorganism serious important
d. Given the history, where is the patient best managed and what precautions need
Virus to be taken? (Note the potential risk of viral haemorrhagic fever (VHF))
Reminder: Make use of the general principles covered in previous sessions

Bacteria

Return to Unit Overview

p151
 Leicester Medical School

e. What would your initial investigations be?

g. What species of malaria is he most likely to be infected with?

h. Describe the features of severe malaria in adults.

(Note: you may refer to the British Infection Association’s UK Malaria Treatment
Guidelines, https://www.journalofinfection.com/article/S0163-4453(16)00047-
5/fulltext

f. How would you manage this patient while awaiting his results?
Consider basic infection management principles from previous sessions.

4 hours later, the laboratory calls telling you that malaria has been found on the
blood film. The parasite count is 11%. His Hb is 75g/L and platelet count is 62. You
go to assess the patient. He has become more unwell since you last reviewed him.
He appears confused and short of breath, and his BP is now 80/55mmHg. The
nursing staff are concerned that he has not passed urine since being on the ward.

Return to Unit Overview

p152
 Leicester Medical School

i. Which groups of people are more likely to develop severe malaria?

j. An arterial blood gas shows that he has a pH of 7.25. His chest X-ray is shown
below. What does it show? Where is the best place for the patient to be managed?
Discuss possible treatment options.

NOTE: the drug treatment of Malaria requires specialist knowledge.

It is worth looking up the names of some of the Malaria drugs and you may be
advised to take these as prevention if you travel to areas with malaria.
There is an increasing problem of resistance to Malaria – there are numerous
research projects in the UK and around the world looking at new and innovative
ways of tackling this issue. Some resistance is due to Kelch Proteins.
https://www.nature.com/articles/s41467-020-20805-w

Return to Unit Overview

p153
 Leicester Medical School

k. After 48hrs of treatment the patient is improving clinically. Daily blood films 9.2 CASE STUDY B - Traveller Returning from Malawi
show that the parasite count is reducing, however the laboratory tell you that they
have also seen evidence of P. vivax infection (i.e. a mixed infection). Which other
treatment is required and why? Which blood test needs to be done before A 22 year old medical student returned from her medical elective
commencing the treatment? to Malawi 7 weeks ago. She went to see her GP as for the last 1
week she had felt unwell with lethargy, low-grade fevers, and
general body ache. She had also been feeling wheezy for the past
few days, and had an itchy rash on her legs. She had first noticed
the rash after a day of swimming in Lake Malawi, but it had
gradually become more pronounced and generalised. She had no
past medical history and was not taking any medication. She
travelled with her boyfriend who was well. She took her malaria
chemoprophylaxis and had all her pre-travel vaccinations.

l. On the day of discharge the patient tells you that he is due to go back to the DRC On examination her temperature is 38.1. Her BP is 129/72, her
the following month for business purposes. You advise him to take malaria heart rate is 92 bpm and her respiratory rate is 16/min. On
chemoprophylaxis, but he tells you that he doesn’t need to as he now has immunity auscultation her chest is clear. She has marked non-tender
to malaria, especially as he used to live in the DRC. How accurate is this statement? hepatosplenomegaly but no lymphadenopathy. There is a
noticeable macular rash by her left ankle.

a. Considering her region of travel and the potential incubation period, what are
the possible infecting organisms?
NOTE: Again you may refer to the lecture on Travel Infections, or the article from
the British Infection Association - See 9.1 Case Study A, Question c.

Return to Unit Overview

p154
 Leicester Medical School

The GP performs some blood tests: c. Look up the lifecycle of the relevant organism to understand how this infection
is transmitted, and how the acute and chronic stages of the infection present and
differ. What are the consequences of chronic infection, and how is it diagnosed?
Malaria – thick and thin film NEGATIVE x3
Albumin 36 g/L (35 to 50)
Alkaline Phosphate 77 iu/L (0 to 130)
Alanine Transaminase (ALT) 25 iu/L (2 to 53)
Total Bilirubin 8 umol/L (0 to 21)
C-Reactive Protein 112 mg/L (0 to 10)
9
White Cell Count 12.6 x 10 /L (4.0 to 11.0)
Haemoglobin 122 g/L (115 to 165)
9
Neutrophil Count 11.62 x 10 /L (1.50 to 7.50)
9
Lymphocyte Count 0.38 x 10 /L (1.00 to 4.00)
9
Eosinophil 4.3 x 10 /L (0.00 to 0.45)
d. What is the treatment for acute and chronic infection?

b. What is the likely diagnosis? What does the high eosinophil count indicate?
(NOTE: Table 7 of the same paper may be helpful & refer back to Lecture 4 Innate
Immunity)

Return to Unit Overview

p155
 Leicester Medical School

9.3 CASE STUDY C - Traveller Returning from Hong Kong

a. What additional questions would you like to ask in the history to help reach a
diagnosis?
A 54 year old woman presents acutely unwell with a 3 day
history of fever, shortness of breath and productive cough. She
had returned from Hong Kong 8 days before where she had been
on holiday, and had stayed in a hotel with family.
On examination she was confused and breathless (respiratory
rate 40/min) with oxygen saturation 85% on air, temperature
39.8oC. Blood pressure was 112/64 and heart rate 96 bpm. On
auscultation of the chest bi-basal crackles were heard.

NOTE: NORMAL O2 SATURATION LEVELS ARE GREATER THAN 96%

(i.e. a measurement of how much oxygen there is in the blood).
You will cover this in the Respiratory Unit.
HEARING CRACKLES IN THE LUNG IS AN INDICATION OF FLUID IN b. What urgent investigations would you request (and why)?
THE ALVEOLI OR INTERSTITIAL SPACES (again, this will be covered
in the Respiratory Unit)

Return to Unit Overview

p156
 Leicester Medical School

c. The initial blood tests and chest X-ray are below. What are the key abnormal
findings in the blood tests? Can you explain these abnormalities?

18/02/2020 06:00 Plasma

Sodium 127 mmol/L (133 to 146)

Potassium 4.0 mmol/L (3.5 to 5.3)
Urea 8.5 mmol/L (2.5 to 7.8)
Creatinine 101 µmol/L (60 to 120)
Albumin 30 g/L (35 to 50)
Alkaline Phosphatase 98 iu/L (30 to 130)
Alanine Transaminase (ALT) 36 iu/L (2 to 53)
Total Bilirubin 8 µmol/L (0 to 21)
C-Reactive Protein 443 mg/L (0 to 10)
White Cell Count 12.6 x 109/L (4.0 to 11.0)
Haemoglobin 122 g/L (115 to 165)
Neutrophil Count 11.62 x 109/L (1.50 to 7.50 )
d. Is the chest X-ray normal or abnormal?
Lymphocyte Count 0.38 x109/L (1.00 to 4.00 )

Return to Unit Overview

p157
 Leicester Medical School

NOTE: YOU WILL COVER PNEUMONIA IN THE RESPIRATORY UNIT NEXT SEMESTER The patient’s condition deteriorates rapidly after admission and the patient is
WITH A WHOLE SESSION ON PNEUMONIA. THIS CASE STUDY IS TO EMPHASISE transferred to ITU for ventilation isolated in a side-room.
THAT IN SOME CASES THERE CAN BE A LINK WITH TRAVEL.
In view of the more detailed history, further microbiology investigations are
e. What is your working diagnosis and how may the severity of this condition be requested
assessed? Are there any particular infective diagnoses that need to be considered
Later that day two microbiological investigations are reported – see below
due to her recent travel?

18/02/2019 06:17 Urine for Antigen Detection

L. pneumophila Sgp1 antigen Detected

f. Should she be nursed in a side room? 18/02/2019 06:18 Nose/Throat swabs

SARS-CoV-2 RNA NOT Detected by PCR

Influenza A virus RNA NOT Detected by PCR
The patient is started on an empiric antibiotic regimen. You are not required to Influenza B virus RNA NOT Detected by PCR
know details of antibiotic treatment at this stage. RSV type A RNA NOT Detected by PCR
However, it is worth noting that in situations like this it is standard to use two RSV type B RNA NOT Detected by PCR
antibiotics to cover the potential pathogens since you are still guessing as to the
Parainfluenza 1 RNA NOT Detected by PCR
exact cause.
Parainfluenza 2 RNA NOT Detected by PCR
In UHL the recommendation is to use co-amoxiclav and clarithromycin or
doxycycline Parainfluenza 3 RNA NOT Detected by PCR
Parainfluenza 4 RNA NOT Detected by PCR
The one agent, the co-amoxiclav is directed against some common, or typical
pathogens like pneumococci; while the clarithromycin is directed against atypical Adenovirus DNA NOT Detected by PCR
pathogens.

Return to Unit Overview

p158
 Leicester Medical School

g. What is the clinical diagnosis?

Notes & Additional Questions: Legionnaires’ Disease

Complete the following if there is time in the group work these will form the basis
of your notes on this atypical pneumonia – you could use the questions to help you
make an infection model for this infection:
Legionnaires’ Disease (Legionella pneumophila)

NOTE: It is important to draw out details about the activities the patient has been
involved in and whether there was air conditioning at the hotel. Water in air
conditioning units or hot water tanks are a common environment for this bacteria
to grow.
h. What type of bacteria is this?

i. How is the infection normally spread?

Return to Unit Overview

p159
 Leicester Medical School

j. Legionella pneumophila uses a feature of the innate immunity to aid its Lecture 17 Summary: Immunocompromised Host
replication. What is this?
Learning Outcomes:
Apply the infection model to a patient who is immunocompromised
Describe the main reasons for a patient to be immunocompromised
Understand the links between the innate and adaptive immune system and
situations and illnesses where a patient is immunocompromised
k. Now a diagnosis has been reached how should the management plan be
amended? To consider primary immune deficiencies linked to patterns of infection.
Describe the immune defects associated with the immunodeficiency
diseases
Describe the warning signs that suggest a primary immunodeficiency
disease
Describe the most common primary immunodeficiency diseases
l. Does this patient need to continue to be cared for in a side room? Use of the clinical presentation to understand the immune defects and
guide the management of primary immunodeficiency diseases
Describe the common causes of secondary immunodeficiencies
To further expand your knowledge of microbial pathogenesis
To consider aspergillus as a cause of fungal infection in the
immunocompromised
To consider the manifestations of varicella-zoster infections in the
m. What is the role of the local UK Health Security Agency (formerly Public Health immunocompetent and immunocompromised
England)?
https://www.gov.uk/government/organisations/uk-health-security-agency The immunocompromised state is when the immune system is unable to
respond appropriately and effectively to infectious microorganisms. This can be
https://www.gov.uk/guidance/notifiable-diseases-and-causative-organisms-how-
due to defect in one or more components of the immune system (either the
to-report innate or adaptive immune system). There are 2 main classes of
immunodeficient state: primary and secondary.

To suspect immunodeficiency – the infection will be defined as “SPUR”

Severe - ie life threatening and requiring IV antibiotics or hospital admission

Return to Unit Overview

p160
 Leicester Medical School

Persistent - ie despite conventional treatment, the disease is not responsive Combined B and T cell defects
/ long treatment time)
Severe combined immunodeficiency (SCID)
Unusual - this depends on the site of infection (ie deep infections) or nature
Wiskott-Aldrich syndrome
of organisms (ie opportunistic infection eg candida)
Ataxia telangectasia
Recurrent - this means that the disease keeps re-emerging in the same
patient T cell defects

PRIMARY IMMUNODEFICIENCY DISEASE Di George syndrome

CD3 deficiency
Primary immuno-deficiency disease diagnosis is often performed late (on average of MHC class II deficiencies
8-12 years!) - therefore, 37% of patients will already have permanent tissue/organ TAP-1 or -2 deficiency (MHC class I)
damage. Primary immunodeficiency diseases is generally due to congenital causes.
This is due to intrinsic gene defect (approximately 275 genes affected – causing Phagocytic defect (10%)
either a missing protein, cell or non-functional components as seen in chronic Defects in respiratory burst
granulomatous disease)
Chronic granulomatous disease (CGD) - normally presents with skin
Let’s look at the different types of primary immunodeficiency disease (the important infections/abscess, pulmonary aspergillosis (Halo sign on HRCT)
ones to remember are highlighted)
Defect in fusion of lysosome/phagosomes
Antibody defects (65%)
Chediak-Higashi syndrome
Defect in B cell development
Defect in neutrophil production and chemotaxis
X-linked agammaglobulinaemia (Bruton’s disease)
Cyclic neutropenia
Defect in antibody production LAD protein deficiencies (LAD is used by neutrophils to get into tissues)
Common Variable Immunodeficiency (most prevalent that requires How to diagnose patients?
treatment!)
Selective IgA deficiency (most prevalent that does not require treatment & Age of symptom onset
most patients are asymptomatic) Onset < age 6 months highly suggests a T-cell or phagocyte defect.
IgG subclass deficiency (IgG2) Onset > 6 months and <5 years old often suggests a B-cell, antibody or
Hyper-IgM syndrome (due to missing CT4 component on T-cell) phagocyte defect.
T-cell defects (15%)

Return to Unit Overview

p161
 Leicester Medical School

Onset >5 years old and later in life usually suggests a B-cell Immunoglobulin replacement therapy (IRT) - goal is for serum IgG >8g/L &
/antibody/complement or secondary immunodeficiency (secondary used for CVID, Bruton’s disease, IgA deficiency, Hyper-IgM syndrome.
immunodeficiency which commonly is caused by malnutrition). Hematopoietic Stem Cell therapy (HSCT, 90% success) - for SCID
Comorbidities
Type of microbes & Sites of infection
Autoimmunity and malignancies
Organ damages (lung function assessment)
Avoid non-essential exposure to radiation

SECONDARY IMMUNODEFICIENCY DISEASE

Secondary immunodeficiency diseases are usually acquired. This is due to the
following reasons:
Decreased production of immune components due to malnutrition, infection (eg
HIV), liver diseases, haematological malignancies, therapeutic treatment
(corticosteroids, cytotoxic drugs) or splenectomy.
Increased loss of immune components due to protein-losing conditions
(nephropathy, enteropathy) or burns.
Increased susceptibility to infections due to chemotherapy, invasive devices.

Mini-Lecture: Vaccinations
Treatments:
Learning Outcomes:
Supportive treatment
Know the key definitions – immunisation, vaccination & vaccines
Infection prevention (eg prophylactic antimicrobials) Understand the concepts of active and passive immunisation
Treat infections promptly and aggressively (eg passive immunization)
Understand the impact of active immunisation (vaccination)
Nutritional support (Vitamins A-D)
Be cognisance of routine immunisations in the UK
Use UV-irradiated, CMV negative blood products only
Appreciate the general contraindications to immunisation
Avoid live attenuated vaccines in patients with severe PIDs (SCID)
Comprehend the risks and misconceptions around vaccines
Specific treatment

Return to Unit Overview

p162
 Leicester Medical School

This is a short lecture and making your own summary would be a useful way of Session 9 Self-Study:
learning and understanding this topic.
Additional note: Passive immunisation is often used to boost the immune systems 1. Complete the case studies.
of immunocompromised individuals such as new monoclonal therapies for the
prevention of COVID-19. Antibody treatments are used for many diseases. Note that 2. Complete the extra work on Legionnaires Disease
snake venom antisera are also considered as passive treatment for snake bites – the
antibodies to the venom are generated in another animal such as a horse and Use the lecture, Lippincott’s and the group work to make study notes on Malaria.
administered to counteract the effects of the venom. This is an important topic include an infection model and use the notes in Session 8:
Preparatory Work to help you.

Return to Unit Overview

p163
 Leicester Medical School

Learning outcomes
Session 10: Immunocompromised Host, E.Coli &
Influenza 16 March 2021 With regard to E. coli
Preparatory Work Read about influenza Describe the biology of E. coli including the identification and serology
View, recall & review Describe the role of E. coli in health and disease
lectures 16 & 17 Describe E. coli as a cause of diarrhoea including its pathogenesis, role of
toxins and clinical features
9.00-10.30 Small Group Work 10 IMMUNOCOMPROMISED
HOST case studies Describe E. coli as a cause of urinary tract infections with virulence factors
(LIVE F2F)
and clinical features
11:00 – 11:50 Lecture 18 Escherishia Coli (E.Coli) Describe E. coli as a cause of blood stream infections and sepsis
(This needs to be viewed Describe the management of E. coli infections
before group work 11)
12.:00 - 12:30 LIVE Q&A Session ONLINE Immunology
With regard to Influenza
12:30 – 13:20 Lecture 19 Influenza
Describe the structure of the Influenza virus – containing a genome of
(This needs to be viewed segmented negative-sense RNAs belonging to three types: A, B, and C and its
before group work 11)
replication.
Notes Herpes zoster Define the concept of an animal reservoir for type A influenza (including
Staphylococcus aureus poultry, horses, pigs, and other animals) and its major surface antigens -
hemagglutinin (HA) and neuraminidase (NA)
Immunocompromised host
Explain how the influenza virus gains entry to the human host through
Febrile neutropenia attachment of the viral HA to sialic acid–containing glycoproteins/glycolipids
Escherichia coli and subsequent uptake into an endocytic vesicle and is spread from person
to person via respiratory droplets that infect the upper and lower respiratory
Influenza
tract.
Self-Study Complete case studies & Describe the clinical symptoms (including headache, high fever, sore throat,
notes runny nose, muscle aches and pains etc.) and complications of influenza
infection (including viral pneumonia, secondary (bacterial) pneumonia,
central nervous system syndromes, or Reye syndrome).
Describe how you would diagnose flu in a clinical setting

Return to Unit Overview

p164
 Leicester Medical School

Briefly outline the management of influenza including treatment options and

prevention Treatment (antivirals, NA inhibitors) and prevention including The government produces regular statistics (this is for the 2019/2020 season):
vaccination and how this is determined by WHO each year.
Define the concepts of antigenic shift (acquisition of a novel HA and NA by
the virus) and antigenic drift (yearly accumulation of mutations in the HA and
NA).

Define the concepts of pandemics and epidemics (seasonality) and how

The CDC website has lots of information on Influenza:
these may arise in relation to influenza.

Session 10: Preparatory Work

1) View, recall and review: View the lectures on Immunocompromised Host

(Lecture 17) and Vaccinations (Mini-Lecture). Recall and review the information
from the lectures before you start the group work. You could do this on your
own before the session or with your group at the beginning of the session or a
combination of both.

2) Preparation for group work: refer back to your lecture summary and notes on
the immunocompromised host from session 9.

3) Preparation for lectures: Read through the lecture slides/summaries for today’s
lectures E.Coli (lecture 18) and Influenza (lecture 19) and add any additional
notes before and after you view the lectures.

4) In preparation for the lecture on Influenza: look at some information on

Influenza below:

Return to Unit Overview

p165
 Leicester Medical School

Small Group Work 10: IMMUNOCOMPROMISED HOST

Case Studies

10.1 CASE STUDIES – Case Study A

Tom is a 19 year old man recently diagnosed with a T-cell Lymphoma. This is a
malignancy of T-cells and commonly presents with a mass related to a site of
lymphoid tissue. This could be in the neck, chest or abdomen. It is treated with
intensive chemotherapy and usually responds well to chemotherapy.
Tom is now three months in to his treatment.
The chemotherapy is anti-mitotic and acts on all rapidly dividing cells within the
body.
Tom’s last course of treatment was ten days ago. Ten days later is when the
toxicity of the chemotherapy on dividing cells is most evident.
Tom is admitted to the recently built Teenage & Young Adult Cancer Unit at the
LRI with a fever and a general feeling of weakness.
His mouth has been sore for the past three days and it has been painful to eat.
He has had a few loose stools; but not watery.
He has no cough, no urinary symptoms and no abdominal pain.

In order to deliver the intravenous chemotherapy Tom has a Hickman Line. A (http://alexsaplasticanaemia.blogspot.co.uk/2009_04_
01_archive.html )
Hickman line is a plastic tube inserted via the subclavian (or jugular) vein and into
the right atrium. It is tunneled under the skin and comes out at a convenient point
on the chest. Opposite is a diagram and a picture of a Hickman line.

Return to Unit Overview

p166
 Leicester Medical School

a. Review the history above. Make a list of all the reasons why Tom is
On admission, Tom has the following observations: immunocompromised
Temperature: 38.7oC Factors affecting the innate immune system:
Respiratory rate: 14/ minute
Pulse: 90/minute
BP: 135/80 mmHg
On examination of his mouth he has MUCOSITIS. Mucositis implies
inflammation of the lining of the mouth, sometimes with superficial ulcers. This
is a consequence of the chemotherapy since mucosal cells have a fairly rapid
turnover and are therefore affected by chemotherapy that targets cell division.
However, there is no other feature of infection in the mouth.
His chest is clear and his abdomen is soft. There is no site of infection around
the site of the Hickman line. There is no rash on his skin and he is fully
conscious and alert. Adaptive Immune system:
The nurses report that a blood test taken the day before shows:

Haemoglobin 75 (N: 120 – 140 g/l)

Platelets 50 (N: 150 – 400 x 109/l)
White cell count 3.1x109/L (N: 4 – 11x109/L)
Neutrophils 0.1x109/L (N: 2 – 7.51x109/L)

Return to Unit Overview

p167
 Leicester Medical School

b. You arrange for some investigations including:

Blood culture Even though patient is stable and there is no site of infection nor a microbial
CRP diagnosis, it is essential to start treatment immediately. This is because the patient
is profoundly immunocompromised and the main risk is death from a bacterial
Blood count
septicaemia. This can develop over a few hours and overwhelm a patient who has
Biochemistry no (or very few) neutrophils. When cancer treatment with chemotherapy was
The blood culture takes up to two days before a result is available. introduced in the 1960’s the policy with fevers in these patients was to collect
The blood count is unchanged from the previous day. samples and watch them for the first 24 hours until there was more evidence of an
infection. The mortality was high – in some cases around 25% or greater. The
principle of starting ‘empiric’ intravenous broad spectrum antibiotics was
CRP = 358 mg/L (Normal: < 5 mg/L) introduced and resulted in a reduced mortality that is now in single figures or in
some cases below 1%.

What is the significance of the raised CRP level?

Look through the sections of the guideline.

There is also a pdf chart that you can open.

c. You are concerned that Tom falls into the category of “Febrile Neutropenia”. A screen shot of the guidance is on the next page.
You wisely decide to look at the treatment guidelines. Open the RxGuidelines If you open it directly on your iPad you will get a clearer copy.
App. Click on secondary care – then secondary care adult – then Haematology
& Oncology – then Febrile Neutropenia

i) Does this meet the criteria for neutropenic sepsis?

ii) What treatment action do you take?
iii) At this stage you do not have a microbiological diagnosis of a bacterial
infection nor a site of infection. Why have you therefore started
treatment?

Return to Unit Overview

p168
 Leicester Medical School

d. Over the next 48 hours the patient continues to spike a fever.

You review the Febrile Neutropenia Guidelines. What action do you take? What
specific organisms are you targeting with reference to the Hickman Line, and why?

e. What further investigations do you perform at 48 hours? What are the routine
tests for a suspected invasive fungal infection? Explain how the tests relate to the
structure of a fungus?

Return to Unit Overview

p169
 Leicester Medical School

f. Despite the additional treatment Tom remains pyrexial and you are now at Day
5. His CRP remains high and you are concerned his condition is starting to
deteriorate. His respiratory rate has increased to 23/minute. He has now
developed a cough.

You arrange for a Chest X-ray and then for a CT scan of his chest. These are shown
below. Try to identify the obvious abnormal features in the lung field. You are not
expected to interpret CT scans at this stage; but it is useful (and interesting) to see
the changes.

Return to Unit Overview

p170
 Leicester Medical School

Return to Unit Overview

p171
 Leicester Medical School

The CT scan report is below: g. Why was the diagnosis not made on a blood culture?
Why did the radiologist offer to do a biopsy?

Clinical History:
T cell lymphoma patient on chemotherapy. Admitted with fever. Treated
with IV antibiotics for 7 days still spiking temperature. CT chest to review
disease process and chest pathology
CT Thorax with contrast:
There are multiple large pulmonary nodules: 3.5cm rounded lesion in the
middle lobe, abutting the pleura with surrounding ground glass
opacification abutting the major fissure. Further 3.6 x 2cm soft tissue
h. The patient is coughing up sputum and you send some to the laboratory.
attenuation lesion in the medial middle lobe, abutting the mediastinal
The sample is stained and a picture is below. What does it show?
pleura. 4.5 x 2 cm soft tissue attenuation lesion in the left upper lobe
abutting the pleura. These large nodules have surrounding ground glass
opacification. Multiple small nodules seen in the left lower lobe, left upper
lobe, middle lobe and right apex.
No clear air bronchograms are seen in the larger lesions.
ASSESSMENT: Appearances are suggestive of fungal infection. If
necessary the right middle lobe mass can be biopsied under CT guidance

Return to Unit Overview

p172
 Leicester Medical School

i. The microbiology laboratory phones you to say they have identified Fungi can be classified as follows:
ASPERGILLUS.
TRUE PATHOGENS
They recommend you start treatment with Amphotericin. Cutaneous
Amphotericin is an antifungal agent and is given intravenously. Subcutaneous
Systemic
Look up some information on Aspergillus and answer the following questions: OPPORTUNISTIC
i) What makes a fungus different from a bacteria? This includes Aspergillus
iii) Where does Aspergillus normally reside?

iv) Does Aspergillus cause infections in hosts with normal immunity?

ii) Why do fungi not respond to standard antibiotics?

In this session we are more interested in the opportunistic fungi.

j. In addition to Aspergillus, name one other opportunistic fungus that commonly

occurs in both normal hosts and immunocompromised hosts?

Return to Unit Overview

p173
 Leicester Medical School

10.2 CASE STUDIES – Case Study B c. Refer back to the lecture on blood borne viruses, where there was a brief
outline of the classification of viruses.
i) What family of viruses does varicella-zoster belong to?
Mr Jones is a 50 year old man recently diagnosed with bowel cancer.
He undergoes surgery and is then offered chemotherapy.
As part of the pre-chemotherapy work-up blood is sent for viral titres. The
following results are obtained: ii) How does this fit into the classification you were given? You should write
Varicella-zoster IgG Positive out the simplified classification below.

Cytomegalovirus IgG Negative

a. What infection does Varicella-zoster cause?

d. Have you, or anyone in your group had an infection with varicella-zoster?

Do you remember anything about it?

Look up some of the main clinical features of the infection. This should include
how it is spread, the incubation period and how this relates to the developing
infection and the main clinical features. See Chapter 25; Section IV

b. How do you interpret the antibody results for varicella-zoster?

Return to Unit Overview

p174
 Leicester Medical School

(ii) Adaptive Immune response:

e. In a healthy young person who develops varicella-zoster infection outline how

the (i) innate immune system and (ii) adaptive immune system deal with the
infection.
(i) Innate Immune system:

Return to Unit Overview

p175
 Leicester Medical School

f. Mr Jones starts treatment. His nutrition is poor. Two months into his g. Why has Mr Jones developed the rash now?
treatment he presents with a rash over the posterior aspect of his shoulder.
The rash consists of papules with surrounding erythema (redness). It is
painful.

h. What does the term “latency” mean?

i) What is the rash?

i. Can this occur in healthy individuals?

ii) What is it due to? Explain, or read up, how it is linked to the previous
infection with varicella-zoster.
j. What factors contribute to developing this illness?

Return to Unit Overview

p176
 Leicester Medical School

k. How do you make the diagnosis?

l. Does Mr Jones need any specific treatment?

Return to Unit Overview

p177
 Leicester Medical School

Lecture 18 Summary: Escherishia Coli (E.Coli)

Learning Objectives

Describe the biology of E. coli including the identification and

serology
Describe the role of E. coli in health and disease
Describe E. coli as a cause of diarrhoea including its pathogenesis,
role of toxins and clinical features
There are many different strains of E-coli. Most of them are harmless.
Describe E. coli as a cause of urinary tract infections with virulence
factors and clinical features The 6 strains of diarrhoeagenic E-coli are:
Describe E. coli as a cause of blood stream infections and sepsis Enterotoxigenic E. coli (ETEC) - causes ‘traveller’s diarrhoea’ through
Describe the management of E. coli infections the production of 2 toxins (heat stable and heat labile) to cause watery
diarrhoea.
Escherichia coli is a Gram-negative cocci bacteria. It is a normal mocrobiota of
Enteropathogenic E. coli (EPEC) - creates a translocation tube to access
the large bowels. It protects us from pathological species such as Salmonella.
and anchor into the enterocyte.
However, they commonly cause urinary tract infections, intestinal infectons
(eg travel-related diarrhoea), sepsis or neonatal meningitis. Shiga toxin-producing E. coli (STEC)—also called Verocytotoxin-
producing E. coli (VTEC) or enterohaemorrhagic E. coli (EHEC). Shiga
They are typically lactose-fermenting – therefore, you can use MacConkey toxin (A & B subunits) inhibits protein synthesis within the cell and this
agar as it contains lactose (which will grow into pink/red colonies if the pH causes cell death.
becomes acidic – when lactose is broken down into lactic acid).
Enteroaggregative E. coli (EAEC)
They contain the O,H,K,F antigens. These antigens encode a specific structure Enteroinvasive E. coli (EIEC)
of the bacteria as shown in the diagram: Diffusely adherent E. coli (DAEC)

EPEC and EIEC are most common among young children in the developing
world.

Return to Unit Overview

p178
 Leicester Medical School

E-coli strains that cause extra-intestinal disease are classified under Extra- Management of UTI-related E-coli infection
intestinal pathogenic E coli (ExPEC). One example is Uropathogenic E coli Antibiotics – trimethoprim or nitrofurantoin are commonly used.
(UPEC) and its virulence factors include:
Lecture 19 Summary: Influenza
Adhesins: • Type 1 fimbriae have adhesive tips that bind to α-D-mannosylated
Learning Outcomes
proteins on uroepithelium, mediating adhesion, invasion of uroepithelium
and the formation of intracellular bacterial communities (IBCs) Toxins • Describe the structure of the Influenza virus – containing a genome of
Lipopolysaccharide (LPS) • α-Haemolysin (HlyA) is a secreted, pore-forming segmented negative-sense RNAs belonging to three types: A, B, and C and
its replication.
toxin, cytotoxic towards epithelial cells in the urinary tract Iron acquisition •
Define the concept of an animal reservoir for type A influenza (including
The availability of iron is extremely restricted in the urinary tract • Bacteria
poultry, horses, pigs, and other animals) and its major surface antigens -
produce their own iron-complexing proteins (siderophores) to acquire iron. hemagglutinin (HA) and neuraminidase (NA)
Management of diarrhoea-related E-coli infection Explain how the influenza virus gains entry to the human host through
attachment of the viral HA to sialic acid–containing
PREVENTION glycoproteins/glycolipids and subsequent uptake into an endocytic vesicle
and is spread from person to person via respiratory droplets that infect the
Avoid foods and drink that could be contaminated with bacteria: Raw
upper and lower respiratory tract.
fruits and vegetables (e.g., salads), raw seafood or undercooked meat
Describe the clinical symptoms (including headache, high fever, sore
or poultry, unpasteurized dairy products, food from street vendors, throat, runny nose, muscle aches and pains etc.) and complications of
and untreated water (including ice) in areas lacking adequate influenza infection (including viral pneumonia, secondary (bacterial)
chlorination. pneumonia, central nervous system syndromes, or Reye syndrome).
Describe how you would diagnose flu in a clinical setting
TREATMENT Briefly outline the management of influenza including treatment options
Most infected persons will recover within a few days, without and prevention Treatment (antivirals, NA inhibitors) and prevention
including vaccination and how this is determined by WHO each year.
requiring any specific treatment.
Define the concepts of antigenic shift (acquisition of a novel HA and NA by
Clear liquids are recommended for persons with diarrhoea to prevent the virus) and antigenic drift (yearly accumulation of mutations in the HA
dehydration and loss of electrolytes. and NA).
Oral rehydration solutions
Define the concepts of pandemics and epidemics (seasonality) and how
Avoid antibiotics – may make illness worse these may arise in relation to influenza.

Return to Unit Overview

p179
 Leicester Medical School

Flu is an acute viral infection of the respiratory tract (nose, mouth, throat,
bronchial tubes and lungs) - it is a highly infectious illness which spreads rapidly
in closed communities and even people with mild or no symptoms can infect
others. Most cases in the UK occur during an 8 to 10 week period during the
winter. It is an orthomyxovirus and is a spherical, enveloped virus containing a
segmented, negative strand RNA genome consisting of 8 genes which encode
11 proteins including an RNA-dependent RNA transcriptase (RdRp) that
synthesizes viral mRNAs using the genomic negative-strand RNA as a template.
The important antigens for both the concept of antigenic drift and antigenic
shift and of course entry to the cell are haemagglutinin (H) – 18 types – binds
to cells of the infected person and neuraminidase (N) – 11 types – which
Influenza viruses are transmitted from person to person via the respiratory
releases the virus from the host cell surface.
route (coughing, sneezing, inhaling) but there are innate immune system
barriers to entry as a first line of defence: 1) Respiratory epithelial cells are
covered by a thick glycocalyx and tracheobronchial mucus that can trap virus
particles; 2) Ciliated respiratory epithelial cells continually sweep mucus up
from the lower respiratory tract into the upper respiratory tract, where it is
usually swallowed; and 3) In the lung, immunologic defences include secretory
IgA, natural killer (NK) cells, and macrophages. Influenza virus attaches to sialic
acid residues on host cell glycoproteins or glycolipids. Entry then occurs via
receptor-mediated endocytosis. Both the attachment and the fusion functions
are associated with the H protein while viral release is facilitated by the
There are three types of virus – 1) influenza A which affects many animals, neuraminidase (N) protein, which cleaves the sialic acid residue of the
undergoes antigenic drift & shift and is responsible for pandemics, 2) influenza glycoprotein (Neu5Ac (NANA)) on the cell surface and allows release of the viral
B which only affects humans and undergoes antigenic drift – it mainly affects particle.
older adults and 3) influenza c which affects humans & pigs and undergoes
antigenic drift and produces mild disease.
The symptoms of influenza include fever, headache, sore throat, cough, aches
and pains but complications, while rare account for the large number of
fatalities every year particularly among the elderly and individuals with

Return to Unit Overview

p180
 Leicester Medical School

underlying co morbidities. The incubation time is normally one to five days and There is a more dramatic genetic change which can occur and this is known as
recovery is usually within seven days. antigenic shift - major changes in the genes of flu viruses that occur suddenly
when two or more different strains combine. This results in a new subtype and
Diagnosis is usually from symptoms and clinical assessment but there are rapid
is the cause of widespread epidemics/pandemics. This refers to major changes
antigen tests and PCR. While we do have treatments for influenza – antivirals
in H and N proteins that occur because the influenza viruses from several
and neuraminidase inhibitors – the main treatment is through vaccination for
species occur in the same host. It does involve a change in the viral subtype
vulnerable groups. This has to be done annually to ensure protection from the
resulting in different H and N proteins. This phenomenon can be easily
circulating viral strains –for adults there is a formalin-inactivated vaccine
explained by the reassortment of different RNA segments from each species in
(quadrivalent/trivalent) by injection against influenza A & B and for children the
a new capsid. There is potentially no previous immunity to the new subtype.
live, attenuated, cold-adapted vaccine (quadrivalent) by nasal spray against
This is what happened in Spanish flu in 1918. There were 3 different waves of
influenza A & B. The virus particles in this vaccine reproduce in the nose and
illness during the pandemic - from March 1918 and subsiding by summer
throat but not in the higher temperatures in the lungs.
of 1919. An estimated 1/3 of the world’s population was infected and there
approximately 50m deaths worldwide. Many of the deaths were among 20 to
Due to the following properties of the virus: 40 year olds as their immune systems had never seen this variant before and
many responded to the infection with a “cytokine storm” i.e. the immune
a) The flu virus is constantly replicating
system “overreacts” – T-cells attack and destroy the tissues in which the virus is
b) Life cycle of approximately 6 hours
replicating – in particular the lungs. Until 2020 the four previous pandemics
c) Viral RNA polymerases have a high error rate
were all influenza based.
The genome is constantly changing in small ways – point mutations – and this
leads to genetic variation in both the surface antigens H & N.
This is known as Genetic Drift - This refers to minor antigenic changes in H and
NOTES: Herpes zoster
N proteins that occur each year. Antigenic drift does not involve a change in the
viral subtype. This phenomenon can be easily explained by random mutations
Herpes zoster
in viral RNA and single or a small number of amino acid substitutions in H and N
Make Study Notes on Herpes Zoster. You should have two pages of condensed notes.
proteins. WHO monitors these changes each year and determines the
Chicken pox and shingles both make good questions.
composition of the vaccines in the February preceding our flu season. Public
Health England and GPs continue to monitor and report the cases and hospital
Include a picture of shingles. Look at a couple of pictures so you can recognise the
admissions and deaths throughout the season.
rash. Understand the anatomical principles of the rash. Try to use the infection
model to help you learn this.

Return to Unit Overview

p181
 Leicester Medical School

NOTES: Staphylococcus aureus

Escherichia coli

Staphylococcus aureus We have covered E. coli on a number of occasions:

A cause of sepsis and peritonitis (Session 4)
We have now had case studies relating to Staph aureus on a number of occasions.
A cause of a urinary tract infection (Session 5)
Make condensed study notes on Staph aureus.
You should already have study notes on E. coli and UTI
NOTES: The Immunocompromised Host Add to those notes with relevant information from the lecture. Alternatively, you
may choose to annotate the lecture slides.

The Immunocompromised host NOTES: Influenza

The lecture slides contained good information.
Influenza
This is potentially a huge topic.
All the necessary information is included in the lecture slides. I suggest you annotate
My advice is to use the slides with some annotations. There is little to be gained
the slides. You can otherwise make condensed notes or an infection model.
from re-writing all the slides.

NOTES: Febrile neutropenia

Session 10 Self-Study:
Febrile Neutropenia

The case study of Febrile Neutropenia makes a good question. All the necessary
1. Complete the case studies if you need to.
information is in the case study. So long as you worked through it you can then learn
directly from your workbook. You do not need to know the UHL Treatment guideline.
2. Complete your notes on the topics outlined above.
That information would be provided. You do need to understand the principles.

NOTES: Escherichia coli

Return to Unit Overview

p182
 Leicester Medical School

• Highlight a range of virulence factors found in Streptococcus pyogenes

Session 11: Streptococcus, Pharyngitis & EBV
• Correlate the virulence factors with clinical aspects of infection, as an
30 March 2021 example of how infectious diseases depends on interaction of pathogen
Preparatory Work Read about Epstein Barr and host factors
Virus & answer the • Describe streptococcal pharyngitis including microbiological features,
questions clinical presentation and complications
View, recall & review • Describe other clinical infections caused by Streptococci
lectures 18 & 19
09:00 – 09:50 Lecture 20 Streptococcus With regard to Pharyngitis
(Live F2F Simulcast Session) Outline common causes of pharyngitis
10:00 – 11:40 Small Group Work 11 Case studies: Use the feverPAIN score to guide decision making
(LIVE F2F) • Pharyngitis Outline management strategies for pharyngitis
• EBV
• Influenza
12:00 – 12:50 Review Lecture Review of the Unit With regard to Epstein-Barr Virus (EBV)
LIVE F2F Mandatory Describe features of EBV

Notes EBV Describe the microbe-host interaction for EBV

Streptococcus Describe the main clinical features of EBV infection

Self-Study Complete the case studies

& notes

Learning Outcomes
With regard to Streptococcus
• Review the microbiology and classification of streptococci

Return to Unit Overview

p183
 Leicester Medical School

Session 11: Preparatory Work

1) View, recall and review: View the lectures on Inflenza (Lecture 18), E.Coli
(Lecture 19) and Streptococcus (Lecture 20). Recall and review the information
from the lectures before you start the group work. You could do this on your
own before the session or with your group at the beginning of the session or a
combination of both.

2) Preparation for group work: In particular look at information on Epstein Barr

virus. This is an important topic and you will need to make notes. While you
can do this after the group work case studies today, you should start the process
if you have time. Please make sure to answer the questions ahead of the group
work.
The three types of viral infections.
VIRAL INFECTIONS (Epstein Barr Virus) At the opposite end of the spectrum is latent infection, which does not result in the
Pathobiology of Viral Infections production of progeny virus. Latent infections, which are caused by DNA viruses or
retroviruses, reflect the persistence of viral DNA either as an extrachromosomal
The signs and symptoms of viral disease are the culmination of a series of
element (herpesviruses) or as an integrated sequence within the host genome
interactions between the virus and the host. After encountering a host cell, a virus
(retroviruses). During cell growth, the genome of the virus is replicated along with
must be able to enter it, undergo primary replication, and then spread to a final
the chromosomes of the host cell. An example of latent infection is that produced
target tissue. Once a virus reaches its target organs, it must infect and successfully
by herpes simplex virus type 1 (HSV-1). The result of reactivation of HSV-1 is fever
replicate in a susceptible population of host cells.
blisters or cold sores. Latent infection by some retroviruses may result in
One of three possible outcomes follows infection of a host organism by a virus: transformation of the cell, which leads to cancer.
acute infection, latent infection, or chronic infection.
Chronic infection differs from acute and latent infections in that virus particles
In an acute infection, the virus undergoes multiple rounds of replication. continue to be shed after the period of acute illness. The mark of chronic infection
Replication results in the death of the host cell, which is used as a factory for virus is release of virus particles, sometimes without death of the host cell or overt
production. Examples of acute infections are those caused by poliovirus or cellular injury. Chronic infection is usually caused by RNA viruses. The amount of
influenza virus. virus produced is usually less than in acute infections, and the viruses are often
altered (“mutated”) from the original ones. Chronic infections are associated with

Return to Unit Overview

p184
 Leicester Medical School

defective host immune responses that are insufficient to clear the infection. Some d. What happens to this cell?
chronic infections do not result in overt disease, although they can produce disease
after a prolonged interval. For example, hepatitis C virus can cause a chronic
e. Of the 3 types of viral infection described above, which type does EBV belong
infection in the liver that eventually leads to chronic hepatitis and even liver
to?
cancer.

f. What is the common name for EBV infection?

QUESTIONS to answer in preparation for small group work (See below)

The small group session is all about ‘PHARYNGITIS’ Are you interested in history?
BUT We will have a case study on Epstein-Barr Virus (EBV). Look up some
This is comparatively recent history. But is an indication of how much will change
information on EBV before the session. in your working life.
There are two pages in Lippincott’s Illustrated Reviews Microbiology. Scroll down to
Section VIII Epstein-Barr Virus

a. What group of viruses does EBV belong to?

b. Which cell is first infected by EBV?

c. Which cell does EBV subsequently infect?

Return to Unit Overview

p185
 Leicester Medical School

Small Group Work 11: Pharyngitis, EBV & Influenza Case

Studies

11.1 CASE STUDY A - A Comparison Of Two Patients With

Pharyngitis

PATIENT 1
A 7 year-old boy is taken to the GP by his mother.
He woke this morning with a sore throat.

a. What questions do you ask with your history?

The redness extends over the tonsils, but they are not especially enlarged or have
any other features.
The GP palpates his neck and there are no additional findings.

b. What are the likely microbial causes?

Examination
His temperature is 37.0oC (Normal 36.5 to 37.1oC)
He is alert and able to drink and eat.
He has symptoms of a cold for the past two days with a runny nose.

This is a picture of his throat.

Return to Unit Overview

p186
 Leicester Medical School

NOTE: A number of scoring systems have been proposed to help GPs and Primary c. Calculate the Fever-PAIN score:
Care staff manage patients with pharyngitis. An important objective is to reduce
antibiotic prescriptions. The CENTOR criteria were previously used. The present
recommendation is to use the Fever-PAIN Score. This includes the following
measures:
Fever in last 24 hours
Rapid attendance (short prior duration of 3 days or less)
moderately bad or worse muscle aches
moderately bad or worse sore throat,
the absence of a bad cough
severely inflamed tonsils (e.g. Pus on tonsils)
Anterior cervical glands
(Note: there were no muscle aches or cough reported when you took the history)
Fever PAIN score of 0-1: only 13-18% have streptococcus, close to background
carriage and therefore a no antibiotic strategy is appropriate with discussion.
 d. What management do you suggest?

Fever PAIN score of 2-3: 34-40% have streptococcus, therefore a back-up/delayed

antibiotic is appropriate with discussion.

Fever PAIN score of >4: 62-65% have streptococcus, therefore consider immediate
antibiotic if symptoms are severe or a short 48 hour delayed antibiotic prescribing
strategy may also be appropriate after agreement with the patient and safety
netting advice

Reference article:

Return to Unit Overview

p187
 Leicester Medical School

f. What is a lymph node?

Next day –
The mother returns with her son. She noticed a lump in his neck when she helped
to dress him that morning. She is now worried. A picture of his neck is below.

The patient is otherwise stable. His temperature is 36.8oC. Examination of his

throat is largely unchanged from yesterday.
g. Is this finding in his neck ‘normal’ in the context of a throat infection?

h. Does this change your management?

e. What additional information do you seek? What is the likely cause of the lump?

You may choose to re-calculate the Fever-Pain score:

Return to Unit Overview

p188
 Leicester Medical School

i. The mother asks you to take a throat swab. Will this help decide how best to Patient 2
manage the child?
Tom is 5-years old.
He woke up during the night complaining of a sore throat. His mother took his
temperature which was 37.8oC. She gave him some Ibuprofen. He refused to eat
or drink. In the morning she took him to the GP.
In the GP surgery he was crying with pain.
There is no history of cough or muscle aches.

j. The mother is increasingly concerned and asks you to please prescribe an

The GP noted bilateral cervical lymph nodes. The largest node was 2cm in
antibiotic. What conversation do you have with the mother?
diameter.
A picture of his throat is below. Can you identify what the picture shows?

Patient advice leaflets:

Somewhat reluctantly the mother agrees with your approach to avoid prescribing
an antibiotic and agrees to see you again in a week to ensure her son is well.
Fortunately he continues to recover and returns to school.

Return to Unit Overview

p189
 Leicester Medical School

a. Calculate his Fever PAIN score: 11.2 CASE STUDY B - EBV

A 17 year-old girl presents to her GP.

She is doing A-levels.
History: She felt ‘unwell’ for the past four days and is increasingly tired. She
developed a sore throat, a headache and mild nausea
b. What is your suggested diagnosis? She stayed at home taking over-the-counter medication.
However her symptoms did not improve and became worse. She developed a high
fever, episodes of shivering (rigors), felt weak and tired and developed swollen
nodes in her neck.

On examination in the GP practice her temperature is 38.5oC

She has bilateral cervical lymphadenopathy
She has a moderate pharyngitis on examination of her throat.
c. Are you confident in your diagnosis?
a. What diagnosis does the GP consider?

d. What management do you recommend?

Return to Unit Overview

p190
 Leicester Medical School

b. The GP examines the patient’s abdomen. What is the GP specifically looking Blood film report
for? Numerous activated lymphocytes. Film consistent with infectious mononucleosis
Suggest repeat to monitor

The GP decides to send off a full blood count. Later that day he receives the
following results:

Full blood count

http://library.med.utah.edu/WebPath/HEMEHTML/HEME013.html
White Blood Count 20.4 x 109/l Normal 4-11x109/l
Differential count: During acute EBV disease, the number of lymphocytes increases to 50–60% of the
Lymphocytes 14.0 x 109/l total leukocytes in the peripheral blood (a count of 20,000–50,000/ml), of which
Neutrophils 4.3 x 109/l 10% are atypical lymphocytes

Monocytes 1.7 x 109/l

The GP also sends a blood sample for EBV serology.
Eosinophils 0.0 The results below are received the following day
Haemoglobin 138g/l Normal 130-165g/l
Platelets 232 x 109/l Normal 150-400 109/l IgM Anti-VCA for EBV Positive
IgG Anti-VCA for EBV Negative

c. What does the Full Blood Count show? Note: VCA = viral capsid antigen

d. How do you interpret this result?

Return to Unit Overview

p191
 Leicester Medical School

Remember the slide in the Adaptive Immunity lecture

e. What general advice do you give the patient?

Return to Unit Overview

p192
 Leicester Medical School

11.3 CASE STUDY C – Influenza – do this in your own time as b. Explain why the boy has flu despite this vaccination.
part of your self-study the answers are all in the lecture slides

IF THERE IS TIME DO THIS CASE STUDY ON INFLUENZA (otherwise complete at

home)

A mother brings her 5-year-old son your surgery. He presents with the following
symptoms – fever, coughing, headache, muscle aches and pains. You suspect
influenza and recommend bed rest, paracetamol, and plenty of fluids. The mother
is very anxious – it transpires that her son recently had the intranasal flu vaccine
and yet he is ill. She has heard that there is a new strain causing many cases
recently.
a. Describe the intranasal flu vaccine – what is it? Which age group is usually
given this form of the vaccine?

c. The mother has heard about antivirals and asks you to prescribe one – why
might you be reluctant to do so?

Return to Unit Overview

p193
 Leicester Medical School

d. Is there another class of drugs that you might consider? Lecture 20 Summary: Streptococcus

Learning Outcomes
With regard to Streptococcus
• Review the microbiology and classification of streptococci
• Highlight a range of virulence factors found in Streptococcus pyogenes
• Correlate the virulence factors with clinical aspects of infection, as an
example of how infectious diseases depends on interaction of pathogen and
host factors
• Describe streptococcal pharyngitis including microbiological features, clinical
presentation and complications
• Describe other clinical infections caused by Streptococci
e. What other, more general advice, might you give the mother as regards the
ongoing care of her ill child?
Streptococci are gram positive chains of cocci. They are classified according to the
way in which they appear on blood agar – α, ß or Ƴ haemolysis. α-haemolytic strep
groups oxidise iron in haemoglobin so appear green on the plate while ß- haemolytic
strep species cause complete rupture of blood cells which appear white/clear on the
plate and Ƴ- haemolytic strep species have no effect on the blood agar. There are
many types of streptococci but we will consider the more commonly encountered
ones.
α-haemolytic – streptococcus pneumoniae, viridans’ streptococci (not a species only
a type – several species)
ß- haemolytic – group A (Streptococcus pyogenes) & group B (Streptococcus
agalactiae)
The Lancefield grouping is a serological method for classifying streptococci into one
of 20 groups (designated by a letter) based on the presence of polysaccharide
antigens in the bacterial cell wall (Lancefield 1933). Some streptococci, for example

Return to Unit Overview

p194
 Leicester Medical School

S. pneumoniae, have not been assigned to a group because their antigen extracts fail
to react with group antisera.

Sherman (1937) classified streptococci in to four groups based on physiological

properties such as 1) pyogenic –“pus forming”, 2) viridans – includes bacteria that do
not fall into the other categories, 3) enterococcal – bile tolerant, penicillin resistant
gut dwelling (faecal sources) and 4) lactic – bacteria from diary sources.
Currently if any confusion or uncertainty we classify according to DNA sequence
analysis.
Streptococcus pyogenes – infrequent but usually pathogenic inhabitant of skin
microbiota. It normally colonises the throat, genital mucosa, rectum and skin. There
are several virulence factors associated with these bacteria (different strains possess
different virulence factors and essentially determine the progress of the disease
and/or complications). One important virulence factor is the surface m protein –
plays a role in adherence to epithelial cells and means that the bacteria is resistant
to phagocytosis. The main infection Streptococcus pyogenes causes is Streptococcal
pharyngitis or strep throat – which peaks in incidence between 5 and 15 years of age
and presents as a sore throat with fever, headache and tonsillopharyngeal exudates.
It is spread by droplets in crowded environments. It normally resolves without
treatment and antibiotics have minimal impact on the duration of the infection and
can actually prevent an adequate immune response which is necessary to deal with
a future infection. There are several complications associated with these infections
including scarlet fever (associated with Streptococcal pyrogenic exotoxins which
cleaves Ig G bound to Group A strep), abscesses in the head and neck region (see
Head & Neck year 2), rheumatic fever and glomerulonephritis. The latter two are present at this point. Strep pyogenes is also responsible for several different skin
associated more with the immune response in which the antibodies to the m protein conditions – Impetigo, Erysipelas, Cellulitis and Necrotising fasciitis.
cross react with host antigens (different m types in each condition) and follow on
several weeks or even months after the initial infection. There is no infective agent

Return to Unit Overview

p195
 Leicester Medical School

The final infection to consider is streptococcus toxic shock syndrome – often fatal -
Deep tissue infection with Strep pyogenes AND Bacteraemia AND Vascular collapse
AND Organ failure - From health to death in hours.

NOTES: Copy of Fever Pain Clinical Score

https://ctu1.phc.ox.ac.uk/feverpain/index.php

Return to Unit Overview

p196
 Leicester Medical School

NOTES: Epstein-Barr Virus (EBV) Immune response to EBV:

Immunology for Medical Students (Elsevier) has a single page on the immune
response to EBV. Chapter 15 (page 109) Box 15.3
Epstein-Barr Virus
Make a set of STUDY NOTES on EBV. Use your preparation for this session, the
group work and the pages from Lippincott’s. You should end up with 2 to 3 pages
of notes and diagrams. Once again, set out your notes within the infection model
framework.

There are two pages in Lippincott’s Illustrated Reviews Microbiology.

If you have difficulty with the link, I have copied the diagram below and two
relevant paragraphs. The additional immunological detail in the textbook is for
interest; but you should easily be able to follow it. Include a few points on the
immune response in your notes.

Return to Unit Overview

p197
 Leicester Medical School

From the point of view of the host response, acute EBV is characterized by a massive
increase in the number of CD8 + T cells in the peripheral blood.
An antibody response, mostly immunoglobulin M (IgM), is also mounted during
acute EBV. After a few months, Ig class switching takes place, and most of the
antibodies against EBV become IgG. The antibody response is not as useful as the
CTL response in limiting this infection. However, the combination of antibody and
CD8 + CTLs reduces but does not eliminate the infection. This infection is a good
example of how the immune system may not always be able to accomplish
“sterilizing immunity” but sometimes has to settle for limiting infection. “

Additional question: What is the link between EBV and Cancer?

If you did not look at the history link for the preparation for this session you can
do so know. There is a one minute video on the web-page.

“Most people have been infected with Epstein-Barr virus (EBV). In the developing
world infection takes place in early childhood, but it is usually asymptomatic. In the CRUK have a linked page with more detail on EBV and cancer.
developed world, infection is usually delayed until adulthood; 70% of people who
become infected develop infectious mononucleosis (IM), also known as glandular
fever. Symptoms of IM include a sore throat, malaise, lymphadenopathy, and
possibly an enlarged spleen. EBV infects its target cell, the B cell, for life, and thus it
There is no requirement for you to know this detail. But having now done some
establishes a latent infection. Infected B cells proliferate, although very little free
immunology you should be able to follow the discussion. We will pick up on some
virus is produced. EBV increases are associated with malignancy: infection leads to a
of these points later in the course.
fivefold increase in the risk of B-cell lymphoma, EBV also increases the risk of
However, you must know that there is a link between EBV and cancer (and be able
autoimmunity; for example, it doubles the risk of multiple sclerosis.
to name at least two of the cancers).

Return to Unit Overview

p198
 Leicester Medical School

You also need to appreciate that a number of viruses have a link to the
development of cancer.
Look up and list at least two other viruses that are linked to cancer. It is likely this
will also be covered in Pathological Processes.

NOTES: Streptococcus pyogenes

Streptococcus pyogenes

Make study notes on Streptococcus pyogenes using the Infection model. You have
the lecture slides and four pages in Lippincott’s.

With regard to the lecture on Streptococcus, the slides contain good information.
You may choose to annotate the slides.

Or you can write your own study notes on Streptococcus. Aim to put the key
information into two pages. As always, aim to frame it within the infection model.

Session 11 Self-Study:

1. Complete the case studies from today’s session

2. Make notes as detailed above on EBV and Streptococcus.

Return to Unit Overview

p199
 Leicester Medical School

Appendix 1 – Themes, Infections & Microbes Give example of skin, mouth and nose, bowel,
urogenital tract
Structure and Understand bacterial cell wall and importance of
TOPICS COVERED IN THE INFECTION UNIT - 2022 pathogenicity Gram stain.
Covered in lecture and notes provided on cell wall.
This is NOT a list of learning outcomes. This is NOT a list to memorise. Please use An Infection model Lecture and repeated links to the infection model
this appendix to compile your own list with pictures, other details, possible as an approach to infection
treatments and other microbes. Diagnosis of infection Supportive investigations e.g. does patient have
general features of an infection and how severely
This is simply a list of topics covered in the Infection Unit. In some cases a whole is patient affected; including FBC, Neutrophil
lecture or case study has been devoted to the topic. For others they have been count, CRP, lactate, oxygen saturation, renal
mentioned briefly to provide a broader coverage of a topic. function, Chest X-ray, etc…..(and will depend on
clinical setting)
Topics or microbes in brackets have been included for completeness but will not be
AND: specific investigations (to identify microbe)
tested in the Year 1 exams. In some cases I have indicated that material will be taught
such as blood culture, Swab, urine culture, gram
in Year 2. In the table I have indicated where topics are included in lectures or case
stain, PCR, serology, etc.
studies. The term ‘notes’ refers to notes provided for you or notes you have been
Management of infection Always divide into:
asked to prepare.
Supportive:
This list of themes, infections, microbes, antimicrobials and host immune topics
Specific:
should serve as a reference.
Principles discussed in lectures and examples given
Your revision material should consist of a series of study notes that you have made
in multiple settings.
week-by-week. Each week the workbook provides clear guidance on what the
Antimicrobial therapy See separate list of antimicrobials. Lecture +
important topics are that you need to make notes on. These should form the basis
various case studies. Use of UHL antimicrobial
for your revision.
website or RxGuidelines App.
Antimicrobial Lecture
stewardship
THEMES
Antimicrobial resistance Lecture. Notes provided on MRSA
Classification of microbes Lecture week 1.
Infection prevention Lecture
Microbiota Importance and relevance of microbiota covered in
Sepsis A key topic. Pathophysiology, definition, examples
different lectures, workbook material and in
(as in case studies). Lecture + multiple case studies
various case studies.
+ Notes

Return to Unit Overview

p200
 Leicester Medical School

Hospital associated Important topic. Lecture. See case studies and Urinary tract infection Uncomplicated UTI – case study
infections notes Complicated UTI will be covered in Year 2.
Infections on a surface / Lecture: Principles and importance. Examples in Skin infections Impetigo
Biofilms case studies and examples in other sessions. Notes Skin abscess
provided Cellulitis Commonly Strep pyogenes and Staph aureus. Case
Travel related infections Including Malaria, Schistosomiasis, Salmonella, study
Dengue, Ebola, Legionnaires. Lecture + case Pharyngitis / Tonsillitis Causes of pharyngitis. Case studies on use of
studies. Notes for malaria. antibiotics. Comparison with Glandular fever
Blood borne viruses Including HIV/AIDS and Hepatitis. Needle stick / (EBV).
Sharps injury Glandular fever Epstein-Barr virus. Case study + notes
The Lecture: Principles, Recognition, Clinical features. Diarrhoea Viral diarrhoea – Norovirus. Case study + notes
Immunocompromised Congenital immune deficiencies and acquired Health Care infections – Clostridium difficile. Case
host immune deficiencies. study + notes.
Case study of febrile neutropenic sepsis. E. coli. Lecture
Risks of splenectomy. Salmonella (under travel-related infections)
Will be covered in more detail in Year 2.
INFECTIONS – by site / Endocarditis The case study showed an example of
type Streptococcus mutans, a mouth commensal,
Sepsis Many different causes. Lecture + case study + causing endocarditis. Notes provided.
notes Staph aureus can also cause endocarditis (as an
Meningococcal sepsis / Neisseria meningitidis. Lecture + notes. example in IV drug users).
meningitis Infected prosthesis or An example of a biofilm infection
Meningitis central line
Upper respiratory tract Viral causes; e.g. Adenovirus. Case study + notes HIV / AIDS A case study of acute HIV (or recently acquired).
infection A case study of HIV with AIDS (i.e. late stage).
Pneumonia Community acquired pneumonia (list main viral An important topic. Lecture + case studies + notes
and bacterial causes). Case study + notes Hepatitis Main points of Hep B and Hep C.
Can be a cause of ‘sepsis’. Interpret Hep B serology as this links to needle-
Atypical microbes and hospital acquired stick injury
pneumonia will be covered in Year 2. Lecture + study notes
Peritonitis An example of sepsis

Return to Unit Overview

p201
 Leicester Medical School

Management of a sharps Reviewed as part of Hepatitis lecture. See relevant Escherichia coli Lecture + case studies + notes.
injury slides. Pseudomonas aeruginosa Lecture + case study + notes
Influenza Lecture – common cause of hospital burden in over Salmonella S. typhi, S. typhimurium, S. enteritidis. Travel-
65s. related infection lecture.
SARS-CoV-2 Lecture – pandemic and now endemic virus Haemophilus influenzae Case study on pneumonia
Malaria Major travel-related infection. Legionella pneumophila Legionnaire’s disease (see travel-related
Lecture and case study + Study notes infection case study). Also a cause of atypical
Schistosomiasis A travel-related infection. pneumonia (Year 2).

Other important Gram-negative bacilli – and will be covered in Year 2:

MICROBES (Proteus species)
BACTERIA (Campylobacter jejuni) Year 2
GRAM POSITIVE COCCI (Shigella) Year 2
Staphylococcus aureus (Vibrio cholera) Year 2
MRSA (Helicobacter pylori) A cause of gastric ulcers. Will be covered in GI
Staphylococcus epidermidis An example of a coagulase negative unit in Year 2
staphylococcus. Important in line infections or MYCOBACTERIA
prostheses. Biofilm. Mycobacterium tuberculosis Case study in HIV/AIDS. Will cover in detail in
Streptococcus pneumoniae Year 2. Leave for year 2 exams.
Streptococcus pyogenes SPIROCHETES
Streptococcus mutans (Treponema pallidum) Causes syphilis. Will cover in Year 2
MYCOPLASMA
GRAM NEGATIVE COCCI (Mycoplasma pneumoniae) A cause of atypical pneumonia. Will cover in
Neisseria meningitidis Year 2
(Neisseria gonorrhoeae) Will be covered in Year 2 (Reproduction) CHLAMYDIA
(Chlamydia pneumoniae) A cause of atypical pneumonia. Will cover in
GRAM POSITIVE BACILLI Year 2
Clostridioides difficile Anaerobic HELMINTHS
Schistosoma Travel-related infection. Schistosomiasis
GRAM NEGATIVE BACILLI (Katayama fever).

Return to Unit Overview

p202
 Leicester Medical School

Lecture + Case study Varicella zoster Case study + notes

RICKETTSIA (Herpes simplex)
(Rickettsia species) Cytomegalovirus
Hepatitis B Lecture. Review Hep B serology for needle stick
PROTOZOA injury.
Plasmodium species Malaria. An important topic. Lecture + case Hepatitis C Lecture
study + notes Influenza virus Lecture + notes.
Toxoplasma gondii Usually asymptomatic in normal individuals. Ebola virus An example of viral haemorrhagic fever
Can cause brain abscess in Dengue fever Travel-related infection. Lecture
immunocompromised (HIV/AID) Zika virus Lecture.
Cryptosporidium Diarrhoea in immunocompromised COVID-19 Lecture
Trypanosoma species Trypanosomiasis (African sleeping sickness) Viruses in bold have been covered in more detail and you should learn these
A number of other viral infections will be covered in Year 2 and in clinical years
FUNGI
Candida albicans A commensal; but can cause infection if
overgrowth or in immunocompromised.
Examples given in lectures and case studies.
Aspergillus Usually in immunocompromised. See case
study
Pneumocystis jiroveci Pneumonia in immunocompromised; e.g. in HIV
/ AIDS. Lecture.
Cryptococcus CNS lesions in immunocompromised

VIRUSES
Adenovirus A cause of upper respiratory tract infection.
Case study + notes
Norovirus A cause of diarrhoea. Case study + notes
Respiratory syncytial virus A cause of pneumonia.
Epstein-Barr virus Case study and notes
HIV Lecture, case studies, notes

Return to Unit Overview

p203
 Leicester Medical School

Appendix 2 – Antimicrobials HIV drugs Understand principles and mechanism of action

in relation to viral replication
This is not an exhaustive list – this is just some of the antimicrobials you will have Oseltamivir (Tamiflu)
encountered during your lectures and group work – please add additional details
such as type of anti-microbial, class of antibiotic, potential mechanisms of action. Amphotericin
Fluconazole
ANTIMICROBIALS Need to know: broad classification (i.e. which Nystatin
group they belong to), clinical situation where
they are used, general mode of action, and in Malaria treatment: Artesunate, Quinine
some cases other relevant fact.
Covered in lecture. Examples given in case
studies. Suggest learn the antimicrobial in
context of the infection or microbe.
Penicillin
Amoxicillin
Flucloxacillin
Ceftriaxone
Trimethoprim
Vancomycin
Gentamycin
Piperacillin
Tazocin Contains Piperacillin and Tazobactam. Is broad
spectrum covering a range of gram-negative
and gram-positive bacteria
Metronidazole Active against anaerobic bacteria and against
protozoa
Fidoxamicin Active against C. difficile

Acyclovir

Return to Unit Overview

p204
 Leicester Medical School

Appendix 3 – Host Immune Response In Relation To Infection Macrophage-derived Macrophage-derived cytokines: IL-1, IL-6 and
cytokines TNF. Role of these cytokines.
HOST IMMUNE RESPONSE IN RELATION TO INFECTION C-reactive protein (CRP) An acute phase protein. Understand pathway for
production of CRP and its clinical value
All the topics below are taken directly from the LECTURE SLIDES. Acute inflammation and Acute inflammation also covered in Pathological
Many are supported by questions in the case studies or by STUDY TASKS (NOTES). sepsis Processes Unit. See notes for Sepsis.

INNATE IMMUNE SYSTEM ADAPTIVE IMMUNE SYSTEM

Innate barriers Describe how barriers work with examples RECOGNITION PHASE
Physical barriers T lymphocyte
Physiological barriers Antigen presenting cells Role of antigen presenting cells
Chemical barriers MHC class I and class II / Basic principles and clinical importance
Biological barriers HLA
Recognition of a bacteria
Role of normal flora / Explain how the normal flora helps to maintain Recognition of a virus
microbiome normal physiology and host health EFFECTOR PHASE
Explain how alterations in the microbiome Activation of T lymphocytes Basic roles of T cells
predispose to infection Activation of B lymphocytes Principles
Examples of how normal flora can cause Outcome of B lymphocyte Produce antibodies. Primary and secondary
infections activation response.
Main phagocytic cells and Also covered in ‘Pathological Processes’ Unit. Function of antibodies
process of phagocytosis. List the phagocytic cells How host deals with a Brief summary
Explain the process of phagocytosis bacteria
Pathogen recognition Outline how pathogens are recognised by How host deals with a virus Brief summary
phagocytic cells.
Opsonins and Complement Outline the role of complement in the host IMMUNOCOMPROMISED HOST
response to infection and inflammation When to suspect? SPUR. Warning signs
Cytokines Recognise the broad family of cytokines and Primary immunodeficiency Gene defect
varied function Give examples:
SCID

Return to Unit Overview

p205
 Leicester Medical School

Low / absent Immunoglobulin levels

Chronic Granulomatous Disease
(neutrophil dysfunction)
Secondary Important examples:
immunodeficiency Splenectomy
Patients on cancer treatment
Infections such as HIV
Others
Investigation and Principles
management
Febrile neutropaenic sepsis Case study. An important clinical example.

Return to Unit Overview

p206