We find ourselves in the midst of the biggest global health crisis of our time and many are calling for increased testing for both the public and staff working in healthcare from primary to secondary.However, confusion reigns on the tests themselves; how they function, the accuracy and the cost to procure. This webinar we examined the role of testing, examining current tests available and explore- * The accuracy and predictability of tests * The function of a test * Their role in your patient pathway * The barriers to adoption of tests * The case studies of success across the UK Speakers John Bagshaw - BIVDA David Watwood - Ciga Healthcare Marc Winrow - Lumos Diagnostics

1. ROLE OF
DIAGNOSTICS
FOR DISEASE &
INFECTION
PREVENTION
Scott Buckler

2. TODAYS WEBINAR SPEAKERS
• John Bagshaw, Chief Operating Officer, BIVDA
• David Watwood, Director of UK Professional Diagnostics,
CIGA Healthcare
• Marc Winrow, Senior Sales & Distribution Manager, Lumos
Diagnostics

3. WEBINAR AIMS
• To highlight the current range of Diagnostics available for
use in Healthcare
• To explore how a test works
• To examine accuracy of a test
• To explore evidence testing can provide for clinical
decision making
• What role a test can play in a patient

4. COVID-19
Testing has been highlighted as a possible solution to the
current COVID-19 epidemic. As we are now seeing tests
are being utilised to support the clinical decision-making
process for patients presenting symptoms and for those
who could be at risk.
Todays webinar is in no way related to these specific tests,
nor does it aim to advocate any of the tests highlighted as
solutions to COVID-19. Today is about sharing learning and
educating our audience on what function a Diagnostic
test can play in our healthcare system

5. QUESTIONS AND ANSWERS
Please feel free, during the webinar, to send us your
questions. This can be done using the question box facility.
If you have any unanswered questions, please email
matthew@4allofus.org.uk

6. In-Vitro Diagnostics (IVDs)
for Infectious Disease Diagnosis
and Prevention
John Bagshaw
JAB Associates
Chair - Market Dynamics Working Party, BIVDA
and Executive Board Member

7. Infectious Disease Diagnosis
• Causes of Infectious Diseases
• A constantly evolving (literally!) story
– Bacteria
– Viruses
– Yeasts
– Parasites – various
– Rikettsiae
– Prions
– Mycoplasma

8. Deaths Due to Infectious Disease

9. Deaths Due to Infectious Disease

10. Deaths Due to Infectious Disease

11. Deaths Due to Infectious Disease

12. Deaths Due to Infectious Disease

13. IVDs for Infectious Diseases
• IVDs have been major contributors to progress in reducing the impact of infectious
disease on humanity

14. Culture media –
• potato, broth, gelatine and eventually agar
• Nutrient, blood, selective, enriching
• Chromogenic
IVDs for Infectious Diseases

15. Automation of Culture methods –
• Blood culture
• Plate inoculation, incubation and digital
reading
• Bacterial and yeast identification and
antibiotic susceptibility testing
IVDs for Infectious Diseases

16. • You can recover, grow, isolate, identify and
characterise (for antibiotic susceptibility)
many infectious agents in 2 – 4 days…
• Problem 1
– Patient may be dead
• Problem 2
– What if the ‘germ’ won’t grow on anything?
• TB
• Viruses
• Chlamydia
• Parasites…etc.
IVDs for Infectious Diseases

17. • Techniques developed from serology,
agglutination reactions, using red blood cells
or latex particles
• In the 80’s – RadioImmunoAssay (RIA)
• Immunoflorescence (IFA) for detecting
intracellular infective agents e.g. Chlamydia
• Enzyme Linked ImmunoAssays (ELISAs)
revolutionised serology
Non-Cultural IVDs

18. • ELISA methods allowed the detection of low
concentrations of antibodies or antigens in
blood and other specimens and are:
– Very specific (mostly)
– Very sensitive (up to a point)
– Quick (usually)
– Easily automated for high volume testing
– Inexpensive (relatively)
The Immunoassay Revolution

19. • Initially performed in tubes, they soon
standardised onto 96 well microtitre plates,
often breakable into strips for smaller
numbers of tests.
• Automation initially consisted of plate
inoculators, washers, incubators and readers,
then these were integrated with computers
and pipetting stations into systems which
could process multiple plates
The Immunoassay Revolution

20. • ELISA methods were soon automated further,
removing the need to use microplates and allowing
racks or turntables of samples to be loaded which
were then processed continuously, meaning
– No need to batch up samples, one-offs could be
done as and when needed
– A larger range of different tests could be run on
the same machine at the same time
– Machines could be incorporated in sample
processing systems which include chemistry
analysers, haematology systems etc.
The Immunoassay Revolution

21. 1. Prevention of disease
i. Blood donation screening - Detection of
transmission risk of Hepatitis B, HIV, Syphilis,
HTLV, Hepatitis C and E
ii. Ante-natal screening – detection of HIV,
Hepatitis B, Syphilis (Rubella was stopped)
iii. Testing of specific groups, e.g. health care
workers for immune status
iv. Targeted interventions in eradication
programmes
How Do These Systems Help?

22. 2. Disease Diagnosis
i. Identification of causative agents, e.g. hepatitis B,
ii. Staging of disease progress
iii. Prognosis
iv. Efficacy of treatment
How Do These Systems Help?

23. • ELISA methods are not sensitive enough for
some purposes:
– HIV serology – ‘window phase’
The ‘Molecular’ Revolution

24. • ELISA methods cannot tell you how much
infectious agent is present:
– HIV viral load
The ‘Molecular’ Revolution

25. • Molecular biology techniques have become
indispensable for many infectious disease
diagnoses and monitoring purposes
• Of all the techniques, PCR has become like the
‘Hoover’ for vacuum cleaners*
The ‘Molecular’ Revolution
* With apologies to Henry

26. • Blood screening now depends on PCR, as does
HIV and other viral load monitoring
• Diagnosis of respiratory diseases is being
revolutionised. Samples from aspirates or
lavages can be processed for ‘flu, RSV and
other pathogens in bulk in a matter of hours
or individually in an hour or less
• High volume systems came into their own
with the ‘flu epidemic, and many were bought
for the PHE labs
The ‘Molecular’ Revolution

27. The ‘Molecular’ Revolution

28. • The latest advance in PCR based diagnostic
tools
• A panel of about 20 tests performed
simultaneously to determine the cause of a
condition, e.g. a meningitis panel, or a lower
respiratory panel
• Instead of a process of elimination, or a
‘cascade’ approach to diagnosis, the complete
set is run at once, to obtain a definitive
answer in about 1 hour
Now ‘Syndromic Testing’

29. • Examples are the BioFire Torch System
Now ‘Syndromic Testing’

30. • …and the GenMark Dx
Now ‘Syndromic Testing’

31. • ‘Rapid’ or ‘Point of Care’ tests are designed to be
able to give a result in a non-laboratory setting, e.g. a
doctor’s surgery, a clinic or even at home
• There are some using PCR technology for single tests,
with cartridges that are easy and quick to use
• Most are based on immunochromatography,
however and are simple looking cassettes like some
pregnancy tests.
• These are called ‘Lateral Flow Tests’ or LFTs, and have
a place in infectious disease diagnosis
What About ‘Rapid Tests’?

32. • LFTs are available for RSV, Influenza, antibody to HIV
and HBsAg, Clostridium difficile, Rotavirus and some
others.
• Development of lines in the test window show
presence of the target
What About ‘Rapid Tests’?

33. • Advantages
– need little training to use, can be used anywhere, are quick
(5 – 30 mins) and need no special equipment
• Drawbacks
– tend to be less sensitive or specific than conventional
ELISA and much less than PCR, they are to some extent
operator dependent for the quality of sample, test
operation and reading and labour intensive for large
numbers, with no data capture and traceability of result to
patient
What About ‘Rapid Tests’?

34. So How Do IVDs Help For Coronavirus?

35. So How Do IVDs Help For Coronavirus?
• ‘Swab’ tests = PCR are the no.1 test for diagnosis
• Please don’t call them ‘Antigen Tests’!
• High volume testing run in specialised labs on automated PCR
platforms
• Initially targeting patients for diagnosis and H/C workers for
clearance if suspicion of symptoms

36. So How Do IVDs Help For Coronavirus?
• ‘Antibody Tests’ = ELISA based or LFT
• Currently none submitted for evaluation have met the required
specifications, but there may be a rethink
• ‘Home Testing Kits’ may or may not exist, none are legally sold in the UK as
yet
• ‘Antigen Tests’ = ELISA based or LFT
• May have a place in specific locations, e.g. cruise
ships, as did ‘flu tests…
• Strategy?
• Targeting?
• Roll out?

37. There is an official webinar immediately after this…..
Possibly?

38. Thank you!

40. Community POC Testing: Barriers
• Distrust in POC tests
• Funding:
• Lack of reimbursement
• Block contracts
• Belief that diagnostic tests cannot/will not be used correctly
outside the laboratory
• Inadequate training
• Inadequate QC/QA

41. Times Are Changing (Have Changed)!
• Anticoagulation management
• Health Checks Programme
• Urine screening
• Pregnancy testing
• HIV Diagnosis and management
• CRP
• Lord O’Neill Report 2018: “Promote
new rapid diagnostics to cut
unnecessary use of antibiotics”
• D-dimer
• BNP
• HbA1c
• Troponin
• Florence Teleheath Programme

42. Community POC Testing
• GP led Urgent Care Centres
• GP practices
• Community Clinics
• Community Hospitals
• Community Pharmacies
• Out of Hours Services
• Private Clinics
• Assisted Care Facilities
• Home

44. The CIGA Proposition
Finecare Point of Care
Analyser
• 30 different rapid tests
available including:
• CRP
• D-dimer
• HbA1c
• Troponin
• BNP

45. The CIGA Proposition
• Urinalysis test strips and
analyser
• Manual D-dimer test
• Rapid Strep A test
• Blood pressure monitors
• Pulse oximeters
• Thermometers
• Self test OTC diagnostics

46. Drivers To Community POC Testing
• Pathway changes in Primary
Care
• Pay per test
• Increased reliance on
Community Pharmacy
• Telehealth including
diagnostics
• Self testing/OTC diagnostics
• Covid-19!!

48. www.lumosdiagnostics.com
Viral vs. Bacterial Infection?
Confidential. This proposal and supporting materials contain confidential and proprietary business information from Lumos Diagnostics and RPS Diagostics.
These materials may be printed for use in evaluating the proposed project, but are not to be shared with other parties.
4 All of Us
Testing for Disease Prevention & Infection Control

49. © Lumos Diagnostics 2019, all rights reserved 49Confidential
Bacterial vs Viral Diagnosis is a significantly unmet need
Global Problem
More than 20% of population
worldwide seek care for acute
respiratory infection annually1,2.
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Diagnostic Uncertainty
Physicians do not have the tools available
to differentiatebacterial from viral
infections
Increased Adverse Events
Approximately5 – 25% of patients experience
an adverse event from Antibiotic use4, and
over-use contributes to spread of disease.
1 in 5 drug related ED visits are due to
Antibiotic reactions.
Over Prescription of
Antibiotics
ARI’s account for over 90% of all
Antibiotics in the US annually (41m
scripts), with up to 50% prescribed
unnecessarily3.
Antibiotic Resistance
Unnecessary use of antibiotics increases
antibiotic resistance, causing more than
25,000 deaths in the EU5, and results in
over $20 billionof direct healthcare
costs in the US annually6.
1. Krishnan A1, Amarchand R2, Gupta V3, et al. Epidemiology of acute respiratory infections in children - preliminary results of a cohort in a rural north Indian community. BMC Infect Dis. 2015 Oct 26;15:462.
2. Ambulatory CareVisits to Physician Offices, Hospital Outpatient Departments, and Emergency Departments: United States, 2001–02.Vital and Health Statistics. 2006; series 13, number 159.
3. Harris AM, Hicks LA, Qaseem A. Appropriate antibiotic use for acute respiratory tract infection in adults. Ann Intern Med 2016; 165:674
4. CDC, USA. Antiobiotic Resistance Threats in the United States, 2013.
5. ECDC/EMEA Joint Working Group (2016). The bacterial challenge: time to react. EMEA/576176. 13-42.
6. Van der Meer, V, Neven AK, van den Broek PJ, Assendelft WJ. Diagnostics value of C reactive protein in infections of the lower
respiratory tract: systematic review. BMJ. 2005; 331: 26.
Doctors are still unable to quickly differentiate bacterial from viral respiratory infections, this can be
even more problematic in a pandemic!

50. © Lumos Diagnostics 2019, all rights reserved 50Confidential
• Intracellular blood protein found in lymphocytes which is stimulated by type I
interferon
• MxA levels remain low with bacterial infection
• Sensitive and specific marker for viral infection
• Healthy people have a low concentration [less than 15 ng/ml]2,3
• Fast induction after infection [1-2 hours]2
• Peaks at 16 hours and remains elevated in the presence of elevated interferon4
• Long half-life [2.3 days]2
• Acute-phase protein synthesized by the liver
• Nonspecific marker for acute inflammation
• At low levels, CRP is very sensitive but nonspecific at confirming a bacterial infection
• At high levels, CRP becomes very specific for bacterial infection, but has low sensitivity
• Bacterial infection is a potent stimulus
• Elevates within 4-6 hours of infection and peaks after 26 hours6-7
• Half-life is 18 hours6-7
FebriDx: Proprietary Combination of MxA and CRP
[1] [1] Haller O, Freese M, Kpchs G. Rev Sci Tech 1998;17(1):220-30. [2] Nakabayashi M, Adachi Y, Itazawa T, et al. Pediatr Res 2006;60:770-774.[3] Kawamura M, Kusano A, Furuya A, et al. J Clin Lab Anal 2012;26:174-183.[4] Goetschy JF, Zeller H, Content J. J Virol 1989;63:2616-2622[5] ] Falk G, Fahey T. Fam Prac 2009;26(1):10-21.[6] Andreola B,
Bressan S, Callegaro S, et al. Ped Infect Dis J 2007;26(8):672-77.[7] Simon L, Gauvin F, Amre DK, et al. Clin Infec Dis 2004;39:206-17.[8] Salonen EM, Vaheri A. J Med Virol 1981;8(3):161-7. [9] Halminen M, Ilonen J, Julkunen I, et al. Pediatr Res 1997;41:647-50.
MxA 1-4
CRP 5-9
FebriDx
Together, MxA and CRP provide an accurate way to differentiate
clinically significant viral from bacterial Acute Respiratory Infections (ARI)

51. © Lumos Diagnostics 2019, all rights reserved 51Confidential
FebriDx: A Simple Test for a Global Crisis
Bacterial infection
Negative Results
FebriDx TEST PROCEDURE
1 2 3 4
• Identifies clinically significant acute
respiratory infection in 10 minutes
• Differentiate viral from
bacterial etiology
• Differentiate systemic infection
from colonization/carrier state
• 99% Negative Predictive Value
(NPV) to rule out bacterial infection
LANCE FINGER COLLECT BLOOD SAMPLE DELIVER BLOOD SAMPLE DELIVER BUFFER
BACTERIAL INFECTION VIRAL INFECTION VIRAL INFECTION
MxA 1-4CRP 5-9

52. © Lumos Diagnostics 2019, all rights reserved 52Confidential
FEBRIDX: PANDEMIC TESTING
• Introduction
- Majority of testing for patients suspected of COVID-19 is molecular based
• lab-based testing with average 48 hours to results causing delay of diagnosis and patient isolation issues
• Sensitivity of Molecular COVID-19 tests is reported to be only 45-74%
• Results
- UK Hospital
• FebriDx detected 34/34 COVID-19 Positive patients
• FebriDx detected 8/8 bacterial infections (COVID-19 negative)
• PCR missed 4 COVID-19
• Awaiting additional data before publication
- Netherlands OutPatient setting
• FebriDx detected 4/4 COVID-19 positive patients (PCR detected 2/4)
• Conclusion
- Based on initial testing FebriDx is sensitive to detect a COVID-19 infection (elevated MxA)
- Importance to detect bacterial infections during COVID-19 Pandemic

53. © Lumos Diagnostics 2019, all rights reserved 53Confidential
FEBRIDX: PANDEMIC TESTING
• FebriDx combines speed, ease of use and accuracy and is a useful diagnostic tool to manage
symptomatic patients in the COVID-19 Pandemic
- Rapidly diagnose viral patients
- Facilitate immediate patient isolation
- Ensure patients with bacterial infections are not missed
- Rule out non-clinically significant illness
- Reduce Inappropriate antibiotic prescriptions
- Optimise clinic workflow and facilitate remote patient testing

54. www.lumosdiagnostics.com
www.FebriDx.com

55. QUESTIONS AND ANSWERS

56. FURTHER INFORMATION
4 All of Us has compiled a range of studies and papers to
date which can also provide information on the role of
testing. You can access these at https://diagnostic-
summit.netlify.com/resources
We are also here to facilitate any questions, queries or
enquiries you may have on tests. To do so email
scott@4allofus.org.uk

57. THANKS FOR LISTENING
A recording of this webinar will be made available in due
course, along with the presentation slides.