How can POC support infection detection

1. MULTIPLEX ARRAYS FOR POINT OF CARE INFECTION
DETECTION
Martin Crockard, PhD
Molecular Diagnostics Manager
martin.crockard@randox.com

2. The Importance of Diagnostics
Diagnostics is the key enabler to improve Healthcare, patient outcomes and
reduce the burden on health services
70% of clinical decisions affecting diagnosis and treatment are based on a
pathology investigation, using under 3% of the healthcare budget
Improved diagnostics will revolutionise healthcare by enabling earlier and
more accurate clinical decision making

3. • Every year over 350 million patients are diagnosed using Randox technology
• Randox manufacture 3.5 billion tests per year
• Every second of every day 100 Randox tests are used across the world
• 5th largest manufacturer of clinical chemistry reagents in the world
• 10% of all cholesterol tests
• 3rd in world in Quality Control and calibrators
•We have more new tests in development than any other diagnostic company
•Committing up to 16% of turnover to R&D each year
Revolutionising Healthcare through improving diagnostics

4. • On review of current practice in healthcare systems, we concluded that
patient diagnostics could be greatly improved
• In particular, we felt the routine 5 – 6 blood tests per patient sample was
inadequate to accurately diagnose the 13,000 known diseases
• So we decided to find a way to measure many tests on one blood sample,
thereby achieving more accurate and earlier diagnosis
• 189 patents later………
Biochip Array Technology

5. Biochip Array Technology
• Solid phase ceramic chip
• Up to 100 Discrete Test Regions (DTRs)
• >4 internal control / reference DTRs to confirm assay functionality
• Extraction / amplification control DTR on every biochip (for MDx)
• Utilises Randox’s Multiplex PCR technology
• Simultaneously performs multiple assays
• Incorporates ELISA methodologies
• Manufactured at Randox in Northern Ireland

6. Using Biochip technology and our advances in Molecular biology, we
have unique and clinically critical tests designed for Point of Care and
central laboratory applications for
infectious diseases
oncology
Molecular Diagnostics and Oncology

7. Biochip Array Technology – Molecular versatility

8. Biochip Array Technology – Molecular versatility

9. Simple, easy to interpret result report

10. What are POC Molecular Diagnostics?
• Devices that facilitate rapid, accurate near-patient testing of a clinical
specimen, performed in a non-specialist setting by non-specialist personnel
• Similar level of user simplicity to making a cup of coffee using a Tassimo or
Nespresso (other brands are available!)
• Provides consistent and excellent quality, with trustworthy results

11. POC Infection Diagnostics Criteria
• Timely detection of the presence of an infectious agent or agents
• Syndrome-based diagnostic panels
• At least equal performance to lab-based equivalents
• Easy to use by non-laboratory personnel
• Placed at the point of need and patient-facing
• Will improve the patient care pathway
• Will improve antibiotic / drug stewardship
• Easy to interpret outputs
• Cost effective (immediate or medium term)

12. POC Infection Clinical Criteria
• Is the patient infected?
• If so, what are they infected with?
• Can I treat this patient?
• If so, what with?
• Can I wait for the test result before I treat the patient?
• Can I trust the result?

13. POC Infection Patient Criteria
•Fix me – NOW!

14. Randox Molecular Diagnostics POC Assays
• In collaboration with Bosch, we have developed a fully automated molecular
system, providing
• All core molecular processes in a closed environment
• Direct from patient sample to result report
• Connectivity via VivaSuite
• Complete in-process Quality Control
• Room-temperature stable test cartridge
Laboratory-standard quality outside the laboratory

15. VivaSuite
Vivasuite software enables remote connectivity via WiFi to;
• Monitor operation of all devices in your network
• Remotely monitor Quality Control to ensure uniform testing across network
• Access data in a secure environment
• Enable potential for infection / outbreak surveillance across sites
• Provide remote software updates for new tests as they become available
• Allow healthcare provider to control who has access to what data

16. Randox Infection Detection Arrays
Image from:
123RF.com

17. • More than 1 million people worldwide acquire an STI every day
• In England 422,000 STIs diagnosed in 2017, including
• 7,137 syphilis: 20% more than 2016 and 148% more than 2008
• 44,676 gonorrhea: 22% increase from 2016
• 203,000 (48%) chlamydia – of STIs being looked for
• 33,000 (8%) non-specific genital infections!
• Many STIs are asymptomatic, thus may remain undiagnosed
• British Association for Sexual Health and HIV (BASHH) recommendations include;
• Chlamydia and gonorrhoeae screening
• Herpes and syphilis (Treponema pallidum) testing in the presence of genital ulceration
• Symptomatic women may also be tested for Trichomonas vaginalis
• Mycoplasma genitalium now also to be considered
All of these tests are included in one STI Biochip
Sexually Transmitted Infections: Need and Capability

18. • Improved patient experience and diagnosis
• Fast and accurate STI testing in the community; reduced reliance on GUM clinics
• Comprehensive multiplex screening
• STI co-infection rates are high – 21% in our study
• Cost savings, Eg., suspected Trichomoniasis, LGV or Mycoplasma infections, where existing
tests are expensive, individual and not standardised
• Labour saving; used by non-specialist staff
• Improved antibiotic stewardship
• MDR Gonorrhea and Mycoplasma genitalium concerns
• Evidence-based decision making at point of need
• Potential for national infection surveillance and management of STIs and MDR
• Availability of POC EQA scheme and IQC controls
Vivalytic STI benefits

19. Vivalytic STI: Performance Comparison
RVH/RCLS result STI VII result Vivalytic
CT CT CT
CT CT CT
CT, UU CT, UU CT, UU
CT CT CT
CT CT CT
CT CT CT
CT, UU CT, UU CT, UU
CT, MH, UU CT, MH, UU CT, MH, UU
NG NG, UU NG, UU
CT, UU CT, UU CT, UU
NG, MH NG, MH NG, MH
NG, UU NG, HSV1, UU NG, HSV1, UU
NG NG, HSV1 NG, HSV1
NG NG NG
CT, MH, UU CT, MH, UU CT, MH, UU
CT, MH, UU CT, MH, UU CT, MH, UU
MH, MG MH, MG MH, MG
CT, MH, MG CT, MH, MG CT, MH, MG
MG MG MG
MG MG MG
CT, MG, UU CT, MH, MG, UU CT, MH, MG, UU
TV, MH TV, MH TV, MH
HSV1, MH, UU HSV1, MH, UU HSV1, MH, UU
Neg Neg Neg
Neg Neg Neg
• Snapshot of test data comparing STI II (Randox) with
Vivalytic
• Clinical Reference Laboratory (Belfast HSC Trust)
also included to show concordance across all
platforms
• CT & NG at Belfast Trust used Roche Cobas as
comparator assay
• Highlights need for multiplex approach, with co-
infections
• In some cases, Randox and Vivalytic outputs detect
additional infections, including HSV1, UU and MH

20. Respiratory Infection
• Lower respiratory tract infections (LRTIs) are the third greatest cause of mortality worldwide,
accounting for 3.5 million deaths, 230,000 in EU (WHO)
• Respiratory illness costs the UK ~£11.1 billion p/a in direct costs: 0.6% of GDP*
• A respiratory cost breakdown, reveals
• 29% to be levied towards COPD and 28% to cancers
• 16% (£1.7 billion) and 1% (£76 million) associated with lower tract and upper tract infection, respectively
• In England and Wales, 25% of the population will visit their GP because of a respiratory
infection and account for 60% of antibiotics prescribed
• The lack of infection-specific symptoms makes diagnosis on clinical presentation problematic
• Treatment approaches are equally variable
• Therefore important to identify the causal agent(s) of infection to aid appropriate therapy
*Ref: Estimating the economic burden of respiratory illness in the UK. 2017

21. Respiratory Multiplex Array
Target organisms detected
Adenovirus
Coronavirus 229E/ NL63
Coronavirus OC43/ HKU1
Coronavirus 229E
Coronavirus HKU1
Coronavirus NL63
Coronavirus OC43
Coronavirus (MERS-CoV)
Human Bocavirus
Human Metapneumovirus
Human Rhinovirus
Human Enterovirus
Human Rhinovirus/Enterovirus
Influenza A
Influenza A H1
Influenza A 2009 H1N1
Influenza A H3
Influenza B
Parainfluenza 1
Parainfluenza 2
Parainfluenza 3
Parainfluenza 4
Respiratory Syncytial Virus
Respiratory Syncytial Virus A
Respiratory Syncytial Virus B
Bordetella pertussis
Bordetella parapertussis
Legionella pneumophila
Mycoplasma pneumoniae
Chlamydophila pneumoniae
Moraxella catarrhalis

22. • Annual UK estimates of 4 million Urinary tract infections (UTIs)
• Prevalent in nursing homes; account for 30-50% of antimicrobial prescriptions
• Increased infection rates often due to medical intervention, e.g. catheters
• Diagnosis is difficult as symptoms are often vague and non-specific
• GP diagnostic tests are dipsticks for leukocytes and nitrite – highly inaccurate
• Lab-based diagnosis is predominantly through culture;
• Slow
• Labour intensive
• Costly
• Antibiotics tend to be prescribed before results are available
• Prudent antibiotic prescribing is a key component of UK action plan
Urinary Tract Infection

23. Acinetobacter baumannii Providencia rettgeri
Candida albicans Providencia stuartii
Citrobacter freundii Serratia marcescens
Citrobacter koseri Staphylococcus aureus
Enterobacter aerogenes Staphylococcus epidermidis
Enterobacter cloacae Staphylococcus saprophyticus
Enterococcus faecalis Streptococcus agalactiae (GBS)
Enterococcus faecium MecA
Escherichia coli TRes 1
Klebsiella oxytoca TRes 2
Klebsiella pneumoniae TRes 3&4
Morganella morganii TRes 5
Proteus spp. VanA
Pseudomonas aeruginosa VanB
UTI Multiplex Array

24. UTI Multiplex Array benefits
• Incorporation of antibiotic resistance profiling facilitates better stewardship
• Trimethoprim resistance is ~23-33%, particularly in E. coli and Klebsiella spp.
• We identified 5 genes that account for ~86% of Trimethoprim resistance in Europe
• Also have MecA (for MRSA) and Vancomycin resistance biomarkers
• Does not disrupt current UTI guidelines, but
• When symptomatic evidence is strong,
UTI Infection Array can improve diagnosis
• May allow re-introduction of Trimethoprim
• Can reduce repeat prescription of failing drugs

25. Randox development pipeline
• Randox are continuously developing new Molecular Multiplex Assays
• All tests will be stable at room temperature and contain all necessary reagents
• POC and laboratory-based automated platforms share common assays
• New CE-IVD Molecular tests (due before end 2020) include;
• Chronic Lung Array: 138-plex for Cystic Fibrosis and COPD-related infections
• Enteric Array: 20-plex for digestive tract infections
• Sepsis Array: 47-plex for infection detection direct from whole blood
• Meningitis: 13-plex for bacterial and viral meningitis / encephalitis
• Pancancer Array: 90+ actionable mutations indicating therapy choice
• Multiple genetic disorder arrays; CF mutation, T1 Diabetes, etc

26. In conclusion
• Randox provide syndromic tests to meet clinical need
• Our network of clinical and academic partners help define our panels
• Syndromic approach provides more complete analysis
• Designed for use by non-specialist personnel, without compromise
• Speed of result encourages single visit for diagnosis and prescription
• Improves antibiotic stewardship
• Earlier detection of infection facilitates earlier, tailored intervention

27. Sepsis
• Sepsis syndromes account for 46% of all intensive care unit bed days with
over 100,000 confirmed cases in the UK annually
• Even with the best treatment, mortality ranges from 15% in patients with
sepsis to 40-60% in patients with septic shock
• Septic shock develops in about 40% of sepsis patients and rates are increasing
• Sepsis is responsible for up to 64,000 deaths every year in UK
• More deaths than from colorectal, breast and prostate cancers combined
• Sepsis patients are 3 times more likely to move into long term care

28. • Blood culture still the diagnostics gold standard, 24-72 hours to result, so
empirical antimicrobial therapy proceeds at presentation
• Patients are monitored in ICUs, with review every 4 hours
• Treatments modified to take account of clinical presentation and diagnostics
• Accurate infection identification, direct from venous blood inside 4 hours
could transform sepsis care pathways
• Randox can meet the sepsis challenge
Sepsis

29. Genus Escherichia Enterobacter Citrobacter Salmonella Klebsiella Morganella Serratia Proteus Enterococcus
Species E. coli E. aerogenes C. koseri S. enteritidis K. oxytoca M. morganii S. marcescens Proteus sp. E. faecium
E. cloacae K. pneumoniae E. faecalis
Genus Listeria Acinetobacter Aspergillus Pseudomonas Neisseria Haemophilus Bacillus
Species L. monocytogenes A. baumannii A.fumigatus P. aeruginosa N.meningitidis H.influenzae B. cereus
Genus Staphylococcus Streptococcus Bacteroides Candida Corynebacterium Fusobacterium
Species S. aureus S. pneumoniae B. helcogenes C. albicans C.jeikeium F. necrophorum
S. epidermidis S. dysgalactiae B. Fragilis C. glabrata C. ulcerans F. nucleatum
S. pyogenes B. ovatus C. parapsilosis
Coagulase-neg. Staph S. agalactiae B. Vulgatus C. krusei
S. hominis S. gallolyticus B. Thetaiotaomicron
S. lugdinensis Resistance
S. haemolyticus Strep anginosus group Van A
S. anginosus Van B
S. constellatus Mec A +
S. intermedius
47 bacterial and fungal sepsis targets
• One cartridge
• Automated platforms
• Direct from blood
• 3 AMR genes
• 4 hour time to result
Sepsis

30. Trust Name
Lothian Universities Hospital Trust
Belfast Health & Social Care Trust
Heart of England NHS Foundation Trust
Western Health & Social Care Trust
Northern Health & Social Care Trust
South Eastern Health & Social Care Trust
Poole Hospital NHS Foundation Trust
Chelsea and Westminster Hospital
University Hospitals Bristol NHS Foundation Trust
University Hospital of South Manchester
Royal Berkshire NHS Trust
University Hospital Southampton NHS Foundation Trust
Medway NHS Foundation Trust
Salford Royal NHS Foundation Trust
Imperial College Healthcare NHS Trust
North Bristol NHS Trust
Blackpool Teaching Hospital NHS Foundation Trust
Hull and East Yorkshire Hospitals NHS Trust
Sherwood Forest Hospitals Foundation Trust
Royal Liverpool and Broadgreen University Hospitals
Surrey & Sussex Healthcare NHS Trust
Wirral University Teaching Hospitals NHS Foundation
Portsmouth - Queen Alexandra Hospital
Royal Cornwall Hospital Trust
Royal Surrey County Hospital NHS Foundation Trust
Mid Yorkshire NHS Trust
Royal Free London NHS Foundation Trust
County Durham and Darlington Foundation Trust
Kings College
Queens Medical Centre
Oxford University Hospitals NHS Trust
Gateshead Health NHS Foundation Trust
Newcastle upon Tyne Hospitals NHS Trust
• Working with Queen’s University Belfast
and the Clinical Trials Network, we have;
• Collected 3,100 samples
• Across 38 ICUs
• Over a 24 month period
• To confirm clinical benefit
• Anonymised and predicate data blinded
• Plus 900 suspected sepsis blood samples
• 12% positive rate
Sepsis