1. Changing Technology in Diagnosis of STI
Syndromic Algorithm Approach- S6
Dr Mat Donati
Bristol Public Health Laboratory
Health Protection Agency
21 November 2018

2. Objectives Why STIs? History of microbial diagnostics
STI syndromic diagnostic algorithm
Impact of changing technology
Case ascertainment
POCT

3. Why STIs? Key public health focus Prevalence/ incidence increasing
Epidemics amongst high risk groups
High infectivity and rapid spread drives need for better diagnostics
Common symptoms, different pathogens
Screening/ asymptomatic infections

4. There Are Lots of STIs

5. Everybody knows how to avoid infection

6. I need another drink

7. That’s not the bottle opener........

8. Trends in diagnoses made in GUM clinics in the UK: 1999 – 2008
Trends over the 10 year period from 1999 to 2008 show a gradual rise in both the number of new STI diagnoses and other STI diagnoses (e.g. recurrent infections). Other diagnoses made in GUM clinics (e.g. candidosis & vaginosis) have remained relatively stable but rose sharply between the years 2006 and 2008.

9. Health Protection Report Vol 5 No. 17 - 28 April 2011

10. Health Protection Report Vol 5 No. 24 - 17 June 2011

11. Estimated number of people living with HIV Infection: United Kingdom, 2010
Total with HIV = 91,500 (85,400 − 99,000) Total diagnosed = 69,250 (67,800 − 70,800) Total undiagnosed = 22,200 (16,350 − 29,650)
In 2010, there were an estimated 91,500 people living with HIV infection (both diagnosed and undiagnosed) in the UK. Overall one quarter were estimated to be unaware of their HIV infection.
HIV in the UK, 2011 report

12. Probable recent infection among people newly diagnosed with HIV by exposure group: England and Northern Ireland, 2010
In 2010, more than 90 HIV clinics and 50 laboratories participated in the national monitoring of recent HIV infections in England and Northern Ireland. Specimens of individuals newly diagnosed with HIV were tested for recent infection using an inhouse HIV avidity assay (modified AxSYM HIV-1/2 ELISA test, Abbott, UK).
Over 3000 samples were submitted to the HPA for a test of recent HIV infection. However, because of poor quality data, only 2258 could be matched to a new diagnosis report resulting in 37% coverage.
Overall, 14% (327/2258) of diagnosed infections were likely to have been recently acquired. This proportion was higher among MSM (24%), compared to heterosexual women (7%) and heterosexual men (9%) .
The group ‘other’ including mother to child transmission, blood transfer and other is not shown here.
HIV in the UK, 2011 report

13. We could try new interventionsOr
We could improve case finding, treat early, educate

14. How To Make A Diagnosis History of microbial diagnostics
Stage of infection
Antibody
Antigen/ Culture
Nucleic Acid (PCR)
Exposure
N/A
Early Infection  
Symptoms
/ 
Immune response
Recovery with immunity
History of microbial diagnostics

15. A Brief History Of Bacterial Diagnostics*
Age of Microscopes and Jelly
Era of no beards
Era of beards
Era of enlightenment (talking to virologists)
Beards optional
Hans Christian Gram
2000
Present
1673
1881
Nothing happens
Nothing happens
1884
Microscopy: Antonie Van Leeuwenhoek
Robert Koch: solid media
*A virologists personal view
Congress of Hygiene and Demography, London 1891

16. A Brief History Of Viral Diagnostics
Era of too small to see
Antigen / antibody era
Era of technology
DNA blot
Sanger sequencing
Monoclonals
Inclusion bodies in smallpox lesions (Guarnieri)
CFT expansion EM
DIF
PCR
bDNA
Arrays
Next gen seq
Personalized diagnostics
Host response
1892
1913
1938
1942
1950’s
EIA
1975
1985
1994
1996
1898
Tissue culture
1941
1948
1960
1971
1976
Real-time,
Hybrid capture
HAI
Cell culture
RIA
Foot and mouth caused by filtrable agent
First HBsAg EIA
1953: Structure of DNA

17. Modern Approach We need a diagnostic approach for STIs that
Detects the most important pathogens
Delivers results in a timely manner
Uses the most appropriate technology
Ensures good practice
UK Standards in Microbiological Diagnosis

18. UK Standards for Microbiology Investigations
What are they?

19. UK Standards for Microbiology Investigations
Recommend good standards (not minimum, not best)
Not mandatory (but labs should be able to demonstrate equivalence, or better)
As a clinical, laboratory and commissioning reference
As a standard for audit
Benchmark against which to assess and improve methods
Covers all elements of testing process, including notification and sample referral (public health)

20. Virology/ Bacteriology
Guidance
Quality
Virology/ Bacteriology
Syndromic

21. Standard Microbiology Investigations
HOW?-The Process

22. Supporting organisations
Steering Group
Working Groups
Supporting organisations
Microbiology Professional Committee of the Association of Clinical Biochemistry

23. Idea to Document Evidence Expert opinion Need (New/ Review) Draft
Working Group
Review
Consultation
Amendments
Issue
Expert opinion
Evidence
ISO 9001

26. S6

32. Future Continuous update of USMI documents
‘One stop shop’ syndromic algorithms
Account for new technology on interpreting test result
Increased incidence due to introduction of IgM
Increased incidence due to high sensitivity tests (PCR)
Wider testing/ POCT and PPV

33. Positive Predictive Value (PPV)
A measure of confidence in the test result for a specific population or group
PPV of 90% means that a positive result will have correctly identified an infected person 9 times out of 10
The equation
PPV=SensxPrev/ (sensxprev)+(1-spec)x(1-prev)
means that population prevalence and test specificity are key to PPV calculations

34. The MD Energy Saving Point (ESP) Of Care HIV Test
Bulb off = Negative
Bulb on = Positive

35. Get Your MD ESP HIV Test Now
Accurate and Reproducible1
Safe2
Environmentally friendly3
Widely available4
Multifunctional5
MD ESP HIV £9.99
In field trails of 10,000 people low risk for HIV infection, the MD ESP identified the correct result in 9,999*
1Always gives the same result 2No risk of electric shock 3Excellent carbon footprint
4It is a bulb 5It is a bulb
*Population prevalence tested 0.01%
Dr MD, MD of MD diagnostics said ‘It’s as if the ESP knows the result before you open the packet’

36. High NPV critical to not miss a true infection
Range of PPV and NPV
Prevalence HIV %
Worst Sensitivity
96% (spec 99.8)
Worst Specificity
95% (sens 99.9)
Worst overall (fictional)
96% sens, 95% spec
Best likely
99.9% sens, 99.8% spec
PPV
NPV
0.01 5%
100%
~0% ~0
0.1
32% 2%
33% 1
83%
17%
16% 6
97%
56%
55% 15
99%
78%
77%
High NPV critical to not miss a true infection
High PPV helps to prevent unnecessary distress/ cost/ loss of belief in testing due to false positives

37. End
Questions?