AUTOMATING TRADITIONAL RAPID PLASMA REAGIN (RPR): CHALLENGES AND BENEFITS.

Godfred Masinde, PhD, MBA, HCLD(ABB), CM (CA)San Francisco Department of Public Health Laboratory

APH Annual MeetingJune 4, 2019

PresenterPresentation NotesI would like to thank APHL for giving me a chance to participate on this panel, my interests have always been to find ways to improve testing in Public Health Labs. Customizing testing for the community helps in being efficient to control STDs and other infectious diseases.

Contents

Background Automated Traditional RPR Laboratory & Clinical Challenges Benefits

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PresenterPresentation NotesI will divide my talk into four areas: backgroundAutomated RPRChallenges and benefitsVerification Data summary

Slide 3Syphilis Trends in San Francisco

PresenterPresentation NotesSyphilis trends in SF are the highest compared to other cities like LA and New York and USA Lab testing has also increased from 28K to 36K excluding manual titers for > or + 256 It has increased by 18% (it is higher waiting for Bob to give the real numbers)

Why Automate Traditional RPR

San Francisco (SF) has high prevalence of positive syphilis SF City Clinic clinicians relay on nontreponemal antibody test to monitor the effect of treatment Handle large volume of tests dailyReduce turn around time(TAT)

Slide 4

PresenterPresentation NotesOur needs for the community is treatment and a test to monitor its progressSan Francisco has a high prevalence of positive syphilis cases, so with reverse algorithm there will still be many to be tested by nontreponemal testOur main purpose for testing is for the clinician to be able to monitor the effect of treatment by reduction in titer using nontreponemal testsThere has been an increase of syphilis specimens and need for faster TAT

Traditional RPR Automation – AIX1000 System

RPR screens & titersPositive specimen ID/Tracking Automated liquid handlingSoftware performs result

interpretation

Slide 5

FDA Cleared

PresenterPresentation NotesDescribe AIX1000 and what it is capable of doingUsing AIX1000, screens and titers up to 256Specimen tracking so there is no confusion and all the liquids needed are handled by the systemsResults are interpreted by the AIX software and no variations as in person to person or one reader to another, it is all uniform.

AIX1000 RPR Results Display Slide 6

PresenterPresentation NotesHow the results look like on AIX1000, with a digital picture available for future review

Slide 7

Laboratory Challenges

Verification:• Manual VDRL vs AIX1000 Automated RPR• Manual RPR vs AIX1000 Automated RPR

PresenterPresentation NotesAccording to PT results by CAP, the correct titers can be up to 4 titers apart Reading the titer results, VDRL are low and RPR are high, for example 1:2 on RPR is negative/weakly reactive for VDRL, how does the clinician use that result if they had already a patient they are following up and in our case we had been screening with VDRL they will think the patient is reinfected?For our community the patients are on treatment and the clinician needs to be clear that anything 1:1 or 1:2 using automated RPR does not raise any alarm, the patient could be serofast too.Most people become negative for RPR with adequate treatment, though some patients who present with later stage disease may maintain a low titer RPR (

VDRL/RPR CAP PT RESULTSSPREAD

Slide 8

PT Event RPR VDRL

G-A-18 1:2 to 1:16 1:1 to 1:8

G-B-18 1:1 to 1:4 1:1 to 1:4

G-C-18 1:4 to 1:32 1:2 to 1:16

PresenterPresentation NotesAccording to CAP PT results the correct titers are up to 4 titers (1:4, 1:8, 1:16, 1:32) apart Using 2018 CAP PT results, the titers spread up to 4 titers apart but still consensus makes them correct We had to decide on how large our titer spread should be between automated RPR vs manual VDRL or RPR so the clinician can decide if it is a reinfection or just difference in the assay

AIX1000 vs Manual VDRL/RPR Slide 9

AIX1000 vs. VDRL

AIX1000 vs. RPR

Sensitivity 99.70% 100%

Specificity 99.50% 98.40%

PresenterPresentation NotesAfter overcoming our challenges, verification analysis was completed with sensitivity of over 98% at 95% CI for both VDRL and RPR.Precision was also performed and the reproducibility was 100%

Laboratory ChallengesSlide 10

Maximum Titers:• Automated titer is 1:256External Control:• Calibrated Control

PresenterPresentation NotesMax titer is 1:256; therefore when result is 1:256 on AIX, lab tech has to do manual dilution to determine titer, as exact quantitative result at time of treatment establishes baseline and is used by provider to assess response to treatment

We had challenges using a pooled external positive controlIt varying daily and failing our runsIt was not calibrated so we could not have an expiry date on itHad to find a calibrated external control that does not vary

Clinical ChallengesSlide 11

• Training clinicians to transition patients from manual VDRL to automated RPR titers

• Automated RPR titers are 1-2 dilutions higher than manual VDRL

PresenterPresentation NotesAIX RPR runs about 1-2 dilution higher than VDRL; therefore clinical staff had to adjust protocol to account for this. If someone who was serofast with a VDRL of 1:4 came in and had an AIX RPR of 1:16 (no symptoms) – should clinician treat as new case of early latent? Case by case; sometimes would repeat test after 1-2 weeks to see if it was sustained rise, especially if patient denied risk factors and was willing to come back for treatment if needed. This caused some initial work in first 12 months after change from VDRL to RPR, which as now settled back downMedical director issued guidance to clinicians

Benefits – Automated RPR, AIX1000Slide 12

• Reduces turn around time• Reduces hands on• Reduces work load and ergonomic injuries• Reduces the potential for technique related errors• Digital results: save data and review on demand • Less Expensive

PresenterPresentation NotesReducing time to setup will reduce the cost of the testSoftware reads and interprets the resultsStores the raw data in digital format for reviewreduces human error or human to human variations

Traditional vs ReverseSlide 13

PresenterPresentation NotesFew steps for traditional RPR making it faster and less expensive

Results used directly by clinicians to monitor patient recovery

Slide 14San Francisco Public Health Lab

PresenterPresentation NotesLocated on the fourth floor of an over 80 years old historic building

Acknowledgement

APHL for the opportunitySF City Clinic StaffSF DPH Lab StaffDisease Control and Prevention

Slide 15

Design by Mehroz Baig v. 2017-4-14

THANK YOU!

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Automating TRADITIONAL Rapid Plasma Reagin (RPR): Challenges and Benefits.ContentsSlide Number 3Why Automate Traditional RPRTraditional RPR Automation – AIX1000 SystemAIX1000 RPR Results Display Laboratory ChallengesVDRL/RPR CAP PT RESULTS�SPREAD AIX1000 vs Manual VDRL/RPR Laboratory ChallengesClinical ChallengesBenefits – Automated RPR, AIX1000Traditional vs ReverseSlide Number 14Acknowledgementthank you!