Point of Care Tests: Clinical Use in 2017

Charlotte A. Gaydos, MS, MPH, DrPHProfessor, Division of Infectious Diseases

Johns Hopkins University, Baltimore, Maryland

Helsinki 31st IUSTI-Europe Congress on STIs

Objectives

1. To discuss current molecular tests and update new POC tests in the pipeline

2. To demonstrate different venues for STI testing outside the clinic, OTC or home STI testing

3. To mention impact of POC testing-advantages and barriers

0

20

40

60

80

100

120

140

160

Chlamydia Gonorrhea Trichomonas143 Syphilis

131 Million

78 Million

143 Million

6 Million

WHO Estimates of Global Prevalence of STIs in 2012

Newman et al. PLOS ONE | OI:10.1371/journal.pone.0143304 December 8, 2015 7 /

36.7 million Adults and Children Living with HIV

Use of POC in Clinical Settings• Immediate treatment before patient

leaves the clinic; no loss to follow-up

• Impact on disease epidemic?– Decrease interval of disease spread

• Impact on behavior?– Counseling on risk reduction

• ASSURED Criteria – When is a test good enough?

Affordable by those at risk of infection

Sensitive few false negatives

Specific few false positives

User-friendly simple to perform: 3-4 steps, with minimal training

Rapid and Robustrapid: to enable treatment at first visitrobust: no requirement refrigerated storage

Equipment-free easily collected non-invasive specimens, e.g. urine, saliva. vaginal

Delivered delivered to end-usershttp://www.who.int/std_diagnostics/about_SDI/priorities.htm

WHO ASSURED Criteria for POC Tests

Overview: Point-of-Care Tests for STIs

Chlamydia trachomatis (CT)Neisseria gonorrhoeae (NG)Trichomonas vaginalis (TV)SyphilisHerpes Simples Virus (HSV)HIV

Gaydos, C. Rapid Tests for STDs Current Infect Dis Reports 2006;8:115-124

Huppert et al. Point of Care tests for STIs: What’s the Point? Point of Care Journal, 2009

Gaydos and Hardick POC diagnostics for sex transmit infect: Perspectives and advances. Expert Review of Anti-infective Therapy. 12:657-672, 2014.

•Chlamydia

•Gonorrhea

•Trichomonas

•Syphilis

•HSV HIV

Overview New POC tests for STIs

Gaydos and Hardick, POC diagnostics for sex transmit infect: Perspectives and advances. Expert Review of Anti-infective Therapy. 12:657-672, 2014.

Organism Test Sample Type Sensitivity* Specificity*

Chlamydia trachomatis Biostar OIA Chlamydia test Cervical Male Urine

59.4-73.8% 98.4-100%

Clearview Chlamydia CervicalVaginal

49.7%32.8%

97.9%99.2%

Quick Vue Cervical 25-65% 100%Chlamydia Rapid Test Vaginal

Male Urine83.5% 98.9%

X-pert CT/NG CervicalVaginalFemale UrineMale Urine

97.4%98.7%97.6%97.8%

99.6%99.4%99.8%99.9%

Neisseria gonorrhoeae Biostar OIA GC test Cervical 60% 89.9%PATH GC-Check Cervical

Vaginal70%54.1%

97.2%98.25

X-pert CT/NG CervicalVaginalFemale UrineMale Urine

100%100%95.6%98.9%

100%99.9%99.9%99.9%

Sensitivity and Specificity of POC/near patient tests for CT & NG

Gaydos and Hardick POC diagnostics for sex transmit infect: Perspectives and advances. Expert Reviews 10.1586/147872.2014.880651, 2014 Adapted from Huppert et al. (2010). * Sensitivity and specificity compared to NAATs

“Near Patient” Test for Chlamydia and

Gonorrhea

GeneXpert® CT/NG, Cepheid (90 minutes)

Gaydos et al. J Clin Microbiol. 51:1666-1672, 2013

Sensitivity: 95-100%Specificity 99-100%

FDA Cleared: CT/NG,TV; urine, cervical, vaginal swabs

Female Results CT/NGXpert CT/NG vs. Patient Infected Status

Specimen Sensitivity SpecificityCT Cervical 97.4% 99.6%

CT Vaginal 98.7% 99.4%CT Urine 97.6% 99.8%NG Cervical 100% 100%NG Vaginal 100% 99.9%

NG Urine 95.6% 99.9%Gaydos et al. J Clin Microbiol. 51:1666-1672, 2013

Male Results

Xpert CT/NG vs. Patient Infected Status

Specimen Sensitivity Specificity

CT Urine 97.5% 99.9%NG Urine 98.9% 99.9%

Atlas Genetics io™ System• Low cost instrument• All reagents are on the Cartridge

• Ambient storage >12 month shelf-life• Broad range of clinical sample types• Disposable cartridge for sample• Results provided as clear output• CE Marked (CT); FDA clinical trials

underway (CT/NG)• Electrochemical label released from

probe hybridized by nuclease enzyme

Atlas Genetics io™ SystemPerformance Characteristics of Atlas Assay Compared to

Laboratory-Based NAAT Testing by Symptom Status

Number TruePositive

FalsePositive

Prevalence (%)

Sensitivity (%)

Specificity (%)

Initial results 284 26 3 10.2 83.9 98.8

AfterDiscordant Testing

284 28 3 9.9 92.9 98.8

Lea Widdice, DeAnna Owens, Barbara Silver, Mathilda Barnes, Perry Barnes, Laura Dize, Charlotte Gaydos,Cincinnati Children’s Hospital Medical Center, Johns Hopkins University Society for Adol Health and Medicine Annual Meet. March 8-11, 2017, New Orleans, LA.

Mobi-NAAT Chlamydia Test / PCR Droplet PCR microfluidic platform / Smartphone

Droplet cartridge platform

02000400060008000

10000120001400016000

0 10 20AU

C F

luor

esce

nce

(AU

)Sample identification number

Shin DJ, et al. Mobile nucleic acid amplification testing (mobiNAAT) for Chlamydia trachomatis screening in hospital emergency department settings Sci Reports 2017 Jul 3;7(1):4495

Mobi-NAAT Chlamydia Test / PCR Droplet PCR microfluidic platform / Smartphone

Shin DJ, et al. Mobile nucleic acid amplification testing (mobiNAAT) for Chlamydia trachomatis screening in hospital emergency department settings Sci Reports 2017 Jul 3;7(1):4495

Shin DJ, et al. Mobile nucleic acid amplification testing (mobiNAAT) for Chlamydia trachomatis screening in hospital emergency department settings. Sci Reports 2017 Jul 3;7(1):4495

Trichomonas vaginalis Diagnostics

Wet Preparation showing motile trichomonads

Electron microscope view of trichomonas on epithelial cell

Stained Trichomonas

• Wet Preparation• Culture• Affirm VPIII • OSOM POC

AmpliVue POCSolana POCAptimaT. vaginalis (ATV)Becton Dickinson (TVQ)

• NAAT Non-NAAT

OSOM Rapid TV Antigen Test•Immunochromato-graphic •TV membrane proteins•Mouse antibodies•Latex beads/ capillary action

Huppert et al , JCM 2005; STI 2007:

Sensitivity 83-90%,Specificity 98-100%

AmpliVue® Trichomonas HDA Assay

1) simple sample preparation with 1-step dilution/heating2) isothermal DNA amplification of target sequence specific to T. vaginalis by Helicase Dependent Amplificat.3) lateral-flow strip based colorimetric detection in a self-contained, disposable device. FDA clearedSensitivity 100%; specificity 98.2% vs. culture/wet prep. Vs. NAAT PPA: 87.2-90.1%

Gaydos et al. STD 2016

Clinical performance of the Solana POC Trichomonas Assay from clinician-

collected vaginal swabs and female urines

HDA amplificationRecently FDA ClearedModerately ComplexGaydos et al. CDC STD meet. Atlanta Sept 2016

Sample Sensitivity Specificity

Swabs 89.7% 99.0%Urine 100% 98.9%

Compared to NAAT reference

Vaginal Sensitivity SpecificityAsym. 100% 98.9%Sympt. 98.6% 98.5%

Compared to wet prep/culture

TV prevalence swabs and/or urines 11.5%

HSV POC Diagnostics

• FDA-cleared for HSV in genital and oral lesions• The IsoAmp HSV has a test-to-result time of <1.5 hr.• Isothermal helicase-dependent amplification (HDA)

technique; no nucleic acid extraction• The rapid and simple characteristics of the IsoAmp

HSV assay make it potentially suitable for POC testing

The IsoAmp® HSV Assay (Biohelix Corp)

Lemieux et al. Expert Reviews Ltd. 437-443, 2012;

25 ulVTM

1 ml buffer

25 ul

25 ul Master mix

640 60 min

Syphilis: Serologic DX requiresdetection of two types of

antibodies•Non-Treponemal RPR, VDRL •Treponemal FTA-abs, TPPA, Many new

automated, POC

Both test types have imperfect specificity•Reactive treponemal test cannot distinguish active from inactive infection

VDRL: Venereal Disease Research Laboratory

RPR: Rapid Plasma Reagin

Treponemal Syphilis Tests: EIA/CIA/POC

Advantages:

• Automated and are cost saving for large volume laboratories

• May detect old untreated syphilis

Disadvantages:

• Less clinical experience with interpretation

• May be less sensitive than FTA-ab in early primary syphilis

• Available in the U. S. - Immunochromatographic strip tests (ICS) • Syphilis Health Check – Trinity Biotech (FDA cleared, CLIA waived)

• Available Internationally• SD Bioline Syphilis 3.0 – Standard Diagnostics/ Alere• Determine Syphilis TP – Standard Diagnostics/ Alere

• Dual HIV/ Syphilis assays• Multiplo TP/HIV – Medmira Inc.• DPP HIV/ Syphilis – Chembio Diagnostics• SD Bioline HIV Syphilis Duo – Standard Diagnostics/ Alere

(WHO Premarket qualified)• INSTI™ HIV/Syphilis Multiplex Test - bioLytical• OnSite™HIV/Syphilis Ab Combo Rapid Test - CTK Biotech• CTK Biotech, Inc.• mChip Assay

Some Rapid POC Syphilis Tests

Laboratory evaluations of syphilis rapid test performance 2010-2014

• Meta-analysis of 33 studies from POCs Sensitivity: 75.12% to 83.78% for blood

75.98% to 92.03% for serumSpecificity: 98.39% to 99.44% for blood

92.68% to 98.51% in serum

Bristow et al Sex Health 12: 119-125, 2015

PPV

Uni-Gold Recombigen

OraQuick Advance

Clearview Complete

Clearview Stat PakINSTI

CLIA-WaivedPoint-of-Care

Rapid HIV Tests

HIV

4th generation HIV-1/2 immunoassay

HIV-1/HIV-2 antibody differentiation immunoassay

(-)Negative for HIV-1 and HIV-2 antibodies

and p24 Ag(+)

HIV-1 +HIV-1 antibodies

detected Initiate care

(and viral load)

HIV-2 +HIV-2 antibodies

detected Initiate care

HIV-1&2 (-) or indeterminate

RNA

RNA (+)Acute HIV-1 infection

Initiate care

RNA (-)Negative for HIV-1

New HIV Diagnostic Algorithm

HIV-1 +/HIV-2 +HIV antibodies

detected

Branson BM, Mermin J. J Clin Vir 2011;52:S3-4; MMWR 62, June 21, 2013. CLSI 2011

Screen

Confirm

HIV Antibody

0 10 20 30 40 50 60 70 80 90 100

HIV p24 Ag

Acute HIV Infection

HIV RNA (plasma)

IgMIgG

Eclipse Period

Infection undetectable

!

Modified after Busch et al. Am J Med. 1997

HIV Infection and Laboratory Markers

Bio-Rad Geenius™

• HIV confirmation and differentiation in less than 30 minutes• 3 sample types : serum, plasma (5ul), whole blood (15 ul) • Software that uses a validated algorithm, Full traceability • Limited data on performance in the lab algorithm suggests comparable

to Mutlispot

Delaney et al CROI 2015 abstract #621

Supplemental assay -Confirmation and differentiation of HIV-1 and HIV-2 antibodies

Alere Determine™HIV-1/2 Ag/Ab Combo

Method: Lateral flowTime to Results: 20 minutesStorage Conditions: 2 - 30°CShelf Life: 9 monthsSample Type: Serum/plasma/whole bloodDistinguishes Ag/Ab reactivity

• We do not know performance characteristics in the lab algorithm-Data collection is underway

• CLIA waived for whole blood

• Data from plasma suggests the assay detects infection ~ 3-5 days After instrumented Ag/Ab combo assays and possibly longer delayswith whole blood

Masciotra et al JCV 2013

In a laboratory setting, test has an overall sensitivity of 92% to detect any stage of HIV-1 infection using sera specimens. It performs relatively well in detecting early HIV and may be beneficial as an initial screening in patients with a recent exposure to HIV.Additional testing in a laboratory setting remains mandatory as a proportion of acute HIV-1 infections are missed with this test.

Van Tienen et al. STI. Published Online First: doi:10.1136/sextrans-2016-052818

Multiplex Real-Time PCR- Viral LoadPlasma 1mlQualitative Dx test from Whole blood~ 2hour run-timeAC power with potential for battery

Cepheid GeneXpert® System

Coming soon

• Multiplex Real-Time PCR- Viral Load• 30 min (500-1000cp/ml), 60 min (50 cp/ml)• Qualitative Dx• Whole Blood or plasma• AC power and battery• Integrated disposable cartridge contains all reagents

for prep, amp & detection

Liat™ Analyzer Roche

• Sample: 25 μL fingerstick whole blood• Sealed system• PCR• Results in 50 minutes• Data Matrix: Expiry QC, assay type, lot

Information• Kit shipped and stored at room temperature

Alere™ q HIV-1/2 Detect

• Built in battery • Simple procedure with built in

controls• Touch screen• Data storage of 1000 tests• Easily transportable, 17.2 lbs.

Alere™ q Analyzer

Alere™ Q System

New Data For Time to Test Reactivity

• Desire to have time since infection/RNA reactive• Used same serconversion panel data and

performed new estimates for time since RNA reactivity

• Inter-test reactivity interval (ITRI) • Eclipse period simulated from published data• Why?

• Valuable to testing providers for interpreting negative HIV test results

• Counseling individuals on when to retest after an exposure.

Delaney et al CID, 2016 http://cid.oxfordjournals.org/content/early/2016/11/03/cid.ciw666.full.pdf?keytype=ref&ijkey=P9Yzswu8ePE5WwP

Considerations for HIV POC Testing

• Locations/populations that lab testing is difficult or not feasibleBetter to use POC than no test

• POC assays continue to improve and have good sensitivity and specificity for established infections but…Be aware of assay limitations Provide informed counseling messagesOral Fluid assays will miss acute infections and

some early infections

1 Stekler et al, JCV 2013, 2 Luo et al JCV 2013

• Of the 40 patients with AHI, 23 (57.5%) had a reactive STAT-VIEW rapid test. • Examining sensitivity of STAT-VIEW over course of AHI duration, probability of HIV detection was

75.5% at 5 weeks. • INSTI provided similar results with respect to proportion of reactive tests (62.5%), with probability

of HIV detection 85.0% at 5 weeks of infection. • Do not rely on a negative result to accurately exclude HIV infection within at least 5 weeks of

potential HIV exposure. Some utility in detecting HIV is observed 5–12 weeks after transmission.

Boukli et al. STI 2017 doi:10.1136/sextrans-2017-053131

Of 1914 identified papers, 18 were included for the meta-analysis of diagnostic accuracy for HIV and syphilis. All diagnostic accuracy evaluation studies showed a very high sensitivity and specificity for HIV and a lower, yet adequate, sensitivity and specificity for syphilis, with some variation among types of test. Dual screening for HIV and syphilis was more cost effective than single rapid tests for HIV and syphilis and prevented more adverse pregnancy outcomes. Qualitative data suggested dual RDTs were highly acceptable to clients, who cited time to result, cost & requirement of a single finger prick as important characteristics of dual RDTs.

Meta-analysis of the diagnostic accuracy of dual HIV/syphilis RDTs, stratified according to manufacturer.

Harriet D Gliddon et al. Sex Transm Infect doi:10.1136/sextrans-2016-053069©2017 by BMJ Publishing Group Ltd

ChemBio

SD Bioline

MedMira

SD Bioline by syphilis

MedMira by syphilis

ChemBio by syphilis

Among 827 sexually active participants, 89% had been tested for HIV. • Most preferred by participants was home

rapid testing (46%), followed by standard-of-care (23%) and rapid testing in healthcare (20%) or community (7%)

• 73% of participants preferred rapid over non-rapid testing, and 56% preferred testing in non-healthcare settings rather than in healthcare settings.

Emergency Departments: Critical Venue HIV TestsFeasibility, Acceptability, and Accuracy

96.4%

3.3% 0.2%

Correct Result?

DefinitelyCorrect

91.7%

8.0% 0.2%

Trust the Result?

VeryMuch

99%

0.7%0.2%

Ease of Performance

Easy

Somewhat EasyNot Easy

85%

11.8%3.1%

Would Test Themselves if Available OTC

Definitely

Probably

Would NotTest

473/955 (49.5%) consented; Median age was 41 years, 59.6 % were female, 74.8% African American

Objectives

1. To discuss current molecular tests and update new POC tests in the pipeline

2. To demonstrate different venues for STI testing outside the clinic, OTC or home STI testing

3. To mention impact of POC testing-advantages and barriers

Female Preference for Type Specimen Collection

Gaydos et al. STD

Self-collected vaginal swabs are acceptable and preferred over urine and cx to women

Focus Group and Clinic Questionnaire about Near Patient Tests (N =371)

Specimen Type Preference

Percent

Cervical 15.4%Vaginal 50.9%Urine 33.7%

Willingness to Wait

Percent

20 min 59.0%40 min 20.8%60 min 10.8%90 min 9.4%Willingness to Pay Percent

$10 46.6%$20 31.0%$30 10.8%$40 2.7%$50 8.9%

80.9%

3.0%16.1%

easy hard OK

Self –collected vaginal swabs

Use of POC Outside the ClinicEmergency Department• 80% of women would “definitely” test themselves at

home if a TV test were available OTC

Pharmacy• Pharmacists are ranked among the most trusted

health care professionals; are accessible 24/7

Internet Iwantthekit Internet Smart Phone

Emergency Department Kiosk-facilitated POC OSOM Trichomonas Self-testing

n= 150 %OSOM Prevalence 16.8%Wet Mount Prevalence

9.8%

100% reading accuracy for negative results96% reading accuracy for positive results

Emergency contraception patients were invited to order a home collection kit for STI testing

Questionnaires for acceptability

Sexual Health 12:472-479, 2015

Pharmacy Testing Acceptability of pharmacy and home based testing

Pharmacy participantsN= 38

IWTK participants kit return (N =81

No IWTK kit return (N=209)

Pharmacies should offer STI tests

Yes 97% 92.6% 90.9%

Likelihood to use Home kit from pharmacy if free or insurance

VerylikelyLikely

81.6%

10.5%

80.2%

18.5%

77.0%

19.1%

• Order a kit online & select Rx clinic

• Kit mailed to home • Collect sample at home• Mail kit to lab• Text or Email sent for when results are ready • Password protected account; obtains results

on line; attends clinic of choice treatment

Internet Outside the Clinic: IWTK

www.iwantthekit.org

Since 2004: Screened 7212 Women, 1313 F rectal 3939 Males; 868 M rectal

Women can perform a self TV test at home

Trichomonas Home Test AnalysisQuestion, N = 92 Easy Somewhat Easy Not Easy

How easy was it for you to collect the vaginal specimen correctly?

88 (95.6%) 3 (3.3% 1 (1.1%)

How easy was it for you to read the test strip and interpret (tell) the result?

84 (91.3%) 6 (6.5%) 2 (2.2%)

Overall, how easy was it for you to perform the test?

85 (92.4%) 5 (5.4%) 1 (1.1%)

Definitely Correct

Probably correct Not Correct

Do you believe that the rapid trichomonas test result was correct for the sample that you collected?

52 (56.5%) 39 (42.4%) 1 (1.1%)

Objectives

1. To discuss current molecular tests and update new POC tests in the pipeline

2. To demonstrate different venues for STI testing outside the clinic, OTC or home STI testing

3. To mention impact of POC testing-advantages and barriers

• Immediate treatment of positivepatients

• Expedite appropriate therapy• Reduce empirical treatment• Lower risk of antibiotic resistance• Improve compliance / minimize

loss to follow-up• Decrease forward transmission• Lower risk of sequelae• Improve the patient experience

Key Applications POC TestsSexually Transmitted Infections

Barriers to Implementation • Financial viability• Money for instruments and consumables • Obtaining CLIA certificate• Validating the new test(s)• Policies and procedures (training manuals)• Operator training (recertification, proficiency)• Getting results into the EMR (interface- $7K?)• Space• Work Flow Disruption• Billing and Reimbursement

Conclusions

• POCTs in primary/STI care and perhaps OTC have great potential

• But there are barriers to successful implementation that need to be overcome which can be costly, time consuming, and require learning new skill sets

• Better POC tests are coming; the future is promising

Acknowledgements•Anne Rompalo•Mary Jett-Goheen•Mathilda Barnes •Justin Hardick•Jeff Holden •Laura Dize•Perry Barnes•Barbara Silver

cgaydos@jhmi.edu410-614-0932

We are trying to POINT the WAY for POC Tests

Novel Microdevices

Self-contained Microfluidic Cartridge

Insert chip into device

Transfer sample into chip, start

On-chip DNA purification

On-chip DNA amplification

Detection and result display

Time to Result <20 minutes

Hands-on time <2 minutes

<1 <1 2 15 <1

Hand-held Assay Automation Instrument

• Sensitivity equivalent to lab qPCR test• Assay was able to detect <5 EB of

Chlamydia• Highly specific to only Chlamydia strains• Preclinical evaluation using clinical samples

underway.

Evolution of Syphilis Test

Traditional syphilis tests - Manual

Automated Test platforms

Rapid syphilis test • Treponemal

• Treponemal

• Nontreponemal• Treponemal

Self-Testing Instruction Guide

• All 5 commercial NAAT assays have approval for clinician-collected and self-collected vaginal swabs for CT/NG

• Sensitivities and specificities 94.5%-100%

• Self-collected vaginal swabs are not FDA cleared for home collection for mailing but used in research studies

Self-Collected Vaginal Swabs

(Aptima, M-2000, ProbeTech Qx Amplified DNA, Cobas 4800, Cepheid)

Schachter STD 2005; Gaydos JCM 2010; Taylor JCM 2011; Van Der Pol STD 2012; Van Der Pol STD 2013; Gaydos JCM 2013

2805 men with syphilis contributing 11, 714 person-years of follow-up, 423 (15.1%) acquired HIV; annual incidence was 3.61% (95% CI, 3.27%, 3.97%).

HIV incidence was high among: MSM (5.56%, 95% CI, 5.02%–6.13%); males with secondary compared with primary syphilis (4.10% vs 2.64%, P < .0001); and males diagnosed with another bacterial STD after syphilis (7.89%, 95% CI, 6.62%–9.24%).

Hazard Ratio for MSM in multivariate analysis was 8.88

CID July 15, 2015

Clinician Collected Vaginal or Cervical vs. Self-Collected Vaginal Swabs

Aptima M-2000 ProbeTechQx Amplified DNA

Cobas4800

GenXPert

CT PVS/CVS PVS/CVSSymptomat.

PVS/CxSwab

PVS vsCxSwab

PVS/CxSwab

Sensitivity 96.7/96.6% 97.7/92.5% 96.5/91.3% 94.5% 98.7/97.4%

Specificity 97.6/97.1% 99.9/98.8% 99.2/98.3% 99.5% 99.4/99.6%

NGSensitivity 98.7/96.2% 96.7/96.8% 100/98.5% 95.3% 100/100%

Specificity 99.6/99.4% 99.7/99.9% 99.1/99.7% 99.9% 99.9/100%

Schachter STD 2005; Gaydos JCM 2010; Taylor JCM 2011; Van Der Pol STD 2012; Van Der Pol STD 2013; Gaydos JCM 2013

0

20

40

60

80

100

Collect OwnSpecimen

Vag swabSafe

Female Questionnaire Results:Self Collection Vaginal Swabs

90.9% 94.5%

0.00

20.00

40.00

60.00

80.00

100.00

Collection Easyto Very Easy

InstructionsEasy to Very

Easy

Use Internet-based SAS

again

Gaydos et al. STD

Male Questionnaire ResultsHome collection (N = 501)

0.0%

20.0%

40.0%

60.0%

80.0%

100.0%

Collection Easy toVery Easy

Instructions Easy toVery Easy

Use Internet-basedSAS again

Penile Swab89.8% 94.0% 91.4%

Urine95.3%

Chai et al . STD

Why do POCTs OCT?

• Improve patient satisfaction (privacy)• Treat patients before infecting others• Increase risk reduction• Decrease interval of disease spread• Improve treatment efficiency for the

patient• Improve medical outcomes for sequelae

STI: 2013; 89:88-89

Netherlands compared three CE-marked POC tests (one enzymatic and other two antigen tests) for diagnostic performance in a high CT-prevalence population (11%), compared with NAATs over 8-months The sensitivity of the tests was disappointing, and ranged from 12% to 27% in 772 women tested

van Dommelen et al. Alarmingly poor performance in Chlamydia trachomatis point-of-care testing. Sex Transm Infect 2010;86:355–9.

• Favorable POCTs (Rapid, Easy to read, Simple to use)• Home testing acceptable – better privacy• Clinic-based- definitive results & immediate treatment• Barriers- cost and ability to read and perform tests• Hispanic patients questioned home test reliability,

wanted bi-lingual instructions

POC tests for STIs: What do “end users” want? (N=58, 5 focus groups)

)

Rompalo et al. Sexual Health 2013;10:541-545

Self-Collection of Urogenital Samples is Acceptable & AccurateSelf-collected vaginal swabs are acceptable and preferred (30.5%) over urine (26.2%) and cx to womenAll 5 commercial companies have clearance to test self-collected vaginal swabs (as well as urine samples)FDA trial surveys by 2,009 females

Question %Written instructions were understood 99.25%Diagrams helpful 96.27%Successfully completed 98.26$No preference 29.87%

Gaydos et al. JCM 43:3236–3243, 2010

Can a pharmacist perform a POC test for STIs in a pharmacy?

Pharmacists are ranked among the most trusted health care professionalsThese healthcare professionals are easily accessible 24/7 Nearly 60,000 community pharmacies in the US Approximately 18% of these pharmacies have CLIA-waived status and can perform any of the approximately 120 CLIA-waived tests Clinical Chemistry 62:679-683, 2016

36.7 million [34.0 million – 39.8 million] 31.8 million [30.1 million – 33.7 million]16.0 million [15.2 million – 16.9 million]3.2 million [2.9 million – 3.5 million]

2.1 million [1.9 million – 2.4 million]1.9 million [1.7 million – 2.1 million] 240 000 [210 000 – 280 000]

1.1 million [940 000 – 1.3 million]1.0 million [1.2 million – 1.5 million] 190 000 [170 000 – 220 000]

Number of people living with HIV in 2015

People newly infected with HIV in 2015

AIDS deaths in 2015

TotalAdults

WomenChildren (<15 years)

TotalAdults

Children (<15 years)

TotalAdults

Children (<15 years)

Global summary: AIDS epidemic

Source: UNAIDS/WHO estimates.

Solana Results Vaginal Swabs for TV vaginal swabs and urines

(N=1044)Vaginal Swabs Sensitivity SpecificityAsymptomatic 100% 98.9%Symptomatic 98.6% 98.5%

Compared to FDA-composite reference method wet preparation & culture

Urine Sensitivity SpecificityAsymptomatic 98.0% 98.4%Symptomatic 92.9% 97.9%

TV prevalence swabs and/or urines 11.5%

Second generation treponemal tests utilize recombinant protein antigens

• Recombinant T. pallidum antigens developed in the 1980sHigh test specificity Solid-phase immunoassays High test sensitivity

• Several EIAs, CIAs, and MFIs have become commercially available

• Reverse Algorithm testinghas been introduced

Syphilis serologicscreening algorithms

EIA/CIA/POC

EIA/CIA+

Quantitative RPR

RPR+Syphilis(past or present)

RPR-

TP-PA

TP-PA+Syphilis (past or present)

TP-PA-Syphilis unlikely

EIA/CIA-Quantitative

RPR

RPR+

TP-PA or other trep. test

TP-PA+Syphilis (past or present)

TP-PA-Syphilis unlikely

RPR-

Traditional Reverse sequence

If at risk for syphilis, repeat RPR in several weeks

Evaluate clinically

CDC recommende algorithm for reverse sequence syphilis screening followed by nontreponemal tes confirmation

Positive predictive values of the immunochromatographic strip test

at various syphilis prevalences

•Rapid qualitative screening for human TP antibodies

• Results in 10 minutes; 2 steps; room temperature

• 98% agreement to other treponemal tests

• Serum, plasma, whole blood or finger-stick

POC Syphilis Health CheckTM

Syphilis Antibody Rapid Immunochromatographic Test

Negative: 1 colored band in control areaPositive: Colored bands in testarea and control areaInconclusive: No distinct color bands in either area

FDA ClearedCLIA Waived

http://www.alere.co.uk/sexual-health/alere-determinetm-syphilis-tp-13/product-listing.htm.

DetectsAntibodies to Treponema pallidum Recombinant TP (15kDa,

17kDa) antigens used as captures and detectorsRapid

Provides accurate and reliable results in 15 minutesConvenient

No refrigeration required (storage 2-30°C)No power or water source is needed to run test

FlexibleUses serum, plasma or whole blood by venipuncture or

finger prick

Standard Diagnostics-Alere Determine™ Syphilis TP POC

DPP® HIV-Syphilis Assay

• Chembio Diagnostic Systems has developed a dual HIV 1/2 and Syphilis Treponemal antibodies POC test (Dual Path Platform (DPP®) technology)

• Immunochromatographic rapid screening POC test• Fingerstick whole blood, venous whole blood, serum,

and plasma

http://www.youtube.com/watch?x-yt-cl=68561176&feature=player_embedded&v=DE4Wxy4byQE&x-yt-ts=1401912551

Video whole Blood Sample:

http://chembio.com/products/human-diagnostics/dpp-hivsyphilis-assay.

SD BIOLINE HIV Syphilis Duo

• SD BIOLINE HIV/Syphilis Duo test is a solid phase immunochromatographic assay

• Qualitative detection of antibodies to all isotypes(IgG, IgM, and IgA) specific to HIV-1/2 and/or Treponema palladium(TP)

• Serum, plasma, or whole blood

• 1-30℃ for 24 months

http://www.standardia.com

http://www.medmira.com/images/uploads/MPSIABPM0001EN_Rev_0_1_Multiplo_TPHIV_Product_Sheet_(English).pdf

18 month shelf-life at 2-30°CNo refrigeration or cold chain requiredNo timers requiredResults are easy to interpretNo specialized equipment required

3 minute test procedure

Whole blood, serum or plasma specimens

No specialized training required

Built-in procedural and reagent control line

Trichomonas Home Test Analysis

Question, N = 92 Trust very much

Trust Somewhat Do Not Trust

How much do you trust the result of the rapid trichomonas test that you collected and tested?

60 (65.2%) 31 (33.7%) 1 (1.1%)

DefinitelyTest

Probably Test Not Test

Would you test yourself at home for trichomonas if the rapid trichomonas test were available over-the-counter?

77 (83.7%) 14 (15.2%) 1 (1.1%)

$10 $20 $30What is the maximum price you would pay to purchase a rapid trichomonas test over-the-counter, if available?

42 (45.6%) 37 (40.2%) 3 (14.1%)

Total: 36.7 million [34.0 million – 39.8 million]

Western & Central Europe

900 000[830 000 – 1.0 million]

Middle East & North Africa300 000

[250 000 – 360 000]

Sub-Saharan Africa23.5 million

[22.1 million – 24.8 million]

Eastern Europe & Central Asia1.4 million

[1.1 million – 1.8 million]

South & South-East Asia4.0 million

[3.1 million – 5.2 million]

Oceania53 000

[47 000 – 60 000]

North America1.4 million

[1.1 million – 2.0 million]

Latin America1.4 million

[1.1 million – 1.7 million]

East Asia830 000

[590 000 – 1.2 million]Caribbean230 000

[200 000 – 250 000]

Adults and Children Living with HIV

People newly infected with HIV in 2015: 2.1 M; AIDS deaths in 2015: 1.1 M

Chlamydia trachomatis and Neisseria gonorrhoeae

Old: Culture and staining. New: PCR and other nucleic acid amplification tests (NAATs)

What about the Small Laboratory?

BD MAXBy Becton Dickinson

• BD MAX can be used for chlamydia, gonorrhea, and trichomonas and for diagnosis of vaginitis

1. Collect 2. Transfer 3. Insert 4. Detect

• Gene Xpert by Cepheid can be used for chlamydia gonorrhea and trichomonas (90 min.)