Point of Care Tests: Clinical Use in 2017
Helsinki 31st IUSTI-Europe Congress on STIs Charlotte A. Gaydos, MS, MPH, DrPH Professor, Division of Infectious Diseases Johns Hopkins University, Baltimore, Maryland 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 WHO Estimates of Global Prevalence of STIs in 2012
143 Million 160 131 Million 140 36.7 million 120 Adults and 100 78 Million Children Living
80 with HIV
60
40
20 6 Million 0 Chlamydia Gonorrhea Trichomonas143 Syphilis
Newman et al. PLOS ONE | OI:10.1371/journal.pone.0143304 December 8, 2015 7 / 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? WHO ASSURED Criteria for POC Tests 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 Robust rapid: to enable treatment at first visit robust: no requirement refrigerated storage Equipment-free easily collected non-invasive specimens, e.g. urine, saliva. vaginal Delivered delivered to end-users http://www.who.int/std_diagnostics/about_SDI/priorities.htm Overview: Point-of-Care Tests for STIs Chlamydia trachomatis (CT) Neisseria gonorrhoeae (NG) Trichomonas vaginalis (TV) Syphilis Herpes 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. Overview New POC tests for STIs •Chlamydia
•Gonorrhea
•Trichomonas
•Syphilis •HSV HIV Gaydos and Hardick, POC diagnostics for sex transmit infect: Perspectives and advances. Expert Review of Anti-infective Therapy. 12:657-672, 2014. Sensitivity and Specificity of POC/near patient tests for CT & NG Organism Test Sample Type Sensitivity* Specificity*
Chlamydia trachomatis Biostar OIA Chlamydia test Cervical 59.4-73.8% 98.4-100% Male Urine Clearview Chlamydia Cervical 49.7% 97.9% Vaginal 32.8% 99.2% Quick Vue Cervical 25-65% 100% Chlamydia Rapid Test Vaginal 83.5% 98.9% Male Urine X-pert CT/NG Cervical 97.4% 99.6% Vaginal 98.7% 99.4% Female Urine 97.6% 99.8% Male Urine 97.8% 99.9% Neisseria gonorrhoeae Biostar OIA GC test Cervical 60% 89.9% PATH GC-Check Cervical 70% 97.2% Vaginal 54.1% 98.25 X-pert CT/NG Cervical 100% 100% Vaginal 100% 99.9% Female Urine 95.6% 99.9% Male Urine 98.9% 99.9% 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)
Sensitivity: 95-100% Specificity 99-100%
FDA Cleared: CT/NG,TV; urine, cervical, vaginal swabs
Gaydos et al. J Clin Microbiol. 51:1666-1672, 2013 Female Results CT/NG Xpert CT/NG vs. Patient Infected Status Specimen Sensitivity Specificity CT 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™ System
Performance Characteristics of Atlas Assay Compared to Laboratory-Based NAAT Testing by Symptom Status
Number True False Prevalence Sensitivity Specificity Positive Positive (%) (%) (%) Initial 284 26 3 10.2 83.9 98.8 results After Discordant 284 28 3 9.9 92.9 98.8 Testing
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
16000 14000 12000 10000 8000 6000 4000 2000 AUC AUC Fluorescence (AU) 0 0 10 20 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
Stained Wet Preparation showing Trichomonas Electron microscope view of motile trichomonads trichomonas on epithelial cell
Non-NAAT • NAAT • Wet Preparation AmpliVue POC • Culture Solana POC • Affirm VPIII AptimaT. vaginalis (ATV) • OSOM POC Becton Dickinson (TVQ) OSOM Rapid TV Antigen Test •Immunochromato-graphic •TV membrane proteins •Mouse antibodies •Latex beads/ capillary action
Sensitivity 83-90%, Specificity 98-100%
Huppert et al , JCM 2005; STI 2007: AmpliVue® Trichomonas HDA Assay
1) simple sample preparation with 1-step dilution/heating 2) 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 cleared Sensitivity 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 Compared to NAAT reference Sample Sensitivity Specificity Swabs 89.7% 99.0% Urine 100% 98.9%
Compared to wet prep/culture Vaginal Sensitivity Specificity Asym. 100% 98.9% HDA amplification Sympt. 98.6% 98.5% Recently FDA Cleared TV prevalence swabs and/or urines 11.5% Moderately Complex Gaydos et al. CDC STD meet. Atlanta Sept 2016 HSV POC Diagnostics The IsoAmp® HSV Assay (Biohelix Corp) 25 ul Master mix
25 ul
25 ul 1 ml buffer VTM
640 60 min • 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
Lemieux et al. Expert Reviews Ltd. 437-443, 2012; Syphilis: Serologic DX requires detection 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: Disadvantages:
• Automated and • Less clinical are cost saving for experience with large volume interpretation laboratories • May be less • May detect old sensitive than FTA- untreated syphilis ab in early primary syphilis Some Rapid POC Syphilis Tests
• 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 Laboratory evaluations of syphilis rapid test performance 2010-2014
PPV
• Meta-analysis of 33 studies from POCs Sensitivity: 75.12% to 83.78% for blood 75.98% to 92.03% for serum Specificity: 98.39% to 99.44% for blood 92.68% to 98.51% in serum
Bristow et al Sex Health 12: 119-125, 2015 HIV CLIA-Waived Point-of-Care Rapid HIV Tests
OraQuick Clearview Complete Advance
Uni-Gold Recombigen Clearview Stat Pak INSTI New HIV Diagnostic Algorithm 4th generation HIV-1/2 immunoassay Screen (-) (+) Negative for HIV-1 and HIV-2 antibodies and p24 Ag Confirm HIV-1/HIV-2 antibody differentiation immunoassay
HIV-1 + HIV-2 + HIV-1 +/HIV-2 + HIV-1&2 (-) or indeterminate HIV-1 antibodies HIV-2 antibodies HIV antibodies detected detected detected RNA Initiate care Initiate care (and viral load) RNA (+) RNA (-) Acute HIV-1 infection Negative for HIV-1 Branson BM, Mermin J. J Clin Vir 2011;52:S3-4; Initiate care MMWR 62, June 21, 2013. CLSI 2011 HIV Infection and Laboratory Markers
HIV RNA (plasma) Eclipse Period HIV Antibody Infection undetectable HIV p24 Ag ! IgM IgG
0 10 20 30 40 50 60 70 80 90 100
Acute HIV Infection
Modified after Busch et al. Am J Med. 1997 Bio-Rad Geenius™
Supplemental assay - Confirmation and differentiation of HIV-1 and HIV-2 antibodies
• 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 Alere Determine™HIV-1/2 Ag/Ab Combo
Method: Lateral flow Time to Results: 20 minutes Storage Conditions: 2 - 30°C Shelf Life: 9 months Sample Type: Serum/plasma/whole blood Distinguishes 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 delays with 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 Cepheid GeneXpert® System Multiplex Real-Time PCR- Viral Load Plasma 1ml Qualitative Dx test from Whole blood ~ 2hour run-time Coming soon AC power with potential for battery Liat™ Analyzer Roche • 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 Alere™ Q System
Alere™ q HIV-1/2 Detect • 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 Analyzer
• Built in battery • Simple procedure with built in controls • Touch screen • Data storage of 1000 tests • Easily transportable, 17.2 lbs. 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?keytyp e=ref&ijkey=P9Yzswu8ePE5WwP Considerations for HIV POC Testing
• Locations/populations that lab testing is difficult or not feasible Better 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 messages Oral 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.
SD Bioline
MedMira
ChemBio
SD Bioline by syphilis
MedMira by syphilis ChemBio by syphilis
Harriet D Gliddon et al. Sex Transm Infect ©2017 by BMJ Publishing Group Ltd doi:10.1136/sextrans-2016-053069 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 Tests Feasibility, Acceptability, and Accuracy Correct Result? Trust the Result? 3.3% 0.2% 8.0% 0.2%
Definitely Very Correct Much
96.4% 91.7%
Would Test Themselves if Available Ease of Performance OTC 0.7%0.2% 3.1% 11.8% Easy Definitely
Somewha Probably t Easy Not Easy Would Not Test 85% 99%
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
Self-collected vaginal swabs are acceptable and preferred over urine and cx to women
Gaydos et al. STD Focus Group and Clinic Questionnaire about Near Patient Tests (N =371) Specimen Type Percent Willingness Percent Preference to Wait Cervical 15.4% 20 min 59.0% Vaginal 50.9% 40 min 20.8% Urine 33.7% 60 min 10.8% 90 min 9.4% Willingness to Pay Percent Self –collected vaginal swabs $10 46.6% 3.0% 16.1% $20 31.0% $30 10.8% 80.9%
$40 2.7% easy hard OK $50 8.9% Use of POC Outside the Clinic Emergency 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 9.8% Prevalence
100% reading accuracy for negative results 96% reading accuracy for positive results Pharmacy Testing
Acceptability Pharmacy IWTK No IWTK kit of pharmacy participants participants return and home N= 38 kit return (N=209) based testing (N =81 Pharmacies Yes 97% 92.6% 90.9% should offer STI tests Likelihood to Very 81.6% 80.2% 77.0% use Home kit likely from pharmacy Likely 10.5% 18.5% 19.1% if free or insurance
Emergency contraception patients were invited to order a home collection kit for STI testing Questionnaires for acceptability
Sexual Health 12:472-479, 2015 Internet Outside the Clinic: IWTK • Order a kit on line & select Rx clinic • Kit mailed to home • Collect sample at home • Mail kit to lab www.iwantthekit.org • Text or Email sent for when results are ready • Password protected account; obtains results on line; attends clinic of choice treatment
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 Analysis
Easy Somewhat Easy Not Easy Question, N = 92
How easy was it for you to collect 88 (95.6%) 3 (3.3% 1 (1.1%) the vaginal specimen correctly? How easy was it for you to read 84 (91.3%) 6 (6.5%) 2 (2.2%) the test strip and interpret (tell) the result? Overall, how easy was it for you 85 (92.4%) 5 (5.4%) 1 (1.1%) to perform the test? Definitely Probably correct Not Correct Correct
Do you believe that the rapid 52 (56.5%) 39 (42.4%) 1 (1.1%) trichomonas test result was correct for the sample that you collected? 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 Key Applications POC Tests Sexually Transmitted Infections • Immediate treatment of positive patients • 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 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 We are trying to POINT the WAY for POC Tests Acknowledgements •Anne Rompalo •Mary Jett-Goheen •Mathilda Barnes •Justin Hardick •Jeff Holden •Laura Dize •Perry Barnes •Barbara Silver
[email protected] 410-614-0932
Novel Microdevices
Hands-on time <2 minutes Hand-held Assay Automation Instrument
Insert chip Transfer sample On-chip DNA On-chip DNA Detection and into device into chip, start purification amplification result display
<1 <1 2 15 <1 Time to Result <20 minutes
• Sensitivity equivalent to lab qPCR test Self-contained Microfluidic Cartridge • 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 • Nontreponemal • Treponemal
Automated Test • Treponemal platforms
Rapid syphilis test • Treponemal Self-Testing Instruction Guide Self-Collected Vaginal Swabs • All 5 commercial NAAT assays have approval for clinician-collected and self-collected vaginal swabs for CT/NG (Aptima, M-2000, ProbeTech Qx Amplified DNA, Cobas 4800, Cepheid)
• Sensitivities and specificities 94.5%-100% • Self-collected vaginal swabs are not FDA cleared for home collection for mailing but used in research studies
Schachter STD 2005; Gaydos JCM 2010; Taylor JCM 2011; Van Der Pol STD 2012; Van Der Pol STD 2013; Gaydos JCM 2013 CID July 15, 2015
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 Clinician Collected Vaginal or Cervical vs. Self-Collected Vaginal Swabs
Aptima M-2000 ProbeTech Cobas GenXPert Qx Amplified DNA 4800 CT PVS/CVS PVS/CVS PVS/Cx PVS vs PVS/Cx Symptomat. Swab CxSwab Swab 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%
NG Sensitivity 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 Female Questionnaire Results: Self Collection Vaginal Swabs
90.9% 94.5% 100
100.00 80 80.00 60 60.00
40 40.00
20 20.00 0.00 0 Collection Easy Instructions Use Internet- to Very Easy Easy to Very based SAS Collect Own Vag swab Easy again Specimen Safe
Gaydos et al. STD Male Questionnaire Results Home collection (N = 501) Penile Swab 94.0% 91.4% 100.0% 89.8% Urine 80.0% 95.3%
60.0%
40.0%
20.0%
0.0% Collection Easy to Instructions Easy to Use Internet-based Very Easy Very Easy SAS again 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. POC tests for STIs: What do “end users” want? (N=58, 5 focus groups) • 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
Rompalo et al. Sexual Health 2013;10:541-545 Self-Collection of Urogenital Samples is Acceptable & Accurate Self-collected vaginal swabs are acceptable and preferred (30.5%) over urine (26.2%) and cx to women All 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 professionals These 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
Global summary: AIDS epidemic
Number of people Total 36.7 million [34.0 million – 39.8 million] living with HIV in 2015 Adults 31.8 million [30.1 million – 33.7 million] Women 16.0 million [15.2 million – 16.9 million] Children (<15 years) 3.2 million [2.9 million – 3.5 million]
People newly Total 2.1 million [1.9 million – 2.4 million] infected Adults 1.9 million [1.7 million – 2.1 million] with HIV in 2015 Children (<15 years) 240 000 [210 000 – 280 000]
AIDS deaths in 2015 Total 1.1 million [940 000 – 1.3 million] Adults 1.0 million [1.2 million – 1.5 million] Children (<15 years) 190 000 [170 000 – 220 000]
Source: UNAIDS/WHO estimates. Solana Results Vaginal Swabs for TV vaginal swabs and urines (N=1044) Vaginal Swabs Sensitivity Specificity Asymptomatic 100% 98.9% Symptomatic 98.6% 98.5% Urine Sensitivity Specificity Asymptomatic 98.0% 98.4% Symptomatic 92.9% 97.9%
TV prevalence swabs and/or urines 11.5% Compared to FDA-composite reference method wet preparation & culture Second generation treponemal tests utilize recombinant protein antigens
• Recombinant T. pallidum antigens developed in the 1980s High test specificity Solid-phase immunoassays High test sensitivity
• Several EIAs, CIAs, and MFIs have become commercially available
• Reverse Algorithm testing has been introduced Syphilis serologic screening algorithms
Traditional Reverse sequence EIA/CIA/POC Quantitative RPR EIA/CIA- CDC recommende EIA/CIA+ algorithm for reverse sequence RPR+ syphilis screening RPR- Quantitative followed by RPR nontreponemal tes TP-PA confirmation or other RPR+ RPR- Evaluate trep. test clinically Syphilis (past or TP-PA present)
TP-PA+ TP-PA+ If at risk for syphilis, repeat TP-PA- Syphilis Syphilis RPR in several weeksTP-PA- Syphilis Syphilis (past or unlikely (past or present) unlikely present) Positive predictive values of the immunochromatographic strip test at various syphilis prevalences POC Syphilis Health CheckTM Syphilis Antibody Rapid Immunochromatographic Test
•Rapid qualitative screening for human TP antibodies • Results in 10 minutes; 2 steps; room temperature FDA • 98% agreement to other treponemal tests Cleared CLIA • Serum, plasma, whole blood or finger-stick Waived Negative: 1 colored band in control area Positive: Colored bands in test area and control area Inconclusive: No distinct color bands in either area Standard Diagnostics-Alere Determine™ Syphilis TP POC http://www.alere.co.uk/sexual- health/alere-determinetm-syphilis-tp- 13/product-listing.htm.
Detects Antibodies to Treponema pallidum Recombinant TP (15kDa, 17kDa) antigens used as captures and detectors Rapid Provides accurate and reliable results in 15 minutes Convenient No refrigeration required (storage 2-30°C) No power or water source is needed to run test Flexible Uses serum, plasma or whole blood by venipuncture or finger prick DPP® HIV- Syphilis Assay http://chembio.com/products/human- diagnostics/dpp-hivsyphilis-assay.
Video whole Blood Sample: http://www.youtube.com/watch?x-yt- cl=68561176&feature=player_embedded&v=DE4Wxy4by QE&x-yt-ts=1401912551
• 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 SD BIOLINE HIV Syphilis Duo http://www.standardia.com
• 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.medmira.com/images/uploads/MPSIABPM0001EN_ Rev_0_1_Multiplo_TPHIV_Product_Sheet_(English).pdf 3 minute test procedure Whole blood, serum or plasma specimens No specialized training required Built-in procedural and reagent control line 18 month shelf-life at 2-30°C No refrigeration or cold chain required No timers required Results are easy to interpret No specialized equipment required Trichomonas Home Test Analysis
Trust very Trust Somewhat Do Not Question, N = 92 much Trust
How much do you trust the result 60 (65.2%) 31 (33.7%) 1 (1.1%) of the rapid trichomonas test that you collected and tested? Definitely Probably Test Not Test Test Would you test yourself at home 77 (83.7%) 14 (15.2%) 1 (1.1%) for trichomonas if the rapid trichomonas test were available over-the-counter? $10 $20 $30 What is the maximum price you 42 (45.6%) 37 (40.2%) 3 (14.1%) would pay to purchase a rapid trichomonas test over-the- counter, if available? Adults and Children Living with HIV
Western & Eastern Europe Central Europe & Central Asia 900 000 1.4 million North America [830 000 – 1.0 million] [1.1 million – 1.8 million] 1.4 million East Asia [1.1 million – 2.0 million] 830 000 Middle East & North Africa [590 000 – 1.2 million] Caribbean 300 000 [250 000 – 360 000] 230 000 South & South-East Asia [200 000 – 250 000] 4.0 million [3.1 million – 5.2 million] Sub-Saharan Africa Latin America 23.5 million 1.4 million [22.1 million – 24.8 million] Oceania [1.1 million – 1.7 million] 53 000 [47 000 – 60 000]
Total: 36.7 million [34.0 million – 39.8 million]
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 MAX can be used BD MAX for chlamydia, By Becton gonorrhea, and Dickinson trichomonas and for diagnosis of vaginitis
• Gene Xpert by Cepheid can be used for chlamydia gonorrhea and trichomonas (90 min.)
1. Collect 2. Transfer 3. Insert 4. Detect