Point of Care Tests: Clinical Use in 2017

Transcription

1 Point of Care Tests: Clinical Use in 2017 Helsinki 31 st IUSTI-Europe Congress on STIs Charlotte A. Gaydos, MS, MPH, DrPH Professor, Division of Infectious Diseases Johns Hopkins University, Baltimore, Maryland

2 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 testingadvantages and barriers

3 WHO Estimates of Global Prevalence of STIs in Million 78 Million 143 Million 36.7 million Adults and Children Living with HIV Million Chlamydia Gonorrhea Trichomonas143 Syphilis Newman et al. PLOS ONE OI: /journal.pone December 8, /

4 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?

5 WHO ASSURED Criteria for POC Tests Affordable by those at risk of infection Sensitive Specific few false negatives 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

6 Gaydos and Hardick POC diagnostics for sex transmit infect: Perspectives and advances. Expert Review of Anti-infective Therapy. 12: , 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: Huppert et al. Point of Care tests for STIs: What s the Point? Point of Care Journal, 2009

7 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: , 2014.

8 Sensitivity and Specificity of POC/near patient tests for CT & NG Organism Test Sample Type Sensitivity* Specificity* Chlamydia trachomatis Biostar OIA Chlamydia test Cervical % % Male Urine Clearview Chlamydia Cervical Vaginal 49.7% 32.8% 97.9% 99.2% Quick Vue Cervical 25-65% 100% Chlamydia Rapid Test Vaginal 83.5% 98.9% Male Urine X-pert CT/NG Cervical Vaginal Female Urine Male 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 Vaginal 70% 54.1% 97.2% X-pert CT/NG Cervical Vaginal Female Urine Male Urine 100% 100% 95.6% 98.9% 100% 99.9% 99.9% 99.9% Gaydos and Hardick POC diagnostics for sex transmit infect: Perspectives and advances. Expert Reviews / , 2014 Adapted from Huppert et al. (2010). * Sensitivity and specificity compared to NAATs

9 Near Patient Test for Chlamydia and Gonorrhea GeneXpert CT/NG, Cepheid (90 minutes) Sensitivity: % Specificity % FDA Cleared: CT/NG,TV; urine, cervical, vaginal swabs Gaydos et al. J Clin Microbiol. 51: , 2013

10 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: , 2013

11 Male Results Xpert CT/NG vs. Patient Infected Status Specimen Sensitivity Specificity CT Urine 97.5% 99.9% NG Urine 98.9% 99.9%

12 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

13 Atlas Genetics io System Performance Characteristics of Atlas Assay Compared to Laboratory-Based NAAT Testing by Symptom Status Initial results After Discordant Testing Number True Positive False Positive Prevalence (%) Sensitivity (%) Specificity (%) 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.

14 Mobi-NAAT Chlamydia Test / PCR Droplet PCR microfluidic platform / Smartphone Droplet cartridge platform AUC Fluorescence (AU) Sample identification number Shin DJ, et al. Mobile nucleic acid amplification testing (mobinaat) for Chlamydia trachomatis

15 Mobi-NAAT Chlamydia Test / PCR Droplet PCR microfluidic platform / Smartphone Shin DJ, et al. Mobile nucleic acid amplification testing (mobinaat) for Chlamydia trachomatis

16 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

17 Trichomonas vaginalis Diagnostics Wet Preparation showing motile trichomonads Stained Trichomonas Electron microscope view of trichomonas on epithelial cell Non-NAAT Wet Preparation Culture Affirm VPIII OSOM POC NAAT AmpliVue POC Solana POC AptimaT. vaginalis (ATV) Becton Dickinson (TVQ)

18 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 %

19 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 selfcontained, disposable device. FDA cleared Sensitivity 100%; specificity 98.2% vs. culture/wet prep. Vs. NAAT PPA: % Gaydos et al. STD 2016

20 Clinical performance of the Solana POC Trichomonas Assay from cliniciancollected vaginal swabs and female urines HDA amplification Recently FDA Cleared Moderately Complex Sample Gaydos et al. CDC STD meet. Atlanta Sept 2016 Compared to NAAT reference Sensitivity Specificity Swabs 89.7% 99.0% Urine 100% 98.9% Compared to wet prep/culture Vaginal Sensitivity Specificity Asym. 100% 98.9% Sympt. 98.6% 98.5% TV prevalence swabs and/or urines 11.5%

21 HSV POC Diagnostics

22 The IsoAmp HSV Assay (Biohelix Corp) 25 ul 25 ul Master mix 25 ul VTM 1 ml buffer 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 , 2012;

23 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

24 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 FTAab in early primary syphilis

25 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

26 Laboratory evaluations of syphilis rapid test performance 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: , 2015

27 HIV CLIA-Waived Point-of-Care Rapid HIV Tests OraQuick Advance Clearview Complete Uni-Gold Recombigen INSTI Clearview Stat Pak

28 New HIV Diagnostic Algorithm Screen Confirm 4 th 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 Branson BM, Mermin J. J Clin Vir 2011;52:S3-4; MMWR 62, June 21, CLSI 2011 HIV-1 +/HIV-2 + HIV antibodies detected HIV-1&2 (-) or indeterminate RNA (+) Acute HIV-1 infection Initiate care RNA RNA (-) Negative for HIV-1

29 HIV Infection and Laboratory Markers Eclipse Period Infection undetectable! HIV RNA (plasma) HIV p24 Ag IgM IgG HIV Antibody Acute HIV Infection Modified after Busch et al. Am J Med. 1997

30 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

31 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

32 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: /sextrans

33 Cepheid GeneXpert System Multiplex Real-Time PCR- Viral Load Plasma 1ml Qualitative Dx test from Whole blood ~ 2hour run-time AC power with potential for battery Coming soon

34 Liat Analyzer Roche Multiplex Real-Time PCR- Viral Load 30 min ( cp/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

35 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.

36 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, e=ref&ijkey=p9yzswu8epe5wwp

37 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

38 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: /sextrans

39 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.

40 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 2017 by BMJ Publishing Group Ltd Harriet D Gliddon et al. Sex Transm Infect doi: /sextrans

41 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.

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43 Emergency Departments: Critical Venue HIV Tests Feasibility, Acceptability, and Accuracy

44 Correct Result? 3.3% 0.2% Trust the Result? 8.0% 0.2% Definitely Correct Very Much 96.4% Ease of Performance 0.7%0.2% Easy 91.7% Would Test Themselves if Available OTC 11.8% 3.1% Definitely 99% Somewha t Easy Not Easy 85% Probably Would Not Test 473/955 (49.5%) consented; Median age was 41 years, 59.6 % were female, 74.8% African American

45 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 testingadvantages and barriers

46 Female Preference for Type Specimen Collection Self-collected vaginal swabs are acceptable and preferred over urine and cx to women Gaydos et al. STD

47 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 Pay Percent $ % $ % $ % $40 2.7% $50 8.9% Willingness to Wait Percent 20 min 59.0% 40 min 20.8% 60 min 10.8% 90 min 9.4% Self collected vaginal swabs 3.0% 16.1% easy hard OK 80.9%

48 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

49 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

50 Sexual Health 12: , 2015 Pharmacy Testing Acceptability of pharmacy and home based testing Pharmacies should offer STI tests Likelihood to use Home kit from pharmacy if free or insurance Pharmacy participants N= 38 IWTK participants kit return (N =81 No IWTK kit return (N=209) Yes 97% 92.6% 90.9% Very likely Likely 81.6% 10.5% 80.2% 18.5% 77.0% 19.1% Emergency contraception patients were invited to order a home collection kit for STI testing Questionnaires for acceptability

51 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 Text or 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

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53 Women can perform a self TV test at home

54 Trichomonas Home Test Analysis Question, N = 92 Easy Somewhat Easy Not Easy How easy was it for you to collect the vaginal specimen correctly? How easy was it for you to read the test strip and interpret (tell) the result? Overall, how easy was it for you to perform the test? Do you believe that the rapid trichomonas test result was correct for the sample that you collected? 88 (95.6%) 3 (3.3% 1 (1.1%) 84 (91.3%) 6 (6.5%) 2 (2.2%) 85 (92.4%) 5 (5.4%) 1 (1.1%) Definitely Correct Probably correct Not Correct 52 (56.5%) 39 (42.4%) 1 (1.1%)

55 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 testingadvantages and barriers

56 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

57 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

58 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

59 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

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61 Novel Microdevices Hands-on time <2 minutes Hand-held Assay Automation Instrument Insert chip into device Transfer sample into chip, start On-chip DNA purification On-chip DNA amplification Detection and result display <1 < <1 Time to Result <20 minutes 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. Self-contained Microfluidic Cartridge

62 Evolution of Syphilis Test Traditional syphilis tests - Manual Nontreponemal Treponemal Automated Test platforms Treponemal Rapid syphilis test Treponemal

63 Self-Testing Instruction Guide

64 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

65 CID July 15, 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

66 Schachter STD 2005; Gaydos JCM 2010; Taylor JCM 2011; Van Der Pol STD 2012; Van Der Pol STD 2013; Gaydos JCM 2013 Clinician Collected Vaginal or Cervical vs. Self-Collected Vaginal Swabs Aptima M-2000 ProbeTech Qx Amplified DNA Cobas 4800 GenXPert CT PVS/CVS PVS/CVS Symptomat. PVS/Cx Swab PVS vs CxSwab PVS/Cx 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%

67 Gaydos et al. STD Female Questionnaire Results: Self Collection Vaginal Swabs % 94.5% Collect Own Specimen Vag swab Safe 0.00 Collection Easy to Very Easy Instructions Easy to Very Easy Use Internetbased SAS again

68 100.0% 80.0% 60.0% 40.0% 20.0% Male Questionnaire Results Home collection (N = 501) Penile Swab 89.8% Urine 95.3% 94.0% 91.4% 0.0% Collection Easy to Very Easy Instructions Easy to Very Easy Use Internet-based SAS again

69 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

70 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.

71 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:

72 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 selfcollected 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: , 2010

73 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 CLIAwaived status and can perform any of the approximately 120 CLIA-waived tests Clinical Chemistry 62: , 2016

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76 Global summary: AIDS epidemic Number of people Total living with HIV in 2015 Adults Women Children (<15 years) 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] People newly infected with HIV in 2015 Total Adults Children (<15 years) 2.1 million [1.9 million 2.4 million] 1.9 million [1.7 million 2.1 million] [ ] AIDS deaths in 2015 Total Adults Children (<15 years) 1.1 million [ million] 1.0 million [1.2 million 1.5 million] [ ] Source: UNAIDS/WHO estimates.

77 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

78 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

79 Syphilis serologic screening algorithms TP-PA+ Syphilis (past or present) RPR+ TP-PA or other trep. test Traditional Quantitative RPR EIA/CIA- TP-PA- RPR- Syphilis unlikely Evaluate clinically RPR+ Syphilis (past or present) Reverse sequence EIA/CIA+ Quantitative RPR EIA/CIA/POC TP-PA+ Syphilis (past or present) TP-PA- TP-PA If at risk for syphilis, repeat RPR in several weeks CDC recommende algorithm for reverse sequence syphilis screening followed by nontreponemal tes confirmation RPR- Syphilis unlikely

80 Positive predictive values of the immunochromatographic strip test at various syphilis prevalences

81 POC Syphilis Health CheckTM Syphilis Antibody Rapid Immunochromatographic Test 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 Negative: 1 colored band in control area Positive: Colored bands in test area and control area Inconclusive: No distinct color bands in either area FDA Cleared CLIA Waived

82 Standard Diagnostics-Alere Determine Syphilis TP POC 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 finger prick or

83 Syphilis Assay Video whole Blood Sample: DPP HIV- QE&x-yt-ts= 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

84 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

85 18 month shelf-life at 2-30 C Rev_0_1_Multiplo_TPHIV_Product_Sheet_(English).pdf No refrigeration or cold chain required No timers required Results are easy to interpret 3 minute test procedure No specialized equipment required Whole blood, serum or plasma specimens No specialized training required Built-in procedural and reagent control line

86 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? Would you test yourself at home for trichomonas if the rapid trichomonas test were available over-the-counter? What is the maximum price you would pay to purchase a rapid trichomonas test over-thecounter, if available? 60 (65.2%) 31 (33.7%) 1 (1.1%) Definitely Test Probably Test Not Test 77 (83.7%) 14 (15.2%) 1 (1.1%) $10 $20 $30 42 (45.6%) 37 (40.2%) 3 (14.1%)

87 Adults and Children Living with HIV North America 1.4 million [1.1 million 2.0 million] Caribbean [ ] Latin America 1.4 million [1.1 million 1.7 million] Western & Central Europe [ million] Middle East & North Africa [ ] Sub-Saharan Africa 23.5 million [22.1 million 24.8 million] Eastern Europe & Central Asia 1.4 million [1.1 million 1.8 million] East Asia [ million] South & South-East Asia 4.0 million [3.1 million 5.2 million] Oceania [ ] 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

88 Chlamydia trachomatis and Neisseria gonorrhoeae Old: Culture and staining. New: PCR and other nucleic acid amplification tests (NAATs)

89 What about the Small Laboratory? BD MAX By Becton Dickinson BD MAX can be used for chlamydia, gonorrhea, and 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