During a nosocomial hepatitis C outbreak, emergency public clinics employed the OraQuick HCV rapid antibody test on site, and all results were verified by a standard enzyme immunoassay (EIA). Of 1,157 persons, 1,149 (99.3%) exhibited concordant results between the two tests (16 positive, 1,133 negative). The sensitivity, specificity, positive predictive value, and negative predictive value were 94.1%, 99.5%, 72.7%, and 99.9%, respectively. OraQuick performed well as a screening test during an outbreak investigation and could be integrated into future hepatitis C virus (HCV) outbreak testing algorithms

Dionne-Odom, Jodie

Gao, Fengxiang

Loring, Carol H

Power, Jill J

Talbot, Elizabeth A.

English

Dartmouth Digital Commons (Dartmouth College)

Dartmouth CollegeDartmouth Digital CommonsOpen Dartmouth: Faculty Open Access Articles4-30-2014Performance of the OraQuick HCV RapidAntibody Test for Screening Exposed Patients in aHepatitis C Outbreak InvestigationFengxiang GaoNew Hampshire Department of Health and Human ServicesElizabeth A. TalbotDartmouth CollegeCarol H. LoringNew Hampshire Department of Health and Human ServicesJill J. PowerNew Hampshire Department of Health and Human ServicesJodie Dionne-OdomDartmouth CollegeFollow this and additional works at: https://digitalcommons.dartmouth.edu/facoaPart of the Clinical Epidemiology Commons, Epidemiology Commons, Health ServicesResearch Commons, and the Infectious Disease CommonsThis Article is brought to you for free and open access by Dartmouth Digital Commons. It has been accepted for inclusion in Open Dartmouth: FacultyOpen Access Articles by an authorized administrator of Dartmouth Digital Commons. For more information, please contactdartmouthdigitalcommons@groups.dartmouth.edu.Recommended CitationGao, Fengxiang; Talbot, Elizabeth A.; Loring, Carol H.; Power, Jill J.; and Dionne-Odom, Jodie, "Performance of the OraQuick HCVRapid Antibody Test for Screening Exposed Patients in a Hepatitis C Outbreak Investigation" (2014). Open Dartmouth: Faculty OpenAccess Articles. 1301.https://digitalcommons.dartmouth.edu/facoa/1301Performance of the OraQuick HCV Rapid Antibody Test forScreening Exposed Patients in a Hepatitis C Outbreak InvestigationFengxiang Gao,a Elizabeth A. Talbot,b,c Carol H. Loring,a Jill J. Power,a Jodie Dionne-Odom,b,c Sharon Alroy-Preis,b Patricia Jackson,bChristine L. BeanaPublic Health Laboratories, Division of Public Health Services, New Hampshire Department of Health and Human Services, Concord,a Division of Public Health Services,New Hampshire Department of Health and Human Services, Concord,b and Geisel School of Medicine at Dartmouth, Hanover,c New Hampshire, USADuring a nosocomial hepatitis C outbreak, emergency public clinics employed the OraQuick HCV rapid antibody test on site,and all results were verified by a standard enzyme immunoassay (EIA). Of 1,157 persons, 1,149 (99.3%) exhibited concordantresults between the two tests (16 positive, 1,133 negative). The sensitivity, specificity, positive predictive value, and negative pre-dictive value were 94.1%, 99.5%, 72.7%, and 99.9%, respectively. OraQuick performed well as a screening test during an out-break investigation and could be integrated into future hepatitis C virus (HCV) outbreak testing algorithms.Clinical signs and symptoms of hepatitis C virus (HCV) infec-tion are generally nonspecific, and many patients with acuteor chronic infection are asymptomatic. As a result, laboratory test-ing for evidence of HCV infection is required for diagnosis. Be-cause of its high sensitivity, ease of automation, and relatively lowcost, enzyme immunoassay (EIA) for the detection of the IgG classof antibodies to HCV (IgG anti-HCV) is the most commonly usedapproach to HCV infection screening. Generally, EIA requires asubsequent patient encounter to provide results. This delay canlead to patient anxiety or loss to follow-up.Recently, rapid HCV antibody tests have been developed andtheir performance has been evaluated (1, 2). The OraQuick HCVrapid antibody test (OraQuick), manufactured by OraSure Tech-nologies, Inc., is the first to gain approval by the Food and DrugAdministration (FDA) (3) and a Clinical Laboratory Improve-ment Amendments (CLIA) waiver (4) for qualitative detection ofHCV antibodies in finger stick or venipuncture whole blood.OraQuick is a single-use lateral-flow indirect immunoassay in-tended for use in symptomatic or high-risk asymptomatic pa-tients. Results can be obtained at the point of care in 20 to 40 min.In earlier evaluations of symptomatic or high-risk asymptomaticpatients, OraQuick demonstrated high sensitivity (97.8 to 100%)and specificity (99.5 to 100%) (1, 5, 6). Few studies have evaluatedthe performance of the test in a low-risk population. One (7)conducted by OraSure Technologies and collaborators examined450 low-risk subjects and demonstrated high sensitivity (100%)and specificity (100%) of OraQuick with both finger stick bloodand venous whole blood. No performance data for OraQuick havebeen reported for screening a large population of patients at mixedrisk for HCV infection, such as during an outbreak investigation.On 25 May 2012, the New Hampshire Division of PublicHealth Services (NH DPHS) confirmed an HCV outbreak at alocal hospital cardiac catheterization laboratory (CCL) (8). Epi-demiologic and laboratory data strongly suggested that theirsource was an infected health care worker (HCW) who was divert-ing narcotics (8). The NH DPHS recommended HCV testing forall patients who received care in all at-risk settings during theperiod of this HCW’s employment at the local hospital. Due to thelarge number of patients indicated for testing, and intense com-munity concern, NH DPHS organized eight emergency publichealth clinics for HCV testing in two stages: OraQuick on site,followed by EIA and any necessary supplemental testing per-formed at the New Hampshire Public Health Laboratories (NHPHL).NH DPHS notified all patients who were indicated for HCVtesting of the eight scheduled public clinics through direct phonecalls and letters as well as the local media. At the clinics, two serumseparator tubes (SSTs) and one lavender (anticoagulant) tubefrom each eligible patient were obtained. The lavender tube wasfor the OraQuick HCV rapid test at the public health clinics, andthe two SSTs were for EIA and supplemental testing at the NHPHL. Patients were counseled and offered their OraQuick testresult on site by trained counselors. Patients who elected not toreceive their result on site were called and/or mailed their results.Laboratorians from the NH PHL and Laboratory ResponseNetwork facilities were trained on the OraQuick HCV rapid anti-body test and proficiency tested by OraSure Technologies, Inc.,technical representatives. Testing was performed on venipuncturewhole blood in accordance with the manufacturer’s instructions(9). Any specimen that tested positive or invalid was retested onsite by a second tester who was blinded to the original result andwas unaware that the test was a repeat test. Once confirmed, aresult was finalized and provided to the patient. All specimenswith positive or invalid OraQuick test results were also repeattested at the NH PHL.Serum specimens were transported from the clinic settings to theNH PHL within 6 h of collection using coolers with cold packs. Uponreceipt, the SSTs were centrifuged and tested for anti-HCV antibodiesby use of the Ortho HCV version 3.0 EIA (Ortho Clinical Diagnostics,Rochester, NY) (10) with the ETI-Max 3000 automated EIA analyzer(DiaSorin). The remaining serum specimens were frozen at 70°CReceived 22 January 2014 Returned for modification 10 February 2014Accepted 15 April 2014Published ahead of print 30 April 2014Editor: Y.-W. TangAddress correspondence to Christine L. Bean, clbean@dhhs.state.nh.us.Copyright © 2014, American Society for Microbiology. All Rights Reserved.doi:10.1128/JCM.00132-142650 jcm.asm.org Journal of Clinical Microbiology p. 2650 –2652 July 2014 Volume 52 Number 7and used for supplemental testing, if necessary. Final results wereobtained within 48 h of specimen collection.Specimens which yielded discordant results between OraQuickand EIA were frozen at 70°C and sent to the laboratory at theDivision of Viral Hepatitis of the Centers for Disease Control andPrevention (CDC) to be tested for anti-HCV using the OrthoVitros immunodiagnostics anti-HCV chemiluminescence immu-noassay (CIA) (Ortho Clinical Diagnostics, Rochester, NY). TheCIA was performed according to the manufacturer’s instructions(11). Specimens which tested positive by either OraQuick or EIAwere tested for HCV RNA by use of the Cobas Amplicor HCV test,v2.0 (Roche Molecular Diagnostics, Almere, Netherlands) (12).Of 1,157 patients presenting to the eight public clinics, 714(61.7%) were female and 443 (38.3%) were male. Their medianage was 53 years (range, 15 to 95 years). After OraQuick testing, 22(1.9%) were found to be positive, 1 (0.1%) had an invalid result,and 1,134 (98.0%) were negative (Table 1). Repeat OraQuick test-ing on specimens yielding positive or invalid results was 100%reproducible both on site and at the NH PHL.Six of the 22 specimens (27%) which were positive byOraQuick were negative by EIA. One specimen with an invalidOraQuick result tested negative by EIA. One of the 1,134 speci-mens (0.1%) which tested negative by OraQuick tested positive byEIA. Excluding the invalid result, the sensitivity and specificity ofOraQuick compared with EIA were 94.4% and 99.4%, respec-tively. The negative predictive value (NPV) and positive predictivevalue (PPV) of OraQuick were 99.9% and 72.7%, respectively.The seven specimens with discordant results underwent CIAtesting at the CDC (Table 2). Of the six that were OraQuick pos-itive and EIA negative, five tested negative and one tested positiveby CIA, suggesting five false-positive results by OraQuick and onefalse-negative result by EIA when agreement of two tests out ofthree (OraQuick, EIA, and CIA) was used as the determinant re-sult. Of note, the specimen that tested positive by CIA (specimen2) gave a CIA signal-to-cutoff ratio of 1.18, just above the cutoff of1.00. Discordant specimen 7, which tested negative by OraQuickand positive by EIA, was positive by CIA, suggesting one false-negative result by OraQuick. All seven specimens tested negativefor HCV RNA by reverse transcription (RT)-PCR.This is the first report of the OraQuick HCV rapid antibodytest for the detection of HCV antibodies in a large population withpotential exposure to nosocomial HCV infection. Compared withEIA, we confirm that the OraQuick assay demonstrated high spec-ificity (99.5%), which is similar to the findings of other reports (1,5, 6). OraQuick also displayed a high NPV (99.9%), which is acritical characteristic for a screening test, especially in the settingof mass testing related to an outbreak, because it is critical toprovide the patient reassurance regarding the absence of diseasewith a high degree of confidence. The sensitivity (94.1%) in ourstudy was slightly lower than previously reported (97.8% to100%) (1, 2), likely an artifact of a relatively small sample size. Weconsider the modest PPV (72%) to not be a significant limitationfor OraQuick as a screening test, because all positive results shouldbe confirmed by additional testing.Nosocomial HCV outbreaks have been increasingly identifiedas a source of HCV transmission and usually require screening oflarge populations. Between 2008 and 2012, 16 hepatitis C out-breaks were reported in the United States and more than 90,000at-risk persons were advised to undergo HCV screening (13).Screening of large populations is challenging, and the use of arapid test can greatly aid testing efforts.We demonstrate that OraQuick can be used in an outbreaksetting to allow rapid screening of a large number of patients. Thiscan identify HCV-infected patients who may be informed of theirstatus and offered counseling to prevent further spread of thevirus. In addition, timely identification or exclusion of HCV in-fection reduces anxiety and frustration among those potentiallyexposed.In this study, CIA results were consistent with the EIA resultsfor all but one specimen. The single patient whose specimen testedpositive by OraQuick, negative by EIA, and positive by CIA maybe explained by early infection/seroconversion or may be a bio-logical false positive due to an unidentified interfering substance.Testing the patient at a later date would be useful to resolve thetesting discrepancy in this single patient.In a previous study (1), false results with OraQuick rangingfrom 0.65% to 1.31% were reported and the association betweengender and false results was determined. In the current report, wefound six specimens (0.52%) displaying false results and five ofthem were from females. This is consistent with the finding in theprevious study that gender was associated with false rapid anti-HCV results of OraQuick testing. It is unclear why a higher occur-rence of false rapid anti-HCV results is observed in females, andmore studies are needed.In this public health response, OraQuick was performed innontraditional emergency public health clinics set up in nonmed-ical community settings (e.g., local school gymnasiums and cafe-terias). The settings exhibited different ambient conditions, suchas non-air-conditioned space in the summer and less-than-ideallighting for reading the results. In spite of these limitations, therewas only one invalid result, and repeat testing under controlledTABLE 2 Summary of test results for patients with discordant resultsbetween OraQuick and EIAaSpecimenidentificationno. OraQuick EIA (SCR) CIA (SCR) HCV RNA1 Positive Negative (0.007) Negative (0.02) Negative2 Positive Negative (0.31) Positive (1.18) Negative3 Positive Negative (0.016) Negative (0.02) Negative4 Positive Negative (0.013) Negative (0.02) Negative5 Positive Negative (0.043) Negative (0.43) Negative6 Positive Negative (0.011) Negative (0.01) Negative7 Negative Positive (5.123) Positive (12.9) Negativea SCR, signal-to-cutoff ratio. Specimens were considered as reactive for antibody toHCV if the SCR was 1.0 in both EIA and chemiluminescence immunoassay (CIA).The HCV RNA test was performed using the Cobas Amplicor HCV test, v2.0.TABLE 1 Summary of test results of OraQuick anti-HCV rapid test incomparison with Ortho HCV version 3.0 EIAOraQuick resultNo. of patients with indicated EIA resultPositive Negative TotalPositive 16 6 22Negative 1 1,133 1,134Invalid 0 1 1Total 17 1,140 1,157Performance of the OraQuick HCV Rapid TestJuly 2014 Volume 52 Number 7 jcm.asm.org 2651conditions at the NH PHL documented perfect reproducibility.One limitation to our discordant analysis is that the recombinantimmunoblot assay (RIBA) became unavailable in March 2012.RIBA had previously been considered a confirmatory test for pos-itive IgG anti-HCV EIA or CIA test results. We were unable toconfirm the anti-HCV results for those specimens with discrepantresults between OraQuick and the EIA due to the manufacturer’sdiscontinuation of RIBA.Recently, the CDC has recommended widespread screening of“baby boomers” (persons born during 1945 and 1965) withoutprior determination of HCV risk because of the high prevalence ofHCV infection and related disease (14). To help health care pro-viders and public health professionals implement this recommen-dation, the CDC proposed a laboratory testing algorithm for iden-tifying current HCV infection (15). This testing algorithmincludes OraQuick as a screening test.Our findings demonstrate that OraQuick is a robust and reli-able field tool to detect HCV infection in the setting of mass test-ing. Supplemental testing using an RT-PCR assay and/or immu-noassays should be performed on any specimen exhibiting apositive result.ACKNOWLEDGMENTSWe acknowledge the following contributors: S. Kamili, J. Drobeniuc, andC. G. Teo of the CDC for facilitating CIA testing and A. Cosser, K. Wolfe,S. Desrosiers, and M. Leveque of Public Health Laboratories, Division ofPublic Health Services, New Hampshire Department of Health and Hu-man Services, for performing EIA testing.OraSure Technologies, Inc., representatives participated in laborato-rian training but did not fund the study nor were they involved in thestudy design or data analysis and interpretation.REFERENCES1. Smith BD, Drobeniuc J, Jewett A, Branson BM, Garfein RS, Teshale E,Kamili S, Weinbaum CM. 2011. Evaluation of three rapid screeningassays for detection of antibodies to hepatitis C virus. J. Infect. Dis. 204:825– 831.2. Shivkumar S, Peeling R, Jafari Y, Joseph L, Pant Pai N. 2012. Accuracyof rapid and point-of-care screening tests for hepatitis C: a systematicreview and meta-analysis. Ann. Intern. Med. 157:558 –566.3. U.S. Food and Drug Administration. 2013. OraQuick HCV rapid anti-body test—P080027. U.S. Food and Drug Administration, Silver Spring,MD. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm220489.htm.4. U.S. Food and Drug Administration. 2011. CLIA waiver expands avail-ability of rapid blood test for antibodies to the hepatitis C virus (HCV).U.S. Food and Drug Administration, Silver Spring, MD. http://www.fda-.gov/ForConsumers/ByAudience/ForPatientAdvocates/ucm281524.htm.5. Lee SR, Kardos KW, Schiff E, Berne CA, Mounzer K, Banks AT, TatumHA, Friel TJ, Demicco MP, Lee WM, Eder SE, Monto A, Yearwood GD,Guillon GB, Kurtz LA, Fischl M, Unangst JL, Kriebel L, Feiss G, RoehlerM. 2011. Evaluation of a new, rapid test for detecting HCV infection,suitable for use with blood or oral fluid. J. Virol. Methods 172:27–31.6. Cha YJ, Park Q, Kang ES, Yoo BC, Park KU, Kim JW, Hwang YS, KimMH. 2013. Performance evaluation of the OraQuick hepatitis C virusrapid antibody test. Ann. Lab. Med. 33:184 –189.7. Lee SR, Yearwood GD, Guillon GB, Kurtz LA, Fischl M, Friel T, BerneCA, Kardos KW. 2010. Evaluation of a rapid, point-of-care test device forthe diagnosis of hepatitis C infection. J. Clin. Virol. 48:15–17.8. New Hampshire Department of Health and Human Services. 23 De-cember 2013, accession date. Hepatitis C outbreak investigation, ExeterHospital. Public report. New Hampshire Department of Health and Hu-man Services, Concord, NH. http://www.dhhs.nh.gov/dphs/cdcs/hepatitisc/documents/hepc-outbreak-rpt.pdf.9. OraSure Technologies, Inc. 2011. OraQuick® HCV rapid antibody testpackage insert. OraSure Technologies, Inc., Bethlehem, PA.10. Ortho Clinical Diagnostics. 2010. Hepatitis C virus encoded antigen(recombinant c22-3, c200 and NS5) ORTHO® HCV version 3.0 ELISAtest system package insert. Ortho Clinical Diagnostics, Rochester, NY.11. Ortho Clinical Diagnostics. 2010. Vitros Immunodiagnostics Productsanti-HCV reagent pack, version 4.2, package insert. Ortho Clinical Diag-nostics, Rochester, NY.12. Roche Diagnostics. 2007. COBAS® AMPLICOR® hepatitis C virus testversion 2.0 package insert. Roche Diagnostics, Indianapolis, IN.13. CDC. 23 December 2013, accession date. Healthcare-associated hepatitisB and C outbreaks reported to the Centers for Disease Control and Pre-vention (CDC) in 2008-2012. Centers for Disease Control and Prevention,Atlanta, GA. http://www.cdc.gov/hepatitis/statistics/healthcareoutbreaktable.htm.14. CDC. 2012. Recommendations for the identification of chronic hepatitisC virus infection among persons born during 1945-1965. MMWR Rec-ommend. Rep. 61(RR04):1–18.15. CDC. 2013. Testing for HCV infection: an update of guidance for clini-cians and laboratorians. MMWR Morb. Mortal. Wkly. Rep. 62(18):362–365.Gao et al.2652 jcm.asm.org Journal of Clinical Microbiology

Performance of the OraQuick HCV Rapid Antibody Test for Screening Exposed Patients in a Hepatitis C Outbreak Investigation

https://digitalcommons.dartmouth.edu/cgi/viewcontent.cgi?article=2304&amp;context=facoa

Performance of the OraQuick HCV Rapid Antibody Test for Screening Exposed Patients in a Hepatitis C Outbreak Investigation

Abstract

Similar works

Full text

Available Versions

Dartmouth Digital Commons (Dartmouth College)