Treatment of HCV with direct-acting antivirals has enabled the discussion of HCV eradicationworldwide. Envisioning this aim requires implementation of mass screening in resource-limited areas, usuallyconstrained by testing costs. We validated a low-cost, rapid diagnosis test (RDT) for HCV in three different continents in 141individuals. The HCV RDT showed 100% specificity and sensitivity across different samples regardless of genotypeor viral load (in samples with such information, 90%). The HCV test validated in this study can allow for HCV screening in areas of need when properly used.Fil: Leathers, James S.. Vanderbilt University; Estados UnidosFil: Pisano, María Belén. Universidad Nacional de Cordoba. Facultad de Medicina. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ré, Viviana Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Instituto de Virología; ArgentinaFil: van Oord, Gertine. Erasmus Medical Center; Países BajosFil: Sultan, Amir. Addis Ababa University; EtiopíaFil: Boonstra, Andre. Erasmus Medical Center; Países BajosFil: Debes, Jose D.. Universidad de Minnesota; Estados Unido

Boonstra, Andre

Debes, Jose D.

Leathers, James S.

Pisano, María Belén

Ré, Viviana Elizabeth

Sultan, Amir

van Oord, Gertine

International Health

English

Leathers, JS

Pisano, MB

Re, V

Sultan, A

Debes, Jose

EUR Research Repository

Validation of a point-of-care rapid diagnostic test for hepatitis C for use in resource-limited settings

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Int Healthdoi:10.1093/inthealth/ihy101Validation of a point-of-care rapid diagnostic test for hepatitis C foruse in resource-limited settingsJames S. Leathersa, Maria Belen Pisanob, Viviana Reb, Gertine van Oordc, Amir Sultand, Andre Boonstracand Jose D. Debesc,e,*aVanderbilt University School of Medicine, 2201, West End Ave., Nashville, TN, USA; bInstituto de Virologia ‘Dr. J.M. Vanella’, Facultad deCiencias Medicas, CONICET, Universidad Nacional de Cordoba, Av. Enfermera Gordillo s/n, Cordoba, Argentina; cDepartment ofGastroenterology and Hepatology, Erasmus MC, Wytemaweg 80, 3015 CE, Rotterdam, The Netherlands; dDivision of Gastroenterology,Addis Ababa University, Churchil Road s/n, Addis Ababa, Ehiopia; eDepartment of Medicine, University of Minnesota, 420 Delaware StSE, Minneapolis, MN, USA*Corresponding author: Tel: +1-612-6246353; Email: debes003@umn.eduReceived 24 September 2018; revised 9 December 2018; editorial decision 24 December 2018; accepted 29 January 2019Background: Treatment of HCV with direct-acting antivirals has enabled the discussion of HCV eradicationworldwide. Envisioning this aim requires implementation of mass screening in resource-limited areas, usuallyconstrained by testing costs.Methods: We validated a low-cost, rapid diagnosis test (RDT) for HCV in three different continents in 141individuals.Results: The HCV RDT showed 100% specificity and sensitivity across different samples regardless of genotypeor viral load (in samples with such information, 90%).Conclusions: The HCV test validated in this study can allow for HCV screening in areas of need when properlyused.Keywords: hepatitis C, rapid diagnostic test, resource-limitedIntroductionHCV is responsible for 400 000 deaths a year, with a large pro-portion of these deaths occurring in low- and middle-incomecountries.1 While new curative therapies for HCV are nowbecoming affordable in more regions of the world, manyinfected persons remain untreated due to limited access to cen-tralized laboratory testing and cost restrictions for mass testingin areas of need.2 We aimed to perform an external validationof a rapid diagnostic test (RDT) for HCV using study populationsfrom three different regions of the world.Material and methodsThe studied RDT measures anti-HCV antibodies in serum (anti-HCVcassette, PRECHEK Bio. Inc., Korea) and gives a qualitative result(positive/negative) within minutes based on double antigen sand-wich immunoassay. Monoclonal antibodies against HCV antigensare conjugated with colloidal gold, deposited in the pad and immo-bilized on the test line in the nitrocellulose membrane. As serum isadded it rehydrates the gold–antibody conjugate. In positive sam-ples the antigen–antibody–gold complex will migrate towards thetest window until the test zone (T), where it is captured by immobi-lized antibodies, forming a visible line, which indicates a positivereaction. Tests were performed according to the manufacturer’sinstructions, using serum obtained from hospitals in TheNetherlands, Argentina and Ethiopia. The performance of the RDTwas assessed by receiver operating characteristic (ROC) curve ana-lysis, using the local diagnostic standard as the reference test(Argentina: ARCHITECT anti-HCV Reagent kit from Abbott, Germany;The Netherlands: LIAISON XL system from Diasorin, Italy; Ethiopia:HCV Rapid Test from Assure Tech, China). Statistical analyses wereperformed using STATA version 15.1 (StataCorp LP, College Station,TX, USA). Patients coinfected with HIV were not included.Results and discussionSerum samples from 141 patients were tested using the anti-HCV RDT. A total of 91 known HCV-positive samples and 50SHORTCOMMUNICATION© The Author(s) 2019. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.1 of 2Downloaded from https://academic.oup.com/inthealth/advance-article-abstract/doi/10.1093/inthealth/ihy101/5375832 by guest on 13 March 2019known HCV-negative samples were tested. Ninety samples weretested in The Netherlands, 41 in Argentina and 10 in Ethiopia.The median age of patients was 46 y (IQR 39–54) and 65%were male. HCV genotype was available in 96 patients, with 61samples belonging to genotype 1, 21 to genotype 2, and 7 eachto genotypes 3 and 4 (Table 1). The median HCV RNA level(available in 67 patients) was 800 000 IU/ml (IQR 80 000–4 200000). The HCV RDT had a sensitivity and specificity of 100% (CI94.9 to 100 and 92.9 to 100, respectively) in all genotypes andall RNA levels, including <15 copies, which was the lower levelof detection for quantitative assays. As the WHO aims toachieve 90% diagnosis of HCV by 2030, it is critical to validaterapid tests in resource-rich as well as resource-limited settings.3In this study, we demonstrate that the PRECHEK Bio. Inc. anti-HCV cassette RDT is highly sensitive and specific for the diagno-sis of HCV. By testing the RDT in three different countries fromthree separate continents, as well as testing four different HCVgenotypes, we are able to establish that the test is likely to bereliable in a variety of populations. While several point-of-careRDTs are commercially available, many rely on expensive instru-ments, making them ill-suited for resource-limited settings.4 Incontrast, the RDT tested in this study is a chromatographicimmunoassay that does not require extra instrumentation,making it both affordable and appropriate for rural sites.Importantly, test results are available in <10 min. Moreover, thecalculated cost of the test is approximately 1–2% that ofapproved WHO ones (depending on order volume and location),making it realistically affordable for limited settings. Some ofthe limitations of our study include a relatively small samplesize, as well as a lack of assessment of active viral replication(HCV RNA) in all samples. However, we believe the ease of use,rapid result yield and very low cost of this RDT could increasethe proportion of patients aware of their HCV status in all geo-graphical regions, thus enabling treatment when possible.Authors’ contributions: JL performed experiments, analyzed data andwrote manuscript; MBP, VR and GvO performed experiments and helpedto analyze the data; AS performed testing and contributed to manu-script editing; AB helped analyzed data, contributed to study develop-ment and edited manuscript; JDD developed study concept, helpedanalyzed data, edited the manuscript.Acknowledgements: None.Funding: This work was supported in part by the Doris Duke CharitableFoundation through a grant supporting the Doris Duke InternationalClinical Research Fellowship Program at the University of Minnesota toJL; the Robert Wood Johnson Foundation, Amos Medical FacultyDevelopment Program to JDD; and a global health seed grant fromUniversity of Minnesota to JDD.Competing interests: The authors of this manuscript do not have anyconflicts of interest to disclose.Ethical approval: This study was approved by blanket internal reviewboard for stored samples, Erasmus MC, Rotterdam, The Netherlands.References1 Thrift AP, El-Serag HB, Kanwal F. Global epidemiology and burden ofHCV infection and HCV-related disease. Nat Rev Gastroenterol Hepatol2017;14:122–32.2 Sonderup MW, Afihene M, Ally R et al. Hepatitis C in sub-SaharanAfrica: the current status and recommendations for achieving elimin-ation by 2030. Lancet Gastroenterol Hepatol 2017;2:910–9.3 Easterbrook PJ, Group WGD. Who to test and how to test for chronichepatitis C infection – 2016 WHO testing guidance for low- andmiddle-income countries. J Hepatol 2016;65:S46–66.4 Llibre A, Shimakawa Y, Mottez E et al. Development and clinical valid-ation of the Genedrive point-of-care test for qualitative detection ofhepatitis C virus. Gut 2018;67(11):2017–24.Table 1. Patient characteristics by countryThe Netherlands Argentina EthiopiaNumber 90 41 10Median age, y1 48 (39–55) 46 (40–50) 48 (39–55)Male gender 67% 61% 67%Genotype2 1 (62%)2 (13%)3 (13%)4 (13%)1 (66%)2 (34%)n/a1Medians are displayed with IQR (Q1–Q3).2Genotype data was unavailable in Ethiopia.J. S. Leathers et al.2 of 2Downloaded from https://academic.oup.com/inthealth/advance-article-abstract/doi/10.1093/inthealth/ihy101/5375832 by guest on 13 March 2019

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Validation of a point-of-care rapid diagnostic test for hepatitis C for use in resource-limited settings

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