Objective: This study was aimed at evaluating the performance of three CE‑ marked rapid diagnostic tests (RDTs): ® ® Multisure‑ HCV, First Response and Toyo ; for screening anti‑ HCV antibody using plasma samples. Results: Overall, 200 plasma samples were used. Sensibility and specificity of these RDTs range from 71 to 99 and 78 to 100% respectively. Multisure scored a sensitivity at 99% (95% CI 97–100%) and First Response reached a specificity at 90% (95% CI 85–94.9%). Further studies should be conducted to establish an algorithm using these RTDs for the detection of HCV infection in Cameroon. Keywords: Cameroon, HCV, Rapid diagnostic test, Performance, Plasma C, were aware of their infection in 2015 . Therefore, Introduction countries need to improve policies and programs to In Cameroon, the prevalence of hepatitis C virus (HCV) increase diagnosis. Rapid diagnostic tests (RDTs) repre- infection is estimated at 1.1% from the samples of the sent an alternative solution to conventional HCV tests. 2011 Demographic Health Survey . This prevalence is Recently, certified RDTs for HCV have been approved estimated at 0.81% for the 15–49 year’s group and 2.51% to track down this infection . The WHO prequalifi - for all individuals aged ≥ 15 years. It is estimated that cation program revealed that only two HCV RDTs (SD about 195,000 individuals in Cameroon were viremic Bioline HCV from Standard Diagnostics and OraQuick in 2011 including 92,000 adults aged 15–59 years and HCV Rapid Antibody Test from OraSure Technologies) 103,000 individuals aged ≥ 60 years . Diagnosis of have been prequalified so far [ 4]. However, since 2014 in HCV infection is based on the use of enzyme-linked Europe, the French “Haute Autorité de Santé” (HAS) has immunoassays for the detection of HCV antibody fol- evaluated CE-marked HCV RDTs and found that these lowed by a molecular confirming test in case of positiv - tests had good performance. In addition, HAS recom- ity . However, accessibility to these conventional assays mends the use of CE-marked HCV RDTs that feature the is a challenge for the majority of people infected with European Union standard (100% of sensitivity and speci- HCV especially for those living in peripheral regions due ficity ≥ 99%) [5, 6]. to the high cost of these assays as well as their availabil- Data collected from the Ministry of Public Health in ity . Diagnosis and testing remains a challenge for the Cameroon showed that none of the HCV RDTs used in elimination of viral hepatitis including HCV. According health facilities is qualified. Therefore this study aimed to WHO reports, only 1 in 5 people living with hepatitis at evaluating the performances of three CE-marked HCV RDTs for the screening of anti-HCV antibodies using plasma samples collected in Resource Limited set- *Correspondence: njouom@pasteuryaounde ‑ .org Virology Department, Centre Pasteur of Cameroon, PO ting. These RTDs included: i) Multisure HCV Antibody Box 1274 Yaounde, Cameroon Assay (MP Biomedical, Asia Pacific, Singapore), ii) First Full list of author information is available at the end of the article © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Fondjo et al. BMC Res Notes (2018) 11:352 Page 2 of 4 Response HCV Card Test (Premier Medical Corporation anti-HCV assay considered as Gold standard. The results Ltd, Watchung, New Jersey), and iii) T oyo Anti HCV were estimated with 95% confidence intervals (CI), and Test (Türklab, Izmir, Turkey). the difference was considered statistically significant with a p < 0.05. Main text Methods Results Study sample and laboratory analysis We assessed the performance of Multisure HCV Anti- ® ® From November 2016 to February 2017, we carried out body Assay, First Response HCV Card Test and Toyo a cross-sectional study on 200 plasma (including 100 Anti HCV Test in a total of 200; 140 and 150 plasma sam- positive and 100 negative) stored at -80 °C at Centre Pas- ples, respectively. The shortage in the remaining samples teur of Cameroon (CPC). These samples were previously may explain the observed inequality in the number of screened for anti-HCV antibodies at the same laboratory RDTs used. The four parameters analyzed to assess the using an automated chemiluminescent microparticle performances of these RDTs were the sensitivity (Se), the immunoassay (Architect anti-HCV assay; Abbott Diag- specificity (Sp), the positive predictive value (PPV), and nostics, Wiesbaden, Germany). Performance (sensitivity, the negative predictive value (NPV). specificity, positive predictive value and negative pre - Multisure featured a clinical sensitivity of 99% (95% dictive value) of Multisure HCV Antibody Assay, First CI 97–100%) followed by First Response 96% (95% ® ® ® Response HCV Card Test, and Toyo Anti HCV Test CI 92.7–99.2%) and Toyo 96% (95% CI 92.8–99.1%) were assessed for anti-HCV antibodies screening using (Table 1). As concerns the specificity, First Response plasma samples. scored 90% (95% CI 85–94.9%) followed by Multisure Multisure HCV Antibody is a qualitative immuno- 83% (95% CI: 77.7–82.2%) and T oyo 78% (95% CI 71.3– chromatographic assay for the detection of antibodies to 84.6%) (Table 1). However, the sensitivity and the speci- Core, NS3, NS4 and NS5 HCV proteins in human whole ficity were not significantly different among the three blood, plasma or serum. Each protein is revealed in a RDTs (p = 0.36 and p = 0.24 respectively). Regarding the separate and distinct line in the test within 15 min. First predictive values, First Re sponse scored the best PPV at Response HCV Card Test and T oyo Anti HCV Test are 96% (95% CI 92.7–99.2%); meanwhile Multisure reached chromatographic immunoassays for qualitative detec- the best NPV at 99% (95% CI 97.6–100) (Table 1). tion of the antibodies against hepatitis C virus in human Since different serum samples were tested with each serum, plasma or whole blood samples. HCV antigens RDT, we assessed the performance of these tests with (Core, NS3, NS4 and NS5) are immobilized at only one only the 90 overlapping samples to compare assay perfor- test line and the result is obtained within 20 min. mance among all of the tests. Multisure had a sensitiv- ® ® The RDTs were performed following the manufac - ity of 100% followed by First Re sponse and Toyo , 96% turer’s instructions, and the interpretation was done by (95% CI 91.7–100%) (Table 2). As concerns the specificity, three independent blinded laboratory technicians. No Multisure had a specificity of 92.5% (95% CI 87.5–97.4%) specific control was included in the study other than the followed by First Response 90% (95% CI 84.7–95.2%) internal control which is incorporated in each assay.and Toyo , 80% (95% CI 74.5–85.4%) (Table 2). However, the sensitivity and the specificity were not significantly Statistical analysis different among the three RDTs (p = 0.35 and p = 0.20 Data was analyzed with SPSS statistics version 20.0.0 respectively). Finally based on the ARCHITECT anti- (IBM Corporation, USA). The relevant accuracy esti - HCV test results, we obtained 50/3 (true positive/false mates of the three RDTs were expressed using the Pear- positive) and 0/37 (true negative/false negative) samples son Chi square test, based on the result of Architect among the 90 overlapping samples with Multisure, 48/4 Table 1 Overall comparison of the three rapid diagnostic tests (RDTs) evaluated for the screening of anti-HCV antibodies HCV RDTs Se Sp PPV NPV % (95% CI) % (95% CI) % (95% CI) % (95% CI) Multisure HCV Antibody assay 99 (97–100) 83 (77.7–88.2) 85 (80–89.9) 99 (97.6–100) First Response HCV Card Test 96 (92.7–99.2) 90 (85–94.9) 96 (92.7–99.2) 90 (85–94.9) Toyo Anti HCV Test 96 (92.8–99.1) 78 (71.3–84.6) 89.7 (83.9–94) 90.7 (86–95.3) Se, sensibility; Sp, specificity; PPV, predictive positive value; NPV, negative predictive value; HCV, hepatitis C virus; RDTs, rapid diagnostic tests; CI, confidence interval Fondjo et al. BMC Res Notes (2018) 11:352 Page 3 of 4 Table 2 Comparison of the three rapid diagnostic tests (RDTs) evaluated for screening anti-HCV with only overlapping samples HCV RDTs Se (95% CI) Sp (95% CI) PPV (95% CI) NPV (95% CI) TP (n) FP (n) TN (n) FN (n) Multisure HCV Antibody assay 100 92.5 (87.5–97.4) 94.3 (89.2–98.7) 100 50 3 37 0 First Response HCV Card Test 96 (91.7–100) 90 (84.7–95.2) 92.3 (87.3–97.2) 94.7 (90.1–99.3) 48 4 36 2 Toyo Anti HCV Test 96 (91.7–100) 80 (74.5–85.4) 85.7 (80.3–91.1) 94.1 (89.4–98.8) 48 8 32 2 Se Sensitivity, Sp specificity, PPV predictive positive value, NPV negative predictive value, TP true positive, FP false positive, TN true negative, FN false negative, n number, HCV hepatitis C virus, RDTs rapid diagnostic tests, CI confidence interval and 36/2 with First Response and 48/8 and 32/2 with Limitations Toyo (Table 2). The evaluation of RDTs was only based on plasma. We did not consider that HCV serology can also be per- formed on the whole blood, serum and crevicular fluid. We could have worked with these four types of samples Discussion on the same panel to see if there are differences in the This study showed none of the RDTs evaluated reached results. the European Union standards (100% of sensitivity and specificity ≥ 99%). These standards are based on different studies carried out in Europe, where conditions in realiz- Abbreviations DBS: dried blood spot; RDTs: rapid diagnostic tests; HCV: hepatitis C virus; HIV: ing assays are practically different from those in resource human immunodeficiency virus; Se: sensitivity; Sp: specificity; PPV: positive limited countries in term of respect of quality assurance predictive value; NPV: negative predictive value. (supply chain reliability, implementation of a standard- Authors’ contributions ized logbook). The WHO (World Health Organization) LKF collected data, performed laboratory analysis and statistical analysis. has clearly demonstrated the high probability in obtain- PATN and LN reviewed the data and interpreted the results. LKF, PATN and LN ing false results using RDTs in case of non-respect of wrote the first draft of the manuscript. RN and JCP conceived, designed and conducted the study. All the authors substantially participated in the work, quality assurance . Furthermore, the studied popula- critically revised the manuscript and approved the final version. tions (North versus South) could also explain the dif- ference observed in this study and European Union Author details Virology Department, Centre Pasteur of Cameroon, PO Box 1274 Yaounde, standards in term of specificity. Nevertheless, the results Cameroon. Hôpital Charles Nicolle, Centre Hospitalier Universitaire de Rouen, obtained from these RDTs are not significantly satisfac - 1 rue de Germont, Rouen, France. tory and suggest that further studies should be conducted Acknowledgements to establish an algorithm using these RTDs for the detec- The authors are grateful to all colleagues at the Centre Pasteur of Cameroon tion of HCV infection in Cameroon. The strategy used for their direct or indirect contribution to the successful accomplishment of for HIV diagnosis based on two RDTs : the most sensi- this study. tive RDTs as the first, then the most specific assay in case Competing interests of positivity, could be evaluated for HCV screening. The authors declare that they have no competing interests. Availability of data and materials All data generated or analysed during this study are Available from RN. Conclusion Consent for publication None of the three RDTs evaluated met the European Not applicable. Union standards. However, the performances obtained are crucial indications for the Ministry of Public Health Ethics approval and consent to participate The study was approved by the ethics committee of the Catholic University of of Cameroon on the choice of RDTs to be used regarding Central Africa/School of Health Science (N°2016/0393/CEIRSH/ESS/MIM). their performance, and especially to promote assessment of HCV RDTs before implementation. Therefore, further Funding This work was supported by Centre Pasteur of Cameroon (CPC) for the study, studies should be conducted to establish an algorithm collection, analysis and interpretation of data; and NEPHROTEK (France) for using these RTDs for the detection of HCV infection in having provided the RDTs. Cameroon. Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in pub‑ lished maps and institutional affiliations. Fondjo et al. BMC Res Notes (2018) 11:352 Page 4 of 4 Received: 24 January 2018 Accepted: 1 June 2018 5. HAS. Place des tests rapides d’orientation diagnostique ( TROD) dans la stratégie de dépistage de l’hépatite C. 2016. 6. HAS. Place des tests rapides d’orientation diagnostique ( TROD) dans la stratégie de dépistage de l’hépatite C. 2014. 7. Adler M, Behel S, Duncan D, Houston J, Kalou M, Lasry A, et al. Consoli‑ dated guidelines on HIV testing services: 5Cs: consent, confidentiality, References counselling, correct results and connection 2015. World Health Organiza‑ 1. Njouom R, Siffert I, Texier G, Lachenal G, Tejiokem MC, Pepin J, et al. The tion 2015; 2015. burden of hepatitis C virus in Cameroon: spatial epidemiology and his‑ 8. MSP‑ Cameroon. Guide national de prise en charge des personnes torical perspective. J Viral Hepat. 2018. https ://doi.org/10.1111/jvh.12894 . vivant avec le VIH/SIDA ‑ Cameroun: Chapitre 2: counselling: Algorithme 2. CDC. Testing for HCV infection: an update of guidance for clinicians and national pour le depistage du VIH. n.d. http://colle ction s.infoc ollec tions laboratorians. MMWR Morb Mortal Wkly Rep. 2013;62:362–5. .org/whoco untry /fr/d/Js688 2f/5.1.html. Accessed 30 May 2017. 3. WHO. http://www.who.int/media centr e/news/relea ses/2017/hepat itis‑c‑ cure/en/. 2017. Accessed 18 Apr 2018. 4. WHO. http://www.who.int/media centr e/facts heets /fs164 /fr/. 2016. Accessed 4 Nov 2016. Ready to submit your research ? Choose BMC and benefit from: fast, convenient online submission thorough peer review by experienced researchers in your ﬁeld rapid publication on acceptance support for research data, including large and complex data types • gold Open Access which fosters wider collaboration and increased citations maximum visibility for your research: over 100M website views per year At BMC, research is always in progress. Learn more biomedcentral.com/submissions
BMC Research Notes – Springer Journals
Published: Jun 5, 2018
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