Hepatitis Screening and Treatment Campaign in Malaysia-Validation of Low-cost Point of Care Screening Tests and Nucleic Acid Tests for Hepatitis B and C

Two major challenges in implementing budget-constrained Hepatitis screening and treatment campaign in Malaysia are the availability of low-cost point of care tests (POCT) and nucleic acid tests (NAT) for hepatitis C virus ribonucleic acid (HCV RNA) and hepatitis B virus dioxyribo nucleic acid (HBV DNA). We evaluated the performance of these tests in this study. We conducted a cross-sectional study to evaluate the diagnostic performance of four POCT brands at 12 sites in Malaysia. We assessed the sensitivity and specificity of the POCTs for the detection of HBsAg and anti-HCV in a finger-stick capillary or venepuncture whole-blood samples compared with test results from lab-based enzyme immunoassay (EIA) or chemi-luminescence immunoassay (CLIA) assay as the reference standard. We also conducted a cross-sectional study on 30 to 139 serum specimen panel to evaluate the diagnostic performance of a low-cost in-house Applied Biosystem TaqMan real-time polymerase chain reaction (PCR) assay (ABS) for the detection of HCV RNA and HBV DNA, compare with Roche Cobas Ampliprep/TaqMan assay (COBAS). Between March and December 2017, we enroll 295 participants for the evaluation of POCT for HBsAg and another 307 participants for POCT anti-HCV evaluation. Three of the four POCT brands dropped out of evaluation early on account of sub-optimal sensitivity. The sensitivity of the remaining POCT for HBsAg was 95.2%and specificity 100%, while the POCT for anti-HCV has a sensitivity of 98.1% and specificity 100%.Hepatitis B virus dioxyribo nucleic acid and HCV RNA concentrations detected by the ABS were systematically higher than those measured by COBAS (mean bias +0.10 and +0.17 log10 IU/mL respectively). The 95% limits of agreement between the two assays are -1.28 to 1.47 log10 IU/mL for HBV DNA and -0.41 to 0.75 log10 IU/mL for HCV RNA. We found adequate evidence for the diagnostic validity of a low-cost POCT for anti-HCV and HBsAg, as well as for an in-house nucleic acid tests (NAT), to provide support for their broader use in our Hepatitis screening and treatment campaign. ABS: Applied Biosystem TaqMan real-time PCR assay, CI: Confidence interval, CLD: Chronic liver disease, CLIA: Chemi-luminescence immunoassay, COBAS: Roche Cobas Ampliprep/ TaqMan assay, DAA: Direct Acting Anti-Viral drugs, EIA: Enzyme immunoassay, HBV: Hepatitis B virus, HCV: Hepatitis C virus, HFPM: Hepatitis Free Pahang Malaysia, LOA: Limits of agreement, LOD: Limit of detection, MOH: Ministry of Health