Diagnostic performance evaluation of hepatitis B e antigen rapid diagnostic tests in Malawi



Stockdale, Alexander J ORCID: 0000-0002-5828-3328, Silungwe, Niza M, Shawa, Isaac Thom, Kreuels, Benno, Gordon, Melita A ORCID: 0000-0002-0629-0884 and Geretti, Anna Maria
(2021) Diagnostic performance evaluation of hepatitis B e antigen rapid diagnostic tests in Malawi. BMC INFECTIOUS DISEASES, 21 (1). 487-.

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Abstract

<h4>Background</h4>The World Health Organization (WHO) has targeted a reduction in viral hepatitis-related mortality by 65% and incidence by 90% by 2030, necessitating enhanced hepatitis B treatment and prevention programmes in low- and middle-income countries. Hepatitis B e antigen (HBeAg) status is used in the assessment of eligibility for antiviral treatment and for prevention of mother-to-child transmission (PMTCT). Accordingly, the WHO has classified HBeAg rapid diagnostic tests (RDTs) as essential medical devices.<h4>Methods</h4>We assessed the performance characteristics of three commercially available HBeAg RDTs (SD Bioline, Alere, South Africa; Creative Diagnostics, USA; and Biopanda Reagents, UK) in two hepatitis B surface antigen-positive cohorts in Blantyre, Malawi: participants of a community study (n = 100) and hospitalised patients with cirrhosis or hepatocellular carcinoma (n = 94). Two investigators, blinded to the reference test result, independently assessed each assay. We used an enzyme-linked immunoassay (Monolisa HBeAg, Bio-Rad, France) as a reference test and quantified HBeAg concentration using dilutions of the WHO HBeAg standard. We related the findings to HBV DNA levels, and evaluated treatment eligibility using the TREAT-B score.<h4>Results</h4>Among 194 HBsAg positive patients, median age was 37 years, 42% were femaleand 26% were HIV co-infected. HBeAg prevalence was 47/194 (24%). The three RDTs showed diagnostic sensitivity of 28% (95% CI 16-43), 53% (38-68) and 72% (57-84) and specificity of 96-100% for detection of HBeAg. Overall inter-rater agreement κ statistic was high at 0.9-1.0. Sensitivity for identifying patients at the threshold where antiviral treatment is recommended for PMTCT, with HBV DNA > 200,000 IU/ml (39/194; 20%), was 22, 49 and 54% respectively. Using the RDTs in place of the reference HBeAg assay resulted in 3/43 (9%), 5/43 (12%) and 8/43 (19%) of patients meeting the TREAT-B treatment criteria being misclassified as ineligible for treatment. A relationship between HBeAg concentration and HBeAg detection by RDT was observed. A minimum HBeAg concentration of 2.2-3.1 log<sub>10</sub>IU/ml was required to yield a reactive RDT.<h4>Conclusions</h4>Commercially available HBeAg RDTs lack sufficient sensitivity to accurately classify hepatitis B patients in Malawi. This has implications for hepatitis B public health programs in sub-Saharan Africa. Alternative diagnostic assays are recommended.

Item Type: Article
Uncontrolled Keywords: Hepatitis B, Hepatitis B e antigens, Reagent kits, diagnostic, Sensitivity and specificity, Malawi, Africa south of the Sahara
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 16 Jun 2021 08:27
Last Modified: 18 Jan 2023 22:34
DOI: 10.1186/s12879-021-06134-3
Open Access URL: http://doi.org/10.1186/s12879-021-06134-3
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3126548