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

Journal article


Stockdale, A.J, Silungwe, N.M, Shawa, I, Kreuels, B, Gordon, M.A and Geretti, A.M 2021. Diagnostic performance evaluation of hepatitis B e antigen rapid diagnostic tests in Malawi. BMC Infectious Diseases. 21, p. 487. https://doi.org/10.1186/s12879-021-06134-3
AuthorsStockdale, A.J, Silungwe, N.M, Shawa, I, Kreuels, B, Gordon, M.A and Geretti, A.M
Abstract

Background
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.

Methods
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.

Results
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 log10IU/ml was required to yield a reactive RDT.

Conclusions
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.

KeywordsHepatitis B; Hepatitis B e antigens; Reagent kits; diagnostic; Sensitivity and specificity; Malawi; Africa south of the Sahara
Year2021
JournalBMC Infectious Diseases
Journal citation21, p. 487
PublisherSpringer Nature
ISSN 1471-2334
Digital Object Identifier (DOI)https://doi.org/10.1186/s12879-021-06134-3
Web address (URL)https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06134-3
https://pubmed.ncbi.nlm.nih.gov/34044776/
Output statusPublished
Publication dates
Online27 May 2021
Publication process dates
Accepted19 Apr 2021
Deposited08 Jun 2023
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