Diagnostic accuracy of three mpox lateral flow assays for antigen detection in the Democratic Republic of Congo and the United Kingdom

Abstract

Background: The ongoing outbreaks of mpox, the disease caused by monkeypox virus (MPXV) highlight the urgent need for a rapid and low cost MPXV diagnostic test to accurately detect and control mpox disease. In this study we assessed the diagnostic accuracy of three brands of rapid diagnostic tests for antigen detection (AgRDT) of MPXV. Methods: We estimated the clinical diagnostic performance of FlowFlex Monkeypox Virus Antigen Rapid Test (ACON Biotech Co., Ltd., Hangzhou, China), Ecotest Monkeypox Antigen Rapid Test (Assure Tech. Co., Ltd, Hangzhou, China), and STANDARDQ Monkeypox Ag Test (SD Biosensor, Inc. Republic of Korea) using skin lesion swabs (SS) and upper respiratory tract swabs (URS) from 68 participants in the Democratic Republic of the Congo (DRC) and from 16 in the United Kingdom (UK). The limit of detection (LOD) of the three AgRDT brands was evaluated using viral culture of the MPXV of the IIb lineage (EVAg, France). Findings: Although the specificity of the three AgRDT was high (100%), sensitivity was estimated as 15.79% (95% CI, 5.52-37.57%) for Flowflex and Ecotest and as 10.53% (95% CI, 2.94 to 31.39%) for StandardQ using SS in the DRC. The sensitivity was estimated as 0.00% (95% CI, 0.0 to 20.6%) among URS in the DRC. In the UK, the sensitivity of the three Ag-RDT was 0.00% among SS (95% CI, 0.0 to 12.7%) and among URS (95% CI, 0.0 to 21.5%). The LOD of all AgRDT was determined to be 1.0x 10e4 pfu/ml (1.3x1e05 copies/mL) using viral culture. Interpretation: None of the three AgRDT reached the target clinical sensitivity and thus we do not recommend these as diagnostic or screening tool for suspected mpox cases. Marked improvement in sensitivity are needed for these AgRDT prior adoption. The recommended analytical LOD in the WHO target product profile (TPP) is at 10e6 pfu/mL, being fulfilled by the three brands of AgRDTs suggesting that the analytical LOD stated in the TPP does not align with the desired clinical sensitivity. There remains an urgent need for accurate rapid AgRDTs for mpox diagnosis.