article · BMC Infectious Diseases
Diagnostic assays routinely used for hepatitis E virus in the Central African Republic show substantial performance limitations when compared to international reference standards. An evaluation of local tools, including a Diapro enzyme-linked immunosorbent assay and an in-house reverse transcription polymerase chain reaction, was conducted across cohorts of blood donors, people living with HIV, and jaundiced individuals. The comparison revealed that the local serological assay suffered from poor specificity, overestimating antibody prevalence, whilst the in-house molecular test had poor sensitivity, missing half of the viremic cases detected by a commercial reference assay. Adjusting the positivity threshold of the local serological test from 1 to 11.5 substantially improved performance, achieving nearly 98 percent specificity while maintaining 100 percent sensitivity. Prospective clinical studies are required to confirm this adjusted threshold before it can be applied in routine practice.
Inaccurate diagnostic tests can lead to misdiagnosed outbreaks, incorrect patient management, and flawed public health data. In settings where reference assays are unavailable or unaffordable, identifying assay limitations and adjusting diagnostic cut-offs helps healthcare providers accurately identify genuine hepatitis E infections without relying on costly replacement platforms.
This work informs diagnostic protocol optimisation for clinical laboratories and public health agencies managing viral hepatitis in low-resource settings. The findings could enable existing assay kits to be repurposed more accurately through adjusted diagnostic cut-offs rather than immediate equipment replacement. However, real-world adoption remains at an intermediate stage, as prospective clinical studies are explicitly required to validate the threshold before implementation.
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In the Central African Republic (CAR), data on the disease burden of hepatitis E virus (HEV) infection are limited despite recurrent epidemics. HEV is not routinely tested for in cases of elevated transaminases. Our objective was to evaluate the sensitivity and the specificity of serological and molecular tools currently available in CAR, against reference standards, using three cohorts. In total, 1695 samples consisting of patients living with HIV (PLHIV, n = 942), blood donors (BD, n = 401), and jaundiced patients who tested negative for yellow fever (YFn, n = 352) were initially tested in CAR using Diapro ELISA tests and an in-house RT-PCR. Subsequently, 361 samples with sufficient volumes ( PLHIV, n = 226, BD, n = 55, and YFn, n = 80) out of the 1695 were used with reference tests commonly used in developed countries: Wantai for serology and the commercial RealStar Altona test for RT-PCR. An initial analysis in CAR found positive IgM in 12.7% (120/942) PLHIV, 9.7% (39/401) BD and 40.3% (142/352) YFn patients. HEV RNA was not detected in PLHIV and BD and detected in only 51.4% (73/142) YFn patients. Subsequent analysis of a subset using reference tests revealed a lack of specificity of the IgM test and a low sensitivity of the in-house RT-PCR. HEV RNA detection with the commercial assay remained negative in PLHIV and BD, but almost doubled in YFn patients, 13.7 vs. 26.2%, and the frequency of positive IgM decreased from 47.7% to 7.6% with the reference test. In addition, among IgM Diapro-positive patients, elevated ALT (i.e., hepatitis) was mainly observed in viremic compared to non-viremic patients (75.0% vs. 19.6%, p = 0.0003), reinforcing the hypothesis of a specificity issue. However, after optimizing the positivity threshold of the Diapro IgM test (from 1 to 11.5), we achieved a specificity of close to 98% and a maintained a 100% sensitivity. The lack of specificity of the IgM assay routinely used in CAR, revealed by our assay comparison, could be overcome by optimizing threshold. Prospective studies are needed to validate this adjusted threshold before clinical implementation.
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DOI: 10.1186/s12879-026-14244-z
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