Limitations of routine hepatitis E virus diagnosis in Central African Republic: a comparative evaluation of serological and molecular assays

Q: What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Hepatitis E virus (HEV) infection (n=1695). Intervention: Diapro HEV IgM ELISA vs. Wantai HEV IgM ELISA. Primary outcome: Specificity for identifying true acute HEV infections at the manufacturer's threshold.

Q: What does this research mean for the field?

The routinely used Diapro IgM assay for Hepatitis E virus in the Central African Republic lacks specificity, but optimizing its positivity threshold can achieve approximately 98% specificity while maintaining 100% sensitivity. Novelty: ClaimNovelty.METHODOLOGICAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Marina Prisca de Marguerite Nombot-Yazenguet; Amal Chaghouri; Alexandre Manirakiza; Lina Mouna; Philippe Armand Zemingui-Bembete; Benjamin Sélekon; A.M. Roque-Afonso; Narcisse Komas

doi:10.1186/s12879-026-14244-z

September 2, 2026BMC Infectious DiseasesOpen Access

Limitations of routine hepatitis E virus diagnosis in Central African Republic: a comparative evaluation of serological and molecular assays

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Key result

Optimizing the Diapro HEV IgM assay threshold improves specificity to ~98% for acute infections.

n=1,695

Why the study?

Data on HEV disease burden in CAR are limited despite recurrent epidemics, and HEV is not routinely tested for in cases of elevated transaminases.

Does optimizing the threshold of the Diapro HEV IgM test improve its specificity for diagnosing acute HEV infection in patients in the Central African Republic?

Key Points

To evaluate the sensitivity and specificity of routinely used serological and molecular assays for hepatitis E virus against international reference standards across three clinical cohorts in the Central African Republic.
Screened 1,695 clinical samples from people living with HIV (n = 942), blood donors (n = 401), and yellow fever-negative jaundiced patients (n = 352) using Diapro ELISA and an in-house RT-PCR assay.
Re-analyzed a subset of 361 samples (PLHIV n = 226, blood donors n = 55, jaundiced patients n = 80) using Wantai ELISA and RealStar Altona RT-PCR reference standards.
Reference testing in jaundiced patients decreased IgM positivity from 47.7% to 7.6% and doubled viral RNA detection from 13.7% to 26.2% relative to routine local assays.
Among IgM Diapro-positive patients, elevated alanine aminotransferase was significantly more frequent in viremic compared to non-viremic individuals (75.0% vs. 19.6%, p = 0.0003).
Increasing the Diapro IgM positivity threshold from 1.0 to 11.5 achieved approximately 98% specificity while maintaining 100% diagnostic sensitivity.

Study Design

Type

Cross-Sectional (n=1,695)

Structured PICO

Does optimizing the threshold of the Diapro HEV IgM test improve its specificity for diagnosing acute HEV infection in patients in the Central African Republic?

P

Population

1,695 individuals from the Central African Republic, comprising people living with HIV, blood donors, and yellow fever-negative jaundiced patients, evaluated for hepatitis E virus infection.

E

Exposure

Diapro HEV IgM and IgG ELISA tests and an in-house RT-PCR (routine tests in CAR)

C

Comparator

Wantai HEV IgM and IgG ELISA tests and RealStar Altona RT-PCR (reference tests)

O

Outcome

Sensitivity and specificity of serological and molecular tools for HEV diagnosissurrogate

Main Result

Absolute Event Rate: 50.4% vs 100%

Optimizing the positivity threshold of the routinely used Diapro HEV IgM assay in the Central African Republic significantly improves its specificity for diagnosing acute hepatitis E infection.

Limitations

The subset of 361 samples selected for advanced testing was enriched for Diapro IgM-positive cases, which may limit the generalizability of the performance estimates.
The use of HEV RNA as a reference standard to define acute HEV infections may miss some cases and lack sensitivity.
Small sample size for IgG avidity testing.
Subset of samples used for reference testing was selected based on available volume and enriched for Diapro IgM-positive samples, potentially affecting sensitivity and specificity estimates
Results cannot be directly generalized to the original clinical population without confirmation in an independent, unselected validation cohort
Small number of samples available for IgG avidity testing

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Answers are grounded in this paper and cite their sources.

Implication

Optimizing Diapro HEV IgM threshold may raise specificity in CAR; leaves open prospective validation before routine use.

Abstract

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.

Discussion

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Cite This Study

Nombot-Yazenguet et al. (2026) conducted a cross-sectional in Hepatitis E virus (HEV) infection (n=1,695). Diapro HEV IgM ELISA vs. Wantai HEV IgM ELISA was evaluated on Specificity for identifying true acute HEV infections at the manufacturer's threshold. The Diapro HEV IgM assay routinely used in the Central African Republic demonstrated a low specificity of 50.4% at the manufacturer's threshold, which improved to 97.6% after optimizing the positivity threshold to 11.5.

synapsesocial.com/papers/6a9a85b05d9e33f25c631054 https://doi.org/10.1186/s12879-026-14244-z

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Limitations of routine hepatitis E virus diagnosis in Central African Republic: a comparative evaluation of serological and molecular assays

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Limitations of routine hepatitis E virus diagnosis in Central African Republic: a comparative evaluation of serological and molecular assays

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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