Impact of Non-Dengue Flavivirus Immunity on Dengue IgG ELISA Specificity in Cambodia

Overview

This study evaluated the specificity of the PanBio dengue virus IgG ELISA in Cambodian children and found a significantly lower specificity (58%) than previously reported. Cross-reactive immunity to non-dengue flaviviruses, particularly West Nile virus, contributed to false-positive results. Adjusting the ELISA cut point improved test accuracy in this flavivirus co-circulation setting.

Background

Dengue virus (DENV) seroprevalence studies are critical for surveillance and vaccine eligibility determination. However, co-circulation of multiple flaviviruses such as Japanese encephalitis virus (JEV), West Nile virus (WNV), and Zika virus (ZIKV), along with vaccination campaigns, complicate serological testing due to antibody cross-reactivity. The PanBio indirect DENV IgG ELISA is widely used for detecting DENV immunity but may yield false positives in populations exposed to other flaviviruses. Accurate serological assays are essential to guide dengue vaccination strategies and public health interventions, especially in endemic regions like Cambodia.

Data Highlights

Key Findings

• The PanBio dengue IgG ELISA demonstrated a specificity of 58% in Cambodian children, substantially lower than prior reports of 93%–100%.
• Nearly half (46%) of false-positive ELISA results had neutralizing antibodies against non-dengue flaviviruses, including ZIKV, JEV, and WNV.
• Notably, 14% of false positives had neutralizing antibodies against West Nile virus, indicating unrecognized WNV exposure in Cambodia.
• Adjusting the ELISA cut point to a higher threshold improved test accuracy in this population with flavivirus co-circulation.
• These findings highlight the impact of flavivirus cross-reactivity on dengue serosurveillance and vaccine eligibility assessments.

Clinical Implications

Clinicians and public health authorities should consider the potential for cross-reactive antibodies from non-dengue flaviviruses when interpreting dengue IgG ELISA results, especially in regions with multiple circulating flaviviruses. Awareness of West Nile virus circulation in Cambodia is important for differential diagnosis and surveillance. Adjusting ELISA cut points may enhance diagnostic specificity and improve vaccine eligibility decisions.

Conclusion

Immunity to non-dengue flaviviruses significantly reduces the specificity of dengue IgG ELISA assays in endemic settings with flavivirus co-circulation. Tailoring serological cut points and recognizing local flavivirus epidemiology are essential for accurate dengue surveillance and vaccination strategies.

References

1. Author/Source/Year -- Influence of Immunity to Non-Dengue Flaviviruses on the Specificity of Dengue Virus IgG ELISA in Cambodia