Rapid Decline of Zika Virus IgM Antibodies Against the NS1 Protein in Imported Israeli Cases

Zika virus (ZIKV) infection during pregnancy may cause severe fetal abnormalities and therefore it is important to diagnose and distinguish between recent and past Zika infection. Serological diagnosis assays detect antibodies against the envelope protein, that suffer from high cross-reactivity. In addition, reports regarding long IgM persistence prevent its use in diagnosis of recent Zika infection. Following the Zika pandemic, a novel ELISA assay based on detection of IgM and IgG antibodies against Zika nonstructural 1 (NS1) protein was developed (NS1-IgM and NS1-IgG). Here, antibodies against NS1 were assessed in Israeli travelers diagnosed with Zika. NS1-IgM and NS1-IgG antibodies from 36 travelers diagnosed with ZIKV infection were detected as early as 5 days after symptom onset. However, while IgG levels were maintained for several months, IgM levels in all samples declined rapidly and by 31 days after symptom onset, no IgM positive samples were detected. Interval-censored survival analysis demonstrated 25%, 50%, and 75% decline in NS1-IgM levels in 29 days (95% CI: 22-34), 34 days (95% CI: 29-44), and 44 days (95% CI: 34-65), respectively. Our results suggest that IgM antibodies against ZIKV NS1 are short lived and can be used as a reliable marker for diagnosis of recent ZIKV infection.