Detection of Specific ZIKV IgM in Travelers Using a Multiplexed Flavivirus Microsphere Immunoassay

Area of Science:

• Virology
• Immunology
• Infectious Diseases

Background:

• Zika virus (ZIKV) poses a significant global health challenge due to its widespread transmission.
• Accurate and timely diagnosis of acute ZIKV infection is often complicated, especially when reverse transcription-polymerase chain reaction (RT-PCR) is negative.

Purpose of the Study:

• To develop and validate a multiplexed flavivirus immunoglobulin M (IgM) microsphere immunoassay (flaviMIA).
• To enable differentiation of ZIKV-specific IgM from cross-reactive antibodies caused by other flavivirus infections in humans.

Main Methods:

• Development of a microsphere immunoassay (flaviMIA) utilizing 12 inactivated flavivirus antigens coupled to distinct beads.
• Interrogation of patient sera against these antigen-coupled beads to detect flavivirus-specific IgM antibodies.
• Validation of flaviMIA results against the gold standard ZIKV plaque reduction neutralization test (PRNT).

Main Results:

• The flaviMIA successfully differentiated ZIKV-specific IgM antibodies from those of other flaviviruses.
• Ninety-nine ZIKV infections were confirmed using a combination of RT-PCR and serological testing.
• Serological diagnosis was sometimes complicated by pre-existing antibodies from prior flavivirus exposure or vaccination.

Conclusions:

• The flaviMIA is a valuable tool for distinguishing ZIKV IgM from other flavivirus infections.
• Careful interpretation of serological results is crucial, especially in individuals with a history of flavivirus exposure or vaccination.
• Paired serum testing is essential for confirming seroconversion or differentiating recent from past ZIKV infections when RT-PCR is negative.