Interim Guidance for Interpretation of Zika Virus Antibody Test Results

Ingrid B. Rabe, MBChB; J. Erin Staples, MD, PhD; Julie Villanueva, PhD; Kimberly B. Hummel, PhD; Jeffrey A. Johnson, PhD; Laura Rose, MTS; Susan Hills, MBBS; Annemarie Wasley, ScD; Marc Fischer, MD; Ann M. Powers, PhD


Morbidity and Mortality Weekly Report. 2016;65(21) 

In This Article

Zika Virus Antibody Testing

An enzyme-linked immunosorbent assay (ELISA) can be used to detect anti-Zika virus IgM antibodies in serum or cerebrospinal fluid; however, the Zika virus IgM ELISA can provide false-positive results because of cross-reacting IgM antibodies against related flaviviruses or nonspecific reactivity. The plaque reduction neutralization test (PRNT) measures virus-specific neutralizing antibody titers and should be performed against various related flaviviruses to rule out false-positive ELISA results. In primary flavivirus infections (i.e., the first time a person is infected with a flavivirus), PRNT also can be used to identify the infecting virus. Usually, this is determined with a neutralizing antibody titer ≥4-fold higher than titers against cross-reacting flaviviruses. Based on earlier flavivirus research and limited preliminary data specific to Zika virus, the historical use of a 4-fold higher titer by PRNT might not discriminate between anti-Zika virus antibodies and cross-reacting antibodies in all persons who have been previously infected with or vaccinated against a related flavivirus (i.e., secondary flavivirus infection).[20,21] Because of the importance of appropriate clinical management of Zika and dengue virus infections, and the risk for adverse pregnancy outcomes in women infected with Zika virus during pregnancy, a conservative approach to the interpretation of antibody test results is now recommended to reduce the possibility of missing the diagnosis of either infection.[9,11]