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

Disclosures

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

In This Article

Interpretation of Zika Virus Testing Results

For persons with suspected Zika virus disease, a positive rRT-PCR result confirms Zika virus infection, and no antibody testing is indicated.[3,4,7] However, because of the decline in the level of viremia over time and possible inaccuracy in reporting of dates of illness onset, a negative rRT-PCR result does not exclude Zika virus infection. Therefore, serum IgM antibody testing for Zika and dengue virus infections should be performed if rRT-PCR is negative. For serum specimens collected <7 days after onset of symptoms, the combination of a negative rRT-PCR result and negative IgM antibody testing suggests that there was no recent infection. However, a negative IgM antibody test, in the absence of rRT-PCR testing, might reflect specimen collection before development of detectable antibodies and does not rule out infection with the viruses for which testing was performed. For specimens collected from 7 days to 12 weeks after onset of symptoms, a negative IgM antibody result to both Zika and dengue viruses rules out recent infection with either virus.

If either the Zika or dengue virus IgM antibody testing yields positive, equivocal, or inconclusive results, PRNTs against Zika and dengue viruses (or other flaviviruses endemic to the region where exposure occurred) should be performed. A PRNT using a 90% cutoff value with a titer ≥10 (the typical starting serum dilution used to establish the presence of virus-specific neutralizing antibodies) against Zika virus, together with negative PRNTs (i.e., <10) against other flaviviruses is confirmatory for recent infection with Zika virus (Table). A PRNT titer ≥10 for both Zika and dengue virus (or another flavivirus) provides evidence of a recent infection with a flavivirus but precludes identification of the specific infecting virus. A negative PRNT against Zika virus in a specimen that is collected >7 days after illness onset rules out Zika virus infection. For specimens collected <7 days after onset of symptoms, the combination of a negative rRT-PCR and a PRNT titer <10 suggests that there was no infection with Zika virus. However, in the absence of rRT-PCR testing, a PRNT titer <10 might reflect specimen collection before development of detectable neutralizing antibodies and does not rule out infection with the viruses for which testing was conducted. Without confirmatory PRNTs, it is not possible to determine whether a presumptive positive IgM antibody result against Zika virus reflects recent flavivirus infection or a false-positive result.

For asymptomatic pregnant women residing in an area with local Zika virus transmission, IgM testing should be performed upon initiation of prenatal care, mid-second trimester, and if any fetal abnormalities are detected during ultrasound evaluation.[9] For asymptomatic pregnant women with a history of travel to areas where ongoing Zika virus transmission is occurring, Zika virus antibody testing should be performed on specimens collected 2–12 weeks post travel.[9] Results are interpreted as for symptomatic persons. If a serum specimen was collected >12 weeks after travel, although IgM might still be present, it is possible that antibody levels have dropped below the detectable limit. Performing routine PRNTs for women in this group is not recommended because any result other than a PRNT titer <10 for Zika virus could represent infection with or vaccination against a flavivirus at any time in the past and does not provide specific evidence of Zika virus exposure during pregnancy.

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