CDC Updates Interim Guidance on Zika Testing and Interpretation

Diana Phillips

June 02, 2016

Because it is difficult to differentiate, via antibody testing, between Zika virus infection and infection from other flaviviruses, the Centers for Disease Control and Prevention (CDC) has revised its earlier recommendations regarding the timing of immunoglobulin M antibody testing and thresholds of plaque reduction neutralization test (PRNT). The new guidance, which expands on recommendations released by the agency in mid-April, are designed to reduce the possibility of missed diagnoses for both Zika and dengue infections.

At this time, PRNT is used to confirm a Zika virus diagnosis in patients with suspected infection and a negative real-time reverse transcription–polymerase chain reaction (rRT-PCR). However, cross-reactivity between Zika and other flaviviruses "can preclude identification of the specific infecting virus, especially when the person previously was infected with or vaccinated against a related flavivirus," such as dengue, medical epidemiologist Ingrid B. Rabe, MBChB, from the CDC, and colleagues explain in an interim guidance document published online May 31 in the Morbidity and Mortality Weekly Report. "This is important because the results of Zika and dengue virus testing will guide clinical management."

Recent research suggests that the historical use of a fourfold higher titer by PRNT might not discriminate between anti-Zika virus antibodies and cross-reacting antibodies in people who have been previously infected with or vaccinated against a related flavivirus. For this reason, the revised guidelines recommend the following serum antibody testing progression and interpretation for patients with suspected infection with a negative rRT-PCR and a positive or equivocal immunoglobulin M to Zika or dengue virus:

  • A PRNT titer higher than 10 should be interpreted as evidence of infection with that specific flavivirus infection when the PRNT to the other flavivirus or flaviviruses tested is lower than 10.

  • A PRNT titer lower than 10 to a specific flavivirus will be interpreted as no evidence of infection with that virus.

  • If PRNTs are positive (ie, 10 or higher) to multiple flaviviruses, this will be interpreted as evidence of recent infection with a flavivirus.

For patients in whom serologic testing is unable to determine the most recent infecting flavivirus, an epidemiologic link to a laboratory-confirmed case of dengue or Zika virus disease, together with data on the epidemiology of viruses known to be circulating in the area of exposure and clinical features of the infections, "can be considered in determining the most likely infecting virus," the authors write. "If serologic testing is inconclusive or there is evidence of recent infection with either Zika or dengue virus, patients should be clinically managed for both infections because they might have been infected with either virus."

The CDC will continue to update its guidance as additional rRT-PCR data become available, the authors write.

The authors have disclosed no relevant financial relationships.

Morb Mortal Wkly Rep. Published online May 31, 2016. Full text

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