Wednesday, June 01, 2016

MMWR: Interim Guidance for Interpretation of Zika Virus Antibody Test Results

Credit CDC


Although the Zika virus wasn't detected in Brazil until May of last year, it had obviously been circulating - undetected - for many months.  The same is likely true for many of the countries that have just recently reported cases.

With symptoms similar to mild Dengue or Chikungunya  (both of which are endemic in South America) - and until recently, no specific Zika test available - it has been easy for the virus to quietly make inroads into new regions.

It has only been in the past 6 months that rRT-PCR testing has become available, but it has a limited window of reliability, and is generally only useful during the first week of illness.

IgM and plaque reduction neutralization test (PRNT) testing can extend that diagnostic window, but can cross react with other flavivirus infections (Dengue, yellow fever), making interpretation difficult. 

While Zika testing continues to evolve, the CDC has released new interim guidance on interpreting these tests.

Media Statement

For Immediate Release: Tuesday, May 31, 2016
Today, CDC published interim guidance for Zika virus antibody testing and interpretation of results. Because of the differences in recommended clinical management of Zika and dengue virus infections, and the risk of adverse pregnancy outcomes in women infected with Zika virus during pregnancy, a conservative approach to the interpretation of antibody test results is necessary to reduce the possibility of a missed diagnosis of either infections. The timing of IgM antibody testing and the thresholds of plaque reduction neutralization test (PRNT) have changed.
  • Serum IgM antibody test should be performed if real-time reverse transcription polymerase chain reaction (rRT-PCR) results are negative regardless of the day the specimen was collected.
  • 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).
  • Together with a positive or equivocal IgM to Zika or dengue virus:
    • A PRNT titer >10 will be interpreted as a evidence of infection with that specific flavivirus infection when the PRNT to the other flavivirus(es) tested is < 10.
    • A PRNT titer < 10 to a specific flavivirus will be interpreted as a no evidence of infection with  that virus.
    • If PRNTs are positive i.e.,  >10 to multiple flaviviruses, this will be interpreted as evidence of recent infection with a flavivirus.
CDC will continue to update this guidance as these data are preliminary and as additional rRT-PCR data becomes available. For more information about this guidance, visit Interim Guidance for Interpretation of Zika Virus Antibody Test Results.

Due to its length and technical nature, I've only posted the link and summary below.  Health care professionals and other interested parties will want to read the MMWR in its entirety.

Ingrid B. Rabe, MBChB1; J. Erin Staples, MD, PhD1; Julie Villanueva, PhD1; Kimberly B. Hummel, PhD1; Jeffrey A. Johnson, PhD1; Laura Rose; MTS1; Susan Hills, MBBS1; Annemarie Wasley, ScD1; Marc Fischer, MD1; Ann M. Powers, PhD1
(Continue . . . )

What is already known about this topic?

Zika virus is a mosquito-borne flavivirus closely related to dengue, West Nile, Japanese encephalitis, and yellow fever viruses. Diagnostic testing for Zika virus infection can be accomplished using both molecular and serologic methods. However, results of Zika virus antibody testing can be difficult to interpret because of cross-reactivity with related flaviviruses, which can preclude identification of the specific infecting virus, especially when the person previously was infected with or vaccinated against a related flavivirus.

What is added by this report?

For persons with suspected Zika virus disease, a positive real-time reverse transcription–polymerase chain reaction (rRT-PCR) result confirms Zika virus infection, but a negative result does not exclude infection. In these cases, antibody testing can identify additional recent Zika virus infections. If immunoglobulin (Ig) M test results are positive, equivocal, or inconclusive, performing a plaque reduction neutralization test (PRNT) is needed to confirm the diagnosis. However, recent evidence suggests that 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. Thus, a more conservative approach to interpreting PRNT results is now recommended to reduce the possibility of missing the diagnosis of either Zika or dengue virus infection.

What are the implications for public health practice?

All patients with clinically suspected dengue should receive appropriate management to reduce the risk for hemorrhagic medical complications. Pregnant women with laboratory evidence of a recent Zika virus infection or flavivirus infection should be evaluated and managed for possible adverse pregnancy outcomes and reported to the appropriate Zika virus pregnancy registry. Health care providers should consult with state or local public health authorities for assistance in interpreting test results.

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