New CDC Interim Guidance Parses Zika Testing Recommendations

MMWR Provides Detailed Breakdown of How to Interpret Results

June 01, 2016 02:10 pm News Staff

The latest word to physicians from the CDC about the ongoing Zika virus outbreak: Don't necessarily believe what test results don't tell you.

[Gloved hand holding blood sample for Zika virus test]

On May 31, the agency issued an early release article in Morbidity and Mortality Weekly Report (MMWR) titled "Interim Guidance for Interpretation of Zika Virus Antibody Test Results"( cautioning that although a positive real-time reverse transcription-polymerase chain reaction (rRT-PCR) result in people with suspected Zika virus disease does, indeed, confirm Zika virus infection, a negative rRT-PCR result does not exclude infection and should be followed up with appropriate serologic testing.

"In these cases, immunoglobulin (Ig) M and neutralizing antibody testing can identify additional recent Zika virus infections," says the MMWR article.

"However," the report continues, "Zika virus antibody test results can be difficult to interpret because of cross-reactivity with other flaviviruses, which can preclude identification of the specific infecting virus, especially when the person previously was infected with or vaccinated against a related flavivirus."

Of particular concern is dengue virus, a flavivirus closely related to Zika virus, because patients with suspected dengue virus infection should be managed appropriately to minimize the risk for hemorrhagic complications, whereas pregnant women with laboratory evidence of a recent Zika virus infection should be evaluated and managed for possible adverse pregnancy outcomes and reported to the appropriate Zika virus pregnancy registry.

For this reason, the agency recommends additional testing to detect -- or rule out -- both viruses.

"An enzyme-linked immunosorbent assay (ELISA) can be used to detect anti-Zika virus IgM antibodies in serum or cerebrospinal fluid," the MMWR article notes, but adds that the Zika virus IgM ELISA can produce false-positive results because of cross-reacting IgM antibodies against related flaviviruses or other, 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," the article advises.

In addition to confirming presumptive positive Zika IgM results with PRNT titers against Zika, dengue and other flaviviruses to which the person might have been exposed, equivocal or inconclusive IgM results that are not resolved by retesting also should have PRNT titers performed to rule out a false-positive result.

Any positive or equivocal Zika or dengue IgM ELISA results should be reported to the state or local health department.

PRNT results may also be used to detect the specific infecting virus in people with primary flavivirus infection. Historically, a neutralizing antibody titer that is four-fold or higher than titers against cross-reacting flaviviruses has been thought to establish the virus responsible for infection.

Now, however, previous flavivirus research and limited preliminary data specific to Zika virus have called this belief into question, suggesting that a four-fold higher titer by PRNT may not be able to distinguish anti-Zika virus antibodies from cross-reacting antibodies in all individuals who have been previously infected with or vaccinated against a related flavivirus.

For this reason, a more conservative approach to interpreting PRNT results( is currently recommended to reduce the possibility of missing the diagnosis of either Zika or dengue virus infection.

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