Patients with suspected Zika virus infection who have negative real-time reverse transcription–polymerase chain reaction (rRT-PCR) test results are not automatically in the clear, officials at the Centers for Disease Control and Prevention warned in new guidelines on the interpretation of Zika virus antibody test results.

The CDC cautions that while a positive rRT-PCR test confirms a Zika virus infection, a negative test cannot exclude infection, because of Zika’s viremic similarity to other mosquito-borne flaviviruses such as dengue, West Nile, Japanese encephalitis, and yellow fever. In cases of a negative rRT-PCR results, patients should undergo immunoglobulin M (IgM) antibody testing; IgM testing should be done on any patient with a negative rRT-PCR test, regardless of the day on which the sample was originally collected. For confirmation of a positive, equivocal, or inconclusive result on the IgM test, patients will require a plaque reduction neutralization test (PRNT) as well.

“Recent evidence suggests that a 4-fold higher titer by PRNT might not discriminate between anti-Zika virus antibodies and crossreacting 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,” CDC officials wrote. The report is in the May 31 issue of Morbidity and Mortality Weekly Report ( doi: ).

Any PRNT titer greater than 10 should be interpreted as proof of infection with the specific tested flavivirus, if the titer is less than 10 for other tested flaviviruses. If multiple flaviviruses are tested and all result in a titer of 10 or greater, than the result is proof of a recent infection with a flavivirus, not Zika specifically. And if the PRNT titer is less than 10 for a specific flavivirus, then that should be interpreted as there being no evidence of infection with that virus.

The CDC urges health care providers who have patients suspected of Zika virus infection to consult with their local and state health agencies to properly interpret any test results. Any pregnant women who have a confirmed Zika virus infection should be reported to the U.S. Zika Pregnancy Registry or the Puerto Rico Zika Active Pregnancy Surveillance System, with continued monitoring for any possible adverse effects to the pregnancy.

“If serologic testing indicates recent flavivirus infection that could be caused by either Zika or dengue virus, patients should be clinically managed for both infections because they might have been infected with either virus,” the CDC cautioned.


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