Which lab testing is recommended in the workup of Zika virus infection?

Updated: Jun 30, 2021
  • Author: Bhagyashri D Navalkele, MD, MBBS; Chief Editor: Michael Stuart Bronze, MD  more...
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Confirmation of Zika virus infection based on diagnostic testing is challenging due to test sensitivity, specificity, and the epidemiological prevelance of Zika. 

Diagnostic testing of Zika virus (ZIKV) infection is based on molecular and serological methods. [32] Nucleic acid amplification testing (NAAT) is standard diagnostic testing for confirmation of acute infection. A negative NAAT for Zika virus does not rule out infection due to transient viremia during active infection. FDA has issued emergency use authorization on Zika NAAT testing to be performed on serum, plasma, whole blood, cerebrospinal fluid, urine or amniotic fluid. 

Serologic testing with immunoglobulin IgM can be performed as early as 7 days after symptom onset. A negative immunoglobulin IgM serologic test does not rule out infection due to lack of precise timing to detect presence of antibody response. Early or late antibody testing can result in false negative result due to lack of antibody development or waning of antibody response post infection, respectively. IgM antibody can remain positive for up to 12 weeks or longer in patients with history of Zika virus infection making it difficult to interpret recent or acute infection. False-positive IgM test result can occur due to cross-reactivity with other flaviviruses (eg, yellow fever, dengue, Japenese encephalitis, West Nile). Zika virus IgM antibody assays can be used on serum, plasma, whole blood, or cerebrospinal fluid.

In presence of concern for cross-reactivity with other flaviviruses, plaque reduction neutralization tests (PRNTs) provides quantitative virus-specific antibody titers for dengue, Zika, and other flaviviruses. CDC uses a PRNT with a 90% cutoff value titer ≥10 in serum and ≥2 in cerebrospinal fluid (the typical starting dilutions) to define positive specimens. A neutralizing antibody titer ≥4- fold higher titers compared to other flavivirus titers is considered diagnostic. Differentiation from other flaviviruses and late diagnosis of Zika virus infection more than 3-months from illness is possible with PRNT. Diagnostic testing using PRNT >1 year past illness is challenging as observed with 27% of persistent neutralizing antibody titers in patients in Florida with inability to distinguish between dengue and Zika.

The last locally-acquired Zika nucleic acid amplification tests (NAAT) confirmed case in the continental United States was in September 2017 and in the US territories was reported in May 2018. As the prevelance of Zika virus infection has declined, potential detection of false-positive tests results is likely. 

The WHO recommends using the Brighton criteria to diagnose Guillain-Barré syndrome. [33]

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