How is serologic testing used 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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Answer

Prompt diagnosis and laboratory confirmation of Zika virus infection is challenging.

Zika virus infection is diagnosed based on detection and isolation of Zika virus RNA from serum using nucleic acid amplification test (NAAT). The highest sensitivity of NAAT is during the initial week of illness, which is characterized by high viremia. After the initial week of illness, serological testing for virus-specific immunoglobin M (IgM) and neutralizing antibodies against Zika virus infection can be performed using enzyme-linked immunosorbent assay (ELISA). [18]  Serum IgM antibody testing should be performed if NAAT results are negative, regardless of when the specimen was collected.

In patients within 7 days of symptom onset, a positive serum NAAT for Zika is suggestive of presence of acute Zika virus infection. The NAAT should be repeated on newly extracted RNA from the same specimen to rule out false-positive test results.

In patients within 7 days of symptom onset, a negative serum NAAT and IgM antibody testing is suggestive of absence of Zika virus infection. 

In patients more than 7 days to 12 weeks from symptom onset, a negative IgM antibody testing is suggestive of absence of Zika virus infection.

In patients with indeterminate IgM antibody testing, repeat IgM testing or confirmatory PRNTs test should be performed. 

In patients with positive IgM antibody testing without positive NAAT, confirmatory PRNTs test should be performed. 

A 4-fold higher titer based on PRNT results might not differentiate anti-Zika virus antibodies from cross-reacting antibodies in all persons with previous infection or vaccination against a related flavivirus.

If IgM testing is positive for Zika or dengue virus or returns equivocal results, the following PRNT interpretations apply:

  • A PRNT titer ≥10 indicates evidence of infection with that specific flavivirus when the PRNT to the other flavivirus(es) tested is < 10.
  • A PRNT titer < 10 to a specific flavivirus indicates an absence of infection with that virus.
  • A positive PRNT result ( ≥10 to multiple flaviviruses) indicates evidence of recent flaviviral infection. 

The table below provides interpretation of dengue and Zika virus diagnostic testing results in nonpregnant and pregnant patients with a clinically compatible illness and risk for infection with both viruses. 

Diagnostic testing to interpret infection from Dengue and Zika virus. Courtesy of the Centers for Disease Control and Prevention (CDC).

Diagnostic testing to interpret infection from Den Diagnostic testing to interpret infection from Dengue and Zika virus. Courtesy of the Centers for Disease Control and Prevention (CDC).

Dengue and Zika virus diagnostic testing interpretation in nonpregnant and pregnant patients. Courtesy of the Centers for Disease Control and Prevention (CDC).

Dengue and Zika virus diagnostic testing interpret Dengue and Zika virus diagnostic testing interpretation in nonpregnant and pregnant patients. Courtesy of the Centers for Disease Control and Prevention (CDC).

Dengue and Zika virus testing recommendations for nonpregnant persons with a clinically compatible illness and risk for infection with both viruses. Courtesy of the Centers for Disease Control and Prevention (CDC).

Dengue and Zika virus testing recommendations for Dengue and Zika virus testing recommendations for nonpregnant persons with a clinically compatible illness and risk for infection with both viruses. Courtesy of the Centers for Disease Control and Prevention (CDC).

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