Zika Virus Workup

Updated: Oct 12, 2017
  • Author: Bhagyashri D Navalkele, MD, MBBS; Chief Editor: Michael Stuart Bronze, MD  more...
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Workup

Approach Considerations

Diagnosis of Zika virus (ZIKV) infection is typically based on serologic testing, although the CDC now recommends urine testing. The CDC has issued interim guidance on Zika virus antibody testing and result interpretation. See Serologic Testing (below).

Urine can be tested via real-time reverse transcription-polymerase chain reaction (rRT-PCR) using samples collected less than 2 weeks following symptom onset. Urine should be tested in conjunction with serum if specimens were obtained less than one week following symptom onset. A positive result on either test confirms Zika virus infection.

The viral level may be higher in urine and for a longer duration than in serum. In Florida, among 55 patients in whom travel-related Zika infection was suspected, urine and serum samples were collected within five days of symptom onset. Fifty-six percent of serum samples tested positive for Zika RNA, while 95% of urine samples tested positive. At day six and afterward, Zika RNA was no longer found in serum, while urine specimens continued to return positive results until day twenty. [20]

All pregnant women should be screened for a travel history to Zika virus–affected areas (see below). [21]

The WHO recommends using the Brighton criteria to diagnose Guillain-Barré syndrome. [22]

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Laboratory Studies

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

Serologic Testing

Zika virus infection is diagnosed based on detection and isolation of Zika virus RNA from serum using reverse-transcriptase polymerase chain reaction (RT-PCR). The highest sensitivity of PCR testing 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). [16] The utility of this test is limited owing to cross-reactivity with other flaviviruses (dengue and yellow fever). Antibodies directed toward individual flaviviruses can be measured using plaque reduction neutralization tests (PRNTs) to facilitate accurate diagnosis of primary flavivirus infection.

The CDC has issued interim guidance on Zika virus antibody testing and interpretation, as follows: [23]

Serum IgM testing should be performed if real-time RT-PCR (rRT-PCR) results are negative, regardless of when the specimen was collected.

A 4-fold higher titer based on plaque reduction neutralization test (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. 

Urine Testing

Urine can be tested via real-time reverse transcription-polymerase chain reaction (rRT-PCR) using samples collected less than 2 weeks following symptom onset. Urine should be tested in conjunction with serum if specimens were obtained less than one week following symptom onset. A positive result on either test confirms Zika virus infection. [20]

Testing for Zika Virus Infection in Pregnant Women

All pregnant women should be screened for a travel history to Zika virus–affected areas. [21] Symptomatic pregnant women with a positive travel history should undergo RT-PCR or serological testing for detection of Zika virus infection. See the flowchart below.

Testing algorithm for pregnant women with history Testing algorithm for pregnant women with history of travel to areas with active Zika virus transmission. Courtesy of the Centers for Disease Control and Prevention (CDC).

Regardless of symptoms and test results, all pregnant women with a history of travel to an area of active Zika virus infection should undergo fetal ultrasonography to evaluate for microcephaly or intracranial calcifications. [21] Detection of a fetal anomaly should be followed by amniocentesis for evaluation of intrauterine Zika virus infection. The sensitivity and specificity of amniocentesis for determination of congenital infection and prediction of fetal abnormality is unknown. [21]

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Imaging Studies

All pregnant women with a history of travel to an area of active Zika virus infection should undergo fetal ultrasonography to evaluate for microcephaly or intracranial calcifications. [21] Detection of a fetal anomaly should be followed by amniocentesis for evaluation of intrauterine Zika virus infection. The sensitivity and specificity of amniocentesis for determination of congenital infection and prediction of fetal abnormality is unknown. [21]

The WHO recommends that newborns with severe microcephaly (more than 3 standard deviations below the mean) undergo neuroimaging. [18]

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Procedures

Detection of a fetal anomaly should be followed by amniocentesis for evaluation of intrauterine Zika virus infection. The sensitivity and specificity of amniocentesis for determination of congenital infection and prediction of fetal abnormality is unknown. [21]

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