Policy Guidelines
Guidelines and Recommendations
Centers for Disease Control and Prevention (CDC)
The CDC states that Zika testing is recommended only for certain people as follows (CDC, 2016) (CDC, 2017):
CDC Testing Guidance for Zika Virus recommends testing anyone with possible Zika virus exposure which includes living in, traveling to, or having unprotected sex with someone who lives in or traveled to an area with risk of Zika. In addition, CDC recommends testing symptomatic pregnant women with possible Zika virus exposure, asymptomatic pregnant women with ongoing possible Zika virus exposure and pregnant women with possible Zika virus exposure who have a fetus with prenatal ultrasound findings consistent with congenital Zika virus infection. The asymptomatic pregnant women with recent possible but not ongoing exposure to Zika virus population is classified as a consider for testing category. CDC does not recommend Zika virus testing for non-pregnant asymptomatic individuals and for preconception screening.
Zika Virus Laboratory Testing
The definitive laboratory diagnosis of Zika virus requires multiple assays and sample types. There are several types of Zika Virus tests available such as RNA NAT (nucleic acid testing), Trioplex Real-time RT-PCR Assay, Serologic test for Zika Virus, Zika MAC-ELISA and Plaque Reduction Neutralization Test (PRNT). They all have their limitations and are recommended or not recommended to use depending on population tested.
Laboratory testing for Zika virus has a number of limitations. Zika virus RNA is only transiently present in body fluids; thus, negative nucleic acid testing (NAT) does not rule out infection.
Serologic testing is affected by timing of sample collection: a negative immunoglobulin M (IgM) serologic test result does not rule out infection because the serum specimen might have been collected before the development of IgM antibodies, or after these antibodies have waned. Conversely, IgM antibodies might be detectable for months after the initial infection; for pregnant women, this can make it difficult to determine if infection occurred before or during a current pregnancy. In addition, cross-reactivity of the Zika virus IgM antibody tests with other flaviviruses can result in a false-positive test result, especially in persons previously infected with or vaccinated against a related flavivirus, further complicating interpretation. Limitations of Zika virus IgM antibody assays that were approved under an Emergency Use Authorization have been recognized; both false-positive and false-negative test results have occurred.
Updated Guidance for Testing of Symptomatic Pregnant Women with Possible Zika virus Exposure
Given the decreasing prevalence of Zika virus infection cases in the Americas and emerging data regarding Zika virus laboratory testing, on July 24, 2017, CDC published updated guidance for testing of pregnant women with possible Zika virus exposure (2). Zika virus NAT testing should be offered as part of routine obstetric care to asymptomatic pregnant women with ongoing possible Zika virus exposure (residing in or frequently traveling to an area with risk for Zika virus transmission); serologic testing is no longer routinely recommended because of the limitations of IgM tests, specifically the potential persistence of IgM antibodies from an infection before conception and the potential for false-positive results. Zika virus testing is not routinely recommended for asymptomatic pregnant women who have possible recent, but not ongoing, Zika virus exposure; however, guidance might vary among jurisdictions (2).
Updated Recommendations for Diagnosis, Clinical Evaluation, and Management of Infants with Clinical Findings Consistent with Congenital Zika Syndrome Born to Mothers with Possible Zika
Virus Exposure in Pregnancy
Zika virus testing is recommended for infants with clinical findings consistent with congenital Zika syndrome and possible maternal Zika virus exposure during pregnancy, regardless of maternal testing results. Testing CSF for Zika virus RNA and Zika virus IgM antibodies should be considered, especially if serum and urine testing are negative and another etiology has not been identified.
Updated Recommendations for Diagnosis, Clinical Evaluation, and Management of Infants without Clinical Findings Consistent with Congenital Zika Syndrome Born to Mothers with Laboratory Evidence of Possible Zika Virus Infection During Pregnancy Laboratory testing. Zika virus testing is recommended for infants without clinical findings consistent with congenital Zika syndrome born to mothers with laboratory evidence of possible Zika virus infection during pregnancy
Updated Recommendations for Diagnosis, Clinical Evaluation, and Management of Infants without Clinical Findings Consistent with Congenital Zika Syndrome Born to Mothers with Possible Zika Virus Exposure in Pregnancy but without Laboratory Evidence of Possible Zika
Virus Infection During Pregnancy
This heterogeneous group includes mothers who were never tested during pregnancy as well as those whose test result could have been negative because of issues related to timing or sensitivity and specificity of the test. Because the latter issues are not easily discerned, all mothers with possible exposure to Zika virus during pregnancy who do not have laboratory evidence of possible Zika virus infection, including those who tested negative with currently available technology, should be considered in this group.
Laboratory testing. Laboratory testing for congenital Zika virus infection is not routinely recommended for infants born to mothers in this category based on the unknown risk for infection; the lower likelihood of congenital Zika virus infection as a result of the declining prevalence of Zika virus infection; and limitations of infant laboratory testing. If abnormal findings are identified, these infants should receive further evaluation, including evaluation and testing for congenital Zika virus infection.
CDC Guidelines for Diagnostic Tests for Zika Virus include (CDC, 2016):
- Molecular Test for Zika Virus – RNA NAT (nucleic acid testing) for symptomatic individuals within the first two weeks after symptom onset and for asymptomatic pregnant women who have traveled to areas with active Zika virus transmission. RNA NAT testing is also indicated for pregnant women who present for care ≥ 2 weeks after exposure and have been found to be IgM positive. A positive RNA NAT result confirms Zika virus infection and no additional testing is indicated, but a negative RNA NAT result does not exclude Zika virus infection and should be followed up with IgM antibody (serological) testing.
- Trioplex Real-time RT-PCR Assay The Trioplex rRT-PCR is a laboratory test designed to detect Zika virus, dengue virus, and chikungunya virus RNA. The Food and Drug Administration (FDA) has not cleared or approved this test. However, FDA has authorized the use of this test under an Emergency Use Authorization (EUA). Serologic Test for Zika Virus Zika virus-specific IgM and neutralizing antibodies typically develop toward the end of the first week of illness. IgM levels are variable, but generally are positive starting near day four post onset of symptoms and continuing for 12 weeks Therefore, if RNA NAT is negative on serum and urine, serum IgM antibody testing for Zika, dengue, and chikungunya virus infections should be performed. In addition, serum samples collected >=14 days after symptom onset, with no earlier samples collected, should be tested for anti-Zika virus, anti-dengue virus, and anti-chikungunya virus IgM antibodies.
- Zika MAC-ELISA The Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA) is used for the qualitative detection of Zika virus IgM antibodies in serum or cerebrospinal fluid; however, due to cross-reaction with other flaviviruses and possible nonspecific reactivity, results may be difficult to interpret.
- Plaque Reduction Neutralization Test (PRNT) – Samples with presumptive positive, equivocal or inconclusive IgM antibody test result should be confirmed by PRNT, which measures virus-specific neutralizing antibodies to Zika virus and other endemic flaviviruses. PRNT must be conducted by CDC or a laboratory qualified by CDC.
The American College of Obstetricians and Gynecologists (ACOG) and Society of Maternal Fetal Medicine (SMFM)
In April 2017, ACOG and SMFM updated the practice advisory on Zika Virus. It recommends that Zika Virus testing should be done in the following situations:
- Non-pregnant women and all men with Zika virus exposure and symptoms consistent with Zika virus.
- Non-pregnant women and all men with Zika virus exposure but without symptoms consistent with Zika virus exposure.
- Pregnant women with Zika virus exposure should be tested regardless of symptom status.
ACOG and SMFM state that all pregnant women should be assessed for possible Zika virus exposure at each prenatal care visit. The practice advisory noted that “routine Zika virus testing is not currently recommended for women or men with possible Zika virus exposure without clinical illness who are attempting pregnancy”. It further stated that “testing of specimens to assess risk for sexual transmission is currently not recommended.”
