Updated guidelines released by the Centers for Disease Control and Prevention outline how to diagnose suspected cases of Zika virus infection among pregnant women based on how quickly they present with symptoms.
The guidance was updated in light of “the emerging data indicating that Zika virus RNA can be detected for prolonged periods in some pregnant women,” the CDC wrote in the July 25 issue of the Morbidity and Mortality Weekly Report (doi: 10.15585/mmwr.mm6529e1).
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All pregnant women should be assessed for Zika virus at each of their prenatal care visits, regardless of their recent travel history or exposure to mosquitoes, by being evaluated for signs and symptoms of infection, such as fever, rash, and arthralgia. From there, management can take one of two directions.
The first direction involves women who are tested within 2 weeks of either symptom onset, or their suspected exposure to the virus. Pregnant women who are asymptomatic and do not live in an area with an ongoing Zika virus outbreak, as well as women who are symptomatic, should have their serum and urine analyzed using a real-time reverse transcription–polymerase chain reaction (rRT-PCR) test. If the result of this test is positive, it should be considered as confirmation that the woman has a “recent Zika virus infection.”
However, if the test results are negative, symptomatic women should undergo immunoglobin M testing for both Zika virus and dengue virus, while asymptomatic women should undergo just Zika virus IgM testing within 2-12 weeks of the possible exposure. In either case, if the tests come back negative, then the patient can be definitively cleared of any recent Zika virus infection. However, if either the Zika virus or dengue virus tests are positive or equivocal, then there is a “presumptive recent Zika virus or dengue virus or Flavivirus infection” in the woman, at which point plaque reduction neutralization testing (PRNT) must be conducted.
The second direction for management involves pregnant women who are initially tested within 2-12 weeks of either symptom onset or suspected exposure to the virus. Asymptomatic women who do not live in an area with active Zika virus transmission, or do live in an area with ongoing Zika virus cases but are already in the first or second trimester of their pregnancy – along with any women who are symptomatic – should have their serum analyzed through IgM testing for both Zika virus and dengue virus.
If both results are negative, then there is no Zika virus infection. If the Zika virus test is negative but the dengue virus test is either positive or equivocal, the woman has a “presumptive dengue virus infection” and should undergo PRNT. If the Zika virus test is either positive or equivocal, then the woman has a “presumptive recent Zika virus or Flavivirus infection,” regardless of the dengue virus IgM result. In the latter case, the next step is to conduct a reflex Zika virus rRT-PCR test on both serum and urine. A negative result on the serum test should be followed by PRNT; a positive result should be taken as proof of a “recent Zika virus infection.”
For any diagnostic chain that ends with a PRNT, the results of that test can be interpreted in one of three ways. If the Zika virus PRNT result is at least 10 and the dengue virus result is less than 10, then there is a recent Zika virus infection. If both the Zika virus and dengue virus PRNT results are 10 or greater, than there is a Flavivirus infection, but the specific one cannot be determined. Finally, if both results are less than 10, then there is no evidence of a recent Zika virus infection.
“For symptomatic and asymptomatic pregnant women with possible Zika virus exposure who seek care [more than] 12 weeks after symptom onset or possible exposure, IgM antibody testing might be considered,” the CDC wrote. “If fetal abnormalities are present, rRT-PCR testing should also be performed on maternal serum and urine [but] a negative IgM antibody test or rRT-PCR result [more than] 12 weeks after symptom onset or possible exposure does not rule out recent Zika virus infection.”
For pregnant women with a diagnosis of a confirmed or presumptive Flavivirus infection, regardless of whether it’s specifically Zika virus or not, the CDC recommends getting serial ultrasounds every 3-4 weeks during pregnancy in order to monitor the fetus’s development, while “decisions regarding amniocentesis should be individualized for each clinical circumstance.” After the child’s birth, rRT-PCR should be conducted on the child’s cord blood and serum; Zika virus and dengue virus IgM are also recommended.