An ad-hoc session was held at the Society for Maternal-Fetal Medicine (SMFM) 36th
Annual Pregnancy Meeting to share knowledge and discuss clinical best
practices for optimizing maternal and perinatal health in the face of
the recent Zika virusepidemic.
Zika is a mosquito-borne single-stranded RNA Flavivirus,
related to dengue virus. According to the CDC, only 1 in 5 people
infected with Zika virus will become symptomatic. Characteristic
clinical findings are an acute onset of fever with maculopapular rash,
arthralgias, or conjunctivitis, usually within 1-2 weeks of infection.1 Other
reported symptoms include a headache or myalgias. The illness is
usually mild, with symptoms lasting for several days to a week. The
actual Zika viral infection rate, incidence of maternal-fetal
transmission, immune response, and any causal relationship to fetal
microcephaly, abnormal brain development, or other adverse pregnancy
outcome, are not currently known. Moreover, the CDC is uncertain on the
sensitivity and specificity of currently available serologic testing
(IgM, no IgG testing available). Current countries with reported active
Zika virus transmission are shown in Figure 1, although CDC cautions
that this map is routinely updated and should be rechecked frequently.
Current guidelines call for at least baseline sonographic screening for
fetal anomalies in general and for head and brain development
specifically for pregnant women with exposure in Zika-endemic areas.
Along with the potential need to discuss alternative differential
diagnoses to explain any reported symptoms or findings, it is prudent
and recommended to refer patients with concerns about Zika exposure or
Zika-associated fetal issues to an MFM subspecialist with specific
knowledge in this area whenever feasible. Subspecialists will then work
directly with local and state health departments to coordinate testing
and interpretation of results. A listing of state and territorial health
departments can be found at http://www.cdc.gov/mmwr/international/relres.html.
Zika testing currently is being performed almost exclusively at the
CDC, but with the approval of a local health authority, many states are
actively developing programs for screening and testing exposed pregnant
women on a more local level.
Appropriate clinical scenarios requiring serum testing are listed below
in the case studies. When sent, Zika serology IgM testing will be the
most commonly run assay, with results reported as a titer, interpreted
as “likely positive,” “inconclusive,” or “likely negative.” If a patient
has been symptomatic in the preceding week (and only then), Zika RNA
testing by reverse-transcriptase PCR (RT-PCR) will be performed. This
emphasizes the importance of taking and providing a detailed travel and
symptom history to the lab performing the testing. The sensitivity of
the IgM assay is currently unknown and is being evaluated. This serum
sample should also be tested for other common flaviviruses endemic to
the area, such as dengue and chikungunya, but these tests must be
ordered separately by the provider through commercial labs. A history
should be obtained for prior exposure (vaccination or infection) to
dengue, yellow fever, Japanese encephalitis or West Nile viruses, as
these antibodies may cross-react with Zika testing. A positive Zika
virus IgM should have a confirmatory neutralizing antibody titer ≥4-fold
higher than dengue virus-neutralizing antibody titers in serum by
plaque-reduction neutralization testing. Testing would be considered
inconclusive if Zika virus-neutralizing antibody titers are < 4-fold
higher than dengue virus-neutralizing antibody titers.
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