Interim Guidance for Interpretation of Zika Virus Antibody Test Results

Abstract

Zika virus is a single-stranded RNA virus in the genus Flavivirus and is closely related to dengue, West Nile, Japanese encephalitis, and yellow fever viruses (1,2). Among flaviviruses, Zika and dengue virus share similar symptoms of infection, transmission cycles, and geographic distribution. Diagnostic testing for Zika virus infection can be accomplished using both molecular and serologic methods. For persons with suspected Zika virus disease, a positive real-time reverse transcription-polymerase chain reaction (rRT-PCR) result confirms Zika virus infection, but a negative rRT-PCR result does not exclude infection (3-7). In these cases, immunoglobulin (Ig) M and neutralizing antibody testing can identify additional recent Zika virus infections (6,7). However, Zika virus antibody test results can be difficult to interpret because of cross-reactivity with other flaviviruses, which can preclude identification of the specific infecting virus, especially when the person previously was infected with or vaccinated against a related flavivirus (8). This is important because the results of Zika and dengue virus testing will guide clinical management. Pregnant women with laboratory evidence of Zika virus infection should be evaluated and managed for possible adverse pregnancy outcomes and be reported to the U.S. Zika Pregnancy Registry or the Puerto Rico Zika Active Pregnancy Surveillance System for clinical follow-up (9,10). All patients with clinically suspected dengue should have proper management to reduce the risk for hemorrhage and shock (11). If serologic testing indicates recent flavivirus infection that could be caused by either Zika or dengue virus, patients should be clinically managed for both infections because they might have been infected with either virus.

Association between Zika virus infection and microcephaly in Brazil, January to May, 2016: preliminary report of a case-control study

“…31 All positive results for Zika virus-specifi c IgM were confi rmed by testing for neutralising antibodies. This approach is recommended by CDC guidelines 32 to rule out false-positive results.…”

Manifestaciones neurológicas de la infección por el virus zika

“…As GBS is often an immune-mediated response to the CNS initiated by a bacterial or viral infection, detection of Zika virus in CSF is not necessary, but is more likely if neurologic symptoms start during the prodromal stage with systemic symptoms, such as rash and arthralgia. Current assays can directly detect Zika virus RNA or the immune response developed by the immune system against the Zika virus (Table 3) (17) .…”

“…The plaque reduction neutralization test (PRNT) allows discrimination of antiZika virus antibodies from other potential cross-reacting antibodies due to other flavivirus infections. Although a PRNT ≥ 4-fold titer is typically used to confirm an infection, the U.S. Centers for Disease Control and Prevention has suggested a more conservative approach using a titer of ≥ 10 against Zika virus and PRNT < 10 against other flaviviruses to confirm infection (17) .…”

One year after the Zika virus outbreak in Brazil: from hypotheses to evidence

“…In pregnant women and in severe cases, it is recommended that positive IgM serology be confirmed by the more specific plaque reduction neutralization test (57) .…”