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Hot Topics: Zika Virus and Allografts, Part 1

Background

Since the Zika outbreak first began in Brazil in late 2015,1 its spread has been of significant concern to the medical community. First identified due to the significant rise in microcephaly among newborns in Brazil, Zika infection has also been associated with other major birth defects including neural tube defects, eye abnormalities, brain abnormalities, and central nervous system dysfunction unrelated to microcephaly.

Studies have estimated the rate of birth defects among completed pregnancies with Zika infections to be 1 in 20, or 5%, with a higher risk of birth defects when infection occurs earlier in pregnancy.2 In addition to complications during pregnancy, Zika infection also has been shown to cause Guillain-Barré syndrome in adults and may result in other lasting neurological complications.3

Spread in the United States

The Zika virus is spread by two species of mosquito, Aedes albopictus and Aedes aegypti. Both of these vectors are native to the United States, but they are at the northernmost range of their territory and are therefore not found in every state. Ten states do not fall into the estimated range of either vector species and are therefore believed to be free of any native Zika transmission risk. The other states, as seen in the maps below, have at least small areas of potential mosquito transmission, though only Florida and Texas are known to have had local mosquito transmission of Zika to date.

Estimated range of Aedes albopictus and Aedes aegypti in the United States, CDC 2016*
*Maps are not meant to represent risk for spread of disease.

Zika became a nationally notifiable disease in 2016, which mandates reporting of cases to the CDC.4 As a result, there is very good surveillance of the disease in symptomatic patients, though many adults infected with Zika may remain asymptomatic or have only mild, flu-like symptoms.5

In 2016, the United States had 5,102 symptomatic cases of Zika reported to the CDC. Of these, only 224 were acquired through domestic mosquito-borne transmission (218 in Florida and 6 in Texas).4 There is a significantly declining prevalence of Zika virus disease in both North and South America, primarily due to the success of robust mosquito control measures and the public’s attention to preventing exposure.2

As of July 26, 2017, the United States has only had 181 symptomatic cases of Zika reported to the CDC for 2017. None were due to domestic transmission.6 It is believed that all prior areas of local mosquito transmission have been eliminated within the United States.

Clinical Testing for the Zika Virus

No diagnostic tests for the Zika virus are presently approved by the FDA for use in patients, though a number of tests have been developed. These tests are available due to an Emergency Use Authorization (EUA) for use in symptomatic patients residing in (or who have recently traveled to) an area with a risk of Zika infection. A total of 15 different tests are currently available under the Zika EUA, including molecular tests like real-time PCR and serological tests like ELISA. The Trioplex Real-Time RT-PCR assay (Nucleic Acid-based Testing) and the Zika MAC-ELISA (IgM antibody-based testing) are the only two tests that are in widespread use and distribution.7

Tests like these are important and clinically useful, but because of their newness and lack of FDA approval through the typical Premarket Application (PMA) process, concrete data on sensitivity, specificity, and predictive values are still being collected. Testing poses three primary challenges. First, the Zika virus is only transiently present in body fluids, which makes identifying the virus difficult using PCR NAT-based molecular testing. Second, serological testing for IgM antibodies using the MAC-ELISA cannot reliably pinpoint whether infection occurred during or prior to a pregnancy. Finally, serologic tests have been found to have cross-reactivity with other flaviviruses like dengue and are prone to false-positive results, which is a problem in zones where infection rates are high for the other flaviviruses.2

Current guidelines continue to recommend testing of symptomatic pregnant women with recent possible Zika exposure. However, the CDC now only recommends that asymptomatic pregnant women with ongoing possible Zika virus exposure be offered Zika virus NAT testing three times during pregnancy. IgM testing is no longer recommended for routine testing in pregnant women with ongoing Zika exposure, since IgM can persist for months after infection and therefore cannot reliably determine whether an infection occurred during the current pregnancy.2 The CDC also no longer recommends routine screening of asymptomatic pregnant women without ongoing Zika exposure, except in cases where prenatal ultrasound findings are consistent with congenital Zika virus syndrome to assist with establishing a diagnosis for the fetus.2

Testing for Zika in Human Allografts

Right now there is no test available to detect the Zika virus in human allografts, a category which includes placental tissues like the amniotic membrane and umbilical cord. The Procleix Zika Virus Assay is currently being tested under an Investigational New Drug (IND) protocol by manufacturer Gryfols and Hologic in conjunction with industry partners, but studies have not yet been completed to allow for FDA approval. The Procleix assay system, if proven effective, will be able to screen blood, plasma, and organ and tissue donations for the Zika virus.

You can read more about how tissue banks are managing risk for Zika virus in this blog post: Hot Topics: Zika Virus and Allografts, Part 2