Zika Virus and the Blood Supply
by G. Paranjape, M.D., Medical Director of Clinical Services, Carter BloodCare
Update: On May 12, 2021, the FDA’s July 2018 ZIKV Testing Guidance was withdrawn because the agency has determined that testing for ZIKV, or pathogen reduction as an alternative to testing for ZIKV, is not necessary because ZIKV is no longer a Relevant Transfusion-Transmitted Infection (RTTI).
Zika virus (ZIKV) is a member of the Flaviviridae group and has been known to cause infection since 1953. It is transmitted to humans primarily by the Aedes aegypti mosquito, but it may also be transmitted by the Aedes albopictus mosquito. Cases of intrauterine, perinatal, sexual, laboratory-acquired and transfusion-associated transmission of ZIKV have been reported.
Symptomatic ZIKV infection presents with fever, joint pain, rash and conjunctivitis. Some neurological manifestations as well as increased incidence of Guillain-Barré syndrome have also been reported. Zika virus infection during pregnancy is a cause of microcephaly and other serious fetal brain anomalies. Other problems have been detected in pregnancies and among fetuses and infants infected with ZIKV before birth, such as miscarriage, stillbirth, absent or poorly developed brain structures, defects of the eye, hearing deficits and impaired growth.
There are now at least 50 countries in the world known to have Zika transmission. This global epidemic came to the Americas in early 2015 with Brazil reporting the first cases of local transmission. The first local transmission of ZIKV in the United States (U.S.) was reported from Puerto Rico in December 2015, and soon thereafter, in American Samoa and the U.S. Virgin Islands. In July 2016, the first cases of local transmission of ZIKV occurring in the continental U.S. were reported from Miami-Dade County, Florida. The possibility of further geographic spread of ZIKV exists in regions where the Aedes aegypti, and possibly the Aedes albopictus, mosquito is present. Since January 2016, Zika virus disease has been added to the list of nationally notifiable conditions in the U.S. as a subtype of Arboviral diseases.
Taking into account all the evidence (including local transmission in Florida), the Food and Drug Administration (FDA) decided that ZIKV meets the criteria to be considered as a relevant transfusion transmissible infection and put out guidance for Immediate Implementation in August of 2016, for U.S. blood collection agencies. Their recommendation was that blood centers either use pathogen inactivation for all blood components (currently not available for all product types; especially for red cells which are the most used component) or test each unit of blood by using an unlicensed investigational Nucleic Acid Amplification (NAT) test. Of note, Zika virus NAT testing is required in the FDA guidance to be done on individual samples and not on pooled samples. NAT tests for most other viruses are done on pooled samples from 8-16 units because sensitivity has been adequate and pooled testing conserves valuable resources. Currently a ZIKV NAT test is available from two manufacturers who are evaluating it under a study protocol. Any unit testing positive will NOT be used for transfusion and the donor will be asked to participate in a follow up study for further testing.
FDA mandated different time lines for test implementation for different states; those at higher risk (including Texas) were given four weeks to implement the test. Carter BloodCare was able to meet the deadline working with the testing laboratory and the test manufacturer and started testing all blood donors on September 23, 2016. Since this testing is IRB-regulated research involving an unlicensed assay, we must require all donors below 18 years of age to have a parental permission slip signed to participate and all donors must read informational materials about the study. If a donor refuses to participate in the study he or she cannot donate blood. The results of the study will help determine the performance characteristics of the Zika test and if it should become FDA-licensed. They will be publicized later with sponsor oversight.