Keeping Blood Transfusion Safe From West Nile Virus: American Red Cross Experience, 2003 to 2012 Roger Y. Dodd a, 1 , Gregory A. Foster b , Susan L. Stramer b, ⁎ a American Red Cross, Holland Laboratory, Rockville, MD b American Red Cross, Scientific Support Office, Gaithersburg, MD abstract article info Available online xxxx Keywords: West Nile virus Nucleic acid test Blood donors Blood safety Transfusion Infection Transfusion transmission Symptoms Viremia Antibodies West Nile virus (WNV) appeared for the first time in the United States in 1999 and rapidly spread across the Western hemisphere within a few years causing hundreds of thousands of human infections and significant disease. In 2002, it was found to be transmissible by blood transfusion, and within less than a year, nucleic acid testing for WNV RNA was in place for all US donations. The American Red Cross (ARC) collects approximately 40% of blood donations in the United States and closely monitors the results of such testing and evaluates donors found to be reactive. This review describes the 10-year results of the ARC testing program during the period 2003 to 2012. Overall, more than 27 million donations were tested during the transmission periods with 1576 RNA-positive donations identified. The temporal and geographic distributions of the infected donors are described. Methods to initiate and discontinue periods of individual donation testing were developed and vali- dated to maximize safety. The nature of WNV infection among donors was investigated, and the distribution of viral titers was defined and was found to be no greater than 720000 RNA copies per milliliter. The distribution of titers by time sequence of appearance of antibodies was determined. Donors who were identified as being in the earliest stages of infection were evaluated for the appearance of symptoms, and 26% developed at least 3 characteristic symptoms. The testing program has been successful in preventing transmission of WNV by trans- fusion, and only 1 of the 13 reported cases since the initiation of testing was attributable to the Red Cross; it was from a granulocyte product transfused before availability of the test result. © 2015 Elsevier Inc. All rights reserved. Contents Emergence of WNV in the United States and development of a national donor testing program . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Materials, Methods, and Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 The Early ARC Testing Program and Its Contributions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Continuing Efforts to Enhance the Sensitivity of WNV Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Validation Studies for Triggering . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Distribution of WNV markers among donors, American Red Cross, 2003 to 2012 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Investigation of donors with reactive test results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Dynamics and immunology of WNV infection among donors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Epidemiologic significance of WNV NAT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Discussion and Commentary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Until 1999, the West Nile virus (WNV), a mosquito-borne Flavivirus, was endemic to many parts of Africa, Southern Europe, the Middle East, Southwest Asia, India, and Australia (Kunjin strain). However, in that year, an unexpected outbreak occurred in Queens, New York, marking the first autochthonous cases in the Americas. A total of 17 confirmed and 20 probable human cases, with 4 deaths, had been reported by September 28, 1999 [1]. West Nile virus spread rapidly throughout the east coast and as far west as the Rocky Mountains [2], with a total Transfusion Medicine Reviews xxx (2015) xxx–xxx Supported by the American Red Cross. Conflict of Interest: The authors have no conflict of interest. ⁎ Corresponding author at: Susan L. Stramer, PhD, American Red Cross, Scientific Support Office, 9315 Gaither Road, Gaithersburg, MD, 20877. E-mail addresses: roger.dodd@redcross.org (R.Y. Dodd), susan.stramer@redross.org (S.L. Stramer). 1 Tel.: +1 240 447 4547. http://dx.doi.org/10.1016/j.tmrv.2015.03.001 0887-7963/© 2015 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Transfusion Medicine Reviews journal homepage: www.tmreviews.com Please cite this article as: Dodd RY, et al, Keeping Blood Transfusion Safe From West Nile Virus: American Red Cross Experience, 2003 to 2012, Transfus Med Rev (2015), http://dx.doi.org/10.1016/j.tmrv.2015.03.001