REAL-TIME SCREENING FOR WEST NILE VIRUS (WNV) OF ORGAN DONORS

1. REAL-TIME SCREENING FOR WEST NILE VIRUS (WNV) OF ORGAN DONORS • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • Claudia Chinchilla, CLSpMB1, Jaime Siriban, CLS1, Dem Brucal, CLS1, James Schellenberg, MBA1, Lisa Stocks2, Edwin Serna3 , Eugene Osborne4, and Marek Nowicki, PhD1. 1Mendez National Institute of Transplantation, Los Angeles, CA, United States; 2LifeSharing OPO, San Diego, CA, United States and 3NDN OPO, Las Vegas, NV, United States, and 4California Transplant Donor Network, Oakland, CA, United States Methods Since June 1, 2009 we tested 159 donors from 2 OPOs (LS & NDN, Fig.3). Both OPO’s elected to screen their donors year long. We used FDA approved EIA for IgM anti-WNV (Focus Technologies, Los Angeles, Fig. 2), with confirmatory assay (Plaque Reduction Neutralization Test, PRNT, CADHS). We also screened all donors using WNV Procleix NAT (Chiron) for WNV RNA (Fig 2) Background West Nile virus (WNV) is a neurotropic Flavivirus. The majority of flaviviruses are arthropod-borne, transmitted by infected mosquito or tick vectors to vertebrates. Humans and animals are accidental, dead-end hosts for WNV. Symptoms usually develop between 2 to 15 days after exposure. The period of viremia begins 6-7 days prior to symptom onset and ends within a week. However, it is possible to isolate WNV and/or detect viral antigen or nucleic acid in cerebrospinal fluid, tissue, and other body fluids several weeks or years after viremia cession (2). Our recent data shows that organ donors with evidence of recent exposure to WNV are more common than expected (1). We have also shown that serological evaluation of all donors during the WNV season (June-November, Fig. 1) complements WNV RNA NAT. Starting in 2009, our laboratory offered WNV testing to all 9 OPOS we serve (Fig. 3). Based on their local WNV risk factors 2 OPOs (LS and NDN) elected to screen their organ donors for WNV. Figure 1. Comparative Line Graphs of West Nile Virus Activity in 2004 - 2009 (CA DHS) Testing for WNV The IgM cross-reactivity was investigated by several groups (3). The IgM antibodies produced against related arboviruses are significantly more specific than IgG antibodies and, therefore, show less cross-reactivity, even after challenge with a related virus. In December 2005, the Gen-Prove TMA/HPA based Procleix WNV assay was FDA approved and intended for qualitative detection of WNV RNA in plasma specimens from individual human donors, including volunteer donors of whole blood and blood components, and other living donors; testing plasma specimens to screen organ donors when specimens are obtained while the donor’s heart is still beating and testing blood specimens to screen cadaveric (non-heart-beating) donors. Rationale Very little is known about exposures to WNV not resulting in an overt disease among organ donors in California. Because NAT alone will not detect viremic donors beyond the very first few days post exposure due to short WNV viremia, organ donors are not routinely screened for WNV RNA.(2). Aim To evaluate results of “real time” organ donor testing for WNV and IgM anti-WNV in Southern California (LS) and Nevada (NDA). • Results • Real -Time Donor Screening: We detected no WNV positive donors (EIA+ or NAT+) from OPOs which elected to test for WNV. However, during the observation period there was one case of WNV transmission from donor recruited by N. California OPO who selected not to test for WNV. We observed no false positive WNV results which would have lead to the loss of donors. • WNV Transmission case: On October 2009 we were contacted by one of the OPOs (CTDN) who did not elect to test their donors for WNV; asking us to test archived serum from one of their donors. The IgM EIA results were negative but WNV NAT was strongly reactive (S/CO 20.82 and 21.52). • The donor was a 53 year old male Caucasian, who died due to a cerebrovascular accident (CVA) and donate his liver in September. The recipient developed symptoms compatible with WNV infection. • Conclusion • The epidemiology of WNV in the US Western States is changing due to vector control measures and emergence of immune individuals. It is difficult to predict before the WNV season, which region will be affected by the virus. Testing algorithm involving IgM anti-WNV testing and NAT offers an affordable and convenient (TAT<5hrs) safeguard against WNV infection with no loss of donors due to false positive results. • References • ATC 2009, abstract #992. Toward rational West Nile Virus (WNV) Screening of Organ Donors – Is WNV Serology Testing a Viable Option to Nucleic Acid Testing (NAT) for WNV? • JID 2010:201, Persistent Infection with West Nile Virus Years after Initial Infection, Kristy Murray, Christopher Walker, Emily Herrington, Jessica A. Lewis, Joseph McCormick, David W. C. Beasley, Robert B. Tesh, and Susan Fisher-Hoch; see also editorial by Ernest A. Gould in the same issue, West Nile Virus: Don’t Underestimate Its Persistence • J Clin Microbiol. 2004 Oct;42(10):4641-8. Performance of immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assays using a West Nile virus recombinant antigen (preM/E) for detection of West Nile virus- and other flavivirus-specific antibodies, Hogrefe WR, Moore R, Lape-Nixon M, Wagner M, Prince HE. Figure 2. WNV Testing Algorithm Figure 3. OPOs with WNV Screening