Improving the Safety of the Blood Supply from West Nile Virus (WNV) Infection by the Development and Evaluation of Diagnostic Tools for Blood Donor Screening

Principal Investigator: Maria Rios, PhD
Office / Division / Lab: OBRR / DETTD / LMV

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Overview

Public Health Issue: West Nile Virus (WNV) was recognized in the US for the first time in 1999, and between 1999 and 2008 between 2 and 4 million people have been estimated to have had WNV infection, resulting in close to 28,000 cases of serious disease and over 1,000 deaths. WNV is transmitted by mosquitoes to several animal species including humans, and from human to human by blood transfusion and transplantation, posing a threat to the public health. Currently, there is no FDA-approved therapy or vaccine available to treat or prevent human WNV disease. WNV is more severe in immune compromised people, i.e., patients who often receive blood transfusions and blood products. WNV diagnostic tests have been developed, evaluated and cleared. Blood donor screening assays for WNV have also been developed and implemented nationwide under a research IND prior to their licensure, and continue to be used after licensure to limit as much as possible WNV spread through blood transfusions. One remaining concern is the continuous recurrence of WNV outbreaks in the U.S. potentially associated with adaptation through fixation of spontaneous mutations in the viral genome. Genetic variations can alter viral phenotype and virulence, resulting in decreased rates of detection by current diagnostic and screening assays, vaccines, and potential therapeutic agents. Therefore the monitoring and identification of mutations in the WNV genome as the epidemics recur is a key factor to assess the performance of licensed assays and to manage the potential residual risk.

Regulatory Contribution: In order to establish regulatory policy regarding blood donors, blood donations and blood product management to assure blood safety, it is critical for CBER to understand parameters impacting sensitivity and specificity of blood and tissue donor screening assays, in addition to monitoring for genetic variants of WNV.

Research Approach: The goals of this research program include: (1) Determination of the genetic variation of WNV to evaluate the impact of naturally occurring mutations in the performance of diagnostics and screening tests; this work will also facilitate the evaluation of efficacy of vaccines and treatments under development; (2) To investigate the relevance of genetic variants to virus fitness and virulence using in vitro culture systems to study WNV infection in human and animal cells; (3) To assess the potential for increasing sensitivity of current assays to improve blood safety;(4) To update the standard reagents with new strains in order to assure proper proficiency of WNV assays and lot release panels by the FDA; and (5) to Investigate the properties and significance of the association of WNV with blood cells, primarily red blood cells (RBCs), and its significance for WNV infection by blood transfusion.

Mission Relevance & Outcomes: Studies of WNV infection are necessary to assess the efficacy of safety measures (blood screening) and estimate the risks remaining after implementation to prevent WNV transmission by transfusion and transplantation, and estimate the remaining risks. The study of the adherence of WNV to blood cells will generate information and about the mechanisms of in vivo spread of the virus, and provide information and tools to understand unclear steps of WNV infection such as course of viremia including time period between infection and viral production and clearance. This information will support decision-making on issues such as the safety and efficacy of blood transfusion, transplantation and vaccines against WNV and may have great impact in policy making.

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Publications

J Virol Methods 2008 Dec;154(1-2):27-40
Microarray-based assay for the detection of genetic variations of structural genes of West Nile virus.
Grinev A, Daniel S, Laassri M, Chumakov K, Chizhikov V, Rios M

J Infect Dis 2008 Nov 1;198(9):1300-1308
In Vitro Evaluation of the Protective Role of Human Antibodies to West Nile Virus (WNV) Produced during Natural WNV Infection.
Rios M, Daniel S, Dayton AI, Wood O, Hewlett IK, Epstein JS, Caglioti S, Stramer SL

Emerg Infect Dis 2008 Mar;14(3):436-44
Genetic Variability of West Nile Virus in US Blood Donors, 2002-2005.
Grinev A, Daniel S, Stramer S, Rossmann S, Caglioti S, Rios M

Clin Infect Dis 2007 Jul 15;45(2):181-6
West nile virus adheres to human red blood cells in whole blood.
Rios M, Daniel S, Chancey C, Hewlett IK, Stramer SL

Neurology 2007 Jan 16;68(3):206-13
Differentiation of HAM/TSP from patients with multiple sclerosis infected with HTLV-I.
Puccioni-Sohler M, Yamano Y, Rios M, Carvalho SM, Vasconcelos CC, Papais-Alvarenga R, Jacobson S

Vox Sang 2006 Jul;91(1):81-7
Dombrock gene analysis in Brazilian people reveals novel alleles.
Baleotti W Jr, Rios M, Reid ME, Hashmi G, Fabron A Jr, Pellegrino J Jr, Castilho L

Transfusion 2006 Apr;46(4):659-667
Monocytes-macrophages are a potential target in human infection with West Nile virus through blood transfusion.
Rios M, Zhang MJ, Grinev A, Srinivasan K, Daniel S, Wood O, Hewlett IK, Dayton AI

J Med Virol 2006 Apr 18;78(S1):S22-S23
Evaluation of FDA licensed HIV assays using plasma from Cameroonian blood donors.
Lee S, Hu J, Tang S, Wood O, Francis K, Machuca A, Rios M, Daniel S, Vockley C, Awazi B, Zekeng L, Hewlett I

J Infect Dis 2006 Feb 1;193(3):427-37
Human T Lymphotropic Virus Types I and II Western Blot Seroindeterminate Status and Its Association with Exposure to Prototype HTLV-I. 
Yao K, Hisada M, Maloney E, Yamano Y, Hanchard B, Wilks R, Rios M, Jacobson S

Clin Infect Dis 2005 Jun 1;40(11):1673-6
Seroprevalence of human T cell leukemia virus in HIV antibody-negative populations in rural Cameroon.
Machuca A, Wood O, Lee S, Daniel S, Rios M, Wolfe ND, Carr JK, Eitel MN, Tamoufe U, Torimiro JN, Burke D, Hewlett IK

Transfus Med 2005 Feb;15(1):49-55.
High frequency of partial DIIIa and DAR alleles found in sickle cell disease patients suggests increased risk of alloimmunization to RhD.
Castilho L, Rios M, Rodrigues A, Pellegrino J Jr, Saad ST, Costa FF

Vox Sang 2004 Oct;87(3):190-5
A novel FY allele in Brazilians.
Castilho L, Rios M, Pellegrino J Jr, Saad ST, Costa FF, Reid ME

Transfusion 2004 Feb;44(2):170-2
Evidence that Hy- RBCs express weak Joa antigen.
Scofield TL, Miller JP, Storry JR, Rios M, Reid ME

Vox Sang 2004 Feb;86(2):136-40
Weakened expression of 'e' owing to concomitant occurrence of Cys16 and Val245 (VS antigen).
Rodrigues A, Rios M, Costa FF, Saad ST, Pellegrino J Jr, Castilho L