Inactivation of transfusion-transmitted vector borne pathogens

Abstract

A variety of viral, bacterial and parasitic human pathogens associated with several different vectors • were inactivated to or below the limit of detection by treatment with the INTERCEPT Process. The INTERCEPT Blood System is highly effective against a spectrum of transfusion-transmitted • vector-borne pathogens. A number of blood-borne pathogens are primarily transmitted to humans by insect vectors. While the blood banking community has been aware of the risks of some vector-borne pathogens, such as malaria, for many years, the awareness of risks from other vector-borne pathogens is much more recent. It has been less than seven years since West Nile virus and chikungunya virus were recognized as serious regional issues for the blood supply, and recognition of the risk of T. cruzi outside of South America and of Babesia in North America is even more recent. Vector-borne pathogens are particularly problematic for blood safety because exposure to the vectors is often frequent (e.g. mosquitoes), rendering donor screening questions insensitive, and infections are frequently asymptomatic, rendering physical findings, such as body temperature, useless. The INTERCEPT Blood SystemTM for pathogen inactivation of platelet and plasma components was developed to prevent transfusion-transmitted infections. This proactive approach to blood safety utilizes amotosalen HCl and UVA illumination (Figure 1) and has been demonstrated to inactivate high levels of the pathogens for which blood is commonly tested (HIV, HBV, HCV, HTLV-I/II, West Nile virus, and Treponema pallidum), as well as a broad spectrum of other pathogens and leukocytes in platelet and plasma components (Table 1, references available on request). The INTERCEPTTM technology is not approved for sale in the U.S.A. Plasma units (~600 mL) and platelet units containing 2.5 – 6.0 x1011 platelets in ~300 mL (35% plasma/65% InterSolTM) were inoculated with the respective pathogens to achieve a target final titer of 6 logs/mL whenever possible. Contaminated units were treated with 150 μM amotosalen and a 3.0 J/cm2 UVA treatment using the appropriate INTERCEPT Blood System processing sets (Figure 2). Pathogen viability titers (log10) were measured before and after treatment. Log inactivation was calculated as log (pre-illumination titer ÷ post illumination titer), with titer expressed as 10x/mL. Viability of pathogens was quantified in various assay systems as appropriate for each organism. Table 2 lists the viability assay system used for each pathogen. Transfusion-transmitted insect vector-borne pathogens were effectively inactivated in both platelet and plasma components (see Table 3). This series of studies evaluated inactivation of important vector borne pathogens in platelet and/or plasma components using the INTERCEPT Blood System. Inactivation of Transfusion-Transmitted Vector Borne Pathogens L. Sawyer1, S. Higgs2, K. Tsetsarkin2, D. Vanlandingham2, R. Johnson3, C. Kodner3, S. Lam4, M. Koh4, F. Rentas5, J. Kinsey1, D. Hanson1, A. Sampson-Johannes1 1. Cerus Corporation, Concord, California; 2. University of Texas Medical Branch, Galveston, Texas; 3. University of Minnesota, Minneapolis, Minnesota