BLOOD COMPONENTS The efficacy of photochemical treatment with amotosalen HCl and ultraviolet A (INTERCEPT) for inactivation of Trypanosoma cruzi in pooled buffy-coat platelets Emma Castro, Nuria Gironés, José Luis Bueno, Javier Carrión, Lily Lin, and Manuel Fresno BACKGROUND: This study evaluated the efficacy of photochemical treatment (PCT) with amotosalen and ultraviolet A (UVA) light to inactivate Trypanosoma cruzi in contaminated platelet (PLT) components. STUDY DESIGN AND METHODS: Fifteen pools of buffy-coat PLTs (BC-PLTs) were inoculated with approximately 5 ¥ 10 3 to 5 ¥ 10 5 per mL of viable T. cruzi of the G, Tulahuen (T), or Y strains. Samples from BC-PLTs were assayed for infectivity before and after PCT with 150 mmol per L amotosalen and 3 J per cm 2 UVA light. Infectivity was determined with three dif- ferent methods: 1) in vitro culture to detect viable epi- mastigotes, 2) [ 3 H]thymidine incorporation in culture, and 3) in vivo inoculation into interferon-g receptor (IFN- gR)-deficient mice. RESULTS: The in vitro assay yielded viable parasite titers of 3.9 ¥ 10 5 , 2.8 ¥ 10 4 , and 5.6 ¥ 10 3 per mL (cor- responding to 5.6, 4.4, and 3.8logs/mL) for the Y, T, and G strains, respectively. PCT was able to inactivate all three strains of T. cruzi to below the limit of detection (10 parasites/mL) in the sensitive in vivo assay. Because 10-mL samples, each concentrated into a 1-mL sample for inoculation, were tested in the in vivo assay, log reductions achieved were greater than 5.6, greater than 4.4, and greater than 3.8 for the Y, T, and G strains of T. cruzi, respectively. CONCLUSIONS: The pathogen reduction system with amotosalen HCl and UVA demonstrated robust efficacy for inactivation of high doses of three different strains of T. cruzi and offers the potential to make the PLT supply safer. A merican trypanosomiasis (Chagas disease) is a zoonosis caused by the hemoflagellate proto- zoan parasite Trypanosoma cruzi. It affects approximately 18 million people in Central and South America. This parasite can be found in the blood of 50 percent of people affected several years after primary infection. For this reason, it is not surprising that this disease can be transmitted through blood transfusion from an asymptomatic carrier donor. 1 Chagas disease associated with blood transfusion is a considerable problem in Latin America where, in some areas, 1 to 25 percent of blood donors are chronically infected by T. cruzi. Currently strategies to prevent transfusion-associated Chagas disease include the identification of blood donors by questionnaire and serologic tests detecting antibodies directed to T. cruzi antigens. Despite these measures, blood recipients are still being infected by T. cruzi. 2 The real incidence of Chagas disease acquired through blood transfusion is unknown because the majority of cases are nonapparent or the etiologic agent is not identified. T. cruzi can survive for up to 18 days in whole blood stored at 4°C. It is also resistant to cryopreservation and ABBREVIATIONS: CAD = component absorbent device; d.p.i. = days postinfection; IFN-gR = interferon-g receptor; Neg-C = negative control; PCT = photochemical treatment; Pos-C = positive control. From the Spanish Red Cross Transfusion Center, and the National Research Council, Autonomous University of Madrid, Madrid, Spain; and Cerus Corp., Concord, California. Address reprint requests to: Dr Emma Castro, Centro de Transfusión de Cruz Roja Española en Madrid, C/Juan Mon- talvo, 3, 28040 Madrid, Spain; e-mail: ecastro@cdscruzroja. infonegocio.com. This work has been partially financed by Baxter. Received for publication May 18, 2006; revision received July 24, 2006, and accepted August 7, 2006. doi: 10.1111/j.1537-2995.2007.01133.x TRANSFUSION 2007;47:434-441. 434 TRANSFUSION Volume 47, March 2007