Trypanosoma cruziInactivation in Human Platelet Concentrates and Plasma by a Psoralen (Amotosalen HCl) and Long-Wavelength UV

Abstract

Trypanosoma cruzi, the protozoan pathogen that causes Chagas' disease, can be found in the blood of infected individuals for their entire life span. This presents a serious challenge in safeguarding blood products. Transmission of T. cruzi from blood products is a frequent occurrence in Latin America, where Chagas' disease is endemic. This study was designed to determine whether T. cruzi could be inactivated in human platelet concentrates and plasma by a photochemical treatment process with long-wavelength UV A light (UVA, 320 to 400 nm) plus the psoralen amotosalen HCl (Cerus Corporation). Units of platelet concentrates (300 ml) and plasma (300 ml) were intentionally contaminated with approximately 10 6 T. cruzi trypomastigotes, the T. cruzi form found in the bloodstream, per ml. The viability of T. cruzi after photochemical inactivation was determined by their ability to replicate in 3T3 fibroblasts. Controls, including treatment with 150 M amotosalen or 3 J/cm 2 UVA alone, did not lead to reduction of the viability of T. cruzi in plasma or platelet concentrates. However, treatment with 150 M amotosalen plus 3 J/cm 2 UVA inactivated T. cruzi to undetectable levels in plasma and platelet concentrates. This represented a >5.4-log reduction of T. cruzi in platelet concentrates and >5.0-log reduction of T. cruzi in plasma. We conclude that the amotosalen plus UVA photochemical inactivation technology is effective in inactivating high levels of protozoan pathogens, such as T. cruzi, in platelet concentrates and plasma, as has been previously shown for numerous viruses and bacteria.

Leukoreduced buffy coat–derived platelet concentrates photochemically treated with amotosalen HCl and ultraviolet A light stored up to 7 days: assessment of hemostatic function under flow conditions

“…20 The option of a pathogen reduction technology is particularly appealing, considering that, for instance, PCT of PCs, in addition to inactivation high titers of a wide variety of bacteria species, 21 is also active against other transfusion transmitted pathogens such as virus and protozoa. 6,22,23 There are available data showing a good preservation of in vitro quality variables when PLTs are stored in plasma for up to 7 days 24 and in PLT AS for up to 12 days. 25 When studied in vivo with radiolabeling techniques, in comparison to 5-day-old apheresis PCs, PCs stored for up to 7 days in plasma showed a decrease in PLT recovery (63% vs. 53.9%) and survival (161 hr vs. 133 hr).…”

Therapeutic efficacy and safety of platelets treated with a photochemical process for pathogen inactivation: the SPRINT Trial

“…Patients received conventional red cell products; more than 98% of red cell units were leukocyte reduced and 99% were gamma irradiated in both treatment groups. Data are summarized from Lin, 14 Lin et al, 15,16,18 Van Voorhis et al, 19,20 Dupuis et al, 21 Savoor et al, 22 and Sawyer et al 23 *Preliminary data; inactivation was performed in 35% B19-infected plasma and 65% PAS III (platelet additive solution III) in the absence of platelets. Studies included a 15-or 30-minute rest between addition of amotosalen and UVA treatment.…”

Photoinactivation of Trypanosoma cruzi in red cell suspensions with thiopyrylium

“…Inactivation of T. cruzi in red cells using a DNA alkylating agent, Inactine, has been reported, but the development of antibodies to the treated red cells has halted further clinical development [13]. Psoralen and long-wavelength treatment has also been shown to inactivate T. cruzi in platelet concentrates and plasma [14]. Methylene blue and light has been demonstrated to photoinactivate T. cruzi in plasma [15].…”