Complete Inactivation of Blood Borne Pathogen Trypanosoma cruzi in Stored Human Platelet Concentrates and Plasma Treated With 405 nm Violet-Blue Light

Abstract

The introduction of pathogen reduction technologies (PRTs) to inactivate bacteria, viruses and parasites in donated blood components stored for transfusion adds to the existing arsenal toward reducing the risk of transfusion-transmitted infectious diseases (TTIDs). We have previously demonstrated that 405 nm violet-blue light effectively reduces blood-borne bacteria in stored human plasma and platelet concentrates. In this report, we investigated the microbicidal effect of 405 nm light on one important bloodborne parasite Trypanosoma cruzi that causes Chagas disease in humans. Our results demonstrated that a light irradiance at 15 mWcm−2 for 5 h, equivalent to 270 Jcm−2, effectively inactivated T. cruzi by over 9.0 Log10, in plasma and platelets that were evaluated by a MK2 cell infectivity assay. Giemsa stained T. cruzi infected MK2 cells showed that the light-treated parasites in plasma and platelets were deficient in infecting MK2 cells and did not differentiate further into intracellular amastigotes unlike the untreated parasites. The light-treated and untreated parasite samples were then evaluated for any residual infectivity by injecting the treated parasites into Swiss Webster mice, which did not develop infection even after the animals were immunosuppressed, further demonstrating that the light treatment was completely effective for inactivation of the parasite; the light-treated platelets had similar in vitro metabolic and biochemical indices to that of untreated platelets. Overall, these results provide a proof of concept toward developing 405 nm light treatment as a pathogen reduction technology (PRT) to enhance the safety of stored human plasma and platelet concentrates from bloodborne T. cruzi, which causes Chagas disease.

Violet‐blue Light Induces “Natural” Photodynamic Plasma Disinfection with Endogenous Sensitizers

“…Maclean and co-worker's report (3) is a part of a growing body of work not only using endogenous porphyrins as sensitizers to disinfect, but also in advancing violet-blue light treatment (4)(5)(6)(7)(8)(9)(10). Their work represents an important contribution in assessing the balance of benefit/damage in high microbe inactivation and low protein oxidation that can lead to success in violet-blue light treatment of human plasma.…”

Interdental Plaque Microbial Community Changes under In Vitro Violet LED Irradiation

“…Thus, PDT is an attractive alternative to antibiotic therapy for solving the problem of antibiotic resistance [ 59 , 60 ]. Recent studies by Tomb et al have shown that even under repeated irradiation of 405 nm light, resistance of specific microorganisms is unlikely to occur [ 59 ]; as such, further applications of 405 nm light for the purpose of clinical treatment and decontamination are expected in the future [ 61 , 62 ]. However, as violet light itself brings oxidation stress to oral tissues, the aggressive administration of antioxidants prior to light treatment is advocated to prevent or mitigate the resulting damage to oral tissues [ 63 ].…”

Violet‐blue 405‐nm Light‐based Photoinactivation for Pathogen Reduction of Human Plasma Provides Broad Antibacterial Efficacy Without Visible Degradation of Plasma Proteins

“…The potential for antiviral activity has also been evidenced (22). Significantly, in addition to nonrequirement of photosensitive additives, studies have demonstrated that photo-inactivation could be achieved in situ in the product storage bag itself; an operational advantage made possible due to the penetrability of these visible light wavelengths (7)(8)(9)(10). These initial studies also identified the light treatment conditions which showed compatibility with PCs, with successful recovery and survival of the treated platelets in a murine model (8,9).…”

“…Proof-of-concept studies have established the efficacious antimicrobial action of violet-blue light for pathogen reduction in both plasma and platelet concentrates (PCs), using selected bacteria, yeast and most recently a blood-borne parasite Trypanosoma cruzi (10). The potential for antiviral activity has also been evidenced (22).…”

“…Violet-blue light, in the region of 405 nm, is being investigated as an alternative antimicrobial approach for pathogen reduction of blood transfusion products, without the need for addition of photosensitive agents (7)(8)(9)(10). Microbial inactivation by exposure to these wavelengths is accredited to the photoexcitation of endogenous porphyrin molecules within microbes, which results in the generation of reactive oxygen species (ROS), inducing nonspecific oxidative damage and cell death (11)(12)(13)(14)(15).…”