David A. Leiby

Transfusion-Transmitted Babesia spp.: Bull's-Eye on Babesia microti

SUMMARY Babesia spp. are intraerythrocytic protozoan parasites of animals and humans that cause babesiosis, a zoonotic disease transmitted primarily by tick vectors. Although a variety of species or types of Babesia have been described in the literature as causing infection in humans, the rodent parasite Babesia microti has emerged as the focal point of human disease, especially in the United States. Not only has B. microti become established as a public health concern, this agent is increasingly being transmitted by blood transfusion: estimates suggest that between 70 and 100 cases of transfusion-transmitted Babesia (TTB) have occurred over the last 30 years. A recent upsurge in TTB cases attributable to B. microti, coupled with at least 12 fatalities in transfusion recipients diagnosed with babesiosis, has elevated TTB to a key policy issue in transfusion medicine. Despite clarity on a need to mitigate transmission risk, few options are currently available to prevent the transmission of B. microti by blood transfusion. Future mitigation efforts may stress serological screening of blood donors in regionalized areas of endemicity, with adjunct nucleic acid testing during the summer months, when acute infections are prevalent. However, several hurdles remain, including the absence of a licensed blood screening assay and a thorough cost-benefit analysis of proposed interventions. Despite current obstacles, continued discussion of TTB without proactive intervention is no longer a viable alternative.

Protecting the Blood Supply From Emerging Pathogens: The Role of Pathogen Inactivation

Although the risk of infection by blood transfusion is relatively low, breakthrough infections still occur, Transfusion-related fatalities caused by infections continue to be reported, and blood is not tested for many potentially dangerous pathogens. The current paradigm for increasing the safety of the blood supply is the development and implementation of laboratory screening methods and restrictive donor criteria. When considering the large number of known pathogens and the fact that pathogens continue to emerge, it is clear that the utility of new tests and donor restrictions will continue to be a challenge when considering the cost of developing and implementing new screening assays, the loss of potential donors, and the risk of testing errors. Despite improving the safety of blood components, testing remains a reactive approach to blood safety. The contaminating organisms must be identified before sensitive tests can be developed. In contrast, pathogen inactivation is a proactive strategy designed to inactivate a pathogen before it enters the blood supply. Almost all pathogen inactivation technologies target nucleic acids, allowing for the inactivation of a variety of nucleic acid–containing pathogens within plasma, platelets, or red blood cells thus providing the potential to reduce transfusion-transmitted diseases. However, widespread use of a pathogen inactivation technology can only be realized when proven safe and efficacious and not cost-prohibitive.

Seroepidemiology of Trypanosoma cruzi, Etiologic Agent of Chagas' Disease, in US Blood Donors

A comprehensive seroepidemiologic study was conducted in two Red Cross regions (Los Angeles and Miami) to determine the prevalence of Trypanosoma cruzi antibodies in at-risk blood donors, to identify additional risk factors, and to assess the likelihood of transmitting T. cruzi by transfusion. At-risk and control donors were stratified by a broad risk question, tested for T. cruzi antibodies, and if confirmed as seropositive, enrolled in case-control and lookback investigations. A total of 299,398 donors were queried; 23,978 at-risk and 25,587 control donations were tested, and T. cruzi antibodies were confirmed in 34 donors (33 and 1, respectively). Seropositive donors shared one risk factor; birth/extensive time in a T. cruzi-endemic area. Lookback studies identified 11 recipients, all negative for T. cruzi antibodies. Screening strategies that use a question are unlikely to identify all seropositive donors. The lack of definitive data on the risk of transmission by transfusion indicates additional studies of donors and recipients are needed.

Transmission of Trypanosoma cruzi by Heart Transplantation

BACKGROUND Trypanosoma cruzi infection (i.e., Chagas disease) is an unusual complication that can occur after solid-organ transplantation and that can result in severe illness or death. In 2006, there were 2 heart transplant recipients in Los Angeles, California, reported to have acute trypanosomiasis during the same month. We conducted an investigation to determine the source of these infections. METHODS We reviewed the medical, organ procurement, and donor transfusion and transplantation records of these 2 heart transplant recipients. The 2 heart transplant recipients were interviewed regarding any kind of natural exposure and were screened for parasites by obtaining blood and other tissue samples for buffy coat, culture, and polymerase chain reaction. Serum samples from the heart transplant recipients, organ donors, and blood donors were tested for T. cruzi antibodies by use of immunofluorescence assay and radioimmunoprecipitation assay. Tissue samples from the organ donors were examined by use of polymerase chain reaction and immunohistochemical staining. Other recipients of organs from the same donors were monitored for T. cruzi infection by use of polymerase chain reaction and immunofluorescence assay. RESULTS Both heart transplant recipients had no apparent risk factors for preexisting T. cruzi infection. Both were seronegative but tested positive for the parasite, indicating recent infection. Both recipients died despite medical treatment. The organ donors tested positive for T. cruzi antibodies by use of radioimmunoprecipitation assay; the blood donors were seronegative. Six other patients had received a liver or kidney from these organ donors. None showed evidence of T. cruzi infection. CONCLUSIONS To our knowledge, this is the first report of T. cruzi transmission associated with heart transplantation. Clinicians and public health authorities should be aware that manifestations of Chagas disease can occur after transplantation, requiring rapid evaluation, diagnosis, and treatment.

A retrospective analysis of microbial contaminants in outdated random‐donor platelets from multiple sites

BACKGROUND: Platelet components contaminated with bacteria are an important source of transfusion‐associated bacterial sepsis. Estimates of contamination rates vary widely (0–10%) and are highly controversial. The present study, designed with stringent testing regimens, retrospectively determined the prevalence of microbial contaminants in platelets from four collection regions.

Transfusion-transmitted Babesia microti identified through hemovigilance.

BACKGROUND: Babesia microti, the primary cause of human babesiosis in the United States, is an intraerythrocytic parasite endemic to the Northeast and upper Midwest. Published studies indicate that B. microti increasingly poses a blood safety risk. The American Red Cross Hemovigilance Program herein describes the donor and recipient characteristics of suspected transfusion‐transmitted B. microti cases reported between 2005 and 2007.

Evaluation of a prototype Trypanosoma cruzi antibody assay with recombinant antigens on a fully automated chemiluminescence analyzer for blood donor screening

BACKGROUND: Chagas disease is caused by Trypanosoma cruzi, a protozoan parasite that can be transmitted by transfusion. The diagnosis of chronic T. cruzi infection is generally made by detecting specific antibodies that bind to parasite antigens. The aim of this study was to assess the sensitivity and specificity of a new serologic assay for antibodies to T. cruzi on a fully automated analyzer (PRISM, Abbott Laboratories).

Trypanosoma cruzi in a low‐ to moderate‐risk blood donor population: seroprevalence and possible congenital transmission

BACKGROUND: Several recent studies documented the seroprevalence of Trypanosoma cruzi in blood donors at high risk for infection, but little information is available regarding donors with lower levels of risk. Thus, the present study was designed to measure the seroprevalence of T. cruzi in a donor population with a low to moderate risk for infection.

A multi-epitope synthetic peptide and recombinant protein for the detection of antibodies to Trypanosoma cruzi in radioimmunoprecipitation-confirmed and consensus-positive sera.

Peptide epitopes of Trypanosoma cruzi have been identified through expression cloning. A tripeptide (2/D/E) containing three epitopes (TcD, TcE, PEP-2) was used in ELISA to detect antibodies to T. cruzi in 239 of 240 consensus-positive sera and 41 of 42 sera confirmed positive by radioimmunoprecipitation assay. The 1 discrepant consensus-positive serum was used to expression-clone a novel gene that contained a repeat sequence. A peptide corresponding to this sequence, TcLo1.2, was specific for T. cruzi. This antigen detected the discrepant consensus-positive serum and enhanced reactivity of low-positive sera in the tripeptide assay. A branched synthetic peptide, 2/D/E/Lo1.2, or a linear recombinant, r2/D/E/Lo1.2, realized all of the diagnostic features of the four epitopes, including the ability to boost reactivity of low-reactive sera. These studies show that peptides and recombinants containing multiple repeat epitopes are powerful tools for developing assays for T. cruzi antibody detection and have direct application in blood screening.

Relationship between tick bites and the seroprevalence of Babesia microti and Anaplasma phagocytophila (previously Ehrlichia sp.) in blood donors

BACKGROUND : Tick‐borne diseases, particularly babesiosis and ehrlichiosis, represent recently emerging infections. Despite an increased recognition of the threat tick‐borne agents pose to blood safety, our understanding of the prevalence and transmissibility of these agents in blood donors is limited.