A novel mitigation strategy for the prevention of transfusion-transmitted malaria.

BACKGROUND: Malaria is caused by protozoa of the genus Plasmodium and transmitted by Anopheles mosquitos. In the US, blood donors are assessed for malaria risk, including donor travel or previous residence in endemic areas and history of malaria by questionnaire and deferred for three months or three years, respectively. METHODS: The Procleix Plasmodium Assay is a qualitative nucleic acid test based on transcription-mediated amplification (TMA) for the detection of 18S ribosomal RNA of P. falciparum, P. ovale, P. vivax, P. malariae, and P. knowlesi for use on the Procleix Panther system. Analytical sensitivity was evaluated with in vitro transcripts and infected red blood cells. For clinical specificity, 12,800 individual donations and 283 pools of 16 samples from routine US donors were screened. Malaria risk was evaluated by testing 862 donors deferred for 3 years. Reactive results were confirmed with in-house real-time TMA assay and serology. RESULTS: Assay sensitivity was 8.47-11.89 RNA copies/mL and 2.10-6.82 infected red cells/mL. Specificity was 99.99% in 12,800 individual donations and 100% in 283 pools of 16. Of 862 tested deferred donor samples, one donor (0.12%) confirmed positive individually and in pools; he remained confirmed positive for 13 months. The infected donor was a prior resident of a malaria-endemic area in West Africa. CONCLUSIONS: The Procleix Plasmodium Assay showed high sensitivity and specificity and detected Plasmodium RNA in an asymptomatic presenting donor. This assay may prove helpful as a screening test versus the use of risk questions to reduce the number of donors deferred for malaria risk.

A case of transfusion-transmission Anaplasma phagocytophilum from leukoreduced red blood cells.

BACKGROUND: Anaplasma phagocytophilum is a tick-borne bacterium and the cause of human granulocytic anaplasmosis (HGA). Here, we report a case of transfusion-transmitted (TT)-HGA involving a leukoreduced (LR) red blood cell (RBC) unit. CASE REPORT: A 64-year-old woman with gastric adenocarcinoma and multiple myeloma who received weekly blood transfusions developed persistent fevers, hypotension, and shortness of breath 1 week after receiving an RBC transfusion. Persistent fevers, new thrombocytopenia, and transaminitis suggested a tick-borne infection. RESULTS: The absence of blood parasites on thick and thin blood smears suggested that malaria and Babesia infection were not present, and the recipient tested negative for antibodies to Borrelia burgdorferi. Blood testing by polymerase chain reaction (PCR) for Ehrlichia and Anaplasma species identified A. phagocytophilum. Treatment with doxycycline resolved the infection; however, the recipient expired due to complications of her known malignancies. The recipient lived in a nursing home and did not have pets or spend time outdoors. The donor was a female in her 70s from Maine who was diagnosed with HGA 3 weeks after donating blood and whose LR-RBCs from the donation were transfused to the recipient 9 days following collection. CONCLUSION: This is a confirmed case of TT-HGA. Although rare, TT-HGA has been reported with LR-RBCs and platelets. In endemic areas, testing for tick-borne associated infections should be considered when investigating post-transfusion complications.

Deferral of blood donors who have ever stayed in a Trypanosoma cruzi endemic area: An international survey.

BACKGROUND AND OBJECTIVES: Trypanosoma cruzi is the etiologic agent of Chagas disease (CD), an anthropozoonosis from the American continent that progresses from an acute phase to an indeterminate phase, followed by a chronic symptomatic phase in around 30% of patients. In countries where T. cruzi is not endemic, many blood transfusion services test blood donors who have stayed in an endemic country ('at-risk stay')-even if they do not present with other risk factors. However, the efficiency of this approach has been questioned. MATERIALS AND METHODS: On 18 September 2023, a worldwide survey was distributed among employees of blood transfusion services. The questions mainly pertained to CD's endemicity in the blood services' region, the current testing policy for T. cruzi and the number of confirmed positive results among donors with a prior at-risk stay alone (i.e., without other risk factors for T. cruzi infection). RESULTS: Twenty-six recipients completed the survey. Of the 22 (84.6%) blood services that operated in a non-endemic region, 9 (42.9%) tested donors for T. cruzi, including 8 (88.9%) that considered the travel history or the duration of the stay (alone) in their testing algorithm ('study blood services'). Over 93 years of observation among all study blood services, 2 donations from donors with an at-risk stay alone and 299 from those with other risk factors were confirmed positive for T. cruzi. CONCLUSION: The study findings question the utility of testing blood donors who have stayed in an endemic country without other risk factors.

Estimated Plasmodium 18S ribosomal RNA prevalence in asymptomatic blood donors from three African countries.

BACKGROUND AND OBJECTIVES: The World Health Organization (WHO) African Region accounts for 94% of malaria cases globally, with variability recognized within endemic regions. To determine the detection rate of Plasmodium RNA in blood donors resident in malaria-endemic areas, samples from three African countries were tested using a Plasmodium nucleic acid test. MATERIALS AND METHODS: Whole blood (WB) samples collected from routine donors in Cameroon, Madagascar and Mali were shipped frozen to the United States. Samples were tested individually from WB lysates with the Procleix Plasmodium assay (transcription-mediated amplification [TMA]). Reactive samples were considered either repeat reactive or initial reactive only, depending on TMA-retest results. When available, matching plasma samples were tested for Plasmodium antibodies by enzyme immunoassay (EIA). RESULTS: Plasmodium repeat reactivity ranged from 41% (91/223 tested) in Cameroon to 12% (26/216) in Mali and 1% (3/249) in Madagascar. Initially reactive samples, where reactivity did not repeat, were identified from Cameroon (5/223; 2%) and Mali (2/216; 1%). The matched-plasma subgroup had EIA reactivity ranging from 86% (113/131 tested) in Cameroon to 59% (10/17) in Mali and 27% (68/248) in Madagascar. CONCLUSION: Plasmodium ribosomal RNA (rRNA) detection and antibody rates varied greatly in the three countries studied. Detection of Plasmodium rRNA can provide an additional tool to address malaria risk in blood donors.

Transfusion-transmitted Babesia spp.: a changing landscape of epidemiology, regulation, and risk mitigation.

Babesia spp. are tick-borne parasites with a global distribution and diversity of vertebrate hosts. Over the next several decades, climate change is expected to impact humans, vectors, and vertebrate hosts and change the epidemiology of Babesia. Although humans are dead-end hosts for tick-transmitted Babesia, human-to-human transmission of Babesia spp. from transfusion of red blood cells and whole blood-derived platelet concentrates has been reported. In most patients, transfusion-transmitted Babesia (TTB) results in a moderate-to-severe illness. Currently, in North America, most cases of TTB have been described in the United States. TTB cases outside North America are rare, but case numbers may change over time with increased recognition of babesiosis and as the epidemiology of Babesia is impacted by climate change. Therefore, TTB is a concern of microbiologists working in blood operator settings, as well as in clinical settings where transfusion occurs. Microbiologists play an important role in deploying blood donor screening assays in Babesia endemic regions, identifying changing risks for Babesia in non-endemic areas, investigating recipients of blood products for TTB, and drafting TTB policies and guidelines. In this review, we provide an overview of the clinical presentation and epidemiology of TTB. We identify approaches and technologies to reduce the risk of collecting blood products from Babesia-infected donors and describe how investigations of TTB are undertaken. We also describe how microbiologists in Babesia non-endemic regions can assess for changing risks of TTB and decide when to focus on laboratory-test-based approaches or pathogen reduction to reduce TTB risk.

Nucleic acid testing for monkeypox in United States blood donor specimens.

BACKGROUND: The 2022 multi-country outbreak of monkeypox (mpox) resulted in blood collection and public health agencies closely monitoring for changes in transmission dynamics that could pose a threat to the blood supply. While mpox virus (MPXV) is not known to be transfusion transmissible, there have been several studies demonstrating the detection of MPXV in blood. We evaluated the performance characteristics of a research use only (RUO) nucleic acid amplification test for MPXV. The assay was developed to detect MPXV DNA in plasma and serum specimens from human blood donors. METHODS AND MATERIALS: The sensitivity of the RUO MPXV Assay was determined using a synthetic DNA sequence, purified full-length genomic DNA, and a chemically inactivated virus. Specificity was determined using fresh plasma samples collected from blood donors during the outbreak. Plasma samples collected from donors considered at increased risk for exposure to mpox were also tested. RESULTS: For sensitivity, the 95% limit of detection (LOD) ranged from 0.26 copies/mL (inactivated virus) to 31.65 copies/mL (synthetic DNA) to 166.61 copies/mL (for full-length DNA). All donor samples tested with the RUO MPXV Assay were nonreactive, resulting in a specificity of 100% (95% CI, 99.93%-100.00%). DISCUSSION: The RUO MPXV Assay was developed as a potential blood donation screening assay in response to the outbreak. While not directly comparable, the 95% LOD fiducial limits obtained from partial- and full-length DNA analysis were similar to other manufacturers' MPXV assays. Additionally, this assay demonstrated high specificity for screening blood donors.

Molecular Screening of Blood Donors for Babesia in Tyrol, Austria.

Introduction: Babesia is a tick-borne intraerythrocytic parasite that is globally ubiquitous, yet understudied. Several species of Babesia have been shown to be transfusion-transmissible. Babesia has been reported in blood donors, animals, and ticks in the Tyrol (Western Austria), and regional cases of human babesiosis have been described. We sought to characterize the risk of Babesia to the local blood supply. Methods: Prospective molecular testing was performed on blood donors who presented to regional, mobile blood collection drives in the Tyrol, Austria (27 May to October 4, 2021). Testing was conducted using the cobas® Babesia assay (Roche Molecular Systems, Inc.), a commercial PCR assay approved for blood donor screening that is capable of detecting the 4 primary species causing human babesiosis (i.e., B. microti, B. divergens, B. duncani, and B. venatorum). A confirmatory algorithm to manage initial PCR-reactive samples was developed, as were procedures for donor and product management. Results: A total of 7,972 donors were enrolled and screened; 4,311 (54.1%) were male, with a median age of 47 years (IQR = 34-55). No positive cases of Babesia were detected, corresponding with an overall prevalence of 0.00% (95% CI: 0.00%, 0.05%). Discussion: The findings suggest that the prevalence of Babesia is low in Austrian blood donors residing in the Tyrol, even during months of peak tick exposure. Although one cannot conclude the absence of Babesia in this population given the limited sample size, the findings suggest that the regional risk of transfusion-transmitted babesiosis is low.

Babesia blood testing: the first-year experience.

BACKGROUND: Babesia is an intraerythrocytic parasite responsible for hundreds of cases of transfusion-transmitted babesiosis in the past 50 years. In May of 2020, blood testing for Babesia was implemented at the American Red Cross (ARC) for all donations in endemic areas of the northeastern and midwestern regions of the United States. METHODS: Between May 2020 and May 2021, 1,816,669 donations from 13 states and DC were tested for Babesia by the ARC. Testing was performed in pools of 16 whole blood lysates using a licensed nucleic acid test (NAT) targeting Babesia 18S rRNA. Reactive donations were tested for B. microti antibody by immunoglobulin G immunofluorescence. Suspected cases of transfusion-transmitted babesiosis (TTB) were investigated if reported. RESULTS: The first 13 months of Babesia screening identified 365 NAT-reactive donations. Antibodies for B. microti were detected in 79% (287) of reactive donations; negative serology samples were prevalent between May and July. Follow-up donations were collected from 142 donors, and 86% (122), collected up to 74 days after index, remained NAT reactive. Reactive donations were mainly collected in MA (77), CT (68), NY (49), NJ (47), and PA (44), but were identified in all states except Delaware. Most reactive blood donors were male (65%) aged between 40 and 80 years. Since the beginning of Babesia testing, no case of TTB was identified. CONCLUSIONS: The absence of TTB cases since implementation of Babesia screening for blood donations collected in endemic areas suggests testing is an effective strategy to eliminate TTB.

Mitigating the risk of transfusion-transmitted infections with vector-borne agents solely by means of pathogen reduction.

BACKGROUND: This study evaluated whether pathogen reduction technology (PRT) in plasma and platelets using amotosalen/ultraviolet A light (A/UVA) or in red blood cells using amustaline/glutathione (S-303/GSH) may be used as the sole mitigation strategy preventing transfusion-transmitted West Nile (WNV), dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) viral, and Babesia microti, Trypanosoma cruzi, and Plasmodium parasitic infections. METHODS: Antibody (Ab) status and pathogen loads (copies/mL) were obtained for donations from US blood donors testing nucleic acid (NAT)-positive for WNV, DENV, ZIKV, CHIKV, and B. microti. Infectivity titers derived from pathogen loads were compared to published PRT log10 reduction factors (LRF); LRFs were also reviewed for Plasmodium and T. cruzi. The potential positive impact on donor retention following removal of deferrals from required questioning and testing for WNV, Babesia, Plasmodium, and T. cruzi was estimated for American Red Cross (ARC) donors. RESULTS: A/UVA and S-303/GSH reduced infectivity to levels in accordance with those recognized by FDA as suitable to replace testing for all agents evaluated. If PRT replaced deferrals resulting from health history questions and/or NAT for WNV, Babesia, Plasmodium, and T. cruzi, 27,758 ARC donors could be retained allowing approximately 50,000 additional donations/year based on 1.79 donations/donor for calendar year 2019 (extrapolated to an estimated 125,000 additional donations nationally). CONCLUSION: Pathogen loads in donations from US blood donors demonstrated that robust PRT may provide an opportunity to replace deferrals associated with donor questioning and NAT for vector-borne agents allowing for significant donor retention and likely increased blood availability.

Antibody Titers Reactive With Rickettsia rickettsii in Blood Donors and Implications for Surveillance of Spotted Fever Rickettsiosis in the United States.

BACKGROUND: Since 2000, the reported prevalence of tick-borne spotted fever rickettsiosis has increased considerably. We compared the level of antibody reactivity among healthy blood donors from 2 widely separated regions of the United States and evaluated the impact of antibody prevalence on public health surveillance in one of these regions. METHODS: Donor serum samples were evaluated by indirect immunofluorescence antibody assay to identify immunoglobulin G (IgG) antibodies reactive with Rickettsia rickettsii. The Georgia Department of Public Health (GDPH) analyzed characteristics of cases from 2016 surveillance data to evaluate the utility of laboratory surveillance for case assessment. RESULTS: Of the Georgia donors (n = 1493), 11.1% demonstrated antibody titers reactive with R. rickettsii at titers ≥64, whereas 6.3% of donors from Oregon and Washington (n = 1511) were seropositive. Most seropositive donors had a titer of 64; only 3.1% (n = 93) of all donors had titers ≥128. During 2016, GDPH interviewed 243 seropositive case patients; only 28% (n = 69) met inclusion criteria in the national case definition for spotted fever rickettsiosis. CONCLUSIONS: These findings suggest that a single IgG antibody titer is an unreliable measure of diagnosis and could inaccurately affect surveillance estimates that define magnitude and clinical characteristics of Rocky Mountain spotted fever and other spotted fever rickettsioses.

Transcription-mediated amplification blood donation screening for Babesia.

BACKGROUND: Transfusion-transmitted Babesia microti is well recognized in the Northeast and upper Midwestern United States. Blood donation screening in Babesia-endemic states has occurred under investigational protocols prior to US Food and Drug Administration-licensed test availability. Here, we provide a prospective screening summary of nucleic acid testing (NAT) as part of a multicenter Babesia pivotal trial followed by extended investigational use. METHODS: From June 2017 to February 2018, 176,928 donation samples were tested with Procleix Babesia Assay (Grifols Diagnostic Solutions), a blood screening NAT for Babesia species ribosomal RNA detection using whole blood samples. During the pivotal trial, donations were collected in 11 endemic states plus Washington, DC, and Florida (nonendemic). Whole blood lysate samples were either tested in pools of 16 or individually. Reactive samples were confirmed by Babesia microti antibody and polymerase chain reaction (PCR) testing. If unconfirmed, further testing used a second PCR assay capable of detecting multiple Babesia species. Follow-up samples were also tested. Extended investigational testing followed pivotal trial completion. RESULTS: The pivotal trial identified 61 confirmed positives (176,608 donations): 35 (57%) PCR positive, 59 (97%) antibody positive, and two (3%) NAT positive/antibody negative, for a total yield of one positive per 2895 donations, including one Florida resident; others were from seven endemic states. During extended investigational testing of 496,270 donations in endemic states through January 2019, 211 (1:2351) repeat reactive donations were identified. CONCLUSIONS: Babesia was detected in donors from multiple US states, including one previously not associated with positive blood donors. This study supports the use of the Procleix Babesia Assay using individual testing or pools of up to 16.

Screening for Babesia microti in the U.S. Blood Supply.

BACKGROUND: Babesia microti, a tickborne intraerythrocytic parasite that can be transmitted by means of blood transfusion, is responsible for the majority of cases of transfusion-transmitted babesiosis in the United States. However, no licensed test exists for screening for B. microti in donated blood. We assessed data from a large-scale, investigational product-release screening and donor follow-up program. METHODS: From June 2012 through September 2014, we performed arrayed fluorescence immunoassays (AFIAs) for B. microti antibodies and real-time polymerase-chain-reaction (PCR) assays for B. microti DNA on blood-donation samples obtained in Connecticut, Massachusetts, Minnesota, and Wisconsin. We determined parasite loads with the use of quantitative PCR testing and assessed infectivity by means of the inoculation of hamsters and the subsequent examination for parasitemia. Donors with test-reactive samples were followed. Using data on cases of transfusion-transmitted babesiosis, we compared the proportions of screened versus unscreened donations that were infectious. RESULTS: Of 89,153 blood-donation samples tested, 335 (0.38%) were confirmed to be positive, of which 67 (20%) were PCR-positive; 9 samples were antibody-negative (i.e., 1 antibody-negative sample per 9906 screened samples), representing 13% of all PCR-positive samples. PCR-positive samples were identified all through the year; antibody-negative infections occurred from June through September. Approximately one third of the red-cell samples from PCR-positive or high-titer AFIA-positive donations infected hamsters. Follow-up showed DNA clearance in 86% of the donors but antibody seroreversion in 8% after 1 year. In Connecticut and Massachusetts, no reported cases of transfusion-transmitted babesiosis were associated with screened donations (i.e., 0 cases per 75,331 screened donations), as compared with 14 cases per 253,031 unscreened donations (i.e., 1 case per 18,074 unscreened donations) (odds ratio, 8.6; 95% confidence interval, 0.51 to 144; P=0.05). Overall, 29 cases of transfusion-transmitted babesiosis were linked to blood from infected donors, including blood obtained from 10 donors whose samples tested positive on the PCR assay 2 to 7 months after the implicated donation. CONCLUSIONS: Blood-donation screening for antibodies to and DNA from B. microti was associated with a decrease in the risk of transfusion-transmitted babesiosis. (Funded by the American Red Cross and Imugen; ClinicalTrials.gov number, NCT01528449 .).

Characteristics of transfusion-transmitted Babesia microti, American Red Cross 2010-2017.

BACKGROUND: Babesia microti, a red blood cell (RBC) parasite transmitted naturally to vertebrate hosts by ixodid ticks, is endemic to the northeastern and upper midwestern United States, with the geographic range of infected ticks expanding. B. microti is a blood safety issue with >200 transfusion-transmissions reported. METHODS: The American Red Cross's Hemovigilance program investigated hospital-reported transfusion-transmitted babesiosis (TTB) cases. Follow-up samples from involved donors were tested for B. microti antibodies and parasite DNA, the latter by real-time polymerase chain reaction (PCR). Test-positive donors were permanently deferred from future donations. RESULTS: B. microti-positive donors were implicated in 77 of 143 suspect TTB cases investigated from 2010 through 2017. In four cases, two positive donors were identified for a total of 81 positive donors. In three cases, a RBC unit was split and components transfused multiple times to the same pediatric recipient. RBCs were the transmitting product in all cases. At follow-up, all involved donors were antibody positive; 25 donors were also PCR positive. Positive donations were collected throughout the year, peaking in the summer. Most donors (78) were resident of, or traveled to (2), an endemic state. One donor resided in a non-endemic state without relevant travel history. One fatality listed babesia as a contributing factor. No implicated donation was screened by an investigational protocol. CONCLUSIONS: Babesiosis remains a blood safety issue. Prior to FDA-licensed screening test availability and final FDA Guidance, blood collectors in endemic states investigationally tested none, a portion, or all collections. Future expanded testing will reduce the frequency of TTB cases.

The impact of Babesia microti blood donation screening.

BACKGROUND: Babesia microti, an intraerythrocytic parasite endemic in the Northeast and upper Midwest United States, is responsible for over 200 reported cases of transfusion-transmitted babesiosis (TTB). The American Red Cross has prospectively screened donations in endemic areas for B. microti since 2012. METHODS: Blood donation samples from Massachusetts, Connecticut, Minnesota, and Wisconsin were tested by arrayed fluorescence immunoassay and real-time polymerase chain reaction. Donors with reactive results by any test were deferred and invited to participate in a follow-up study. RESULTS: Screening of 506,540 donations (June 2012-May 2018) yielded 1299 reactives, 177 of which were DNA and antibody positive and 25 DNA positive only. During the same time, 23 unscreened RBC units collected in Connecticut and Massachusetts were involved in TTB cases, making the risk of transmitting the infection from an unscreened donation in these two states 15.6-times greater than from a Babesia-negative unit. B. microti screening in Connecticut and Massachusetts has been associated with a reduction in TTB cases; none reported from blood donors residing in Connecticut since 2016. The positive donor rate has also decreased in Connecticut from 0.67% in 2013 to 0.23% in 2017. Ongoing follow-up testing has shown that only 10% of antibody-positive donors serorevert within 1 year, while 94% of polymerase chain reacton-positive donors become negative within 12 months. CONCLUSIONS: Blood donation screening for B. microti in endemic areas effectively mitigates TTB risk. Screening should be considered for all areas demonstrating ongoing risk defined as clinical cases or positive blood donors including those associated with TTB cases.

Prevalence of Babesia in Canadian blood donors: June-October 2018.

BACKGROUND: The erythrocytic protozoan parasite Babesia microti, the cause of human babesiosis, is transmitted not only by tick bites but also via blood transfusion. B. microti is endemic in the northeastern/upper midwestern United States, where partial screening of blood donations has been implemented. In Canada, a 2013 study of approximately 14,000 donors found no B. microti antibody-positive samples, suggesting low risk at that time. METHODS: Between June and October 2018, 50,752 Canadian donations collected from sites near the US border were tested for Babesia nucleic acid by transcription-mediated amplification (TMA). Reactive donations were tested for B. microti by IgG immunofluorescence assay and polymerase chain reaction. A subset of 14,758 TMA nonreactive samples was also screened for B. microti antibody. Donors who tested reactive/positive were deferred, asked about risk factors, and were requested to provide a follow-up sample for supplemental testing. RESULTS: One sample from Winnipeg, Manitoba, was TMA and antibody reactive. Of the 14,758 TMA-nonreactive donations tested for antibody, four reactive donations were identified from southwestern Ontario near Lake Erie. None of the interviewed donors remembered any symptoms, likely tick exposure, or relevant travel within Canada or the United States. CONCLUSIONS: This is the largest B. microti prevalence study performed in Canada. The results indicate very low prevalence, with only one TMA-confirmed-positive donation of 50,752 tested. This donor was from the only region in Canada where autochthonous infection has been reported. Seropositive donations in southwestern Ontario suggest low prevalence; travel should not be ruled out given the proximity to the US border.

Transfusion-transmitted and community-acquired babesiosis in New York, 2004 to 2015.

BACKGROUND: Babesiosis is a potentially life-threatening zoonotic infection most frequently caused by the intraerythrocytic parasite Babesia microti. The pathogen is usually tickborne, but may also be transfusion or vertically transmitted. Healthy persons, including blood donors, may be asymptomatic and unaware they are infected. Immunocompromised patients are at increased risk for symptomatic disease. STUDY DESIGN AND METHODS: All reported community-acquired babesiosis cases in New York from 2004 to 2015 were evaluated, enumerated, and characterized. All potential transfusion-transmitted babesiosis (TTB) cases reported through one or more of three public health surveillance systems were investigated to determine the likelihood of transfusion transmission. In addition, host-seeking ticks were actively collected in public parks and other likely sites of human exposure to B. microti. RESULTS: From 2004 to 2015, a total of 3799 cases of babesiosis were found; 55 (1.4%) of these were linked to transfusion. The incidence of both community-acquired babesiosis and TTB increased significantly during the 12-year study period. The geographic range of both ticks and tickborne infections also expanded. Among TTB cases, 95% of recipients had at least one risk factor for symptomatic disease. Implicated donors resided in five states, including in 10 New York counties. More than half of implicated donors resided in counties known to be B. microti endemic. CONCLUSION: The increasing incidence of TTB correlated with increases in community-acquired babesiosis and infection of ticks with B. microti. Surveillance of ticks and community-acquired cases may aid identification of emerging areas at risk for Babesia transfusion transmission.

Transfusion-transmitted babesiosis: one state's experience.

BACKGROUND: The risk for tickborne exposure to Babesia microti infection exists statewide in Massachusetts. Broad exposure complicates investigations of transfusion-transmitted babesiosis (TTB). We summarize 8 years of the epidemiology of TTB and highlight the role of public health in prevention and control. STUDY DESIGN AND METHODS: Cases of babesiosis are routinely reported to the Massachusetts Department of Public Health. These are investigated to determine whether they meet the surveillance case definition and to identify whether they were potentially transfusion transmitted. Frequencies from 2009 to 2016 are described and incidence rates calculated using population denominators from the US census. Changes over time were analyzed using simple linear regression. RESULTS: From 2009 to 2016, there were 2578 cases of babesiosis reported; of these, 45 (1.7%) were transfusion transmitted. Of the 45 cases of TTB, 15 (33%) received blood products from two or more suppliers. In 11 TTB cases, the Department of Public Health was notified first, who in turn notified the appropriate blood provider. In 2009, the crude rate of reported babesiosis was 1.2 per 100,000 population and increased significantly through 2016 to 7.8 per 100,000 population (p = 0.006). The number of blood donors reported with laboratory evidence of B. microti infection increased from 19 in 2012 to 78 in 2016; at the same time, the number of TTB cases decreased from six to three. CONCLUSION: TTB remains a major challenge, and blood donor screening strategies are currently in the process of implementation. While population and environmental changes facilitate increases in babesiosis, donor screening has the potential to eliminate TTB.

Description of 15 DNA-positive and antibody-negative "window-period" blood donations identified during prospective screening for Babesia microti.

BACKGROUND: Blood donation screening detecting only antibodies fails to identify donors in the earliest stage of infection, before a detectable immunologic response, that is, the "window period" (WP). We present data on WP donations identified during prospective screening for Babesia microti, a transfusion-transmissible parasite of increasing concern in the United States. STUDY DESIGN AND METHODS: Blood donations collected in Connecticut, Massachusetts, Minnesota, and Wisconsin were screened using polymerase chain reaction (PCR) and arrayed fluorescence immunoassay (AFIA) to detect B. microti DNA and antibodies, respectively. Parasite loads were estimated using quantitative PCR. Red blood cell (RBC) samples were inoculated into hamsters to assess infectivity. Donors screening reactive were indefinitely deferred, tested by supplemental methods, and followed to assess DNA and antibody clearance. Demographic data from WP donors (i.e., those screening PCR positive and AFIA negative) were compared to data from other positive donors. RESULTS: Of 220,479 donations screened from June 2012 to August 2016, a total of 700 were positive, of which 15 (2% of positive donations or 1 per 14,699 screened donations) were confirmed WP donations. The median estimated parasite load in WP donations was 350 parasites/mL, no different than AFIA-positive and PCR-positive donors. Parasite loads in RBC samples from WP units ranged from 14 to 11,022 parasites/mL; RBC samples from three of 10 (30%) WP donations infected hamsters. The mean age of WP donors was 48 years (range, 17-75 years); three (20%) were female. WP donor demographics did not differ significantly from demographics of other donors. CONCLUSIONS: We report one per 15,000 B. microti WP infections in blood donors in endemic areas, demonstrating the importance of nucleic acid testing to mitigate the risk of transfusion-transmitted babesiosis.

Inactivation of Babesia microti in red blood cells and platelet concentrates.

BACKGROUND: With an increasing number of recognized transfusion-transmitted (TT) babesiosis cases, Babesia microti is the most frequently TT parasite in the United States. We evaluated the inactivation of B. microti in red blood cells (RBCs) prepared in Optisol (AS-5) using amustaline and glutathione (GSH) and in platelet components (PCs) in 100% plasma using amotosalen and low-energy ultraviolet A (UVA) light. STUDY DESIGN AND METHODS: Individual RBCs and apheresis PCs were spiked with B. microti-infected hamster RBCs (iRBCs) to a final concentration of 106 iRBCs/mL and treated with the respective inactivation systems according to the manufacturer's instruction. Samples were collected before (control) and after (test) each treatment. Dilutions of the control samples to 10-6 were inoculated into hamsters, while the test samples were inoculated neat or at 10-1 dilution. At 3 and 5 weeks postinoculation, hamsters were evaluated for B. microti infection by microscopic observation of blood smears and 50% infectivity titers (ID50 ) were determined. Log reduction was calculated as control log ID50 minus test log ID50 . RESULTS: Parasitemia was detected in hamsters injected with as low as 100,000-fold diluted control samples, while no parasites were detectable in the blood smears of any hamsters receiving neat test samples. Mean log reduction was more than 5 log/mL by amustaline/GSH for RBCs and more than 4.5 log/mL by amotosalen/UVA for PCs. CONCLUSION: B. microti was inactivated to the limit of detection in RBCs and PCs after the respective inactivation treatment. Complete inactivation of B. microti was achieved in this animal infectivity model, and pathogen reduction treatment inhibited transmission of infection.