RESUMO
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.
Assuntos
Babesia/patogenicidade , Doadores de Sangue/estatística & dados numéricos , Programas de Rastreamento/métodos , Transcrição Gênica/genética , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
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.
Assuntos
Anticorpos Antiprotozoários/sangue , Babesia microti , Babesiose , Doadores de Sangue , Imunoglobulina G/sangue , Adolescente , Adulto , Babesiose/sangue , Babesiose/epidemiologia , Canadá/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Amplificação de Ácido Nucleico , Prevalência , Fatores de RiscoRESUMO
BACKGROUND: Because of the potential severe clinical consequences of Zika virus (ZIKV) infection, the large numbers of asymptomatic travelers returning from ZIKV-active areas, the detection of ZIKV nucleic acid in blood, and reports of transmission of ZIKV through transfusion, in 2016 the Food and Drug Administration released recommendations for individual-unit nucleic acid testing to minimize the risk of transmission of ZIKV through blood transfusions. METHODS: The American Red Cross implemented investigational screening of donated blood for ZIKV RNA by means of transcription-mediated amplification (TMA). Confirmatory testing of reactive donations involved repeat TMA, TMA testing in exploratory minipools, real-time reverse-transcriptase polymerase chain reaction, IgM serologic testing, and red-cell TMA. Viral loads in plasma and red cells were estimated by means of end-point TMA. The costs of interdicting a donation that was confirmed to be positive were calculated for the 15-month period between June 2016 and September 2017. RESULTS: Of the 4,325,889 donations that were screened, 393,713 (9%) were initially tested in 24,611 minipools, and no reactive donations were found. Of the 3,932,176 donations that were subsequently tested individually, 160 were initially reactive and 9 were confirmed positive (a 1:480,654 confirmed-positive rate overall; positive predictive value, 5.6%; specificity, 99.997%). Six (67%) of the confirmed-positive donations were reactive on repeat TMA, of which 4 were IgM-negative; of these 4, all 3 that could be tested were reactive on minipool TMA. Two confirmed-positive donors had infections that had been transmitted locally (in Florida), 6 had traveled to ZIKV-active areas, and 1 had received an experimental ZIKV vaccine. ZIKV RNA levels in red cells ranged from 40 to 800,000 copies per milliliter and were detected up to 154 days after donation, as compared with 80 days of detection in plasma at levels of 12 to 20,000 copies per milliliter. On the basis of industry-reported costs of testing and the yield of the tests in our study, the cost of identifying 8 mosquito-borne ZIKV infections through individual-unit nucleic acid testing was $5.3 million per ZIKV RNA-positive donation. CONCLUSIONS: Screening of U.S. blood donations for ZIKV by individual-donation TMA was costly and had a low yield. Among the 9 confirmed ZIKV-positive donations, only 4 were IgM-negative; of these donations, all 3 that were tested were reactive on minipool TMA. (Funded by the American Red Cross and Grifols Diagnostic Solutions.).
Assuntos
Doadores de Sangue , Sangue/virologia , Análise Custo-Benefício , Programas de Rastreamento/economia , Infecção por Zika virus/diagnóstico , Zika virus/isolamento & purificação , Adulto , Idoso , Feminino , Humanos , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Técnicas de Amplificação de Ácido Nucleico , RNA Viral/sangue , Cruz Vermelha , Sensibilidade e Especificidade , Estados Unidos/epidemiologia , Carga Viral , Adulto Jovem , Zika virus/genética , Zika virus/imunologia , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/virologiaRESUMO
BACKGROUND: Trypanosoma cruzi is endemic to the Americas where it demonstrates multiple lineages over a vast geographic range (i.e., United States to Argentina). These lineages possess divergent geographic and biologic characteristics, including variations in disease manifestations. Herein, we report the frequency of parasitemia among seropositive US blood donors and the potential association between parasite lineage and transfusion transmission. STUDY DESIGN AND METHODS: Blood donors identified as T. cruzi seropositive during screening were enrolled in follow-up studies, including hemoculture testing and a risk factor questionnaire. Positive hemocultures were expanded to obtain sufficient parasites for molecular lineage determination and analysis. Country of birth, obtained from the questionnaire, was used to predict parasite lineage in the absence of demonstrable parasitemia for infected donors. RESULTS: Eighteen (6.8%) of 263 seropositive donors were hemoculture positive. Among the 17 hemocultures expanded for lineage determination, TcV was identified more frequently (n = 12), compared to TcI (n = 2), TcII (n = 1), and TcVI (n = 2). When presumptive parasite lineages were compared to hemoculture results, only two of 157 (1.3%) TcI versus 13 of 38 (34.2%) TcII/TcV/TcVI non-US donors were parasitemic; three of 44 (6.8%) US donors were TcV or TcVI. CONCLUSIONS: Based on lineage determination for donors with parasitemia; hemoculture positivity associated with presumptive parasite lineage; and implicated donors from US, Canadian, and Spanish transfusion cases, donors from Southern South America are significantly more likely to have parasitemia and transmit infection to blood recipients (TcII, TcV, or TcVI vs. TcI). Thus, parasite lineage may be associated with risk of transfusion-transmitted T. cruzi.
Assuntos
Doadores de Sangue/estatística & dados numéricos , Parasitemia/epidemiologia , Reação Transfusional , Trypanosoma cruzi/patogenicidade , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Parasitemia/parasitologia , Parasitemia/transmissão , Reação em Cadeia da Polimerase , Fatores de Risco , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Human granulocytic anaplasmosis, caused by Anaplasma phagocytophilum, poses an increasing public health risk in the United States. Since 2000, case reports have increased annually; 2782 cases were reported in 2013. Despite the increasing frequency of clinical cases, only eight cases of transfusion-transmitted anaplasmosis (TTA) have been reported. We investigated if current leukoreduction practices impact transfusion risk. STUDY DESIGN AND METHODS: Whole blood units (WBUs) with integral red blood cell (RBC) leukoreduction filters were collected and spiked with A. phagocytophilum-infected HL-60 cells equivalent to 0.01, 1, or 5% of total neutrophils. After 24 hours at 4°C WBUs were processed into plasma and RBCs, the latter subsequently leukoreduced (LR RBCs). To evaluate the removal of A. phagocytophilum by filtration, pre- and postfiltration samples were compared by culture and polymerase chain reaction (PCR). RESULTS: Compared to Day 0 or Day 1 positive controls, LR RBCs demonstrated reduced levels of A. phagocytophilum by culture and PCR. At 0.01% infection levels LR RBCs yielded no positive cultures and a log reduction of 2.5 by PCR. Similarly, at 1 and 5% infections levels, LR RBCs produced only 44% (4/9) and 56% (5/9) positive cultures, respectively. PCR results were comparable, 3.0 log reduction for 1% and 3.3 log reduction for 5% infection levels. CONCLUSIONS: The recent increase in TTA suggests that A. phagocytophilum may represent an emerging blood safety issue. However, the current study indicates that the widespread practice of leukoreduction might passively reduce, but not eliminate, TTA risk. In the absence of viable testing or pathogen inactivation and/or reduction options, leukoreduction may offer some protection from transmission risk.
Assuntos
Anaplasma phagocytophilum/isolamento & purificação , Anaplasmose/prevenção & controle , Bacteriemia/prevenção & controle , Segurança do Sangue/métodos , Granulócitos/microbiologia , Procedimentos de Redução de Leucócitos/métodos , Anaplasmose/sangue , Anaplasmose/transmissão , Animais , Bacteriemia/sangue , Bacteriemia/transmissão , Técnicas Bacteriológicas , Sangue/microbiologia , Segurança do Sangue/instrumentação , DNA Bacteriano/sangue , Eritrócitos/microbiologia , Células HL-60/microbiologia , Humanos , Procedimentos de Redução de Leucócitos/instrumentação , Plasma/microbiologia , Comportamento de Redução do RiscoRESUMO
BACKGROUND: Babesia microti is an intraerythrocytic parasite, transmitted naturally to humans by infected ixodid ticks, that causes babesiosis. In recent years, B. microti has been identified as a growing public health concern that has also emerged as a critical blood safety issue in the absence of appropriate interventions to reduce transmission by blood transfusion. Thus, we evaluated the ability of the Mirasol pathogen reduction technology (PRT; CaridianBCT), which uses riboflavin (RB) and ultraviolet (UV) light, to diminish the presence of B. microti in apheresis plasma and platelets (PLTs). STUDY DESIGN AND METHODS: Apheresis plasma and PLT units were spiked with B. microti-infected hamster blood and subsequently treated using the Mirasol PRT system. Control and experimental samples were collected at different stages during the treatment process and injected into hamsters to detect the presence of viable parasites. Four weeks postinoculation, hamster blood was tested for B. microti infection by blood smear and real-time polymerase chain reaction analysis. RESULTS: None of the blood smears from animals injected with samples from PRT-treated plasma or PLT units were positive by microscopy, while all the non-PRT-treated plasma and PLT units were demonstrably parasitemic. Parasite load reduction in hamsters ranged between 4 and 5 log in all PRT-treated units compared to untreated controls. CONCLUSION: The data indicate that the use of RB and UV light efficiently reduces the presence of viable B. microti in apheresis plasma and PLT products, thereby reducing the risk of transfusion-transmitted Babesia potentially associated with these products. Based on this observed "proof of principle," future studies will determine the efficacy of the Mirasol PRT in whole blood.