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.
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.
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.
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 .).
Babesiosis is an emerging infectious disease caused by intraerythrocytic Babesia parasites that can cause severe disease and death. While blood type is known to affect the mortality of Plasmodium ...falciparum malaria patients, associations between red blood cell (RBC) antigens and Babesia microti infection and disease severity are lacking.
We evaluated RhD and ABO blood types of Babesia-infected (18S rRNA reactive) blood donors in 10 endemic states in the Northeastern and northern Midwestern United States. We also assessed possible associations between RhD and ABO blood types and disease severity among hospitalized babesiosis patients in Connecticut.
A total of 768 Babesia-infected blood donors were analyzed, of which 750 (97.7%) had detectable B. microti-specific antibodies. B. microti-infected blood donors were more likely to be RhD- (OR of 1.22, p-value 0.024) than RhD+ donors. Hospitalized RhD- babesiosis patients were more likely than RhD+ patients to have high peak parasitemia (p-value 0.017), which is a marker for disease severity. No differences in RhD+ blood type were noted between residents of the Northeast (OR of 0.82, p-value 0.033) and the Midwest (OR of 0.74, p-value 0.23). Overall, ABO blood type was not associated with blood donor B. microti infection, however, B. microti-infected donors in Maine and New Jersey were more likely to be blood type B compared to non-type B (OR 2.49 p = 0.008 and 2.07 p = 0.009, respectively), while infected donors from Pennsylvania were less likely to be type B compared to non-type B (OR 0.32 p = 0.02).
People expressing RhD antigen may have a decreased risk of B. microti infection and babesiosis severity. The association of B antigen with B. microti infection is less clear because the antigen appeared to be less prevalent in infected Pennsylvania blood donors but more prevalent in Maine and New Jersey infected donors. Future studies should quantify associations between B. microti genotypes, RBC antigens, and the frequency and severity of B. microti infection to increase our understanding of human Babesia pathogenesis and improve antibody, vaccine, and RBC exchange transfusion strategies.
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.
Babesia microti, an intraerythrocytic parasite, is tickborne in nature. In contrast to transmission by blood transfusion, which has been well documented, transmission associated with solid organ ...transplantation has not been reported. We describe parasitologically confirmed cases of babesiosis diagnosed ≈8 weeks posttransplantation in 2 recipients of renal allografts from an organ donor who was multiply transfused on the day he died from traumatic injuries. The organ donor and recipients had no identified risk factors for tickborne infection. Antibodies against B. microti parasites were not detected by serologic testing of archived pretransplant specimens. However, 1 of the organ donor's blood donors was seropositive when tested postdonation and had risk factors for tick exposure. The organ donor probably served as a conduit of Babesia parasites from the seropositive blood donor to both kidney recipients. Babesiosis should be included in the differential diagnosis of unexplained fever and hemolytic anemia after blood transfusion or organ transplantation.
are tick-borne intra-erythrocytic parasites and the causative agents of babesiosis.
, which are readily transfusion transmissible, gained recognition as a major risk to the blood supply, particularly ...in the United States (US), where
is endemic. Many of those infected with
remain asymptomatic and parasitemia may persist for months or even years following infection, such that seemingly healthy blood donors are unaware of their infection. By contrast, transfusion recipients are at high risk of severe babesiosis, accounting for the high morbidity and mortality (~19%) observed in transfusion-transmitted babesiosis (TTB). An increase in cases of tick-borne babesiosis and TTB prompted over a decade-long investment in blood donor surveillance, research, and assay development to quantify and contend with TTB. This culminated in the adoption of regional blood donor testing in the US. We describe the evolution of the response to TTB in the US and offer some insight into the risk of TTB in other countries. Not only has this response advanced blood safety, it has accelerated the development of novel serological and molecular assays that may be applied broadly, affording insight into the global epidemiology and immunopathogenesis of human babesiosis.
Babesia, a tick-borne genus of intraerythrocytic parasites, is understudied in humans outside of established high-endemic areas. There is a paucity of data on Babesia in Africa, despite evidence that ...it is regionally present. A pilot study suggested that Babesia was present in a rural district of Tanzania.
A cross-sectional study was conducted July-August 2017: residents in a case hamlet that had clustering of subjects with high signal-to-cut off (S/CO) ratios for antibodies against B. microti in the pilot study, and a control hamlet that had lacked significant signal, were evaluated for B. microti. Subjects aged ≥15yrs (n = 299) underwent clinical evaluation and household inspections; 10ml whole blood was drawn for Babesia transcription mediated amplification (TMA), B. microti indirect fluorescent antibody testing (IFA) and rapid diagnostic testing (RDT) for Plasmodium spp. Subjects aged <15yrs (n = 266) underwent a RDT for Plasmodium and assessment by ELISA for B. microti antibodies. A total of 570 subjects participated (mean age 22 <1 to 90yrs) of whom 50.7% were female and 145 (25.5%) subjects were Plasmodium RDT positive (+). In those <15yrs, the median ELISA S/CO was 1.11 (IQR 0.80-1.48); the median S/CO in the case (n = 120) and control (n = 146) hamlets was 1.19 (IQR 0.81-1.48) and 1.06 (IQR 0.80-1.50) respectively (p = 0.4). Children ≥5yrs old were more likely to have a higher S/CO ratio than those <5yrs old (p<0.001). One hundred (38%) subjects <15yrs were Plasmodium RDT+. The median S/CO ratio (children <15yrs) did not differ by RDT status (p = 0.15). In subjects ≥15yrs, no molecular test was positive for Babesia, but four subjects (1.4%) were IFA reactive (two each at titers of 128 and 256).
The findings offer further support for Babesia in rural Tanzania. However, low prevalence of seroreactivity questions its clinical significance.
The tumor suppressor retinoblastoma protein (Rb) plays a pivotal role in the regulation of cell proliferation and sensitivity to apoptosis through binding to E2F transcription factors. Loss of Rb in ...response to genotoxic stress or inflammatory cytokines can enhance cell death, in part, by eliminating Rb-mediated repression of proapoptotic gene transcription. Here we show that calpain cleavage of Rb facilitates Rb loss by proteasome degradation and that this may occur during tumor necrosis factor alpha-induced apoptosis. The cytoprotective, Rb-binding protein SerpinB2 (plasminogen activator inhibitor type 2) protects Rb from calpain cleavage, increasing Rb levels and enhancing cell survival. Chromatin immunoprecipitation assays show that the increased Rb levels selectively enhance Rb repression of proapoptotic gene transcription. This cytoprotective role of SerpinB2 is illustrated by reduced susceptibility of SerpinB2-deficient mice to multistage skin carcinogenesis, where Rb-dependent cell proliferation competes with apoptosis during initiation of papilloma development. These data identify SerpinB2 as a cell survival factor that modulates Rb repression of proapoptotic signal transduction and define a new posttranslational mechanism for selective regulation of the intracellular levels of Rb.
Babesia blood testing: the first‐year experience Tonnetti, Laura; Dodd, Roger Y.; Foster, Gregory ...
Transfusion (Philadelphia, Pa.),
January 2022, 2022-01-00, 20220101, Letnik:
62, Številka:
1
Journal Article
Recenzirano
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.
BACKGROUND
Borrelia miyamotoi,
the agent of relapsing fever, is a tick‐borne spirochete first isolated in Japan in 1994. Since then, the spirochete has been detected in ticks globally, generally in ...the same vectors as the Lyme disease agent. Human infection has been reported in Russia, Europe, Japan, and the United States, as influenza‐like febrile illness. In addition, two cases of meningoencephalitis caused by
B. miyamotoi
have also been reported in immunocompromised patients. Here we evaluate the ability of the spirochete to survive in human blood components stored under standard blood bank conditions.
STUDY DESIGN AND METHODS
Freshly collected human whole blood was spiked with in vitro cultured
B. miyamotoi
or
B. miyamotoi
–infected mouse plasma and separated into red blood cells (RBCs), plasma, and platelets. Components were either injected into immunocompromised (SCID) or wild‐type immunocompetent mice or cultured in vitro, right after separation and after storage at the appropriate conditions. Infection was monitored by microscopic observation, blood smears, and polymerase chain reaction.
RESULTS
In vivo, all the SCID mice challenged with the components before storage and the RBCs stored for up to 42 days developed the infection. Wild‐type mice also developed the infection when injected with prestorage samples from all components, while a lower number of mice were infected by RBCs stored for 42 days. In vitro, spirochetes grew in all samples but frozen plasma.
CONCLUSIONS
This study demonstrated that
B. miyamotoi
can survive standard storage conditions of most human blood components, suggesting the possibility of transmission by blood transfusion.
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.
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