Blood Recipients Research Articles

Motivations for blood donation by HIV-positive individuals on antiretrovirals in South Africa: A qualitative study.

We performed a mixed-methods study to explore the motivations associated with blood donation by donors with known, but undisclosed HIV-positive status and ARV use (HIV+/ARV+), seeking potential strategies to reduce such donations and mitigate risk for blood recipients. Here, we report predominantly the qualitative component. A safe and sustainable blood supply is dependent in part, on effective pre-donation donor assessment. We previously described failure by HIV+/ARV+ blood donors to disclose their status. Such donations may lead to transfusion-transmitted HIV. The social ecological model provided the conceptual framework for this study. Previously identified HIV+/ARV+ donors were invited to complete a survey (including a validated stigma scale) and qualitative interview, which underwent inductive and deductive thematic analysis. We uncovered two primary motivational paths to HIV+/ARV+ blood donations: privacy and altruism. The latter included a motivation not previously reported in the literature: donating specifically for other people living with HIV (PLWH). The other primary factor was a lack of privacy. These accounts often included donors encountering donation opportunities when accompanied by people to whom they had not and did not plan to disclose their HIV status. Most were highly confident their donations would be identified as HIV-positive and discarded. We demonstrated a complex interaction between individual, social, cultural, and structural/policy factors in blood donations by PLWH who take ARV. Recommendations to limit HIV + ARV+ donations include: (1) Targeted communication strategies to increase knowledge among PLWH of their deferral from blood donation-without increasing stigma, and (2) development of procedures to assist those who feel unable to opt-out of donation due to privacy concerns.

Umbilical Cord Blood Transplantation: Connecting Its Origin to Its Future.

Transplantation of umbilical cord blood (UCB) is an attractive alternative source of hematopoietic stem cells (HSCs). The unique properties of cord blood and its distinct immune tolerance and engraftment kinetics compared to bone marrow (BM) and peripheral blood progenitor cells, permit a wider disparity in human leukocyte antigen levels between a cord blood donor and recipient after an unrelated umbilical cord blood transplant (UCBT). In addition, it is readily available and has a lowered risk of graft-versus-host disease (GvHD), with similar long-term clinical outcomes, compared to BM transplants. However, the relatively low number of cells administered by UCB units, as well as the associated delayed engraftment and immune reconstitution, pose limitations to the wide application of UCBT. Research into several aspects of UCBT has been evaluated, including the ex vivo expansion of cord blood HSCs and the process of fucosylation to enhance engraftment. Additionally, UCB has also been used in the treatment of several neurodegenerative and cardiovascular disorders with varying degrees of success. In this article, we will discuss the biology, clinical indications, and benefits of UCBT in pediatric and adult populations. We will also discuss future directions for the use of cord blood.

Whole blood administration within USCENTCOM

Introduction Blood product use by the U.S. military has evolved during the conflicts in the U.S. Central Command's area of responsibility to become the preferred resuscitative fluid for damage control procedures. This study evaluates the transition to a whole blood-based trauma system over the past 5 years. Methods Patients who received blood product transfusion within USCENTCOM between January 1, 2017, and December 31, 2021, were identified from the Medical Situational Awareness in Theater (MSAT) blood reports. Transfusion recipients were categorized as recipients of whole blood only, component therapy only, or mixed therapy. The type of transfusions, number of recipients, number of available blood products were compared over the 5-year period. Results A total of 1762 unique patients were included. Of this population, 220 (12.5%) received whole blood only, 1196 (68.9%) received component therapy, and 346 (19.6%) received mixed therapy. The monthly proportion of individuals receiving whole blood (only or mixed) significantly increased over the 5-year period ( p < .0001). The number of individuals requiring transfusions over this same period decreased significantly ( p < .0001). Individuals receiving component therapy (only or mixed) were transfused component platelets 15.7% of the time. The mean and median number of units required per patient receiving whole blood was 2.39 and 1 unit of blood respectively (IQR 1.0–2.5). Conclusion Whole blood use increased significantly within USCENTCOM's AOR secondary to increased supply and low clinical requirement. Without a long-lasting platelet component, component therapy cannot be expected to provide a balanced therapy to casualties in remote locations.

Emergency, ABO-Incompatible Living Donor Liver Re-Transplantation for Graft Failure Complicated by Pneumonia-Associated Sepsis.

Although liver re-transplantation is the only therapeutic option for acute and chronic graft failure, few studies have addressed the use of ABO-incompatible living donors in the emergency setting. Here, based on our experience, we report a successful case of emergency, ABO-incompatible, adult-to-adult, living donor liver re-transplantation (LDLT) for late graft failure from chronic rejection complicated by pneumonia-related sepsis. A fifty-five-year-old man had undergone LDLT for hepatocellular carcinoma accompanied by hepatitis C virus (HCV)-related cirrhosis in 30 September 2013. The voluntary donor was his 56-year-old wife, who was also a carrier of HCV. The donor and recipient blood types were the same: O and Rh positive. She underwent a right hepatectomy and was discharged on postoperative day (POD) seven. The patient was also discharged without complications on POD eleven and was followed up with on an outpatient basis. Abdominal distension and jaundice were developed at 6 months after LDLT, when the serum total bilirubin level was 2.7 mg/dL. The serum total bilirubin levels increased rapidly to 22.9 mg/dL over the next 4 months. Chronic rejection was diagnosed via liver biopsy. On 3 October 2014, he developed pneumonia-related sepsis and showed the progressive deterioration of liver function. Liver re-transplantation using the right liver from his ABO-incompatible, 20-year-old nephew was performed as an emergency in 15 October 2014. The donor blood type was A and Rh positive. The resection of the failed graft and the implantation of a new graft was performed by the intragraft dissection technique to re-use previously transplanted graft vessels in order to cope with severe adhesions. The recipient went through a gradual recovery process and was finally discharged on POD 50 with normal liver function, while the donor had an uneventful recovery and was discharged on POD 7. Biloma due to bile leak was detected three months after re-transplantation and was cured by percutaneous interventional procedures. Since then, the postoperative course has been event-free at regular outpatient follow-ups. The patient has so far had normal laboratory findings and no signs of complications. It has been 98 months since the re-transplantation, and the recipient and two donors are still in good condition with normal liver function, having complete satisfaction with the results obtained from this re-transplantation. In conclusion, long-term, satisfactory outcomes can be achieved in emergency, ABO-incompatible, adult-to-adult, living donor liver re-transplantation for graft failure complicated by pneumonia-related sepsis in selected patients.

BK virus in kidney transplant recipients with graft dysfunction

ABSTRACT This study was to estimate the viral load of BK virus (BKV) in the urine and blood of Kidney transplant recipients (KTRs) with graft dysfunction and its effect on the development of graft dysfunction. This analysis included all KTR outpatients who visited the clinic at Urology and Nephrology Center during their routine follow-up visits from September 2017 to May 2019. A total of 100 patients were divided into 62 KTR patients with kidney dysfunction (case group) vs. 38 KTR patients without kidney dysfunction (control group). BKV DNA quantification in urine and plasma samples was examined in all patients by the real time PCR method. The BKV DNA was detected in the urine samples of 5 patients, all with kidney dysfunction (8%) vs. none in the control group. The BKV viral load of the 5 cases ranged from 105 to 244000 copies/ml. The BKV DNA was not detected in the blood samples of the 5 urine-positive cases. It was concluded that all patients with kidney dysfunction should be screened for BKV in their urine samples to prevent the development of BKV-caused nephropathy and further graft failure.

Cytomegalovirus breakthrough and resistance during letermovir prophylaxis.

Letermovir is a relatively new antiviral for prophylaxis against cytomegalovirus (CMV) after allogeneic hematopoietic cell transplantation (HCT). CMV-seropositive HCT recipients who received letermovir prophylaxis from 2018 to 2020 at our center were evaluated for letermovir resistance and breakthrough CMV reactivation. Two-hundred twenty-six letermovir recipients were identified and 7/15 (47%) with CMV DNAemia ≥200 IU/mL were successfully genotyped for UL56 resistance. A single C325Y resistance mutation was identified in an umbilical cord blood recipient. Ninety-five (42%), 43 (19%), and 15 (7%) patients had breakthrough CMV at any level, ≥150 IU/mL, and ≥500 IU/mL, respectively. Risk factors for breakthrough CMV reactivation at each viral threshold were examined. Cumulative steroid exposure was the strongest risk factor for CMV at all evaluated viral thresholds. Graft-versus-host disease prophylaxis with post-transplantation cyclophosphamide (aHR 2.34, 95% CI 1.28-4.28, p = 0.001) or calcineurin inhibitors plus mycophenolate (aHR 2.24, 95% CI 1.30-3.86, p = 0.004) were also associated with an increased risk of CMV reactivation at any level. De novo letermovir resistance is rare and can be successfully treated using other antivirals. Letermovir effectively prevents clinically significant CMV, however, subclinical CMV reactivation occurs frequently at our center.

Alternative forms of portal vein revascularization in liver transplant recipients with complex portal vein thrombosis

Complex portal vein thrombosis (PVT) is a challenge in liver transplantation (LT). Extra-anatomical approaches to portal revascularization, including renoportal (RPA), left gastric vein (LGA), pericholedochal vein (PCA), and cavoportal (CPA) anastomoses, have been described in case reports and series. The RP4LT Collaborative was created to record cases of alternative portal revascularization performed for complex PVT. An international, observational web registry was launched in 2020. Cases of complex PVT undergoing first LT performed with RPA, LGA, PCA, or CPA were recorded and updated through 12/2021. A total of 140 cases were available for analysis: 74 RPA, 18 LGA, 20 PCA, and 28 CPA. Transplants were primarily performed with whole livers (98%) in recipients with median (IQR) age 58 (49-63) years, model for end-stage liver disease score 17 (14-24), and cold ischemia 431 (360-505) minutes. Post-operatively, 49% of recipients developed acute kidney injury, 16% diuretic-responsive ascites, 9% refractory ascites (29% with CPA, p <0.001), and 10% variceal hemorrhage (25% with CPA, p= 0.002). After a median follow-up of 22 (4-67) months, patient and graft 1-/3-/5-year survival rates were 71/67/61% and 69/63/57%, respectively. On multivariate Cox proportional hazards analysis, the only factor significantly and independently associated with all-cause graft loss was non-physiological portal vein reconstruction in which all graft portal inflow arose from recipient systemic circulation (hazard ratio 6.639, 95% CI 2.159-20.422, p= 0.001). Alternative forms of portal vein anastomosis achieving physiological portal inflow (i.e., at least some recipient splanchnic blood flow reaching transplant graft) offer acceptable post-transplant results in LT candidates with complex PVT. On the contrary, non-physiological portal vein anastomoses fail to resolve portal hypertension and should not be performed. Complex portal vein thrombosis (PVT) is a challenge in liver transplantation. Results of this international, multicenter analysis may be used to guide clinical decisions in transplant candidates with complex PVT. Extra-anatomical portal vein anastomoses that allow for at least some recipient splanchnic blood flow to the transplant allograft offer acceptable results. On the other hand, anastomoses that deliver only systemic blood flow to the allograft fail to resolve portal hypertension and should not be performed.

T Cell-Depleted Peripheral Blood versus Unmanipulated Bone Marrow in Matched Sibling Transplantation for Aplastic Anemia

Bone marrow (BM) is the recommended stem cell source for hematopoietic stem cell transplantation (HSCT) from matched sibling donors (MSDs) in patients with severe aplastic anemia (SAA) for its superior survival and graft-versus-host disease (GVHD) outcomes compared to recipients of unmanipulated peripheral blood (PB) HSCT. Nevertheless, no studies comparing BM with ex vivo T cell-depleted (TCD) PB have been reported to date. The aim of the present study was to compare the transplantation outcomes of MSD HSCT recipients with SAA using PB (with partial ex vivo TCD targeted cell dose grafts) with those of MSD HSCT recipients with SAA using unmanipulated BM. We performed a matched-pair analysis of MSD-HSCT using TCD PB in a single institution with unmanipulated BM MSD-HSCT in the United States between 2013 and 2019 reported to the Center for International Blood and Marrow Transplant Research. We compared 23 recipients of TCD PB HSCT for SAA (cases) and 69 recipients of unmanipulated BM grafts (controls) matched for age, Karnofsky Performance Status, Hematopoietic Cell Transplantation-Specific Comorbidity Index, time from diagnosis to transplantation, and recipient cytomegalovirus serostatus. We found significantly faster neutrophil and platelet recovery in the TCD PB cohort (P < .001 and P=.03, respectively), as well as a lower incidence of grade II-IV acute GVHD (0% versus 17%; P=.05) and similar overall survival (96% versus 97% at 3 years; P=.8). Our study shows that TCD PB can be considered a safe source for MSD-HSCT in patients with SAA, with potential advantages in engraftment and GVHD that could challenge the standard with BM. These findings provide a basis for future research in a prospective controlled clinical trial.

Platelet and cryoprecipitate transfusions from female donors improve coagulopathy in vitro.

Females are relatively hypercoagulable compared with males, with increased platelet aggregation and improved clot dynamics. However, sex differences in coagulation have not yet been considered in transfusion guidelines. Therefore, our objective was to evaluate hemostatic differences in sex concordant and sex discordant cryoprecipitate and platelet transfusions. We hypothesized that transfusion of blood products from female donors results in improved coagulopathy compared with male blood products. This was a cohort study evaluating sex dimorphisms in coagulation assays and clotting factors in healthy volunteer plasma and cryoprecipitate. Sex dimorphisms in transfusions were evaluated using an in vitro coagulopathy model. Female or male platelets or single-donor cryoprecipitate was added to "recipient" whole blood after dilution of recipient blood with citrated saline to provoke a coagulopathic profile. Citrated native thromboelastography was then performed. Liquid chromatography/mass spectroscopy was performed on single-donor cryoprecipitate to evaluate sex dimorphisms in the proteome of cryoprecipitate. Females have an increased proportion of functional fibrinogen. Transfusion of female-donor platelets and cryoprecipitate induces a larger decrease in R time and greater increase in angle than male-donor platelets or cryoprecipitate. Female-donor cryoprecipitate has increased factor V and factor XIII compared with male cryoprecipitate, and comprehensive proteomics revealed sex differences in several proteins with potential immunological significance. Platelets and cryoprecipitate from female donors improve coagulopathy more than male blood products in vitro. Increased factor V and factor XIII activity as well as increased fibrinogen activity in female donors appears to drive this disparity. Sex differences in the proteome of cryoprecipitate may influence how transfusions modulate the thromboinflammation of trauma. The differing hemostatic profiles of female and male blood products suggest the potential role of sex-specific transfusions guidelines in hemostatic resuscitation.

Intra-Peritoneal Transplantation for Generating Acute Myeloid Leukemia in Mice.

There is an unmet need for novel therapies to treat acute myeloid leukemia (AML) and the associated relapse that involves persistent leukemia stem cells (LSCs). An experimental AML rodent model to test therapies based on successfully transplanting these cells via retro-orbital injections in recipient mice is fraught with challenges. The aim of this study was to develop an easy, reliable, and consistent method to generate a robust murine model of AML using an intra-peritoneal route. In the present protocol, bone marrow cells were transduced with a retrovirus expressing human MLL-AF9 fusion oncoprotein. The efficiency of lineage negative (Lin-) and Lin-Sca-1+c-Kit+ (LSK) populations as donor LSCs in the development of primary AML was tested, and intra-peritoneal injection was adopted as a new method to generate AML. Comparison between intra-peritoneal and retro-orbital injections was done in serial transplantations to compare and contrast the two methods. Both Lin- and LSKcells transduced with human MLL-AF9 virus engrafted well in the bone marrow and spleen of recipients, leading to a full-blown AML. The intra-peritoneal injection of donor cells established AML in recipients upon serial transplantation, and the infiltration of AML cells was detected in the blood, bone marrow, spleen, and liver of recipients by flow cytometry, qPCR, and histological analyses. Thus, intra-peritoneal injection is an efficient method of AML induction using serial transplantation of donor leukemic cells.

Prevalence of antibody to hepatitis B surface antigen among qualified blood donors in Nanjing, China

ABSTRACT Universal infant hepatitis B vaccination has been implemented more than three decades. This study aimed to determine the prevalence of antibodies to hepatitis B surface antigen (anti-HBs) and to hepatitis B core antigen (anti-HBc) in qualified blood donors in Nanjing, China. Plasmas of 815 qualified blood donors, collected from February through May 2019, were measured for anti-HBs and anti-HBc by enzyme-linked immunosorbent assay. There were 449 (55.1%) male and 366 (44.9%) female blood donors, with a median age of 28.9 years (18–60). The seroprevalence of anti-HBs was 58.8%, with no significant difference in different genders and different age groups. The overall prevalence of anti-HBc was 7.0%, with an increasing trend with age, from 0% in 18–20 years old group to 17.9% in 51–60 years old group (χ 2 = 46.7965, p < .0001). The prevalence of anti-HBc in donors born after the implementation of universal hepatitis B vaccination was significantly lower than that in donors born before (1.0% vs 15.5%; χ 2 = 63.6033, p < .0001). Our data suggest that more than half of the blood donors in Nanjing are anti-HBs positive. Since a blood recipient usually receives more than one unit of red blood cells or plasma, passively acquired anti-HBs in blood recipients may neutralize hepatitis B virus potentially presented in blood donors with occult hepatitis B infection. In addition, the presence of anti-HBs and/or anti-HBc in blood donors may cause unique hepatitis B serological profile in blood recipients.

Blood, Gut, and Oral Microbiome in Kidney Transplant Recipients.

Recent reports describe the existence of a blood microbiome profile not associated with an infection state. Given the high impact that the dysbiotic human microbiome appears to have in chronic kidney disease and, in particular, in the outcome of kidney transplant recipients (KTRs), we aimed to explore the variations and correlations of the gut, oral, and blood microbiome of recipients, 3 months after kidney transplantation. We conducted a cross-sectional study where the microbiome of stool, saliva, and blood collected from recipients 3 months after kidney transplantation (N = 6) was analyzed by polymerase chain reaction (PCR) amplification and sequencing of the V3-V4 hypervariable regions of the 16S rRNA gene using MiSeq Illumina® technology. Blood of KTRs harbors a distinct low-abundance microbiome dominated by Proteobacteria and Firmicutes. Gut and oral microbiome of KTRs also present distinct profiles. The existence of a proportion of shared operational taxonomic units among the different body sites is reported, mainly classified as Proteobacteria and Firmicutes. This study provides evidence of existence a blood microbiome in KTRs, different from the gut and the oral microbiome profiles, with a small number of operational taxonomic units representing a shared microbiome. The clinical relevance of this observation should be further explored in these patients.

Detecting and Quantifying Donor derived cell free DNA in the blood of kidney transplant recipients as a biomarker for graft injury and immunosuppression

Detecting and Quantifying Donor derived cell free DNA in the blood of kidney transplant recipients as a biomarker for graft injury and immunosuppression

Scenario of HIV infection in Pakistan

Human immunodeficiency virus (HIV) infection, which was previously lethal, has evolved into a chronic disease that may be treated and well-managed. HIV levels in the bloodstream may become undetectable with antiretroviral therapy (ART). All those providing care for people living with HIV should be aware of the risk factors, transmission, diagnosis, and treatment, acute HIV infection, possible opportunistic infections, and malignancies. Preexposure and postexposure prophylaxis regimens allow for preventive treatment. Home healthcare specialists can help people follow their drug schedules, assess the effectiveness of their treatments, and identify HIV problems and ART side effects. The ability to support, inform, and counsel people living with HIV and their families is most crucial [1].&#x0D; Approximately 38.9 million people worldwide were living with HIV, 25.4 million had access to antiretroviral therapy (ART), 1.7 million had just recently contracted the virus, and 690,000 had passed away from AIDS-related illnesses, according to a Joint United Nations Program on HIV/AIDS 2020 report. Although Pakistan's national HIV/AIDS control program was established in 1987, the number of new HIV/AIDS cases has been rising quickly ever since. In Pakistan, 160,000 people were living with HIV/AIDS as of 2018, yet only 10% of them were receiving ART. 3 Increasing people with HIV/AIDS' access to ART has a number of positive effects, including delaying the advancement of the disease, extending life expectancy, and enhancing people's quality of life and mental health [2].&#x0D; "More than 1,000 new HIV cases are reported each month from all four provinces, including the capitol city Islamabad, Azad Kashmir, and Gilgit Baltistan. This demonstrates unequivocally that homosexuals, persons who inject drugs, male, female, and transgender sex workers, and other critical demographics are now spreading HIV to the broader community. During the final 10 months of 2022, 9,773 people in Pakistan had HIV tests that were positive, casting significant doubt on HIV preventive and control initiatives and amply demonstrating the spread of HIV from important populations to the general public. New HIV infections account for a sizable portion of low-risk males, females, and clients of critical communities, showing an increase in HIV transmission to bridging populations [3].&#x0D; The increased rate of HIV in Pakistan pose a risk to a healthy population, blood recipients etc. Therefore, surrounding communities should also be checked for HIV. The government should direct public education campaigns in coordination with NGOs. To prevent any future epidemics, barbers and unlicensed health professionals in remote regions should receive training.

Incidence, Risk Factors, and Outcomes of Kidney Transplant Recipients With BK Polyomavirus-Associated Nephropathy

BK polyomavirus-associated nephropathy (BKPyVAN) is associated with graft dysfunction and loss; however, knowledge of immunosuppression reduction strategies and long-term graft, and patient outcomes across the disease spectrum is lacking. This cohort study included 14,697 kidney transplant recipients in Australia and New Zealand (2005-2019), followed for 91,306 person years. BKPyVAN occurred in 460 recipients (3%) at a median posttransplant time of 4.8 months (interquartile range, 3.1-10.8). Graft loss (35% vs. 21%, P< 0.001), rejection (42% vs. 25%, P< 0.001), and death (18% vs. 13%, P= 0.002) were more common in the BKPyVAN group. The most frequent changes in immunosuppression after BKPyVAN were reduction (≤50%) in tacrolimus (172, 51%) and mycophenolate doses (134, 40%), followed by the conversion of mycophenolate to leflunomide (62, 19%) and tacrolimus to ciclosporin (20, 6%). Factors associated with the development of BKPyVAN included (adjusted hazard ratio [HR]; 95% confidence interval) male sex (1.66; 1.34-2.05), recipient age (≥70 vs.<20 [2.46; 1.30-4.65]), recipient blood group (A vs. B [2.00; 1.19-3.34]), donor age (≥70 vs.<20 [2.99; 1.71-5.22]), earlier era (1.74; 1.35-2.25), donor/recipient ethnic mismatch (1.52; 1.23-1.87), tacrolimus use (1.46; 1.11-1.91), and transplantation at a lower-volume transplant center (1.61; 1.24-2.09). The development of BKPyVAN was associated with an increased risk of all-cause (1.75; 1.46-2.09) and death-censored graft loss (2.49; 1.99-3.11), but not mortality (1.15; 0.91-1.45). BKPyVAN is associated with an increased risk of all-cause and death-censored graft loss, but not death. Interventional trials are urgently needed to evaluate the efficacy of immunosuppression reduction and novel strategies to minimize the adverse outcomes associated with BKPyVAN.

Analysis of Transfusion-Transmitted Bacterial Infections according to German Hemovigilance Data (2011–2020)

Introduction: Following the first assessment of the effects of safety measures taken against transfusion-transmitted bacterial infections (TTBI), the Paul-Ehrlich-Institut (PEI) decided to newly analyze risk minimization measures (RMM) using German hemovigilance data from 2011 to 2020, focusing on blood components, recipients, and bacterial strains. Materials and Methods: The PEI assessed the imputability of all reported serious adverse reactions (SAR) relying mainly on microbiological test results. Reporting rates (RR) of suspected, confirmed, and fatal confirmed TTBI were calculated and compared to the previous reporting 10-year period (2001–2010) using Poisson regression to estimate RR ratios (RRR). Furthermore, details on blood component age, patients’ medical history, and bacterial pathogenicity were collected. Results: With respect to the previous 10-year period, the number of suspected TTBI increased (n = 403), while fewer cases were confirmed (n = 40); the number of deaths remained more or less unchanged (n = 8). The RR for suspected TTBI were 7.9, 18.7, and 1.6 cases per million units transfused for red blood cells (RBC), platelet concentrates (PC), and fresh frozen plasma (FFP), respectively. RRR showed a statistically significant 2.5-fold increase in the RR for suspected TTBI after RBC administration from 2001–2010 to the period under review (p < 0.0001). The RR for confirmed TTBI were 0.4, 5.0, and 0.0 cases per million units transfused for RBC, PC, and FFP, respectively. Compared to the period 2001–2010, there was a statistically significant decrease in the RR of confirmed TTBI by half for PC (p = 0.0052). The RR for confirmed PC-caused TTBI with fatal outcome was 1.4 cases per million units transfused. Regardless of type of blood product transfused and outcome of SAR, the majority of TTBI occurred after administration of a product at the end of shelf life (40.0%) and to recipients of advanced age (median age: 68.5 years) and/or with severe immunosuppression (72.5%) due to decreased myelopoiesis (62.5%). 72.5% of the involved bacteria had a middle/high human pathogenicity. Conclusion: Despite a significant decrease in confirmed TTBI following PC transfusion in Germany after implementation of RMM, the current manufacture of blood products can still not prevent TTBI with fatal outcomes. As demonstrated in various countries, RMM like bacterial screening or pathogen reduction may measurably improve the safety of blood transfusion.

Assessment of Risk of Exposure to Leishmania Parasites among Renal Disease Patients from a Renal Unit in a Sri Lankan Endemic Leishmaniasis Focus.

Leishmania donovani causes both cutaneous and visceral leishmaniasis (CL and VL) in Sri Lanka, where chronic kidney disease (CKD) and kidney transplant recipients' (KTR) geographical areas overlap. This study aimed to determine the risk of exposure to Leishmania infection among renal patients. This cross-sectional study in a renal unit assessed clinical symptoms and signs of CL and VL in recipients of blood/kidney or immunosuppressives. Sera were tested with Leishmania-specific DAT and rK-39 ELISA. There were 170 participants. A total of 84.1% (n = 143) were males (CKD: 101, KTR; 42, mean age 45) and 27 were females (females: CKD: 23, KTR: 4, mean age 39 years). Recipients of blood transfusion/s within last 2 years: 75.9% (CKD: 115, KTR: 14), on immunosuppressive therapy: 34.1% (CKD: 13, KTR: 45). Two CKD patients repeatedly showed clear positive titres (1: 12,800 and 1: 3200) with Leishmania-DAT and another two (CKD) became marginally positive with rK39-ELISA. Prevalence of anti-Leishmania antibodies: 2.4% (4/170). All four patients were clinically asymptomatic and were recipients of recent blood transfusions. Attributable risk of exposure to Leishmania infection through blood transfusions was 0.032, OR 2.99 (95% CI = 0.16 to 56.45, p = 0.47). Therefore, routine screening of kidney/blood donors and CKD and KTR patients in Sri Lanka may not be necessary.

1970. SARS-CoV-2 T-cell specific responses in allogeneic hematopoietic stem cell transplant recipients after second and third dose of BNT162b2 mRNA vaccine

Abstract Background Cell-mediated immunity (CMI) after anti-Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 vaccines has been poorly explored in recipients of allogeneic hematopoietic stem-cell transplantation (HSCT), especially with regard to the 3rd dose (booster). Aim of the study was to assess the specific T-cell responses before and after the 3rd dose of BNT162b2 mRNA vaccine in a cohort of allogeneic HSCT recipients, and compare it with healthy donors (HD). Methods Allogenic HSCT recipients and HD were enrolled before receiving the 3rd dose of BNT162b2 mRNA vaccine. Whole blood for T-cell specific responses was collected before (T1) and 8 weeks after (T2) the booster administration. T-cell responses were assessed with an Interferon (IFN)-γ release assay (IGRA), after overnight stimulation of heparin whole blood with pools of lyophilized peptides, covering the immunodominant sequence of the Spike (S) protein. IFN-γ production was assessed with an enzyme linked immunosorbent assay (ELISA). Statistical analysis was performed with GraphPadPrism. Results 14 HSCT recipients (8M, 6F) and 15 HD (7M, 8F) were enrolled (table 1). Median age was 47 [39-59] and 41 [31-48] years in the HSCT and HD groups, respectively. Time between the vaccine 2nd dose and T1 was significantly longer in HD than HSCT recipients (p&amp;lt; .001), while the time between T1 and T2 did not differ between the two groups. SARS-CoV-2 S specific T-cell responses at T1 were inferior in HSCT recipients compared to HD (median IFN-γ production: 463 vs 231 ng/ml, respectively), although the difference did not reach the statistical significance. No differences were observed at T2. In a before-after analysis, SARS-CoV-2 S specific T-cell responses were significantly increased in HSCT recipients at T2 compared to T1 (median IFN-γ production: 267 vs 881 ng/ml, p=0.02) (Figure 1). At T1, 3 HSCT recipients showed very low or no IFN-γ production, while at T2 only 1 patient still had undetectable IFN-γ production after S peptide stimulation. Table 1:Clinical characteristics of allo-HSCT recipients and HDHSCT: hematopoietic stem-cell transplantation; IQR: interquartile range; ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; MDS: myelodysplastic syndrome; T-ALL: T-cell acute lymphoblastic leukemia; AA: aplastic anemia; PMF: primary myelofibrosis; MUD: matched unrelated donor; MMUD: mismatched unrelated donors; NA: not applicable; ns: not significant.Figure 1:IFN-γ Production after Spike peptide stimulation of whole blood from allogenic HSCT recipients and HD.Comparison of IFN-γ production after Spike peptide stimulation of whole blood in allogenic HSCT recipients and HD at T1 (1.A) and T2 (1.B) (before and after BNT162b2 mRNA vaccine 3rd dose, respectively). Before-after representation of IFN-γ production after Spike peptide stimulation in HD and allogenic HSCT recipients (1.C). Conclusion SARS-CoV-2 IGRA represents a useful tool to assess CMI, also in immunocompromised hosts. An additional 3rd BNT162b2 mRNA vaccine booster dose seems to enhance CMI in allogenic HSCT recipients. Further studies are needed to evaluate the duration of SARS-CoV-2 CMI in HSCT recipients compared to HD. Disclosures All Authors: No reported disclosures.

231. Outcomes by Baseline Pathogen and Susceptibility in the ReSTORE Phase 3 Trial of Rezafungin Once Weekly Compared with Caspofungin Once Daily in Patients with Candidemia and/or Invasive Candidiasis

Abstract Background Rezafungin is a next-generation, once-weekly echinocandin in development for treatment of candidemia and invasive candidiasis (IC), and for prevention of invasive fungal diseases caused by Candida, Aspergillus, and Pneumocystis in allogeneic blood and marrow transplant recipients (Fig 1). ReSTORE (NCT03667690) is a global, double-blind, double-dummy, 1:1 randomized, controlled, Phase 3 non-inferiority trial that evaluated the efficacy and safety of rezafungin once weekly (QWk) versus caspofungin once daily (QD) in patients with candidemia and/or IC. This analysis of the completed ReSTORE trial was conducted to evaluate outcomes by baseline pathogen and susceptibility. Methods In ReSTORE, adults (≥18 y) with systemic signs and mycological confirmation of candidemia and/or IC received either rezafungin QWk (400 mg Week 1, then 200 mg QWk) or caspofungin QD for ≥14 days (up to 4 weeks) with optional oral fluconazole step-down in the caspofungin arm. The primary endpoints were global cure at day (D) 14 (per Data Review Committee confirmation of investigator-assessed clinical cure [and radiological cure for IC) + mycological eradication]) and all-cause mortality (ACM) at D30 (Fig 2). Secondary endpoints included mycological eradication at D14. For this analysis, D14 global cure and mycological eradication by treatment group were analyzed by Candida species and in vitro susceptibility at baseline (CLSI broth microdilution MIC values; M27 Ed4) (Fig 3). Results A total of 204 Candida isolates were recovered in 187 patients across both treatment groups. Of the 204 isolates, C. albicans was the most common species, followed by C. glabrata, C. tropicalis, and C. parapsilosis; 61% of all baseline isolates were non-albicans Candida (Fig 3). The rates of D14 global cure and mycological eradication by pathogen are shown in Tables 1 and 2. Overall, outcomes by Candida species and MIC did not appear to be affected by MIC values for either rezafungin or caspofungin (Table 3). Conclusion Rezafungin was efficacious across multiple Candida species in the Phase 3 ReSTORE trial that demonstrated non-inferiority of rezafungin to caspofungin. There was no clear correlation between increased MIC values and clinical outcomes. Disclosures George R. Thompson, III, MD, Amplyx: Advisor/Consultant|Amplyx: Grant/Research Support|Astellas: Advisor/Consultant|Astellas: Grant/Research Support|Cidara: Advisor/Consultant|Cidara: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Merck: Grant/Research Support|Pfizer: DSMB|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support Alex Soriano, MD, MSD, Pfizer, Shionogi, Angelini, Menarini, Gilead: Honoraria Oliver A. Cornely, Prof. Dr., Abbott: Honoraria|Abbvie: Advisor/Consultant|Actelion: Board Member|Al-Jazeera Pharmaceuticals: Honoraria|Allecra Therapeutics: Board Member|Amplyx: Advisor/Consultant|Amplyx: Grant/Research Support|Astellas: Honoraria|Basilea: Advisor/Consultant|Basilea: Grant/Research Support|Biocon: Advisor/Consultant|Biosys: Advisor/Consultant|BMBF: Grant/Research Support|Cidara: Advisor/Consultant|Cidara: Board Member|Cidara: Expert Testimony|Cidara: Grant/Research Support|CoRe Consulting: Stocks/Bonds|Da Volterra: Advisor/Consultant|DLR: Grant/Research Support|DZIF: Grant/Research Support|Entasis: Board Member|EU Directorate-General for Resarch and Innovation: Grant/Research Support|F2G: Grant/Research Support|German Patent and Trade Mark Office: German patent (DE 10 2021 113 007.7)|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Grupo Biotoscana/United Medical/Knight: Honoraria|Hikma: Honoraria|IQVIA: Board Member|Janssen: Board Member|Matinas: Advisor/Consultant|Matinas: Grant/Research Support|MedPace: Advisor/Consultant|MedPace: Grant/Research Support|MedScape: Honoraria|MedUpdate: Honoraria|Menarini: Advisor/Consultant|Merck/MSD: Grant/Research Support|Merck/MSD: Honoraria|Molecular Partners: Advisor/Consultant|MSG-ERC: Advisor/Consultant|Mundipharma: Grant/Research Support|Mylan: Honoraria|Noxxon: Advisor/Consultant|Octapharma: Advisor/Consultant|Octapharma: Grant/Research Support|Paratek: Board Member|Pardes: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Projektträger Jülich: Grant/Research Support|PSI: Advisor/Consultant|PSI: Board Member|Pulmocide: Board Member|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support|Seres: Advisor/Consultant|Shionogi: Board Member|Wiley (Blackwell): Editor-in-Chief, Mycoses Bart-Jan Kullberg, MD, FRCP, FIDSA, Cidara: Independent Data Review Committee Jeffrey B. Locke, PhD, Cidara Therapeutics: Employee|Cidara Therapeutics: Stocks/Bonds Taylor Sandison, MD, MPH, Cidara Therapeutics: Employee|Cidara Therapeutics: Stocks/Bonds.

Seroprevalence of Cytomegalovirus infection among pregnant women in some selected hospitals in Lokoja Metropolis, Kogi State, Nigeria

Cytomegalovirus is one of the most common viruses which causes congenital defects in babies from infected mothers. Sensoneural hearing loss (SNHL) and neurodevelopmental delay are typical occurrences in childhood resulting from congenital defects which presents no symptoms at birth. The aim of this study was to determine the cytomegalovirus IgM infection among pregnant women attending antenatal clinics at KSSH and FMC in Lokoja metropolis, Kogi State, Nigeria. A total of 184 serum samples were collected and analyzed using CMV IgM ELISA kit diagnostic Automation, INC (USA). The study revealed that out of the 184 samples collected, 40 turned out positive for CMV IgM antibodies giving a prevalence of 21.7% while the negative sample result had a prevalence of 78.3%. a total of 92 samples each was collected from both hospitals; KSSH had 30 CMV IgM positive samples having a percentage 32.6% and FMC with 10 CMV IgM having a percentage of 10.86%. Based on the research, there was no significant association between the risk factors such as marital status, type of marriage, occupation and scarification related to the infection. This could be due to the limited number in sample size. Other socio-economic factors that had statistical significant p value with the infection were education (0.035), hand wash (0.027) and previous history of blood transfusion (0.003). The study has shown the need for sensitization of the populace especially to pregnant women, the need for constant and proper personal hygienic practices be done to reduce the risk of infection and possibly stop its transmission to fetus. In addition, inclusion of screening for cytomegalovirus antibodies among blood donors may be useful tool in preventing transmission of cytomegalovirus to blood recipients.