The International Society of Blood Transfusion (ISBT) Public Health Research Toolkit: A report from the Surveillance, Risk Assessment and Policy Sub-group of the ISBT Transfusion Transmitted Infectious Diseases Working Party.

BACKGROUND AND OBJECTIVES: Data provided from blood donors have contributed to the understanding of public health epidemiology and policy decisions. A recent example was during the severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) pandemic when blood services monitored the seroprevalence in blood donors. Based on this experience, blood services have the opportunity to expand their role and participate in public health surveillance and research. The aim of this report is to share available resources to assist blood services in this area. MATERIALS AND METHODS: The Surveillance, Risk Assessment and Policy (SRAP) Sub-group of the International Society of Blood Transfusion (ISBT) Transfusion Transmitted Infectious Diseases (TTID) Working Party developed a Public Health Research Toolkit to assist blood services and researchers interested in expanding their role in public health research. RESULTS: The ISBT Public Health Research Toolkit provides resources for what blood services can offer to public health, examples of donor research studies, the utility of donor data and website links to public health agencies. The toolkit includes a customizable template for those interested in establishing and managing a biobank. CONCLUSION: The ISBT Public Health Research Toolkit includes resources to increase the recognition of the role blood donors can play in public health and to help blood services gain commitment and funding from various agencies for new research and surveillance.

Status of hospital-based blood transfusion services in low-income and middle-income countries: a cross-sectional international survey.

OBJECTIVES: Blood transfusion is life-saving for patients experiencing acute blood loss and severe anaemia. In low-income and middle-income countries (LMICs), low blood donation rates and unavailability of whole blood and blood components (blood products) impairs timely blood transfusion. To fulfil patient-specific blood orders, a hospital blood transfusion service (HBTS) receives orders from a prescriber for blood transfusion, tests and prepares blood products for the patient. This study sought to describe the current state of LMIC HBTS. DESIGN: A cross-sectional survey explored LMIC HBTS access to blood products, testing methods, policies and structure. Surveys were administered in English, Spanish, French and Russian, followed by a mixed-methods analysis. SETTING: HBTS within LMICs. PARTICIPANTS: From among 124 public and private facilities invited to participate, we received 71 (57%) responses. Of these responses, 50 HBTS from 27 LMICs performed on-site blood transfusions. RESULTS: Most LMIC HBTS perform blood collection to generate blood products for their patients (36/47, 77%); few relied exclusively on an external supply of blood products (11/47, 23%). The primary reason for blood transfusion was adult anaemia for non-malignant conditions (17/112, 15%). Testing methods varied by gross national income per capita. Blood transfusion delays to patients were common (17/30, 57%) attributed to inadequate blood inventories (13/29, 45%). Other barriers included lack of regular clinician education about transfusion (8/29, 28%) and sustainable financial models for the HBTS (4/29, 14%). CONCLUSION: This survey describes the status of HBTS in diverse LMICs, illustrating that the availability of blood products remains a principal problem, requiring HBTS to generate its own facility's blood supply. Currently, blood shortages are not reported as a patient-specific adverse event making systematic tracking of delays in transfusion difficult. These findings highlight areas for further exploration related to the lack of available blood inventories for transfusions at HBTS in LMICs.

Detection of Babesia RNA and DNA in whole blood samples from US blood donations.

BACKGROUND: Human babesiosis is a zoonotic infection caused by an intraerythrocytic parasite. The highest incidence of babesiosis is in the United States, although cases have been reported in other parts of the world. Due to concerns of transfusion-transmitted babesiosis, the US Food and Drug Administration (FDA) recommended year-round regional testing for Babesia by nucleic acid testing or use of an FDA-approved device for pathogen reduction. A new molecular test, cobas Babesia (Roche Molecular Systems, Inc.), was evaluated for the detection of the four species that cause human disease, Babesia microti, Babesia duncani, Babesia divergens, and Babesia venatorum. STUDY DESIGN AND METHODS: Analytical performance was evaluated followed by clinical studies on whole blood samples from US blood donations collected in a special tube containing a chaotropic reagent that lyses the red cells and preserves nucleic acid. Sensitivity and specificity of the test in individual samples (individual donation testing [IDT]) and in pools of six donations were determined. RESULTS: Based on analytical studies, the claimed limit of detection of cobas Babesia for B. microti is 6.1 infected red blood cells (iRBC)/mL (95% confidence interval [CI]: 5.0, 7.9); B. duncani was 50.2 iRBC/mL (95% CI: 44.2, 58.8); B. divergens was 26.1 (95% CI: 22.3, 31.8); and B. venatorum was 40.0 iRBC/mL (95% CI: 34.1, 48.7). The clinical specificity for IDT was 99.999% (95% CI: 99.996, 100) and 100% (95% CI: 99.987, 100) for pools of six donations. CONCLUSION: cobas Babesia enables donor screening for Babesia species with high sensitivity and specificity.

Detection of dengue, chikungunya, and Zika RNA in blood donors from Southeast Asia.

BACKGROUND: Chikungunya (CHIKV), dengue (DENV), and Zika (ZIKV) viruses are of concern due to the potential of transfusion transmission in blood, especially in regions such as Southeast Asia where the viruses are endemic. The recent availability of nucleic acid testing (NAT) to screen blood donations on an automated platform provides the opportunity to detect potentially infectious units in asymptomatic donors. STUDY DESIGN AND METHODS: Three thousand blood donations from Vietnam and 6000 from Thailand were screened with a real-time polymerase chain reaction (PCR) test (cobas CHIKV/DENV, Roche Diagnostics, Indianapolis, IN) and equal numbers on cobas Zika (Roche Diagnostics). Reactive samples were tested by alternative NAT with resolution of discordant results by heminested PCR. Throughput of simultaneous testing of the two assays on the cobas 8800 system (Roche Diagnostics) was evaluated. RESULTS: In Vietnam, 9 of 3045 samples were reactive for DENV and all were confirmed, for a prevalence (with 95% confidence interval [CI]) of 0.296% (0.135-0.560). In Thailand, 2 of 6000 samples were reactive for CHIKV, 4 of 6000 for DENV, and 1 of 6005 for ZIKV, and all confirmed. The prevalence of CHIKV is 0.033% (0.004-0.120), DENV 0.067% (0.018-0.171), and ZIKV 0.017% (0.000-0.093). The overall specificity for the cobas CHIKV/DENV and cobas Zika tests was 100% (99.959-100). For the simultaneous assay testing, 960 test results were available in 7 hours and 53 minutes. CONCLUSION: Detection of CHIKV, DENV, and ZIKV RNA in donor samples in Vietnam and Thailand indicate the presence of the virus in asymptomatic blood donors. The cobas 6800/8800 systems (Roche Molecular Systems, Pleasanton, CA) enable screening blood donations in endemic areas for these viruses together or separately.

Duplex nucleic acid test for the detection of chikungunya and dengue RNA viruses in blood donations.

BACKGROUND: Chikungunya (CHIKV) and dengue (DENV) viruses are primarily mosquito-borne, but transfusion transmission can occur (DENV) or is likely (CHIKV). In the absence of commercially available blood screening assays, a variety of strategies to ensure recipient safety in the face of expanding CHIKV and/or DENV outbreaks have been used. STUDY DESIGN AND METHODS: Performance of cobas CHIKV/DENV, a qualitative RNA detection assay for use on the cobas 6800/8800 Systems, was evaluated at two sites (Roche Molecular Systems, Inc. [RMS], and the American Red Cross [ARC]). Analytical sensitivity, genotype inclusion, correlation with other assays, and reproducibility used clinical CHIKV- or DENV-positive samples and secondary standards for DENV Types 1 to 4 and for three CHIKV genotypes (Asian; East Central South African; and West African); each secondary standard was traceable to international reference panels or reagents. Evaluation of analytic specificity assessed other microorganisms for interference and cross-reactivity; clinical specificity was determined by individually testing 10,528 volunteer blood donations from the continental United States. RESULTS: The 50 and 95% limit of detection (LoD) obtained by RMS for CHIKV, Asian genotype was 1.8 and 6.8 Detectable Units (DU)/mL, respectively, and 0.14 and 0.63 International Units (IU)/mL, respectively for DENV-1. No significant differences in detection occurred by testing at a second site, the ARC (2.4 and 10.5 DU/mL for CHIKV and 0.15 and 0.60 IU/mL for DENV). Clinical specificity was 100% (95% confidence interval, 99.965%-100%) for CHIKV and DENV. CONCLUSIONS: The high sensitivity and specificity of the cobas CHIKV/DENV test, as demonstrated in these evaluations, indicate its suitability for blood donation screening.

Evaluation of a new West Nile virus nucleic acid test for screening of blood donations.

BACKGROUND: West Nile virus (WNV) is transmitted to humans through mosquito bites and can be further transmitted to humans through transfusion or transplantation. Because most infected individuals are asymptomatic, blood donor screening is important in areas where WNV is endemic. These studies evaluated the performance of a new test for detection of WNV RNA in blood donations. STUDY DESIGN AND METHODS: Analytical performance evaluation included sensitivity, specificity, inclusivity, and correlation. A clinical specificity study was conducted at four blood donor testing laboratories in parallel with the cobas TaqScreen WNV Test (Roche Molecular Systems, Inc.). RESULTS: The 95% and 50% limit of detection for cobas WNV was 12.9 copies/mL (95% confidence interval [CI], 10.8-16.3) and 2.1 copies/mL (95% CI, 1.9-2.4) for WNV lineage 1, respectively, and 6.2 copies/mL (95% CI, 4.8-8.9) and 1.1 copies/mL (95% CI, 0.8-1.3) for WNV lineage 2, respectively. Clinical specificity was 100% in 10,823 donor samples tested individually (95% CI, 99.966%-100%) and 63,243 tested in pools of 6 (95% CI, 99.994%-100%). Samples of other members of the Japanese encephalitis virus serocomplex, including St Louis encephalitis, Japanese encephalitis, Murray Valley encephalitis, Usutu, and Kunjin viruses were detected by cobas WNV. CONCLUSION: The cobas WNV test for use on the cobas 6800/8800 System, a fully automated test system, demonstrated high sensitivity and specificity and is suitable for the detection of WNV in blood donors.

Report of a workshop on ensuring sustainable access to safe blood in developing countries: International Blood Safety Forum, March 24, 2017.

On March 24, 2017, more than 90 experts in blood safety and international development from blood centers, industry, government, and international and nongovernmental organizations gathered in Arlington, Virginia, for the Third International Blood Safety Forum, cosponsored by America's Blood Centers and Global Healing. This report summarizes presentations and major conclusions. The meeting explored ways to increase access to affordable, safe blood for low- and lower-middle-income countries (LMICs) in an era when funding from the US President's Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund has been redirected from preventing the spread of human immunodeficiency virus (HIV) to diagnosing and treating the 25 million-plus people living with HIV in LMICs. More effective management systems must be developed to improve cost recovery for blood. While blood systems become more sustainable, continued investment is required to keep them operating. The traditional model of large grants from bilateral and multilateral donors will need to be supplemented (or replaced) with public-private partnerships and nongovernmental investment. A continued emphasis on quality is fundamental. Blood systems must build quality programs, based on accepted standards, including hospitals, clinics, and rural health care providers to ensure proper and safe use of blood. Proposals to resolve health care inequities between LMICs and high-income countries (HICs) must include helping LMICs to define sustainable national policies and practices for blood availability and utilization to suit local contexts. The blood safety lexicon should be revised to include availability, accessibility, and affordability of safe blood and blood products as the goal of all blood safety initiatives.

Tracking Nile Delta vulnerability to Holocene change.

Understanding deltaic resilience in the face of Holocene climate change and human impacts is an important challenge for the earth sciences in characterizing the full range of present and future wetland responses to global warming. Here, we report an 8000-year mass balance record from the Nile Delta to reconstruct when and how this sedimentary basin has responded to past hydrological shifts. In a global Holocene context, the long-term decrease in Nile Delta accretion rates is consistent with insolation-driven changes in the 'monsoon pacemaker', attested throughout the mid-latitude tropics. Following the early to mid-Holocene growth of the Nile's deltaic plain, sediment losses and pronounced erosion are first recorded after ~4000 years ago, the corollaries of falling sediment supply and an intensification of anthropogenic impacts from the Pharaonic period onwards. Against the backcloth of the Saharan 'depeopling', reduced river flow underpinned by a weakening of monsoonal precipitation appears to have been particularly conducive to the expansion of human activities on the delta by exposing productive floodplain lands for occupation and irrigation agriculture. The reconstruction suggests that the Nile Delta has a particularly long history of vulnerability to extreme events (e.g. floods and storms) and sea-level rise, although the present sediment-starved system does not have a direct Holocene analogue. This study highlights the importance of the world's deltas as sensitive archives to investigate Holocene geosystem responses to climate change, risks and hazards, and societal interaction.

Strategies for advancing transfusion medicine and cellular therapies: taking control of our future.

This special edition of TRANSFUSION is dedicated to those colleagues in the transfusion medicine and cellular therapy field who have wondered about what the future holds for their chosen professions. Each of the six peer-reviewed Think Tank articles included in this special edition focuses on an administrative issue that is critical to the survivability and enhancement of the industry. Each issue is examined from two perspectives: Where are we now? And where are we heading?

NMR and X-ray crystallographic studies of the conformation of a 3,4,6-triphenyl-delta-lactone.

1-Oxa-3S,4S,6R-triphenyl-2-cyclohexanone and its enantiomer were synthesized, and the structure was determined by NMR and X-ray crystallography. The X-ray crystal structure showed that the delta-lactone adopts a boat conformation in the solid. The X-ray data showed a shortened C-O bond between the carbonyl carbon and the ether oxygen, consistent with delocalization involving the ester group. (1)H and (13)C NMR measurements in acetone-d(6) showed that the lactone is biased in favor of a boat conformation. In the less polar solvent chloroform-d(1), changes in the (1)H NMR coupling constants indicate a shift in the equilibrium in favor of a less rigid twist-boat conformation. The IR absorption of the lactone carbonyl at 1740 cm(-)(1) would suggest a half-chair conformation inconsistent with the dominance of the boat forms shown by NMR and X-ray.