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.

First cases of Zika virus-infected US blood donors outside states with areas of active transmission.

BACKGROUND: Zika virus (ZIKV) is transmitted by Aedes mosquitos and can result in severe congenital and adult neurologic abnormalities. ZIKV has rapidly spread northward through Central America and the Caribbean and autochthonous cases have been identified in the continental United States. High rates of ZIKA RNA positivity were detected in blood donors during previous epidemics. ZIKV transmission by transfused blood from healthy donor components has been a growing concern. STUDY DESIGN AND METHODS: Individual-donation aliquots of plasma from volunteer blood donors were tested individually with an investigational Procleix ZIKV assay. Initially reactive samples were tested for ZIKV RNA in plasma and red blood cells (RBCs) and for ZIKV-specific antibodies in serum. A confirmed positive classification required confirmation of RNA and/or detection of ZIKV antibodies in index and/or follow-up samples. RESULTS: Between September 19 and November 30, 2016, a total of 466,834 donations were screened for ZIKV RNA. Five donors (one in approx. 93,000) were reactive for ZIKV RNA by both the Procleix ZIKV assay and supplemental testing. The donations were collected outside areas considered as having active transmission, and all five donors had travel exposures. A lookback case demonstrated no infection despite transfusion of a Zika IgG-positive platelet (PLT) component with probable low levels of ZIKV RNA. CONCLUSIONS: This report describes the first ZIKV-positive donors detected outside areas with active transmission. These donors most likely represent travel-acquired "tail-end infections" with prolonged RBC-associated ZIKV RNA. The lack of transmission to the recipient of an apheresis PLT may suggest that these units are not infectious.

Mitigating the Risk of Transfusion-Transmitted Dengue in Australia.

Dengue viruses (DENV 1-4) are a risk to transfusion safety, with several transfusion-transmitted (TT) cases reported globally. DENV 1-4 are endemic in over 100 countries, with seasonal outbreaks occurring in northeastern Australia. To mitigate TT-DENV risk in Australia, fresh blood components are not manufactured from donors returning from any area (domestic/overseas) with known dengue transmission. Alternatively, TT-DENV risk may be mitigated using an appropriate blood donor screening assay. We aimed to determine the rate of dengue infection in donors during dengue outbreaks in Australia. Plasma samples were collected from blood donors during local dengue outbreaks. All samples were tested for the presence of DENV RNA and selected samples were tested for DENV antigen (nonstructural protein 1, NS1) with two assays. No donors residing in high risk areas had detectable levels of DENV RNA or NS1 and no cases of DENV viremia were detected in blood donors residing in areas of Australia experiencing DENV outbreaks. Definitive conclusions could not be drawn from this study; however, the lack of detection of DENV RNA or antigen in donations suggests that the current risk of TT-DENV is low and maintaining the fresh component restriction for "at-risk" donors is appropriate.

Hepatitis E virus RNA in Australian blood donations.

BACKGROUND: Hepatitis E virus (HEV) poses a risk to transfusion safety. In Australia, locally acquired HEV is rare and cases are mainly reported in travelers returning from countries endemic for HEV. The risk posed by HEV to transfusion safety in Australia is unknown; therefore, we aimed to measure the rate of current HEV infection in Australian blood donations. STUDY DESIGN AND METHODS: A total of 14,799 blood donations were tested for HEV RNA by transcription-mediated amplification, with confirmatory testing by reverse transcription-polymerase chain reaction. Viral load quantification and phylogenetic analysis was performed on HEV RNA-positive samples. RESULTS: One (0.0068%; 95% confidence interval [CI], 0.0002%-0.0376%) sample was confirmed positive for HEV RNA, resulting in a risk of collecting a HEV-viremic donation of 1 in 14,799 (95% CI, 1 in 584,530 to 1 in 2,657). The viral load in this sample was approximately 15,000 IU/mL, and it was determined to be Genotype 3. DISCUSSION: Our finding of 1 in 14,799 Australian donations positive for HEV RNA is lower than that from many other developed countries; this is consistent with the relatively low seroprevalence in Australia. As this HEV RNA-positive sample was Genotype 3, it seems likely that this infection was acquired through zoonotic transmission, either within Australia or overseas in a developed nation. HEV has the potential to pose a risk to transfusion safety in Australia; however, additional, larger studies are required to quantify the magnitude of this risk.

Detection of emergent strains of West Nile virus with a blood screening assay.

BACKGROUND: West Nile virus (WNV) is a threat to transfusion safety. WNV Kunjin strain (WNVKUN ) is endemic across parts of Australia; however, human infection is believed to be infrequent and is often associated with relatively minor symptoms. A virulent strain, closely related to WNVKUN (termed WNVNSW2011 ) was recently identified as the etiologic agent of encephalitis in Australian horses. The aim of this project was to investigate whether a commercially available WNV blood screening assay can detect different strains of WNVKUN , including the virulent WNVNSW2011 , in human blood donor samples. STUDY DESIGN AND METHODS: Plasma samples were spiked with four different strains of WNVKUN , as well as a prototype WNV strain, at high, medium, and low viral loads. Spiking was confirmed with real-time reverse transcription-polymerase chain reaction (RT-PCR), before testing with the Procleix WNV transcription-mediated amplification (TMA) blood screening assay (Grifols). RESULTS: All WNV strains used were detectable by RT-PCR after being spiked into plasma. Additionally, all viral spiked samples were reactive by WNV TMA. CONCLUSION: We experimentally demonstrate that a commercially available WNV blood screening assay can detect different strains of WNVKUN . Given that WNV can be transfusion transmissible, it is essential to confirm that emergent strains are detectable by existing blood screening methods.

Failure to confirm XMRV/MLVs in the blood of patients with chronic fatigue syndrome: a multi-laboratory study.

Murine leukemia viruses (MLVs), including xenotropic-MLV-related virus (XMRV), have been controversially linked to chronic fatigue syndrome (CFS). To explore this issue in greater depth, we compiled coded replicate samples of blood from 15 subjects previously reported to be XMRV/MLV-positive (14 with CFS) and from 15 healthy donors previously determined to be negative for the viruses. These samples were distributed in a blinded fashion to nine laboratories, which performed assays designed to detect XMRV/MLV nucleic acid, virus replication, and antibody. Only two laboratories reported evidence of XMRV/MLVs; however, replicate sample results showed disagreement, and reactivity was similar among CFS subjects and negative controls. These results indicate that current assays do not reproducibly detect XMRV/MLV in blood samples and that blood donor screening is not warranted.

Summary of the AABB Interorganizational Task Force on Bacterial Contamination of Platelets: Fall 2004 impact survey.

BACKGROUND: New voluntary standards in the United States regarding bacterial contamination of platelets (PLTs) led to the formation of the AABB Interorganizational Task Force on Bacterial Contamination of Platelets. This article summarizes a survey conducted by the Task Force to assess the impact of bacterial detection. STUDY DESIGN AND METHODS: An Internet-based survey of AABB member institutions was conducted from September 17, 2004, to October 1, 2004. The survey was designed principally to assess PLT usage, supply, and outdating and the currently used bacteria detection methods. RESULTS: Of 900 facilities surveyed, 350 responded (38%). These facilities collected approximately 43.3 and 65.9 percent and transfused approximately 19.1 and 22.2 percent of the whole blood-derived PLT concentrates (WBPCs) and apheresis PLTs in the United States, respectively. Most facilities (64-91%) indicated that their ability to provide PLTs for transfusion had not been affected. Approximately half (50-57.1%) indicated no changes in their PLT inventory. Two-thirds (66-68%) indicated no increased PLT outdating. More than 90 percent of apheresis PLTs are tested with a culture-based method, whereas WBPCs are tested with a variety of methods (mostly non-culture-based) resulting in a 4.6-fold decrease in the confirmed positive detection rate compared with apheresis PLTs (p < 0.001). CONCLUSION: After the implementation of AABB Standard 5.1.5.1, the majority of facilities responding to this survey experienced no (or modest) impact on PLT availability or outdating. Nevertheless, a substantial portion of facilities experienced both increased outdating and decreased availability. Some facilities were greatly impacted. Based on the data gathered, it is impossible to conclude whether such shortages resulted from production or distribution problems or were due to decreased shelf life and increased outdates.