Platelet safety strategies in Japan: impact of short shelf life on the incidence of septic reactions.

BACKGROUND: Transfusion-transmitted bacterial infections (TTBIs) often have serious consequences for patients. The Japanese Red Cross (JRC) has not implemented culture screening for platelet concentrate (PC), but it has maintained a shelf life of 85 hours for PC. STUDY DESIGN AND METHODS: The JRC collected reports of suspected TTBI and investigated causal relationships using PC samples and patient blood samples. PCs showing apparent abnormalities were retrieved and cultured and analyzed for bacterial growth. RESULTS: The JRC analyzed 86 samples available from 135 transfused PCs with suspected TTBIs that were collected over the past 12 years; 17 (19.8%) were culture-positive. One, 6, and 10 TTBIs developed in patients on Days 1, 2, and 3 after PC collection, respectively. Assuming that PC is transfused on the day of issue, the TTBI risk was fourfold higher on Day 3 than on Day 2, after adjusting the TTBI incidence for the number of PCs issued per day. Compared with the model of issuing all PCs on Day 3, issuing PCs with the current distribution of storage time could have decreased the TTBI incidence by 56%. During the past 8 years, the JRC retrieved 960 PC units because of apparent abnormalities, 2.8% of which were culture-positive. CONCLUSION: The short shelf life of PC is associated with a low incidence of reported TTBIs, more than half of which occurred on Day 3 relative to earlier time points. Visual inspection of PC before transfusion is crucial in detecting bacterially contaminated PC despite its low positive predictive value.

Reduction in adverse transfusion reactions with increased use of washed platelet concentrates in Japan-A retrospective multicenter study.

Plasma removal by washing platelet concentrates (PCs) is effective in preventing adverse reactions to PC transfusions. The Japanese Red Cross Society (JRCS) started releasing washed PCs (WPCs) as a commercially approved blood product in September 2016. This retrospective multicenter study investigated the change in the number of transfused WPCs and the impact on the incidence of adverse reactions to PCs before and after the release. The numbers and types of transfused PCs and the adverse reactions to the PCs for a year before the start of the WPC release and for a year after the release were reported by 27 medical institutes in Japan. Transfusion information for approximately 8% of the amount of PCs supplied in Japan was analyzed during the study period. After the start of WPC release by the JRCS, the number of transfused WPCs doubled. The rate of adverse reactions to PCs decreased significantly (p = 0.0223), from 4.30% before the release to 4.05% after the release. The rates of adverse reactions to unwashed and WPCs were 4.13% and 0.84%, respectively. Allergic adverse reactions were significantly decreased after the release (3.60% before versus 3.37% after). No severe allergic reactions to WPCs were reported. The release of WPCs by the JRCS significantly reduced transfusion-related adverse reactions to PCs in Japan.

Seroprevalence of Trypanosoma cruzi infection among at-risk blood donors in Japan.

BACKGROUND: Chagas disease is caused by Trypanosoma cruzi and is endemic in Latin America. In nonendemic countries, including Japan, Chagas disease is primarily a problem in the context of transfusion transmission. Approximately 250,000 immigrants from Latin America reside in Japan, and many of those individuals serve as active blood donors. This study surveyed the seroprevalence of T. cruzi infection among at-risk blood donors in Japan, defined as those who themselves (or whose mothers) were born (or raised) in Latin America, or those with a travel history to Latin America. STUDY DESIGN AND METHODS: Blood samples were obtained from at-risk donors in two periods, 2004-2012 and 2013-2016. Collected samples were tested for T. cruzi antibodies using both an enzyme-linked immunosorbent assay and a chemiluminescent immunoassay. Samples that tested positive in both assays were additionally tested by polymerase chain reaction, and look-back investigation was conducted when necessary. RESULTS: Of 18,484 samples obtained from 18,076 at-risk donors, 3 (1:6,025, 0.017%) donors showed seroreactivity by enzyme-linked immunosorbent assay and chemiluminescent immunoassay. All antibody-positive donors were born in Latin America. One of them also was positive for T. cruzi DNA. Eleven previous donations from this donor were subjected to look-back investigation, and five recipients were tested. All five recipients tested negative for T. cruzi antibodies. CONCLUSION: Seroprevalence of T. cruzi was 0.017% among at-risk donors in Japan. Transfusion-transmitted infection of Chagas disease has not been confirmed to date. Screening for T. cruzi antibodies by targeting at-risk donors is an appropriate strategy for ensuring blood safety in Japan.

Sequence analyses of variable cytomegalovirus genes for distinction between breast milk- and transfusion-transmitted infections in very-low-birth-weight infants.

BACKGROUND: Cytomegalovirus (CMV) transmission to very-low-birth-weight infants (VLBWIs) sometimes induces serious clinical symptoms. Although breast milk is considered a major source of transmission, transfusion-transmitted CMV (TT-CMV) infection is often suspected when CMV disease develops after transfusion. Thus, it is clinically important to distinguish between transfusion-transmitted and breast milk-transmitted CMV infections. STUDY DESIGN AND METHODS: Study A: The incidence of acquired CMV transmission was prospectively investigated in 65 VLBWIs. Study B: To determine the transmission routes in 18 TT-CMV-suspected VLBWIs who had been reported in our hemovigilance system, we performed polymerase chain reaction for CMV DNA in fed breast milk and/or repository blood samples related to transfused leukoreduced blood products. Furthermore, we evaluated the identity of CMV strains in patients' urine/blood samples and fed breast milk by sequence analyses of variable CMV genes UL139 and UL146. RESULTS: Study A: Acquired CMV infection was found in 4 of 65 VLBWIs (6.2%). Study B: CMV DNA was detected in fed breast milk for 12 of 14 TT-CMV-suspected cases, for which breast milk was available. Furthermore, CMV DNA sequence-matching rates between fed breast milk and patients' urine/blood for both UL139 and UL146 genes were 100% or nearly 100% in 11 patients. In contrast, repository blood samples for 11 of 14 patients were CMV DNA negative. CONCLUSION: CMV is principally transmitted through breast milk in VLBWIs. The risk of TT-CMV seems to be extremely low when using leukoreduced blood products. Sequence analyses of the variable CMV genes are useful for evaluating CMV transmission routes.

The HIV care cascade: Japanese perspectives.

Japan has been known as a low HIV-prevalence country with a concentrated epidemic among high-risk groups. However, it has not been determined whether Japan meets the 90-90-90 goals set by the Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO). Moreover, to date, the HIV care cascade has not been examined. We estimated the total number of diagnosed people living with HIV/AIDS (PLWHA) (n = 22,840) based on legal reports to the Ministry of Health, Labour and Welfare by subtracting the number of foreigners who left Japan (n = 2,273) and deaths (n = 2,321) from the cumulative diagnosis report (n = 27,434). The number of total undiagnosed PLWHA was estimated by age and sex specific HIV-positive rates observed among first-time blood donors between 2011-2015 in Japan. Our estimates show that 14.4% (n = 3,830) of all PLWHA (n = 26,670) were undiagnosed in Japan at the end of 2015. The number of patients retained in care (n = 20,615: 77.3% of PLWHA), the percentage of those on antiretroviral therapy (n = 18,921: 70.9% of PLWHA) and those with suppressed viral loads (<200 copies/mL; n = 18,756: 70.3% of PLWHA) were obtained through a questionnaire survey conducted in the AIDS Core Hospitals throughout the country. According to these estimates, Japan failed to achieve the first two of the three UNAIDS/WHO targets (22,840/26,670 = 85.6% of HIV-positive cases were diagnosed; 18,921/22,840 = 82.8% of those diagnosed were treated; 18,756/18,921 = 99.1% of those treated experienced viral suppression). Although the antiretroviral treatment uptake and success after retention in medical care appears to be excellent in Japan, there are unmet needs, mainly at the surveillance level before patients are retained in care. The promotion of HIV testing and treatment programs among the key affected populations (especially men who have sex with men) may contribute to further decreasing the HIV epidemic and achieving the UNAIDS/WHO targets in Japan.

Unique clinical courses of transfusion-transmitted hepatitis E in patients with immunosuppression.

BACKGROUND: The high prevalence of specific immunoglobulin G for hepatitis E virus (HEV) in Japanese people raises the possibility of a high incidence of HEV-viremic blood donors and therefore frequent transfusion-transmitted HEV (TT-HEV). STUDY DESIGN AND METHODS: TT-HEV cases established in Japan through hemovigilance and those published in the literature were collected. Infectivity of HEV-contaminated blood components and disease severity in relation to immunosuppression were investigated. RESULTS: Twenty established TT-HEV cases were recorded over the past 17 years. A lookback study verified that five of 10 patients transfused with known HEV-contaminated blood components acquired HEV infection. The minimal infectious dose of HEV through transfusion was 3.6 × 104 IU. Nine of the 19 TT-HEV cases analyzed had hematologic diseases. Only two cases showed the maximal alanine aminotransferase level of more than 1000 U/L. Two patients with hematologic malignancy and two liver transplant recipients had chronic liver injury of moderate severity. CONCLUSION: The infectivity of HEV-contaminated components was 50%. Immunosuppression likely causes the moderate illness of TT-HEV, but it may lead to the establishment of chronic sequelae. Transfusion recipients, a population that is variably immunosuppressed, are more vulnerable to chronic liver injury as a result of TT-HEV than the general population is as a result of food-borne infection.

Residual risk of transfusion-transmitted hepatitis B virus (HBV) infection caused by blood components derived from donors with occult HBV infection in Japan.

BACKGROUND: Nucleic acid amplification testing (NAT) for hepatitis B virus (HBV) during blood screening has helped to prevent transfusion-transmitted HBV infection (TT-HBV) in Japan. Nevertheless, 4 to 13 TT-HBV infections arise annually. STUDY DESIGN AND METHODS: The Japanese Red Cross (JRC) analyzed repository samples of donated blood for TT-HBV that was suspected through hemovigilance. Blood donations implicated in TT-HBV infections were categorized as either window period (WP) or occult HBV infection (OBI) related. In addition, we analyzed blood from 4742 donors with low antibody to hepatitis B core antigen (anti-HBc) and antibody to hepatitis B surface antigen (anti-HBs) titers using individual-donation NAT (ID-NAT) to investigate the relationship between anti-HBc titer and proportion of viremic donors. RESULTS: Introduction of a more sensitive NAT method for screening minipools of 20 donations increased the OBI detection rate from 3.9 to 15.2 per million, while also the confirmed OBI transmission rate increased from 0.67 to 1.49 per million. By contrast the WP transmission rate decreased from 0.92 to 0.46 per million. Testing repository samples of donations missed by minipools of 20 donations NAT showed that 75 and 85% of TT-HBV that arose from WP and OBI donations, respectively, would have been interdicted by ID-NAT. The ID-NAT trial revealed that 1.94% of donations with low anti-HBc and anti-HBs titers were viremic and that anti-HBc titers and the frequency of viremia did not correlate. CONCLUSIONS: The JRC has elected to achieve maximal safety by discarding all units with low anti-HBc and anti-HBs titers that account for 1.3% of the total donations.

Symptomatic parvovirus B19 infection caused by blood component transfusion.

BACKGROUND: Although a risk of transfusion-transmitted human parvovirus B19V (TT-B19V) infection has been a concern, there have been very few reports of clinically relevant TT-B19V caused by the transfusion of a B19V-containing blood component. It has therefore been a matter of debate whether a universal B19V screening with an appropriate sensitivity is required. STUDY DESIGN AND METHODS: Through the Japanese Red Cross hemovigilance system, clinical reports on possible TT-B19V were collected from 1999 to 2008, during which B19V donor screening (sensitivity, 10(10) IU/mL) was conducted and repository blood samples from donors were available. RESULTS: Eight patients with TT-B19V caused by component transfusion have been identified. Four patients developed sustained anemia and pure red blood cell (RBC) aplasia and one patient developed pancytopenia. The underlying diseases in these five patients were either hematologic malignancy or hemolytic diseases. The viral loads of the responsible components for these cases ranged from 10(3) to 10(8) IU/mL. Two patients who underwent surgical treatment without any hematologic disorder exhibited only moderate symptoms. The B19V DNA sequence identity between a patient and the linked blood donor was confirmed in five of the eight patients. All of the components responsible for the eight cases were positive for anti-B19V immunoglobulin (Ig)M. CONCLUSION: Vulnerability to serious B19V-related hematologic disorders depended on the patient's underlying disease state of an enhanced erythropoiesis, not on the viral load of the component transfused. To prevent clinically relevant TT-B19V, a strategy is suggested in which patients at risk of acquiring RBC aplasia or pancytopenia are targeted.

Lengths of hepatitis B viremia and antigenemia in blood donors: preliminary evidence of occult (hepatitis B surface antigen-negative) infection in the acute stage.

BACKGROUND: The Japanese Red Cross (JRC) implemented a fully automated pooling and nucleic acid amplification test (NAT) system for testing seronegative donations. The JRC sample repository and repeat blood donations allowed for lookback and follow-up studies of hepatitis B virus (HBV) DNA-positive donors, who tested negative for hepatitis B surface antigen (HBsAg) and anti-hepatitis B core antigen in the JRC screening system. STUDY DESIGN AND METHODS: From February 1, 2000, to March 31, 2003, 17,314,486 units were tested in 50-sample pools with a semiautomated multiplex assay system (AMPLINAT MPX test, Roche). During this period, 328 HBV DNA-positive donations were found. From 26 of these donors, sequential samples were available at short intervals. This enabled us to examine the dynamics of viral markers in acute HBV infection. The length of detectable periods of plasma viremia and antigenemia were estimated by regression analysis from the results obtained in the quantitative polymerase chain reaction assay (JRC) and HBsAg enzyme immunoassay (Auszyme II, AxSYM, Abbott) and chemiluminescence immunoassay (Abbott). RESULTS: The median length of detectable HBV DNA in individual donation and 20-sample minipool (MP) NAT format was estimated to be 74 and 50 days, respectively, whereas the median length of detectable HBsAg was estimated to be 42 days. Six of the 26 donors were infected with mutant viruses, and 3 of these 6 donors did not develop detectable HBsAg during the entire observation period, despite a moderately high viral load of 10(4) to 10(5) HBV DNA copies per mL. CONCLUSION: Transmission of mutant virus may cause occult HBV infection in the acute stage. HBV NAT, even in MP configuration, is more effective than HBsAg testing and capable of interdicting infected donors in the pre- and post-HBsAg window periods.

Infectivity of blood components with low hepatitis B virus DNA levels identified in a lookback program.

BACKGROUND: Japanese Red Cross (JRC) blood centers implemented anti-hepatitis B core antigen (HBc) screening in 1989 and 50-minipool (MP)-nucleic acid testing (NAT) in 2000. A systematic lookback study has been conducted to determine the hepatitis B virus (HBV) transmission risk of donations drawn in the pre-hepatitis B surface antigen (HBsAg) and/or MP-NAT window phase and by donors with occult HBV infection. STUDY DESIGN AND METHODS: JRC blood centers have been storing aliquots of every blood donation since 1996. On the basis of the complete repository tube archives, all donations from repeat donors received from 1997 to 2004 were subjected to a lookback study. When repeat donors turned positive for HBV viral marker(s), repository tubes from their previous donations were tested for HBV with individual-donation (ID)-NAT. The frequency of ID-NAT-only-positive donations and the HBV transmission risk by the transfusion of those components were investigated. RESULTS: HBV ID-NAT was performed on 15,721 repository tubes, and 158 tubes (1.01%) were found positive for the presence of HBV DNA. Of these 158 ID-NAT-only-positive donations, 95 (60%) were derived from carriers with low anti-HBc titers. Of 63 patients transfused with ID-NAT-only-positive components, 12 (19%) proved to be infected with HBV. Only 1 of 33 components with low anti-HBc titers could be identified as infectious, whereas 11 of 22 anti-HBc-negative components proved to be infectious. None of the 16 identified hepatitis B surface antibody-positive components showed serologic evidence of infection. CONCLUSION: The clinically observed HBV infection risk caused by blood components from occult HBV carriers with low anti-HBc titers who slip through the JRC screening system is more than 10-fold lower than the transmission risk by donations in the pre-HBsAg and/or MP-NAT window phase.