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.

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.

No viremia of pandemic (H1N1) 2009 was demonstrated in blood donors who had donated blood during the probable incubation period.

BACKGROUND: In the spring of 2009, the novel swine-origin influenza A (pandemic [H1N1] 2009) virus emerged and spread globally. Although no established cases of transfusion-transmitted influenza have been reported, the widespread outbreak of pandemic (H1N1) 2009 caused serious concern regarding the safety of blood products. The Japanese Red Cross Blood Centers have intercepted blood products with accompanying postdonation information indicating possible pandemic (H1N1) 2009 infection. To study the risk of transmission of pandemic (H1N1) 2009 by blood transfusion, we searched for the viral genome in such products using nucleic acid amplification technology. STUDY DESIGN AND METHODS: Between June and December 2009, blood components were collected from 579 blood donors who were diagnosed as or strongly suspected of having pandemic (H1N1) 2009 within 7 days after donation. Viral RNA was extracted from plasma and red blood cell (RBC) products, and RNA samples were subjected to real-time reverse transcription-polymerase chain reaction of the hemagglutinin and matrix genes of the pandemic (H1N1) 2009 virus. RESULTS: A total of 565 plasma and 413 RBC products from the 579 blood donors were available. No viral RNA of the pandemic (H1N1) 2009 was detected in any of the blood samples from the 579 blood donors. CONCLUSION: No viremia of pandemic (H1N1) 2009 was demonstrated in any of the 579 blood donors who had most likely donated blood during the incubation period. It is considered that the risk of transmitting pandemic (H1N1) 2009 by blood transfusion is extremely low.

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.

A nationwide survey for hepatitis E virus prevalence in Japanese blood donors with elevated alanine aminotransferase.

BACKGROUND: Although we reported two cases of transfusion-transmitted hepatitis E in Japan, the prevalence of hepatitis E virus (HEV) in Japanese blood donors is not very clear. STUDY DESIGN AND METHODS: Blood samples of donors who were deferred from donation because of elevated alanine aminotransferase (ALT) levels were collected from all Japanese Red Cross Blood Centers and subjected to HEV tests. RESULTS: Among the 41 donors with elevated ALT levels higher than 500 IU per L in Hokkaido, HEV RNA was detected in 8 (19.5%) samples. In 1389 donor samples with ALT levels of higher than 200 IU per L in nationwide Japan, the numbers of positive HEV RNA, immunoglobulin M (IgM) anti-HEV, and immunoglobulin G (IgG) anti-HEV samples were 15 (1.1%), 14 (1.0%), and 45 (3.2%), respectively. Although RNA-positive donors were predominantly male and found in any geographic area of Japan, they tended to be higher in number in eastern Japan including Hokkaido and lower in number in western Japan. Of the 23 HEV-positive samples, 19 were Genotype 3 and 4 were Genotype 4. DNA sequences of the 9 isolates showed more than 98.5 percent homology with the known swine HEV isolates. In 1062 donor samples with ALT levels of 61 to 199 IU per L, the percentages of IgM and IgG anti-HEV-positive samples were 0.1 and 2.7 percent, respectively, although there was no HEV RNA-positive sample. CONCLUSION: HEV markers (HEV RNA and anti-HEV) were detected in donors with elevated ALT levels who were widely distributed over Japan. The prevalence and incidence were higher in eastern Japan than in western Japan.

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.