Anti-HBc-nonreactive occult hepatitis B infections with HBV genotypes B and C in vaccinated immunocompetent adults.

Absence of anti-HBc reactivity with detectable anti-HBs was observed in blood donors with occult hepatitis B virus (HBV) infection (OBI). The prevalence and mechanisms underlying this uncommon condition were investigated over time in Chinese blood donors with OBI. Isolated anti-HBs OBI status was identified from 466,911 donors from Dalian, China, and monitored in follow-up (range: 2.6-84.3 months). HBV vaccination status was documented, and infecting viral strains were characterized. Of 451 confirmed OBIs (1:1035), 43 (9.5%; 1:10,858) had isolated anti-HBs as only serological marker. Isolated anti-HBs OBIs differed from anti-HBc-reactive OBIs by significantly younger age (median 24 years), higher HBV DNA (median: 20 IU/ml) and anti-HBs (median 60.5 IU/L) levels, paucity of mutations in HBV Core and S proteins, and high vaccination rate (72%). Vaccinated isolated anti-HBs OBIs (n = 31) differed from unvaccinated (n = 11) by significantly younger age (22 vs 38 years), higher anti-HBs level at index (48% vs 9% with anti-HBs >100 IU/L) and higher frequency of anti-HBs immune response (44% vs 20%). Of 15 vaccinated and 5 unvaccinated OBIs follow-up, 65% (8 vaccinated and 5 unvaccinated) became HBV DNA negative suggesting aborted recent infection, while 35% (7 vaccinated) had low persistent viraemia 2 to 65 months post index. In conclusion, isolated anti-HBs OBI in Chinese blood donors appears associated with young, vaccinated, adults exposed to HBV who predominantly develop low level aborted infection revealed by transient HBV DNA and immune anti-HBs response. However, a subset of individuals still experienced low but persistent viral replication whose clinical outcome remains uncertain.

Follow-up program for blood donors with unconfirmed screening results reveals a high false-positive rate in Dalian, China.

BACKGROUND: Chinese blood donors with unconfirmed serological and/or molecular screening results are deferred permanently. This study investigated the implementation and performance of a follow-up program aiming to improve the notification and management of deferred donors in Dalian, China. STUDY DESIGN AND METHODS: From January 2013 to February 2018, 411,216 donations were tested for HBsAg, anti-HCV, anti-HIV/HIV antigen, and antibodies to Treponema pallidum. HBV, HCV, and HIV nucleic acid testing (NAT) was performed in mini-pools of six or in individual donations (IDs). Reactive donations were evaluated further with alternative serological assays and ID-NAT re-testing. A follow-up procedure was developed to evaluate a subset of deferred donors that were either potential NAT yield cases, serology non-reactive and NAT non-repeated reactive (NRR), or serology NRR irrespective of NAT result. RESULTS: Serological and molecular routine, plus supplemental testing, identified HBV, HCV, HIV, and TP in 503 (0.12%), 392 (0.09%), 156 (0.04%), and 2041 (0.49%) donations, respectively. Overall, 683 of 4156 (16.4%) eligible donors and 205 donors deferred prior 2013 participated in the program. They included 664 serology NRR and 224 NAT yield cases, and 58.8% repeat donors. All markers combined, follow-up documented false reactivity, primary acute infections, and OBI in 61.9% (550/888), 3.3% (29/888), and 12.8% (114/888) of these donors, respectively. Isolated anti-HBc or anti-HBs reactivity was observed in 22% of cases. CONCLUSION: Follow-up testing refined infection status in 78.0% (693/888) of deferred donors with unconfirmed screening results. This high false-positive rate encouraged to reevaluate the current screening strategies and to consider donor reentry.

The prevalence of human T-cell leukemia virus in blood donors in China.

BACKGROUND: China has not yet incorporated routine human T-lymphotropic virus (HTLV)-1/2 blood donor screening, even though HTLV has been reported in the southeastern coastal region. This study was conducted to investigate the prevalence of HTLV in five major regions across of China. METHODS: From January 2016 to December 2017, blood samples were collected in 20 blood centers located in different regions of China. These samples were screened for HTLV-1/2 antibodies using enzyme-linked immunosorbent assay (ELISA). If the test samples were reactive, the samples were confirmed with a western blot (WB) assay. If the results of WB were indeterminate, the donor was interviewed after a minimum lapse of 8 weeks. All follow-up samples from donors were tested for anti-HTLV-1/2 with ELISA and WB. RESULTS: There were 875,453 donor samples tested for anti-HTLV-1/2 by ELISA. In all, 365 samples tested negative, 22 samples tested positive by WB, and 14 samples with HTLV status undetermined due to being lost to follow-up. The prevalences were 11.09, 5.96, 3.16, 2.88 and 0.98 per 100,000 in Xiamen, Changsha, Beijing, Shenzhen, and Nanjing blood center, respectively. The prevalences were 0 per 100,000 for all 15 other blood centers. There was significant differences in the prevalence of HTLV in different regions of China (p = 0.0011). CONCLUSION: In China, HTLV-1 confirmed positive donors are mainly from southeastern coastal areas. It may be necessary to conduct HTLV screening in these areas to reduce the risk of transfusion-transmitted HTLV.

The current incidence, prevalence, and residual risk of hepatitis B viral infections among voluntary blood donors in China.

BACKGROUND: There are few data available on the prevalence, incidence, and residual risk of transfusion-transmitted HBV (TT-HBV) infections among Chinese blood donors. This study investigated the demographic characteristics of blood donors, as well as the prevalence, incidence, and residual risk (RR) of TT-HBV infections in six large blood centers in different regions of China. METHODS: The demographic characteristics and HBV screening test results of blood donors from six blood centers in different regions in China were collected and analyzed. The hepatitis B surface antigen (HBsAg) yield approach was used to estimate the incidence of HBV. Then, the RR of TT-HBV infections was evaluated using the incidence-window period model. RESULTS: The majority of donors were between 18 and 35 years old (including 35), with the exception of the Changzhi Blood Center where a majority of donors were between 35 and 55 years old (including 55). The prevalences of HBV were 0.13%, 0.078%, 0.16%, 0.07%, 0.20%, 0.25% in Hefei, Dalian, Changzhi, Kaifeng, Mianyang and Fujian, respectively. The estimated corresponding incidences were 213.44, 161.59, 989.80, 278.05, 125.31 and 352.19 per 105 person-years. Using an infectious window period of 59 days, the RR for HBV was estimated to be 34.14, 25.85, 158.35, 44.48, 20.04 and 56.35 per 105 person-years in Hefei, Dalian, Changzhi, Kaifeng, Mianyang and Fujian, respectively. CONCLUSION: Despite the introduction of more sensitive assays in blood screening, our data revealed that the current residual risk of TT-HBV infection was still high (overall 56.53 per 105 py). A continuous monitoring of the residual risk of transfusion-transmitted infections is crucial for safe blood management.

Establishing a reentry procedure for human immunodeficiency virus screening-reactive donors in China.

BACKGROUND: Screening of blood donors for antibody to human immunodeficiency virus Types 1 and 2 (anti-HIV-1/2) and/or HIV nucleic acid test (NAT) is a well-established venue to prevent HIV transfusion-transmitted disease. However, with the current available technologies, HIV testing may result in donor loss due to false-positive results. This study intended to establish a donor reentry procedure for HIV screening-reactive donors in China. STUDY DESIGN AND METHODS: From September 1, 2013, to August 31, 2014, a total of 465 donors from 14 Chinese blood centers were enrolled in this study. Enrollment criteria include all donors who were screened reactive or belonged to the "gray zone" by enzyme-linked immunosorbent assay and/or reactive by NAT when tested at the local blood centers. All donor samples were sent to a central HIV confirmation laboratory where anti-HIV-1/2 and HIV individual-donation NATs were conducted. If the results were reactive for anti-HIV-1/2, then the samples were tested with a recombinant immunoblot assay. RESULTS: Based on the repeat testing at the central HIV confirmation laboratory 8 or 16 weeks after the study, 252 donors of 465 (54.2%) who completed the study could be classified in two categories for HIV status: 45 (18%) true positive and 207 (82%) false positive. A total of 213 of 465 (45.8%) donors were lost on follow-up and, thus, their HIV status cannot be determined with certainty. Based on these data, a donor reentry procedure was proposed. CONCLUSION: Based on our proposed donor reentry procedure for HIV screening-reactive donors, a majority of screening-positive donors (82%, 207/252) can be reentered safely.

Re-Entry Evaluation of Chinese Blood Donors with Unconfirmed Hepatitis B Screening Results.

The hepatitis B virus (HBV) remains a high priority for Chinese blood banks due to the high prevalence of infection. HBV blood safety has been significantly improved by the implementation of highly sensitive and specific serological and molecular HBV screening assays. The multiplication of viral markers tested and the ever-increasing analytical sensitivity of the tests can make the interpretation of the results difficult. False-positive or indeterminate results may lead to permanent donor deferrals and conflicts between donors and blood banks. To avoid blood shortages, blood services aim to limit unnecessary donor losses by developing procedures for the re-entry of donors temporarily deferred due to an unconfirmed HBV reactivity. The development of such procedures based on donor follow-up and HBV confirmation remains limited. A review of the scarce data available revealed considerable heterogeneity in testing methods and re-entry algorithms, limited validation studies, and a lack of accurate assessment of the residual infectious risk potentially associated with donor re-entry. In conclusion, systematic and widely validated confirmatory testing and prolonged follow-up are essential for safe re-entry of temporary deferred donors. Standardization of HBV testing methods and the establishment of dedicated expert laboratories are needed because of the complexity of HBV infection in blood donors.

Alternative hepatitis B virus DNA confirmatory algorithm identified occult hepatitis B virus infection in Chinese blood donors with non-discriminatory nucleic acid testing.

BACKGROUND: Multiplex viral nucleic acid testing (NAT) and a discriminatory testing algorithm have been used to detect viral infections in blood donors. Non-discriminated reactive (NDR) results may arise from low hepatitis B virus (HBV) DNA levels and are challenging for donor management by blood services. The aim of this study was to evaluate the performance and feasibility of alternative viral particle concentration methods to confirm and to characterise HBV infection status in NDR donors from Dalian, China, in order to improve routine donor management according to the potential residual risk estimate. MATERIALS AND METHODS: Individual donations were tested with ULTRIO Plus, and discriminated when reactive. Virions were concentrated from 12 and 6 mL plasma samples by ultracentrifugation (UC) and polyethylene glycol (PEG) precipitation, respectively. HBV DNA was detected with four nested polymerase chain reactions (95% limit of detection: 5-25 IU/mL). Amplified products were sequenced for definitive confirmation. Anti-HBc and anti-HBs were tested. RESULTS: Of 77,556 donors, 79 (0.1%) were NAT NDR. After viral particle concentration by UC and PEG precipitation, HBV DNA was detected in 46 (58.2%) and 34 (43.0%) NDR donors, respectively, including 61.7% of samples that were repeatedly non-reactive with multiple NAT testing. Anti-HBc and anti-HBs (median titre: 37 mIU/mL) were detected in 87.3% and 46.8% of NDR donors, respectively. Sequencing confirmed HBV DNA in 65.8% of NDR donors, of whom 96.2% were occult HBV carriers with rare mutations in S and core proteins. DISCUSSION: A HBV DNA confirmatory procedure with limited technical constraints was implemented successfully. The majority of NDR donors had occult HBV infections with extremely low viral DNA levels, which may constitute a potential residual threat for blood safety. Only a minority of anti-HBc+ NDR donors had anti-HBs levels high enough to consider their reinstatement as donors. The data support the permanent deferral of NDR donors to ensure maximum blood safety in areas of high HBV endemicity.