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OBJECTIVE To evaluate the development of blood transfusion services in Mainland China within the context of health-care system reform. BACKGROUND China launched a health-care reform program in 2009 to redistribute health-care resources, which are currently over-concentrated in well-developed cities. A geographically equitable blood transfusion service is key to achieving this goal. METHODS Based on the national survey of blood establishments in July 2015, total blood collection, whole-blood donations per 1000 population and the supply and demand relationship were analysed at the administrative region level. Areas at different developmental levels were compared in terms of total blood collection and human resources. RESULTS In 2014, Mainland China's 31 provinces showed wide variation, with total blood collection in blood facilities ranging from about 1000 units to over 600 000 units (each 200 mL), and the whole-blood donation rate per 1000 population, ranging from 1·48 to 17·09. 69% of the country's total collection, was concentrated in 29 provincial capitals, and 31% was in 311 non-capital cities. Of 97 personnel with doctorates, 74 worked in 32 provincial blood establishments, whereas the remaining 23 worked at the other 318 blood stations. In most provinces, per permanent resident donation was within 2-4 mL, and blood volume per inpatient was 10-35 mL regardless of the development of the transfusion service. CONCLUSION In 2014, China had an imbalanced development and insufficient access to blood transfusion services. This service must be redeployed at the national level to facilitate health-care reform in China.

We performed an evolutionary analysis using whole genome sequence isolates of hepatitis C virus (HCV) 6a from Guangdong Province and reference sequences from various countries. Less than 5% of the HCV genome was found to be under positive selection. The E1 and E2 proteins had the highest proportion of positively selected sites both within and outside of CD8 T cell epitopes in all of the strains. Regions corresponding to CD8 T cell epitopes were under negative selection except in the isolates from Guangdong. Furthermore, we found evidence of three introductions of the virus into Guangdong from Vietnam and other Southeast Asian countries. Thus, this study provides information about the transmission of HCV 6a by comparison of full-length sequences, indicating the impact of selective constraints in Guangdong and across China. Supplementary Information The online version contains supplementary material available at 10.1007/s00705-021-05358-7.

Background A nationwide ban on family/replacement donation (FRD) went into effect on April 1, 2018 in China. To date, no reports relevant to the trend of plateletpheresis donations before and after a nationwide ban on FRD were found. Methods We used two independent full samples, consisting of 135,851 and 82,129 plateletpheresis donors from Guangzhou and Chengdu between October 2012 and September 2019, respectively. A pseudo-panel data approach was applied by grouping three time-invariant covariates – gender, blood donation history, and birth year across 14 cross-sections (a 6-month interval each) to form a total of 24 cohort groups (14 × 24 = 336 cohorts, i.e., cells) with each having common covariates. The outcome was average apheresis platelet units per donor in each cell. We performed a two-piecewise linear mixed model with the cross-section (i.e., time) just right before the ban as a time breakpoint (i.e., 11th cross-section) to examine the trend of outcome with the adjustment of three time-invariant covariates. We removed the FRDs in each of the first 11 cross-sections to detect its possible influence on the trend. Results The final model for the samples from Guangzhou presented a two-piecewise linear trend of the outcome over time with a horizontal line to the left of the breakpoint (βtimeBefore11 = 0.0111, p = 0.0976) and a significantly positive linear trend to the right (βtimeAfter11 = 0.0404, p Conclusion The significant increase of the average apheresis platelet units per donor over time after the FRD ban may be related to the implement of the FRD ban and the improved donation behavior of male donors and/or donors with platelet donation history after the ban. Our findings may potentially motivate the policymakers in other countries where the FRD for plateletpheresis donation is still legitimate to phase out their FRD strategy and ultimately achieve 100% voluntary plateletpheresis donation.

Objectives To screen RhCE variants in the Chinese Southern Han donors for molecular genetic analysis. Background More than hundreds of RhCE variant alleles have been described to resulting in weak and/or partial expression of RhCE antigens, generation of low-prevalence antigens and/or absence of a high-prevalence antigen of Rh system, which mainly reported in the people of African origin. In this study, the serological screening and molecular genetic analysis of RhCE variants were performed in the Chinese Southern Han donors. Methods The blood samples of E(+) donors were preliminarily collected. Then, RhCE antigens of the E(+) samples were further typed by using two sets of monoclonal anti-C, anti-c, anti-e and another anti-E. When weak expression of RhCE antigens was found, direct sequencing for 10 exons of RHCE gene, RH genotyping analysis by using multiplex ligation-dependent probe amplification, flow cytometric analysis and even cDNA sequencing were performed. Results A total of 4487 E(+) samples were collected and four samples with weak expression of antigens were detected. RHCE*Ce375G and RHCE*Ce667T variant alleles were identified in two samples with weak expression of e antigen, respectively. But no variant alleles were found in another two samples with weak expression of C antigen. Conclusion The variant RHCE*Ce375G validated by mRNA sequencing and the deduced RHCE*Ce667T alleles were firstly identified in the Chinese population. The DCE haplotype might account for the weak expression of C antigen in two donors.

Hepatitis C virus (HCV) genotype 3 (GT-3) represents 22–30% of all infections and is the second most common genotype among all HCV genotypes. It has two main subtypes, GT-3a and GT-3b, that present epidemiological differences in transmission groups. This report generated 56 GT-3a and 64 GT-3b whole-genome sequences to conduct an evolutionary kinetics and selective force analysis with reference sequences from various countries. Evolutionary analysis showed that HCV GT-3a worldwide might have been transmitted from the Indian subcontinent to South Asia, Europe, North America and then become endemic in China. In China, GT-3a may have been transmitted by intravenous drug users (IDUs) and become endemic in the general population, while GT-3b may have originated from IDUs and then underwent mutual transmission between blood donors (BDs) and IDUs, ultimately becoming independently endemic in IDUs. Furthermore, the spread of GT-3a and GT-3b sequences from BD and IDU populations exhibit different selective pressures: the proportion of positively selected sites (PPSs) in E1 and E2 from IDUs was higher than in BDs. The number of positive selection sites was higher in GT-3b and IDUs. These results indicate that different selective constraints act along with the GT-3a and GT-3b genomes from IDUs and BDs. In addition, GT-3a and GT-3b have different transmission routes in China, which allows us to formulate specific HCV prevention and control strategies in China.

To systematically characterize the prevalence and evolution of human T-cell lymphotropic virus (HTLV) infection among voluntary blood donors (BDs) in Guangdong province, China. A three-year survey for HTLV epidemiology among BDs was performed in Guangdong during 2016–2018. Anti-HTLV-1/2 was screened by ELISA and ECLIA, and subsequently confirmed by western blot (WB) and nucleic acid testing (NAT). The prevalence of HTLV in donors from different cities was calculated. The identified HTLV-positive cases were phylogenetically genotyped and analyzed in a Bayesian phylogenetic framework. Among 3,262,271 BDs, 59 were confirmed positive for HTLV-1 (1.81 per 100,000) and no HTLV-2 infection was found. The prevalence of HTLV-1 varied significantly among 21 cities in Guangdong province, China. The highest prevalence was found in donors from Shanwei (13.94 per 100,000), which is a coastal city in eastern Guangdong. Viral genomic sequences genotyped from 55 HTLV-1 carriers showed that 39 were transcontinental subtype and 16 were Japanese subtype. Specially, 13 out of 39 transcontinental subtype sequences were characterized with L55P mutation and 21 out of 55 sequences were characterized with L19F mutation in viral gp46 protein. The L55P mutation seemed be specific to eastern Asia since it only presented in the sequences from Japan, mainland China, and Taiwan. Phylogenetic analysis of gp46 gene shows that HTLV-1a may have been introduced to Guangdong through four different introduction events and formed major transmission clusters: clades I(13,602 years ago), II(16, 010 years ago), III(15,639 years ago) and IV(16,517 years ago). In general, Guangdong is considered to be a low-prevalence region for HTLV-1 infection, but the prevalence is significantly higher in Shanwei city. Transcontinental and Japanese subtype lineages dominate the prevalence in Guangdong. In terms of blood safety, HTLV antibody screening for first-time blood donors can effectively reduce the risk of HTLV transmission., Author summary Human T-cell lymphotropic virus type 1 distributed all over the world. Since 1988, serological screening has been included in routine blood screening in certain developed countries and regions such as American countries and some parts of Western Europe and East Asia. However, data from some highly populated countries such as China are still not available. We performed a 3-year large-scale blood screening survey to systematically characterize the prevalence of HTLV infection among blood donors in Guangdong province in south China during 2016–2018. In general, Guangdong was considered to be a low-prevalence region for HTLV-1 infection, but the prevalence is significantly higher in Shanwei, a coastal city of eastern Guangdong. Transcontinental and Japanese subtype lineages dominate the prevalence in Guangdong. Moreover, similar molecular characteristics of prevalent HTLV-1 sequences in Mainland China, Taiwan and Japan suggested a same origin of these viruses.

BACKGROUND The coronavirus disease 2019 (COVID‐19) epidemic affected blood collection in Guangzhou, China. STUDY DESIGN AND METHODS This paper included three studies. The observational study reported the trends of blood collection during the epidemic in Guangzhou, China. The cross‐sectional survey investigated factors influencing blood donation during the COVID‐19 epidemic, and a self‐administered questionnaire was given to 1,584 street whole blood donors (SWBDs) who donated during the epidemic. The randomized controlled trial involved 19,491 SWBDs who donated in 2019 but did not donate during the epidemic. Trial participants were randomly assigned to two intervention groups: group 1 completed Questionnaire 1, which contained precautionary measures in response to COVID‐19 and other messages about blood donation during the epidemic; and group 2 completed Questionnaire 2, which did not include this information. A control group did not receive any questionnaire. RESULTS As measures implemented, the number of blood donors increased accordingly. Both first‐time and repeat SWBDs perceived the same level of blood need and donated blood because it would save lives. SWBDs who completed Questionnaire 1 expressed a greater intention to donate during the epidemic. Enabling blood donors to perceive a higher level of blood need and a lower level of COVID‐19 infection risk related to blood donation mobilized experienced SWBDs to donate within three weeks. Intention‐to‐treat analyses and average‐treatment‐effect‐on‐the‐treated estimations confirmed that Questionnaire 1 could motivate SWBDs to actually donate blood. CONCLUSION Various measures could ease blood shortage during the COVID‐19 epidemic. Administration of Questionnaire 1 could increase blood donations during the epidemic. This article is protected by copyright. All rights reserved.

The need for physicians and technical consultants specialized in transfusion medicine is urgent in China, as there are 20 000 hospitals and 500 blood centers in need of staff with this expertise. The progress made in transfusion medicine as a specialty has been relatively slow in China. Current Chinese medical education and service systems have not developed transfusion medicine as a stand-alone medical specialty. Most physicians receive only minimal training in transfusion medicine in medical school. This training is usually integrated into surgical training and addresses the most common technologies. In 2008, a 5-year bachelor's diploma program in transfusion medicine was established as an undergraduate specialty in Southern Medical University, Guangzhou, China. This article intends to summarize the 8 years of experience educating undergraduates in the specialty of transfusion medicine.

Background CD36 is a multifunctional receptor in cells that plays a role in important cellular processes including immune regulation. Evidence indicates that mutations in the CD36 gene are associated with malaria. Moreover, studies on the frequency of CD36 deficiency have been conducted in specific provinces of China. However, the frequency of CD36 deficiency may differ among various ethnic populations. In this study, we analyzed the frequency of CD36 deficiency among seven different provinces and minorities in China. Methods and materials In this study, 5313 samples were randomly collected from seven provinces in China. CD36 deficiency on platelets and monocytes was determined via flow cytometry using a monoclonal antibody (mAb) against CD36. DNA sequencing analysis was performed to identify mutations associated with CD36 deficiency. Results The frequency of CD36 deficiency among individuals from different provinces (n = 7) was 1.60%, comprising 0.38% of type-I deficiency and 1.22% of type-II deficiency. The distribution among provinces ranged from 0.81% to 1.99%. The largest ethnic group, Han, showed a lower frequency of deficiency than ethnic minorities (1.30% versus 2.37%). The most common mutations found in our overall cohort were 329-330delAC and 1228-1239delATTGTGCCTATT. Significant high frequencies of CD36 deficiency were detected in two ethnic minorities, Zhuang (3.69%) and BuYi (3.05%), living in southern China. Conclusions Through an analysis of a large cohort, we determined the frequencies of CD36 deficiency among different Chinese ethnic groups. A high frequency of type-I deficiency was found in certain minorities living in southern China, which is known to be vulnerable to malaria epidemics. These findings may help us understand the phenotypic consequences of CD36-deficient alleles associated with malaria.

Specific human leukocyte antigen (HLA) class I and class II alleles have been associated with spontaneous clearance or persistent infection of hepatitis C virus (HCV), which seemed to be restricted by the host's ethnicity and viral genotype. Recently we reported a high prevalence and spontaneous clearance rate of HCV in a cohort of Chinese Li ethnicity who were infected with new variants of HCV genotype 6. In this study, we found that the distribution of HLA class I and class II alleles in HCV infected individuals of Chinese Li ethnicity (n = 143) was distinct from that of Chinese Han ethnicity which was reported in our previous study. HLA-DRB1*11:01 and DQB1*03:01 were more prevalent in Chinese Li subjects who cleared HCV spontaneously than those who were chronically infected (P = .036 and P = .024, respectively), which were consistent with our previous report regarding the Chinese Han population. Multivariate logistic regression analysis showed that DQB1*03:01 (odds ratio = 3.899, P = .017), but not DRB1*11:01, associated with HCV spontaneous clearance, independent of age, sex, and IFNL3 genotype. Because DQB1*03:01 and DRB1*11:01 were tightly linked because of linkage disequilibrium, our results clearly supported the associations of these two alleles with HCV spontaneous clearance in Chinese Li as well as Han ethnicity.

The distribution of hepatitis C virus (HCV) genotypes/subtypes varies among different populations. Here, we investigated HCV infection and its genotype distribution in injection drug users (IDUs) in Guangdong Province of China. A total of 318 IDUs from two prisons were recruited. The genotypes/subtypes of HCV in IDUs were determined by phylogenetic analysis using E1 and/or NS5B gene sequences. Our previous data on blood donors (BDs) with no history of drug use were used as control population data for comparison. Our results showed that the prevalence of HCV 3b (20.9% vs. 3.6%, P = 3.4E-9) and 6a (57.0% vs. 39.8%, P = 1.2E-5) was higher in IDUs than in BDs. In contrast, the prevalence of HCV 1b (43.4% vs. 5.6%, P = 9.8E-23) in BDs was higher than in IDUs. Phylogeographic analysis indicated that HCV 3b migrated from Yunnan to Guangdong Province and became endemic, with further transmission to other regions of China. The trend of HCV 3b dissemination in China in IDUs requires further attention, and a strategy for prevention and therapy is needed.

Background: Although human leukocyte antigens (HLA) have been shown in association with the outcomes of hepatitis C virus (HCV) infection among different ethnic groups, such studies remain absent in China, where the HCV prevalence is higher than the global average. Methods: In this study, 426 HCV-infected and 709 uninfected blood donors were analyzed, among whom the HLA alleles were sequenced using a high-resolution genotyping method. Results: At the 2-digit level, none of the alleles showed a statistical difference between the HCV-infected and uninfected groups. However, at the 4-digit level, the HLA-B alleles B*15:01 and B*15:02 showed an opposite association with HCV infection, i.e. B*15:01 was significantly higher in the HCV-infected group (odds ratio, OR = 1.561, p = 0.010), while B*15:02 was significantly higher in the uninfected group (OR = 0.778, p = 0.016). We also identified a higher frequency of B*13:02 in the HCV-infected group (OR = 1.515, p = 0.009) and a higher frequency of B*07:05 in the uninfected group (OR = 0.299, p = 0.001). Conclusions: The frequencies of four HLA alleles, B*07:05, B*13:02, B*15:01, and B*15:02, were found to be significantly different between the HCV-infected and uninfected blood donors in China, revealing an inverse relation of B*15:01 and B*15:02 with HCV infection. This finding suggests that the ethnic genetic variations of HLA may greatly affect the host immune responses against HCV.

The evolutionary and epidemic history and the regional differences of hepatitis C virus (HCV) are complex and remain unclear in the vast territory China. Here we recruited 1540 HCV-RNA positive patients sampled in 29 provinces across whole China, which is the largest sample capacity and the most comprehensive geographic coverage of China to our knowledge. 1b, 2a, 3b, 6a and 3a were the major subtypes in China. 1b was the most predominant subtype which presented in every province. The second most predominant subtype, 2a, appeared to concentrate in the north of China. Subtypes 3a and 3b were mainly found in the Southwest region, while 6a was restricted in the South region. We further estimated the origins of the dominating subtypes and discovered for the first time that a Chinese-specific transmission pattern for some strains of subtype 2a which was restricted in north China, and Chinese subtype 3b originated from Thailand.

Background Human pegivirus type 2 (HPgV-2) is a novel blood-borne human pegivirus that mainly infects hepatitis C virus (HCV)-infected subjects. We have investigated the prevalence of HPgV-2 in China, its association with HCV and human immunodeficiency virus type 1 (HIV-1), and the impact on HCV viral load and liver damage. Methods A cross-sectional study was conducted with both blood donors and HCV- and HIV-1-infected patients in Guangzhou, China. All subjects were screened for anti-HPgV-2 and HPgV-2 RNA. Demographic and clinical information were obtained from electronic medical records. Results We tested 8198 serum or plasma samples. Only 0.15% (6/4017) of healthy blood donors were positive for anti-HPgV-2 and negative for HPgV-2 RNA. No HPgV-2 viremia was detected in hepatitis B virus- or HIV-1-monoinfected individuals. The relatively high frequency of HPgV-2 infection was observed in 1.23% (30/2440) and 0.29% (7/2440) of HCV-infected persons by serological assay and reverse-transcription polymerase chain reaction, respectively. Furthermore, anti-HPgV-2 and HPgV-2 RNA were detected in 8.91% (18/202) and 3.47% (7/202), respectively, of HCV/HIV-1-coinfected subjects. HPgV-2 persistent infection was documented in about 30% of anti-HPgV-2-positive individuals. In addition, HPgV-2 infection may not affect HCV-related liver injury and HCV viral load. Conclusions Our results indicate the rarity of HPgV-2 infection in the general population and tight association with HCV, in particular with HCV/HIV-1 coinfection. HPgV-2 appears not to worsen HCV-related liver damage. Our study provides new findings about the association of HPgV-2 and HCV/HIV-1 and the impact of HPgV-2 infection on HCV replication and pathogenesis.

Natural killer (NK) cells are critical components in innate immune response to viral infection. Killer cell immunoglobulin-like receptors (KIRs) are involved in regulating the balance of activation or inhibitory function of NK cells. However, the association of KIRs with the spontaneous clearance of hepatitis C virus (HCV) remains unclear in the Chinese population.A total of 407 HCV-seropositive voluntary blood donors were recruited, including 203 with spontaneous viral clearance and 204 with chronic infection. The presence of KIR genes was detected individually by polymerase chain reaction with sequence-specific primers. Data of HLA and interleukin-28B (IL28B) genotypes were extracted from our previous study.Our results showed that KIR2DL2, 2DS2, 2DL2/2DL3, and 2DL5A-/2DL5B+ were more frequent in subjects with HCV clearance than those with chronic infection (odds ratio [OR], 1.640, p = 0.034; OR, 1.664, p = 0.032; OR, 1.636, p = 0.040; and OR, 2.601, p = 0.012, respectively). Multivariate logistic regression analysis showed that KIR2DL5A-/2DL5B+ associated with HCV clearance (OR, 2.448, p = 0.027), independent of sex, IL28B, and other KIRs. In contrast, KIR2DL3/2DL3 (OR, 0.610, p = 0.034) as well as 2DL3/2DL3+HLA-C1 or C1C1 (OR, 0.580, p = 0.017; and OR, 0.639, p = 0.025, respectively) was found associated with chronic HCV infection. The presence of the homozygous KIR2DL3 with or without its HLA ligand increased the OR of developing chronic HCV infection in the context of IL28B.In this study we identified KIR2DL5A-/2DL5B+ associated with HCV spontaneous clearance, while KIR2DL3/2DL3, 2DL3/2DL3+HLA-C1, or C1C1 associated with chronic infection. Our study highlighted the fact that the roles of KIR and KIR-HLA contributed to the control of HCV infection by innate immune responses.

The status of chronic and occult HBV infection (OBI) in neonatal hepatitis B vaccine and immunoglobulin (HBIG) vaccinated infants born to HBsAg+ mothers was investigated at a major hospital in China. Seventy-seven and 15 blood samples were collected in first or second follow-up detection from the vaccinated babies aged 3-36 months born to 43 HBsAg+ or plus 25 HBeAg+ mothers. HBV infection was analyzed between the paired baby and mother by serology and DNA analysis. Among 77 children born to 68 HBsAg+ mothers, 3.9% (3/77) were HBsAg+, and 36.4% (28/77) were HBV DNA+/HBsAg- (OBIs) by a single PCR, respectively. Thirteen of 28 HBV DNA+/HBsAg- samples were conformed by two PCRs or S sequence, which accounted for 16.9% (13/77) of children. Three HBsAg+ and six OBIs were genotyped in consistent with their mother's HBV strains. Of 77 babies' blood samples, anti-HBs reactivity varied slightly according to age groups, while passively transmitted anti-HBc reactivity declined from 100% high reactivity at age 3-5 months to mostly negative at age ≥12 months. Babies with apparent OBI had higher levels of anti-HBc and lower levels of anti-HBs than those without OBI but all eight OBI babies with second follow-up samples became HBV DNA negative beyond 1 year of age. The vaccinated infants born to HBsAg+ mothers presented the low rate of HBsAg occurrence as vaccination failure and high frequency of viral persistence in the form of transient OBIs since no evidence of active HBV infection occurred beyond 1 year of age.

In 2014, an outbreak of dengue virus (DENV) infection led to 45 171 clinical cases diagnosed in Guangdong province, Southern China. However, the potential risk of blood donors asymptomatically infected with DENV has not been evaluated . In the current study we detected anti-DENV IgG antibody and RNA in volunteer Chinese blood donors. We found that anti-DENV IgG antibody was positively detected in 3.4% (51/1500) and two donors were detected as being DENV RNA positive out of 3000 blood samples. We concluded that the presence of potential DENV in blood donors might be potential risk for blood safety. Therefore, screening for DENV infection should be considered in blood donations during a period of dengue outbreak in high epidemic area of China.

We characterized a novel group of HCV variants that are genetically related but distinct from each other belonging to genotype 6 (HCV-6). From 26 infected Austronesian-descended aborigines on Hainan Island, China, HCV sequences were determined followed by genetic analyses. Six nearly full-length genomes and 20 E1 sequences of HCV were obtained, which differ from each other and from all known HCV lineages by nucleotides above the intra-subtype level of 13%. Together with subtypes 6g and 6w, they constitute a phylogenetic group sharing a common ancestor dating from the end of the 12th century. Conclusion Our data indicate the maintenance of an isolated HCV-6 indigenous circulation on Hainan Island at least for six centuries.

We investigated the migration patterns of hepatitis C virus (HCV) in China. Partial E1 and/or NS5B sequences from 411 volunteer blood donors sampled in 17 provinces and municipalities located in five large regions, the north-northeast, northwest, southwest, central south, and southeast, were characterized. The sequences were classified into eight subtypes (1a,n= 3; 1b,n= 183; 2a,n= 83; 3a,n= 30; 3b,n= 44; 6a,n= 55; 6n,n= 10; 6v,n= 1) and a new subtype candidate. Bayesian evolutionary analysis by sampling trees of the E1 sequences of the five major subtypes revealed distinct migration patterns. Subtype 1b showed four groups: one is prevalent nationwide with possible origins in the north-northeast; two are locally epidemic in the central south and northwest, respectively, and have spread sporadically to other regions; and the fourth one is likely linked to the long-distance dispersion among intravenous drug users from the northwest. Subtype 2a showed two groups: the larger one was mainly restricted to the northwest and seemed to show a trend toward migration via the Silk Road; the smaller one was geographically mixed and may represent descendants of those that spread widely during the contaminated plasma campaign in the 1990s. Subtype 3a exhibited three well-separated geographic groups that may be epidemically unrelated: one showed origins in the northwest, one showed origins in the southwest, and the other showed origins in the central south. In contrast, subtype 3b had a mixture of geographic origins, suggesting migrations from the southwest to the northwest and sporadically to other regions. Structurally resembling the tree for subtype 3a, the tree for subtype 6a showed four groups that may indicate migrations from the central south to southeast, southwest, and northwest. Strikingly, no subtype 6a strain was identified in the north-northeast.IMPORTANCEWith a population of greater than 1.3 billion and a territory of >9.6 million square kilometers, China has a total of 34 provinces and municipalities. In such a vast country, the epidemic history and migration trends of HCV are thought to be unique and complex but variable among regions and are unlikely to be represented by those observed in only one or at best a few provinces and municipalities. However, due to the difficulties in recruiting patients, all previous studies for this purpose have been based only on data from limited regions, and therefore, geographical biases were unavoidable. In this study, such biases were greatly reduced because we utilized samples collected from volunteer blood donors in 17 provinces and municipalities. To our knowledge, this is the first study in which the HCV isolates represented such a large portion of the country, and thus, the results should shed light on the current understanding of HCV molecular epidemiology.

In this study, we characterized the full-length genomes of 16 HCV isolates obtained from patients in a single hospital in China using overlapping PCR followed by DNA sequencing. The obtained genomes are 9,414-9,628 nucleotides in length, and each genome contains a single ORF of 9,021-9,102 nucleotides. Nine genomes represent the common subtypes 1a, 1b, 2a, 2b, 3a, 3b, and 6a, while seven represent the infrequent lineages 1c, 2f, 4d, and 5a, and two novel genotype 6 variants. GZ51969 and GZ52540 are subtype 1b isolates belonging to two unique clusters designated A and B, which account for 29.5% and 59.5% of the 1b infections in China, respectively. ZS542 and GZ98799 represent the first two complete genomes of the provisionally assigned subtype 2f. ZS96 and ZS202 are novel genotype 6 variants that may qualify for two new subtypes. ZS17, ZS537, and ZS631 represent three alien subtypes, namely, 1c, 4d, and 5a, which were detected in China for the first time in this study and may have been recently introduced as a result of globalization. Taken together, these results confirmed a large variety of HCV taxonomic lineages in China through the sequencing of their full-length genomes. These lineages represent six genotypes, 11 subtypes, and two novel variants. They were characterized for achieving a better understanding of the HCV genetic variation patterns and for possible future research applications.

Item does not contain fulltext BACKGROUND: Genotyping platforms for common red blood cell (RBC) antigens have been successfully applied in Caucasian and black populations but not in Chinese populations. In this study, a genotyping assay based on multiplex ligation-dependent probe amplification (MLPA) technology was applied in a Chinese population to validate the MLPA probes. Subsequently, the comprehensive distribution of 17 blood group systems also was obtained. STUDY DESIGN AND METHODS: DNA samples from 200 Chinese donors were extracted and genotyped using the blood-MLPA assay. To confirm the MLPA results, a second independent genotyping assay (ID Core+) was conducted in 40 donors, and serological typing of 14 blood-group antigens was performed in 91 donors. In donors who had abnormal copy numbers of an allele (DI and GYPB) determined by MLPA, additional experiments were performed (polymerase chain reaction, sequencing, and flow cytometry analysis). RESULTS: The genotyping results obtained using the blood-MLPA and ID Core+ assays were consistent. Serological data were consistent with the genotyping results except for one donor who had a Lu(a-b-) phenotype. Of the 17 blood group systems, the distribution of the MNS, Duffy, Kidd, Diego, Yt, and Dombrock systems was polymorphic. The Mur and Sta antigens of the MNS system were distributed with a frequency of 9% (18 of 200) and 2% (4 of 200), respectively. One donor with chimerism and one who carried a novel DI*02(A845V) allele, which predicts the depression of Dib antigen expression, were identified. CONCLUSIONS: The blood-MLPA assay could easily identify the common blood-group alleles and correctly predicted phenotype in the Chinese population. The Mur and Sta antigens were distributed with high frequency in a Southern Chinese Han population.

SummaryCD36 (also known as GPIV) deficiency is known to be responsible for the production of anti-Naka antibodies in different clinical settings such as fetal/neonatal alloimmune thrombocytopenia (FNAIT), platelet transfusion refractoriness (PTR) and post-transfusion purpura (PTP). However, no data regarding the relevance of CD36 immunisation is currently available for China. In this study, healthy blood donors were typed for CD36 deficiency using flow cytometry. Nucleotide sequencing was performed to identify the molecular basis underlying the CD36 deficiency. Anti-Naka antibodies in CD36-deficient individuals were analysed by ELISA and flow cytometry. By analysis of 998 healthy blood donors, 18 individuals failed to express CD36 on their platelets. In 5/12 individuals no CD36 expression was detected both on platelets and monocytes. This result suggested that the frequencies of type I CD36 deficiency (platelets and monocytes) and type II CD36 deficiency (platelets only) are approximately 0.5 and 1.3%, respectively. Nucleotide sequencing analysis of type I CD36 deficient individuals revealed eight different mutations; four of them were not described so far. However, 1228–1239de/ ATTGTGCCTATT and 329–330de/AC appear to be the most common mutations related to type I CD36 deficiency in South Chinese population. Further analysis showed that 1/5 type I CD36 deficient individuals developed anti-Naka antibodies. In addition, anti-Naka antibodies could be identified in two cases of thrombocytopenia associated with FNAIT and PTR. In conclusion, more than 0.5% of CD36 type I-deficient individuals are at risk to be immunised through blood transfusion or pregnancy in China. Testing of anti-Naka antibodies should be considered in FNAIT and PTR suspected cases. A registry of CD36-deficient donors should be established to allow treatment of immune-mediated bleeding disorders caused by anti-Naka antibodies.

Understanding the biology of spontaneous clearance of hepatitis C virus (HCV) infection could lead to improved strategies to prevent the sequelae associated with chronic HCV infection. Chronic infections with hepatitis virus are very common in China, but the factors associated with spontaneous clearance of HCV have not been adequately studied. We evaluated the spontaneous clearance of HCV among 1918 drug users and 1526 HCV-seropositive blood donors in Guangzhou, China. Among participants who were co-infected with hepatitis B virus (HBV), 41.38% of drug users and 39.47% of blood donors had cleared their HCV infection without antiviral therapy compared to 9.41% of drug users and 16.73% of blood donors who were mono-infected with a single virus (P

An HCV outbreak occurred in 2012 in China, affecting hundreds of patients. We characterized HCV subtype 2a and 6a sequences from 60 and 102 patients, respectively, and co-analyzed them with 82 local controls and 103 calibrating references. The close grouping of the patients׳ sequences contrasted sharply with the diversity of local controls. Scaled by the calibrating references, the emergence of patients׳ isolates was estimated at 2–5 years before sampling. In contrast, the controls intermingled with the calibrating references that were much older. For both subtypes, the major and minor clusters could be defined, with the closeness to indicate linked transmission. Conclusion : HCV sequences from the study patients grouped into three subtype 2a and two subtype 6a clusters, in addition to three 6a solitary branches, representing descendants of eight earlier strains that were distinct and otherwise sporadic. Due to iatrogenic transmission through reusing needles, five strains were highly selected and preferentially spread.

Here, the complete genome sequences for three hepatitis C virus (HCV) variants identified from China and belonging to genotype 6 are reported: km41, km42 and gz52557. Their entire genome lengths were 9430, 9441 and 9448 nt, respectively; the 5′ untranslated regions (UTRs) contained 341, 342 and 339 nt, followed by single open reading frames of 9045, 9045 and 9057 nt, respectively; the 3′ UTRs, up to the poly(U) tracts, were 41, 51 and 52 nt, respectively. Phylogenetic analyses showed that km41 is classified into subtype 6k and km42 into subtype 6n. Although gz52557 clustered distantly with subtype 6g, it appeared to belong to a distinct subtype. Analysis with 53 and 105 partial core and NS5B region sequences, respectively, representing 17 subtypes from 6a to 6q and three unassigned isolates of genotype 6 in co-analyses demonstrated that gz52557 was equidistant from all of these isolates, indicating that it belongs to a novel subtype. However, based on a recent consensus that three or more examples are required for a new HCV subtype designation, it is suggested that gz52557 remains unassigned to any subtype.

In one of our recent studies, two HCV genotype 6 variants were identified in patients from Hong Kong and Guangxi in southern China, with injection drug use and HIV-1 co-infection. We report the complete genomic sequences for these two variants: GX004 and HK6554. Their entire genome lengths were 9,468 and 9,462 nt; the 5' UTRs were 338 nt followed by single ORFs of 9,069 nt; the 3' UTRs were 61 and 55 nt including 29 and 23 nt poly(U) tracks. Phylogenetic analysis using a maximum likelihood method showed that HK6554 was classified into subtype 6g and GX004 represented the first complete genome sequence for subtype 6e. Further analysis with reference sequences in three different genomic regions revealed that GX004 closely clustered with a group of subtype 6e variants, which were previously exclusively found in Vietnam and recently increasingly identified in injection drug users from the Guangxi province in southern China that borders Vietnam. This suggests that subtype 6e could become epidemic in southern China by network transmission among injection drug users.

To determine hepatitis C virus (HCV) genotype distribution in China, a total of 148 HCV RNA positive serum samples were collected from nine geographic areas and subjected to RT-PCR followed by direct DNA sequencing and phylogenetic analysis of the core, E1, and NS5B regions. HCV was genotyped in 139 (93.9%) samples. Among them subtype 1b was the most predominant [66% (92/139)] followed by 2a [14% (19/139)]. Of 92 subtype 1b isolates, 35 (38%) and 30 (33%) formed two clusters, designated groups A and B. Group A was prevalent throughout China, while group B was predominant in the central and southern regions. In three cities in the Pearl River Delta, subtype 6a replaced 2a as the second most predominant subtype, and in Kunming (southwest) multiple HCV genotypes/subtypes were present. New variants of HCV genotype 6 were discovered in three samples from Kunming and one in Guangzhou in the Pearl River Delta.

We characterized the full-length genomes of 22 hepatitis C virus genotype 6 (HCV-6) isolates: 10 from Vietnam (classified into subtypes 6e, 6h, 6p, 6r, 6s, and 6u), one from China (confirmed as a new subtype 6xd), and 11 from the Lao PDR (representing a new subtype 6xe plus eight novel variants). With these 22 new genomes, HCV-6 now has a diverse and extended taxonomic structure, comprised of 28 assigned subtypes (denoted 6a-6xe) and 27 unassigned lineages, all of which have been represented by full-length genomes. Our phylogenetic analyses also included many partially-sequenced novel variants of HCV-6 from Lao PDR. This revealed that Lao HCV isolates are genetically very diverse and are phylogenetically distributed in multiple lineages within genotype 6. Our results suggest that HCV-6 has been maintained in Laos, a landlocked country, since the common ancestor of genotype 6 and indicates historical dispersal of HCV-6 across Southeast Asia., Highlights • We characterized 22 full-length genomes of HCV-6. • They confirmed two new subtypes 6xd and 6xe plus eight novel variants. • We also reanalyzed many partially-sequenced novel HCV-6 variants from Lao PDR. • They are phylogenetically distributed across the whole of genotype 6. • They indicate historical dispersal of HCV-6 across Southeast Asia.

Different hepatitis C virus (HCV) genotypes exhibit differences in disease pathogenesis and progression, as well as disease outcomes and response to therapy. Tracking the change of HCV genotypes in various epidemiological settings is critical for both disease surveillance and the development of improved antiviral treatment. Here, we tracked the changes in the prevalence of the HCV genotypes in China between 2004-2007 and 2008-2011. HCV-RNA-positive sera were collected from volunteer blood donors during the period 2008-2011. The genotypes were determined by phylogenic analysis using the NS5B and E1 sequences. Geographical and demographic distribution patterns related to the HCV genotypes obtained in 2008-2011 were compared with our previous study, which recorded data in the period 2004-2007. Pearson chi-square test and t-test were used to statistically analyze the results. In 2008-2011, HCV subtypes 1b and 6a were detected in 43.8 % (184/420) and 34.3 % (144/420), respectively. The male/female ratio was found to be higher for HCV genotype 6 than for genotypes 1 and 2. When compared with the period of 2004-2007, although no significant difference was found in gender or age for genotypes 1, 2, 3 and 6, the subtype 6a frequency was significantly increased from 11 % to 26.5 % in the blood donors from outside of Guangdong Province in 2008-2011. A pattern of increase in HCV subtype 6a was found in blood donors outside of Guangdong Province, indicating that HCV subtype 6a has rapidly spread from Guangdong to other regions of China over the past 10 years. Electronic supplementary material The online version of this article (doi:10.1007/s00705-014-2185-1) contains supplementary material, which is available to authorized users.

Background Recently in China, HCV 6a infection has shown a fast increase among patients and blood donors, possibly due to IDU linked transmission. Methodology/Findings We recruited 210 drug users in Shanwei city, Guangdong province. Among them, HCV RNA was detected in 150 (71.4%), both E1 and NS5B genes were sequenced in 136, and 6a genotyped in 70. Of the 6a sequences, most were grouped into three clusters while 23% represent emerging strains. For coalescent analysis, additional 6a sequences were determined among 21 blood donors from Vietnam, 22 donors from 12 provinces of China, and 36 IDUs from Liuzhou City in Guangxi Province. Phylogeographic analyses indicated that Vietnam could be the origin of 6a in China. The Guangxi Province, which borders Vietnam, could be the first region to accept 6a for circulation. Migration from Yunnan, which also borders Vietnam, might be equally important, but it was only detected among IDUs in limited regions. From Guangxi, 6a could have further spread to Guangdong, Yunnan, Hainan, and Hubei provinces. However, evidence showed that only in Guangdong has 6a become a local epidemic, making Guangdong the second source region to disseminate 6a to the other 12 provinces. With a rate of 2.737×10−3 (95% CI: 1.792×10−3 to 3.745×10−3), a Bayesian Skyline Plot was portrayed. It revealed an exponential 6a growth during 1994–1998, while before and after 1994–1998 slow 6a growths were maintained. Concurrently, 1994–1998 corresponded to a period when contaminated blood transfusion was common, which caused many people being infected with HIV and HCV, until the Chinese government outlawed the use of paid blood donations in 1998. Conclusions/Significance With an origin from Vietnam, 6a has become a local epidemic in Guangdong Province, where an increasing prevalence has subsequently led to 6a spread to many other regions of China.

The MICA gene encodes nonclassical major histocompatibility complex class I molecules, centromeric to HLA-B and telomeric to HLA-DRB1. The MICA genes are polymorphic. The immune response against MICA may correlate with a decrease in graft survival after transplantation. However, data on the frequency of MICA polymorphisms in different populations are limited. In this study, we determined MICA allelic frequencies in a Han population living in Guangdong Province in south China. A total of 15 MICA alleles were identified using sequence-based typing. The most frequent allele was MICA*010 (22.22%), followed by MICA*002:01(18.56%), MICA*008:01(16.32%), and MICA*019(14.93%). The MICA null gene (MICA*Del) exhibited a frequency of 1.743% in this population. MICA and HLA, MICA-HLA-B, and MICA-HLA-A/HLA-B/HLA-DRB1 haplotype frequencies were estimated. The most common 2-, 3- and 4-locus haplotypes were HLA-B*40:01-MICA*008:01 (13.70%), HLA-A*11:01-B*40:01-MICA*008:01(8.25%), and HLA-A*33:03-B*58:01-DRB1*03:01-MICA*002:01(5.22%). A new MICA allele, MICA*061, was identified and appears to be evolutionarily related to MICA*012:01. This study provides high-resolution information on the distribution of haplotypes with MICA, HLA-A, HLA-B, and HLA-DRB1 in China. This information should help determine the mechanisms underlying diseases and allotransplant rejection associated with MICA polymorphisms in the southern Chinese Han population.

Antibodies against polymorphic structures on human neutrophil antigens (HNAs) play a role in alloimmune-mediated neutropenia and are the leading cause of antibody-mediated transfusion-related acute lung injury (TRALI). This study aimed to determine the frequencies of HNAs in the major Han ethnic group living in Guangdong Province, Southern China.A total of 493 healthy Chinese Han blood donors from Guangzhou were recruited. DNA samples were isolated and typed for all five HNA-1, -2, -3, -4, and -5 systems using allele-specific polymerase chain reaction approaches. Results were compared with available data from other Chinese cohorts and other Asian and Caucasian populations.In this cohort, the gene frequency for HNA-1a (0.667) was approximately twice that of HNA-1b (0.333). In contrast to Caucasian populations, HNA-1a represents the most frequent allele in the Chinese population. HNA-3 system genotyping revealed comparable frequencies for HNA-3a (0.738) and -3b (0.262) in Chinese and Caucasian populations. Homozygous HNA-3 bb individuals were found in 5.64% of our cohort. HNA-4 genotyping revealed no HNA-4 bb homozygous individuals. In contrast, HNA-5 bb homozygous individuals represented 2.43% of the population. Typing the HNA-2 system for the single-nucleotide polymorphism C42G showed that the C-allele (69%) is overrepresented and is associated with an increased number of HNA-2a-positive neutrophil subpopulations.This study describes for the first time the frequencies of all HNA systems, including the newly identified HNA-3, within one cohort of Chinese Han population. Comparison with Caucasian populations may allow assessment of anti-HNA alloimmunization and estimation of alloimmune neutropenia and TRALI incidence in Chinese populations.

Background: Typing of human platelet antigens (HPA) has proven to be useful in some clinical situations related to platelet alloimmunization. Objective: The objective of this study was to investigate HPA 1–16 and to determine genotype and allele frequencies by polymerase chain reaction-sequence specific primer (PCR-SSP) in apheresis platelet donors in Guangzhou Blood Center. Methods: A total of 200 random samples from donors were involved in the study. Genotype and allele frequencies of HPA 1 to 16 were detected by PCR-SSP method. Results: The frequencies obtained from these donors were 99·50 and 0·50% for HPA-1a and -1b; 96·25 and 3·75% for HPA-2a and -2b; 54·25 and 45·75% for HPA-3a and -3b; 99·50 and 0·50% for HPA-4a and -4b; 99·00 and 1·00% for HPA-5a and -5b; 97·00 and 3·00% for HPA-6a and -6b and 42·25 and 57·75% for HPA-15a and -15b. There is only a/a homozygosis detected in HPA-7, -8, -9, -10, -11, -12, -13, -14 and -16. In this study, none of HPA-1b/ 1b, -2b/2b, -5b/5b homozygosis were detected which were found in other racial groups. One homozygosis of HPA-6b/6b in 200 individuals was detected which was not found in a study involving 1000 Chinese (Feng et al., 2006). Conclusion: The HPA-3 and -15 appear to the highest priority and HPA-2, -6, -5 -1 and -4 to be the second priority in Chinese Cantonese when it comes to the diagnosis of neonatal alloimmune thrombocytopenia and to provide the HPA-matched platelet for patients with platelet transfusion refractoriness. The PCR-SSP method makes it possible to detect genotype of HPA-1 to -16 in less than 4 h and to establish a donor database for HPA genotype in a blood bank.

Platelet transfusion refractoriness (PTR) is the major complication of long-term platelet supportive care. To improve the effectiveness of platelet transfusion therapy in PTR patients, we aimed to establish a platelet donor registry in our region (Guangzhou, China) by typing the human leukocyte antigen (HLA) and human platelet antigen (HPA). Blood donors (n = 864) from our population were genotyped for HLA-A, HLA-B and HPA systems by polymerase chain reaction amplification with sequence-specific primer(PCR-SSP) techniques. Using this cohort, we compared the results of platelet transfusions (matched vs. random) in 23 patients with PTR. Matched platelets were selected either by HLA antigen matching or by HLA antibody matching, as predicted by antibody specificity prediction (ASP) analysis. Significantly higher platelet recovery (PPR) values were obtained with HLA-matched platelets in comparison with random platelets. No significant difference in PPR was observed between HLA matching and ASP methods. In two patients, platelet-specific alloantibodies (alloabs) (anti-HPA-3b and anti-HPA-5b) were detected besides HLA class I alloabs. Transfusion with HLA- and HPA-compatible platelets in both the patients resulted in significantly higher PPR when compared with HLA-compatible platelet transfusion alone. In this study, we demonstrated that the establishment of an HLA- and HPA-typed platelet aphaeresis donor registry is useful to improve the treatment outcome of PTR patients and to maintain a long-term platelet transfusion strategy.

Subtype 1b is the most common strain ofHepatitis C virus(HCV) in China. Here, the molecular epidemiology and epidemic history of this strain were investigated by conducting phylogenetic and population genetic analyses of E1 and NS5B gene sequences sampled from nine Chinese cities. The phylogenetic analysis indicated the presence of two clusters of Chinese strains that did not include reference strains from other countries, suggesting that these clusters represent two independent chains of HCV transmission within China. The remaining Chinese isolates were more closely related to reference strains from other countries. The date of origin and past population dynamics of the two groups were investigated using a new population genetic method, the Bayesian skyline plot. The estimated dates of origin of both groups coincide with the period of the Chinese ‘Cultural Revolution’ during the years 1966–1976. Both groups grew at a rapid exponential rate between ∼1970 and ∼1990, after which transmission slowed considerably. Possible explanations for the groups' fast spread and subsequent slowdown are discussed, including parenteral transmission by unsafe injection, iatrogenic transmission by infected blood or blood products and improvements in blood safety since 1990. These results shed light on HCV transmission in China and may help to predict the future burden of HCV-related disease in the country.

Background In China, high prevalence of HBV and HCV parallels with the growing epidemic of syphilis and HIV in the general population poses a great threat to blood safety. This study investigated the prevalence of serologic markers for transfusion transmissible infections (TTIs) among four Chinese blood centers. Methods We examined whole blood donations collected from January 2000 through December 2010 at four Chinese blood centers. Post-donation testing of TTIs (HIV, HBV, HCV and syphilis) were conducted using two different enzyme-linked immunosorbent assay kits for each seromarker. The prevalence of serologic markers for TTIs (%) was calculated and additional analysis was conducted to examine donor characteristics associated with positive TTIs serology. Results Of the 4,366,283 donations, 60% were from first-time donors and 40% were from repeated donors. The overall prevalence of HIV, HBsAg, HCV and syphilis was 0.08%, 0.86%, 0.51% and 0.47%, respectively. The prevalence profile of TTIs varied among different blood centers and appeared at relatively high levels. Overall, the prevalence of HBsAg and HCV demonstrated a decline trend among four blood centers, while the prevalence of HIV and syphilis displayed three different trends: constantly steady, continually increasing and declining among different centers. Conclusions This study reflects the risk of TTIs has been greatly reduced in China, but blood transfusion remains an ongoing risk factor for the spread of blood-borne infections, and further work and improvements are needed to strengthen both safety and availability of blood in China.