Skip to main content

The impact of nucleic acid testing to detect human immunodeficiency virus, hepatitis C virus, and hepatitis B virus yields from a single blood center in China with 10-years review

Abstract

Background

Since 2010, the Blood Center of Zhejiang province, China, has conducted a pilot nucleic acid amplification testing (NAT) screening of blood donors for Hepatitis B virus (HBV), Hepatitis C virus (HCV), and Human immunodeficiency virus (HIV). This study aims to assess the results of NAT testing over 10 years to establish the effects and factors influencing NAT yields of HBV, HCV, and HIV.

Methods

Blood donations from seven different blood services were screened for HBV DNA, HCV RNA, and HIV RNA using 6 mini pools (6MP) or individual donation (ID)-NAT method between August 1, 2010, and December 31, 2019, at the NAT centralized screening center. We compared 3 transcription-mediated amplification (TMA) assays and 2 polymerase chain reaction (PCR) assays. Further, HBV, HCV, and HIV NAT yields were calculated and donor characteristics and prevalence of HBV NAT yields analyzed. Donors with HCV and HIV NAT yield were also followed up.

Results

1916.31 per million donations were NAT screening positive overall. The NAT yields for HBV, HCV, HIV and non-discriminating reactive were 1062.90 per million, 0.97 per million, 1.45 per million, and 850.99 per million, respectively, which varied in the seven blood services and different years. HBV NAT yields were higher than those of HCV and HIV and varied across demographic groups. Risk factors included being male, old age, low education level, and first-time donors. We found no differences in NAT yields of HBV, HCV, and HIV between the 3 TMA and 2 PCR assays; nonetheless, statistically, significant differences were noted between the five assays.

Conclusion

In summary, NAT screening in blood donations reduces the risk of transfusion-transmitted infections and shortens the window period for serological marker screening. Therefore, a sensitive NAT screening method, ID-NAT workflow, and recruitment of regular low-risk donors are critical for blood safety.

Peer Review reports

Backgrounds

Blood transfusion saves millions of lives annually across the globe. Nonetheless, transfusion transmissible infections (TTIs) remain a major problem. The main TTIs include hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and Treponema pallidum (TP) [1,2,3]. Notably, HIV, HBV, and HCV are causative agents of AIDS, hepatitis B, and C infection, respectively. Regardless of the low viral load, the risk of transmitting these viruses through transfusion of infected blood is markedly higher than through other routes [4]. The prevalence of these viral infections among blood donors varies by geography and nationality; it directly hinges on their prevalence in the general population. Based on the global estimates by the WHO (World Health Organization) till 2015, HBV and HCV chronically infected 257 million people and 71 million people, respectively. By the end of 2019, 38 million individuals were newly infected by HIV. Nevertheless, the prevalence of HBV, HCV, and HIV infections among blood donors in different countries and world regions varies from 0.003 to 5.54%, 0.002 to 2.23%, and 0.00 to 1.66%, respectively. For over 10 years, chronic hepatitis B is the leading among 27 infectious diseases reported by the Chinese government. Approximately 50% of the Chinese population has a history of HBV infection, out of which, 7.18% are chronic carriers of hepatitis B surface antigen (HBsAg) [5, 6]. Therefore, HBV is a major threat to blood safety in China.

Of note, advances in molecular screening for TTIs have significantly reduced the risk of infection transmission via blood transfusion. Nucleic acid amplification testing (NAT) is used to diagnose viral infections in transfusion medicine and is mandatory for blood services in China since 2016. The benefits of NAT include the capacity to directly detect viral genomes (DNA or RNA) with high specificity. Its sensitivity is several orders of magnitude greater than that of antigen and/or antibody immunological assays. Besides, NAT has markedly reduced the assay window for immunological assays [7]. In the present study, we assess the results of NAT over 10 years and analyze their effects on blood safety at the Blood Center of Zhejiang Province, China, where the infection rate of HBV is higher than that in the general population.

Methods

Blood sample collection

Nucleic acid amplification testing (NAT) centralized screening policy was implemented in Zhejiang Province, China, and the Blood Center of Zhejiang province, one of the centralized screening sites. Study samples were respectively collected from voluntary unpaid donors at the Blood Center of Zhejiang Province, and Xiaoshan, Jiande, Yiwu, Shaoxing, Jiaxing, and Huzhou blood stations, between August 1, 2010, and December 31, 2019. The Blood Center of Zhejiang province is located in the Hangzhou region; Xiaoshan and Jiande are counties in the Hangzhou region. Thus, blood donors from the Blood Center of Zhejiang Province were divided into three regions, including Hangzhou, Xiaoshan, and Jiande. During the implementation of Zhejiang Province’s NAT centralized screening policy, the start time for NAT detection varied depending on the blood service center. NAT was used from August 1, 2010, at the Blood Center of Zhejiang province; from May 29, 2013, at Xiaoshan and Jiande; from September 5, 2013, at Yiwu; and from March 1, 2016, at Shaoxing, Jiaxing, and Huzhou. All samples were collected, stored, and handled following the manufacturer’s instructions after obtaining informed consent from blood donors.

Pre- and post-donation screening of blood donors

Based on the guidelines for blood donation in China, the donors filled in a risk factor questionnaire excluding those at risk of exposure to transfusion transmissible infections. Safe donors were physically examined by a doctor before acceptance for donation. Thereafter, the donors underwent pre-donation screening, including determination of ABO blood group, hemoglobin concentration, ALT level, and HBsAg status. Donors with low hemoglobin concentration (male: < 120 g/L; females:  < 110 g/L before July 1, 2012, or  < 115 g/L from July 1, 2012 due to a policy change), abnormal ALT level (> 40 IU/L before July 1, 2012, and > 50 IU/L since July 1, 2012, due to a policy change) or positive HBsAg results were temporarily deferred.

After donation, blood samples were tested for ALT level and ABO type then screened for HBsAg, anti-HCV, anti-HIV, and anti-TP using 2 ELISA kits from different manufacturers (Additional file 1: Table S1). Reactive samples on either kit for any viral marker were defined as positive for that marker (ELISA+). Assays were conducted as per the manufacturer’s instructions.

Nucleic acid amplification testing (NAT) assays

The HBV, HCV, and HIV NAT assays were run in parallel for the relevant donor samples using 6 mini pools NAT (6MP-NAT, Roche Diagnostics, Manheim, Germany) or individual NAT (ID-NAT, Novartis Diagnostics, Emeryville, CA, USA) modes, based on the manufacturer’s instructions (Table 1). The workflow for ID-NAT using a transcription-mediated amplification (TMA) was performed on initially positive blood donations retested in parallel using a similar ID-NAT screening and discriminatory assays, leading to two types of results, i.e., positive screening tests but non-discriminating, or results that discriminate between HBV, HCV or HIV. Nonetheless, all were defined as positive. Donated blood was analyzed using individual NAT to whether they were reactive in the 6MP-NAT mode, yielding positive or negative results on individual NAT confirmatory tests for utilizing the TaqMan PCR platform. NAT+ELISA donors should be deferred according to the guideline in China.

Table 1 NAT reagents used for screening donors in different methods and systems

Comparison of two NAT systems for detection of low viral load level OBI samples

Partial NAT+/ELISA samples were collected between May 1, 2017 and May 1, 2018. Out of these, 103 samples had previously tested positive in non-discriminating reaction, whereas 39 were HBV DNA positive. Anti-HBc was detected via electroluminescence on a Cobas e601 analyzer (Roche Diagnostics Company, Shanghai, China). Viral load was established on a Roche Cobas AmpliPrep with RT-PCR performed on a Cobas TaqMan analyzer (Roche Diagnostics Company, Shanghai, China). Samples were tested thrice on ID-NAT mode using these systems to compare the Ultrio Elite and MPX 2.0 NAT systems; the results were considered positive if at least one test was positive.

Supplementary assays and follow-up study

Anti-HIV reactive samples were confirmed by Western blot assay at the Centre of Disease Control, Hangzhou, Zhejiang province as per China’s state regulations.

Blood donors positive for HCV or HIV after NAT yet negative by ELISA (NAT+/ELISA) were followed up and subjected to tests by serology and NAT.

Statistical analysis

Statistical analyses were performed on the SPSS 22.0 software. Differences in the rates across various blood services were analyzed using the chi-square test and Fisher’s exact tests, as appropriate. P < 0.05 was considered statistically significant.

Results

Overall NAT yield rates are various in the difference blood services

A total of 2,071,695 blood donations were NAT screened between August 1, 2010, and December 31, 2019 at Hangzhou, Xiaoshan, Jiande, Yiwu, Shaoxing, Jiaxing, and Huzhou blood service centers. Among these, 1,160,355 (56.01%) were analyzed on ID-NAT mode using the TMA method; the remaining 911,340 (43.99%) were analyzed using the TaqMan PCR method on 6MP-NAT mode. All the NAT yields (NAT+/ELISA) cases are shown in Table 2. The overall NAT yield rate was 1916.31 per million. NAT yields rates for HBV, HCV, HIV and non-discriminating reactive were 1062.90 per million, 0.97 per million, 1.45 per million, and 850.99 per million, respectively. Notably, NAT yields rates differed across the 7 blood service centers (χ2 = 514.27, p < 0.01), with the highest yield at Jiande (4579.84 per million) and the lowest yield at the Jiaxing (1450.31 per million).

Table 2 Numbers and proportions of donations in NAT detection and the results of NAT yields in the seven blood services

The difference in NAT yields rates between the TMA and PCR methods

A big gap in NAT yield rate was found in the TMA vs PCR method (2625.06 per million vs 1013.89 per million, χ2  = 692.78, p < 0.01, Table 3). This gap suggests that 6 mini pools NAT (MP-NAT) exhibit less sensitivity, whereas ID-NAT lacks specificity. HBV NAT yield rates were similar in TMA vs PCR methods, at 1102.25 per million vs 1012.79 per million (p > 0.05, Table 3). NAT yields rates of HCV and HIV were higher under the TMA method than that under the PCR method; however, the difference was not statistically significant (p values = 0.507 and 1.000, respectively, Fisher’s exact test). Notably, all the NAT yield rates (HBV, HCV, and HIV) in the TMA method were significantly higher than that in the PCR method (χ2 = 4.04, p < 0.05); this may be attributed to the sensitivity methods and differences in NAT screening modes.

Table 3 The results of NAT yields for five different assays using the TMA and PCR methods

Comparison of NAT yield rates in the different assays using TMA and PCR methods

Further, we compared the NAT yields rates for the 3 TMA and 2 PCR assays used in this study (Table 3). Analysis of NAT yield rates in the TMA assays revealed that the NAT yield rates of Ultrio Plus and Ultrio Elite assays were higher than those of the Ultrio assay (χ2  = 113.19, p < 0.01). HBV NAT yield rates were the highest in the Ultrio Elite assay, followed by Ultrio Plus and Ultrio assays (χ2  = 162.11, p < 0.01). Nonetheless, only 2 HCV NAT yield cases were found by the Ultrio Plus assay (p < 0.05, Fisher’s exact test). Moreover, we found two HIV NAT yields individuals using the TMA method. Differences in HIV NAT yield rates were not statistically significant in the 3 TMA assays.

NAT yield rates of HBV, HCV, and HIV did not significantly differ between the MPX and MPX2.0 PCR methods (χ2 = 0.96, p > 0.05). Notably, a comparison of HBV NAT yield rates across the 5 assays revealed that HBV NAT yields rate is lower in the MPX assay compared to that in the Ultrio Elite assay (χ2  = 20.01, p < 0.01). HBV NAT yields rate in the MPX 2.0 assay was higher than in the Ultrio and Ultrio Plus assays but lower than that in the Ultrio Elite assay (χ2  = 170.10, p < 0.01), whereas HCV NAT yields were higher in Ultrio Plus (p < 0.01, Fisher’s exact test). Nevertheless, HIV NAT yield rates did not significantly differ between the 5 assays (p > 0.05, Fisher’s exact test).

Ultrio Elite and MPX2.0 assays in ID-NAT mode with similar HBV detection capacity

In total, 103 positive screening tests but non-discriminating reactive samples and 39 HBV NAT yield OBI samples were detected using the Ultrio Elite and MPX2.0 assays in ID-NAT mode. All samples were anti-HBc positive with low viral load (< 12 IU/mL and < 20 IU/mL in non-discriminating reactive and HBV NAT yields samples, respectively). Among the 103 non-discriminating reactive samples, the Ultrio Elite and MPX2.0 assays detected 17 (16.50%) and 23 (22.33%) HBV-DNA reactive samples as positive, respectively (Fig. 1). However, the reactive rates did not significantly differ (χ2  = 1.12, p > 0.05) between the 2 assays. Out of the 39 HBV NAT-yield samples, Ultrio Elite and MPX2.0 assays detected 13 (33.33%) and 17 (43.59%) HBV-DNA reactive samples, respectively (χ2  = 0.87, p > 0.05). The overall proportion of HBV-DNA reactive results did not significantly differ between the Ultrio Elite assay (17.54%) and the MPX2.0 system (22.81%). Using the ID-NAT mode, no difference was noted between the Ultrio Elite and MPX2.0 assays in the detection of low HBV loads. However, unlike the Ultrio Elite assay in ID-NAT mode, the MPX2.0 assay in MP-NAT mode might have lower HBV-NAT yields (Table 3).

Fig. 1
figure 1

Comparison of HBV-DNA positive results on 103 non-discriminating reactive and 39 HBV NAT-yield samples in the Ultrio Elite ID-NAT (□) and MPX2.0 ID-NAT (■). Non-discriminating reactive indicates 103 screening tests positive but non-discriminating reactive samples, HBV NAT-yield indicates 39 HBV NAT+ELISA yield OBI samples, and overall refers to all 142 specimens

Non-discriminating reactive in ID-NAT using the TMA method

Non-discriminating reactive implies reactive donations using NAT screening by the TMA method but not in discriminatory assay. Over the 10 years, 1,763 blood donations (850.99 per million) were non-discriminating reactive (Table 3). The rate of non-discriminating reactive in Shaoxing, Jiaxing, and Huzhou was much lower than that in Xiaoshan, Jiandem, and Yiwu (p < 0.05, Additional file 1: Table S2).

Notably, the rate of non-discriminating reactive yields in all donations exhibited a downward trend annually (Additional file 1: Table S2). NAT yields rate of non-discriminating reactive using the TMA method was highest in 2012 and lowest in 2019 (Additional file 1: Table S2). Additionally, the rate of non-discriminating reactive yields in all NAT yields varied across the 3 TMA assays (Fig. 2). In contrast with the Ultrio assay, the Ultrio Plus and Ultrio Elite assays demonstrated better discrimination capacity, which appeared to match the sensitivity of different TMA assays and the gap between screening and discriminatory assays (Fig. 2). The use of Ultrio Elite assay after September 22, 2016, decreased the non-discriminating reactive NAT yields rate because of a smaller screening and discriminatory sensitivity gap than that of the other 2 TMA assays (Fig. 2).

Fig. 2
figure 2

Non-discriminating reactive NAT yields in the blood service centers. The scale at the left indicates NAT yields (per million) in the TMA method, the donations were non-discriminating reactive (□); the scale at the right indicates the LOD (IU/mL) of different reagents in the TMA method in ID-NAT assays () and HBV discriminatory assay ()

HBV NAT yields in the blood services

In 10 years, 2202 blood donations were HBV NAT+ ELISA. In total, the HBV NAT yield rates exhibited annual fluctuations and varied across blood service centers (Additional file 1: Table S3). HBV NAT yield rate was lowest in Hangzhou (883.58 per million) and highest in Jiande (2581.83 per million). Also, HBV NAT yields rates were associated with TMA assay sensitivity. Therefore, the total HBV NAT yields rates started to increase when the use of the Ultrio Elite assay began in 2017, suggesting that the Ultrio Elite assay in ID-NAT mode had effective HBV screening and discriminating capacities.

Effects on HBV NAT+ELISA yields in the blood service centers

Analysis of HBV NAT+ELISA yields by demographic groups showed that over 10 years, compared to female donors, overall HBV NAT+ELISA yield prevalence was higher in male donors (Additional file 1: Table S4, χ2 = 174.02, p < 0.01) and in each blood service except the Xiaoshan (χ2 = 2.85, p > 0.05) and Jiande (χ2 = 2.51, p > 0.05). Analysis by age group (18–25, 26–35, 36–45, 46–55, > 55) discovered a higher HBV NAT yield rate in the age group 46–55 (χ2 = 1796.99, p < 0.01) at all blood service centers. Analysis by the level of education revealed that donors with higher education had lower rates of HBV NAT+ELISA yields, which were much higher in the junior high school group (30.88%, χ2 = 1042.21, p < 0.01), whereas, they were higher in the middle school group in Xiaoshan and Jiande. We found that HBV NAT yields rates were higher in clerk donors (23.30%, χ2 = 699.07, p < 0.01), except in Jiande and Yiwu, where they were higher in farmer donors. HBV NAT yield prevalence was much higher in first-time donors compared to repeat donors (χ2 = 218.70, p < 0.05) at all blood service centers. Collectively, these data suggest that risk factors associated with HBV NAT+ELISA yields include male gender, old age (between 46 and 55), low education (middle school and below), lower technology worker including Farmer as well as Worker, and first-time donors.

HCV and HIV NAT+ELISA yields in blood donors

Among the 2,071,695 blood donations, 2 were HCV NAT+ELISA yield donations whereas 3 were HIV NAT+ELISA yield donations (Table 2). Two HCV NAT+ELISA yield donors were followed up for > 1 year and based on NAT and/or ELISA, none was HCV positive during the follow-up period (Additional file 1: Table S5). All 3 HIV NAT+ELISA yield donors were followed-up and re-sampled after about a month (Additional file 1: Table S6), suggesting that they were in the acute HIV infection phase.

Discussion

In China, NAT was first used as a pilot project in key blood centers in 2000 [8, 9], including the Blood Center of Zhejiang Province. Herein, we discovered that NAT yield rates for HBV, HCV, and HIV varied over time and between the seven blood service centers. Specifically, the NAT yield rates for HCV (1.54 per million) and HIV (2.31 per million) in Hangzhou were similar to other regions of China (NAT yield range: 0–3.4 per million for HCV [10], 0–3.55 per million for HIV [11]. In our study, the HCV NAT yield rate (0.97 per million) was lower than that in Mediterranean countries with high endemic HCV infection (2.15 per million in Spain, 5.97 per million in Greece, 2.5 per million in Italy, 4.27 per million in Slovenia) [12,13,14,15]. HIV NAT yield rate (1.45 per million) was similar to that in the US (0.43 per million) [16] and European countries such as Italy (1.8 per million) and Germany (0.43 per million) [15, 17], but lower than that in HIV-1 endemic countries including South Africa (25.56 per million donations) [18].

In follow-up HCV NAT and serological testing, two HCV NAT-yield cases were negative. Nevertheless, all 3 HIV NAT yield donors were in the acute HIV infection phase. Reports indicate that 15–25% of HCV infections are self-limiting and vary depending on the HCV genotype. According to Lefrère et al., a few immunocompetent HCV-positive patients were found to be negative after self-limiting using ELISA, RIBA, and HCV-RNA test [19]. Therefore, we speculated that these two HCV NAT-yield donors may have had self-limiting HCV infection or were false positives upon HCV NAT tests. Moreover, Akuta et al. [20] reported HBeAg-negative and HBeAb-positive cases where chronic HBV infection persisted while acute HCV infection was spontaneously resolved. In this patient, HCV infection was interestingly accompanied by the appearance of PreC wild type (G1896); an increase in transiently suppressed HBV viral load at a level that was higher than that established before HCV infection. This case was similar to the BD2 case in our study, which was negative in HBV NAT and serological tests and HCV NAT reactive, but HCV-RNA was undetectable one year later and HBV-DNA positive. Therefore, NAT tests employing in HCV low risk population have low positive predictive value, results must be repeated to confirm.

HBV NAT yield rate was much higher than that of HCV and HIV, ranging from 883.58 to 2582.83 per million at different blood service centers (1:387 in Jiande to 1:1132 in Hangzhou). This rate was a little higher than the average figure of China (1:1482, range:1:1861 to 1:1269) [21], and much higher than that in other low HBV endemic countries including USA, Canada, Germany, Switzerland, and New Zealand [22,23,24,25,26], as well as Mediterranean countries with moderate endemism [12,13,14]. We found that despite common routes of transmission and similar risk factors, the HBV NAT yield rate is higher than that of HCV and HIV, possibly because HBV is highly prevalent in China [5]. Conversely, the extremely low TTI residual risks for HCV and HIV may be attributed to their low prevalence in the population and short window periods of HCV and HIV testing using ID-NAT [16, 27].

Several studies have compared the sensitivity of NAT systems for HBV, HCV, and HIV [28,29,30,31,32,33,34]; as a consequence, differing findings have been reported. Using PROCLEIX ULTRIO (Ultrio) assay and TaqScreen multiplex (Cobas MPX) test, Margaritis et al. reported equal HBV NAT yields rate in donations from Hong Kong [29]. However, Phikulsod et al. in Thailand reported that TaqMan MP6 was more sensitive than Ultrio in ID format [30]. Using the Ultrio Plus assay relative to the Ultrio ID-NAT and TaqMan MP6, Marion et al. in South Africa found a significantly higher proportion of replicate assays on HBV NAT yields [28]. In this work, we compared NAT yields rates in five different assays, including Ultrio, Ultrio Plus, and Ultrio Elite assays using the TMA method in ID format, as well as MPX and MPX2.0 using the PCR method in 6MP-format. Consequently, there were no statistically significant differences in HBV, HCV, and HIV NAT yield rates between the 2 NAT methods. Nonetheless, among the 5 assays, Ultrio Plus was effective at non-discriminating reactive and HCV detection, whereas Ultrio Eilte exhibited the highest HBV NAT yield in the screening test. Interestingly, MPX2.0 was slightly but not significantly more sensitive in detecting low viral load OBI samples using the ID format. Collectively, these results indicate that besides reagents sensitivity, the capacity of NAT methods to detect HBV, HCV, and HIV, particularly at low viral loads depends on pool size.

In addition to HBV, HCV, and HIV, some samples were screening tests-positive, but non-discriminating reactive using the TMA method. The reasons for these non-resolved results were potential because of a sensitivity gap between screening and discriminatory reagents in the TMA method, or the viral loads in the donations may have been too low to be detected by discriminatory reagents. Some non-resolved results were found with HBV DNA positive through increasing number of tests, concentrating with high-speed centrifugation, and using other NAT methods [35,36,37]. In China, Ye et al. [37, 38] found that 91.1% of non-discriminated reactive donors were anti-HBc reactive OBI with low viral loads. Thus, non-discriminating reactive donations have a great risk for HBV transmission and should be excluded. Also, we found that the HBV NAT yields risk factors included male gender, older age, low education level, lower technology work, and first-time donors. Therefore, NAT screening for TTIs and higher sensitivity screening, specifically for HBV, improve the safety of blood supply. Differences in NAT yield at different blood service centers may be attributed to NAT screening methods and virus prevalence in the general population.

Conclusion

In conclusion, high HBV NAT yield rates were discovered in an analysis of NAT yield rates at seven Chinese blood service centers. Besides, the efficiency of HBV, HCV, and HIV NAT yield was similar for TMA and PCR methods but different in the 5 reagent assays. NAT screening at blood donation reduces the risk of transfusion-transmitted infections, shortens the duration of serological tests, and increases blood safety. Nonetheless, NAT yields rates varied across blood services and hinged on the NAT detection mode and blood donor features.

Availability of data and materials

The data used in this study is available from the corresponding author on reasonable request.

Abbreviations

ALT:

Alanine aminotransferase

CLIA:

Chemiluminescent immunoassay

dHBV:

Discriminatory test for HBV DNA

dHCV:

Discriminatory test for HCV RNA

dHIV:

Discriminatory test for HIV RNA

DNA:

Deoxyribonucleic acid

ECLIA:

Electrochemiluminescence immunoassay

ELISA:

Enzyme linked immunosorbent assay

HBcAb:

Antibody to hepatitis B core antigen

HBeAb:

Antibody to hepatitis B E antigen

HBeAg:

Hepatitis B E antigen

HBsAb:

Antibody to hepatitis B surface antigen

HBsAg:

Hepatitis B virus surface antigen

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

HCV-Ab:

Antibody to hepatitis C virus

HIV:

Human immunodeficiency virus

ID:

Individual donation

LOD:

Limit of detection

MP:

Mini pool

NAT:

Nucleic acid amplification testing

OBI:

Occult hepatitis B virus infection

PCR:

Polymerase chain reaction

RNA:

Ribonucleic acid

TMA:

Transcription-mediated amplification

TTIs:

Transfusion transmission infections

WP:

Window period

References

  1. Song Y, Bian Y, Petzold M, Ung COL. Prevalence and trend of major transfusion-transmissible infections among blood donors in Western China, 2005 through 2010. PLoS ONE. 2014;9: e94528.

    Article  Google Scholar 

  2. Biadgo B, Shiferaw E, Woldu B, Alene KA, Melku M. Transfusion-transmissible viral infections among blood donors at the North Gondar district blood bank, northwest Ethiopia: a three-year retrospective study. PLoS ONE. 2017;12: e0180416.

    Article  Google Scholar 

  3. Farshadpour F, Taherkhani R, Tajbakhsh S, Gholizadeh Tangestani M, Hajiani G, Sharifi N, Taherkhani S, Nejadbolkheyr A. Prevalence and trends of transfusion-transmissible viral infections among blood donors in south of Iran: an eleven-year retrospective study. PLoS ONE. 2016;11: e0157615.

    Article  Google Scholar 

  4. Nwokeukwu HI, Nwabuko CO, Chuku A, Ajuogu E, Dorathy OA. Prevalence of human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and syphilis in blood donors in a tertiary health facility in south eastern Nigeria. Hematol Leukemia. 2014;2:4.

    Article  Google Scholar 

  5. Liang X, Bi S, Yang W, Wang L, Cui G, Cui F, Zhang Y, Liu J, Gong X, Chen Y, et al. Epidemiological serosurvey of hepatitis B in China—declining HBV prevalence due to hepatitis B vaccination. Vaccine. 2009;27:6550–7.

    Article  Google Scholar 

  6. Ye X, Li T, Xu X, Du P, Zeng J, Zhu W, Yang B, Li C, Allain JP. Characterisation and follow-up study of occult hepatitis B virus infection in anti-HBc-positive qualified blood donors in southern China. Blood Transfus. 2017;15:6–12.

    PubMed  PubMed Central  Google Scholar 

  7. Chaurasia R, Rout D, Zaman S, Chatterjee K, Pandey HC, Maurya AK. Comparison of Procleix Ultrio Elite and Procleix Ultrio NAT assays for screening of transfusion transmitted infections among blood donors in India. Int J Microbiol. 2016;2016:2543156.

    Article  Google Scholar 

  8. Zheng X, Ye X, Zhang L, Wang W, Shuai L, Wang A, Zeng J, Candotti D, Allain JP, Li C. Characterization of occult hepatitis B virus infection from blood donors in China. J Clin Microbiol. 2011;49:1730–7.

    Article  Google Scholar 

  9. Ye X, Yang B, Zhu W, Zheng X, Du P, Zeng J, Li C. Six-year pilot study on nucleic acid testing for blood donations in China. Transfus Apher Sci. 2013;49:318–22.

    Article  Google Scholar 

  10. Shan H, Ren FR, Zhao HY, Zhang YZ, Wen GX, Yao FZ, Gao GJ, Yan LX, Jiang CF, Bai XH, et al. A multi-Chinese blood center study testing serologic-negative donor samples for hepatitis C virus and human immunodeficiency virus with nucleic acid testing. Transfusion. 2007;47:2011–6.

    Article  Google Scholar 

  11. Zhang R, Sun Y, Wang L, Zhang K, Xie J, Li J. Blood screening for human immunodeficiency virus: a new algorithm to reduce the false-positive results. Transfus Med. 2013;23:260–4.

    Article  CAS  Google Scholar 

  12. Safic Stanic H, Babic I, Maslovic M, Dogic V, Bingulac-Popovic J, Miletic M, Jurakovic-Loncar N, Vuk T, Strauss-Patko M, Jukic I. Three-year experience in NAT screening of blood donors for transfusion transmitted viruses in Croatia. Transfus Med Hemother. 2017;44:415–20.

    Article  Google Scholar 

  13. Velati C, Romanò L, Fomiatti L, Baruffi L, Zanetti AR, SIMTI Research Group. Impact of nucleic acid testing for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus on the safety of blood supply in Italy: a 6-year survey. Transfusion. 2008;48:2205–13.

    Article  Google Scholar 

  14. Katsoulidou A, Moschidis Z, Sypsa V, Chini M, Papatheodoridis GV, Tassopoulos NC, Mimidis K, Karafoulidou A, Hatzakis A. Analytical and clinical sensitivity of the Procleix Ultrio HIV-1/HCV/HBV assay in samples with a low viral load. Vox Sang. 2007;92:8–14.

    Article  CAS  Google Scholar 

  15. Levicnik Stezinar S, Nograsek P. Yield of NAT screening in Slovenia. Zdrav Vestn. 2012;81:257–64.

    Google Scholar 

  16. Busch MP, Glynn SA, Stramer SL, Strong DM, Caglioti S, Wright DJ, Pappalardo B, Kleinman SH, NHLBI-REDS NAT Study Group. A new strategy for estimating risks of transfusion-transmitted viral infections based on rates of detection of recently infected donors. Transfusion. 2005;45:254–64.

    Article  Google Scholar 

  17. Fiedler SA, Oberle D, Chudy M, Scheiblauer H, Henseler O, Halbauer J, Heiden M, Funk M. Effectiveness of blood donor screening by HIV, HCV, HBV-NAT assays, as well as HBsAg and anti-HBc immunoassays in Germany (2008–2015). Vox Sang. 2019;114:443–50.

    Article  Google Scholar 

  18. Fang CT, Field SP, Busch MP, Heyns AduP. Human immunodeficiency virus-1 and hepatitis C virus RNA among South African blood donors: estimation of residual transfusion risk and yield of nucleic acid testing. Vox Sang. 2003;85:9–19.

    Article  CAS  Google Scholar 

  19. Lefrère JJ, Girot R, Lefrère F, Guillaume N, Lerable J, Le Marrec N, Bouchardeau F, Laperche S. Complete or partial seroreversion in immunocompetent individuals after self-limited HCV infection: consequences for transfusion. Transfusion. 2004;44:343–8.

    Article  Google Scholar 

  20. Akuta N, Suzuki F, Kobayashi M, Tsubota A, Suzuki Y, Hosaka T, Someya T, Kobayashi M, Saitoh S, Arase Y, et al. Effect of acute self-limited hepatitis C virus (HCV) superinfection on hepatitis B virus (HBV)-related cirrhosis. Virological features of HBV-HCV dual infection. Dig Dis Sci. 2004;49:281–8.

    Article  Google Scholar 

  21. Liu C, Chang L, Ji H, Guo F, Zhang K, Lin G, Zhang R, Li J, Wang L. Prevalence of HBV DNA among 20 million seronegative blood donations in China from 2010 to 2015. Sci Rep. 2016;6:36464.

    Article  CAS  Google Scholar 

  22. Niederhauser C. Reducing the risk of hepatitis B virus transfusion-transmitted infection. J Blood Med. 2011;2:91–102.

    Article  Google Scholar 

  23. Kleinman SH, Strong DM, Tegtmeier GG, Holland PV, Gorlin JB, Cousins C, Chiacchierini RP, Pietrelli LA. Hepatitis B virus (HBV) DNA screening of blood donations in minipools with the COBAS AmpliScreen HBV test. Transfusion. 2005;45:1247–57.

    Article  CAS  Google Scholar 

  24. Roth WK, Seifried E. The German experience with NAT. Transfus Med. 2002;12:255–8.

    Article  CAS  Google Scholar 

  25. Stolz M, Tinguely C, Graziani M, Fontana S, Gowland P, Buser A, Michel M, Canellini G, Züger M, Schumacher P, et al. Efficacy of individual nucleic acid amplification testing in reducing the risk of transfusion-transmitted hepatitis B virus infection in Switzerland, a low endemic region. Transfusion. 2010;50:2695–706.

    Article  Google Scholar 

  26. Flanagan P, Charlewood G, Horder S, Drawitsky M, Hollis H. Reducing the risk of transfusion transmitted hepatitis B in New Zealand. Vox Sang. 2005;89:23–4.

    Article  Google Scholar 

  27. Yang BC, Ye XL, Zhu WG, Zeng JF, Lee H, Zhuang NB. Evaluation on residual risk of HIV transfusion transmission after screening assay in voluntary blood donors. Chin J Blood Transfus. 2008;21:840–1.

    Google Scholar 

  28. Vermeulen M, Coleman C, Mitchel J, Reddy R, van Drimmelen H, Ficket T, Lelie N. Sensitivity of individual-donation and minipool nucleic acid amplification test options in detecting window period and occult hepatitis B virus infections. Transfusion. 2013;53:2459–66.

    Article  CAS  Google Scholar 

  29. Margaritis AR, Brown SM, Seed CR, Kiely P, D’Agostino B, Keller AJ. Comparison of two automated nucleic acid testing systems for simultaneous detection of human immunodeficiency virus and hepatitis C RNA and hepatitis B DNA. Transfusion. 2007;47:1783–93.

    Article  CAS  Google Scholar 

  30. Phikulsod S, Oota S, Tirawatnapong T, Sakuldamrongpanich T, Chalermchan W, Louisirirotchanakul S, Tanprasert S, Chongkolwatana V, Kitpoka P, Phanuphak P, et al. One-year experience of nucleic acid technology testing for human immunodeficiency virus Type 1, hepatitis C virus, and hepatitis B virus in Thai blood donations. Transfusion. 2009;49:1126–35.

    Article  CAS  Google Scholar 

  31. Assal A, Barlet V, Deschaseaux M, Dupont I, Gallian P, Guitton C, Morel P, David B, De Micco P. Comparison of the analytical and operational performance of two viral nucleic acid test blood screening systems: Procleix Tigris and cobas s 201. Transfusion. 2009;49:289–300.

    Article  Google Scholar 

  32. Assal A, Barlet V, Deschaseaux M, Dupont I, Gallian P, Guitton C, Morel P, Drimmelen HV, David B, Lelie N, et al. Sensitivity of two hepatitis B virus, hepatitis C viris (HCV) and human immunodeficiency virus (HIV) nucleic acid test systems relative to hepatitis B surface antigen, anti-HCV, anti-HIV and p24/anti-HIV combination assays in seroconversion panels. Transfusion. 2009;49:301–10.

    Article  Google Scholar 

  33. Louisirirotchanakul S, Oota S, Khuponsarb K, Chalermchan W, Phikulsod S, Chongkolwatana V, Sakuldamrongpanish T, Kitpoka P, Chielsilp P, Tanprasert S, et al. Occult hepatitis B virus infection in Thai blood donors. Transfusion. 2011;51:1532–40.

    Article  Google Scholar 

  34. Stramer SL, Krysztof DE, Brodsky JP, Fickett TA, Reynolds B, Phikulsod S, Oota S, Lin M, Saldanha J, Kleinman SH. Sensitivity comparison of two Food and Drug Administration–licensed, triplex nucleic acid test automated assays for hepatitis B virus DNA detection and associated projections of United States yield. Transfusion. 2011;51:2012–22.

    Article  Google Scholar 

  35. Dong J, Wu Y, Zhu H, Li G, Lv M, Wu D, Li X, Zhu F, Lv H. A pilot study on screening blood donors with individual-donation nucleic acid testing in China. Blood Transfus. 2014;12:172–9.

    PubMed  PubMed Central  Google Scholar 

  36. Danxiao W, Xiaojuan W, Fangjun F, Dairong W, Yiqin H, Yang Y, Jihong H, Min W, Jie D, Yaling W, et al. Characteristic of HBV nucleic acid amplifcation testing yields from blood donors in China. BMC Infect Dis. 2021;21:714.

    Article  Google Scholar 

  37. Ye X, Li T, Shao W, Zeng J, Hong W, Lu L, Zhu W, Li C, Li T. Nearly half of Ultrio plus NAT non-discriminated reactive blood donors were identified as occult HBV infection in South China. BMC Infect Dis. 2019;19:574.

    Article  Google Scholar 

  38. Ye X, Zhao Y, Li R, Li T, Zheng X, Xiong W, Zeng J, Xu M, Chen L. High frequency occult hepatitis B Virus infection detected in non-resolved donations suggests the requirement of anti-HBc test in blood donors in southern China. Front Immunol. 2021;12: 699217.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

None.

Funding

All cost for the screening of the blood donors was from the government of Zhejiang Province. This work was sponsored by the Science Research Foundation of Zhejiang Healthy Bureau (2019KY068 and 2018KY042).

Author information

Authors and Affiliations

Authors

Contributions

Danxiao Wu performed the research, analyzed data and wrote the paper. FF, XW, Dairong Wang, YH, YY, JH and MW performed the research. JD, YW and HZ performed the research and analyzed data. YW and HZ designed the research study and wrote the paper. FZ designed the research study and wrote the paper. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Yaling Wu, Hong Zhu or Faming Zhu.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the ethics committee of Blood Center of Zhejiang Province, China. All participants provided written informed consent. To guarantee donor confidentiality, donors were anonymized via de-identification (through the use of codes). All methods were carried out in accordance with the principles of the Declaration of Helsinki. Anti-HIV reactive samples underwent confirmation tests by the Centre of Disease Control, Hangzhou, Zhejiang province—China, in accordance with China’s state regulations.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1: Table S1.

ELISA reagents used for screening donors in HBsAg, anti-HCV, anti-HIV1/2 and anti-TP. Table S2. Non-discriminating reactive NAT yields in the seven blood services. Table S3. HBV NAT yields rates in the seven blood services. Table S4. HBV NAT yields for tested donations with HBsAg negative in the different demographic groups. Table S5. The follow-up results of 2 HCV NAT yields blood donors. Table S6. The follow-up results of 3 HIV NAT+ELISA- blood donors.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wu, D., Feng, F., Wang, X. et al. The impact of nucleic acid testing to detect human immunodeficiency virus, hepatitis C virus, and hepatitis B virus yields from a single blood center in China with 10-years review. BMC Infect Dis 22, 279 (2022). https://doi.org/10.1186/s12879-022-07279-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12879-022-07279-5

Keywords

  • Nucleic acid amplification test
  • Blood screening
  • Detection capacity
  • NAT yields