HTLV screening using chemiluminescence immunoassay among blood donors in three blood centers in China


 Background Human T-cell lymphotropic virus (HTLV) remains a concern for blood safety. The detection of HTLV has not yet been applied for routine blood screening in China, even though lots of HTLV positive cases have been reported in southeastern China. However, data on the prevalence of HTLV infection among blood donors is limited. Objective The objective was to investigate the prevalence of HTLV among blood donors in three representative blood centers in China and evaluate the feasibility of chemiluminescence immunoassay (CLIA) for blood screening. Methods From November 2018 to March 2019, blood plasma samples collected from Hebei, Changsha and Shenzhen blood centers were screening for HTLV-1/2 antibody using Lumipulse G HTLV-I/II Immunoreaction Cartridges set (CLIA) and enzyme-linked immunosorbent assay (ELISA), followed with confirmatory test using INNO-LIA HTLV I/II. Results A total of 59929 blood donations were collected and screened for HTLV-1/2. The reactive rate of CLIA and ELISA among donations in Shenzhen blood center (0.0943%, 27/28621) was higher than Hebei (0.0248%, 4/16144) and Changsha (0.0198%, 3/15164) ( P <0.05). After confirmation, 3 samples were confirmed as indeterminate for HTLV antibodies, only 1 sample from Shenzhen blood center was confirmed and typed as HTLV-1. The overall prevalence of HTLV-1/2 was 1.67 per 100,000 (1/59929). The HTLV-infected blood donor was a first female donor at age 32 with high school degree, born in Fujian province, and SHE minority. Conclusion In summary, the overall prevalence of HTLV-1/2 among blood donors in the tree blood centers in China remains relatively low. However, blood donations with positive or indeterminate results for HTLV antibodies found in the study reminded us the importance of HTLV screening among blood donors in China. In the view of HTLV prevalence and cost, all the first-blood donors should undergo HTLV screening as a systematic strategy to reduce the risk of transmission of HTLV through blood transfusion.


KEYWORDS
Human T-cell lymphotropic virus (HTLV), blood donors, chemiluminescence immunoassay (CLIA), blood screening, prevalence Abstract Background Human T-cell lymphotropic virus (HTLV) remains a concern for blood safety. The detection of HTLV has not yet been applied for routine blood screening in China, even though lots of HTLV positive cases have been reported in southeastern China. However, data on the prevalence of HTLV infection among blood donors is limited.

Objective
The objective was to investigate the prevalence of HTLV among blood donors in three representative blood centers in China and evaluate the feasibility of chemiluminescence immunoassay (CLIA) for blood screening.

Methods
From November 2018 to March 2019, blood plasma samples collected from Hebei, Changsha and Shenzhen blood centers were screening for HTLV-1/2 antibody using Lumipulse G HTLV-I/II Immunoreaction Cartridges set (CLIA) and enzyme-linked immunosorbent assay (ELISA), followed with confirmatory test using INNO-LIA HTLV I/II.
The HTLV-infected blood donor was a first female donor at age 32 with high school degree, born in Fujian province, and SHE minority.

Conclusion
In summary, the overall prevalence of HTLV-1/2 among blood donors in the tree blood centers in China remains relatively low. However, blood donations with positive or indeterminate results for HTLV antibodies found in the study reminded us the importance of HTLV screening among blood donors in China. In the view of HTLV prevalence and cost, all the first-blood donors should undergo HTLV screening as a systematic strategy to reduce the risk of transmission of HTLV through blood transfusion.

Introduction
Human T-cell lymphotropic virus (HTLV) discovered in the early 1980s is the first human retrovirus [1] and classified as type 1, 2, 3, and 4 [2]. HTLV is high risk factor for lymphoproliferative inflammatory and disorder, can cause adult T-cell leukemia/lymphoma (ATL) and neurological disorder [3][4][5]. HTLV-3 and HTLV-4 have not been reported to lead to disease [2]. It is estimated that almost 10-20 million people are infected by HTLV-1/2 in the world [6]. HTLV-1 is mainly endemic in southwestern Japan, South America, Caribbean islands, Sub-Saharan Africa, Middle East and Austro-Melanesia [7], whereas HTLV-2 infection found in Amerindian and pygmy tribes is endemic in Africa, South, North and Central America [8] The latest data described that the overall prevalence of HIV-1/2 was 2.51 per 100,000in major areas of China, which was lower than the US, Japan and other European countries and areas [9][10][11][12][13]. The routes of transmission of HTLV-1/2 occur through intravenous drug use, blood transfusion and sex contact, from mother-to child mainly through breastfeeding [14]. Along with the migration of population, HTLV can spread throughout China from the southeastern region (high prevalence of HTLV) [9].
Limited data about HTLV screening among blood donors in China is available. Furthermore, blood screening laboratories conduct HTLV screening using enzyme-linked immunosorbent assay (ELISA), according to the requirement of the Blood Donation Law. Automated CLIA, including sample pre-processing system and result analysis system et al. from the same manufacturers, are fully automated and self-contained platforms which minimize operator involvement and have good reproducibility, and partly avoid the false positive/negative brought by operator factors [15,16]. This study firstly investigated the prevalence of HTLV-1/2 among blood donors in three blood centers (South region: Shenzhen blood center, Central region: Changsha blood center, North region: Hebei blood center), using CLIA and ELISA at the same time.

Material And Method
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Discussion
Blood screening laboratories has not performed HTLV-1/2 screening on route blood donations, according to the Blood Donation Law in China. This study firstly conducted HTLV-1/2 screening among blood donors and reported the prevalence of HTLV-1/2 among blood donors in three blood centers, which were located in south, central and north region of China, respectively.
From November 2018 to March 2019, no HTLV-infected blood donors were found in Changsha and Hebei blood center, only 1 blood donors from Shenzhen blood center was confirmed as positive for HTLV-1 antibodies. The prevalence of HTLV among blood donors in Shenzhen blood center was 0.0035%, which was similar to the latest survey about the prevalence (0.0028%) of HTLV among volunteer blood donors in Shenzhen [9], while this survey found 1 blood donor with HTLV infection out of 16767 donors in Changsha blood center from January 2016 to December 2017 [9]. Moreover, blood screening laboratories in this study remain relatively few. Future research must focus on expanded sample size and geographical coverage to get a more comprehensive dataset about HTLV prevalence to improve blood safety.

Data Availability
The data used to support this study are available from the corresponding author upon request.

Ethics approval
The institutional review boards of the Shenzhen, Changsha and Hebei blood centers respectively have approved the study. The methods in the study were in accordance with the guidelines of the Declaration of Helsinki. Written informed consent was obtained from all subjects participating in this research.  Figure 1 The study routes of HTLV screening test and confirmatory test.